Osteoporosis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

OSTEOPOROSIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Osteoporosis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83720-1 1. Osteoporosis-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on osteoporosis. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON OSTEOPOROSIS .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Osteoporosis ................................................................................ 26 E-Journals: PubMed Central ..................................................................................................... 152 The National Library of Medicine: PubMed .............................................................................. 155 CHAPTER 2. NUTRITION AND OSTEOPOROSIS .............................................................................. 293 Overview.................................................................................................................................... 293 Finding Nutrition Studies on Osteoporosis............................................................................... 293 Federal Resources on Nutrition ................................................................................................. 302 Additional Web Resources ......................................................................................................... 303 CHAPTER 3. ALTERNATIVE MEDICINE AND OSTEOPOROSIS ........................................................ 309 Overview.................................................................................................................................... 309 The Combined Health Information Database............................................................................. 309 National Center for Complementary and Alternative Medicine................................................ 310 Additional Web Resources ......................................................................................................... 323 General References ..................................................................................................................... 332 CHAPTER 4. DISSERTATIONS ON OSTEOPOROSIS .......................................................................... 333 Overview.................................................................................................................................... 333 Dissertations on Osteoporosis.................................................................................................... 333 Keeping Current ........................................................................................................................ 334 CHAPTER 5. CLINICAL TRIALS AND OSTEOPOROSIS .................................................................... 335 Overview.................................................................................................................................... 335 Recent Trials on Osteoporosis.................................................................................................... 335 Keeping Current on Clinical Trials ........................................................................................... 354 CHAPTER 6. PATENTS ON OSTEOPOROSIS..................................................................................... 357 Overview.................................................................................................................................... 357 Patents on Osteoporosis ............................................................................................................. 357 Patent Applications on Osteoporosis ......................................................................................... 441 Keeping Current ........................................................................................................................ 463 CHAPTER 7. BOOKS ON OSTEOPOROSIS ........................................................................................ 465 Overview.................................................................................................................................... 465 Book Summaries: Federal Agencies............................................................................................ 465 Book Summaries: Online Booksellers......................................................................................... 467 The National Library of Medicine Book Index ........................................................................... 485 Chapters on Osteoporosis........................................................................................................... 486 Directories.................................................................................................................................. 490 CHAPTER 8. MULTIMEDIA ON OSTEOPOROSIS ............................................................................. 493 Overview.................................................................................................................................... 493 Video Recordings ....................................................................................................................... 493 Bibliography: Multimedia on Osteoporosis................................................................................ 494 CHAPTER 9. PERIODICALS AND NEWS ON OSTEOPOROSIS .......................................................... 497 Overview.................................................................................................................................... 497 News Services and Press Releases.............................................................................................. 497 Newsletters on Osteoporosis ...................................................................................................... 502 Newsletter Articles .................................................................................................................... 503 Academic Periodicals covering Osteoporosis ............................................................................. 505 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 507 Overview.................................................................................................................................... 507 U.S. Pharmacopeia..................................................................................................................... 507

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Commercial Databases ............................................................................................................... 510 Researching Orphan Drugs ....................................................................................................... 511 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 515 Overview.................................................................................................................................... 515 NIH Guidelines.......................................................................................................................... 515 NIH Databases........................................................................................................................... 517 Other Commercial Databases..................................................................................................... 521 The Genome Project and Osteoporosis....................................................................................... 521 APPENDIX B. PATIENT RESOURCES ............................................................................................... 525 Overview.................................................................................................................................... 525 Patient Guideline Sources.......................................................................................................... 525 Associations and Osteoporosis ................................................................................................... 545 Finding Associations.................................................................................................................. 548 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 551 Overview.................................................................................................................................... 551 Preparation................................................................................................................................. 551 Finding a Local Medical Library................................................................................................ 551 Medical Libraries in the U.S. and Canada ................................................................................. 551 ONLINE GLOSSARIES................................................................................................................ 557 Online Dictionary Directories ................................................................................................... 559 OSTEOPOROSIS DICTIONARY............................................................................................... 561 INDEX .............................................................................................................................................. 657

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with osteoporosis is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about osteoporosis, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to osteoporosis, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on osteoporosis. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to osteoporosis, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on osteoporosis. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON OSTEOPOROSIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on osteoporosis.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and osteoporosis, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “osteoporosis” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Osteoporosis in Men Source: American Family Physician. 67(7): 1521-1526. April 1, 2003. Summary: This journal article presents information on the pathogenesis, diagnosis, and treatment of osteoporosis in men. Osteoporosis in men is now recognized as an increasingly important public health issue. About 30 percent of hip fractures occur in men, and one in eight men older than 50 years old will have an osteoporotic fracture. Because of their greater peak bone mass, men usually present with hip, vertebral body, or distal wrist fractures 10 years later than women. Hip fractures in men, however, result in a 31 percent mortality rate at one year after fracture versus a rate of 17 percent in women. Major risk factors for osteoporosis in men are glucocorticoid use for longer than six months, osteopenia seen on plain radiographs, a history of nontraumatic fracture, hypogonadism, hyperparathyroidism, and advancing age. Medium risk causes

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for osteoporosis include excessive alcohol consumption, tobacco use, rheumatoid or other inflammatory arthritis, lymphoma or multiple myeloma, family history of osteoporosis, anticonvulsant drug use, and hypothyroidism or hyperthyroidism. Screening measures include dual energy x-ray absorptiometry of the hip and spine, ultrasonography of the heel, or quantitative computed tomography. Bisphosphonates and teriparatide (recombinant parathyroid hormone) have recently been approved for use in men and should be considered along with supplemental calcium and vitamin D. Physical therapy to help patients use a cane or walker and regular exercise are also recommended. Increased awareness by physicians of risk factors for male osteoporosis, early diagnosis, and treatment are needed to decrease the morbidity and mortality resulting from osteoporotic fractures. 1 figure, 5 tables, and 32 references. (AAM). •

Osteoporosis in Men: A Serious but Under-Recognized Problem Source: Journal of Musculoskeletal Medicine. 18(6): 310-316. June 2001. Summary: This journal article, the second in a special series on diagnosis and management of osteoporosis, provides health professionals with information on the epidemiology, etiology, diagnosis, and management of osteoporosis in men. Osteoporosis can produce profound morbidity and mortality in men, much as it can in women. Although osteoporosis is often asymptomatic, its end result, fragility fracture, creates a heavy medical and financial burden for society. Each year in the United States, between 850,000 and 1.5 million fractures occur in people who are at least 65 years old. Of these fractures, 20 percent are sustained by men. Abnormalities affecting the factors involved in normal bone turnover constitute primary and secondary causes of osteoporosis. Primary factors are usually related to aging or genetic factors, whereas secondary factors are external and can usually be avoided and corrected. Most men have secondary contributors to osteoporosis. Male hypogonadism, or testosterone deficiency, is a secondary cause of osteoporosis in up to 30 percent of men. Hypogonadism contributes to osteoporosis in men by blunting calcitonin secretion and osteoblastic activity. Estrogen deficiency may also contribute to osteoporosis in some men. Bone density studies are recommended for men older than 70 and earlier in the presence of osteoporosis risk factors. Once the diagnosis has been confirmed, management focuses on adequate calcium and vitamin D intake, regular exercise, prevention of falls, and administration of alendronate. Testosterone replacement may hold promise. 4 tables and 38 references. (AA-M).

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Osteoporosis in Patients With Rheumatic Diseases: Prevention and Management Source: Journal of Musculoskeletal Medicine. 18(5): 240-246,249. May 2001. Summary: This journal article, the first in a special series on the diagnosis and management of osteoporosis, provides health professionals with information on the identification of osteoporosis in patients who have rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Patients with rheumatic disease are at particular risk for osteoporosis as a consequence of disease mediated effects, antirheumatic medications such as corticosteroids, and lifestyle restrictions. Secondary contributors to osteoporosis include hyperparathyroidism, resulting from renal impairment, and hypogonadism, as a consequence of inflammation or ovarian failure. Physicians should maintain a particularly high index of suspicion for osteoporosis in the young, premenopausal patient who has a rheumatic disease such as RA or SLE. Bone mineral density should be measured at baseline and regularly thereafter in all patients who are perimenopausal or starting long term treatment with corticosteroids, heparin, or certain antirheumatic agents. Osteoporosis management

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focuses on adequate calcium and vitamin D intake; participation in weight bearing activity; and use of corticosteroid sparing agents, hormone replacement therapy, and nonestrogen agents. 6 tables and 28 references. (AA-M). •

Steroid-Induced Osteoporosis in Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 311-329. May 2000. Summary: This journal article provides health professionals with information on the mechanisms of glucocorticoid induced osteoporosis in systemic lupus erythematosus (SLE) and outlines strategies for prevention and treatment. The patient with SLE is at considerable risk of osteoporosis because of the inflammatory disease itself, its consequences, and its treatments. Risk factors and mechanisms for osteoporosis in SLE include environmental factors, hormonal factors, the effects of inflammation, renal disease, and medications used to treat SLE. Because of their extensive use, glucocorticoids are thought to be the most frequent cause of drug induced osteoporosis and may be responsible for much of the bone loss in SLE. Glucocorticoids predominantly affect trabecular bone and the cortical rim of the vertebral body, but over time, the cortex of long bones also becomes susceptible to the demineralizing effects of these drugs. Mechanisms of steroid induced osteoporosis include abnormalities of gonadal function, mineral metabolism, and bone cell function, and steroid effects on local skeletal growth factors and on muscles. Assessment of the patient with SLE may involve determining bone mineral density and measuring baseline serum levels of vitamin D1 and osteocalcin, as well as urinary calcium excretion and pyridinoline cross links. Calcium, vitamin D, and a weightbearing program are suitable first line measures. Thiazides are useful for the glucocorticoid treated patient with hypercalciuria. Unless otherwise contraindicated, hormone replacement therapy should be used in patients who are deficient in sex hormones. If bone loss continues despite these therapies, antiresorptive therapies are recommended. Therapies under investigation include parathyroid hormone, ipriflavone, growth hormone, and insulin like growth factor. 120 references. (AA-M).

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Corticosteroid-Induced Osteoporosis: Prevention and Management Source: Journal of Musculoskeletal Medicine. 17(2): 68-70,76-81. February 2000. Summary: This journal article, the first in a special series on the prevention, diagnosis, and management of osteoporosis, provides health professionals with information on the pathophysiologic mechanisms that contribute to corticosteroid induced osteoporosis and its diagnosis and management. The benefits of corticosteroids are offset by the significant bone loss that occurs within the first 3 to 6 months of therapy and is never fully regained. This effect occurs in men and women of all ages. One mechanism by which corticosteroids interfere with normal bone remodeling is through their influence on gonadal hormone levels. Corticosteroids directly inhibit ovarian and testicular production of estrogen and testosterone and disrupt the hypothalamic pituitary gonadal axis. Corticosteroids may also decrease calcium absorption from the gut and increase urinary calcium secretion. Further, corticosteroids inhibit bone formation through mechanisms that include the direct inhibition of osteoblast replication, decreased synthesis of bone collagen by osteoblasts, and attachment to bone matrix. Patients starting corticosteroids at 7.5 milligrams per day or more for at least 3 months are candidates for osteoporosis prevention. In these patients, the physician should rule out secondary causes of osteoporosis and obtain a baseline bone mineral density measurement. Weight bearing exercise and adequate calcium and vitamin D intake are important, but drugs are usually needed. Estrogen and testosterone replacement are

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recommended for postmenopausal and hypogonadic patients. Calcitonin stabilizes bone mineral density in the spine but not the hip. Bisphosphonates act directly on osteoclasts to decrease bone resorption, and they have proven efficacy for both prevention and treatment of corticosteroid induced osteoporosis. 2 figures, 4 tables, and 41 references. (AA-M). •

Management of Corticosteroid-Induced Osteoporosis Source: Seminars in Arthritis and Rheumatism. 29(4): 228-251. February 2000. Summary: This journal article provides health professionals with information on the pathophysiology of corticosteroid induced osteoporosis, the assessment methods used to evaluate this condition, and the results of clinical trials of drugs. In addition, the article explores a practical approach to the management of corticosteroid induced osteoporosis based on data collected from published articles. The cause of corticosteroid induced osteoporosis is multifactorial and occurs in addition to normal age and menopause associated bone loss. There are two purported abnormalities in bone metabolism that develop in patients with this condition. The first is a reduction in bone formation, and the second is an increase in bone resorption. Risk factors that should be examined in patients receiving corticosteroids include family history, hormonal status, fracture history, age, other medications that may interfere with normal bone metabolism, and lifestyle habits. Measurements of urinary calcium concentrations are helpful in assessing calcium balance, susceptibility to secondary hyperparathyroidism, and possible treatment options for corticosteroid treated patients. Distinctive characteristics of corticosteroid induced osteoporosis may be observed on radiographs. Early changes in bone mineral density can be observed in the lumbar spine and femoral neck using dual x-ray energy absorptiometry or quantitative computed tomography. Therapeutically, the use of alternative therapy or early discontinuation of corticosteroids is the best means of preventing corticosteroid induced osteoporosis. Several interventions have been proposed in the management of corticosteroid induced bone loss. Bisphosphonate (diphosphonate) therapy is beneficial in both the prevention and treatment of corticosteroid induced osteoporosis. Data for the bisphosphonates are more compelling than for any other agent. For patients who have been treated but continue to lose bone, hormone replacement therapy, calcitonin, fluoride, or anabolic hormones should be considered. Although calcium and vitamin D and its analogs appear to have weak positive effects on bone in those receiving corticosteroids, they may not be potent enough to be used alone. As such, they should be administered in combination with other agents. The article concludes that bisphosphonates have shown significant treatment benefit and are the agents of choice for both the treatment and prevention of corticosteroid induced osteoporosis. 2 figures, 6 tables, and 146 references. (AA-M).

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Corticosteroid-Induced Osteoporosis: Access the Risk, Protect Your Patient Source: Journal of Musculoskeletal Medicine. 14(1):43-44,46, 53-55; January 1997. Summary: This journal article for health professionals reviews the pathophysiology of corticosteroid-induced osteoporosis, identifies the at-risk population, and discusses management strategies. Long-term corticosteroid therapy causes a rapid loss of trabecular bone through disruption of calcium homeostasis, inhibition of bone formation, and reduction in sex hormone levels. Pharmacologic doses of corticosteroids inhibit the synthesis or action of several growth factors having anabolic effects on bone. It is reasonable to measure bone mineral density and to start preventive care as soon as possible in patients beginning long-term corticosteroid therapy. Calcium supplements, vitamin D, sex hormone replacement, and a weight-bearing exercise program are

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suitable first-line therapies to counteract bone loss. Thiazide diuretics and sodium restriction are useful in reducing hypercalciuria. Other agents, such as bisphosphonates, calcitonin, or fluoride, may be indicated for patients who cannot take hormones or in whom initial interventions do not retard bone loss. Agents that stimulate bone formation in the presence of corticosteroids may become available in the future. 11 references, 2 figures, and 1 table. (AA-M). •

Osteoporosis: Current Pharmacologic Options for Prevention and Treatment Source: Postgraduate Medicine. 101(1):129-132,136-137, 141-142; January 1997. Summary: This journal article for health professionals reviews data on the efficacy and safety of therapeutic agents currently available to prevent and treat osteoporosis. Information on estrogen replacement therapy includes its effect on osteoporotic fracture, its cardiovascular benefits, the risk of breast and endometrial cancer associated with its use, and mortality risks. Data on bisphosphonates, calcitonin, and sodium fluoride are presented. The cost of various agents given for osteoporosis is provided. An approach to preventing and treating this disease is also suggested. 21 references, 1 figure, and 2 tables.

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Osteoporosis: Up-to-date Strategies for Prevention and Treatment Source: Geriatrics. 52(4):92-94,97-98; April 1997. Summary: This journal article for health professionals presents an interview with the past president of the American Federation for Aging Research. This interview focuses on a research-based approach to the prevention and treatment of osteoporosis in older patients being treated by primary care physicians. Topics discussed include whether osteoporosis is part of the normal aging process or whether it is a disease, the processes that lead to osteoporosis, the role of personal habits in the development of osteoporosis, whether drugs cause osteoporosis, and whether hormone replacement decreases the risk of osteoporosis in postmenopausal women. The interviewee also explains how the diagnosis of osteoporosis has changed and identifies other drugs available to decrease the risk or treat the complications of osteoporosis. 8 references and 1 table.

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Osteoporosis in Active Women. Prevention, Diagnosis, and Treatment Source: Physician and Sportsmedicine. 25(11):61-62,64, 67-68,71-72, 74; November 1997. Summary: This journal article for health professionals presents an overview of osteoporosis in active females, focusing on the causes, diagnosis, prevention, and treatment of this disease. Insufficient estrogen can cause osteoporosis in young female athletes and in postmenopausal women. The most common technique for diagnosis is dual-energy, x-ray absorptiometry. Prevention and treatment depend on the woman's age, but may include increased calcium intake, weight gain, weight-bearing and resistance exercise, and estrogen replacement therapy. Alendronate and /or calcitonin may be used as alternatives to estrogen therapy. 6 references, 2 tables, and 1 photograph. (AA-M).

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Osteoporosis: It Steals More than Bone Source: American Journal of Nursing. AJN. 96(6):27-33. June 1996. Summary: This journal article for nurses examines osteoporosis, its adverse effects on a patient's quality of life, and primary and secondary prevention strategies, i.e., preventing the disease from developing (primary), and preventing fractures in those

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who have the disease (secondary). How breaking a bone can permanently alter a person's life is illustrated, and management of one case is continued throughout the article to describe the disease and strategies to prevent it. How a patient can severely alter their life to avoid potential bone fractures is discussed along with advice on steps that can be taken in limiting the toll of the disease. The article describes who is most at risk for osteoporosis, then explores the role of dietary changes and exercise as well as improvements in medical management, including the use of hormone replacement therapy and sodium fluoride. Nonhormonal treatment for osteoporosis using alendronate sodium to increase bone mineral density in women at risk is also highlighted. 10 references. •

Pathogenesis and Early Identification of Osteoporosis in Postmenopausal Women Source: Clinical Geriatrics. 4(10):73-75,79-80,84-86; September 1996. Summary: This journal article for health professionals discusses the pathogenesis and early identification of osteoporosis in postmenopausal women. The bone remodeling cycle is explained. Primary risk factors for osteoporosis are identified, including heredity, lifestyle, gynecologic factors, eating disorders, scoliosis, and endocrinopathies. The use of bone densitometry for assessment and management of osteoporosis is discussed in terms of a method of selectively and cost-effectively monitoring women at risk of osteoporosis, access to and accuracy of bone densitometry, and the vertebral deformities required for the diagnosis of osteoporosis. Biochemical markers of bone remodeling that may be useful in clinical practice are described, including serum alkaline phosphatase activity and urinary calcium excretion, and the clinical use of biochemical markers is explained. In addition, the issue of evaluating the secondary causes of osteoporosis is addressed. 24 references, 3 figures, and 2 tables.

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Current Investigative and Clinical Experience With Alendronate in Osteoporosis Source: Today's Therapeutic Trends. 14(2):103-118; Third Quarter 1996. Summary: This journal article for health professionals examines the investigative and clinical experience with alendronate in osteoporosis. This condition may be characterized as an age-related disorder of bone metabolism in which the rate of bone resorption exceeds the rate of bone formation in the presence of increased bone turnover. Drugs that inhibit bone resorption and decrease bone turnover or that stimulate bone formation may be used to treat osteoporosis. Alendronate, an aminobisphosphonate, preferentially inhibits bone resorption at doses that do not inhibit mineralization and may therefore be administered continuously. The pharmacologic properties of alendronate are described. The findings of preclinical and clinical studies are presented. Preclinical studies in animal models of osteoporosis have shown that alendronate reduces bone turnover and increases bone mass and bone strength. Clinical studies in osteoporotic postmenopausal women have confirmed that alendronate reduces bone turnover; increases bone mass at the spine, hip, forearm, and total body; and reduces the risk of vertebral fractures and height loss. In addition, alendronate has been shown to reduce the incidence of new vertebral and nonvertebral fractures. 41 references and 4 figures. (AA-M).

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The Epidemiology of Osteoporosis Source: Journal of Rheumatology. 23(45):2-5. 1996. Summary: This journal article for physicians describes the types of osteoporosis, discusses bone loss during adult life, explores the socioeconomic impact of osteoporosis

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and its worldwide demographic shift, examines morbidity and mortality due to the disease, and identifies persons at risk. Compared to normal bone, osteoporotic bone shows a reduction in the number of trabeculae, thinning of the trabeculae, and loss of connectivity of the trabeculae. The proportion of persons who are currently affected by, and who are at risk for, osteoporosis is increasing exponentially, and its consequent fractures are the cause of significant morbidity and mortality among both men and women. The author indicates that potential effect on health resources is likely to be considerable unless measures are taken to prevent associated fractures. While some risk factors are well defined, including advanced age, early menopause, and chronic corticosteroid use, there are other potential risk factors needing to be further defined to differentiate persons at high risk from those at negligible risk. The use of bone mineral density assessment in clinical decision making for treatment of osteoporosis is recommended. 1 table, 1 figure, and 20 references. •

Current Treatment Options for Osteoporosis Source: Journal of Rheumatology. 23(Supplement 45):11-14. 1996. Summary: This for physicians examines various approaches to preventing and treating of osteoporosis, including increasing calcium intake and use of drug and hormone therapies. It indicates that the goals for treating patients with osteoporosis are to maintain normal bone and to prevent the deterioration of normal bone to osteoporotic bone. Achievement of these goals, combined with a successful approach for preventing falls, may substantially decrease the incidence and risk of fractures. Using drug therapy to stimulate bone formation (e.g., fluoride, anabolic steroids), and drugs to inhibit bone resorption (e.g., estrogen replacement therapy, calcitonin, bisphosphonates) are recommended. 14 references.

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Role of Vitamin D in the Pathogenesis and Treatment of Osteoporosis Source: Journal of Rheumatology. 23(Supplement 45):15-18. 1996. Summary: This journal article for physicians explains the pathogenesis of osteoporosis types 1 and 2, the effects of 1,25-dihydroxyvitamin D (calcitriol) on calcium balance, changes in bone mineral density during calcitriol treatment and maintenance of the treatment effect. Evidence on reducing vertebral fractures with calcitriol treatment is also provided. The author explains that patients with postmenopausal osteoporosis usually exhibit some degree of calcium malabsorption and commonly have low serum concentrations of calcitriol. Administration of calcitriol has been shown to normalize calcium absorption in patients with osteoporosis and, over the long term may stimulate bone formation. Clinical trials have shown a significant reduction in osteoporotic fractures among calcitriol-treated patients. Hypercalcemia and hypercalciuria are infrequent complications of calcitriol therapy with physiologic doses (0.25 microgram twice daily), and are most commonly related to excessive calcium intake (i.e., greater than 1,000 milligrams daily). 7 figures, and 25 references. (AA-M).

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Osteoporosis Prevention and Treatment Source: American Family Physician. 54(3): 986-992. September 1, 1996. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org.

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Summary: This journal article for physicians examines the preventive strategies, evaluation, and treatment options for osteoporosis. The author indicates that bone fragility resulting from osteoporosis places a significant percentage of elderly women and other patient groups at risk for bone fracture. Risk factors for osteoporosis include hypogonadal states (particularly menopause), smoking, low calcium intake, lack of weight-bearing exercise, family history and use of certain medications. Preventive strategies are based on achieving and maintaining optimal bone mass through diet, exercise, appropriate use of hormone replacement therapy and avoidance of adverse influences, particularly smoking and certain medications. Laboratory investigations are of limited use in the detection and assessment of osteoporosis, but new techniques may help physicians identify patients with accelerated bone metabolism. Currently, the most precise method of radiologically assessing osteoporosis is dual-energy x-ray absorptiometry. Many new agents for the treatment of osteoporosis are being examined. First-line therapies currently include alendronate and calcitonin. The choice of therapy must be individualized and combined with advice about nutrition and exercise, both to optimize bone density and to minimize the risk of trauma. 2 tables, and 31 references. •

Alendronate: A Bisphosphonate for Treatment of Osteoporosis Source: American Family Physician. 54(6):2053-2057,2060. November 1, 1996. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article for health professionals focuses on the use of the bisphosphonate alendronate in the treatment of postmenopausal osteoporosis. The bisphosphonates have been investigated over the past two decades for the treatment of various diseases of bone and calcium metabolism that are characterized by increased bone resorption. Alendronate is discussed in terms of pharmacokinetics, contraindications, adverse reactions, teratogenicity and effects in pregnancy, and drug interactions. In postmenopausal osteoporosis, alendronate has been shown to increase bone mineral density and to decrease the rate of new fractures. Adverse effects are not usually a problem when 10 milligrams per day of alendronate is given with at least 6 ounces of water 30 minutes before ingestion of the first food or beverage of the day. The efficacy of using alendronate in the treatment of Paget's disease and hypercalcemia of malignancy is also discussed. 31 references and 2 figures. (AA-M).

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Osteoporosis: What's New in Prevention and Treatment Source: Patient Care. 24-28,30-31,35-36,38,44,46,49,53; August 15, 1996. Summary: This journal article for health professionals reports on advances in the prevention and treatment of osteoporosis. Risk factors for osteoporosis are discussed, including advancing age, female gender, and inadequate peak bone mass. Radiographic methods that are available for measuring bone mass are described, including dual energy x-ray absorptiometry. The potential usefulness of metabolic benchmarks in monitoring patient compliance and drug efficacy is discussed. The advantages and disadvantages of using estrogen replacement therapy for the prevention and treatment of osteoporosis are presented. Other options for treating osteoporosis are described, including the bisphosphonates, particularly alendronate and etidronate disodium; injectable calcitonin-salmon; and unestablished strategies, such as slow-release sodium fluoride, tamoxifen citrate, and thiazide diuretics. In addition, lifestyle strategies that women can adopt to eliminate the risk factors for osteoporosis are presented, including

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ingesting adequate amounts of calcium and vitamin D, undertaking some sort of weight-bearing exercise, and minimizing the chance of injury in the home. 8 references, 2 figures, and 3 tables. •

Effect of Three Years of Oral Alendronate Treatment in Postmenopausal Women with Osteoporosis Source: American Journal of Medicine. 101:488-501. November 1996. Summary: This 3-year, randomized, double-blind, multicenter study assessed the efficacy and safety of oral alendronate sodium as a specific inhibitor of osteoclastmediated bone resorption in 478 postmenopausal women with osteoporosis. Subjects received either placebo, alendronate 5 or 10 mg/day for 3 years, or 20 mg/day for 2 years followed by 5 mg/day for 1 year (20/5 mg). All subjects received 500 mg/day of supplemental calcium. Bone mineral density (BMD) was measured by dual energy x-ray absorption (DXA). Results after 3 years show that alendronate 10 mg induced marked increases in BMD of the lumbar spine, femoral neck, and trochanter versus decreases with placebo. Progressive increases at these sites in the alendronate 10 mg group were significant during both the second and third years. Alendronate 10 mg increased total body BMD and prevented loss but did not increase BMD at the 1/3 forearm site. Alendronate 20/5 mg was no more effective, whereas alendronate 5 mg was significantly less effective than 10 mg at all sites. Bone turnover decreased to a stable nadir over 3 months for resorption markers (urine deoxypyridinoline) and over 6 months for formation markers (alkaline phosphatase and osteocalcin). Mean loss of stature was reduced by 41 percent in alendronate treated subjects. Results indicate that the safety profile of alendronate was similar to that of placebo. At 10 mg, there were no trends toward increased frequency of any adverse experience except for abdominal pain, which was usually mild, transient, and resolved with continued treatment. 6 tables, 4 figures, and 43 references.

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Preventing and Managing Osteoporosis Source: American Journal of Nursing. AJN. 97(1):16B-16D. January 1997. Summary: This article discusses the prevention and treatment of osteoporosis, including its assessment, hormone strategies, and pharmacological and non-pharmacological management options. Osteoporosis is not curable, however, advances in treatment have been made to stabilize bone loss. Part of assessing patient risk is exploring the common factors such as being female, family history, small-framed body, sedentary lifestyle, excessive use of alcohol, and smoking. Biochemical markers of bone turnover can also be measured to diagnosis or track the disease's progress. Prevention strategies include calcium and vitamin D (calciferol) intake, and prevention efforts during adolescence may significantly reduce the incidence of osteoporosis in the elderly. Additionally, patients of any age may gain benefit from regular weight-bearing activities and other exercise. Estrogen replacement therapy may be prescribed to postmenopausal women to prevent osteoporosis, and for men, testosterone replacement therapy may also be appropriate, although long-term effects are unknown. Currently, calcitonin, fluoride, and a class of drugs called bisphosphonates are available. Nonpharmacologic measures include physical therapy, counseling, and home environment safety adjustments. 9 references.

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OA: Protection from Osteoporosis? Source: Arthritis Today. p. 8-10. November-December 1996.

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Summary: This article discusses new directions in the treatment of osteoarthritis and rheumatoid arthritis, and the notion that osteoarthritis may have a preventive effect on osteoporosis. The author reveals that new biodegradable chemicals called alkanoates can help drugs, such as anti-infammatories, better penetrate the skin barrier with less irritation. There is also a new theory in rheumatoid arthritis drug therapy that suggests using DMARDs (disase-modifying antirheumatic drugs) early in the disease process to lessen the pain and disabling effects of the disease. Tracking changes in lupus through clinical tests has arisen because of positive findings from a study that used clinical measures on a monthly basis in 23 lupus patients. Another study has shown that injectable collagen may not lead to the autoimmune disorders polymyositis and dermatomyositis. This conclusion is based on a followup study of 150,000 collagen users from which only seven developed probable or definite polymyositis or dermatomyositis. Finally, research on pairs of identical and fraternal twins reveals a strong genetic link among women who have osteoporosis in the hands and knees. •

Osteoporosis: It's Not Inevitable Source: Female Patient. 11-15; 1996. Summary: This journal article for the general public presents an overview of osteoporosis. The process of bone mass loss in women after the age of 35 is explained. The risk factors for osteoporosis are outlined, and its symptoms are presented. The use of bone mineral density tests to diagnose osteoporosis in its early stages, that is, before fractures occur, is discussed. Ways of preventing osteoporosis are suggested, including consuming adequate amounts of calcium and vitamin D, making some form of weightbearing exercise part of one's daily routine, and quitting smoking. In addition, therapies that can help slow the progression of osteoporosis and make bone fractures less likely are highlighted, including using estrogen replacement therapy, hormone replacement therapy, calcitonin nasal spray, and alendronate. 1 figure and 2 tables.

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Osteoporosis: Talk Isn't Cheap, It's Essential Source: Journal of Family Practice. 43(6):542-544; December 1996. Summary: This article for health professionals discusses the need for physicians to give more attention to osteoporosis. Although osteoporosis appears to be a popular topic of discussion across the United States, this wave of interest has not reached the offices of family physicians. Women who participated in focus groups for the development of a questionnaire on the community burden of osteoporosis stressed the fact that their physicians did not tell them enough about osteoporosis. These women also identified areas in which osteoporosis affected aspects of their daily living. Women with osteoporosis who had and had not experienced a fracture expressed various concerns about their lives, as did younger women with low bone mineral density. Despite the lack of attention given to osteoporosis by physicians, the data indicate that women should be screened and treated for osteoporosis. Family physicians need to become more involved in preventing, treating, and studying osteoporosis. Preventive efforts include the provision of information about diet, exercise, and hormone replacement therapy to women. 22 references.

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Ten Questions Commonly Asked by Physicians About Osteoporosis Source: Journal of Clinical Rheumatology. 2(1):33-40; February 1996. Summary: This journal article for health professionals answers 10 questions commonly asked by physicians about osteoporosis. Questions deal with the use of fluoride therapy

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to increase spinal bone mass, the prevention of bone loss in patients receiving chronic glucocorticosteroid therapy, the effectiveness of calcium supplements in the treatment of osteoporosis, options for preventing bone loss in early menopause if estrogen replacement is not possible, and the advantages and disadvantages of calcium carbonate versus calcium citrate. Questions also focus on the differences between osteoporosis and osteomalacia; the effectiveness of estrogen replacement therapy in treating osteoporosis after 65 years of age; the management of an elderly patient with severe, established osteoporosis; noninvasive radiographic techniques for assessing bone density; and the management of vertebral compression fractures. 26 references and 2 tables. •

Osteoporosis: Using 'Bone Markers' for Diagnosis and Monitoring Source: Geriatrics. 51(4):24-30; April 1996. Summary: This journal article for health professionals discusses the use of new techniques that measure biochemical bone markers in diagnosing and monitoring osteoporosis. Bone is continuously resorbed and formed in the process of remodeling. Osteoporosis results when bone loss is sufficient to cause increased risk of fracture. High rates of bone turnover can be identified by measuring biochemical byproducts of resorption and formation. Collagen crosslinks and associated peptides measured in urine are newly recognized markers for bone resorption. Bone-specific alkaline phosphatase and osteocalcin are serum markers for bone formation. The clinical utility of these new techniques is two-fold: to identify adults at high risk of osteoporosis so that preventive therapy can be instituted and to provide noninvasive, sensitive tools for monitoring clinical course and effect of therapy, adjusting dosage when appropriate, and determining the consequences of discontinuing treatment. Information obtained from bone mineral density assessment and biochemical markers can be useful for making decisions about estrogen replacement therapy and antiresorptive therapy. 25 references, 2 tables, and 1 illustration. (AA-M).

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Finally, There's Real Help for Women with Osteoporosis, and a Good Reason for Doctors to Find Out Who Else Is At Risk Source: Hippocrates. 67-69. May 1996. Summary: This article discusses two new, FDA approved, drug treatments for osteoporosis, alendronate and calcitonin in nasal-spray form, and a slightly risky, nonFDA approved, slow-release sodium fluoride that can rebuild bones. The author also provides advice on using bone scans to help physicians and their patients decide on treatment options; explores the question of whether younger women just entering menopause can or should use these drugs as a preventive measure; highlights the advantages of estrogen usage and the benefits and problems associated with slowrelease sodium fluoride; and examines the nutritional and lifestyle considerations for combating the condition, including taking vitamin D and calcium supplementation.

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Osteoporosis Update: Strategies to Counteract Bone Loss, Prevent Fracture Source: Consultant. 36(7):1387-1390,1393-1396; July 1996. Summary: This journal article for health professionals reviews the effects of aging on bone remodeling and the process by which disturbance in the remodeling process can lead to osteoporosis. Risk assessment in both asymptomatic and symptomatic persons is discussed, focusing on obtaining a medical history; performing a physical examination; and conducting diagnostic tests, such as densitometry. Identification of persons at risk for osteoporosis and intervention during the asymptomatic phase may reduce the

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incidence of fractures. Bone densitometry quantitatively assesses bone mass and monitors therapeutic effects. Current approaches to therapy are also examined. Patients should be encouraged to maintain sufficient calcium intake throughout their lives and to exercise regularly. Antiresorptive therapy for established disease includes estrogen, salmon calcitonin, and bisphosphonates. When each of these agents is used, patients must maintain calcium intake. Since calcitonin may have some analgesic effect, it may help relieve the pain of vertebral fracture. In addition, suggestions for preventing falls that may result in fractures are presented. 26 references, 3 figures, and 1 table. (AA-M). •

Osteoporosis or Osteoarthritis: Which Do I Have? Source: Women's Health Digest. 2(2):128-130; 1996. Summary: This journal article for individuals with bone disorders explains the differences between osteoporosis and osteoarthritis. Osteoporosis is a process of painless bone loss throughout the entire skeleton, whereas osteoarthritis involves pain, stiffness, and sometimes mild swelling in the joints. The pathogenesis of osteoporosis and osteoarthritis are briefly described. The characteristics of patients with type I and type II osteoporosis are highlighted. Factors that can accelerate osteoporosis are discussed. The use of bone density testing in the diagnosis and treatment of osteoporosis is described. Ways of preventing bone loss are identified, including consuming adequate amounts of calcium, undergoing estrogen replacement therapy, and taking calcitonin or bisphosphonate drugs. In addition, pharmacologic and nonpharmacologic methods of treating osteoarthritis are presented. 3 references and 1 illustration.

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Osteoporosis Its Diagnosis, Management and Treatment With a New Oral Bisphosphonate Agent, Etidronate Source: Today's Therapeutic Trends. 14(1):13-24; 1996. Summary: This journal article for health professionals presents an overview of osteoporosis. The pathophysiology of osteoporosis is explained, and its clinical presentation is described. Risk factors for osteoporosis are identified. Tools used to diagnose osteoporosis are presented, including laboratory investigations, bone biopsy, bone scan, radiographic assessment, and bone mass measurement. Ways of preventing and treating osteoporosis are considered, focusing on consuming adequate amounts of calcium and vitamin D and using estrogen replacement therapy, calcitonin, slow-release fluoride, and bisphosphonates. The effectiveness and adverse effects of two bisphosphonates, alendronate and etidronate, are discussed. 41 references.

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Osteoporosis in Young, Athletic Women Source: Journal of Musculoskeletal Medicine. 13(6):15-22; June 1996. Summary: This journal article discusses factors associated with bone loss in women athletes, offers advice for early detection of osteoporosis, and provides guidelines on preventing osteoporosis and suggestions for managing it when it does occur. The authors reveal that exercise, calcium intake, and estrogen levels all affect the status of bone in young women athletes. In premenopausal women, menstrual dysfunction, especially amenorrhea, suggests a lack of estrogen and is a special cause for concern because of its association with low bone mineral density (BMD) and increased incidence of stress fracture. The condition is more common in athletes; lean body weight, caloric restriction, and a strenuous training regimen may be contributing factors. Diagnosis is based on the office evaluation, which may be supplemented with BMD measurement (dual-energy x-ray absorptionmetry is the most accurate method). Successful

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management depends on a program of education, diet, and exercise modification. Some patients may also benefit from estrogen replacement therapy. 4 figures, 31 references. (AA-M). •

Osteoporosis: Taking a Fresh Look Source: Hospital Practice. 59-64,67-68; May 15, 1996. Summary: This journal article for health professionals discusses the pathogenesis, diagnosis, prevention, and treatment of osteoporosis. Perceptions of osteoporosis are changing as a result of new strategies of risk identification and more sensitive techniques of bone density assessment. Although bone density assessment allows for earlier detection of osteoporosis and the refinement of risk factors permits better analysis of risk, the clinical diagnosis of osteoporosis remains one of exclusion. The preferable method of assessing bone density is dual energy x-ray absorptiometry. Measures to prevent osteoporosis should begin in adolescence and should include impact- loading exercise and dietary measures to ensure adequate intake of calcium and vitamin D. At menopause, estrogen replacement therapy may be used. Active treatments currently available for use against osteoporosis include gonadal hormones, calcitonin, and bisphosphonates. All three types of treatment suppress bone resorption. Trials of slow-release sodium fluoride preparation have shown promise in increasing bone mass. 4 figures and 1 table.

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Vitamin D and Calcium in the Prevention of Corticosteroid Induced Osteoporosis: A 3 Year Follow up Source: Journal of Rheumatology. 23(6):995-1000; 1996. Summary: This journal article for health professionals describes a study that determined the efficacy and safety of using 50,000 units per week of vitamin D and 500 milligrams per day of calcium in the prevention of corticosteroid-induced osteoporosis. A minimized double blind, placebo controlled trial was used to evaluate corticosteroidtreated patients in a tertiary care university affiliated hospital. Patients were eligible for the study if they had polymyalgia rheumatica, temporal arteritis, asthma, vasculitis, or systemic lupus erythematosus. There were 22 women and 9 men in the treatment group, and 20 women and 11 men in the control group. The primary outcome measure was the percentage change in bone mineral density (BMD) of the lumbar spine in the two treatment groups from baseline to 36 months followup. Results indicate that BMD of the lumbar spine in the vitamin D and calcium treated group decreased by a mean of 2.6 percent at 12 months, 3.7 percent at 24 months, and 2.2 percent at 36 months. In the placebo group, there was a decrease of 4.1 percent at 12 months, 3.8 percent at 24 months, and 1.5 percent at 36 months. The observed differences between groups were not statistically significant. Results suggest that vitamin D and calcium may help prevent the early loss of bone seen in the lumbar spine as measured by densitometry of the lumbar spine; however, long-term vitamin D and calcium in those undergoing extended therapy with corticosteroid does not appear to be beneficial. 14 references, 2 figures, and 7 tables. (AA-M).

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Strategy for Osteoporosis in Gastroenterology Source: European Journal of Gastroenterology and Hepatology. 10(8): 689-698. August 1998. Contact: Available from Lippincott Williams and Wilkins, 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390.

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Summary: Osteoporotic fractures are a major public health problem that results not only in considerable morbidity and mortality, but also in increased costs, including acute hospital care and long-term care in the home or nursing home. Gastroenterologists see many patients at risk of osteoporosis, particularly those with celiac disease and inflammatory bowel disease (IBD). In this article, the authors review the extent of this problem and outline a strategy of investigation and treatment. The authors first review methods of screening for osteoporosis, particularly the methods for measuring bone mineral density (BMD), the primary means of determining osteoporosis. The mechanism of osteoporosis in celiac disease is likely to be related to calcium malabsorption, which leads to increased parathormone secretion. This in turn increases bone turnover and cortical bone loss. The authors note that studies of osteoporosis in IBD are less consistent than in celiac disease; This finding is not surprising given the great variation in site, extent, and severity of disease, as well as the use or non-use of steroid drugs in patients with IBD. The authors outline a strategy for preventing and treating osteoporosis that includes patient education, particularly about dietary and lifestyle risks; the timing of densitometry (to measure BMD); the role of hormone replacement therapy, biphosphonates, and calcitonin; the duration of treatment; and the use of steroids and combination treatment. For patients on steroids, the authors recommend 800 units of vitamin D daily for the duration of therapy. BMD should be measured and repeated every year in which steroids are given. If osteoporosis is found, the care plan would include a biphosphonate, usually in addition to vitamin D. The appendix summarizes the recommended strategies for different patient populations (based on age, gender, and presence of other risk factors and diseases). The article is published with the opinions of the referees who commented on the text during the peer review process; the editor explains that this was done in light of the general importance of this article and the discussion it had generated. 1 appendix. 80 references. (AA-M). •

Detection of Osteoporosis in Patients with Inflammatory Bowel Disease Source: European Journal of Gastroenterology and Hepatology. 9(10): 931-933. October 1997. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 750, Philadelphia, PA 19106. (800) 552-5866 or (215) 574-2210. Summary: This article reviews the detection of osteoporosis in patients with inflammatory bowel disease (IBD). The author stresses that the risk of osteoporosis is increased in patients with inflammatory bowel disease, particularly in those with additional strong risk factors such as glucocorticoid therapy, hypogonadism, and past history of fragility fracture or malnutrition. Where possible, bone densitometry should be performed to identify those in need of treatment, to avoid unnecessary treatment if bone density is normal, and to monitor the effects of treatment designed to prevent bone loss. If bone densitometry is not available, treatment should be advised on the basis of strong risk factors. Hormone replacement therapy should be given to patients with hypogonadism and biphosphonate therapy to those receiving long-term glucocorticoid treatment. The dose of glucocorticoids should be kept to a minimum and, where present, vitamin D deficiency should be corrected. 19 references. (AA-M).

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Review Article: Osteoporosis, Corticosteroids and Inflammatory Bowel Disease Source: Alimentary Pharmacology and Therapeutics. 9(3): 237-250. June 1995. Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001.

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Summary: This review article summarizes current knowledge about the clinical and pathophysiological aspects of osteoporosis. The author reviews the prevalence, pathogenesis, and treatment of osteoporosis associated with inflammatory bowel disease (IBD). The pathogenesis of osteoporosis associated with IBD is theorized to be multifactorial, with corticosteroid therapy, calcium and vitamin D deficiency, hypogonadism, and malnutrition all potential contributory factors. The author stresses that bone density measurements to predict fracture risk and to define thresholds for prevention and treatment should be performed routinely in patients with inflammatory disease. Hormone replacement therapy is effective in prevention of bone loss in peri-and postmenopausal patients, but the treatment of younger women and men of all ages requires further study. 9 figures. 5 tables. 115 references. (AA-M). •

Osteoporosis: A Serious Complication of Inflammatory Bowel Disease. (editorial) Source: European Journal of Gastroenterology and Hepatology. 6(9): 757- 760. 1994. Summary: This editorial describes recent advances in the understanding of osteoporosis associated with inflammatory bowel disease (IBD). The authors stress that the growing evidence that IBD is a major risk factor for osteoporosis should encourage clinicians to monitor bone density in patients with IBD and to introduce prophylactic measures where needed. Topics include an overview of osteoporosis and its risk factors; osteoporosis in IBD; recommendations for clinical practice; investigations used, including bone densitometry, radiology, and bone biopsy; and prophylaxis and treatment considerations, including nutrition, corticosteroid therapy, lifestyle risk factors, estrogen deficiency, and other drug treatment. 36 references. (AA-M).

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Osteoporosis and IBD Source: Foundation Focus. p. 20-21. November 1993. Contact: Available from Crohn's and Colitis Foundation of America, Inc. 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 932-2423 or (212) 685-3440. Summary: This newsletter article, written for people with inflammatory bowel disease (IBD) discusses osteoporosis. Written in a question-and-answer format, the article covers topics including a definition of osteoporosis, risk factors for developing osteoporosis, why corticosteroids present a risk, how often osteoporosis occurs in people who take corticosteroids, therapeutic alternatives available for people who rely on corticosteroids but risk developing osteoporosis, how to know if osteoporosis is present, preventing osteoporosis, considerations for people who are lactose intolerant, and information for people who have already developed osteoporosis. 1 figure.

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Osteoporosis: How Women With Diabetes Are Affected Source: Diabetes Forecast. 56(5): 41-42. May 2003. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Osteoporosis is a bone condition characterized by low bone mass and poor bone quality. Regardless of age or type of diabetes, many women may be experiencing bone loss, already have osteoporosis and not know it, or both. This article helps women with diabetes to know their risk factors and understand strategies to help prevent osteoporosis. The author reviews normal bone physiology and the impact of type 1 and type 2 diabetes on that bone metabolism. The author also considers how body mass

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index (BMI) influences bone mass density, the role of hormone replacement therapy (HRT), and various risk factors that can put women at risk for developing fractures. •

Are You at Risk for Osteoporosis? Source: Clinical Diabetes. 20(3): 158. Summer 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Osteoporosis is a bone condition defined by low bone mass, increased fragility, decreased bone quality, and an increased fracture risk. This patient handout covers the risk factors for osteoporosis and discusses specific concerns that patients with diabetes may encounter. Osteoporosis can cause many changes that the patient may not notice but that can be identified through screening tests. The fact sheet stresses the importance of regular screening for people who may be at risk for osteoporosis. If osteoporosis is found, treatment can be started to avoid bone fractures. Bone mineral density testing provides an easy and accurate measure of risk for osteoporosis. The fact sheet concludes by noting the many different drugs are available for treating osteoporosis. This patient handout accompanies an article for health professionals on the interrelationship between diabetes and osteoporosis.

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Osteoporosis and Diabetes Source: Clinical Diabetes. 20(3): 153-157. Summer 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Osteoporosis is a bone condition defined by low bone mass, increased fragility, decreased bone quality, and an increased fracture risk. This article reviews the interrelationship between osteoporosis and diabetes. The authors focus on the importance of identifying and evaluating populations at increased risk of developing osteoporosis in order to achieve optimal levels of disease prevention and management. The article covers modifiable and non-modifiable risk factors for osteoporosis; type 1 diabetes; type 2 diabetes; gestational diabetes; prevention; evaluation; and treatment including nonpharmacological and pharmacological (drug) therapies. Having either type 1 or type 2 diabetes increases a patient's risk of developing an osteoporosis-related fracture. Bone mineral density (BMD) measurements, although supportive of the diagnosis of osteoporosis in the diabetes population, are not fool proof assessment tools. All diabetes-related factors should be considered in assessing osteoporosis, and fracture risk reduction should be recommended to patients with diabetes. A educational patient handout on the interrelationship between diabetes and osteoporosis accompanies this article. 3 tables. 35 references.

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Preventing Osteoporosis: Bone Up On Health Source: Diabetes Forecast. 54(4): 33-35. April 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article uses a question and answer format to provide women with information on osteoporosis. This bone disease, which usually goes unnoticed until fractures in the hip and spine occur, is characterized by low bone mass and thinning of the bone tissue. Factors that put some women at risk for losing bone include estrogen

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deficiency, smoking, physical inactivity, steroid usage, inappropriate thyroid medication dosage, body type, and nutritional deficiencies. Osteoporosis is a concern because it can lead to fractures of the spine, hip, and wrist; result in loss of height and back pain; and limit activity. The disease can be monitored by bone scan that measures bone density. Osteoporosis can be prevented by consuming adequate amounts of calcium and vitamin D, taking medications as prescribed to treat thyroid or parathyroid conditions, being as active as possible, quitting smoking, reducing alcohol intake, and taking certain medications. •

Bone up on Osteoporosis Source: Diabetes Forecast. 54(5): 62, 63. May 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reviews ways women with diabetes can reduce their risk of osteoporosis. This condition occurs when bone loss outpaces bone formation. Risk factors include being Caucasian or Asian, having a family history of the disease, consuming too much alcohol, being thin and small boned, smoking, eating a diet low in calcium, being postmenopausal, and having type 1 diabetes. Osteoporosis can be caused by eating disorders, lactose intolerance, physical inactivity, or a vitamin D deficiency. Osteoporosis can be treated and prevented when identified early. Dual energy x-ray absorptiometry (DEXA) is a painless test that can detect the presence and extent of bone loss. Options for preventing or reducing bone loss include undergoing drug treatment with estrogen, alendronate, and risedronate; consuming an adequate amount of calcium; and exercising.

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Osteoporosis in Patients with Diabetes Source: Practical Diabetology. 17(2): 6-8, 11-14. June 1998. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: This article uses a question and answer format to address unresolved issues related to the occurrence of osteoporosis in patients with diabetes. Topics include the epidemiology and demographics of osteoporosis in people with diabetes, the effects of diabetes on bone, the assessment of patients with osteoporosis, the impact of diabetes treatment on osteoporosis, the impact of osteoporosis treatment on diabetes, and the management of patients with both diseases. Although numerous investigations have attempted to determine the incidence of osteoporosis in people with diabetes, evidence concerning the presence of osteoporosis in people with type 1 and type 2 diabetes is controversial. Diabetes does have multiple nonspecific effects on bone, but there does not appear to be a specific diabetic bone disease. Insulin affects bone mass, and the microarchitecture of bone may be altered in people with diabetes. Diabetic complications and diabetic treatment may increase the risk of osteoporosis. Some aspects of osteoporosis treatment, including hormone replacement therapy, may affect diabetes. Physicians caring for patients with both osteoporosis and diabetes should address dietary issues, suggest exercise and lifestyle interventions, assess the risks and benefits of their goals for glucose management, and counsel patients on ways to prevent falls. 3 figures. 2 tables.

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What You Should Know About Osteoporosis Source: Diabetes Self-Management. P. 38-42. September-October 1993. Summary: This article explains simple preventive strategies for avoiding the problems of osteoporosis, as well as some helpful treatments for those who have already developed osteoporosis. Topics include assessing bone mass with bone densitometry; controlling risk factors for osteoporosis, including the role of calcium, vitamin D, exercise, and estrogen replacement therapy; treatments for osteoporosis, including calcitonin, and phosphate derivatives; and falls and fractures. The authors focus on prevention of osteoporosis as the best approach, especially for women with diabetes. The article concludes with the contact information for the National Osteoporosis Foundation.

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Osteoporosis in End-Stage Renal Disease Source: Seminars in Nephrology. (19)2: 115-122. March 1999. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: This article describes how maintaining the intricate bone mineral homeostasis in patients with chronic renal failure (CRF) and renal osteodystrophy is a complex and challenging process. In addition to the well described high turnover bone disease caused by secondary hyperparathyroidism and low turnover disease in the form of osteomalacia (either from aluminum or a dynamic bone disease), osteopenia is also present in end-stage renal disease (ESRD) patients. In contrast to abnormalities in the ability of bone to remodel (osteodystrophy), osteopenia is a deficiency in bone mass or volume. The prevalence of fractures in dialysis patients, regardless of histomorphometry (e.g., their bone mineral density) appears to exceed that observed in elderly women. This osteopenia occurs in CRF patients secondary to multiple factors that include hypogonadism, medications (such as corticosteroids), immobilization, and the typical osteopenia associated with aging. Abnormalities in bone turnover may contribute to abnormalities in bone mass, and, conversely, decreased bone mass caused by other factors could amplify the risk of fracture in dialysis patients. 2 figures. 3 tables. 61 references. (AA-M).

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Oral Bone Loss, Osteoporosis, and Preterm Birth: What Do We Tell Our Patients Now? Source: Compendium of Continuing Education in Dentistry. 22(1): 22-27. 2001. Contact: Available from Dental Learning Systems. 241 Forsgate Drive, Jamesburg, NJ 08831. (800) 926-7636. Summary: The relationship between oral diseases, such as periodontal disease, and systemic diseases continues to fascinate researchers and clinicians. Growing evidence suggests an association between periodontal disease and other systemic illness, including osteoporosis (loss of bone density), cardiovascular disease, and diabetes. Researchers are also tracking an association between periodontal disease and preterm birth. An 'association' simply suggests a higher prevalence (or incidence) of one disease with another; it does not prove that one disease causes the other or determines the best modalities of treatment for either. This article reviews the interrelationships of oral bone loss, osteoporosis, and preterm (premature) birth. The authors discuss the possible links between preterm birth and periodontal disease, the common risk factors for both osteoporosis and periodontal disease, the treatment and prevention strategies for these

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two diseases, and the role of the dentist in informing the patient about these risk associations. The authors note that the role of the dentist in informing the patient is increasingly complex. Dentists must first examine for, diagnose, and treat intraoral bone loss, such as periodontal disease. But they must also be knowledgeable about the risk factors common to both diseases and be educated about the latest information on treatments for osteoporosis as well as their possible efficacy for the treatment of periodontal disease. 3 figures. 4 tables. 32 references. •

General and Oral Aspects of Osteoporosis: A Review Source: Clinical Oral Investigations. 5(2): 157-161. June 2001. Contact: Available from Springer-Verlag, New York Inc. Journal Fulfillment Services Department, P.O. Box 2485, Secaucus, NJ 07096-2485. Fax (202) 348-4505. Summary: This review article offers a short summary of up to date clinical knowledge of systemic osteoporosis (a condition characterized by abnormal loss of bone density) in order to focus on the clinical dental studies on osteoporosis of the jaws. Diagnosis of jaw osteoporosis requires assessment of the bone mineral content (BMC) or density (BMD) using specially constructed jaw bone scanners and the development of a corresponding gender-related set of normal BMC and BMD values for young adults, as in other sites of the skeleton. If other factors are excluded, jaw osteoporosis may involve the risk of minor accentuation of alveolar bone loss after wearing a full denture, in cases of periodontitis and in peri-implant areas. However, implant-supported overdentures conserve bone because of their positive load-related effect on the jaw. Estimation of BMC and BMD is also advisable for edentulous (without teeth) patients with osteoporosis. Systemic treatment involving the bone metabolism affects the jaw BMC and BMD positively or negatively as in other skeletal sites, but the magnitude of this effect is site-specific. Future studies of the effect of biphosphonates on the jaw BMC and alveolar bone loss, and analyses of the bone quality and jaw BMC and BMD in relation to implant treatment, without or with bone transplantation, are required. 1 figure. 5 tables. 115 references.

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Postmenopausal Bone Loss and Osteoporosis as Possible Risk Factors in Periodontal Disease: An Update Source: Ontario Dentist. 78(1): 31-36. January-February 2001. Contact: Available from 4 New Street, Toronto, ON M5R 1P6. (800) 387-1393. Fax (416) 922-9005. Website: www.oda.on.ca/. E-mail: [email protected]. Summary: This article considers the role of postmenopausal bone loss and osteoporosis as possible risk factors in periodontal disease. The author reviews current research and conclusions in the areas of peak bone mass and bone loss, osteoporosis and osteopenia, the relationship between systemic and mandibular (lower jaw) bone density, common risk factors for both osteoporosis and periodontal disease, and common strategies for the treatment of osteoporosis and periodontal disease. The author concludes that while a relationship between osteoporosis and oral bone loss has long been postulated, the existing studies have been preliminary in nature. The author calls for longitudinal studies that could make it possible to determine if the progression of periodontal disease is more rapid in patients with osteopenia than in patients with normal bone density. This, in turn, may lead to better diagnostic measures and treatment outcomes for both periodontal disease and osteoporosis. 4 tables. 22 references.

22 Osteoporosis

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Osteoporosis, Alveolar Bone Loss, and Drug Development Source: General Dentistry. 48(3): 218-225. May-June 2000. Contact: Available from Academy of General Dentistry (AGD). 211 East Chicago Avenue, Chicago, IL 60611. 312-440-4300. E-mail: [email protected]. Website: www.agd.org. Summary: This article reviews research in the areas of osteoporosis, alveolar bone loss, and drug development. The author first summarizes research showing the connection between osteoporosis and alveolar (jaw bones) loss, then discusses studies on inflammatory factors for alveolar bone metabolism. The final section focuses on drug development studies. Drug development to arrest alveolar bone loss is predicated on agents that arrest the course of osteoporosis, such as the biphosphonates, and agents that block the production of inflammatory factors, such as the NSAIDs (nonsteroidal anti-inflammatory drugs). 37 references.

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Building a Better Mousetrap: Toward an Understanding of Osteoporosis Source: JADA. Journal of the American Dental Association. 130(11): 1632-1636. November 1999. Summary: In this article, the author reviews osteoporosis, with a eye toward the implications of osteoporosis for oral health. Osteoporosis is the most common human bone disease; it weakens bones slowly and steadily over time until they break under stresses that should not cause fractures. The author discusses risk factors, including differences in incidence by gender; the economic effects of osteoporosis; osteoporosis treatments, including estrogen therapies, calcitonin, alendronate, raloxifen, and treatments under investigation; the genetics of osteoporosis, current National Institutes of Health (NIH) research on osteoporosis and related bone diseases; and risk factors, including female gender, inadequate calcium intake, and lack of weight bearing exercise. The author concludes by encouraging health professionals to focus on osteoporosis and its prevention. One sidebar offers a list of organizations to contact for further information (including web sites). 21 references.

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Osteoporosis: A Case Study Source: Access. 13(10): 31-34. December 1999. Contact: Available from American Dental Hygienists' Association. 444 North Michigan Avenue, Chicago, IL 60611. Summary: This case study familiarizes dental hygienists with the oral manifestations of osteoporosis and the advances in the prevention, detection, and treatment of the disease. The case study describes a 62 year old female who came to the dental office for a recall appointment. In updating her medical history, she stated that her physician had prescribed Fosamax (sodium alendronate) following a bone density assessment that revealed osteoporosis. The authors review the patients oral and radiographic examination of this patient, then discuss osteoporosis in general, its prevalence, etiology and risk factors, diagnosis, prevention, and treatment. The authors discuss the role of exercise, hormone replacement therapy (HRT), and other prescription therapies. Dental hygienists are encouraged to take an active role in assessing clients for osteoporosis, including assessing the risk factors for the disease: smoking, early menopause, inactivity, milk allergies, and excessive use of alcohol. The dental hygienist should not hesitate to discuss with clients the signs, symptoms, and oral manifestations of osteoporosis. 1 figure. 1 table. 15 references.

Studies 23

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Osteoporosis and Aveolar Bone Loss Source: PROBE. 32(1): 11-13. January-February 1998. Contact: Available from Canadian Dental Hygienists Association (CDHA). 96 Centrepointe Drive, Nepean, Ontario, Canada K2G 6B1. (800) 267-5235. Fax (613) 2247283. Summary: A primary focus of dental hygiene is the prevention and treatment of periodontal diseases and the maintenance of oral health. Dental hygiene professionals, who are taking and increasingly comprehensive approach towards dental hygiene care, must be knowledgeable about the oral implications of systemic diseases. This article reviews current literature on the possible relationship between osteoporosis and oral bone loss. Both animal and human studies have been undertaken in this area. The authors stress that, although osteoporosis generally affects the elderly, preventive actions must start much earlier in life. The authors note the difficulties in interpreting levels of bone mass loss relative to osteoporosis; controversy remains as to whether osteoporosis is manifested in alveolar bone and whether bone quality, quantity, or both, is affected. Prevention and treatment strategies are outlined briefly, with the authors encouraging dental hygienists to watch for clues in their patients. Clients need to be asked about diet and calcium intake. Periodontal bone loss should be monitored closely. Just as dental hygienists do not hesitate to refer a client for a suspicious oral lesion, they should not hesitate to discuss signs, symptoms, and oral manifestations of osteoporosis and the possible need for referral. 18 references. (AA-M).

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Osteoporosis: A Possible Modifying Factor in Oral Bone Loss Source: Annals of Periodontology. 3(1): 312-321. July 1998. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611. (312) 787-5518. Fax (312) 787-3983. Website: www.perio.org. Summary: There has been increasing interest in the interrelationship between systemic osteoporosis, oral bone loss, tooth loss, and risk factors for these conditions. Because the severity of alveolar bone loss increases with age, it has long been hypothesized that it may, in part, be related to systemic conditions that also predispose the patient to osteoporosis or osteopenia. This paper reviews the risk factors for osteoporosis and periodontitis, as well as the evidence that loss of oral bone mineral may be related to systemic osteopenia. The author also explores the evidence that therapies designed to influence systemic bone mineral density, such as hormone replacement and biphosphate therapy, may be associated with less tooth loss and a slower loss of alveolar bone, respectively. The author reports on current research efforts, particularly those undertaken since the 1992 NIH Workshop of Osteoporosis and Oral Bone Loss. 6 tables. 50 references. (AA-M).

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Osteoporosis and Oral Bone Loss Source: Dentomaxillofacial Radiology. 26(1): 3-15. January 1997. Contact: Available from Stockton Press. 345 Park Avenue South, 10th Floor, New York, NY 10010-1707. (212) 689-9200. Fax (212) 689-9711. Summary: This article is a review of the literature on the possible association between osteoporosis and oral bone loss, with an emphasis of radiological studies. This association was first suggested in 1960. Subsequent studies showed that after the age of

24 Osteoporosis

50, there was a marked increase in the cortical porosity of the mandible (lower jaw), with this increase being greater in the alveolar bone than the mandibular body. With this increase in porosity, there was a concomitant decrease in bone mass, which appeared to be more pronounced in females than in males. The loss in bone mineral content was estimated to be 1.5 percent per year in females and 0.9 percent in males. Subsequent clinical studies reported associations between the bone densities of jaws and metacarpals, forearm bones, vertebrae, and femurs. The researchers suggested that systemic factors responsible for osteoporotic bone loss may combine with local factors (i.e., periodontal diseases) to increase rates of periodontal alveolar bone loss. Although not all studies found associations between osteoporosis and oral bone loss, the conclusion of this review is that such an association exists. Additional longitudinal investigations are needed to confirm this and inexpensive methods must be developed for sensitive and specific measures of oral bone loss. 141 references. •

Mandibular Bone Mineral Density as a Predictor of Skeletal Osteoporosis Source: British Journal of Radiology. 69(827): 1019-1025. November 1996. Contact: Available from British Journal of Radiology c/o Mercury Airfreight Int. Ltd. 2323 Randolph Avenue, Avenel, NJ 07001. Summary: A considerable amount of work has been performed on methods of detecting individuals with low bone mass at an early stage. This article reports on a study undertaken to investigate the relationship between mandibular (lower jaw) bone mineral density (BMD) and that of other skeletal sites commonly used for bone densitometry in the detection of osteoporosis. The second aim was to assess the validity of mandibular BMD as a predictor of BMD in these other sites. The study included 40 edentulous females who underwent various dual energy x-ray absorptiometry (DXA) investigations. Significant correlations were observed between BMD in the mandibular body, ramus and symphysis and all other skeletal sites. Where a diagnostic threshold for low mandibular BMD was set at one standard deviation below the mean, the mandibular body BMD measurement gave high sensitivity and specificity, the symphysis BMD low sensitivity but a high specificity, while the ramus BMD had a moderate level of sensitivity and high specificity. It is concluded that mandibular (lower jaw) BMD assessed by DXA correlates significantly with BMD measurements of other important skeletal sites. The authors conclude that this site should be used for any potential clinical application of dental radiographs in detection of osteoporosis. 1 figure. 4 tables. 28 references.

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Osteoporosis and Periodontal Disease: A Review Source: CDA Journal. California Dental Association Journal. 22(3): 69-75. March 1994. Contact: Available from California Dental Association (CDA). 1201 K Street, Sacramento, CA 95814. (916) 443-0505. Summary: This article reviews existing information on the relationship between osteoporosis and periodontal disease. The authors present background information concerning osteoporosis and periodontal disease, summarize the animal and human research on possible interrelationships between the two diseases, and suggest areas that need further research. The authors conclude that there is histologic and radiographic evidence from animals and man that osteoporosis does affect alveolar bone by decreasing bone mass and trabeculation. Studies suggest that a greater percentage of patients with osteoporosis are edentulous than patients without osteoporosis; the reason for this finding has not been explained. 3 tables. 34 references.

Studies 25

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Systemic Osteoporosis and Oral Bone Loss: Evidence Shows Increased Risk Factors Source: JADA. Journal of the American Dental Association. 124(11): 49-56. November 1993. Summary: This article reviews the risk factors for systemic osteoporosis and explores the role of the dentist in diagnosis and referral for treatment of this problem. Topics covered include the links between periodontitis, residual ridge resorption, and age-related systemic osteoporosis; the morbidity caused by oral bone loss; the prevalence of residual ridge resorption; the mechanisms of bone loss; terminology used in this area; and efforts toward preventing oral bone loss, including plaque control, prevention of tooth loss, and identification of patients at risk for bone loss. The authors also discuss the use of intraoral radiographs to identify patients at risk. 5 figures. 3 tables. 42 references.

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Post-Menopausal Bone Loss and Its Relationship to Oral Bone Loss Source: Periodontology 2000. 23(1): 94-102. June 2000. Contact: Available from Munksgaard International Publishers Ltd. Commerce Place, 350 Main Street, Malden, MA 02148-5018. (781) 388-8273. Fax (781) 388-8274. Summary: Osteoporosis and osteopenia are characterized by reductions in bone mass and both may lead to skeletal fragility and fracture. This article reviews postmenopausal bone loss and its relationship to oral bone loss. Women are at greater risk for osteoporosis after menopause. The authors review this risk factor and others, discuss methods used to measure of bone mass and density, consider the relationship between systemic and mandibular (lower jaw) bone density, report preliminary data from the Women's Health Initiative Oral Ancillary Study, and outline common strategies for treatment of osteoporosis and periodontal disease. The authors conclude that while a possible relationship between osteoporosis and oral bone loss has long been postulated, the existing studies have been preliminary in nature. Longitudinal studies will make it possible to determine if the progression of periodontal disease is more rapid in patients with osteopenia than in patients with normal bone density. 6 figures. 3 tables. 52 references.

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Role of Osteopenia in Oral Bone Loss and Periodontal Disease Source: Journal of Periodontology. 67(10 Supplement): 1076-1084. October 1996. Summary: This article considers the role of osteopenia in oral bone loss and periodontal disease. Osteopenia is a reduction in bone mass due to an imbalance between bone resorption and formation, resulting in demineralization and leading to osteoporosis. Periodontitis is characterized by inflammation of the supporting tissues of the teeth, resulting in resorption of the alveolar bone as well as loss of the soft tissue attachment to the tooth; it is a major cause of tooth loss and edentulousness in adults. The authors review the studies in which the relationship of osteopenia to oral bone loss and periodontal disease has been addressed. They note that interpretation of the literature is complicated by the variety of methods used to assess osteopenia, oral bone mass, and periodontal disease. The authors also present the results of a previously unpublished study which suggest that severity of osteopenia is related to loss of alveolar crestal height and tooth loss in post-menopausal women. Clearer understanding of this relationship may aid health care providers in their efforts to detect and prevent osteoporosis and periodontal diseases. 3 tables. 108 references. (AA-M).

26 Osteoporosis

Federally Funded Research on Osteoporosis The U.S. Government supports a variety of research studies relating to osteoporosis. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to osteoporosis. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore osteoporosis. The following is typical of the type of information found when searching the CRISP database for osteoporosis: •

Project Title: 1H MRS TO DIAGNOSE BONE WEAKENING FROM AGING /INACTIVITY Principal Investigator & Institution: Schellinger, Dieter; Professor; Radiology; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2003 Summary: Dual energy X-ray absorptiometry (DEXA) measures bone density which may be only one of several elements responsible for biomechanical competence. It has been suggested in the literature that bone strength is multi-factorial and may depend not only on bone density but also on bone marrow quality. 1H MRS of human vertebra has been used to quantify both fat content and bone density measurement. It is believed that an animal study will allow a more precise and systematic correlation between a) bone fat content and age and b) bone fat content and experimentally induced bone involution / osteoporosis.. Therefore an animal model will allow to confirm experiences and insights obtained in the human study. It is hypothesized: (I) that increased marrow fat content, as seen with aging and with certain pathologic bone conditions, i.e. osteoporosis, can affect bone strength and that lipid-water ratio (LWR), fat fraction (FF) or per cent fat fraction (%FF) can quantify bone fat content; (II) that susceptibility changes due to the trabecular bone loss cause line width (LW) narrowing. The goal of this proposal is to use an animal model (rat tibia) to acquire both LWR and LW as an objective method to evaluate age related bone changes and predict bone weakening. To achieve the goal we have the following research design. 1) Specific Aim #1: To determine age dependence of LWR and LW. In group A, twelve healthy female rats, 3 animals in the age categories of 3, 12 , 21, 30 months, will be submitted to hindleg tibial NM and 1HMRS on nine occasions. The first measurements are obtained after one week of acclimatization. This will be followed by measurements at monthly intervals, for a total of 8 followup examinations. LWR and LW functions will be determined and correlated to the age of the animals. Both LWR and LW data will be tabulated in 1month increments and analyzed using the linear regression method and polynomial fit respectively. 2) Specific Aim #2: To determine the dependence of LWR and LW on bone

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies 27

involution / osteoporosis in tibiae of partially immobilized, back-suspended rats. In group B, twelve female Wistar rats will be used. There will be three animals in each age category (3, 12, 21, and 30 months). These animals will be submitted to hindleg tibial NM and 1HMRS after a period of back-suspension. The period of back suspension will be 3 weeks. Each animal of group B will first undergo MRI and 1H MRS after one week of acclimatization. The animals will then be back-suspended for three weeks and scanned at 7,14 and 21 days of back suspension. This experimental protocol will be used for all four age groups (3,12, 21, 30 months of age). Both LWR and LW will be measured versus the degree of inactivity. Each subset of data (totals 3 subsets) will be tabulated and be analyzed against the corresponding age normal rats (group A) using two-tailed Student t-test method. P < 0.05 is considered significant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: 5 LIPOXYGENASE IN BONE Principal Investigator & Institution: Bonewald, Lynda F. Lefkowitz Professor; Oral Biology; University of Missouri Kansas City Kansas City, MO 64110 Timing: Fiscal Year 2001; Project Start 01-MAY-1993; Project End 31-AUG-2003 Summary: The underlying hypothesis for this application is that metabolites of the enzyme 5-lipoxygenase (5LO) play an important role in bone by stimulating osteoclastic bone resorption and inhibiting osteoblastic bone formation. 5LO metabolites of arachidonic acid may also be partially responsible for the bone loss which occurs due to estrogen deficiency. The specific aims of the proposal are: 1. To determine if the osteoclast is a producer of 5LO metabolites. 2. To determine the effects of 5LO metabolites on osteoblast function. 3. To characterize the dynamic and static features of bone in the 5LO knockout mice, and 4. To determine if 5LO plays a role in the increased bone loss associated with estrogen withdrawal. For Specific Aim 1, in situ hybridization for 5LO mRNA expression in bone and bone cells and quantitation of 5LO metabolite production by isolated osteoclasts will be performed. To determine if bone resorbing agents regulate mRNA and protein for 5LO, ribonuclease protection assays, immunoprecipitation, and immunoblotting will be performed. For Specific Aim 2, the effects of 5LOand bone-like nodule formation will be tested, as well as effects one bone formation in calvarial organ cultures. Osteoblast function in 5LO knockout animals will be compared to osteoblast function in wild- type animals. As the 5LO knockout mice have increased cortical bone, Specific Aim 3 will be performed to determine if this increase in bone is due to a decrease in osteoblast numbers or activity, an increase in osteoblast function, or a combination. The biomechanical properties of these bones will also be determined. In Specific Aim 4, it will be determined if 5LO metabolites mediate the effects of estrogen withdrawal by comparing bone loss in ovariectomized 5LO knockout mice with their wild-type controls. The proposed studies will provide important new insights into the role of 5LO metabolites in bone-a research are which is so far relatively unexplored. These studies may have clinical relevance to bone diseases such as osteoporosis and bone loss due to inflammatory conditions. Hence, these studies may also have profound implications for the increasing number of asthmatic patients who are currently being treated with steroids and 5LO inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: A NEW SYSTEM FOR ULTRASONIC BONE ASSESSMENT Principal Investigator & Institution: Kaufman, Jonathan J. President& Ceo; Cyberlogic, Inc. 611 Broadway, Ste 707 New York, NY 10012

28 Osteoporosis

Timing: Fiscal Year 2002; Project Start 01-NOV-1997; Project End 31-AUG-2004 Summary: (provided by applicant): The long-term objective of this research is to establish ultrasound as a safe, effective, and non-invasive method for assessing fracture risk, an important component in clinical management of osteoporosis.. Osteoporosis afflicts over 20 million people in the U.S., responsible for more than 275,000 hip fractures annually. Currently, the primary means for assessment relies on densitometric techniques. These methods subject the patient to ionizing radiation, are relatively expensive, and do not always provide good estimates of bone strength. Ultrasound offers several potential advantages. It is non-ionizing and relatively inexpensive. Moreover, since ultrasound is a mechanical wave and interacts with bone in a fundamentally different manner than electromagnetic radiation, it may be able to provide more accurate estimates of bone strength compared with current densitometric methods. The goal of this research is to significantly improve the effectiveness of current ultrasonic bone assessment techniques by demonstrating the feasibility of a new ultrasonic system to assess bone. The system employs a novel parametric signal processing approach which is ideally suited for analog and real-time implementation. Thus this research may enable less expensive and easier to use ultrasound devices, which are also less sensitive to various experimental artifacts. The specific aims are to measure a set of new ultrasonic parameters and compare them with presently used features, namely BUA and ultrasound velocity, in calcaneal bone samples. A comparison will be made of their respective capabilities to estimate bone density and bone strength. This comparison will include cost, ease of use, and accuracy and precision of the bone density and bone strength estimates. PROPOSED COMMERCIAL APPLICATION: Osteoporosis is a major health concern in the United States, afflicting over 20 million people, and whose incidence is increasing as the average age of the U.S. population increases. An effective, relatively inexpensive and safe technique such as ultrasound for assessing osteoporosis would be an extremely emportant benefit to the patient population, and represents an enormous commercial opportunity. Ultrasound's importance will grow as various new pharmacologic agents are approved for treatment, thus requiring periodic assessments of efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A NOVEL STRATEGY FOR OSTEOPOROSIS GENE THERAPY Principal Investigator & Institution: Douglas, Joanne T. Assistant Professor; Pathology; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2004 Summary: (Taken from the application): Osteoporosis is a group of diseases of diverse etiology in which the rate of bone resorption by osteoclasts exceeds that of bone formation by osteoblasts, resulting in a reduction in the mass of bone per unit volume. Patients with end-stage, 1ow-turnover osteoporosis do not respond to existing therapies. Osteoblasts in end-stage osteoporosis can be activated by parathyroid hormone (PTH); however, this also invokes an increase in osteoclastic activity that limits the effectiveness of this approach. In this project, we propose to develop a gene therapy method to allow PTH activation of osteoblasts that will have reduced ability to produce RANKL, a key regulator of osteoclastogenesis. We hypothesize that this could be accomplished by employing an intracellular single-chain antibody (sFv) to achieve osteoblast-specific downregulation of RANKL. This approach mandates the use of a gene delivery vehicle, or vector, which can target expression of the sFv specifically to osteoblasts. Capitalizing on the ability of recombinant adenoviral (Ad) vectors to accomplish efficient gene transfer, we hypothesize that Ad-mediated gene delivery can

Studies 29

be targeted specifically to osteoblasts. The first Specific Aim is to develop an Ad vector targeted to osteoblasts at the transductional and transcriptional levels. Transductional targeting will be achieved using a bispecific antibody with specificities for the adenovirus fiber protein and an osteoblastrelated marker protein, while transcriptional targeting will be achieved by placing the transgene under the control of the osteoblastspecific osteocalcin promoter. The second Specific Aim is to derive an intracellular sFv to selectively downregulate the expression of RANKL. In the third Specific Aim, we will employ the targeted Ad vector to direct the intracellular expression of this sFv specifically within osteoblasts and will determine whether the downregulation of RANKL results in a reduction in osteoclast recruitment in vitro. The realization of these Specific Aims would establish the feasibility of this approach as a rational strategy for gene therapy in patients with end-stage, low-turnover osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A SCHOOL PROGRAM TO ENHANCE BONE HEALTH IN GIRLS Principal Investigator & Institution: Hoelscher, Deanna M. Assistant Professor; Human Nutrition Center; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001; Project Start 20-AUG-1999; Project End 31-JUL-2003 Summary: (Adapted from Applicant's Description): Osteoporosis is a geriatric disease that has pediatric origins. Development of peak bone mass, which is achieved by the third decade of life, is influenced by behaviors during childhood and adolescence, most notably calcium consumption and physical activity. During the pubertal years, 45% of the adult skeletal mass and 15% of adult height are gained. National and local surveys indicate that adolescent girls have inadequate calcium intakes and lower than recommended levels of physical activity. Although school-based programs have shown promise in affecting risk factors for cardiovascular health, application of behaviorallybased programs to target bone health have been limited. The primary goal of this proposal is to develop and evaluate a school-based nutrition and physical activity program, called BONES (Beat Osteoporosis Now by Exercising and Eating Smart), to enhance future bone health in girls. Elements of the BONES program will be based on Social Cognitive Theory (SCT) and will include both behavioral (student-oriented classroom lessons) and environmental (school food service, physical education) components. The program will consist of two phases: a feasibility trial in which intervention materials and measures will be pre-tested and validated, and the main intervention trial. Eighteen ethnically diverse middle schools from central Texas will be randomized into control or intervention conditions, with schools serving as the unit of randomization and analysis. Nine of the schools will receive the 2-year intervention (BONES), while the control schools will continue their usual health programs. It is hypothesized that students in intervention schools will, on average, (1) have a 3% greater calcaneus ultrasound Stiffness Index, (2) consume 2 more servings/day of calcium- containing foods, and (3) engage in 17 more minutes/day of vigorous physical activity compared to students in the control schools. Secondary hypotheses at the student level are: intervention students will (1) demonstrate higher scores in selfefficacy, knowledge of bone health, calcium-containing foods and exercise; and (2) have higher mean intakes of calcium and average greater frequencies of weight bearing type exercises per day compared to students in the control schools. Secondary hypotheses at the school level are: intervention schools will offer (1) more calcium-containing foods; and (2) more opportunities for weight-bearing activities than control schools. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

30 Osteoporosis

•

Project Title: A WEIGHTED VEST TO PREVENT LEG WEAKNESS AND OSTEOPOROSIS Principal Investigator & Institution: Greendale, Gail A. Associate Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 30-JUN-2001 Summary: This project will consist of a 2-year intervention development study (IDS) followed by a 3-year intervention study (IS). The overall objective of the project is to test whether wearing a weighted vest can prevent muscular weakness and osteoporosis.. First, an IDS will be conducted to further refine the vest dose and to assess whether biomechanical approximations of bone loading by vest use can be measured. Second, a randomized controlled trial will be conducted to test the effect of the vest on muscular strength and bone mineral density. The nylon vest can be weighted to a maximum of 12 kg and is prescribed as a percent of body weight (%BW). Subjects wear the vest during routine daily activities (eg, chores, walks) for 2 hours per day, 4 days per week. No additional specific physical activity prescription is required. The IDS will consist of a 27week, 3-armed (control, 3%BW, 5%BW) pre-post study in 60 subjects to compare the effects of these doses on knee extensor strength, side-effects, and adherence. Prior vest studies suggest that 5%BW is the maximum tolerated in this population; thus, maximum and 1/2 maximum dose are selected for the IS. The dose for the RCT will be decided based on the effect of each on: knee extensor strength; safety; and adherence. The IDS will evaluate whether proposed biomechanical measures of hip loading, hip joint reaction forces and hip moments-of-force, change with vest use. The effects of each vest dose on: 1) bone turnover indicators; 2) gait and balance; 3) self-reported functional status and observed physical performance will be assessed. Adherence to vest use 3 and 6 months after the termination of the intervention will also be examined. The IS will consist of a 24-month, single blinded, two armed randomized controlled trial in 66 subjects. It will examine the effects of one dose of the vest (determined by the IDS) compared to an attention control group on the following: 1) total hip BMD; 2) amount and time course of change in isokinetic knee extensor strength; and 3) long-term safety of and adherence to vest use. If the IDS has been successful in quantifying the postulated biomechanical measures of hip loading, a fourth primary objective of the RCT will be to assess the ability of the biomechanical measures to predict changes in BMD, to explore the mechanism by which the vest accomplishes bone tropism. The secondary RCT objectives include measurement of the effect of vest use on: spinal BMD; total body calcium; body composition; bone turnover markers; gait and balance; functional status; and physical performance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADOPTION OF OSTEOPOROSIS SCREENING IN OLDER WOMEN Principal Investigator & Institution: Neuner, Joan M. Medicine; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): At least 40% of postmenopausal women in the United States will suffer an osteoporotic fracture, yet little is known about current physician and patient practices in bone mineral density screening to identify patients at high fracture risk. This proposal describes an integrated, mentored program of career development and research that will lead to the applicant's development into an independent investigator in prevention of fractures in aging patients. The central career development goal of this proposal is to gain skills in both analysis of screening patterns

Studies 31

in large national administrative datasets and in survey methodology through an investigation of patterns in and barriers to the adoption of osteoporosis screening. In sum, at the end of this award, I will have gained skills in sophisticated analyses of national patterns in preventive behaviors, methodology for measuring risk perceptions and health literacy, and survey research. Osteoporotic fractures are very common and cause great morbidity, there are proven interventions to prevent fractures, and guidelines advocating screening have been published. Despite this, evidence from other preventive care suggests adoption of osteoporosis screening will be slow and have unexpected influences. This adoption can be accelerated if current patterns in and barriers to care of osteoporosis are understood. To develop this understanding we aim to 1) Develop a methodology for using Medicare administrative claims data to assess rates of bone mineral density (BMD) testing 2) Examine the adoption of BMD with respect to patient characteristics 3) Examine the use of bone density testing among panels of patients cared for by primary care physicians, 4) Determine the relative contribution of patient and physician factors to adoption of BMD, and 5) Use survey methodology to further explore disparities by factors such as age and SES found in the initial analyses. We will examine Medicare data from women in three states in 1998-2002 linked with physician information from the AMA to examine aims 1-4. We then will survey primary care patients to evaluate the effect of risk perceptions, health literacy and numeracy, and other barriers on patient disparities in screening. It is important that we identify patients at greatest risk for lack of osteoporosis screening, the providers who employ it least, and patient reports of barriers to screening to improve future osteoporosis care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALENDRONATE, OSTEOPOROSIS

MIACALCIN

IN

POSTMENOPAUSAL

Principal Investigator & Institution: Brzezinski, W A.; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANABOLIC ACTIONS OF CA2+-RECEPTOR IN OSTEOBLASTIC CELLS Principal Investigator & Institution: Chattopadhyay, Naibedya;; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 03-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Osteoporosis is a metabolic bone disease with low bone mass and abnormal skeletal microarchitecture that increases bone fragility and, consequently, fracture risk. The skeleton constantly turns over owing to the carefully regulated breakdown of bone by osteoclasts and the ensuing replacement of the missing bone by osteoblasts. Progressive bone loss, with eventual compromise of its structural integrity. is caused by differences in the relative rates of bone resorption and formation, with an excess of the former over the latter. Most available drug treatments for osteoporosis are anti resorptive, inhibiting bone breakdown without directly affecting bone formation. Their effectiveness is necessarily limited, because when bone resorption is reduced, the rate of formation eventually diminishes as well due to the coupling of resorption and formation. Recruitment of osteoprogenitor cells is the most important

32 Osteoporosis

step controlling bone formation rate and is followed by their differentiation to mature, boneforming osteoblasts. A major goal of osteoporosis research is to develop effective anabolic agents that will enhance osteoblast recruitment, differentiation and/or their ability to form mineralized bone. Extracellular calcium (Ca++) exerts various direct actions on the tissues maintaining Ca++ homeostasis, several of which are mediated by the Ca++ sensing receptor (CaR) cloned in 1993. High Ca++ also has direct actions on bone cells, stimulating the proliferation and chemotaxis of preosteoblasts and their differentiation to osteoblasts actions that could contribute to the known timulatory effect of high Ca++. The preliminary data presented here provide evidence that osteoblast-like cell lines express the CaR. This proposal's overall goal is to prove that the CaR acts on osteoblasts and their precursors to mediate anabolic actions of Ca++ on bone. This work may also provide a foundation for the future development of better treatments for osteoporosis an important cause of morbidity and disability in the aging population worldwide that actually increase bone formation. The specific aims of the proposal are as follows: Aim 1, To show that the CaR mediates high Ca++ evoked chemotaxis and proliferation of preosteoblastic cells, Aim 2, To show that the CaR promotes alkaline phosphatase and osteocalcin expression in osteoblastic cells, which reflect CaR induced differentiation to a more mature phenotype, Aim 3, To show that the CaR enhances the deposition of mineralized bone in vitro by comparing bone formation by osteoblastic cells and calvaria from wild type mice and homozygous CaR knockout mice in culture; and Aim 4, To prove the CaR's role as an important contributor to bone formation in vivo by generating a mouse model with selective "knock out" of the CaR in osteoblasts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANABOLIC AND CATABOLIC ACTIONS OF PTH IN ANIMAL MODELS OF ESTROGEN DEFICIENCY Principal Investigator & Institution: Iida-Klein, Akiko;; Helen Hayes Hospital Rt 9 W West Haverstraw, NY 10993 Timing: Fiscal Year 2001 Summary: Osteoporosis has become a major health problem as the life expectancy of the general population has risen rapidly in recent years. Post-menopausal women are at greater risk because of accelerated bone loss induced by estrogen deficiency superimposed on age related bone loss.. One of the important etiological factors in postmenopausal osteoporosis is the interaction between estrogen and PTH. PTH is known to be an important initiator of bone remodeling and persistent elevation of PTH, such as in hyperparathyroidism, presents as a risk factor for the development of osteoporosis.. However, intermittent administration of PTH has been shown to be a promising regimen for improve bone mass in both the animals and humans. The dichotomy of this issue is not fully understood, especially in the estrogen deficient population. This project attempts to understand further the dualistic role of PTH as a catabolic and anabolic hormone in animal models of estrogen deficiency. The proposed study will have the following specific aims. Specific Aim 1. To differentiate the anabolic action of continuous elevation of PTH from its catabolic action. Specific Aim 2. To demonstrate the interactions of dietary calcium intakes with continuous and intermittent PTH administration under estrogen deficiency state, and Specific Aim 3. To study the interactions of PTH, cytokines and anti-resorptive agents at both tissue and subcellular levels in a mouse model of estrogen deficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies 33

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Project Title: ARTHRITIS

ANDROGEN

AS

ADJUNCT

THERAPY

IN

RHEUMATOID

Principal Investigator & Institution: Davis, John C. Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 30-JUN-2003 Summary: Rheumatoid arthritis (RA) is a chronic, debilitating multisystem disease affecting nearly two million persons in the United States alone. The incidence of RA in men under the age of forty-five is less than that reported in women, however the incidence approaches that of women in older age groups of men. This increased incidence in males coincides with decreasing levels of sex hormones. A hypogonadic condition characterized by low serum testosterone has been previously described in male RA patients compared with age-matched controls with osteoarthritis, ankylosing spondylitis and healthy controls. Patients with RA have significant disability with decreased function over time. Androgens have the potential to increase nitrogen retention, lean body mass, strength, and body weight which could slow the decline in function. Patients with RA also have both local and systemic forms of osteoporosis.. There is evidence that androgens may stimulate the proliferation and differentiation of osteoblasts and osteoblast-like cells in vitro which may help reduce the rate of bone loss in RA. Previous studies in both animal models and humans seem to suggest that androgen administration may be beneficial in a number of autoimmune diseases including RA. In this study, we will examine the role of transdermal testosterone versus placebo in male patients with RA over a two-year period. Specifically, we will examine (1) the effect of testosterone on lean body mass and muscle strength with the use of whole body dual xray absorptiometry (DXA) scan and muscle strength testing, (2) the effect of testosterone on bone mineral density by DXA scan of the spine and hip, and (3) the effect of testosterone on disease specific measures of quality of life with validated instruments for quality of life. Additionally, measure of disease activity and side effects will also be assessed. The results of this study will (1) help to define the role of androgen administration and its effects on function through assessment of muscle mass and strength, (2) explore the potential benefits of testosterone therapy on bone mineral density in patients with both localized and systemic forms of osteoporosis, (3) define changes in quality of life in patients with RA treated with androgen, and (4) help to define the potential role of androgen therapy in other systemic illnesses where muscle wasting has a profound impact on quality of life (e.g. both inflammatory and noninflammatory muscle disease). In addition, this K-23 grant will provide opportunity for further career development through mentorship provided by an committee with multiple areas of expertise and formal education in the areas of clinical research design and conduct, outcome assessment development and analysis, and clinical trial analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BEAT OSTEOPOROSIS: NOURISH & EXERCISE SKELETONS (BONE) Principal Investigator & Institution: Economos, Christina D. None; Tufts University Medford Boston Ave Medford, MA 02155 Timing: Fiscal Year 2001; Project Start 04-JUN-1999; Project End 31-MAY-2004 Summary: Osteoporosis affects more than 28 million Americans and accounts for more than 1.5 million fractures annually, at a cost of 513.8 billion. One of the most effective ways to prevent osteoporosis is to build a strong, dense skeleton during the growing years to act as a reserve in later life. Furthermore, changes in individual behaviors and

34 Osteoporosis

lifestyle preferences in younger children may last through the critical adolescent period and continue into adulthood, providing a lifetime of optimal bone health. The primary aim of this study is to develop, implement and evaluate a multi-faceted intervention in after-school programs that will increase bone accretion and muscular strength in early elementary school children. The intervention will include weight loading physical activity and calcium-rich snacks for children as well as age- appropriate, behaviorally focused active learning to promote skill building and self-competence. It will also include a parent/caregiver communications module that by provides specific activities and practical information to complement and reinforce the direct intervention with the children. A mascot and logo will be used to foster positive attitudes about calcium-rich foods and physical activity; incentives and goal setting will be used to encourage sustained behavior. One thousand eight hundred first and second grade children from 60 after-school programs in up to 10 diverse communities throughout Massachusetts will be randomized and studied for 24 months. Matched program groups will receive either The BONES Project (n=24), The BONES Project plus a parent/caregiver component (n=12); or they will serve as controls (n=24). Follow-up will continue for 12 months after the intervention period. The primary outcomes will be bone quality and muscular strength. Secondary outcomes will include physical activity levels, calcium consumption, body composition, self-perception of physical abilities and appearance, and influencing factors toward relevant healthy lifestyle behaviors, such as knowledge and attitudes. The control group will receive a "delayed" intervention after termination of the 36-month study. Focus group research with after-school program leaders, parents/caregivers, and children prior to initiation will provide information to optimize the campaign design. Findings from this study will promote our understanding of health behaviors in young children and the effect of parental involvement on these behaviors. Implementation of the same intervention within this widely diverse set of communities will guide appropriate cultural, community and socioeconomic-specific modifications and permit easier replication of the program. Because the intervention utilizes the existing after-school framework large numbers of children can be reached. Results from this study will provide an appropriate model for national replication and sustainability of a program to beat osteoporosis by nourishing and exercising skeletons early in life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BEHAVIORAL STRATEGIES TO PREVENT OSTEOPOROSIS IN GIRLS Principal Investigator & Institution: French, Simone A. Associate Professor; Epidemiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: Osteoporosis currently affects over 25 million people in the US. The majority of fractures experienced by older women are related to low bone density independent of age and therefore are osteoporotic in nature. Because calcium intake and physical activity are two modifiable behaviors associated with peak bone mass, interventions targeting these behaviors among youth have tremendous public health potential for preventing osteoporosis.. Youth are particularly important to target for intervention because eating and exercise behaviors track from childhood through young adulthood. The primary aim of the proposed study is to assess the feasibility and effectiveness of a two-year behavioral program to increase calcium intake and physical activity among a cohort of fifth grade girls (age 9-11) enrolled in the Girl Scouts of St Croix Valley and

Studies 35

Greater Minneapolis. Thirty troops will be recruited and randomized to one of two conditions: 1) eating and exercise behavior change program; or 2) no intervention control. Intervention components focus on behavioral skills development, goal setting, and self-monitoring for dietary calcium intake and physical activity, and increasing social support from peers and parents. Intervention will take place during 5th and 6th grade for ten weeks each of two years plus supporting programs during winter and summer breaks. Outcome assessments will be conducted at baseline, six, 12 and 24 months. Primary outcomes are increases over 24 months in: 1) dietary calcium intake (mg/day); 2) physical activity (minutes/week); 3) bone mineral density (mg/cm2/year). Innovative aspects of the proposed study include: 1) a unique focus on behavioral approaches to increase calcium intake and physical activity; 2) a focus on young girls in a free-living setting as they transition into adolescence; 3) an innovative, communitybased intervention implemented in collaboration with the Girl Scouts Councils that could serve as a national model program for osteoporosis prevention among girls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOBEHAVIORAL RISK FACTORS FOR BONE LOSS IN ATHLETES Principal Investigator & Institution: Ward, Kenneth D. Psychology; University of Memphis Memphis, TN 38152 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: Moderate levels of physical activity are associated with a number of health benefits, including reduced risk of coronary heart disease, essential hypertension, diabetes mellitus, and colon cancer. There also is strong evidence that moderate physical activity reduces the risk of osteoporosis by increasing bone mineral levels. However, there is growing evidence that high levels of physical activity, particularly endurancetype activity (e.g., running, soccer, and basketball) causes reductions in bone mineral. Several recent cross-sectional studies have reported reductions in bone mineral among athletes engaged in high levels of activity (runners, cyclists, swimmers) compared to athletes engaged in less intense training. Recent prospective data collected in the investigators laboratory indicate that collegiate athletes engaged in high levels of endurance activity (basketball players) show substantial drops in bone mineral over time. Declines in bone mineral among young athletes are a major public health concern for two reasons. First, a low bone mineral level is a primary risk factor for stress fractures in athletes and young adults. Stress fractures among high school and collegiate athletes are highly prevalent, painful, and costly. Second, bone mineral among young athletes should be increasing during adolescence and young adulthood. Peak bone mass, which typically is not achieved until the third decade of life is a primary determinant of osteoporosis in later life. Thus, exercise-induced bone mineral loss could place adolescents at increased risk of osteoporosis in later life. Clearly, recent prospective findings of exercise-related bone mineral loss among young athletes need to be replicated in a larger, more heterogeneous cohort. The Specific Aims of this project are to: (1) conduct a two-year longitudinal study of bone mineral density (BMD) changes comparing male and female high-school athletes (basketball players) to age-, sex-, and race-matched non-athletes. (2) to identify risk factors for bone mineral loss among adolescent athletes, including gender, race, body composition, dietary calcium intake, reproductive hormone status, and training intensity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

36 Osteoporosis

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Project Title: BIOMATERIALS (MG/ZN/F-BCPS)FOR OSTEOPOROSIS THERAPY Principal Investigator & Institution: Legeros, Racquel Z. Biomaterials and Biomimetics; New York University 15 Washington Place New York, NY 10003 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Osteoporosis is a 'silent' progressive and debilitating disease characterized by bone loss, thinning cortical bone and disorganized trabecular bone leading to bone fragility and fracture. Osteoporosis results when the processes of bone formation and bone resorption become uncoupled and the rate of bone resorption becomes much greater than that of bone formation. FDA-approved pharmaceutical interventions have antiresorptiive properties. Some of these drugs have serious side effects. Fluoride (F) therapy as sodium fluoride is the only one shown to consistently increase bone mass, but was also reported to increase fracture risk. The goal of the proposed research is to develop novel materials incorporating magnesium (Mg), zinc (Zn), F ions in a calcium (Ca) phosphate system (Mg/Zn/F-BCP). Separately, these ions have been associated with bone formation, biomineralization and osteoporosis therapy. Specific aims are to: (1) prepare and characterize the crystallographic, morphologic, and chemical properties of a series of Mg/Zn/F-BCP materials; (2) determine the short and long term initial dissolution rates and release of Ca, Mg, Zn, P and F ions of the materials prepared in Aim 1; (3) determine in vitro response of bone forming (osteoblasts) and bone resorbing (osteoclasts) cells to Mg/Zn/F-BCPs of various compositions using human osteoblast-like cells and rat osteoclast-like cells; (4) determine the effect of orally administered various Mg/Zn/F-BCPs on (a) bone properties (mechanical strength, density, quality, composition, and histomorphometric parameters and bone mineral (crystallinity, composition and dissolution) of adult and aged female and male rats; and (b) on the development of osteoporosis (deficient-diet induced) in adult rats; and (5) determine therapeutic effect of various injected Mg/Zn/F-BCPs on ovariectomized rats using biomechanical, histomorphometric measurements and chemical analyses on bone and plasma analyses. Hypothesis: Biomaterials with Zn, Mg and F ions in a calcium phosphate matrix (used as dietary supplement and ion releasing injectible 'implants') will improve bone health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BISPHOSPHONATE ZOLEDRONATE PREVENTS OSTEOPENIA AFTER OVARIECTOMY IN ADULT RHESUS Principal Investigator & Institution: Binkley, Neil C.; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: OBJECTIVE To demonstrate that the development of progressive osteopenia in ovariectomized rhesus monkeys can be prevented by treatment with the potent bisphosphonate zoledronate. RESULTS Ovariectomy produced rapid bone loss of ~8% at the lumbar spine and total body. This was prevented in a dose-dependent fashion by zoledronate. This study was the most comprehensive assessment of estrogen depletion bone loss and the effect of a bisphosphonate compound on this loss in non-human primates. Elevated skeletal turnover was clearly demonstrated and was suppressed dose dependently by zoledronate. Biomechanical testing observed reduced bone strength following ovariectomy which was prevented by zoledronate. These results suggest that this compound will likely prove efficacious in the prevention and treatment of osteoporosis in postmenopausal women. FUTURE DIRECTIONS Quantitative histomorphometric assessment of samples from this study are pending. KEY WORDS

Studies 37

osteoporosis, bisphosphonate, estrogen-depletion, bone density, bone strength FUNDING Novartis pharmaceuticals PUBLICATIONS Davidowitz, B. I., Banovetz, S., Boehm, K., & Binkley, N. 1998 Increased lead concentration in the drinking water of an animal care facility. AALAS Contemporary Topics in Animal Science 37:51-53. [J] Binkley, N., Kimmel, D., Bruner, J., Haffa, A., Davidowitz, B., Meng, C., Schaffer, V., Green, J. 1998 Zoledronate prevents the development of absolute osteopenia following ovariectomy in adult rhesus monkeys. J. Bone Miner Res. 13:1775-1782. [J] Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BMP RECEPTOR SIGNALING AND BONE REMODELING Principal Investigator & Institution: Chen, Di; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Problem: Bone formation is a dynamic process and is regulated by local bone growth factors. The mechanisms of bone formation during bone remodeling remain undefined. Bone morphogenetic proteins (BMPs) are multifunctional growth factors, which regulate a variety of biological functions. The physiological role of BMP receptor signaling in bone formation and bone remodeling in adult mice is not fully understood. Purpose: We will determine the role and mechanism of BMP receptor signaling in bone formation. The underlying hypothesis is that BMP receptor signaling plays an essential role in bone formation during bone development, postnatal bone growth and adult bone remodeling. Methods: To investigate the role of the type I BMP receptors in bone formation in vivo, we have generated transgenic mice, which overexpress a dominant-negative type IB BMP receptor (dnBMPR-IB) transgene. Expression of dnBMPRIB was targeted to ostcoblasts by using a type I collagen promoter, which is specific for the osteoblast lineage. Characterization of the skeletal phenotype of these transgenic mice has shown that BMP receptor signaling, bone growth and bone formation are impaired in 1-month-old transgenic mice. Bone mineral density, bone volume and bone formation rates in these transgenic mice are significantly reduced compared with 1-month-old wild-type littermates. Our results show that BMP receptor signaling is a necessary component for postnatal bone formation in vivo. In the proposed studies, we plan to further determine the role of BMP receptor in bone formation and bone remodeling using the same adult transgenic mice. Our working hypothesis is that BMP receptor signaling plays a critical role m bone formation and bone remodeling in adult mice. The specific aims are that we will use the CollaldnBMPR-IB transgenic mouse model to determine 1) the role of the type 1 BMP receptor in bone formation and bone remodeling in adult mice and 2) whether the bone regulatory growth thctors IGF-I and FGF-2 or the bone anabolic agent PTH induce bone formation through activating BMP signaling. Expected Outcomes: The proposed studies will lead to a better understanding of the physiological importance of BMP signaling in bone formation during bone remodeling and likely uncover the pathological consequences for osteoporosis and other related diseases. Benefit: These studies will provide molecular insights into the mechanism involved in bone formation and bone remodeling in adult mice and define molecular targets for drug development for the treatment of osteoporosis and other bone-loss associated diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

38 Osteoporosis

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Project Title: BONE DENSITY AMONG LAOS IMMIGRANTS IN OLMSTED COUNTY MN: CROSS-SECTIONAL AND LON Principal Investigator & Institution: Melton, L. Joseph. Eisenberg Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001 Summary: Osteoporosis is a growing public health problem as a consequence of its associated fractures, especially of the proximal femur. Although the focus in the past has been on the problem of osteoporosis in white women, there is increasing recognition that osteoporotic fractures also pose a threat to other populations. In 1995, for example, 6.5% of the total cost of osteoporotic fractures in this country, $901 million, was due to fractures in nonwhites. However, the epidemiology of bone loss and fractures in populations of Asian heritage is still poorly known, and most studies to date have been carried out overseas in China and Japan. Whether or not osteoporosis represents a potential problem among refugees from Vietnam, Cambodia or Laos is unknown. The goal of this proposal is to assess the skeletal status of Olmsted County residents orginally from Laos in order to help design prevention programs should osteoporosis prove to be common in this population. The specific aims of this study are as follows: 1) to provide health education on osteoporosis and on possible preventive measures such as dietary calcium, hormone replacement therapy and exercise; 2) to determine bone mineral density levels among the Laotian men and women residing in Olmsted County and to compare these with the distribution of bone density among white residents of the County and among residents from Cambodia and Vietnam; to examine the association between bone density and life-style and, for the women, reproductive factors; 4) on the basis of these data, to recommend strategies to prevent osteoporosis among Laotians; and 5) in follow-up at two-year intervals, to inquire what lifestyle changes have been made and to assess changes in BMD of the hip and spine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BONE POPULATIONS

DENSITY

AND

LATER

BONE

LOSS

IN

RURAL

Principal Investigator & Institution: Specker, Bonny L. Professor; Health Science; South Dakota State University Brookings, SD 57007 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: Genetics and lifestyle factors are major determinants of bone density and ultimately the risk for developing osteoporosis.. Higher bone density was reported in rural vs. urban adolescents. We recently reported high bone density Z scores among female members of the Hutterite Brethren, a religious group living a rural communal lifestyle. We concluded that high levels of physical activity beginning in the teen years in the presence of adequate calcium intake over a lifetime might result in increased bone gain and subsequent above normal adult bone density. However, it is not known whether Hutterites have higher bone density than other populations living similar lifestyles, or whether the higher bone density among older Hutterites is due to a slower rate of later bone loss.. The aim of this study is determine whether a rural lifestyle is conducive to optimizing peak bone mass in young adulthood and minimizing rates of later bone loss, thereby explaining the high bone density among the rural Hutterite population. The proposed aim will be addressed with a three-year longitudinal study of 1,164 men and women aged 20 to 65 years with equal numbers of Hutterites, rural nonHutterites, and non-rural non- Hutterites. We will obtain yearly bone measurements and quarterly assessments of activity levels and dietary intake. The project will

Studies 39

determine whether bone density during young adulthood and the rate of later bone loss, among the Hutterites is similar to other populations, and whether greater activity levels and calcium intake can account for the high bone density observed among the Hutterites. Further understanding of the role of lifestyle factors as determinants of bone density among Hutterites is necessary because they appear to be significantly less susceptible to the development of osteoporosis than the normal U.S. population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE DENSITY IN AGING MEN OF DIVERSE RACE AND ETHNICITY Principal Investigator & Institution: Mckinlay, John B. Senior Vice President and Director; New England Research Institutes, Inc. 9 Galen St Watertown, MA 02472 Timing: Fiscal Year 2002; Project Start 15-MAY-2002; Project End 31-MAR-2006 Summary: (provided by applicant): The National Institutes of Health (NIH) has identified the prospective investigation of osteoporosis in gender, age, and racially/ethnically diverse populations as an urgent research priority (Consensus Development Conference on Osteoporosis Prevention, Diagnosis, and Therapy. 2000). Male osteoporosis is a highly prevalent medical condition, with enormous impact on the health, medical-care expenditures, and quality of life of the aging U.S. male population. Race/ethnic-specific estimates of the prevalence of osteoporosis from population based. cross-sectional data are limited by: (1) Incomplete information on the range of variables that may be related to both bone density and race/ethnicity (e.g., bone turnover, hormone levels, lifestyle, nutrition, vitamin D status, and others) that might account for the racial/ethnic difference in prevalence; and (2) Limited data on Hispanics other than Mexican Americans, despite the well-known heterogeneity of ethnicities within Hispanic populations. The New England Research Institutes (NERI) has received an award from NIDDK to begin a large epidemiological research study of 3,000 randomly selected, community dwelling Hispanic, non-Hispanic African American, and non-Hispanic Caucasian men ages 40-79 years (1,000 per racial/ethnic group), to provide normative data on four urologic conditions. The proposed study will take advantage of this newly assembled cohort by adding a cross-sectional, populationbased sub-study of bone density and osteoporosis in men. We will recruit 900 men from the parent study and describe the distribution of bone mineral density (BMD) and low BMD by race/ethnicity and determine to what extent variables (e.g., health status, lifestyle, sociodemographics, biochemical measures of bone turnover and hormone levels, fracture history) correlate with BMD, and whether the effect of these variables on BMD varies with race/ethnicity. To prepare for the possibility of a future, separately funded prospective study, we will initiate panel maintenance activities with the cohort. This design represents a cost-efficient approach to gathering detailed information focused on bone health in a randomly selected, population-based sample, while taking advantage of the activities currently underway as part of the parent study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BONE DENSITY/RISKS--NEW TECHNOLOGIES & MATERIAL MODEL Principal Investigator & Institution: Ganezer, Kenneth S.; California State UnivDominguez Hills Carson, CA 90747 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2005

40 Osteoporosis

Summary: The objective of this four year project is to develop improved techniques for diagnosing, determining the risk for, and monitoring the course of treatment of osteoporosis.. To achieve this goal we will undertake four studies. These include ultrasound and DEXA measurements, on human subjects, the construction of a new radiological scanning device for measuring bone density, the construction of a new ultrasound scanner for determining Broadband Ultrasonic Attenuation (BUA) and the Speed of Sound (SOS) in cortical bone, hypothesis of a composite model of bone and of fracture risk. Our human subject studies will test the hypothesis that high levels of correlation can be obtained between cortical and trabecular bone measurements using ultrasound. Human studies will also allow us to follow the course of treatment of patients taking osteoporosis medications. Our new radiological scanner will use the highly sensitive coherent to Compton photon scattering ratio (CSR) technique to measure the "true" volumetric. We will test the hypothesis that right-left differences in the calcaneus and distal radius are good indices of osteoporosis.. We will test our new CCSR and ultrasound scanners on human subjects. A model of bone as a composite material made of collagen and mineral will be used to calculate fracture and osteoporosis.. We will test our new CCSR and ultrasound scanners on human subjects. A model of bone as composite material made of collagen and mineral will be used to calculate fracture and osteoporosis risks and to plan treatment for those diagnosed with or at significant risk for osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE DENSITY--A RISK FACTOR FOR ORTHODONTIC SIDE EFFECTS Principal Investigator & Institution: Bollen, Anne-Marie; Associate Professor; Orthodontics; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 15-JUL-1999; Project End 30-JUN-2004 Summary: During this 5-year career development award Dr. Shiboski intends to integrate a study of oral disease in renal transplant recipients (RTRs) with a training plan that would expand her background in Oral Medicine and Epidemiology. The objectives of the proposed 5-year prospective cohort study are to 1) investigate the longterm side effects of corticosteroids and new generation immunosuppressants on the incidence of oral soft tissue disease and on changes in mandibular bone structure; and 2) determine if change in the fractal dimension of mandibular bone predicts change in bone mineral density of various skeletal sites, and may be used as a diagnostic tool to detect osteoporosis in this high risk population. RTRs (N = 360) will be recruited from the UCSF kidney post-transplant clinic, and followed at 1-year intervals. Measurements will include an oral soft tissue examination, evaluation of periodontal parameters, vertical bitewing radiographs, and an interview. In addition, fractal analysis will be conducted on dental radiographs and explored in relation to bone mineral density measured on two skeletal sites on a sub-sample of participants by Dr. Majumdar, an Associate Professor in Radiology. The training aspect of the award will be under the guidance of two mentors. Dr. John Greenspan will assist the candidate in learning aspects of molecular immunopathology and immunohistochemistry that are relevant to her research area. Dr. Ira Tager will advise the candidate about methodologic difficulties inherent in a longitudinal study of immunosuppressed subjects with complex medical histories. The candidate earned a PhD in Epidemiology and received post- graduate training in Oral Medicine as part of an individual Dentist Scientist Award. The proposed career development award would allow Dr. Shiboski to apply and expand her skills as a clinical oral epidemiologist to the study of oral disease in a chronically

Studies 41

immunosuppressed population with various underlying systemic disorders (e.g., hyperparathyroidism; diabetes). The candidate intends to devote 80 percent effort to the proposed project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE EXTRACELLULAR MATRIX CHEMISTRY IN OSTEOPOROSIS Principal Investigator & Institution: Mccreadie, Barbara;; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 30-APR-2006 Summary: Osteoporosis is a widespread and expensive healthcare problem. Bone mineral density is used clinically to diagnose osteoporosis and generate an estimate of fracture risk. However, there is a large overlap in bone mineral density between those who fracture and those who do not. Additional factors have been sought to explain this overlap. A recent study has suggested that the chemistry of the bone extracellular matrix may in some way contribute to the propensity to fracture. Therefore, the purposes of this study are (1) to evaluate whether the differences previously seen are local to the fracture site or systemic, and (2) to determine whether the chemical differences seen are related to the architecture differences. A set of existing specimens will be obtained. Twenty specimens from individuals will vertebral fracture and a matching set of specimens from normal individuals will be evaluated to determine whether the carbonate/phosphate and mineral/matric (phosphate/amide I) ratios obtained using Raman spectroscopy are able to predict fracture. A separate subset of specimens will be used to determine whether the chemistry is related to the architecture. The first purpose has clear implications for the future direction of out research ? whether fatigue at the fracture site and the resulting remodeling is causing these changes, or whether systemic differences are related to a generalized propensity to fracture. This also is critical in understanding the potential of this technology for non- or minimally-invasive assessment of fracture risk. The second purpose is important in understanding whether this difference we have previously found is associated with architecture (as would be expected if it influences mechanotransduction) or is an independent risk factor for osteoporotic fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BONE ADAPTATION

FLUID

FLOW

AND

ITS

REGULATORY

ROLE

IN

Principal Investigator & Institution: Qin, Yi-Xian; Biomedical Engineering; State University New York Stony Brook Stony Brook, NY 11794 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Musculoskeletal complications, such as osteoporosis and aging related osteopenia, are major societal and health problems. Load-induced intracortical bone fluid flow is proposed as a critical mediator in initiating and regulating bone surface and osteonal adaptation. Using oscillatory pressurized marrow fluid flow stimuli, the physiological fluid stimulus was found to initiate new bone formation and reduce intracortical bone porosities caused by disuse, even in the absence of direct tissue strain. The new bone formation and inhibition of resorption were found to correlate with quantified flow parameters, i.e., fluid pressure gradients. This flow initiated bone adaptation occurs at a specific frequency range, i.e., 20-30 Hz, and is interdependent with the dose of anabolic fluid pressure. While bone remodeling was demonstrated to be sensitive to high strain frequency and low intensity physiological

42 Osteoporosis

loading, the role of fluid flow perhaps explains, at least in part, the cellular response mechanism to anabolic stimuli. In the work proposed, we will examine the general hypothesis that bone fluid flow, mediated at specific physiological magnitudes and high frequencies, promotes osteogenic adaptation. Indeed, improving our understanding in which mechanical signals influence the temporal and spatial dynamics of bone remodeling may help to devise a biomechanically based intervention for treating osteoporosis, accelerating fracture healing or promoting bony ingrowth into prostheses. In this revised application (1-R01-AR049286-01), the goal will be achieved by a series of sub-hypotheses and specific aims: (1) The role of anabolic fluid flow, driven by daily intramedullary pressure (IMP), can initiate surface adaptive response and inhibit intracortical bone loss in a disuse bone. The remodeling response will be evaluated in a disuse in-vivo model in the absence of matrix strain following 4-week exposure of a short period of daily stimuli, consisting of a series of frequencies (0.5,1,5,10,20 & 40 Hz). (2) Osteogenic response to anabolic fluid flow stimuli is fluid pressure sensitive associated with the rate/frequency of loading. The anabolic potential response to hydraulic intensity will be evaluated in a disuse model following 4-week of daily ImP at 10, 20 and 80 mmHg with 1,5, and 20 Hz. (3) The potentials of fluid flow initiated adaptation are interdependent with specific fluid components, i.e., pressure gradient and fluid shear stress, which are responsible for restoring or inhibiting bone loss and new surface bone formation. A poroelastic finite element analysis will be developed, which will evaluate the correlation between fluid flow and resultant adaptation. (4) The osteogenic potentials response to fluid flow stimuli is initiated by osteoblastic activation of bone lining cells, following a daily but short duration (e.g., <10 days) of loading. Ultrastructural osteoblastic features of cell and nuclei will be examined via histomorphometric analysis of cell area, nuclear area, cell number, cell and nuclei shapes, in which associated fluid components will be identified. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE LOSS AND ITS PREVENTION IN HIV PATIENTS Principal Investigator & Institution: Ross, F. Patrick. Professor; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, MO 63110 Timing: Fiscal Year 2002; Project Start 11-APR-2002; Project End 31-MAR-2003 Summary: (Provided by the applicant): The use of HIV protease inhibitors (PIS), combined with other anti-retroviral agents, is central to dramatic decline in the morbidity and mortality of HIV infection. Our group recently discovered that PI-treated patients have decreased bone mineral density (BMD), which led us to examine the effects of individual PIS on osteoblast (OB) and osteoclast (OC) formation and function. We find that one PI, Indinavir, induces bone loss in mice. The drug exerts its osteoporotic effect by arresting OB precursor differentiation, and in so doing, dampens expression of the specific osteoblast transcription factor, Cbfal. In contrast to the osteoporotic properties of Indinavir, Ritonavir is bone sparing, in vivo, exerting its effect, in an M-CSF independent manner, by blunting OC formation and function. Since osteoclastogenesis requires only M-CSF and RANK ligand (RANKL) the drug must impact RANKL-initiated signaling. Finally, we provide data that a fusion protein comprising GST linked to the ectodomain of RANKL is a potent bone anabolic agent. We therefore hypothesize that: 1. lndinavir arrests bone formation by inhibiting Cbfal expression in OB precursors; 2. Ritonavir, by blunting RANKL-induced signaling, inhibits OC differentiation and function; and 3. Administration of Ritonavir, or GSTRANKL, will prevent andlor rescue Indinavir-induced osteoporosis.. Thus, our specific aims are to determine: 1. the mechanism by which lndinavir inhibits Cbfal expression in

Studies 43

OB precursors; 2. The mechanism by which Ritonavir, blunts RANKL-induced signaling, in OCs and their precursors; 3. If administration of Ritonavir, or GST-RANKL, will prevent and/or rescue Indinavir-induced osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE RESPONSE TO COMBINED MECHANICAL AND PTH STIMULATION Principal Investigator & Institution: Guo, X. Edward. Associate Professor; Mechanical Engineering; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, NY 10027 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: (provided by applicant): Trabecular bone adaptation plays a significant role in the etiology of many metabolic bone diseases such as osteoporosis and osteopetrosis, bone loss in microgravity, and the long term success or failure of porous implants in total joint arthroplasty. Parathyroid hormone (PTH) is an important anabolic agent when administered intermittently. We have developed a novel in vivo rat-tail vertebra model coupled with an uCT image based finite element technique. Specifically, a controlled mechanical load can be applied to a rat-tail vertebra and a detailed threedimensional (3D) stress/strain environment in the trabecular bone tissue can be determined using an advanced finite element microstructural model. In this proposal, we designed a full-scale, long-term study to systematically quantify the molecular/cellular responses and changes in 3D morphology in trabecular bone to combinations of mechanical loading and PTH treatment. The molecular responses will be assayed using RT-PCR and in situ hybridization. The bone cellular response will be quantified using bone histomorphometric techniques. The specific aims of this project are: Specific Aim 1: To determine the changes in gene expression (c-fos, cbfa-1, IGF-1, collagen a1(I), osteopontin, osteocalcin, alkaline phosphatase, RANK-L, and osteoprotegerin) by RT-PCR and in situ hybridization, bone cell activities by bone histomorphometry, and 3D trabecular bone morphology by uCT of rat tail vertebrae at various levels of mechanical loading (ON, 50N and lOON) ranging from 1 day to twelve weeks. Specific Aim 2: To determine the changes (using the same measurements cited in Specific Aim 1) in rat-tail vertebrae in response to daily PTH administration (3O-ug/kg and 6Oug/kg) for various lengths of time. Specific Aim 3: To determine the changes (using the same measurements cited in Specific Aim 1) in rat tail vertebrae mechanically loaded at various magnitudes (ON, SON, and lOON) in the presence of PTH (30ug/kg and 6O ug/kg) for various lengths of time. Specific Aim 4: To perform uCT based PEA of the loaded vertebrae in Specific Aims 1 and 3, and to determine the changes in the distribution of trabecular bone tissue stress/strain parameters following the various treatments. Results from this study will help to clarify, in a quantitative manner, the cellular and molecular mechanisms of bone adaptation to mechanical loading, which are important in the understanding of the etiology and optimizing therapeutic interventions of menopausal, microgravity or age related osteoporosis, and improvement in total joint replacements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BONE-SPARING BY CA SALTS WITH & WITHOUT EXTRA PHOSPHORUS Principal Investigator & Institution: Heaney, Robert P. John A. Creighton University Professor; Medicine; Creighton University 2500 California St Omaha, NE 68178

44 Osteoporosis

Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant) Bone mineral is basically calcium phosphate, and both elements (Ca and P) are required for bone acquisition. Typical Ca intakes in the U.S. are lower than current recommendations, and typical P intakes, higher. Thus attention has been focused mainly on increasing Ca intake, by supplementation and food fortification. The salt most commonly used for these purposes is calcium carbonate. But while the average P intake tends to be adequate or generous, nevertheless substantial proportions of older women ingest less than 70 percent of the RDA for phosphorus on any given day, and hence may be said to be at risk for P deficiency. When these women are given a combination of anabolic therapy and supplemental Ca (as the carbonate), the added Ca may uncover and aggravate the latent P deficiency. This is both because Ca binds phosphate in the gut and reduces its absorption (thereby effectively lowering the P intake still further) and because the induced bone anabolism will itself consume phosphorus, as a result of which absorbed phosphorus may not be sufficient to support the increase in bone mineral mass made possible by this therapy. To test the possible importance and value of supplementing both of the components of bone mineral in support of anabolic therapy of osteoporosis, we propose a 1-year randomized trial, comparing, in two groups of teriparatide-treated postmenopausal osteoporotic women, calcium supplements with and without extra phosphorus (i.e., Ca phosphate vs. Ca carbonate). The principal outcome measure will be change in bone mineral content over the one year of the trial. A secondary outcome is measurement of bone resorption biomarkers so as to assess whether the phosphate salt elevates remodeling relative to the carbonate salt. A finding of superiority of the phosphatecontaining Ca supplement would provide evidence leading to a cost-neutral change in Ca sources and a corresponding improvement in osteoporosis co-therapy (and possibly osteoporosis prophylaxis as well). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BREAST CANCER SURVIVORS: EXERCISE AND RALOXIFENE Principal Investigator & Institution: Schwartz, Anna L. Associate Professor; Primary Care Nursing; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 29-FEB-2004 Summary: It is estimated that 178,799 women will be diagnosed with breast cancer in 1998. While breast cancer has become more treatable, the long-term treatment-related side effects have a significant negative effect on morbidity and non-cancer related risk of mortality. The increasingly common use of adjuvant chemotherapy for breast cancer has led to a rise in long-term treatment- related side effects including osteoporosis, early menopause, increased risk for cardiovascular disease, and declines in quality of life. Osteoporosis is a major public health problem and a common finding in breast cancer survivors. Nationally, 20 million women are estimated to be at risk for osteoporosis, with 1.3 million sustaining osteoporotic fractures. Four factors place breast cancer survivors at high risk for muscle, bone and cardiovascular complications: inactivity, menopause (especially premature menopause), chemotherapy and catabolic steroids. This innovative study will use a randomized placebo-controlled design to test the effects of (a) exercise and (b) raloxifene in postmenopausal breast cancer survivors (N=240) between 3 months and one year after completing chemotherapy on: one resorption, formation and density (serum osteocalcin and bone specific AST, urine n-telopeptide, DEXA scan); multidimensional quality of life (SF-36, 12-minute walk, muscle strength, fatigue, menopausal vasomotor symptoms positive and negative affect, and Trail Making); and lipid profile (serum lipid levels). Subjects in the exercise intervention will

Studies 45

follow a supervised home-based exercise program and asked to exercise 5 days/week. Exercise dose and adherence will be monitored with Caltrac accelerometers, exercise logs, regularly scheduled follow-up phone calls and supervised exercise sessions, and results on 12-minute walks and 1-repetition maximum tests. Subjects in the ralosifene and placebo control groups will be asked to take the medication (60mg/day) or placebo as prescribed. Subjects in the exercise+raloxifene group will be asked to take the medication and follow the exercise program. All subjects will be instructed to take a daily calcium supplement (1000mg/day). Subjects will be followed for 2 years. All measures will be re-evaluated at 3- month intervals except the DEXA scans, which will be obtained at 12-month intervals. Results of this study may reduce the morbidity, mortality and health care costs of these common, long- term complications that confront breast cancer survivors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCIUM ABSORPTION AND BONE FORMATION DURING PUBERTY Principal Investigator & Institution: Abrams, Steven A. Professor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 15-MAR-1996; Project End 31-MAY-2006 Summary: (Scanned from the applicant's abstract) Background: Rapid increases in bone mass occur during Liberty Optimizing calcium absorption (Ca abs) and bone calcium deposition (V0+) during puberty can enhance peak bone mass and ultimately decrease the lifetime risk of osteoporosis.. In this study, we will determine the influence of hormonal, genetic and dietary factors that lead to maximal Ca-abs and Vo+ in pubertal boys and girls. This proposal is a logical extension of our recent findings that; 1) changes in calcium metabolism in early puberty are correlated to serum luteimzing hormone (LH) level, ethnicity, family history of osteoporosis, and the genotype of vitamin D receptor polymorphisms, and 2) the addition of small amounts of nondigestible oligosaccharides (NDO) can significantly increase calcium absorption in pubertal children on relatively high calcium-containing diets. Hypotheses: Our overall hypotheses are that dynamic changes in mineral metabolism in early adolescence are based on identifiable hormonal and genetic factors and that specific nutritional interventions can enhance bone mass accumulation. Specifically, in this proposal we will evaluate the following: 1) Early nighttime increases in pubertal hormones will be closely correlated to Ca-abs and V0+ in both boys and girls. In contrast, serum leptin will be negatively correlated with V0+; 2) Putative genetic markers of osteoporosis, including vitamin D receptor polymorphisms, will be significantly correlated to Ca-abs and V0+; 3) The addition of NDO will increase Ca-abs and Vo+ in pubertal children receiving recommended dietary calcium intakes. Study Methods: We will enroll 50 girls and 50 boys who are healthy, 5th to 95th percentile body mass index for age, and Tanner Stage 2 or 3. They will participate in comprehensive dual-tracer calcium stable isotopic kinetic studies. Results will be compared with pubertal hormonal studies, biochemical bone turnover markers, and dual-energy X-ray absorptiometry (DXA) measures of whole body and regional bone mineral content. Genetic markers related to bone mass will be assessed and related to both hormonal and calcium kinetic measurements. After these baseline studies, subjects will be randomized to receive calcium fortified foods either with or without added NDO. Calcium absorption will be measured again after 2 months. After 12 months, the baseline calcium kinetic, hormonal and DXA studies will be repeated to assess the effects both of pubertal development and the dietary intervention. At the conclusion of that study, supplementation with NDO will be

46 Osteoporosis

stopped and a final DXA study performed 12 months later to assess whether bone mass differences identified during supplementation were maintained post-intervention. Conclusions: By identifying the relationships among hormonal changes of puberty, genetics and calcium metabolism, the characteristics leading to maximal calcium absorption and utilization can be identified. These insights will enable interventional strategies to enhance bone mass to be specifically related to identifiable population characteristics, with the ultimate goal of decreasing the incidence and severity of bone loss and osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALMODULIN AND CGMP CONTROL OF OSTEOCLASTIC H+ SECRETION Principal Investigator & Institution: Blair, Harry C. Professor of Pathology and of Cell Biolo; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-SEP-1994; Project End 30-JUN-2004 Summary: Management of osteoporosis is limited by poor understanding of how bone mass is regulated. Osteoclasts are the acid-secreting cells that degrade bone. We found that Ca+2/calmodulin at the acid-secreting membrane of osteoclasts is required for HCI production. In contrast, inactivation of acid secretion is calmodulin independent, but is mediated by the cGMP- dependent enzymes function in a coordinated counterregulatory processes that mediates the reversible phosphorylation of proteins in the acid secreting membrane to regulate osteoclastic activity. We will study this hypothesis using human osteoclasts in vitro. Aim 1 will determine the role of local intracellular Ca+2 increases (calcium puffs or sparks) that occur near the acid-secreting cell membrane. H+- ATPase or acid secretion will be modified, and effects on intracellular calcium puffs will be measured using fluorescent indicators. The effects of calcium transport antagonists will be studied to identify the mechanism(s) that cause the calcium puffs, and the effects of calcium puffs on membrane protein phosphorylation will be determined. Aim 2 will use adenovirus infection to modify osteoclastic expression of the cGMP- dependent protein kinase and calcineurin (the calmodulin-dependent phosphatase). Eliminating the kinase should promote acid transport and abolish cGMP effects in osteoclasts; constitutive kinase should inactivate acid secretion. In cells without calcineurin, phosphorylation of membrane regulatory proteins should increase, decreasing acid secretion. Aim 3 will characterize the interaction of cGMP and Ca+2 signals in osteoclasts. How calmodulin-dependent cGMP phosphodiesterase activity varies with cGMP, acid secretion, and calcium puff activity will be assessed, using Western analysis and immune localization, to establish the role of this enzyme in balancing cGMP and Ca+2/calmodulin effects. Interactions of cGMP- and calmodulindependent kinases/phosphatases in the acid-secreting cell membrane will also be studied, using kinase, membrane activity, and immune localization assays. This will show whether Ca+2/calmodulin and cGMP counter- regulation occurs via common target proteins, and how distribution of regulatory proteins varies with cGMP and calcium signals. These studies will characterize an intracellular regulatory system that controls osteoclastic activity. This knowledge will be useful in understanding how osteoporosis develops, and may assist in the design of treatments to reduce bone resorption and prevent osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies 47

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Project Title: CELIAC DISEASE IN OSTEOPOROSIS Principal Investigator & Institution: Stenson, William F. Professor; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, MO 63110 Timing: Fiscal Year 2001; Project Start 15-JUN-2000; Project End 31-MAY-2005 Summary: (Abstract of the application) There is compelling evidence that the prevalence of celiac disease in the general population in the United States is higher than is generally appreciated and that patients with the symptoms classically associated with celiac disease, primarily diarrhea and weight loss, form a relatively small portion of the total celiac population. Some patients with celiac disease have medical problems associated with the malabsorption of specific nutrients without having problems with diarrhea and weight loss. Celiac disease is associated with the malabsorption of calcium and vitamin D resulting in osteoporosis.. Although the prevalence of osteoporosis in the population of patients with celiac disease is known to be increased compared to the prevalence in the general population, the contribution of celiac disease to osteoporosis in the general population and the prevalence of celiac disease in the population of patients with osteoporosis are unknown. The central hypotheses of this proposal are: 1. The prevalence of celiac disease in the population of patients with osteoporosis is significantly increased above that of the general population. 2. Management of osteoporotic patients with celiac disease would be facilitated by the diagnosis and treatment of their celiac disease. These two premises taken together would justify a public health recommendation for screening patients with osteoporosis with serological tests for celiac disease. We have the unique resource of a Bone Health Clinic with a database that includes more than 2,000 individuals with osteoporosis as well as an even larger number of patients with normal bone density. In addition, the Bone Health Clinic sees more than 750 new patients per year of which 50% have osteoporosis.. We propose to use the resources of our Bone Health Clinic to test this hypothesis. We have two Specific Aims: 1. To define the prevalence of celiac disease in a population of patients with osteoporosis and to compare the prevalence in a case control group of individuals with normal bone mass indices. This Specific Aim will be pursued using patients from the Bone Health Clinic database that will already have been defined as having osteoporosis and new patients accrued to the Bone Health Clinic. If the prevalence of celiac disease in the osteoporotic population is high enough one could justify a public health recommendation that all patients with osteoporosis undergo serologic screening for celiac disease. Studies under this Specific Aim will also allow recommendation for which sequence of serologic tests is most likely to be helpful in identifying patients with osteoporosis who also have celiac disease. 2. To determine if there are any significant differences in the clinical histories, laboratory studies or response to therapy between the populations of newly diagnosed and previously untreated osteoporotic patients with and without celiac disease. Specific studies will include: a. We will compare the population of patients with osteoporosis and celiac disease with the population of patients with osteoporosis without celiac disease in terms of their clinical characteristics and biochemical parameters determined at the time of diagnosis. b. We will compare patients with osteoporosis and celiac disease with patients with osteoporosis without celiac disease in terms of their response to therapy. Patients with osteoporosis without celiac disease will receive calcium and vitamin D for one year, whereas patients with osteoporosis and celiac disease will receive calcium, vitamin D and a gluten-free diet for one year. At the end of the year of therapy, bone mass indices will be repeated and the response to the therapy of the two groups will be compared. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CELLULAR CALCIFICATION

/MOLECULAR

MECHANISMS

OF

VASCULAR

Principal Investigator & Institution: Bostrom, Kristina I. Assistant Professor of Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: This Project is focused on understanding the molecular mechanisms involved in vascular calcification and osteoporosis.. Matrix GLA protein (MGP) was strongly implicated in the pathogenesis of vascular calcification when an MGP knockout mouse was found to have extensive vascular calcification. Based on this mouse model, MGP might be thought to be an inhibitory factor in vascular calcification. However, in calcified lesions of mice that have a normal MGP gene and in human lesions, MGP expression is postively correlated with the degree of lesion calcification. During the current grant period we demonstrated that MGP regulates bone morphogenetic protein (BMP-2), During the next grant period we will determine the molecular basis for the regulatory role of MGP in the artery wall and its interaction with BMP-2. Other work from this Project during the current grant period provided important clues as to why many patients with progressive vascular calcification also have progressive osteoporosis.. Oxidized lipids were shown to promote calcification of calcifying vascular cells (CVC) but inhibited the osteoblastic differentiation and mineralization of marrow stromal cells that are the precursors to mature bone osteoblasts. This was true whether the oxidized lipids were added in vitro or were produced by feeding atherosclerosis suceptible C57BL/6J (BL6) mice an atherogenic diet. These oxidized lipids were also shown to promote osteoclastogenesis and osteoclast activation in vitro. In vivo, feeding an atherogenic diet to atherosclerosis susceptible BL6 mice produced a dramatic reduction in bone mineral density and bone mineral content. Feeding an atherogenic diet to atherosclerosis resistant C3H/HeJ mice causes the same degree of hyperlipidemia as in BL6 mice, but there was no significant reduction in either bone mineral density or bone mineral content in the C3H/HeJ mice. In the next grant period we propose to determine the molecular mechanisms for these observations and we will determine if high density lipoproteins (HDL), components of HDL, and mimetics of HDL will protect against bone loss in mouse models of atherosclerosis. These studies may identify potential new therapeutic targets in vascular calcification and osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARBOXYLASE

CHARACTERIZATION

OF

DEFECTIVE

G-GLUTMYL

Principal Investigator & Institution: Baker, Dale; Microbiology, Immunology & Pathology; Colorado State University Fort Collins, CO 80523 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): This application is a request for R24 funding through the National Center for Research Resources (NCRR) of the project entitled "Characterization of Defective Gamma-Glutamyl Carboxylase in Rambouillet Sheep." Human patients with hereditary deficiencies of gamma-glutamyl carboxylase have severe bleeding clinically, but more recently, acquired defects of carboxylation have been implicated in degenerative diseases of the aged such as vascular mineralization and osteoporosis.. While hereditary deficiency of gamma-glutamyl carboxylase is uncommon, atherosclerosis and osteoporosis are significant diseases of the aged. A

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model of defective gamma-glutamyl carboxylation does not exist despite previous efforts to produce one through knockout mouse technology. The Specific Aims of this project are: (1) Develop and maintain a flock of sheep with defective gamma-glutamyl carboxylase activity equivalent to human gamma-glutamyl carboxylase deficiency, and provide affected lambs and tissue to investigators of gamma-glutamyl carboxylase; (2) verify that the genetic defects identified in the gamma-glutamyl carboxylase gene is responsible for diminished function, and develop a heterozygous carrier detection test for identification of carrier animals; (3) characterize the skeletal phenotype in defective gamma-glutamyl carboxylase of homozygous affected lambs; and (4) develop an in vitro gene therapy technique that may eventually be applied in vivo to this and other models of defective coagulation. Specific Aims 1, 2, and 4 will be performed at CSU under the supervision of Drs. Baker and Jennifer MacLeay, and Specific Aim 3 will be carried out at Yale University by Dr. Caren Gundberg. Preliminary studies in these sheep have identified the coagulation defect that occurs in homozygous affected lambs, and the underlying cause of this coagulopathy is markedly decreased gamma-glutamyl carboxylase activity. Genetic mutations of the gamma-glutamyl carboxylase gene have also been identified. These sheep represent the only known model of this defect in existence, but much of the underlying genetic and functional aspects of the abnormalities other than defective hemostasis are unknown. One ram and seven ewes are known heterozygous carriers of the gene. The investigators plan to identify and increase the numbers of known carrier rams to three and ewes to 24 to produce six homozygous affected lambs per year, and make rams and ewes available to investigators of gamma-glutamyl carboxylase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLIN CTR CLIN TRIAL/OBSERVATIONAL STUDY OF WHI Principal Investigator & Institution: Chlebowski, Rowan T.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, CA 90502 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 14-SEP-2005 Summary: The Women's Health Initiative is a randomized controlled clinical trial conducted in 40 clinical centers across the United States addressing some of the most common causes of death, disability, and impaired quality of life in postmenopausal women ages 50-79: cardiovascular disease; breast and colon cancer; and osteoporosis.. The three components of this disease prevention trial are: (1) hormone replacement therapy with a primary outcomes of coronary heart disease and stroke and secondary outcomes of hip and other fractures; (2) low fat dietary intervention with primary outcomes of breast cancer and colorectal cancer and a secondary outcome of coronary heart disease; and (3) calcium and vitamin D supplementation with a primary outcome of hip fractures and secondary outcomes of colorectal cancer and combined fractures. A concurrent observational study will provide estimates of health effects of known risk factors and new predictors for disease. Each clinical center will collect data through questionnaires and biological specimens over 8-12 years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPREHENSIVE EVALUATION OF OSTEOPOROSIS Principal Investigator & Institution: Pak, Charles Yc. Professor of Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001

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Summary: This study of patients with osteoporosis comprises a systematic outpatient and or inpatient assessment of a careful history for risk factors, state of bone (bone density in spine, proximal femur and radius), skeletal activity (serum osteocalcin, alkaline phosphatase, urinary hydroxyproline, iliac bone biopsy), and seconday causes of bone loss (e.g. thyroid function, adrenal status). The ultimate goal is to develop a "metabolic classification" of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--BONE HISTOMORPHOMETRY Principal Investigator & Institution: Dempster, David W.; Helen Hayes Hospital Rt 9 W West Haverstraw, NY 10993 Timing: Fiscal Year 2001 Summary: This histomorphometry core has been in integral part of our SCOR program since its inception in 1987. In the present application, the core provides histomorphometric support for four of the five projects and for the feasibility project on assessment of 3-d structure. Over the course of the five years the core will prepare and analyze over 600 rat and mouse specimens and 200 human biopsies. Bone histomorphometry will be employed to characterize the skeletal phenotype of transgenic mice which lack the p53 tumor suppressor gene. Bone histomorphometry will be used extensively to explore the mechanism of the anabolic action of PTH and interaction between dietary calcium deficiency and PT administration. Bone histomorphometry will be employed to characterize the cellular and structural effects of parathyroidectomy in postmenopausal women with mild primary hyperparathyroidism. Bone histomorphometry will be used to explore the mechanism of the initial intense anabolic action of PTH in patients with osteoporosis.. Structural variables, assessed by MicroMRI, will be correlated with histomorphometric variables of both cancellous and cortical bone structure. This core will employ state of the art technology and will bring over 15 years of experience to the analysis of the samples and interpretation of the data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--RESEARCH DEVELOPMENT Principal Investigator & Institution: Besdine, Richard W. Professor; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2001 Summary: The Research Development Core (RDC) of the Claude Pepper OAIC at University of Connecticut Health Center (UCHC) will 1) recruit junior investigators of promise from UCHC clinical and basic science departments; 2) provide Senior and New Mentors to oversee training in an enriched environment of independence-enhancing aging research; 3) conduct an independence-oriented research training curriculum; 4) implement a Pilot grants program; and 5) create an RDC executive board to set policy, award Pilot funds, pick trainees and monitor progress. A major resource is the Travelers Center on Aging (TCA), the University- wide center charged with conduct and oversight of research and teaching related to the well-being of older adults, and its Geriatrics Fellowship Training Program. Other components participating in the RDC include the General Clinical Research Center (Director, L Raisz); the endowed Travelers Research Institute on Health Promotion and Aging; and the UCHC Human Performance Laboratories, consisting of Balance and Gait Enhancement (L Wolfson, J Judge) and Exercise Research and Osteoporosis (G Dalsky). The TCA Geriatrics Fellowship has graduated 27 physicians; all but one hold full-time faculty positions in aging, and 9 are

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research-intensive. The RDC core leader (R Besdine) has extensive experience (18 yrs, UCHC and Harvard) in developing and training new faculty in aging research. Seven experienced research mentors (Drs. Dalsky, Hesselbrock, Katz, Raisz, Reisine, Rothfield, Wolfson) will directly precept individual junior faculty enrolled in the RDC, using their proven special expertise (exercise, clinical trials, epidemiology, osteoporosis, behavioral studies, arthritis, balance, respectively) concerning musculo-skeletal aging and its complications. Senior Mentors will be assisted in research training activities by a cadre of recently independent (New Mentors) investigators, examples of ongoing program success (Drs. Judge, Morse, Pilbeam, Prestwood; gait and balance, epidemiology, basic osteoporosis, clinical osteoporosis, respectively). Most training will occur by mentortrainee collaboration in design, conduct, analysis and reporting of research, complemented by project- specific training in other UCHC research programs or graduate courses. Evaluation of trainee-mentor pairs by executive board will be quarterly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CSF1 GENE EXPRESSION IN OSTEOCLAST BIOLOGY Principal Investigator & Institution: Abboud, Sherry L. Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001; Project Start 01-JAN-1994; Project End 31-DEC-2002 Summary: CSF-1, released by osteoblasts and stromal cells, stimulates the proliferation and differentiation of osteoclast progenitors and enhances osteoclast survival. In the op/op mouse model, a thymidine insertion in the coding osteopetrosis. The long-term goal of this proposal is to determine the effect of soluble(s) and membrane-bound (m) CSF-1 isoforms on osteoclastogenesis and define cell-specific cis-acting elements in the 5' flanking region of the CSF-1 promoter that regulate their expression. Our first hypothesis is that sCSF-1 and mCSF-1 are differentially synthesized and stimulate osteoclast formation due, in part, to their interaction with the c-fms receptor. To address this issue in vitro, op/op stromal cells will be transfected with sCSF-1 or mCSF-1 cDNA and stable transfectants examined for CSF-1 synthesis, bioactivity, osteoclast support and c-fms tyrosine kinase activation in target cells. The effect of each isoform on osteoclast formation in vivo will be explored by targeting isoform to ameliorate osteopetrosis in op/op mice, genetic crosses between sCSF-1 and mCSF-1 transgenic mice and heterozygous op/wt mice, genetic crosses between sCSF-1 and mCSF-1 transgenic mice and heterozygous op/wt mice will be carried out to establish op/op mutants expressing each transgene. Mice will be examined for serum CSF-1 bone growth, incisor eruption and resolution of osteopetrosis. Bone sections will be assessed for osteoclast activity; histomorphometric analysis will evaluate both static and dynamic indices of bone remodeling. The in vivo therapeutic effect of targeting each isoform to the bone in op/op mice will be assessed using adenoviral vectors designed to limit CSF1 expression in osteoblasts. Our second hypothesis is that specific regulatory elements in the 5' flanking region of the CSF-1 promoter direct cell-specific gene expression in vitro and in vivo during murine development. The temporal and spacial expression of CSF-1 during murine skeletal development will be assessed by in situ hybridization and immunohistochemistry. To determine potential cis-acting elements that control cellspecific expression of CSF-1, deletion constructs generated from the 5' flanking region of CSF- 1 will be tested for their ability to direct transcription in osteoblast, stromal, liver, muscle, epithelial and B cell lines. Relevant CSF-1 cell specific promoter sequences will be assessed in vivo by generating transgenic mice harboring cell-specific CSF-1 promoter segment(s) linked to the bacterial lacZ reporter gene. These studies should

52 Osteoporosis

increase our understanding of the molecular mechanisms that activate CSF-1 during development and may suggest novel therapeutic strategies designed to regulate osteoclast formation in a variety of bone disorders such as osteoporosis and bone fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCITONIN

DEGRADABLE

HYDROGELS

FOR

ORAL

DELIVERY

OF

Principal Investigator & Institution: Kopecek, Jindrich N. Professor and Chairman; Pharmaceutics/Pharmaceutl Chem; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-DEC-2003 Summary: Osteoporosis is a major cause of morbidity and mortality in postmenopausal women. In an United States,, an estimated 13% to 18% of women have osteoporosis.. The financial burden is substantial, with an estimated yearly cost of $10 billion in the United States alone. The lifetime risk for osteoporotic fractures in Caucasian women 50 years of age is about 30-40%. Between 13-19% of postmenopausal women who have a hip fracture die within the following year. We propose to use a combination of human calcitonin (hCT) and polymer-bound cathepsin K inhibitor (CKI) as a novel treatment of osteoporosis.. The rationales for hCT use in osteoporosis therapy are the stimulation of osteoblasts, specific inhibition of bone resorption by osteoclasts, and prevention of fusion of osteoclast precursors. Clinical studies have shown that a significant gain in bone mass can be achieved by administration of CT. An osteoclast-specific cysteine proteinase, cathepsin K, plays a specialized role in the resorption of organic bone matrix. It was shown that cathepsin K inhibitors (CKI) are effective in reducing osteoclastmediated bone resorption both in vitro and in vivo. The binding of CKI to a macromolecular carrier will change the mechanism of CKI internalization by osteoclasts from diffusion (CKI) to endocytosis (polymer-bound CKI). Consequently, the polymerbound CKI will localize in the sealed zones of the ruffled border (resorption lacuna), i.e. exactly in the place where bone resorption mediated by cathepsin K occurs. We hypothesize that the combination of the actions of hCT and CKI will produce cures which cannot be achieved with hCT or CKI alone. Establishing an oral delivery system for hCT and CKI is of great importance because it is expected that for treatment of chronic disorders in non-life threatening situations, such as postmenopausal osteoporosis, parenteral administration will lead to poor patient compliance and thus restricted utility. hCT is an excellent candidate for the development of alternate delivery routes due to its size and wide therapeutic index. The size of CKIs will be modified with semitelechelic poly[(N-2- hydroxypropyl)methacrylamide] (ST-PHPMA) chains to achieve comparable hydrodynamic volumes of CT and of the ST-PHPMA-CK conjugate, which will simplify the design of the delivery system and have beneficial biological consequences. Novel hydrogels were designed in the first period of research; they contain azoaromatic crosslinks, susceptible to degradation by bacterial enzymes in the colon and hydrolyzable side-chains, which control the kinetics of swelling in the small intestine. The structure and properties of biodegradable hydrogels will be optimized. A new macromolecular CKI will be synthesized. Its efficacy will be evaluated in an osteoclast culture in vitro as well as on an animal model in vivo. The effect of combination therapy will be compared with individual therapies. The bioavailability of hCT and ST-PHPMA-CKI conjugates in rabbits and dogs using hydrogel based delivery devices and a penetration enhancer will be determined. The efficacy and biocompatibility of an hCT and CKI delivery device in an animal model of osteoporosis

Studies 53

will be studied. Based on in vivo animal data criteria will be studied. Based on in vivo animal data criteria will be established for the design of an oral hCT and CKI delivery system for the treatment of postmenopausal osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DENTAL RADIOGRAPHIC PREDICTORS OF OSTEOPOROTIC FRACTURE Principal Investigator & Institution: White, Stuart C. Professor; Diagnostic & Surgical Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (investigator's abstract): Osteoporosis, one of the most common disorders in the elderly, results in over 1.5 million fractures of the hip, spine and other sites each year in the US. Early diagnosis and treatment of osteoporosis is vital to slow or stop bone loss, reduce fracture risk, and decrease disability and death. Our long-range goal is to devise a safe, effective, low-cost screening tool that can be used in a dental practice or public health clinic to identify patients likely to develop a fragility (osteoporotic) fracture. As over three-fourths of adults visit their dentist annually, the dental office is an ideal site for such screening. The objective of this application is to use dental radiographic features and clinical information to develop a statistical-based predictor of fracture risk. Our central hypothesis is that measurable changes in jawbone radiographic features predict patients who will develop osteoporotic fractures. We have found such changes in the maxilla and mandible of osteoporotic patients. We further hypothesize that risk factors differ between individuals with fracture and controls and that such patient-risk factors will provide additional discriminating data. Identification of key radiographic and clinical features associated with osteoporotic fracture will allow us to develop an efficient screening tool using radiographs routinely taken by dentists for other purposes. We are well prepared to undertake the proposed research because we have already measured radiographic features of the jaws in patients with osteoporosis.. Further, we have data from the Leisure World Cohort Study, an elderly cohort (mean age = 85 years) of nearly 14,000 individuals that has been studied for 19 years. We propose a prospective cohort study using all subjects who entered the cohort with no history of adult fracture to evaluate radiographic and patient risk factors of those who develop fracture. To accomplish the goal of our project and test our hypothesis, we will pursue 3 specific aims: 1) identify and validate patient risk factors associated with osteoporotic fracture in the Leisure World Cohort, 2) identify morphologic features of dental radiographs associated with osteoporotic fracture, and 3) determine the optimum combination of radiographic and patient risk factors to quantify an individual's osteoporotic fracture risk as a function of time. We expect that as we found such radiographic changes in patients with osteoporosis, we will find comparable measurable features of the jawbones of patients who develop osteoporotic fractures. Similarly, we expect that these individuals can also be characterized by demographic and behavioral risk factors. We anticipate that these findings can be combined to form a safe, effective risk-assessment model for identifying patients at risk of osteoporotic fracture. This result will be significant because such a diagnostic screening tool would be applicable to a large fraction of the population at little expense and prevent needless morbidity and mortality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

54 Osteoporosis

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Project Title: DETECTION OF THE SPONTANEOUS FRACTURE MOUSE MUTANT GENE Principal Investigator & Institution: Gu, Weikuan;; Loma Linda Veterans Assn/Research Educ for Research Education (Llvare) Redlands, CA 92374 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: Osteoporosis affects up to 40 percent of women and 12 percent of men worldwide and is one of the major health problems in our aging population. Bone fracture is the essential feature of osteoporosis.. Accordingly, studying the molecular mechanism of bone fracture is important for the prevention and treatment of osteoporosis.. We recently discovered a new mouse model to study the genetic mechanism leading to bone fractures. The mutation in this model causes the spontaneous fracture of the bone, called sfx (spontaneous fracture). Our study has shown that sfx mice have reduced bone mass, abnormalities of bone architecture and begin to fracture spontaneously at about 5 weeks. The animal dies at the age of about 6 weeks. Furthermore, we found very little or no osteoid in the femoral metaphysis by histological analysis, thus indicating a severe impairment in bone formation, which our preliminary data suggest is due to osteoblast dysfunction. Because in a histological section of the femoral metaphysis there was no apparent deficiency of osteoblast numbers in the sfx mutant, we tentatively concluded that the decrease in bone formation is due to poor osteoblast differentiated cell function. This proposal, therefore, will use the sfx mice to study the genetic mechanism responsible for the regulation of the osteoblast function. Our data indicate that the sfx mutant is controlled by a single autosomal recessive locus. We further localized the sfx locus on chromosome 14 and mapped the sfx locus into a region of 12 cM flanked by two molecular markers: D14mit203 and D14mit34. We then examined the known genes within this region and found that none of these genes is known to function in a manner that could cause the sfx phenotype or is related to bone formation. Therefore, these data indicate that the sfx mouse phenotype is most likely caused by a new gene. Accordingly, if the gene is identified, it not only can be used to study the regulation of bone formation but also has the potential to be used in the therapeutic application in the treatment of the osteoporotic fracture. This proposal is designed to use state-of-the-art techniques to determine the identity of the mutated gene in the sfx mouse. Our goal in this proposal is to eventually identify the sfx gene. According to the data on the genetic information of sfx mice, we propose the following steps to identify the sfx gene: (1) We will further narrow down the sfx locus to the size of less than 0.5 cM. (2) We will construct BAC contig and sequence the BAC clones. We will analyze for candidate genes within the region of the sfx locus. (3) We will confirm the function of the candidate genes with an in vitro functional assay by approaches involving informatics, microarray and sequencing. It is anticipated that the research in this proposal will lead to the isolation of the gene that causes the spontaneous fracture of the sfx mouse. This will provide an understanding of the mechanism of the sfx phenotype and the identification of similar genes in humans. Therefore, there are potential applications in clinical diagnoses based on the DNA polymorphism and in therapy for the prevention and treatment of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIFFERENTIAL EFFECTS OF GONADAL STEROIDS ON BONE Principal Investigator & Institution: Leder, Benjamin Z.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006

Studies 55

Summary: Osteoporosis in men is an important cause of morbidity and mortality, especially in the elderly. Hypogonadism is a well described risk factor for osteoporosis in men, but the mechanisms underlying hypogonadism-induced bone loss are incompletely understood. A fundamental unresolved question in this area concerns the differential effects of androgens and estrogens on the male skeleton. To address this question, in the first of 3 proposed studies, normal men will be randomly assigned to receive: 1) a GnRH analog alone for 12 weeks (suppressing endogenous gonadal steroids to pre-pubertal levels), 2) a GnRH analog plus testosterone (T) (normalizing circulating T and estradiol levels), or 3) a GnRH analog plus T plus an aromatase inhibitor (normalizing T but causing selective estrogen deficiency). Bone turnover markers will be measured every 4 weeks. Bone turnover will increase in Group 1 and should remain unchanged in Group 2. If estrogens are required to maintain normal bone turnover in men, bone turnover should also increase in Group 3. In the second study, normal men will be randomized into similar treatment groups for 8 weeks with the addition of a group that will receive a GnRH analog plus physiologic estradiol. PTH infusions will be performed every 4 weeks and bone turnover markers will be measured every 6 hours during each infusion. By comparing the rates of change in these markers during PTH infusion, the selective effects of androgens and estrogens on the skeletal sensitivity to PTH will be assessed. In the third protocol, murine stromal cell lines and primary mouse osteoblasts will be exposed to estrogens and androgens to assess their differential effects on osteoprotegerin (OPG) and osteoprotegerin-ligand (OPG-L) mRNA expression. These studies will help elucidate the mechanisms by which gonadal steroids act on bone and enable the candidate to appreciate basic developments in bone biology as well as develop and perform future translational research projects. The training portion of the proposal includes regular mentoring with Drs. Finkelstein and Bringhurst, extensive interaction with the Endocrine Unit faculty, and meetings with the GCRC biostatistician. The candidate will also enroll in the Harvard School of Public Health's Clinical Effectiveness Program and participate in courses offered by the MGH Clinical Research Program. These combined research and didactic endeavors will prepare the candidate to achieve his long-term goal to develop an independent research program focusing on the role of gonadal steroids in bone metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIFFERENTIATION OSTEOBLASTS

AND

PROLIFERATION

OF

HUMAN

Principal Investigator & Institution: Pereira-Smith, Olivia M. Professor; Cellular & Structural Biology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: Clinically important bone loss is a sum of Type I osteoporosis, Type II osteoporosis and the secondary causes. In women, maximum bone mass is attained before age 35 and evidence of trabecular bone loss is already apparent at age 40, before the onset of menopause. During the post- menopausal period, the rate of bone loss is increased (Type I) for approximately 5-10 years, and after this period, bone loss continues at a decreased rate due to Type II osteoporosis.. In men, the rate of bone loss is not as rapid as that of women, it is persistent and due solely to Type II osteoporosis as well as secondary causes. Longitudinal studies of vertebral bone loss reveal relatively rapid rates of osteoporosis, approaching that seen in women. The differences between the types of osteoporosis is clear but the relative importance is less clear. If estimates are correct then 1 in every 3 women will have had a hip fracture by age ninety compared to

56 Osteoporosis

1 in 6 men. The mortality associated with hip fracture in men aged greater than 75 years is 30%, triple that reported for women. Therefore Type II osteoporosis is a very important public health issue, not only for the impact on the healthspan of men, but also for the additive role it plays in women as well. In this condition of bone loss there is normal to slightly decreased osteoclastic activity in conjunction with greatly decreased bone forming ability. This form of osteoporosis is thought to be caused by decreased osteoblast activity/function and has been attributed to various factors such as deficits in recruitment, proliferation and differentiation of these cells at needed sites, as well as changes in the milieu as a result of other age- related processes. It has been shown that there is no bone formation in mice in which the gene encoding the transcription factor for osteocalcin (a gene expressed only in osteoblasts) OSF2/Cbfal has been inactivated. We here propose to test the hypothesis that deficits in differentiated function and/or decreased proliferative ability due to cell senescence occurs with aging in osteoblast cells and contributes to age related osteoporosis.. We will test this by determining OSF2/Cbfal expression, and expression of senescence related genes in bone tissue from young and old donors and proliferation potential as well as expression of these genes in osteoblasts derived from the bone. We will also determine whether osteoblasts can form tissue in a transplatation model system in vivo. The results will provide the preliminary data and evidence that we can perform these techniques for an R01 proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DXA: HEALTH BELIEFS & OSTEOPOROSIS PREVENTION BEHAVIORS Principal Investigator & Institution: Sedlak, Carol A. Associate Professor; None; Kent State University at Kent Research & Graduate Studies Kent, OH 44242 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2003 Summary: Prevention of osteoporosis is an important nursing and health care concern. The purpose of this study is to evaluate the effect of DS (dual energy x-ray absorptiometry) screening on Osteoporosis Preventing Behaviors (OPB) of postmenopausal women between the ages of 50 to 65 at 6 and 12 months post DXA. The theory base is the Health Belief Model (HBM). It is believed that the DXA screening will increase knowledge and influence OPB through potentially mediating health beliefs (perceived susceptibility, seriousness, benefits, barriers, motivation, and self-efficacy). The independent variable is DXA (an objective measure of bone density) which is hypothesized to increase knowledge to increase knowledge of osteoporosis and to affect the dependent variables which are the OPBs (increased calcium intake, weight bearing exercise, smoking cessation, alcohol intake moderation, hormonal replacement therapy and non-hormonal drug therapy) through the mediating HBM variables. The HBM variables, in turn, will influence the OPB. Specific aims are to: 1) Compare HBM variables and Knowledge of Osteoporosis between postmenopausal women who have a first DXA screen and those who have not; 2) Compare performance of OPB health behaviors between postmenopausal women who have a first DXA screen and those who have not; 3) Determine which variables (DXA screen, HBM variables, Knowledge of Osteoporosis) are most predictive of the performance of OPB; 4) Determine if health beliefs are related to the performance of OPB; 5) Determine the mechanism through which DXA screen affects Osteoporosis Preventing Behaviors. The research questions are: 1) Does having a DXA screen cause an increase in Knowledge of Osteoporosis? 2) Does having a DXA screen cause a change in Health Belief scores? 3) Does having a DXA screen cause an increase in OPB? 4) Does an increase in Knowledge of Osteoporosis in OPB? 5) Are Health Belief variable scores related to OPB scores? 6)

Studies 57

Does having a DXA screen cause an increase in OPB when controlling for Knowledge of Osteoporosis? 8) Does Knowledge of Osteoporosis of Health Beliefs have the stronger causal effect on OPB? 9) What are the effect parameters of the proposed model? Statistical analyses are tailored to the aims and derived hypotheses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT METABOLISM

OF

DIETARY

PROTEIN

SOURCE

ON

CALCIUM

Principal Investigator & Institution: Sellmeyer, Deborah E. Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-JAN-2007 Summary: (provided by applicant): Osteoporosis is a major health concern worldwide. While there are drugs available for the treatment and prevention of osteoporosis, they are not practical for population-wide prevention efforts. Demonstrating the effectiveness of safe and widely available dietary interventions to prevent osteoporosis could have important public health ramifications. Different food sources of dietary protein may have different effects on bone metabolism. Animal foods provide a dietary acid load that may lead to negative calcium balance and increased bone resorption. In contrast, vegetable sources of protein, while providing some acid due to their protein content, provide proportionally more base that counters the dietary acid load. The effect of dairy products, which are rich in animal protein but also contain potential base precursors not found in vegetable foods, has not been established. Finally, soy protein sources may have a dual benefit: soy foods provide base precursors as well as plant estrogens that may have a beneficial effect on bone. We are resubmitting this proposal to randomize postmenopausal women to one of four diets equal in calories, protein, calcium, and sodium. The diets will differ by having 80 percent of the protein from one of four sources: non-dairy animal, vegetable, dairy, or soy foods, resulting in significant differences among the diets in acid, base, and isoflavone content. All food will be prepared and provided by the General Clinical Research Center. The subjects will consume the diets for 6 weeks with measurements of acid-base status, isoflavone excretion, and calcium metabolism. In this resubmission, we address the concerns raised by the initial reviewers, followed by a revised research plan that incorporates those changes. This will be the first intervention study to examine the effect of different sources of dietary protein in whole foods on calcium metabolism. Eventually our findings could have substantial public health implications and provide a widely available and low risk means to help prevent osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF DIETARY RESTRICTION ON BONE MINERAL CONTENT OF RHESUS MONKEYS Principal Investigator & Institution: Colman, Ricki J. Assistant Scientist; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: OBJECTIVE To assess the effect of dietary restriction and aging upon bone metabolism in rhesus monkeys. RESULTS Bone mass was lower in dietary restricted animals, however this reflects smaller body size and not pathological osteopenia. In addition, dietary restriction may protect against the development of spinal osteoarthritis. DISCUSSION The pathogenesis of age-related bone loss is unclear. As dietary restriction (DR) retards many aspects of aging, it may also alter skeletal changes.

58 Osteoporosis

The purpose of this study was to examine the effects of moderate DR (30% reduction in caloric intake from individual baseline values) on bone. Bone mass (dual-energy X-ray absorptiometry), turnover (osteocalcin, ICTP, and NTx) and lumbar spine osteoarthritis (OA; radiographs) were examined longitudinally in male (15 Control [C], 15 Restricted [R]; after 96 months of DR) rhesus macaques 8-14 years of age at the onset of DR. Total body bone mass was lower in R compared to C males and females. In the females, R bone mass was also lower than C at the posterior-anterior spine and radius (except for distal radius bone mineral content). Serum turnover markers, and calcium and phosphorus concentration were not different between C and R groups. In addition, testosterone and FSH in the males were unchanged. There was less evidence of spi nal OA in R males. We believe the lower bone mass reflects the smaller body size, and not pathological osteopenia. In this model, DR does not cause deleterious endocrine effects and may afford protection against spinal OA. FUTURE DIRECTIONS We plan to continue using DXA, radiographs and markers of bone metabolism to better characterize the skeletal aging process in rhesus monkeys, making them better understood models for osteoporosis research. KEY WORDS osteoporosis, bone density, aging, bone metabolism, DXA FUNDING NIH PO1 AG11915 Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF HYPOESTROGENISM ON BONE MINERAL DENSITY IN MARMOSETS Principal Investigator & Institution: Saltzman, Wendy;; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: OBJECTIVE To determine whether female marmosets undergo a reduction in bone mineral density following ovariectomy or socially induced hypoestrogenic anovulation. RESULTS Chronic reduction in estrogen causes a reduction in bone mineral density (BMD) and an increase in osteoporosis in most species in which it has been studied. In marmosets, socially subordinate females regularly become anovulatory and may remain hypoestrogenemic for extended periods of time. To determine whether marmosets might possess a mechanism to protect them from the deleterious skeletal consequences of hypoestrogenism, we examined the effect of ovariectomy-induced or socially induced hypoestrogenism on BMD. No differences in BMD were found between ovary-intact and ovariectomized females, or between dominant and subordinate females. A longitudinal study also failed to reveal any effects of ovariectomy on BMD. Thus, marmosets may possess a unique adaptation protecting them from hypoestrogenism-induced bone loss, and might provide a novel model for the investigation and treatment of osteoporosis.. FUTURE DIRECTIONS We plan to confirm and extend our preliminary findings and to begin to investigate the possible biochemical and cellular mechanisms by which estrogen depletion is decoupled from bone loss in female marmosets. KEY WORDS dual-energy X-ray absorptiometry, skeletal system, osteoporosis FUNDING Saltzman, W., C, FED, AG15621, $62,000, NIH. PUBLICATIONS Colman, R.J., W. Saltzman, D.H. Abbott, J.W. Kemnitz, and N. Binkley. 1998. Lack of estrogen depletion bone loss in common marmosets. International Symposium on Biology of Menopause, Newport Beach, CA. [A] Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECT OF RALOXIFENE ON NEURONAL PHYSIOLOGY Principal Investigator & Institution: Audesirk, Teresa E. Biology; University of Colorado at Denver Campus Box 129 Denver, CO 802173364

Studies 59

Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Selective estrogen receptor modulators (SERMs) are synthetic compounds that bind to genomic estrogen receptors (ER), mimicking estrogen in some tissues, and antagonizing it in others. The SERM raloxifene antagonizes estrogen in both the breast and uterus, conferring a degree of protection against breast and uterine cancers, while it serves as an estrogen agonist in lipid and bone metabolism, providing some protection against both osteoporosis and heart disease. In 1997, the U.S. FDA approved the use of raloxifene for the prevention of osteoporosis.. As a result, raloxifene will soon be used by millions of postmenopausal women. There is a large and rapidly growing literature concerning the effects of b-estradiol on the brain, both on brain function generally (maintenance of cognitive abilities and protection against Alzheimer's disease) and on individual neurons (promotion of neurite outgrowth and dendritic spine production, nitric oxide synthase activation, and neuroprotection). A major gap in the current understanding of raloxifene is how it influences the brain. We will use cultured rat hippocampal and cortical neurons to accomplish the following aims: 1. To test the hypothesis that raloxifene will either mimic or antagonize the neuroprotective effects of b-estradiol against oxidative stress in vitro. 2. To test the hypothesis that raloxifene will mimic or antagonize the effects of b-estradiol on calcium levels in neurons. 3. To test the hypothesis that raloxifene will either reduce or enhance calmodulin activation. The SERM tamoxifen reduces calmodulin activity, suggesting that raloxifene should also be tested for this property. 4. To test the hypothesis that raloxifene will mimic or antagonize the effects of b-estradiol on nitric oxide synthase. The production of NO, which has been implicated in several aspects of neuronal differentiation and learning, is enhanced by b-estradiol. This enhancement is blocked by the SERM tamoxifen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF SOYBEANS ON BONE AND THE REPRODUCTIVE TRACT Principal Investigator & Institution: Bahr, Janice M. Professor; Animal Sciences; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, IL 61820 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: (adapted from the applicant's abstract) Some postmenopausal women use hormone replacement therapy (HRT) to maintain bone. This treatment is, however, not acceptable to all women. An alternative approach is intake of foods rich in phytoestrogens - natural plant estrogens such as soybeans. The hypothesis is that soy protein protects against postmenopausal bone loss by slowing resorption and enhancing bone formation due to organ-selective estrogenic effects of the isoflavones genistein and daidzein. The applicant proposes four questions: 1. Efficacy: What is the effect of soy protein and soy isoflavones on bone formation and resorption? 2. Safety: Do soy isoflavones and estrogen have differential effects on bone and female reproductive tissues? 3. Safety: Do soy proteins or isoflavones antagonize the effects of endogenous estrogen on bone and the reproductive tract? 4. Mechanism: Do soy isoflavones differentially affect estrogen-dependent bone resorption and formation through estrogen receptor-mediated mechanisms? In vivo studies will use ovariectomized rats, an established model for osteoporosis, and intact rats. In vitro studies will use mouse calvarial explant culture and an estrogen receptor reporter system. To answer questions 1-3 ovariectomized and inteact rats will be fed diets of various concentrations of soy or isoflavones for 3 months. Measurements during and at termination of experiments are

60 Osteoporosis

urinary deoxypyridine, an indicator of bone breakdown; bone mineral density; and bone formation by histomorphometry. The reproductive tract will be evaluated by histology and production of Complement C3 by the uterus and measurement of estradiol and luteinizing hormone in plasma. In vitro studies (question 4) will determine if isoflavones act through an ER and which subtypes, ERa or ERb. These studies are necessary to identify efficacious and safe alternative approaches to HRT readily accessible to all women. Knowledge of active agents and mechanism of action will allow standardization of soy supplements; identification of doses that maintain bone health without compromising other systems, e.g. reproductive; and assurance against interactions from like compounds in other drugs and food, including supplements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF VITAMIN D AND CALCIUM ON BONE IN PEDIATRIC HIV Principal Investigator & Institution: Arpadi, Stephen M.; St. Luke's-Roosevelt Inst for Hlth Scis Health Sciences New York, NY 10019 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): We have recently observed that HIV-infected children, living in an urban setting in the northeastern United States, have decreased bone mass compared to healthy children. As childhood and adolescence are the critical periods during life for skeletal development and, as it is widely recognized that optimal bone mass accretion during childhood and adolescence may prevent osteoporosis later in life, this observation has serious implications for future risk of osteoporosis and fractures in HIV-infected children. While Highly Active Antiretroviral Treatment (HAART) has been implicated in the etiology of the skeletal demineralization in adults, it remains possible that other factors important for skeletal health, such as vitamin D deficiency, could contribute to or exacerbate bone loss in HIV-infected children. In this regard, we have found that 50% of a small group of HIV-infected children have deficient or insufficient body stores of vitamin D, as measured by serum 25-hydroxyvitamin D levels below 20 ng/ml. The central hypotheses of this proposal are that the prevalence of vitamin D deficiency and insufficiency is increased in HIV-infected children receiving HAART and is related to the decreased bone mass observed in these children. We also hypothesize that supplementation with vitamin D and the recommended daily allowance of calcium will improve bone mineral accrual in these patients, as it does in healthy individuals. We will test these hypotheses in 1. a crosssectional study comparing HIV-infected and healthy children and adolescents with respect to relationships between HIV-infection, vitamin D status, and bone mass, and in 2. a twoyear randomized, controlled clinical trial in which the effects of vitamin D and calcium supplementation on bone mass accrual are compared to placebo in HIV-infected children and adolescents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS METABOLISM

OF

LIPID

OXIDATION

PRODUCTS

ON

BONE

Principal Investigator & Institution: Parhami, Farhad; Associate Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by the applicant) Age-related osteoporosis is characterized by decreased osteoblast number and bone forming activity, and increased bone marrow

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adipocyte content. This suggests a shift in bone marrow mesenchymal stem cell (MSC) differentiation pathways, with increased adipocyte and decreased osteoblast production. The mechanisms underlying these changes have not been defined. Recently, our laboratory has demonstrated that lipid oxidation products (LOPs) inhibit the differentiation of preosteoblastic cells into osteoblasts and promote their adipogenic differentiation in vitro, in parallel with altered responsiveness to bone morphogenic protein-2 (BMP2) and other bone-growth factors. Moreover, mice fed an atherogenic high-fat diet exhibited decreased bone mineral density (BMD) and a reduced capacity of their MSCs to differentiate into osteoblastic cells in vitro. Therefore, it is hypothesized that LOPs contribute to age-related osteoporotic bone loss by decreasing bone cell growth factor production and/or responsiveness, and enhancing adipogenic differentiation of bone marrow stem cells at the expense of osteoblast production. To examine this hypothesis, we will pursue the following specific aims: 1) further characterize the in-vivo effects of high-fat diet on bone resorption and formation as assessed by quantitative bone histomorphometry, bone turnover markers, and changes in bone mass, in parallel with measurements of serum and bone LOP levels and indices of calcium and vitamin D metabolism; 2) examine the in-vivo effects of high-fat diet on bone marrow stem cell adipogenic (PPARg, aP2, and lipoprotein lipase)and osteoblastic (bone-associated alkaline phosphatase and osteocalcin) gene expression and phenotype; 3 ) determine whether treatment with the dietary antioxidant lutein can inhibit the adverse effects of high-fat diet on bone marrow stem cell differentiation, as assessed by effects on bone histomorphometry and adipocyte vs osteoblast specific gene expression; and 4) further define the in-vivo and direct in-vitro effects of LOPs on osteoblast and osteoblast precursor expression of, and responsiveness to, key bone growth factors including TGF-a, IGF-I/1I and BMP-2/4. In particular, we will pursue our recent observation that LOPs both inhibit BMP2 stimulation of marrow stem cell osteoblastic differentiation and promote adipogenesis in vitro, by examining the mechanisms of this effect in terms of changes in BMP2 type IA and lB receptor expression and second messenger generation. It is anticipated that these studies will identify new targets for interventions to prevent and treat age-related osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOSTEAL BONE VOLUME REGULATION AND OSTEOPOROSIS Principal Investigator & Institution: Mohan, Subburaman; Research Professor; Medicine; Loma Linda University Loma Linda, CA 92350 Timing: Fiscal Year 2001; Project Start 01-AUG-1981; Project End 30-JUN-2002 Summary: Adapted from the Applicant's Abstract): The applicants' long-term objective is to identify the molecular mechanisms responsible for the pathogenesis of senile (type II) osteoporosis.. Because impaired bone formation (BF) is a major contributor to this disease, and because insulin-like growth factors (IGFs) have been shown to be important simulators of BF in vitro and in vivo, their studies have been focused towards identifying the role of the IGF system in regulation of BF. This renewal application is focused on one of the IGF system components, IGF binding protein-5 (IGFBP-5). Recent in vitro and in vivo findings support the premise that IGFBP-5 is a key component of the IGF system in bone: first, IGFBP-5 stimulates both basal and IGF-induced osteoblast (Ob) cell proliferation in vitro. Second, IGFBP-5 appears to function as a traditional IGFBP to promote IGF action, and, in addition, appears to act independently of IGF action through its own signal transduction pathway. Third, IGFBP-5 treatment in vivo, in both rats and mice, causes stimulation of BF, as indicated by increases in serum osteocalcin. Fourth, the serum level of IGFBP-5 is significantly decreased in hip fracture

62 Osteoporosis

patients, compared to control patients, which raises the possibility that a deficiency in IGFBP-5 could be a contributing factor to senile osteoporosis.. The first goal of this application is to understand the role of an Ob-derived IGFBP-5-specific protease in regulating the effective concentration of IGFBP-5 in local areas of bone. Towards this goal, the applicants propose to purify the IGFBP-5 protease produced by human Obs and clone the full-length cDNA of the IGFBP-5-specific protease. IGFBP-5 protease will be expressed by recombinant means for biochemical and functional characterization. The functional significance of IGFBP-5 protease will be studied by comparing the biological activity of protease-resistant IGFBP-5 analogs with that of native IGFBP-5 both in vitro, using serum-free cultures of human Obs, and in vivo, using a mouse model system, or alternatively by transgenic approach involving antisense and overexpression of IGFBP-5 protease in human Obs. The function of IGFBP-5-specific protease will also be evaluated by testing the activity of recombinant IGFBP-5 fragments which are identical to those generated by IGFBP-5-specific protease. The application's second goal is to evaluate the IGF-independent effects of IGFBP-5. Towards this end, the investigators propose to determine the in vitro and in vivo effects of IGFBP-5 on BF parameters in transgenic mice lacking functional genes for IGF-I, IGF-II, or type I IGF receptor. The applicants anticipate that these studies will lead to an increased understanding of the role of IGFBP-5 and its protease in the regulation of BF, and in the pathogenesis of osteoporosis.. In addition, if the hypothesis that IGFBP-5 increases BF in vivo is confirmed, this would raise the possibility that IGFBP-5 or its analogs could serve as therapeutic agents in the treatment of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENGINEERING BONE FROM HUMAN ADIPOSE DERIVED STEM CELLS Principal Investigator & Institution: Hedrick, Marc H. Associate Professor; Dental Research Institute; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: Bone engineering with osteoprogenitor cells has enormous clinical potential for the treatment of aging-related bone loss (osteoporosis) or traumatic bone defects. Osteoprogenitor cells such as mesenchymal stem cells (MSCs) from bone marrow are a source of such cells. When combined with polymeric scaffolds and/or osteogenic growth factors these cells may provide new therapies for bone replacement. Our longrange objective is the development of new treatments for human bone loss through tissue engineering. Our central hypothesis is that human adipose tissue contains stem cells or adipose-derived stem cells (ADSCs) which offer advantages over MSCs and other osteoprogenitor cell types. The specific aims of this application are: (1) to clone and characterize human ADSCs, (2) to investigate their ability to form bone both in vitro and in vivo and (3) to determine their ability to repair non-healing bone defects. An understanding of ADSC function and ultimately their regulation, has important implications. First, tissue engineering strategies will benefit by an autologous stem cell source (adipose tissue) that is easily obtainable in 'liter' quantities through a minor surgical procedure (liposuction) that is well tolerated by patients. Second, a detailed understanding of the regulation of stem cell differentiation in adipose tissue could significantly impact the treatment of diseases that are characterized by dysregulated mesodermal cell growth and differentiation such as osteoporosis, heterotopic calcification and obesity. Finally, fundamental issues of mesodermal cell differentiation, mesodermal phylogeny and ontogeny, may be better understood by study of these cells.

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At the completion of this grant, our expectation is that human adipose tissue will be shown to be a reservoir of stem cells. We will also begin to have a basic understanding of the phenotypic changes occurring in differentiating ADSCs after commitment to the osteogenic lineage. Finally, we will assess the clinical utility of ADSCs to repair criticalsized bone defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY OF AGE RELATED BONE LOSS AND FRACTURES Principal Investigator & Institution: Khosla, Sundeep L. Professor and Research Chair; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2002; Project Start 01-JUN-1980; Project End 31-MAY-2005 Summary: This application is for renewed funding for yrs 21 to 25 of RO1 AR27065 "Epidemiology of Age-Related Bone Loss and Fractures." Osteoporosis accounts for at least 1.5 million fractures and costs $14 billion annually in the United States. We will continue our population-based studies on risk factors for osteoporosis using conventional methodologies and the infrastructure of the Rochester Epidemiology Project. However, we will also employ, for the first time in an epidemiologic study, two new state- of-the-art technologies--spiral volumetric quantitative computed tomography (QCT) of the spine and hips (CV 0.7-0.9%) and ultra-high resolution, 3-dimensional peripheral QCT (CV equal to or < 0.4%) of the distal radius and tibia. These instruments allow quantitative measurement of bone macrostructure, such as shape and size, separate determination of cancellous and cortical volumetric bone mineral density (BMD), and assessment of bone microstructural characteristics, such as cortical porosity and trabecular connectivity ("noninvasive bone biopsy"). The proposed research will extend followup on two age-stratified cohorts of Rochester, MN residents (304 women enrolled approximately 1980 and 351 women and 348 men enrolled approximately 1990) but most studies will be made in a new age-stratified cohort of 350 Rochester women and 350 men. Our Specific Aims are: 1) to validate a nationally-employed fracture prediction model; 2) to define the age-related, sex-specific changes of bone macro- and microstructure and to use these to test a number of hypotheses related to pathophysiology and to clinical issues; 3) to test the hypotheses that specific measurements of bone macrostructural and microstructural variables will greatly enhance fracture prediction as compared with BMD by dual-energy x-ray absorptiometry; 4) to assess the pathophysiologic mechanisms by which estrogen (E)deficiency causes bone loss by testing the hypotheses that postmenopausal women with lower levels of E and E-metabolites have greater bone loss, that secondary hyperparathyroidism in late postmenopausal women interacts with E deficiency to protect against cancellous bone loss but to enhance cortical bone loss, and that alterations in levels of serum l,25(OH)2D3 and IGF-I contribute to bone loss in E deficient women; and 5) in aging men, to test the hypotheses that E-deficiency is the main cause of calcellous bone loss and T- deficiency is the main cause of cortical bone loss.. The new bone structure measurements should take us to a new level of understanding of the causes of age-related bone loss and fractures and improve substantially the assessment of risk for osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN METABOLITES EFFECTS ON BONE Principal Investigator & Institution: Turner, Russell T. Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905

64 Osteoporosis

Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: A serious obstacle to the rational design of innovative approaches for preventing and/or treating osteoporosis is the idiopathic nature of postmenopausal bone loss.. Menopause is the most important risk factor for osteoporosis.. However, not all postmenopausal women develop osteoporotic fractures indicating that cessation of the menstrual cycle is insufficient to fully account for the disorder. Our working hypothesis is that the denovo production and metabolism of estrogens are among the most important factors influencing the rate of postmenopausal bone loss.. Estrone (E1) and its metabolites, 16alpha-Hydroxyl estrone ( (16alpha-OHE1) and 2-hydroxyesterone (2-OHE1), are the most abundant estrogens in postmenopausal women. 16alpha-OHE1 has been recently shown to be a negative risk factor (reduced risk) for postmenopausal bone loss, whereas 2-OHE1 has been positive risk factor (increased risk). 2-OHE1 does not have estrogenic activity in ovariectomized (OVX'd) rats. In contrast, 16alpha-OHE1 appears to be a tissue selective estrogen agonist with a profile of activity similar to the anti-breast drug tamoxifen; 16alpha-OHE1 is a much more effective estrogen agonist on bone and liver than on reproductive tissues. These observations suggest that differences in the skeletal activities on 2-OHE1 and 16-alpha-OHE1 are responsible for the observed association between bone mass and circulating levels of these metabolites in postmenopausal women. We propose to test this hypothesis in ovary intact and OVX'd rats. The specific aims are to determine the dose response effects of 2-OHE1 and 16alpha-OHE1 on the expression of immediate response genes in bone and other estrogen target tissues; and establish the long-term effects of the estrone metabolites on bone architecture, turnover and strength. The proposed research will characterize the probably cellular mechanisms of action. The results of these studies are likely to be relevant to women because of the similarity between postmenopausal bone loss and OVX-induced bone loss in rats, as well as the previous success the rat model has enjoyed for predicting the response of the human skeleton to estrogen agonists and markers to predict the rate of postmenopausal bone loss;; 2) manipulation of estrone metabolism by changes in diet or by pharmacological intervention may be a valuable tool for reducing bone loss;; and 3) analogs of 16alpha-OHE1 may be useful for prevention and treatment of postmenopausal osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN REGULATION OF OSTEOCLASTOGENESIS IN OLDER MEN Principal Investigator & Institution: Taxel, Pamela; Medicine; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2004 Summary: This R03 proposal is in response to Research Objective #17, entitled Basic Underlying Mechanisms of Musculoskeletal Aging. Male osteoporosis and hip fractures, primarily diseases of older men, have been poorly studied until recently. While there are numerous factors that cause osteoporosis and determine fracture risk, decreases in gonadal steroids with aging are known to influence bone metabolism in both men and women. Recent evidence has demonstrated the importance of estrogen (E2) in male bone health. E2 exerts a variety of important physiological effects, which are mediated via two estrogen receptors found in adult bone, although the mechanisms by which they interact is not well understood. In preliminary work we have found that ovariectomy in mice is rapidly followed by an increase in the ability of bone marrow cells to differentiate into osteoclasts, the cells that mediate bone resorption. This finding suggests that E2 regulates the ability of hematopoietic precursor cells to differentiate

Studies 65

into osteoclasts, a process that has not been adequately examined. The studies of this proposal represents a collaboration between basic and clinical researchers who wish to determine if human bone marrow cells from older men respond to E2 in a manner similar to that which we have demonstrated in our murine model. Since increased rates of bone resorption appear to be the earliest known effects of estrogen withdrawal on the human skeleton, a better understanding of this process may lead to more effective therapies for the treatment of osteoporosis in both men and women. A unique model in which to better understand the role of E2 in men is that of men undergoing hormonal suppression with LHRH agonists for locally advanced prostate cancer. This therapy leads to hypogonadism, with both low testosterone (T) and E2 levels within a few weeks. Since E2 therapy has been previously used to achieve medical castration, adding back E2 in these men is acceptable and allows the study of the mechanisms of E2 action on bone without the simultaneous influence of T. As the mechanisms of E2 action on male bone metabolism are better understood, it should be possible to analyze these interactions more precisely and develop more specific interventions based on a better understanding of these interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETHANOL EFFECTS ON BONE FORMATION IN PREGNANCY Principal Investigator & Institution: Ronis, Martin Jj. Professor; Arkansas Children's Hospital Res Inst Research Institute Little Rock, AR 72202 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 30-APR-2007 Summary: (provided by applicant): It is well known that women are more susceptible to the adverse effects of alcohol than men. An estimated 5-20 percent of American women consume alcohol during pregnancy. Yet, almost no research has examined the effects of ethanol on pregnant and lactating women. We have developed a total enteral nutrition (TEN) -model that supports the additional nutritional demands of pregnancy. Using the TEN system we have made several important observations: First, with constant infusion of ethanol, blood and urine ethanol concentrations of male and non-pregnant female rats cycle between almost zero and over 500 mg/dl with a frequency of one pulse every 5-7 days. Second, the amplitude of these ethanol pulses is markedly reduced (80 percent) in pregnant female rats suggesting that ethanol metabolism is significantly increased in pregnancy. This would be protective since the rate of ethanol metabolism, at a given ethanol intake, determines the maternal blood ethanol concentrations and toxicity. Third, we have observed that undernutrition during pregnancy significantly elevates the amplitude of pulsatile ethanol concentrations to higher levels. This would be expected to increase maternal toxicity. Fourth, chronic ethanol infusion results in reduced bone formation and strength in non-pregnant animals. This effect is reversed by TNFa and IL-1f3 blockers. Fifth ethanol treatment during pregnancy results in significant reductions in trabecular and cortical bone mineral density at the end of gestation, over and above the effects of pregnancy itself Osteoporosis is an area of significant health care and concern. Normally there is no increased risk of osteoporosis with parity. However, we hypothesize that ethanol will inhibit bone formation during the period of high bone turnover in the latter part of pregnancy, increase bone loss during lactation and inhibit the anabolic phase of bone rebuilding which occurs postpartum in the absence of breast feeding or post-weaning in lactating mothers. This may result in permanent deficits in bone mineralization and strength. These effects may be exacerbated by undernutrition. The TEN system will used to determine the effects of ethanol/nutritional interactions on maternal bone in pregnancy and lactation and on

66 Osteoporosis

skeletal rebuilding post-partum. The role of CYP2E1 and free radicals in the skeletal toxicity of ethanol during these periods will also be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETHANOL MEDIATED OSTEOPOROSIS AND INTERLEUKIN 6 Principal Investigator & Institution: Keller, Evan T. Associate Professor; Laboratory Animal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 20-FEB-1998; Project End 30-NOV-2002 Summary: (Adapted from the Investigator's Abstract): It is well established that chronic ethanol exposure can induce osteoporosis, a debilitating and costly disease. However, the molecular mechanisms through which ethanol achieves its influence on bone is unknown. There is evidence that ethanol may both increase bone resorption and inhibit bone production, resulting in osteopenia. The proinflammatory cytokine, interleukin-6 (IL-6), is an important mediator of osteoclast activity on bone. Furthermore, the investigators provide evidence that ethanol induces IL-6 expression and IL-6 promoter activity in a human bone marrow stromal cell line and increases serum IL-6 levels in mice. Accordingly, they hypothesize that ethanol induces IL-6 gene transcription in bone and the bone microenvironment culminating in osteoclast-mediated bone resorption. To explore this hypothesis, the investigators will perform the following specific aims: 1. Elucidate the mechanism of ethanol s influence on transcriptional activity of the IL-6 promoter in human bone marrow stromal cells; 2. Determine the degree and method of ethanol s influence on IL-6 mRNA stability in human bone marrow stromal cells; 3. Demonstrate that IL-6 contributes to the mechanism of ethanolinduced bone loss in vivo in mice. Aim 1 will be accomplished by a) evaluation of ethanol s effect on nuclear transcript production, b) mutational analysis of the IL-6 promoter for ethanol-responsive cis-acting elements, and c) measurement of ethanolmediated changes in transcription factor activity in a human marrow stromal cell line and primary human stromal cells. Aim 2 will be accomplished by evaluation of a) ethanol induced modulation mRNA half-life, b) mutational analysis of the 3untranslated region (UTR) of the IL-6 mRNA to identify regions effected by ethanol, and c) identification of ethanol-induced changes in trans-acting factors on the 3 -UTR in human marrow stromal cell line and primary human stromal cells. Aim 3 will be accomplished by evaluating for differences in bone metabolism in mice which cannot express IL-6 (IL-6 gene knockout) and control mice (which can express IL-6) fed a liquid ethanol diet for 3 or 24 weeks. Bone metabolism will be evaluated by a variety of measurements including alterations in bone mineral content as assessed by total skeletal ash, bone marrow osteoclast production by marrow culture, osteoclast activity by pit resorption assay, in vivo bone resorption by urinary pyridinoline crosslinks, and osteoclast activity by bone histomorphometry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ETHNICITY, BODY COMPOSITION, BONE DEN AND BREAST CANCER Principal Investigator & Institution: Chen, Zhao; None; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-AUG-2003 Summary: (Adapted from applicant's abstract). Recently two studies reported a strong association between high bone mass and increased risk of breast cancer. According to

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the applicant, this result raises new questions in decision-making for HRT and suggests a potential use of bone mass as an indicator of lifetime estrogen exposure for assessing risk of breast cancer. Additional studies in different ethnic groups appear warranted, because there is significant ethnic variation in frequencies, distributions and severity levels of both osteoporosis and breast cancer. Given the fact that the bone mineral density (BMD) is higher, but the rate of breast cancer is lower in Hispanic older women compared with Anglo women, the Hispanic postmenopausal women would be a model to further evaluate the relationship between breast cancer and bone mass. To date, most knowledge of risk factors of osteoporosis and breast cancer is mainly based on results from Anglo women. It is critical to examine those risk factors in the Hispanic population in order to form specific prevention strategies for this population. The Women's Health Initiative (WHI) provides a unique opportunity to undertake nested case-control studies (NCCS) to further examine these issues in different ethnic groups. However, within the WHI there will not be a sufficient number of breast cancer cases to form a NCCS in Hispanic women, both because the number of Hispanic women in the WHI BMD study cohorts is small (expected n=800) and because breast cancer rate is lower in Hispanic women compared with Anglo. The proposed study is a case-control research design. The controls will be chosen from the Hispanic participants of the Arizona WHI observation study group. No additional data will be collected from the controls. The case (n=140) will be newly diagnosed Hispanic postmenopausal breast cancer patients in Arizona (obtained through collaborative oncologists and surgeons). Measurements will include anthropometry, body composition, BMD, peripheral white blood cells and WHI questionnaires. The relationship between BMD and breast cancer will be evaluated using logistic regression analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION OF OSTEOPOROSIS PREVENTION IN THE ELDERLY Principal Investigator & Institution: Tosteson, Anna N. Associate Professor; Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2002; Project Start 05-JAN-1995; Project End 31-AUG-2007 Summary: (provided by applicant): The broad objective of this research proposal is to improve the health of elderly men and women by identifying more effective osteoporosis prevention and treatment strategies. Osteoporosis disproportionately affects the elderly and is associated with fractures that result in disability, death, and a large expenditure of health care resources. A growing number of interventions are available to prevent, diagnose, and treat osteoporosis.. Cost-effective use of most such interventions requires selective targeting of high-risk populations, yet our previous research documents significant variation in clinical outcomes, cost, and intervention acceptance even among those at highest risk. Thus, the public health benefit of these interventions has yet to be fully realized. We hypothesize that this shortfall stems from multiple patient, provider and health system factors whose contribution to treatment and outcome variation is not yet understood. The proposed extension of AG 12262 entails four aims that will provide new information concerning variation in osteoporosis treatment and outcome. First, through surveys of patients and their healthcare providers, we will identify opportunities to improve intervention among elderly persons who have sustained a fracture; and will characterize correlates of longterm treatment continuation. Second, we will extend our study of fracture outcomes to a national sample to identify the patient, provider and health system attributes that contribute to variation in cost and adverse health outcomes. Third, we will develop a discrete state/event microsimulation model incorporating data from the first two aims

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to assess the cost-effectiveness of alternative osteoporosis interventions. This aim will also provide guidance to those planning future osteoporosis outcome studies through analyses addressing the correspondence between preference-based health outcomes measures and an osteoporosis-targeted health status instrument. Fourth, we will study the use of the microsimulation model as a tool for synthesizing evidence in patientcentered osteoporosis decision aids. Our proposed research will provide results useful in guiding both osteoporosis-related health policy and patient-centered decision making. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXERCISE AND CALCIUM EFFECT ON PUBERTAL BONE GAIN Principal Investigator & Institution: Lappe, Joan M. Professor; Medicine; Creighton University 2500 California St Omaha, NE 68178 Timing: Fiscal Year 2001; Project Start 10-APR-1998; Project End 31-MAR-2002 Summary: (Adapted from Applicant s Description): Osteoporosis is a major public health problem. This application focuses on the problem early in life. Since there are few known safe, effective methods for restoring lost bone to the osteoporotic skeleton, prevention of osteoporosis is crucial. If skeletal development can be maximized during growth, young people will begin adulthood with optimal bone quality and be less likely to develop osteoporosis in later years. Yet bone health of children has not been adequately addressed. This proposal will build on 4 previous studies of bone quality in children. Bone quality in this application is defined as bone mineral content (BMC), determined by densitometry and patellar apparent velocity of ultrasound (AVU). The aims of this experimental study are 1) to test the effect of a weight-bearing exercise program on increases in bone quality in pubertal females beginning at age 9; and 2) to compare the effect of a weight-bearing exercise program with the effect of a highcalcium diet and a weight-bearing exercise program on increases in bone quality in pubertal females beginning at age 9. The primary hypotheses to be tested are: 1) Pubertal females who have completed a 3-year weight bearing exercise program will have higher spine BMC and patellar AVU than pubertal females who have maintained their usual activity level, and 2) pubertal females who have completed a 3-year weightbearing exercise program and a high calcium diet intervention of 1500 mg/day will have higher spine BMC and patellar AVU than pubertal females who have completed the exercise program but have maintained their usual calcium intake. A convenience sample of 114 nine yr. old girls will be randomly assigned to 1 of 3 groups: 1) a group who will be enrolled in a weight-bearing exercise program which meets 3 times/week and who will consume their usual diets; 2) a group who will be enrolled in a weightbearing exercise program which meets 3 times/week and will be given high calcium foods to supply 1500 mg/day; or 3) a control group who will consume their usual diet and maintain their customary activity level. Measurements of spine BMC, patellar AVU, usual dietary intake, height, weight, Tanner Stage, physical activity, and medical and social history will be made on all subjects at baseline, every three months, and at the end of 3 years. Evidence of a positive effect of increased weight-bearing exercise and/or increased calcium intake from food sources on bone quality will be followed by another proposal to determine if the treatment cohorts can maintain their skeletal advantage into late adolescence. The overall long-term aim of the P.I.'s work is to test interventions designed to bring about conscious increases in calcium intake and physical activity in children to improve their bone health and develop lifelong bone healthy behaviors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FACTORS ASSOCIATED WITH GAPS IN OSTEOPOROSIS TREATMENT Principal Investigator & Institution: Feldstein, Adrianne;; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, CA 94612 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 30-SEP-2003 Summary: The human and economic tool of osteoporotic fractures is staggering. Individuals who have had prior fractures are at increased risk of future fractures. Evidence-based clinical practice guidelines and effective treatment are readily available but incompletely utilized in this high-risk group. This is a retrospective cohort study designed to evaluate the treatment gap in older women who have had fracture associated with osteoporosis, to provide the foundation for designing in future secondary prevention programs for re-fracture. The treatment gap, as defined for this study, is that a woman does not receive pharmacologic treatment for osteoporosis.. The gap may be due to clinicians not following guidelines if she either goes untreated without BMD screening, or does not receive a BMD screening and appropriate subsequent treatment, within six months of the index fracture. Or the gap may be due to the lack of patient compliance if treatment is offered but not used. The primary aims are to determine if woman aged 50-89 years with a prior study-eligible clinical fracture 1) the fraction of women with an osteoporosis treatment gap, and what fraction of the gap is due to clinicians not following the guidelines and what is fraction is due to the lack of patient compliance; 2) the distribution of treatment duration and the distribution of patient compliance; and 3) which patient, health care provider, and health care benefit characteristics available in our electronic databases are significantly associated with treatment gaps. The primary outcomes are: 1) provider initiation of treatment, whether or not within 6 months after the index fracture a pharmacologic agent for osteoporosis is dispensed, or BMD by dual x-ray absorptiometry (DXA) screening is completed followed by treatment for a femoral neck T-score at or below -2.5; and 2) for patient compliance with treatment, the percent of time after the index fracture the dispensed medication is taken. This proposal is significant because we will be able to longitudinally evaluate a large dataset of women who have had any index fractures associated with osteoporosis using clinical database. Through our extensive integrated systems we can investigate a broad range of factors for associations with osteoporosis screening, treatment, and compliance with treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FAMILY STUDIES OF IDIOPATHIC OSTEOPOROSIS IN MEN Principal Investigator & Institution: Kurland, Etah S. Medicine; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2002; Project Start 15-MAY-2002; Project End 30-APR-2007 Summary: (provided by applicant): Osteoporosis is one of the most important disorders of our aging population. Many epidemiologic studies provide evidence for a strong genetic component to this disease. However, genetic studies have so far yielded inconclusive and often conflicting results. This is probably a result of the complex etiology of this disorder, and the likelihood that there are multiple mechanisms by which an individual can attain the same, often clinically indistinguishable phenotype of osteoporosis.. Thus, heterogeneous patient populations can undermine progress in identifying which and how genes influence the pathophysiologic processes associated with osteoporosis.. In this proposal the challenge of studying a complex trait will be addressed in three ways. (1) A group of 100 severely affected men with idiopathic

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osteoporosis will be identified and characterized. (2) These individuals will be compared to an equal number of carefully matched, healthy male control subjects with specific reference to hormonal and physiologic indices, bone structural parameters and bone density. The range of phenotypes represented by these indicators and their relationship to osteoporosis will be described. Finally (3) approximately 400 family members of the index patients will be studied, with emphasis on recruiting large numbers of individuals from selected families, to test whether any physiologic and structural indicators cosegregate with osteoporosis in families and whether there is a gender- specificity to the transmission pattern of this disease. This grant will enable the applicant to develop an academic career in metabolic bone diseases with expertise in genetic analysis by allowing her (1) to continue to hone her research skills (2) to learn and apply methods of molecular, epidemiological and statistical genetics, and (3) to acquire independence as a clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FREE OSTEOPOROSIS

IRON,

ESTROGEN

AND

POSTMENOPAUSAL

Principal Investigator & Institution: Liu, Gang; Radiology; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: The goal of this study is to test the hypothesis that loss of estrogen results in loss of control of the levels of free iron in bone which are powerful catalysts for free radical formation, and thus cause oxidative damage. This results in the development of osteoporosis in man postmenopausal women as well as the development of osteopenia in ovariectomized (ovx) adult female rats. To do this, an ovx rat model will be used. Six month old rats will be ovariectomized, followed by a two month period for osteopenia to develop. They will then be treated for three months with (1) estrogen, (2) iron chelator or (3) a combination of estrogen and iron chelator. The animals will be sacrificed at the end of the treatment period and their free iron and mineral levels will be determined by electron paramagnetic (EPR) and x-ray absorptiometry (pDEXA and pOct) respectively. The iron chelator used will be one which has been developed in our laboratory and has been shown to have the ability to efficiently remove heavy metals from bone. The EPR techniques which we will use were also developed in our laboratory. We believe that this small but important project will provide novel insights into the mechanism by which loss of estrogens results in the development of osteoporosis.. Moreover, this new approach will permit the reevaluation of the role of estrogen and will expedite the development of novel pharmaceutical agents for the prevention or treatment of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FT-IR OSTEOPOROSIS

MICROSCOPY

OF

MINERAL

STRUCTURE

IN

Principal Investigator & Institution: Boskey, Adele L. Starr Chair in Mineralized Tissues; Hospital for Special Surgery 535 E 70Th St New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-JAN-1993; Project End 31-JUL-2005 Summary: (provided by applicant): Osteoporosis is estimated to affect 15-20 million people (both women and men) each year, causing significant morbidity and mortality. The widely used predictors of fracture risk are bone mineral density (BMD) and incidence of a previous fracture. One of the dilemmas in the management of

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osteoporosis is that two individuals with the same bone density and similar life-styles can show extensive diversity in their tendency to fracture. There is little information on what, other than differences in life style and fall severity, can account for this discrepancy. The underlying hypothesis of this grant is that discrete differences in mineral and matrix properties contribute to the altered fracture risk in these individuals. Over the past two funding periods, we have shown that Fourier transform infrared microspectroscopy (FTIRM) and imaging (FTIRI) provide reproducible and valuable information on the mineral and matrix properties of bone. We now wish to extend this approach to two new research questions: Aim 1) Do the mineral and matrix properties differ in biopsies from patients with fracture compared with patients without fractures while controlling for age, gender, bone mineral density, and architecture? This question will be tested by assessing biopsied specimens from individuals with different fracture histories and with known age, gender, and bone mineral density. MicroCT will be used to assess architecture of the specimens, and FTIR will be used to characterize mineral and matrix properties. Under this specific aim, we will also examine associations between FTIR parameters and nanoindentation in a subset of biopsies to establish the nanoindentation technique and to test for significant correlations between mineral/matrix properties and indentation modulus and hardness. We will also develop the use of imaging ATR to establish an IR approach that does not required thin sections of embedded bone. Aim 2) Do therapeutic agents reverse the observed alterations in mineral and matrix properties? Specifically we shall examine the relative effects of a SERM (selective estrogen receptor modulator), raloxifene, Hormone Replacement Therapy, and a bisphosphonate (Risedronate) on the mineral and matrix properties in pre- and post- therapy biopsies, to identify the agent(s) that reverse(s) the observed alterations in mineral and matrix properties. Emphasis will be placed on those properties identified in Aim 1 that are most predictive of fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER DIFFERENCES IN OSTEOPOROSIS Principal Investigator & Institution: Barrett-Connor, Elizabeth L. Professor; Family and Preventive Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 01-AUG-1987; Project End 30-NOV-2002 Summary: This is a proposal to extend the Rancho Bernardo Study (RBS) of osteoporosis in order to prospectively examine sex specific rates and risk factors for bone loss and fracture (clinical and vertebral) in older adults. Nearly 1500 men and women aged 55 and older were studied in 1988- 1991 and again in 1992-1995 under a MERIT award, when they were characterized for multiple behavioral, biological and genetic risk factors for osteoporosis and had measurements of bone mineral density (BMD) at the hip and spine obtained four years apart. RBS is the largest prospective community-based study of osteoporosis in the United States in which men and women were studied concurrently using dual energy x-ray absorptiometry (DEXA). Work to date shows striking similarities in accelerated bone loss in the older men and women (greater than or equal to 75 years of age) over four years, and striking differences in the association of BMD with diabetes, insulin IGF-1, and serum testosterone. The cause of gender differences (and their absence) can provide new insights into the etiology, prevention and treatment of osteoporosis in both men and women. In the present study, 550 men and 650 women (>60% aged 70+ years) will have repeat evaluations for selected risk factors and bone turnover markers, repeated BMD measures at the hip and spine; repeat radiographs of the thoracic and lumbar spine; continued follow-up for new

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clinical fractures; reassessment of functional status, quality of life and fall- related comorbidities (including vision, cognition, and muscle strength); and first time evaluation of 25 OH vitamin D; 1, 25 (OH)/2 vitamin D, intact parathyroid hormone, and selected measures of bone size and geometry. This study was designed to provide (1) measures of BMD over a 10 year interval, necessary to determine the timing, frequency and antecedents of accelerated bone loss in both men and women, and (2) continued followup for fractures, necessary to provide adequate numbers of vertebral fractures and clinical fractures to determine fracture risk, risk factors, and consequences in both sexes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC & LIFE-STYLE FACTORS IN MENOPAUSAL BONE DENSITY Principal Investigator & Institution: Salamone, Loran M. Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 15-DEC-1997; Project End 30-NOV-2002 Summary: (Adapted from Investigator's Abstract) This is a revised submission of a FIRST Award. Bone mineral density (BMD) in later life is attributed to peak BMD attained in early adulthood and both menopause and age-related bone loss.. There is compelling evidence to suggest that BMD and its subsequent loss are determined by a combination of genetic and environmental factors. The primary objective of this study is to gain a more comprehensive understanding of genetic and gene-environment interactions as correlates and determinants of BMD in a cohort of 535 healthy women (aged 44-50 years) enrolled in the NIH-funded Women's Healthy Lifestyle Project (WHLP; HL45167; Drs. Kuller and Wing, co-principal investigators). The study proposed will add two candidate genes for osteoporosis, the type I collagen gene and the estrogen receptor gene, using DNA isolated from the baseline examination. The second aim of this application is to examine the effect of a Lifestyle-Intervention aimed at weight loss across the menopause on BMD. The investigators will determine whether differences in BMD between Assessment and Intervention Groups can be explained by differences in markers of bone turnover, including serum osteocalcin and urinary Ntelopeptides. They state that this epidemiological study can improve our understanding of the individual variations in BMD and changes in BMD during the critical menopausal years, and the degree to which these differences are mediated by gene-environment interactions. They further state that gaining insight into these mechanisms has important implications for effective prevention and more efficient identification of those individuals at the greatest risk of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC BASIS OF OSTEOPOROTIC FRACTURES AND BONE MASS Principal Investigator & Institution: Deng, Hong-Wen W. Associate Professor; Medicine; Creighton University 2500 California St Omaha, NE 68178 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-MAR-2006 Summary: (Taken from the applicant's abstract): With diverse research experience in ecology and genetics, the candidate will strive to become an independent and prominent genetic epidemiologist in area of osteoporosis research. Utilizing skills in statistical genetics, the candidate proposes to develop approaches in molecular and genetic epidemiology to search for genes underlying complex traits and to study genotype-byenvironment (GXE) interaction. Osteoporotic fractures (OF) are a major public health

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problem associated with aging. Bone mineral density (BMD) is one major risk factor for OF. Multiple environmental and genetic factors underlie BMD variation and OF risk. Recent studies revealed several genes of potential importance for BMD with little consensus. Few studies investigated the interaction between genetic and environmental factors in determining BMD. Plans are proposed to: 1) investigate the importance of several significant genes in determining the susceptibilities to OF and BMD variation; 2) investigate the differential susceptibilities to deleterious smoking effects on bone for people of different genotypes (GXE interaction). We will recruit 1) 400 random healthy subjects (with smokers and nonsmokers, age 25-50) for a BMD study; 2) 800 random healthy subjects age 60-75, 400 with and 400 without OF, with both groups having smokers and nonsmokers; 3) genotype these subjects with RFLP and microsatellite markers; 4) analyze phenotype and molecular data by adjusting for covariates important for BMD variation and OF. Characterizing environmental and genetic factors and their interactions for BMD and OF is said to be essential for developing effective preventive interventions of OF. The research plan is well written and well conceived. The many strengths of the previous applications remain. In the last submission, the reviewers highlighted three weaknesses, which have been addressed in detail in the Introduction to Revised Application section. There are only a few remaining minor concerns. Five years of support are recommended with an outstanding level of enthusiasm. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC DETERMINANTS OF BONE DENSITY Principal Investigator & Institution: Reis, Robert J. Professor; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, AR 72205 Timing: Fiscal Year 2001; Project Start 27-AUG-1996; Project End 31-MAR-2006 Summary: Osteoporosis, defined by low bone density leading to increased risk of fractures, afflicts many millions in the U.S. Measurement of bone density, together with evaluation of risk factors (e.g., sex, age, and race; low intake of calcium and vitamin D; and chronic exposure to alcohol, cigarette smoke, or glucocorticoids), provides the beast means to identify susceptible individuals. Bone density is largely under genetic control, with heritability-the genetic portion of variance calculated at 60-80%. This proposal seeks to identify gene regions responsible for low bone density in a mouse model of osteoporosis, the SAMP6 strain, and to test them for a similar effect in humans. When SAMP6 mice are crossed to either of two control strains, bone density varies widely among the "grandchildren" of such crosses. By scanning the genome for locations segregating with bone density, and thus associated with it, genes influencing that trait can be positioned. At least 5 high significant genetic regions have been identified that govern bone density of mature mice, and other, distinct loci were found that affect postmaturity change in bone density. To more precisely map some of these genetic regions, offspring of crosses will be mated to one parental strain, and progeny inheriting the implicated region from the other strain will be detected using strain-specific markers. That process is repeated for 8-10 generations, with selection of late-arising recombinants, to create lines of mice retaining only part of a marked region from the "donor" strain, isolated in the "recipient" genetic backgrounds. By defining overlaps among donor segments of many such lines, and measuring bone density for many such lines, the area affecting bone density can be narrowed to a precise span, and then subdivided by further recombinants. Genes in these smaller intervals will be sequenced to reveal differences among the three strains, and bone related traits will be characterized for each line to ascertain divergence from the nearly identical recipient strain. The corresponding gene regions will be tested for linkage to bone density in extended human families, and

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individuals at genes within a narrowed interval, which distinguish between humans having high vs. low bone density. Such studies may give insights into the genetic regulation of bone density and molecular mechanisms underlying osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC DETERMINANTS OF BONE FRAGILITY Principal Investigator & Institution: Econs, Michael J. Associate Professor; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 30-JUN-2005 Summary: Age-related osteoporotic fractures are largely due to an increased propensity to fall and an increase in bone fragility due to a reduction in bone strength with aging. Several factors contribute to bone strength including bone mineral density (BMD), bone structure, bone quality and bone turnover, all four of which have phenotypes that are highly heritable. The long-term goal of this application is to identify genes that underlie bone fragility using the positional cloning/candidate approach. The first step to attaining this goal is to identify chromosomal regions that harbor genes that affect the components of bone fragility and predisposition to fracture. Identification of these genes may: 1) lead to molecular tests that predict the risk of osteoporosis, thereby allowing the early institution of preventive measures; 2) provide insight into the basic skeletal biology that underlies bone fragility and the predisposition to fracture; and 3) identify molecular targets for the development of therapeutic agents aimed at increasing bone strength. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC DETERMINANTS OF OSTEOPOROSIS SUSCEPTIBILITY Principal Investigator & Institution: Cohn, Daniel H. Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, CA 90502 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC EPIDEMIOLOGY OF AGING AND BODY COMPOSITION Principal Investigator & Institution: Towne, Bradford; Associate Professor; Community Health; Wright State University Colonel Glenn Hwy Dayton, OH 45435 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: Conducting a modern genetic epidemiologic study of aging poses formidable logistic and analytic challenges. The key logistic challenge is to have sufficient familial data from individuals aged from middle age on up; the key analytic challenge is that from the process of aging biologically meaningful phenotypes suitable for analysis must be obtained. Significant body composition changes occur in both men and women throughout their adult lives. These changes affect the amount of bone and muscle, and the amount and distribution of fat. These changes in body composition contribute to the risks for complex diseases such as osteoporosis, sarcopenia and heart disease. The logistic goal of the proposed study is to create from existing resources a genetic epidemiologic study of an essential aspect of aging-changes in body composition. The analytic goal is to elucidate the genetic architecture of age-related changes in body composition, broadly defined to include (and acknowledge the inter-relatedness of)

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measures of bone, muscle and fat, cardiopulmonary functioning, lipids and hormones. Familial data for the proposed study will consist of data collected as part of four currently conducted studies, and data to be specifically collected for the proposed study from these study participants and their relatives. These studies are the Fels Longitudinal Study, the Genetics of Hypertension Follow-Up Study, the Health Assessment 2000 Study, and the Osteoporosis Risk Study. The proposed study has three specific aims: 1) Pedigree organization and expansion - will focus on individuals 40 years of age and older; recruited individuals will be selected to maximize the number of relationships between them and their kin; 2) Data organization and expansion - will focus on quantitative measures of body composition and related traits that pertain to specific disease risks, including osteoporosis risk (e.g., bone mineral density), overweight and obesity (e.g., percent body fat), sarcopenia (e.g., fat-free mass), cardiopulmonary functioning (e.g, heart rate, blood pressure, and oxygen uptake), and cardiovascular disease (e.g., lipid and endocrine assays); and 3) Statistical genetic analyses - will proceed from univariate quantitative genetic analyses of cross-sectional data, to multivariate quantitative genetic analyses of cross-sectional and longitudinal data, to linkage analyses of both cross- sectional and longitudinal data in a subset of the data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC EPIDEMIOLOGY OF BONE TURNOVER MARKERS Principal Investigator & Institution: Czerwinski, Stefan A. Community Health; Wright State University Colonel Glenn Hwy Dayton, OH 45435 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2003 Summary: More than 25 million people suffer from osteoporosis in the United States. Osteoporosis is a complex disease of aging that is likely to be attributable to several as yet unidentified genetic and environmental influences. Unlike other tissues in the body that cause to grow after adolescence, bone tissue is continuously growing and resorbing in a process known as remodeling. During most of adult life, growth and resorption rates are in equilibrium. At older ages, however, the rate of resorption outpaces the rate of new bone formation. The result is a progressive loss of bone mineral density leading to increased bone fragility. The overall objective of this study is to collect preliminary data on bone turnover markers in 500 adult family members participating in the Fels Longitudinal Study in order to determine the nature of genetic effects on these traits using quantitative genetic analysis. The results of this one-year pilot grant will be used as the foundation for a larger R01 application analysis. The results of this one-year pilot grant will be used as the foundation for a larger R01 application with a primary research goal of isolating and locating specific genes influencing normal variation in bone mineral density and related phenotypes. For the proposed pilot study, several markers of bone turnover will be assayed from stored serum samples using commercially available kits. These assays include bone-specific alkaline phosphatase, osteocalcin, pyridinoline crosslinks, total deoxypyridinoline crosslinks, C-terminal propeptide of type I collagen and YKL-40. All of these measures of bone loss, yet little research has focused on understanding the genetic basic of phenotypic variation in these traits. The working hypothesis of the proposed study is that genetic factors influence normal quantitative variation in bone turnover. And further, genetic effects on measures of bone turnover ultimately influences bone mineral density and subsequent risk for osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC EPIDIMOLOGY OF OSTEOPOROSIS Principal Investigator & Institution: Xu, Xiping; Associate Professor & Director; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, MA 02460 Timing: Fiscal Year 2001; Project Start 06-SEP-2000; Project End 30-JUN-2005 Summary: Osteoporosis is a chronic disorder characterized by low bone mass and fractures. It affects more than 25 million men and women in the United States alone, where related health care expenditures approach 13 billion/dollars year. The objective of the current proposal is to identify human genes responsible for osteoporosis and to enhance our understanding of the pathophysiology of osteoporosis.. Using peripheral DXA (pDXA) technology to measure proximal radial BMD, a strong predictor for osteoporosis, this proposed investigation will screen 15,000 sib pairs aged 40-64 years in an isolated population in Anqing, China. This will yield 762 sib pairs with extreme values (i.e., in the top or bottom decile of covariate-adjusted proximal radial BMD). The genetic analyses will aim: [1] to perform a total genomic scan at a 10-cM resolution on all 762 ESPs (341 high concordant sib pairs, 327 low concordant sib pairs, and 94 extremely discordant sib pairs) and their parents, and to carry out linkage analysis using the recently improved Haseman-Elston method; [2] to perform further linkage analysis using markers spaced 1-cM apart to saturate regions with significant LOD scores; [3] to develop single nucleotide polymorphism (SNP) markers using DHPLC with an average 100-kb interval covering the regions confirmed by further linkage studies; [4] to identify SNPs in (a) previously reported osteoporosis candidate genes as well as genes involved in major biological pathways of osteoporosis: calcium homeostasis, hormonal dysfunction, osteoblast and osteoclast development and regulation, cartilage matrix metabolism and lipoprotein metabolism; (b) previously identified positional candidates on chromosomal region 2p21.1-24, and (c) positional candidate genes residing in the chromosomal regions suggested by fine mapping efforts; [5] to perform an association study on 800 cases (i.e., below the 10th percentile) and 800 controls (i.e., above the 90th percentile) selected from these 15,000 sib pairs aged 40-64 utilizing SNPs within or in strong linkage disequilibrium with the above candidate genes; and [6] to test the positive findings from the case-control analysis by performing transmission disequilibrium tests (TDT) based on the ESP families. The Human Genome Project (HGP) has set a new goal to complete the human genome sequence by the end of 2003. Therefore, by the time our initial genome scan and the follow-up linkage analyses are completed, almost all human genes will be sequenced and mapped. Such an interaction with HGP will greatly accelerate the speed of our gene discovery process and will provide crucial guidance for our consequent gene assessment and gene evaluation. After candidate variants have been defined, their clinical value for prediction of osteoporosis could be tested in over 7,000 well characterized women who have been followed for over 10 years in the Study of Osteoporotic Fractures and in participants of the Health and Body Composition (HABC) and Mr. OS (Osteoporosis in Men) studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS OF BONE AND VASCULAR CALCIUM IN TYPE 2 DIABETES Principal Investigator & Institution: Carr, John J. Div of Radiologic Sciences; Wake Forest University 2240 Reynolda Rd Winston-Salem, NC 27106 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2005

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Summary: (provided by applicant): The broad long-term objectives are to improve health and reduce deaths in people from osteoporosis, CVD and type 2 diabetes. The specific aims are focused on the genetic and environmental factors that contribute to vascular calcification (VC) and bone mineralization (BM) in type 2 diabetic families. The health relatedness is that cardiovascular disease (CVD) is the number one cause of death in the U.S. and the risk of CVD is significantly increased in individuals with type 2 diabetes. Osteoporosis is present in 10 million citizens with another 18 million estimated to have low bone mass. This is an ancillary proposal to the "Genetic Epidemiology of Subclinical CVD in Type 2 Diabetes" (HL67348) also know as the "Diabetes Heart Study" or DHS. DHS uses a family study design and quantitative measurement of CVD phenotypes to locate and identify genes contributing to subclinical atherosclerosis in sibling pairs concordant for type 2 diabetes. The impact of lifestyle and environment on gene expression for subclinical disease as measured by BM and VC will be determined. In this proposal, measures of bone mineralization and aortic VC will be added to our existing array of CVD phenotypes, which include vascular calcium (VC) of the coronary and carotid arteries. We will use the additional quantitative measures of BM (QCT, DXA, QUS & Biomarkers) to understand the genetic relation between BM, VC, CVD, osteoporosis and type 2 diabetes. The Specific Aims are: 1) Measure and describe BM & VC in a high-risk population for CVD, families with sibling pairs concordant for type 2 diabetes and unaffected family members. 2) Measure the strength of association between vascular calcium and bone mineralization - further characterize the association by presence or absence of type 2 diabetes, ethnicity, and gender. 3) Estimate the familial aggregation and heritability of BM & VC in the Diabetes Heart Study families.4) Investigate if candidate gene polymorphisms, previously identified for BM & VC, are associated with the primary phenotypes measured in DHS. 5) Identify specific chromosomal regions containing quantitative trait loci (QTLs), which influence BM &VC, using the genome-wide screen. 6) Perform fine mapping, conduct association and haplotype analyses, and identify novel candidate genes for chromosomal regions with strong evidence for linkage to the primary phenotypes, BM, VC and CVD. An established and active multidisciplinary team of investigators using advanced methods of phenotype quantification, molecular genetics, and genetic epidemiology will conduct this research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF OSTEOPOROSIS IN THE AMISH Principal Investigator & Institution: Shuldiner, Alan R. Professor of Medicine; Medicine; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 30-JUN-2005 Summary: Our overall objective is to localize chromosomal loci (and ultimately genes) that predispose to osteoporosis by performing a genome wide search using state-of-theart molecular and statistical genetic approaches in a unique family collection, the Amish Family Osteoporosis Study. The Old Order Amish are ideal for these studies since they are a closed founder population who are relatively genetically homogeneous, and have very large family sizes and well documented genealogies. Since February 1997, Dr. Shuldiner recruited and studied 368 Amish individuals from 30 families. This proposal brings together three strong research groups with complementary interests: Alan Shuldiner, M.D. and Elizabeth Streeten, M.D. at the University of Maryland, Braxton Mitchell, Ph.D. at the Southwest Foundation for Biomedical Research, and Daniel McBride, Ph.D. at Johns Hopkins University. First, we will expand the Amish Family Osteoporosis Study from 368 to 1,000 subjects (about 100 families) by recruiting and

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phenotypically characterizing additional Amish subjects. Second, we will perform genome-wide quantitative trait linkage (QTL) analyses of bone mineral density and related traits to locate chromosomal regions containing osteoporosis susceptibility genes utilizing 391 polymorphic short tandem repeat (STR) markers spaced at approximately 10 cM intervals. Genome-wide association analyses, using transmission disequilibrium tests and other tests of association will be performed, to evaluate whether specific alleles and/or haplotypes shared across families are associated with variation in bone density and related phenotypes. We will also determine whether previously described genetic variation in genes for the vitamin D receptor (VDR), collagen type I alpha 1 (COLAIA1), and the estrogen receptor, influence phenotypic variation in bone density, and measures of bone formation and bone resorption. Finally, we will type additional markers in chromosomal regions showing possible linkage and/or associations and will perform linkage and association analyses using this denser marker set in order to strengthen signals and improve localization of genes influencing bone density and related quantitative traits. Discovery of osteoporosis susceptibility genes will provide (i) critical insights into molecular mechanisms, (ii) new molecular targets for therapeutics, and (iii) blood tests for the early detection of susceptibility individuals so that preventative interventions can be instituted. These advances will impact substantially on the quality of life of millions of older Americans with osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF SEX EFFECTS ON BONE DENSITY AND TURNOVER Principal Investigator & Institution: Havill, Lorena M.; Southwest Foundation for Biomedical Res San Antonio, TX 782450549 Timing: Fiscal Year 2003; Project Start 28-JUN-2003; Project End 27-JUN-2004 Summary: (provided by applicant): Osteoporosis and its associated skeletal fragility are paramount public health concerns. With 10.1 million individuals currently diagnosed with osteoporosis, 77% of whom are women, the need to understand the biological mechanisms behind this complex phenotype is immediate. The dramatic sex difference in fracture risk requires explanation, and may provide clues for deciphering the causes of osteoporosis.. Low bone mineral density, the most reliable indicator of osteoporosis susceptibility, results from complex interactions between genes and environment. Using existing data for areal bone mineral density (aBMD, g/cm2), as measured by DEXA at six skeletal sites, and serum measures of bone turnover in 676 adult, pedigreed baboons, this project aims to (A) detect and characterize the effects of sex, age, and female reproductive history variables on the phenotypic variance in aBMD and serum measures of bone, (B) quantify the effects of genotype-by-sex, genotype-by-age, and genotype-by-reproductive history variable interactions on normal quantitative variation in aBMD and serum measures of bone turnover, and (C) incorporate genotype-byenvironment (GxE) interactions in variance component linkage models to assess the contributions of bone-related QTLs, previously localized in these baboons, on detected GxE interactions and conduct whole genome linkage screens to localize new QTLs responsible for detected GxE effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLUCOCORTICOIDS AND OSTEOBLAST APOPTOSIS Principal Investigator & Institution: Gronowicz, Gloria;; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806

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Timing: Fiscal Year 2001; Project Start 30-SEP-1987; Project End 31-JUL-2005 Summary: Description (Taken from the application): Our objective is to understand the contribution of apoptosis in determining bone mass and skeletal structure, in particular if apoptosis of osteoblasts contributes to the decrease in bone mass found with high dose glucocorticoids. We have shown that glucocorticoids induce apoptosis and estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro. Glucocorticoids were shown to decrease bcl-2 and up-regulate bax levels creating a dose-dependent decrease in the bcl-2/bax ratio that resulted in cell death. We propose to study the effect of bcl-2 overexpression on, osteoblasts responses to glucocorticoids in vitro by transfection of osteoblasts. The extent of bcl-2 expression, the rate of apoptosis and proliferation, and the expression of bone markers will be assayed. We will then determine if bcl-2 overexpression in vivo will prevent the glucocorticoid-induced decrease in bone mass. A transgenic mouse will be constructed that overexpresses bcl-2 targeted to osteoblasts by the 2.3 kDa promoter region of the Type I collagen gone (Co12.3Bc1-2) and its bone phenotype will be characterized. Then these mice and their wild-type litter mates will be treated with and without glucocorticoids. Static and dynamic histomorphometry will be performed along with assays for apoptosis. Our hypothesis is that bcl-2 overexpression will partially prevent glucocorticoid-induced osteopenia. The specific osteoblast functions that are protected from glucocorticoids action in the Co12.3Bc1-2 mouse, will be studied. Finally, we will determine the time course and extent of apoptosis in bone cells after ovariectomy in wild-type and Co12.3Bc1-2 transgenic mice. Bone mass and apoptosis will be assessed. Since little is known about the role of apoptosis in determining skeletal structure and mass, these studies will test the hypothesis that systemic hormones, such as glucocorticoids, affect bone cell function and ultimately bone mass through the regulation of programmed cell death. We also seek to elucidate the contribution of apoptosis to glucocorticoid-induced osteoporosis.. If apoptosis is an important determinant of bone mass, then our longrange goal is to develop novel strategies to prolong osteoblast survival and function during glucocorticoid therapy, and after menopause in patients at risk for osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEALTHY CHILDREN AND HEALTHY FAMILIES PROGRAM Principal Investigator & Institution: Hovell, Melbourne F. Professor and Director; Graduate School of Public Hlth; San Diego State University 5250 Campanile Dr San Diego, CA 92182 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: This study is designed to determine whether parent training is an effective means of increasing children~s consumption of a high calcium diet and increase their strength and aerobic exercise in order to prevent osteoporosis as adults. Sedentary children (N = 180) with a history of low calcium intake and a family history of osteoporosis will be recruited sequentially. Males and females form different racial/ ethnic backgrounds will be included. One child/family will see as the unit of random assignment A 2 X 2 X 7 random assignment, repeated measures, design will be employed. Children and their parents will be divided into two groups. The experimental group will receive educational and support services for diet and exercise change in the target child (N = 90). Each of these conditions will be divided again at random into two subgroups: one ( N = 45) will obtain parent-training concerning the target topic (i.e. Safety or diet and exercise); the second group (N=45) will obtain the same instruction plus episodic coaching. Training will require 12 weekly classes and will emphasize principle of behavior and contingency management techniques. Coaching

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procedures will be provided over 9 months and will assist parents with problem-solving in order to refine and maintain parenting skills. Measures will be obtained seven times, prior to parent-training, at the end of parent training ( at 3 months) , and repeatedly through the coaching and one year follow up period. Outcome measures will include 24 hour recall estimates of change in diet., and change in physical activity. These will be validated by objective outcome measures, including 5Rm strength and , VO2 max fitness measures. Using stat of the art DXA scans, total bone calcium, bone density and specific site bone density will be obtained. Body composition and skeletal age also will be assessed by DXA Generalized estimating equations will be employed to estimate main effects covariates, and interactions to test study hypothesis. Exploratory analyses will include assessment of hypothetical processes, such as parenting practices and child/parent interactions (based on objective video tape measures as mediating variables in achieving changes in bone density. Results will inform clinical and educational prevention of osteoporosis in male and female from different racial/ethnic backgrounds at risk of osteoporosis as adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIP OSTEOPOROSIS

RADIOGRAPHS:

NOVEL

METHOD

TO

DIAGNOSE

Principal Investigator & Institution: Arnaud, Claude D. Professor Emeritus; Imaging Therapeutics, Inc. 1720 S Amphlett Blvd, St 240 San Mateo, CA 94402 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2004 Summary: (provided by applicant): This Small Business Innovation Research Phase I project is designed to develop techniques for the diagnosis of osteoporosis and for assessing fracture risk by quantifying trabecular structural elements in hip x-rays. Osteoporosis is a public health threat for 44 million women in the United States alone. The inability to identify persons at risk for the disease is a major impediment in dealing with this epidemic. In fact, less than 30% of persons with osteoporosis are aware that they have it. This is due to the high cost and resulting small installed base of commercially available osteoporosis testing systems. Imaging Therapeutics Inc. proposes to develop technology for low-cost bone structural analyses by linking readily available x-ray equipment to novel image analysis algorithms. While measurements of bone mineral density (BMD) are easy to perform and are helpful in determining when to intervene therapeutically, low BMD accounts for only a portion of fracture risk. Progressive disruption of trabecular structure contributes the better part of the remainder of that risk. The aims of this proposal are: 1) To develop new image processing techniques for automated measurement of 2D-trabecular bone structural elements in hip radiographs. 2) To determine the influence of x-ray beam angulation, soft-tissue attenuation and radiographic technique on radiographic measurements of bone structure. 3) To determine the clinical validity of those 2 D measurements in vitro by a) comparing them, in cores of cadaver proximal femora, to similar measurements made using 3D micro CT and b) determining if they correlate significantly with biomechanical failure loads and stiffness. 4) To directly apply the technology developed in Phase I of this proposal to a series of clinical trials that will be developed for Phase II to prove the clinical utility of that technology in the diagnosis of osteoporosis and prediction of osteoporotic fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SARCOPENIA

IGF-1/BP-3

IN

GLUCOCORTICOID

OSTEOPENIA

AND

Principal Investigator & Institution: Fairfield, Wesley P.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: Osteoporotic fractures and myopathies are disabling consequences of chronic glucocorticoid (GC) therapy. In vitro and in vivo, GCs inhibit osteoblast production of insulin-like growth factor I(IGF-I), a hormone known to promote collagen synthesis and cell replication in bone. GC therapy may also interfere with systemic action of IGF-I by increasing levels of a circulating IGF-I inhibitor. Negative GC effects on IGF-I production and action, therefore, appear to be important mechanisms by which GCs induce osteoporosis.. Furthermore, GC therapy often results in muscle atrophy and weakness. IGF-I has been shown to have anabolic effects on skeletal muscle and may prevent the catabolic changes induced by GCs. The proposed studies will investigate the pathophysiology of GC effects upon bone and muscle and determine whether administration of IGF- I/BP-3 may prevent GC-induced osteoporosis and myopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IGF-I AND BONE LOSS IN WOMEN WITH ANOREXIA NERVOSA Principal Investigator & Institution: Klibanski, Anne; Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 19-MAY-1997; Project End 31-AUG-2003 Summary: (Adapted from the Applicant's Abstract): Anorexia nervosa is an increasingly common disorder among young women, characterized by self-imposed restrictive nutritional practices, which occurs in 0.5 to 1.0% of college age women in the United States. This psychiatric disorder results in significant medical complications, which cause morbidity and increased mortality. One of the most prevalent and predictable comorbid conditions is osteopenia. Bone loss is a severe, frequent and often permanent comorbid medical complication of anorexia nervosa, resulting in crush fractures. The majority of young women have evidence of bone loss and 50% of women have bone density measurements greater than 2SD below normal and below the fracture threshold. The extreme rapidity of bone loss in anorexia nervosa is well-documented. Of importance, bone loss can occur in less than one year. Reduced bone mass is often permanent, despite recovery, and such young women will have a permanent increased risk of fractures throughout life. Anorexia nervosa is a unique state of imbalanced bone turnover, with decreased bone formation and increased resorption. In contrast to other states of bone loss associated with estrogen deficiency, estrogen therapy is ineffective in stabilizing or improving bone mass. Therefore, it is suggested that the bone loss seen in anorexia nervosa is unique in terms of severity and pathogenesis. Given the complex medical and compliance issues in patients with this disorder, approaches to the prevention and treatment of osteoporosis differ from other populations. Effective therapy of bone loss during acute illness would reduce fracture risk throughout life. Of importance, a therapeutic intervention may only need to be used for a relatively short period of time while the disease is still active in many patients. Because there are currently no treatments for this serious medical sequela of anorexia nervosa, it is critical to develop efficacious treatment strategies to prevent the significant morbidity associated with osteopenia in this population. Insulin-like growth factor-I is a nutritionally regulated hormone with potent autocrine/paracrine effects on bone growth and remodeling. Anorexia nervosa leads directly to pathologic state of IGF-I

82 Osteoporosis

deficiency. It is hypothesized that IGF-I administration plays a critical role in normalizing bone turnover and, long-term, will improve bone density and prevent the progressive debilitating osteopenia in young women with anorexia nervosa. The applicants have now demonstrated a dose-dependent effect of short-term rhIGF-I administration to increase markers of bone formation and/or resorption. They note that these are the first data to show that IGF-I can increase bone turnover and, more specifically, bone formation in patients with anorexia nervosa. Because of its effects on bone formation, rhIGF-I may represent a novel approach to treating the severe osteoporosis resulting from anorexia nervosa in young women. In the current proposal, they will investigate the physiology of the effects of acute administration of rhIGF-I to reverse the IGF-I deficiency state. They will investigate the time course of effects on bone turnover and whether rhIGF-I administration has prolonged effects on bone formation. They will determine whether chronic administration of rhIGF-I increases bone mass, and the interaction of IGF-I and gonadal steroids to both increases bone formation and decreases resorption. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IL-6 AND ESTROGEN AND PTH INDUCED BONE RESORPTION Principal Investigator & Institution: Masiukiewicz, Urszula S. Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 15-AUG-1998; Project End 30-JUN-2003 Summary: (Taken from the applicant's Abstract): Osteoporosis is an important disease of aging. The age-specific incidence of Osteoporosis is an important disease of aging. The age-specific incidence of the disease is table or increasing, and when this is coupled with the greater number of older Americans in the at risk population, it is clear that the prevalence of this disease will rise for the foreseeable future. Already nearly one million fractures occur annually in persons over the age of 65, and the vast majority of these are due to osteoporosis.. Osteoporosis is due to the permanent loss of otherwise normal bone from the skeleton. Of the various subtypes of this disease, postmenopausal osteoporosis is by far the most common. Increased bone resorption is the principle mechanism for bone loss in postmenopausal osteoporosis, and recent evidence indicates that rates of bone resorption are important predictors of bone mass in older individuals. Parathyroid hormone (PTH) is the principle regulator of bone resorption on a day to day basis, and increasing sensitivity to PTH may underlie the increased bone resorption seen in osteoporosis.. We have demonstrated that the pro-resorptive cytokine, IL-6, is regulated by PTH in vitro and in vivo and plays a crucial role in mediating the resorptive actions of PTH. Thus we have recently shown that circulating levels of IL-6 are elevated in states of parathyroid excess, are low in hypoparathyroidism, and correlate strongly with markers of bone resorption in patients with primary hyperparathyroidism. In experimental animals, we have demonstrated that PTH infusions cause serum IL-6 levels to rise and that neutralizing antisera to IL-6 block PTH-induced increases in bone resorption. Finally, in both cultured bone cells and mice, we have demonstrated that estrogen withdrawal increases IL-6 production in response to PTH. We hypothesize that IL-6 is an important mediator of PTH's resorptive actions in bone and that in the estrogen deficient state, PTH-dependent IL-6 production increases. To test this hypothesis: (1) We will examine the response of postmenopausal women to an infusion of PTH, before and after estrogen replacement, to determine if estrogen affects PTH-induced changes in IL-6. (2) We will determine whether neutralizing IL-6 in vivo blocks PTH-induced bone loss in mice and whether IL-6 knock-out mice do not lone bone in response to PTH, we will also examine if

Studies 83

ovariectomy augments PTH-induced bone loss and PTH-induce increases in circulating IL-6 in mice. (3) We will study the molecular mechanism of the PTH-induced increase in IL-6 production by bone cells and the modulating effect of estrogen on this process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVEMENTS IN RAPID MIX FLOW CELL DESIGN FOR SUB MILLISECOND PROTEIN FOLDING Principal Investigator & Institution: Marinkovic, Nebojsa;; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001 Summary: Osteoporosis is a disease characterized by reduction in bone mass, resulting in a fragile skeleton. It is clear that bone loss occurs in the disease; however, the quality of bone remodeled after the onset of Hthe disease is unknown. We are using synchrotron infrared microspectroscopy to analyze the chemical composition of bone remodeled before versus after the onset of osteoporosis.. In our study, female cynomolgus monkeys were ovariectomized or sham-ovariectomized. After ovariectomization, many monkeys developed osteoporosis.. After surgery, the monkeys were administered fluorescent drugs every six months for two years prior to necropsy. These fluorochromes (tetracycline, calcein, and xylenol orange) are taken into newly remodeled bone tissue. Thus, by combining fluorescence microscopy and infrared microspectroscopy, we are able to identify and compare the chemical composition of new versus older bone Hgrowth. We are examining the mineral/matrix ratios, mineral composition, and matrix composition as a function of bone age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: INDUCING BONE FORMATION--LOW DOSE DOXYCYCLINE FOR POSTME Principal Investigator & Institution: Gruber, Barry;; State University New York Stony Brook Stony Brook, NY 11794 Timing: Fiscal Year 2001 Summary: Osteoporosis is a prevalent disease with widespread devastating clinical consequences. Treatment to date has involved agents which by and large prevent bone loss rather than induce new bone formation; thus we have obvious limitations in treatment options for the patient with established disease. No safe effective bone forming agent has yet to be approved for the treatment of this disease. The purpose of this study is to test the safety and efficacy of Low Dose Doxycycline for stimulation of bone formation in postmenopausal women with osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: INHIBITORS OF RANK AND RANKL IN OSTEOPOROSIS TREATMENT Principal Investigator & Institution: Singh, Sujay K.; Imgenex 11175 Flintkote Ave Ste E San Diego, CA 92121 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2004 Summary: (provided by applicant): Osteoporosis is a major health problem affecting nearly 1.5 million people every year. The reduction of sex hormone levels in both men and women increase production of certain factors that lead to osteoporosis.. One-third of all post-menopausal Caucasian women experience at least osteoporotic fracture

84 Osteoporosis

during their lifetime. In addition, more than 70 percent of patients with advanced breast or prostate cancer have skeletal metastases leading to bone degradation due to osteoclastogenesis. Ongoing osteoclast activity appears to be involved in the generation and maintenance of ongoing and movement-evoked pain. Blockade of ongoing osteoclast activity appears to have the potential to reduce bone cancer pain in patients with advanced tumor-induced bone destruction. Recent studies have shown that RANKL, a member of the tumor necrosis factor superfamily, by acting through its receptor RANK can induce osteoclast formation leading to osteoporosis.. In the present study, we propose to identify peptide inhibitors by screening peptide display libraries. The ability of these peptides to interfere with RANKL induced osteoclast formation will be tested. The inhibitory effect of selected peptides in animal models will be tested in the Phase II study. The selected peptides can be used to design even smaller peptides or small molecule non-peptide mimetics, which can be used as therapeutic drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTEGRATED METHODS TO DISCOVER NOVEL DISEASE PATHWAYS Principal Investigator & Institution: Del Mastro, Richard G.; Genome Therapeutics Corporation 100 Beaver St Waltham, MA 02453 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2004 Summary: (provided by applicant): Our goal is to accelerate the rate of discovery of novel therapeutic agents by rapidly assigning function to genes with no experimental functional data (NEFD) and organizing them within Protein Interaction Network (PIN) maps. This will facilitate the identification of novel candidate drug targets in diseaseassociated pathways, such as osteoporosis and Alzheimer's Disease. To begin with, we have mined the public domain and identified a sub-set of NEFD genes (1241) to populate a prototype knowledge database. The design of the database is based on a generic data model with a web based user interface. The aim is to build an Integrated Knowledge Workbench (IKW) in which all data, determined in silico and experimentally, will be incorporated. To transition the prototype to the IKW, we will integrate a suite of bioinformatics analysis tools that will be used to generate detailed in silico fingerprints for every NEFD gene. Furthermore, in Phase I we will integrate protein interaction data derived from our yeast two-hybrid experimental platform. Results from these analyses will be incorporated systematically into the knowledgebased component of the database. To test the platform we will randomly select 5 NEFD genes, generate in silico fingerprints and identify their protein interactors. These data will be integrated to assign a function and produce PIN maps that will chart each of the NEFD genes in a pathway. This test of the system will illustrate the utility of the integrated platform to obtain pertinent information about genes of unknown function and will begin to assist in the determination of their potential role in osteoporosis and Alzheimer's disease-associated pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTRACELLULAR SIGNALING OF BONE MORPHOGENETIC PROTEINS Principal Investigator & Institution: Huang, Hui-Chuan C. Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 30-NOV-2002

Studies 85

Summary: Osteoporosis is a common disease among the elderly, especially in postmenopausal women. Current treatments for osteoporosis are aimed at inhibiting bone resorption. Thus, treatments that promote bone formation could provide a major improvement in the therapy of osteoporosis.. Bone morphorgenetic proteins (BMPs) are able to induce ectopic bone formation and have been proposed as possible agents to stimulate new bone formation in patients with osteoporosis.. Downstream components of the BMP signaling pathway may also serve as targets for therapy in osteoporosis, but little is known about how BMPs signal from the cytoplasm to the nucleus, particularly how they activate gene expression in responsive cells. Our long term goals are to use the molecules we identify in Xenopus to characterize BMP regulated gene expression in other BMP responsive tissues, particularly osteogenic precusors, and to explore these molecules as potential therapeutic targets in the treatment of osteoporosis.. Xenopus embryos will be used for much of the experiments described here, since they have provided a highly successful model system for the study of other BMP functions as well as the characterization of activin/TGF-beta regulated gene expression. The specific goals of this proposal are to determine the promoter sequences that mediate Mix.2 gene expression in response to BMP-4 in Xenopus laevis and to characterize the transcription factors that interact with these sequences. Our preliminary evidence suggests a direct role for Smad proteins in the induction of the Mix.2 gene, and this role will be further explored by characterizing the interactions between Smad genes, BMP-4 regulated transcription factors, and the DNA elements within the BMP-4 regulated promoter. Several novel genes have been identified in a yeast two-hybrid screen that interact with the Smad1 protein. These clones will be characterized further by examining their patterns of expression and their ability to interact in vivo with Smad1 and/or transcription factor complexes regulating Mix.2 gene expression. In future studies, these proteins characterized from Xenopus will be identified in mammalian tissues, particularly osteogenic precursor cells, and examined for their roles in mediating bone formation in mammals in response to BMPs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: JOINT CALCIFICATION

DETERMINANTS

OF

BONE

DENSITY

AND

CVD

Principal Investigator & Institution: Mitchell, Braxton D. Professor; Medicine; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): There is growing evidence of a link between osteoporosis and atherosclerosis. Recent studies document that bone mineral density (BMD) is inversely correlated with severity of aortic and coronary artery calcification, markers of atherosclerosis. Several common pathways have been proposed to link these two disorders. The overall objective of this project is to evaluate the relationship between BMD and coronary artery and aortic calcification, measured by Electron Beam CT, in 700 members of a large Amish pedigrees already participating in the Amish Family Osteoporosis Study (AFOS). By focusing on families, we can tease out the respective contributions of genetic and non-genetic factors to this clustering of traits. The AFOS was initiated in 1997 to identify genes influencing susceptibility to osteoporosis in families ascertained for fracture risk. Through NIH funding available to the AFOS parent study, we will genotype 391 highly polymorphic short tandem repeat (STR) markers spaced at approximately 10 cM intervals and perform a genome-wide scan to detect quantitative trait loci (QTLs) associated with variation in BMD and related traits. The Old Order Amish are ideal for the funded and proposed studies since they

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are a closed founder population who are relatively genetically homogeneous, have very large family sizes, and well-documented genealogies. The study proposed here will use the available measures of BMD, related traits, and genotypes in the AFOS along with the newly collected measures of vascular calcification. This study, a natural extension of the AFOS, brings together a strong interdisciplinary team of researchers with a substantial track record in both cardiovascular disease and osteoporosis and expertise in epidemiology, statistical genetics, and molecular genetics. The specific goals proposed are to determine if BMD is correlated with coronary artery and aortic calcification CAC and, if so, to determine the contribution of common genes or shared environments to this association in families. We will next assess genetic heritability and non-genetic contributions to variability in vascular calcification determinants of CAC in these families. We will assess the individual and joint contributions of lipid oxidation to BMD and vascular calcification CAC. Using the extensive genotyping that will be available, we will perform a genome wide scan of coronary artery and aortic calcification CAC. These results will complement the similar analyses obtained on the bone-related phenotypes. Finally, we will determine if chromosomal regions linked to variation in BMD are also linked to variation in vascular calcification or to another possible joint determinant such as CAC (or to lipid oxidation). These studies will provide insights into joint determinants osteoporosis and atherosclerosis. Such insights could lead to elucidation of specific genetic pathways that can be exploited in the future for early identification of high-risk individuals, as well as development of new preventive and therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEAD EFFECTS ON SKELETAL STEM CELLS AND FRAC Principal Investigator & Institution: Schwarz, Edward M. Associate Professor; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by the applicant): The unifying hypothesis of this Program Project is that Pb exposure causes osteoporosis, which at the cellular level is known to be the result of an imbalance between bone resorption and bone formation. This condition is also associated with defective skeletal repair, which represents a significant component of the disease, as it has been shown that ~24% of osteoporosis patients that sustain a hip fracture die from associated complications. Critical data in support of this theory are that animals feed Pb in their diet become osteoporotic. At present the mechanism of this Pb-induced osteoporosis and the effects of Pb on fracture healing are unknown. This project will test the hypotheses that 1) Pb-induced osteoporosis is caused by preferential inhibitory effects on bone stem cells (osteoblast >>osteoclast progenitors) and 2) this inhibition has significant effects on skeletal repair (fracture healing). To test this the investigators will utilize two different Pb exposure regimens: Chronic Pb exposure (adult mice continually fed Pb in their drinking water) and osteoporosis-induced exposure (adolescent mice are exposed to Pb during development to incorporate Pb into their bones following 2 month of a Pb free diet, to clear the systemic Pb, the mice are overiectomized to commence the osteoporosis-induced exposure). Utilizing these exposures regimens with the dosing of 0,200 or 500ppm of Pb in their drinking water, to achieve a blood Pb concentration of (<5, 15, and 40ug/dl respectively), the investigators will evaluate the effects of Pb on bone stem cells (Aim 1) and fracture healing (Aim 2). The effects of Pb exposure on osteoblast progenitor cells will be analyzed in nodule formation, alkaline phosphatase, and gene expression assays on primary bone marrow cells from mice. Effects on osteoclast progenitor cells will be evaluated in splenocyte

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CFU-M colony and osteoclastogenesis (TRAP) assays to determine osteoclast precursor frequency; and bone wafer resorption assays to evaluate effects on osteoclast activity. The effects of Pb exposure on fracture healing will be evaluated utilizing a stabilized tibia fracture model with quantitative radiology and histomorphometry at various time points after fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEAD EPIDEMIOLOGY

EXPOSURE,

GENETICS

AND

OSTEOPOROSIS

Principal Investigator & Institution: Korrick, Susan A. Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-AUG-2003 Summary: The primary objective is to study the effects of environmental lead exposures and allelic variants of the vitamin D receptor (VDR) gene on the development of osteoporosis in middle-aged women. The study will be conducted as a prospective evaluation of three major hypotheses: (1) Lead exposure is associated with declines in bone mineral density (BMD) and increases in bone turnover (defined by serum osteocalcin and urinary cross-linked N telopeptide of type I collagen or NTX) in middleaged women. (2) Specific restriction fragment length polymorphisms within the VDR gene defined by the endonucleases Bsml and Taql are associated with declines in BMD and increases in bone turnover. (3) Lead exposure modifies the effects of VDR genotype on the determination of changes in both BMD and bone turnover. The study is designed to use information collected through two ongoing studies: the Nurses' Health Study(NHS), an established longitudinal investigation of chronic disease in female registered nurses, and an NIEHS R01-ES05257 supported evaluation of lead exposure and cognitive and renal function in middle-aged adults that includes large sample of NHS participants. As part of this ongoing research, two measures of BMD at the lumbar spine and hip (measured 4 or 5 years apart) and information regarding bone lead levels, blood lead levels, diet , medication use, hormone use, reproductive history, fracture and medical history will be available for 427 NHS participants. The current proposal includes laboratory analyses of archived biological specimens from these 427 women for assessment of VDR genotype, serum osteocalcin, and urine NTX. Results of preliminary studies include findings of: (1) cross-sectional inverse associations of bone lead levels with BMD, and (2) cross-sectional positive associations of both blood and bone lead with urine NTX in a subsample of the first 302 women studied to date. These results provide initial support for the hypothesis that increased bone lead levels are associated with prospective decreases in BMD and increased bone turnover activity. BMD is a critical risk factor for osteoporosis and osteoporotic fractures, which are associated with annual cost of 18 billion and pose the same estimated lifetime risk of death (in women) as does breast cancer. Evaluating potential environmental risk factors for osteoporosis, corroborating results of recent studies of the genetics of this disease, and achieving and understanding of possible gene-environment interactions related to the development of this disorder are of great public health importance as a means for identifying appropriate strategies for osteoporosis treatment and prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

88 Osteoporosis

•

Project Title: LEAD OSTEOPOROSIS

TOXICITY

IN

THE

SKELETON

&

ITS

ROLE

IN

Principal Investigator & Institution: Puzas, J Edward. Donald and Mary Clark Professor of Ortho; Orthopaedics; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): This Program Project grant application seeks to define the mechanisms of Pb toxicity in the skeleton. The investigators have evidence that the adverse effects of this heavy metal on bone and cartilage function contribute to diseases such as osteoporosis and hinder osteoporotic fracture healing. The Program Project is made up of four projects, two of which are cellular and molecular in nature, one is animal-based and one is clinical. Two cores are also proposed, an Administrative Core and a Histopathology Core. Project 1: Molecular mechanism of lead's effect on osteoclasts and osteoblasts; this project will examine how Pb influences the key regulatory genes controlling bone resorption and bone formation. Preliminary data have implicated osteoprotegrin (OPG), RANK ligand, and TRIP as the genes responsible. The project will have both in vitro and in vivo components. Project 2: Cellular and molecular effects of lead on chondrogenesis and cartilage differentiation; this research seeks to demonstrate that primordial regulators of chondrogenesis and cartilage differentiation; (i.e. the BMP's Indian hedgehog, PTHrP, etc.) are influenced in a complex way by Pb. Lead exposure leads to inappropriate skeletal development and predisposes affected individuals to osteoporosis.. Project 3: Lead effects on skeletal stem cells and fracture healing; Project 3 will use an animal model to document that the findings in Project 1 and 2 are manifested in vivo. Additionally, this work will characterize the mechanism of the effect of Pb on hindering normal fracture healing. Project 4: Clinical diagnostic and therapeutic approaches to skeletal lead toxicity; this project extends the basic science investigations into a clinical trial. It seeks to determine if therapeutic approaches for osteoporosis are effective in Pb-containing skeletons and in controlling blood Pb levels. This Program Project will define novel molecular pathways to explain the adverse effects of Pb on bone and cartilage. The pathways will be examined and validated in animals, and ultimately the findings will be translated into clinical trials. This Program Project provides the opportunity to investigate the skeletal effects of Pb from "the bench" to the "bedside". It is unique in this regard. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIFESTYLE CHANGE TO INCREASE BONE DENSITY IN TEEN GIRLS Principal Investigator & Institution: Debar, Lynn L.; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, CA 94612 Timing: Fiscal Year 2003; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: The annual cost of osteoporosis-related fractures in the US is $8 billion, most of which is borne by women in spite of an abundance of research on factors that might ameliorate the postmenopausal drop in bone mineral density (BMD). An important component of a lifelong prevention strategy would be to create methods for young women in the years 14-20 to maximize their bone mineral content and maintain it until menopause. This proposal will rigorously test two comprehensive lifestyle interventions, both oriented toward healthy diet and sustainable exercise, one based on individual counseling and the other on group intervention, against an attention control. The aim is to build bone and prevent bone loss among young women 14 to <16 years of

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age at recruitment. This trial draws upon our experience in 2 important studies of teens and nutrition--the Teen Lifestyle Project, DISC--and the ongoing fruit and vegetable study, DASH. The design is a parallel-group randomized clinical trial. with 300 participants equally divided among the groups, and measurements at baseline and three follow-ups to 27 months. This will provide power 0.90 to detect differences of l%-2% in TBBMD rates of change between groups. Secondary analysis will compare the achievement of the diet and exercise goals as compared to control, measured by objective markers (serum folate and carotenoids urinary sodium, lean body mass, accelerometer measure of physical activity) as well as by self-reports. The tertiary analysis will examine the same diet and exercise outcomes between the two intervention groups. and also in relation to process measures (adherence, evaluations, retention). The final analysis will explore potential causal pathways to bone mineral health involving a wider variety of factors, such as family history, biological and behavioral factors, hormonal influences and markers of bone metabolism. The investigators have a substantial amount of expertise in behavioral modification, research on teenage girls, nutrition and exercise interventions. They have substantial experience with assessment of bone mineral, body strength, exercise patterns, and diet, and with the biostatistical and qualitative research approaches required. The project will be carried out at the Kaiser Permanente Center for Health Research, a fully equipped research center with a mission of biomedical research in the public domain, in collaboration with the Oregon Health Sciences University. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIPID AND LIPOPROTEIN METABOLISM IN ATHEROSCLEROSIS Principal Investigator & Institution: Fogelman, Alan M. Professor of Medicine & Chief; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2003; Project Start 01-JUL-1983; Project End 31-JUL-2008 Summary: (provided by applicant): The major focus of this Program Project relates to the role of lipids and lipoproteins in initiating and regulating processes central to atherosclerosis, vascular calcification, and osteoporosis.. During the current grant period we identified oxidized phospholipids which differentially regulate inflammatory responses and demonstrated the molecular mechanisms by which they increase monocyte binding to endothelial cells (EC). The IL-8 promoter element responsive to these oxidized lipids was different from those which respond to cytokines and LPS. An oral apoA-I mimetic peptide (D-4F) dramatically reduced atherosclerosis in LDL receptor null and apoE null mice independent of plasma or HDL-cholesterol levels. D-4F also prevented the increased macrophage traffic into arteries of LDL receptor null mice after a Western diet and influenza A infection. Matrix GLA protein was shown to regulate BMP-2 activity and an atherogenic diet induced osteoporosis in atherosclerosis suceptible but not atherosclerosis resistant mice. When a paraoxonase-1 (PON1) null mouse was constructed and bred on to an apoE null background atherosclerosis increased. Conversely, a transgenic mouse overexpressing PON1 was protected from atherosclerosis. A myeloperoxidase null mouse was constructed and surprisingly had increased atherosclerosis. The nuclear receptor LXR was shown to activate an internal promoter that produced a novel alternative form of human ABCG1. Macrophage cholesterol efflux was found to be controlled by LXRalpha. The farnesoid X-activated receptor (FXR) was shown to induce apoC-II. MRP2 was shown to be controlled by the nuclear receptors PXR, FXR, and CAR. The atherosclerosis susceptibility and resistance, respectively, of C57BL/6 and C3H/HeJ mice was shown to be due to differences in the

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response of their EC to mildly oxidized LDL and was independent of plasma lipids or macrophages. Using QTL analysis a segment on chromosome 6 of CAST/Ei mice was identified as being responsible for the dramatic resistance of these hyperlipidemic mice to atherosclerosis and 5-Lipoxygenase was identified as the responsible gene. Based on these findings we propose 7 Projects and 4 Cores for the next grant period. The proposed experiments will use biochemistry, cell biology, molecular biology, mouse genetics and genetically engineered mice to determine the molecular mechanisms by which lipids and lipoproteins cause atherosclerosis, vascular calcification and osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIPID REGULATION OSTEOCLASTOGENESIS

OF

VASCULAR

AND

BONE

Principal Investigator & Institution: Demer, Linda L. Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Vascular calcification is now recognized as a widespread, clinically significant process similar to bone formation. Paradoxically, it correlates with osteoporosis.. Both are linked to atherosclerosis and hyperlipidemia. We have recently provided evidence that oxidized lipids regulate mineralization, promoting matrix calcification by vascular cells and blocking matrix calcification by bone cells in vitro. We further showed that hyperlipidemia is associated with significantly reduced bone mineral density and content in mice. Bone mineral density in vivo is regulated not only by osteoblastic activity, but also by resorptive activity of osteoclasts. and effects of oxidized lipids and hyperlipidernia on osteoclastic differentiation and function are not known. In osteoporosis, osteoclastic activity overtakes osteoblastic activity. We now hypothesize that oxidized lipids regulate differentiation and function of mineralresorbing osteoclastic cells in bone and artery wall. These regulatory effects of lipids on osteoclastic differentiation could also be dependent on factors produced by stromal cells in the two tissues. Specifically, we hypothesize (1) that osteoclast-like cells are present in artery wall as well as in bone and are regulated by oxidized lipids in both tissues, (2) that oxidized lipids regulate stromal cell production of and response to osteoclastogenic factors such as M-CSF, RANKL, PTH, and IL-6, and (3) that the atheroprotective enzyme paraoxonase also prevents both hyperlipidemia-induced vascular calcification and bone loss in vivo. To test these specific hypotheses we will: 1) examine human and mouse arterial specimens for osteoclastic markers and activity and test whether oxidized lipids affect osteoclastogenesis using in vitro models of vascular and bone tissue, 2) assess stromal cell production of M-CSF, IL-6 and RANKL before and after treatment with oxidized lipids and test stromal cell responsiveness to osteolytic stimuli, PTH and IL-6 in vitro and in vivo. and 3) determine whether deactivation of oxidized lipids by paraoxonase blocks oxidized lipid and hyperlipidemla- induced vascular calcification and bone loss in vitro and in vivo. Elucidating the mechanism by which oxidized lipids regulate mineral resorption will allow novel treatment approaches for osteoporosis and vascular calcification, including the possibility of biologically controlled regression of vascular calcification. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONG TERM GENE THERAPY FOR OSTEOPOROSIS Principal Investigator & Institution: Ponnazhagan, Selvarangan; Assistant Professor of Molecular; University of Alabama at Birmingham Uab Station Birmingham, AL 35294

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Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: Osteoporosis is characterized by a reduction in the mass of bone per unit volume. Hence, therapies directed towards improving the bone forming cells should provide amelioration for the patients. Most of the therapy for osteoporosis so far involves treatments with purified recombinant proteins or drugs that show only modest effects and also are short lived and expensive. Hence, development of novel therapeutic strategies are needed to improve the pathophysiology of the disease. Gene therapy approaches using the adeno-associated virus (AAV) vectors have the potential for the long-term treatment of osteoporosis.. AAV is a non-pathogenic vector that stable integrates into host genome. AAV infects both dividing and non-dividing cells in vitro and in vivo. We hypothesize that autologous transplantation of bone marrow stromal cells, transduced ex vivo with recombinant AAV encoding bone morphogenetic protein (BMP) gene sequences should provide a constant source of osteoblast production in vivo. The hypothesis is based on the recent identification that the pluripotent bone marrow stromal cells (MSCs) differentiate into bone-forming osteoblasts and also that expression of the key proteins of TGF-beta family, particularly the BMPs, precisely regulate this process. The relatively easy methods to isolate and expand the MSCs offer an ideal source for autologous gene therapy. Our preliminary results also indicate that the recombinant AAV vectors transduce the ex vivo expanded human and murine MSCs in high efficiency. Hence, by using rAAV vectors to transduce the ex vivo expanded human and murine MSCs in high efficiency. Hence, by using rAAV vectors to transduce the MSCs we plan to achieve increased bone density. Further, we hypothesize that by using osteoprogenitor cell- specific promoters to regulate the expression of BMP genes using AAV vectors, we will also accomplish osteopoietic differentiation of the ex vivo modulated MSCs and regulate the expression of BMP-2 only in bone forming cells. Thus, in the present preclinical pilot studies, we propose to systematically evaluate the efficiency of rAAV vectors for the treatment of osteoporosis in an osteopenic rat model. A successful outcome of these studies should lead to the development of novel treatment modalities for osteoporosis in an osteopenic rat model. A successful outcome of these studies should lead to the development of novel treatment modalities for osteoporosis and other osteopenic bone diseases in future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONGTERM CONSEQUENCES OF LUPUS; VASCULAR AND BONE COMPLICATIONS Principal Investigator & Institution: Ramsey-Goldman, Rosalind; Northwestern University Office of Sponsored Programs Chicago, IL 60611

Professor;

Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Survival has improved over the last two decades for patients with systemic lupus erythematosus (SLE). Attention is now focused on modifying complications leading to late mortality and progressive morbidity. Fracture M), stroke (CVA), and myocardial infarction (MI) commonly occur in young women with SLE, who should be protected from such events. Our preliminary data demonstrates in women with SLE an association between low bone mineral density (BMD) at the spine and hip with the presence of vascular calcifications in the coronary arteries. These observations are unique and suggest common mechanisms linking atherosclerosis and osteoporosis, clinical problems noted previously in non-SLE postmenopausal women. Potential common features in bone and vascular biology include 1) inflammatory markers/mediators, 2) autoantibodies, and 3) tumor necrosis factor (TNF) superfamily members. These features may be relevant in explaining why

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atherosclerosis and osteoporosis affects young women with SLE. The overriding hypothesis for this epidemiologic study is that vascular calcification and early atherosclerosis are associated with low bone mineral density (BMD), and that low BMD predicts cardiovascular outcomes in SLE women, even after accounting for traditional cardiovascular risk factors. The three specific aims of this study of 200 women with SLE and 200 age and race matched controls are to 1) measure BMD in the spine, hip, and wrist by DXA; calcification in arteries (coronary and aorta) by electron beam computed tomography (EBCT); and carotid plaque by B-mode ultrasound, 2) measure traditional cardiovascular risk factors (e.g. lipids); inflammatory markers/mediators (e.g. CRP, soluble CD40); autoantibodies (phospholipids, neoepitopes to oxLDL); and TNF superfamily molecules (OPG), and 3) contact study participants every 6 months to ascertain clinical vascular events and repeat carotid B-mode ultrasound and risk factors measurements in years 4 and 5 to assess vascular progression. Descriptive statistics and regression models will be used to analyze data. Understanding the underlying pathogenesis of, and identifying surrogate markers and risk factors for, atherosclerosis and osteoporosis are essential steps in developing intervention and prevention strategies for fx, CVA, and MI outcomes in SLE. Indeed, SLE may be an ideal 'experiment of nature' in which to further examine the role of inflammation and immune mechanisms in osteoporosis and atherogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LOW COST METHODS TO ASSESS OSTEOPOROTIC FRACTURE RISK Principal Investigator & Institution: Bouxsein, Mary L. Assistant Professor; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 28-FEB-2003 Summary: Osteoporosis is a common condition that presently affects more than 25 million persons in the US, contributing to over 1.5 million fractures annually. The economic and social impact of these fractures on health care delivery and on the elderly population are staggering. Furthermore, if current trends continue, the number of fractures and associated costs are projected to double or triple in the next 30 years due to the aging of our population. Early identification, through widespread screening programs, and intervention in those persons at high risk may improve the success of fracture prevention strategies. The most commonly used technique for assessing fracture risk, dual-energy x-ray absorptiometry (DXA), though proven effective as a predictor of future fracture risk, may not be the ideal screening tool due to the relatively high capital investment required, the need for specialized operator training, and limited portability. Recently, alternatives to DXA have been developed. We propose studies designed to further our basic understanding and to evaluate the potential usefulness of two of these alternative methods: image analysis of conventional radiographs and quantitative ultrasound (QUS). In the first two aims we will evaluate a diagnostic technique based on image processing of conventional forearm radiographs. In this technique, a bone index representing the character of the projected trabecular pattern is computed from standard radiographs. We will compare this bone index to the strength of cadaveric femurs and thoracolumbar vertebrae, and assess its ability to predict hip fracture risk in case-control study of women with an acute hip fracture and similarly-aged women who have not suffered a fracture. In our final aim, we will examine the capabilities of QUS. It has been proposed that QUS measures aspects of bone "quality", such as trabecular architecture, material properties, or accumulated microdamage, that are independent of bone density. However there have been few studies relating QUS measurements on intact feet

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(rather than excised bone specimens) to aspects of bone quality. We will use human cadaveric specimens to characterize the relationship between QUS measurements of on intact feet and trabecular bone morphology, mechanical properties, and microdamage. The significance of the proposed work is that is will provide new information regarding the potential usefulness of two technologies that may be capable of widespread osteoporosis testing and assessment of fracture risk. This information is important, as early identification of those at risk for fracture represents the most promising approach for effective fracture prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LOW-DOSE DOXYCYCLINE EFFECTS ON OSTEOPENIC BONE LOSS Principal Investigator & Institution: Payne, Jeffrey B. Professor and Assistant Dean for Researc; Surgical Specialties; University of Nebraska Medical Center Omaha, NE 681987835 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: Osteoporosis represents a major public health problem in the United States. Osteoporosis is associated with decreased systemic bone mineral density (BMD), an increased incidence of vertebrae, wrist and hip fractures, and tooth loss. The dominant pathogenic factor for osteoporosis in postmenopausal women is estrogen (E2) deficiency. In longitudinal NIH-supported clinical trials, we have shown accelerated alveolar crestal bone height and density loss in postmenopausal, E2- deficient women with a periodontitis history relative to E2-sufficient women, and in osteoporotic/osteopenic women versus women with normal lumbar spine BMD. Because of this relationship between E2- deficiency, osteoporosis and oral bone loss, it is desirable to test therapeutic strategies to mitigate alveolar bone loss in postmenopausal women. A recent discovery by Dr. Golub (Co-PI) showed that tetracyclines, including low-dose doxycycline (LDD), by virtue of a non- antimicrobial property, can: a) inhibit host-derived, tissue-destructive matrix metalloproteinases (MMPs), including collagenases, involved in bone resorption; and b) stimulate osteoblast activity and bone formation. These biological properties make tetracyclines compelling candidates for use in postmenopausal women with periodontitis. Therefore, the objective of this research is to investigate the therapeutic potential of LDD in postmenopausal osteopenia and periodontitis, diseases characterized by excess collagen breakdown and bone resorption. The hypothesis of this proposal is that LDD (compared to placebo) can improve radiographic, clinical and biochemical parameters of periodontitis in E2-deficient, osteopenic postmenopausal women with periodontitis. Accordingly, the specific aim of this proposal is to use a 2- year double-blind, placebocontrolled trial of E2-deficient women to determine the effect of LDD on: a) alveolar bone crestal and subcrestal density (measured by computer-assisted densitometric image analysis) and linear alveolar crestal bone height; b) clinical periodontal measurements such as probing depth and relative clinical attachment level; and c) gingival crevicular fluid markers of bone turnover (e.g., C- terminal telopeptide pyridinoline crosslinks [ICTP, a collagen breakdown fragment]). As a secondary aim, the study will evaluate the effect of LDD on systemic bone mineral density at the lumbar spine and femoral neck by dual-energy x-ray absorptiometry (DEXA) and the effect of LDD on serum and urine biochemical markers of bone turnover. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MAGNESIUM DEFICIENCY: EFFECT ON BONE AND MINERAL Principal Investigator & Institution: Rude, Robert K. Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2005 Summary: The objective of this proposal is to increase our understanding of the role of magnesium (Mg) deficiency in the etiology of osteoporosis.. While sex steroid deficiency is a major factor in postmenopausal osteoporosis, nutrition is also important. Dietary Mg intake has been associated with bone mass in aging and postmenopausal osteoporosis.. Disorders in which Mg deficiency is common such as alcoholism, malabsorption syndrome and diabetes also have an increased risk of osteoporosis.. The average dietary Mg intake in women is 68 percent of the RDA indicating that a large proportion of our population have substantial dietary Mg deficits. Severe Mg deficiency in the rat results in impaired bone growth, osteopenia and skeletal fragility. The level of dietary Mg intake that results in osteoporosis in rat or human is unknown. In our proposal, we will employ dietary Mg deprivation in the rat at 10 percent, 25 percent, and 50 percent of recommended nutrient requirement. This reduction in Mg intake reflects levels of dietary Mg inadequacy in our population. Our first specific aim is to determine the dietary intake that will result in Mg deficiency as assessed by bone Mg content. Another specific aim is directed at assessing the effect of these dietary Mg intakes on bone histology, histomorphometry and bone turnover; ie. at what level of Mg intake does osteoporosis occur and is it reflected by alteration in osteoblast and osteoclast activity. The mechanism for the previously observed osteoporosis in severe Mg deficiency is unclear but may involve systemic hormones or local factors regulating bone cell activity. Severe Mg deficiency in humans and rats result in low serum parathyroid hormone (PTH) and 1,25(OH)2-vitamin D which may contribute to reduced bone formation. We will quantify the effects of low Mg intake on calcium homeostasis by determining serum calcium, PTH and 1,25(OH)2-vitamin D levels. The cause of increased osteoclastic bone resorption in severe Mg deficiency is unclear. Cytokines can increase osteoclastic bone resorption and are implicated in postmenopausal osteoporosis.. Mg deficiency in the rat results in an increase in serum substance P which in turn stimulates production of various cytokines. We will therefore measure serum substance P, TNFalpha, IL1beta, and IL6 in the Mg deficient rat and perform immunohistochemical staining of bone for these cytokines. Parallel studies will be performed in which a specific substance P receptor inhibitor will be administered to directly test whether generation of these cytokines are responsible for Mg deficiencyinduced bone loss.. These studies should substantiate our hypothesis that Mg depletion contributes to osteoporosis and provide mechanistic explanations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS TRANSCRIPTION

OF

ESTROGEN

REPRESSION

OF

TNF-A

Principal Investigator & Institution: Leitman, Dale C. Ob, Gyn and Reproductive Scis; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Osteoporosis is one of the leading causes of mortality and disability in older women. Osteoporosis causes 68,000 deaths per year, which is equivalent to the number of deaths from breast cancer and all gynecological cancers combined. One of the most effective strategies to prevent osteoporosis is to replace estrogen at the onset of menopause. Unfortunately, prolonged treatment with

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estrogen leads to adverse effects, including an increased incidence of breast and endometrial cancer. Clearly, estrogens that retain their beneficial effects on bone, but do not elicit a proliferative effect on breast or endometrial cells, have the potential to become first-line drugs to prevent osteoporosis.. One approach to discover safer and more selective estrogens is to dissect the molecular mechanisms whereby estrogens activate and repress gene transcription. In contrast to transcriptional activation, very little is known about the mechanisms of repression. We studied how estrogens and phytoestrogens repress the tumor necrosis factor (TNF-alpha) promoter, because TNF-a causes osteoporosis by stimulating osteoclasts to resorb bone. Based on these studies, we hypothesized that estrogen receptor (ERbeta) is more effective than ERalpha at repressing gene transcription, and that the activation function-2 surface of ERs and coactivator proteins are required for estradiol-mediated repression. Whereas these findings are novel and important, their interpretation is limited, because they were done with the TNF-alpha promoter linked to reporter genes in transient transfected cells. The goals of this proposal are to extend these observations to the native TNF-alpha gene, and to further probe the basic molecular mechanisms whereby ERs repress gene transcription. In this proposal we will use chromatin immunoprecipitation assays to characterize the protein-protein interactions that occur at the native TNF-alpha promoter between estrogen receptors, transcription factors, such as c-jun and NFKB, and p160 and p300 coregulatory proteins in bone cells that are stably transfected with ERalpha or ERbeta controlled by a tetracycline-inducible promoter. We hypothesize that identifying the proteins involved in repression, and determining how these factors interact with each other is key to developing repression-selective estrogens. We believe that repression-selective estrogens have the potential to become first-line drugs for preventing osteoporosis, because we hypothesize that these estrogens will prevent osteoporosis, but will not promote breast or endometrial cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF IGFBP5 STIMULATION OF BONE CELL FUNCTION Principal Investigator & Institution: Andress, Dennis L. Professor of Medicine; Medicine; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 14-AUG-1998; Project End 31-JUL-2003 Summary: Insulin-like growth factors (IGFs) are proteins that stimulate osteoblast activity. IGF-I is secreted by osteoblasts and so may function in an autocrine manner to regulate their function. Factors that affect the action or production of IGF-I are therefore likely to be important in the pathogenesis and treatment of bone diseases characterized by inactive osteoblast activity. IGF-binding proteins (IGFBPs) affect the function of osteoblast-like cells by modulating the binding of IGF-I with its surface receptor. IGFBP5 is known to enhance IGF-I stimulation of osteoblast activity and in addition, to have independent effects on osteoblast function. This independent effect may be related to its ability to bind to a 420 kDa osteoblast membrane protein which becomes phosphorylated upon exposure to IGFBP-5. To further investigate the mechanisms in which IGFBP-5 controls osteoblast activity the current proposal will determine the identity of the IGFBP-5-receptor by expression cloning and by established purification and sequencing methods. Osteoblasts transfected with IGFBP-5-receptor constructs and IGFBP-5-receptor antibodies will be used to establish structure-function relationships between the receptor and its phosphorylating activities. Receptor phosphorylation will also be characterized by identifying phosphorylation binding sites and substrate specificities. Structural studies will be conducted to assess internalization and nuclear

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localization of IGFBP-5 and selected peptide substitutions of the putative nuclear localization sequence will be used to define minimum structural requirements for the nuclear transport of IGFBP-5. The results of these studies should define novel mechanisms in which IGFBP-5 stimulates osteoblast function and may suggest strategies to alter these processes in ways that enhance osteoblast activity and improve defective bone formation in osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEDIATORS OF VASCULAR CALCIFICATION AND BONE DISEASE Principal Investigator & Institution: Giachelli, Cecilia M. Associate Professor; Bioengineering; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAY-2005 Summary: (provided by applicant): Vascular calcification is an actively regulated process contributing to increased morbidity and mortality in, patients with uremia, diabetes, aortic stenosis and bioprosthetic heart valves. Epidemiological studies have linked vascular calcification with osteoporosis and cardiovascular disease, suggesting that common regulatory mechanisms exist, and that ectopic calcification may increase the risk of heart disease. In human blood vessels and valves, both diffuse calcification and ectopic bone have been observed under pathological conditions. The relationship between these types of mineralization is unclear. It is also unknown if media or intimal vascular calcification contributes to formation and/or progression of atherosclerotic lesions. We hypothesize that mineral deposition in blood vessels involves mediators including osteopontin (OPN), osteoprotegerin (OPG) and matrix gla proteins (MGP), that also critically control formation of the skeleton, and that once mineral forms in the vessel wall, an adaptive response ensues and initiates cellular differentiation and inflammatory mechanisms that 1) lead to neointima formation and hence increased susceptibility to plaque formation, and 2) mimic endochondral bone formation that may explain the appearance of ectopic bones in calcified vascular lesions. In order to identify common mechanisms! controlling bone and vascular calcification, and to understand the relationship between vascular calcification, cartilaginous metaplasia, and arterial lesion development, three aims are proposed. Aim I will determine the mechanism of medial vascular calcification, neointimal formation, and cartilaginous metaplasia in MGP X OPN mutant mice. Aim 2 will determine the mechanism of bone and tooth defects found in MGP X OPN mice. Aim 3 will determine the effect of hyperlipidemia on cartilaginous metaplasia, vascular calcification and osteoporosis in a mouse model of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEDICATIONS, GENETIC VARIABILITY & BREAST CANCER Principal Investigator & Institution: Newcomb, Polly A. Member and Acting Head; Laboratory for Cancer Research; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2003; Project Start 01-APR-1992; Project End 31-MAR-2008 Summary: (provided by applicant): Recent evidence suggests that commonly used medications may be determinants of breast cancer risk. In this fourth renewal of our highly successful breast cancer case-control studies, we propose a new project to investigate the relation between breast cancer incidence and the use of non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants, and drugs to treat osteoporosis..

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Specific hypotheses include: 1) regular use of NSAIDs is associated with a decreased risk of breast cancer; 2) antidepressant use is associated with increased risk of breast cancer; 3) use of drugs to prevent or treat osteoporosis is associated with a decreased risk of breast cancer; and 4) these associations are modified by genetic predisposition, specifically in polymorphisms related to the oxidation and glucoronidation of these compounds. To test these and other hypotheses, we will interview 3,564 women under 70 years of age with newly diagnosed breast cancer, identified through Wisconsin's statewide mandatory tumor registry. For comparison, we will interview 3,546 similarlyd female community members selected at random from the population using lists of licensed drivers. Study subjects will be interviewed by telephone regarding their use of the medications of interest and breast cancer risk factors. Participants will contribute buccal cells for DNA to be genotyped for CYP2C9, UGTIA6, and CYP2D6 polymorphisms. We will also bank DNA for future gene-environment studies. Building on existing and long-standing protocols allows us to evaluate the association of these increasingly common exposures with breast cancer risk in an efficient and timely manner. Further study of these modifiable exposures and relevant genotypes will provide more information on which women and their physicians can base decisions regarding behavior and may provide insights into the biology of this common tumor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORED DEVELOPMENT

PATIENT-ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Von Scheven, Emily; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 29-SEP-2006 Summary: (provided by applicant): Increased survival of children with SLE into adulthood has resulted in the emergence of morbidities not previously well studied. Effective evaluation of this morbidity requires longitudinal study designs with attention to disease severity at onset and timing of disease onset relative to growth and development. Thus, a primary goal is to develop a well characterized Northern California longitudinal pediatric and adolescent SLE cohort demonstrating diversity across age (minimum seven years), ethnicity, and gender with a corresponding longitudinal tissue bank. The cohort will serve as a resource for the future study of many aspects of long-term outcome in this population. The career development component of this application includes completion of the UCSF Master in Clinical Research degree program with a focus on learning methods designed to analyze repeated measurements, multiple variables, and molecular epidemiology, all important skills for analyzing longitudinal multi- system disease data-sets. The scientific component of this application addresses the development of osteoporosis in pediatric onset SLE. Coincident timing of disease onset and achievement of normal peak bone mass may result in an increased risk for future osteoporosis and fracture. Annual measurements of SLE-associated reductions of bone mineral density (BMD) assessed utilizing dual energy X-ray absorptiometry (DEXA) and single energy quantitative computed tomography (QCT) will be correlated with disease-, treatment- and hostrelated factors and corresponding markers of bone metabolism. The relationship between skeletal maturation assessed by bone age and longitudinal changes of BMD will be determined by evaluating the timing and level of peak bone mass, and the contribution of the timing of disease to reductions of BMD. The findings of this project may result in the development of bone age- specific treatment regimens for pediatric SLE, and ultimately will contribute to improving the quality of adult life for individuals

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with childhood-onset SLE. Furthermore, development of this well characterized SLE cohort will serve as an important future resource and builds a foundation for studying many lifelong effects of childhood-onset SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MIDCAREER INVESTIGATOR AWARD PATIENT-ORIENTED RESEARCH Principal Investigator & Institution: Lane, Nancy E. Associate Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Nancy E. Lane, MD is an Associate Professor of Medicine at the University of California, San Francisco (UCSF). She is an established clinical investigator in musculoskeletal diseases with a special emphasis on osteoporosis and osteoarthritis. She is currently an NIH-funded investigator conducting a study to determine if PTH can reverse glucocorticoid-induced osteoporosis and to determine risk factors for the development and progression of hip OA. The purpose of this K24 award is to mentor and teach clinical research in osteoporosis and osteoarthritis at UCSF by 1) Developing an interdisciplinary clinical research seminars in osteoporosis and osteoarthritis that both topical lectures and work in progress research presentations by junior investigators; 2) Meeting individually with all junior clinical investigators UCSF in the field of osteoporosis and osteoarthritis to review research progress, provide study design analysis suggestions, and to establish additional resources for the investigators; 3) Becoming a core faculty member in the Master's in Clinical Research Program at UCSF by teaching a seminar on Developing a Clinical Research Protocol and mentoring master's students on research methodology; 4) Mentoring junior investigators in clinical research with my currently funded NIH grants on glucocorticoid-osteoporosis and on the epidemiology of hip OA. The specific aims of the currently funded NIH proposal to determine if PTH can reverse glucocorticoid-induced osteoporosis are to: l) To determine the changes in BMD caused by two years of treatment with hPTH (1-34) or placebo in postmenopausal women with GC-induced osteoporosis who are taking estrogen, calcium, vitamin D and chronic low doses of GCs; 2) To determine if estrogen or alendronate will preserve the high bone mass state created by two years of hPTH (134) treatment; 3) To determine the association of biochemical markers of bone turnover with hPTH (1-34) both during and after treatment. Monitoring for specific aim 3 will be accomplished by obtaining serum bone specific alkaline phosphates, serum osteocalcin, and urinary deoxypyridinoline cross-links at 3-month intervals; 4) To compare, as possible, the fracture incidence between the hPTH (1-34) and placebo treatment groups. Monitoring for specific aims I and 2 will be accomplished by annual spinal and proximal femur trabecular bone mineral content by quantitative computed tomography (QCT) and semi-annual dual x-ray absorptiometry (DXA) of the spine, hip, and forearm. The specific aims for the natural history of hip CA are to identify cases of new or worsening radiographic osteoarthritis (OA) of the hip by obtaining a second x-ray of the pelvis after an average of 8 years of follow-up in order to describe the natural history of radiographic hip OA and to determine the risk factors for hip OA. This Study of Osteoporotic Fractures cohort of elderly Caucasian women age - 65 have had radiographs of the pelvis obtained at baseline and after 8 years of follow-up in addition to bone mass measurements and other questionnaire and medication information. The data have been obtained and analyses are required. Dr. Lane has the enthusiastic support of her department of medicine and epidemiology at UCSF to pursue both her mentoring and continued research efforts in-patient oriented clinical research goals. She

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will strengthen her role senior mentor to young clinical investigators, she will teach clinical research methodology and develop a strong interdisciplinary clinical research group for musculoskeletal disease oriented research at UCSF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODULATION OF LOCAL BONE TISSUE MATERIAL PROPERTIES Principal Investigator & Institution: Les, Clifford M. Bone and Joint Center; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, MI 48202 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-MAY-2005 Summary: (provided by applicant): Compact bone mineral density is distributed nonuniformly within the normal bone structure. This is reflected in local variation in mechanical properties (strength and stiffness) that we believe helps to limit bending to those planes where muscles and ligaments have maximal mechanical influence. Challenges to normal bone mineral metabolism may affect this material distribution, and have structural effects disproportionate to the overall mineral loss. For instance, in postmenopausal osteoporosis, there is increased turnover of bone, and a generalized loss of bone mass, but this fully explains neither the strong association with fracture incidence, nor the substantial overlap between unaffected and fracture patients in most clinical screening measures of bone quality. Given the pre-existing material heterogeneity, any change in material properties, be it random, uniform, or systematic, is likely to have significant effects on the mechanical behavior of the structure. Therefore, therapeutic interventions designed to simply affect an overall increase in bone mass without considering regional mechanical property variation may be ineffective in preventing fracture. In compact bone, an increase in bone turnover may be seen as a branching problem in angiogenesis: new osteons, and their blood vessels, must arise from pre-existing osteons and blood vessels. If estrogen depletion were associated with a global increase in vascular and osteonal branching, the major early effects of remodeling would be seen in regions with high concentrations of pre-existing osteons. Such a scenario would produce an immediate systematic change in regional bone density that would be related not to original density, but to pre-existing remodeling patterns. Furthermore, we hypothesize that the new bone that is laid down in the estrogen-depleted condition is less densely populated by osteocytes than in the intact animal. If changes in osteocyte density were associated with alterations in the final mineralization of new bone, a more permanent change in the distribution of material properties would then ensue. We will test these hypotheses using the ovariectomizedsheep model of estrogen depletion. The radius/ulna will be tested for structural damping, stiffness, and strength before sectioning into regions for materials testing and histology. Remodeling activity will be quantified by dynamic and static histomorphometry, and by analysis of osteonal density patterns. Finally, local osteocyte population densities will be determined and compared with osteonal mineral measurements, and with mineral-independent measurements of local tissue age. In this way, we will address the issue of compact bone material heterogeneity in postmenopausal osteoporosis at the structural, materials, cell population, and biochemical levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODULATION OF OSTEOCLASTOGENESIS BY CALMODULIN KINASE II Principal Investigator & Institution: Zhang, Liang; Pathology; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Osteoporosis is a major bone disorder that affects both men and women during aging. The pathogenesis is due largely to the increased osteoclast activity which is largely attributed to the increased generation of osteoclasts (osteoclastogenesis). Thus, understanding the cellular and molecular mechanisms in the regulation of osteoclastogenesis is of paramount importance in the battle against osteoporosis.. Efforts proposed in this application are directed toward identifying novel targets for the treatment of osteoporosis.. Accumulated preliminary data from both in vivo and in vitro studies, indicate a specific and important role of Ca2+/calmodulin dependent kinase II (CaMKII) in the regulation of osteoclastogenesis. Experimental aims are designed to address the hypothesis that CaMKII regulates osteoclastogenesis. Specific aims to accomplish this are: Specific Aim 1. Characterization of the roles of different CaMKII subtypes involved in osteoclastogenesis, i. Determine the cellular distribution of different CaMKII subtypes (apha and or gamma) in bone marrow, ii. Characterize CaMKII in cells from CaMKIIalpha mutant mice during osteoclastogenesis, iii. Characterize bone mineral density (BMD) changes in CaMKIIalpha mutant mice. iv. Further characterize the specificity of CaMKII alpha and or gamma in osteoclastogenesis by viral mediated gene transfer. Specific Aim 2. Determine the molecular mechanisms of CaMKII regulation of osteoclastogenesis, i. Does CaMKII regulate RANKL signaling? ii. Identify the substrates of CamKII in RANKL signaling pathways, iii. Does CaMKII regulate macrophage fusion molecules? Elucidation of the molecular events responsible for CaMKII's involvement in osteoclastogenesis, will reveal detailed molecular mechanisms, which may provide new targets for designing rational therapeutic strategies to combat osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR & CELLULAR MECHANISMS OF OSTEOPOROSIS Principal Investigator & Institution: Manolagas, Stavros C. Director; Internal Medicine; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, AR 72205 Timing: Fiscal Year 2001; Project Start 27-AUG-1996; Project End 31-MAY-2006 Summary: Five interrelated projects supported by three cores to improve the understanding of pathophysiology in osteoporosis by elucidating the cellular, molecular, and genetic mechanisms that underlie loss of bone, and by examining the role of osteocytes in preserving bone integrity and strength. The central theme remains that loss of bone in the adult skeleton is mainly the result of disordered control of cell number, specifically that too many osteoclasts exist relative to the need created by bone resorption. Extensions of these themes are that the importance of deficient cell number applies also to the osteocyte, and that for all three bone cell types cell death as is important as cell birth in determining overall cell numbers. Molecular and cellular biology approaches, gene mapping, and generation of transgenic and knockout mice will be used to test the projects' interrelated hypotheses. O'Brien's project will further explore the molecular links between osteoclastogenesis and osteoblastogenesis during normal bone remodeling and clarify the mechanism of coupling of bone resorption. Manolagas's project will attempt to unravel the molecular mechanisms for the separate effects of estrogen deficiency on cell production and on cell lifespan; it will also seek an

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explanation for the paradox of the bone protective efficiency of estrogen in males in androgen in females. Jilka's project will focus on the importance of osteoblast progenitor cell proliferation and apoptosis, and further study Jilka's project will focus on the importance of osteoblast progenitor cell proliferation and apoptosis, and further study the inverse relationship between adipogenesis and osteoblastogenesis in aging bone marrow. Reis's project will narrow the search for the molecular genetic basis of osteopenia in the SAMP6 mouse, and use the results to extend genetic studies to human subjects. Bellido's project will elucidate the signals that control osteocyte viability in response to both pharmacological agents and mechanical forces. In addition to the management, administration, and statistics Core which will support interactions between research projects, the Animal Research Core and the Bone morphometry and Molecular Imaging Core will each provide crucial services supporting several projects in a cost effective and scientifically advantageous manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF BONE FORMATION Principal Investigator & Institution: Li, Yi-Ping;; Forsyth Institute Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): There is clear clinical evidence that genetic modulated osteoporosis results from functional defects in osteoblast cells. However, the genes underlying these genetic syndromes of osteoporosis remain largely unknown. In order to identify genes that are important for bone formation, we employed subtractivedifferential screening and promoter-trap mutagenesis techniques. Surprisingly, a zincfinger protein, cellular nucleic acid binding protein (CNBP), was identified by both approaches. We have found that the expression of CNBP gradually increases during osteoblast differentiation in vitro. In vivo, CNBP is predominantly expressed in osteoblasts, and is detected throughout the osteoblast lineage, from early osteoprogenitors to osteocytes during bone development. The CNBP homozygous mutant mice generated from promoter-trap mutagenesis die in the prenatal period and heterozygous mice survive to develop postnatal skeletal abnormalities associated with osteoporosis.. Examination of mutant embryos during development indicated that impaired bone formation may be due to fewer pre-osteoblasts and osteoblasts with reduced functional capability. CNBP directly regulates osteocalcin expression and overexpression of CNBP increases osteoblast proliferation in vitro. Based on our preliminary data, we hypothesize that CNBP controls the differentiation of mesenchymal progenitor cells into mature osteoblasts and the proliferation of osteoblasts. To test this hypothesis, we propose four Specific Aims. In Aim 1, we will examine the spatial and temporal expression of CNBP, which will be correlated with bone marker gene expression during bone development and postnatal life. The expression of bone marker genes in CNBP mutants will be studied to evaluate the molecular basis of the bone defect phenotype. In Aim 2, we propose to define the functional role of CNBP in osteoblast proliferation and differentiation in vitro using forced expression and co-transfection methods. In Aim 3, to overcome the early embryonic lethality in CNBP mutants, we propose to study the role of CNBP in bone formation in vivo by conditional knockout of the CNBP gene in osteoblasts using Cre/loxP technology. The effect of the mutation on osteoblast proliferation and differentiation will be examined. In Aim 4, we will generate transgenic mice that overexpress CNBP in osteoblasts in order to examine the role of CNBP in bone formation during embryonic development and postnatal life, and in the prevention of osteoporosis using ovariectomized transgenic mice. The ultimate goal of these studies is

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to understand how CNBP and other bone transcription factors interact during bone development, and to apply this knowledge to develop new diagnostics and therapeutics for human osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF ECTOPIC BONE FORMATION Principal Investigator & Institution: Lietman, Steven A. Orthopaedic Surgery; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 30-APR-2007 Summary: (provided by applicant): Osteoporosis is a public health problem that affects approximately 25 million people in the United States. Regardless of the etiology, osteoporosis is characterized by an imbalance in bone remodeling. Bone remodeling involves coordinated interaction between osteoblasts and osteoclasts. Information about mechanisms of bone formation may lead to new insights into the development of strategies to induce bone formation in diseases in which bone mass is low such as osteoporosis.. Patients with Albrights Hereditary Osteodystrophy (AHO) and progressive osseous heteroplasia (POH), despite differences in other clinical features, form ectopic bone. Patients with AHO and POH also have heterozygous germline GNASI mutations of the gene encoding the alpha chain of the Gs G protein. These G proteins in turn regulate activity of intracellular signal effectors, most notable of which is adenylyl cyclase, the enzyme that synthesizes the second messenger cAMP. The mechanisms by which cAMP affects bone development and or remodeling are incompletely understood, but likely involve control of gene expression. The basis for the distinct differences in the clinical features and variable phenotypes of patients with similar inactivating GNASI mutations remains unclear as well. Understanding the heterogeneity in patients with GNASI mutations might allow more precise determination of the mechanisms of bone formation. Specifically, efforts are proposed to: 1) Assess genotype/ phenotype correlations in patients with ectopic bone forination. 2) Determine whether the mosaic distribution of ectopic ossification in patients with AHO and POH reflects the acquisition of a somatic clonal mutation, in the wild type Gscc allele. 3) Reduce the expression of Gs(X in human mesenchymal cells and observe the effects on bone formation of these altered levels. 4) Examine separate candidate genes and their products to explain the somatic mosaicism of the ectopic bone. 5) Examine microarray patterns of gene expression from bone and other tissues from patients with AHO and POH. This award might afford the opportunity to gain added experience and knowledge necessary to become an independent investigator by increasing protected time in the laboratory. In the future I would like to mentor other students or junior faculty memjbers like myself and perpetuate the unique and exciting and exciting perspective clinicla and basic science training bring to scientific to scientific investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NATIONAL OSTEOPOROSIS RISK ASSESSMENT Principal Investigator & Institution: Bruder, Jan;; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001 Summary: The National Osteoporosis Risk Assessment (NORA) is a public health initiative that will create a longitudinal, observational data base of as many as 500,000 post-menopausal women. The data collected from these patients will offer opportunities

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to conduct longitudinal research to examine the relationship between risk factors for osteoporosis including low bone mineral density and patient outcomes such as changes in BMD and fracture risk. The initial objective is to determine the relationship between BMD measurements at each of a number of skeletal sites and a patient's long and short term risk of fracture. This analysis will attempt to determine the incremental predictive value of each of the measurements as well as identify combinations of BMD measures that, when considered in conjunction with other risk factor information, offer a more predictive and cost-effective method of evaluating a patient's overall risk of fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW OSTEOPOROSIS

METHODS

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MONITORING

TREATING

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Principal Investigator & Institution: Brand, Richard; Professor of Biostatistics; Epidemiology and Biostatistics; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): The main goal of this project is to develop and apply methods using finite-mixture statistical models to provide a patient-specific estimate of the probability that the patient has responded to treatment. The estimated probability of response will provide an empirically grounded and conceptually sound statistical technique for monitoring success of treatment for osteoporosis.. The methods also can be used for basic research on patient factors associated with responsiveness to treatment. Since phenotypes defined in terms of response to treatment can be related to genetic markers, these methods are applicable to the emerging field of pharmacogenomics. This project will extend our recently published methodological work [1], in which we focused on methods and application to the use of a patient's pre to post treatment change in total hip bone mineral density (BMD) for judging whether or not the patient has responded to treatment with alendronate. We calibrated the procedure with data from FIT [2], a randomized placebo-controlled trial, which evaluated alendronate for treatment of osteoporosis.. We found that clinicians may be overly ready to conclude that treatment with alendronate has failed. For example, when a treated subject has no increase in total hip BMD from baseline, there is only a small probability that a treated patient has actually failed to respond to treatment. Although different from current clinical opinion, this conclusion results from proper consideration of background changes in placebo-treated control subjects as a backdrop for judging the changes in treated subjects. To make the previously published methods more versatile, the proposed developments will: (1) deal with many of the different configurations of patient monitoring data that are typically encountered in clinical practice, and (2) can take patient-specific characteristics like age, race, BMI, baseline BMD, genetic markers, etc. into consideration. Application of the methods to FIT, MORE [3] and other data will provide new substantive results that will: (1) contribute to useful clinical guidelines for judging how well an individual patient is responding to osteoporosis treatment, and (2) provide basic empirical evidence about responsiveness to treatment. We expect that the results from this project will be of both methodological and clinical interest so articles appropriate for both biostatistical and substantive journals will be prepared to present the findings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW YORK REGION THALASSEMIA CENTER Principal Investigator & Institution: Giardina, Patricia J. Pediatrics; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (Adapted from the applicant's abstract) The overall objective of this proposal is to establish a New York Regional Thalassemia Center (NYRTC) that could participate in the development and establishment of the NIH Thalassemia Clinical Research Network (TCRN). Key research in thalassemia and the meaningful evaluation of new therapies would be greatly enhanced by the creation of this network. In preliminary work, the investigators have developed a group of 12 regional institutions caring for more than 200 patients and have begun compiling a patient database. Members of the NYRTC have identified two central subjects for investigation as models for collaborative trials: hepatitis C( HCV) infection and osteoporosis.. The first study proposes combination therapy to treat HCV, a complication common among patients transfused before blood screening which leads to increased risk of liver disease (fibrosis, cirrhosis, cancer) from both iron overload and HCV. Interferon alone is effective in only 10% of cases. Pilot studies combining interferon and ribavirin show promise. The investigators propose to include analysis of iron status patient and host specific disease modifiers, including mutations of the HFE gene. These mutations affect gastrointestinal iron absorption and the investigators have found are associated with low CD8 immunotype. The second study centers on evaluation and treatment of osteoporosis.. Iron overload influences bone metabolism both directly and indirectly through effects on the immune, endocrine and hematopoietic systems. Markers of bone formation and resorption will be correlated with bone mineral density and a variety of iron-related parameters as well as the above mentioned host specific disease modifiers. A clinical trial will be undertaken to assess the effectiveness of pamidronate, a drug that inhibits bone resorption. Again, the impact of iron and the disease modifiers will be examined. These studies are ideally suited to multicenter collaborations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NIH OSTEOPOROSIS & RELATED BONE DISEASES RESOURCE CENTER Principal Investigator & Institution: Dawson-Hughes, Bess V. Professor of Medicine; National Osteoporosis Foundation 1232 22Nd St Nw Washington, DC 20037 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: (Taken from the Application) In 1993, Congress issued a mandate to increase awareness and knowledge about osteoporosis and related bone diseases. In response, the leading national nonprofit organizations in the field, the National Osteoporosis Foundation (NOF), The Paget Foundation (PF), and the Osteogenesis Imperfecta Foundation (OIF), were selected to establish the first national resource center in the field. In 1997, with 28 million Americans diagnosed or at risk for osteoporosis, 1.5 million painful fractures, $14 billion in health care costs, and millions affected by Paget's disease, osteogenesis imperfecta, and other related bone diseases, Congress renewed the Center's mandate. NOF and its collaborating partners propose to broaden and expand the reach of the current NIH Osteoporosis and Related Bone Diseases National Resource Center. Aim 1 focuses on strengthening the Center's infrastructure and broadening its services. Under the guidance of an Advisory Council, specific tasks include expanding the acquisition of research information and inquiry services; promoting the Center to physician and public audiences through exhibits, public service

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announcements and other means; and widely disseminating information via Web sites and other electronic methods, a speaker's bureau, and print publications such as bibliographies, fact sheets, and an expanded newsletter, to medical professionals, managed care organizations, and underserved and at-risk populations, including youth, men, and Hispanic and Asian American women. Aim 2 focuses on developing partnerships to create and evaluate a model education program to enhance bone health and reduce future risk of osteoporosis among a key group---adolescent females. The program will be based on a Center-sponsored communications study of the delivery of health promotion messages to this audience. Aim 3 is intended to expand awareness and use of research data. Specific efforts include supporting the National Osteoporosis Data Group, collecting and disseminating definitive statistics on bone diseases and on conditions co-morbid with osteoporosis, and preparing summary reports. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NMR IMAGING AND STEREOLOGIC ANALYSIS OF TRABECULAR BONE Principal Investigator & Institution: Wehrli, Felix W. Professor; Radiology; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-JAN-1993; Project End 31-MAR-2004 Summary: Most osteoporotic fractures occur at skeletal locations rich in cancellous (trabecular) bone. The most widely used criterion for risk assessment is bone mineral density (BMD). However, it is well known that BMD is not a satisfactory predictor of fracture risk. Indeed, there is now compelling theoretical, experimental and clinical evidence for the role of architecture as an additional predictor of the bone's mechanical competence. During the past cycles of this project we have shown both in the laboratory and in patient studies that magnetic resonance micro-imaging (mu-MRI), in conjunction with image analysis, can predict the trabecular bone's mechanical behavior and clinical outcome, respectively. In preliminary work we have conceived a new approach toward a complete quantification of cancellous bone architecture based on three-dimensional digital topological analysis and have shown that this techniques accurately describes the conversion of trabecular plates to rods, a process well known to occur during aging and, in particular, in osteoporosis.. Paralleling these developments we have made significant progress in data acquisition, processing and analysis, which improved both sensitivity and precision of mu-MRI to the extent that longitudinal studies are now feasible. During the next phase of the project we propose (i) to further develop and evaluate digital topological analysis and additional structural analysis tools; (ii) to determine the precision of the mu-MRI-derived topological and scale parameters in specimens and representative patients; (iii) to assess the sensitivity of the method to detect architectural changes during early menopause in a pilot project involving women treated with estrogen and their controls; (iv) to compare sensitivity and precision of mu-MRI with DEXA and p-QCT. The overall hypothesis to be tested is that mu-MRI-based cancellous bone structural analysis is sensitive and reproducible and capable of detecting changes in cancellous bone architecture as they occur over time, either as a result of normal changes or in response to treatment. The long-term goal of the work proposed is to establish "virtual bone biopsy," analogous to physical bone biopsy, by three-dimensional architectural analysis of mu-MRI data collected in vivo, as a means to follow patients longitudinally, either as a method for assessing osteoporosis risk or for evaluating treatment efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NUTRITIONAL REGULATION OF BONE TURNOVER Principal Investigator & Institution: Shapses, Sue A. Associate Professor of Nutrition; Nutritional Sciences; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, NJ 08901 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 28-FEB-2005 Summary: Osteoporosis affects approximately 28 million Americans, and is a leading cause of death among older men and women. It has been estimated that in women (50+ years), up to 50% have osteopenia (low bone mass) and 18% have osteoporosis.. The risk of osteoporosis increases in women of low body weight or those who have a history of weight loss. In addition, the PIs have shown that moderate weight loss results in bone mobilization and loss in obese women. Moreover, studies of involuntary wt loss show that the magnitude of the bone loss is greater in thinner than heavier women. Hence, these studies will address whether bone mobilization and loss is greater in overweight (body mass index, BMI 25-29.9) than obese (BMI more than 30 ) pre- and post menopausal women during moderate voluntary wt loss. Our data show that an increase in serum parathyroid hormone (PTH) and a decrease in sex hormones may be regulating the rise in bone turnover with wt loss. It is hypothesized that a reduced calcium absorption during caloric restriction is responsible for the rise in PTH. We propose to study the basis for the rise in turnover and PTH during caloric restriction by examining total fractional calcium absorption during wt loss. In obese women, the PIs found that 1.6 mg/d of Ca can suppress the bone mobilization and loss associated with wt loss. However, it is not known if this level of Ca intake can suppress bone mobilization in "thinner" overweight women during caloric restriction. Also, it is possible that the current recommended level of intake (1-1.2 g/d) is not adequate during wt loss based on studies of wt loss induced bone loss by others. Therefore, these studies will examine bone turnover and mass during caloric restriction at 2 levels of Ca intake (adequate or high) to determine optimal levels for wt loss. Importantly, rat studies show that fracture risk is increased with caloric restriction (despite adequate Ca intake). To understand how the quality of bone is altered with wt loss, and whether it is dependent on initial body wt, we will examine the ultrastructural properties of bone after chronic caloric restriction in obese and lean rats. Long-term goals of these studies are to determine nutritional influences on bone which can be applied in the prevention and treatment of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORAL RECOMBINANT PTH(1-31)NH2 FOR OSTEOPOROSIS Principal Investigator & Institution: Mehta, Nozer M.; Unigene Laboratories, Inc. 110 Little Falls Rd Fairfield, NJ 07004 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAR-2002 Summary: (Scanned from the applicant's description): Current osteoporosis therapies such as calcitonin, estrogen and bisphosphonates are primarily antiresorptive agents. Parathyroid hormone (PTH) and its fragments have a potent anabolic effect, enhancing skeletal mass and quality of bone. PTH(1-31)NH2, an N-terminal fragment of PTH, has recently been shown to induce an osteogenic response comparable to that of intact PTH, but not the hypercalcemic response associated with long-term therapy with other forms of PTH. We hypothesize that orally delivered recombinant PTH(1-31)NH2 can be developed as an effective anabolic agent to treat osteoporosis, with enhanced patient compliance in chronic usage. Phase I of this proposal addresses the following specific aims: 1. Produce recombinant rhPTH(1-31)NH2 using our proprietary "direct

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expression" and amidation technologies; 2. Demonstrate by in vitro assays that the material is bioactive after purification; 3. Perform a preliminary pharmacokinetic oral study in rats with chemically synthesized peptide using our patented oral delivery formulation. During Phase II, we will carry out oral delivery studies in ovariectomized and intact rats to determine efficacy. Also, we will test an oral solid dosage form in dogs to demonstrate bioavailability, and carry out pilot studies in man designed as a basis for the clinical development of oral rhPTH(1-31)NH2. PROPOSED COMMERCIAL APPLICTION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPOROSIS APPROACH BASED ON BONE RESORPTION BLOCKADE Principal Investigator & Institution: Rosenblatt, Michael; Vice President; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001; Project Start 01-APR-1995; Project End 30-JUN-2004 Summary: (Adapted from the Applicant's Abstract): This research proposal focuses on elucidating the nature of integrin-ligand interactions for the predominant cell surface adhesion molecule displayed on human osteoclasts, the alpha(v) beta(3) integrin (vitronectin receptor). The investigators propose to map the ligand binding surface of alpha(v) beta(3) using an integrated approach, which combines chemistry of photoaffinity scanning, followed by protein digest mapping of the ligand integrin receptor photoconjugates, and structure-function analysis of the receptor utilizing the molecular biology of site-directed mutagenesis. In the proposed studies, the "contact sites" between ligand the cloned human alpha(v) beta(3) receptor will be examined using a novel set of "tagged" peptide analogs, which incorporate a photoreactive group and a photoreactive iodine or biotinylated derivative. An alpha(v)beta(3) affinity column will be used to select high affinity ligands from a large mixture present in synthetic combinatorial libraries. Putative contact sites will be confirmed by making substitutions in the receptor by site-directed mutagenesis. The investigators hope to develop an experimentally-derived model of the alpha(v)beta(3) integrin ligand bimolecular complex, which can then serve as a template for rational design of alpha(v)beta(3) antagonists for the treatment of osteoporosis and other disorders of bone metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OSTEOPOROSIS CANDIDATE GENES: IN SILICO AIDED DISCOVERY Principal Investigator & Institution: Ardlie, Kristin G.; Genomics Collaborative, Inc. 99 Erie St Cambridge, MA 02139 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Our understanding of the gene interactions that underlie molecular pathogenesis is expanding rapidly, yet despite continuing technical advances in the area, genetic studies of common diseases remain costly and time consuming. Initial linkage and/or genome scan studies are rarely definitive, and require further focused genetic follow-up and/or validation studies often on additional patient cohorts. Current solutions include sample pooling to defray the considerable genotyping costs of whole genome studies, or reduced and selective focal candidate gene approaches. The success of the latter, however, depends on knowledge of the disease and pathways, which is growing but still limited. Our goal is to determine

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whether simulating the biological pathways of putative candidate genes prior to testing those candidates, can enable us to more accurately target higher-likelihood candidates and reduce both the cost and time involved in identifying the genes associated with disease, as well as to define the likely role of these targets in a future diagnostic or therapeutic setting. We will test this in a genetic study of Osteoporosis aimed at identifying the gene(s) underlying the observed linkage to chromosome 1p36. Osteoporosis is a disease of reduced bone mineral density (BMD) that is associated with increased risk of bone fracture and for which the treatment and care of hip fractures exceeds $9 billion annually. Numerous twin and family studies have shown that as much as 80% of the individual risk in BMD is under genetic control. Moreover the genetic basis of the disease is likely to be polygenic, involving multiple gene products implicated in both bone modeling (growth) and remodeling (loss and gain). Our goals in this phase of the study are 1) to evaluate all genes in the linkage region 1p36 in a novel biological modeling and simulation platform, "BoneFusion", for their impact and importance in bone remodeling, 2) to genotype SNPs in the genes identified as high value candidates in order to identifying associations between the gene candidates and osteoporosis, and test the model, and 3) to further use the BoneFusion computer simulation to define the potential of any genes showing strong association with the disease, as a therapeutic target and/or diagnostic marker. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPOROSIS IN HYPERCALCURIC KIDNEY STONE FORMERS Principal Investigator & Institution: Asplin, John R. Medical Director; Litholink Corporation 2250 W Campbell Park Dr Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 15-APR-2001; Project End 30-SEP-2001 Summary: (Adapted from the Applicant's Abstract): The aim of our research is to determine the risk of bone disease in hypercalcuric kidney stone formers and their families by establishing an algorithm that takes into account bone mineral density (BMD), demographic characteristics, diet history, and urine chemistries, including markers of bone turnover. This algorithm will allow us to determine which hypercalcurics need clinical evaluation for osteoporosis and will form the basis of a disease management product. In the process of creating this algorithm, we will be the first to determine the prevalence of bone disease in hypercalcuric stone formers and their families and over time make some estimates of incidence rates. A longer-term goal of our research is to study the genetic underpinnings of osteoporosis and nephrolithiasis. PROPOSED COMMERCIAL APPLICATION: Litholink provides disease managment services for kidney stone patients. We hope to use the algorithm developed in this research to expand our services to include bone disease management in kidney stone forming patients and their families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OSTEOPOROSIS IN MEN Principal Investigator & Institution: Marcus, Robert A. Professor; Medicine; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 30-JUN-2006 Summary: There has long been an appreciation of the importance of osteoporosis in women, and decades of research have yielded a strong foundation of mechanistic and practical knowledge that underlies clinical decision- making. On the other hand, very little information is available to direct the management of osteoporosis in men. The

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primary goal of this study (MR.OS) is to determine the extent to which fracture risk in order men is related to bone mass, bone geometry, lifestyle factors, biochemical measures, fall propensity, and other variables. This information is essential for understanding the genesis of fractures, and for the formulation of clinical algorithms for detection and treatment of osteoporosis in men. A second goal is to determine the relationships between osteoporotic fracture and two common chronic conditions in older men prostate cancer and osteoarthritis (OA). This will be a multicenter, prospective study of risk factors for vertebral and all non- vertebral fractures in older men (> 65 years). A total of 5,700 men will be recruited in six diverse geographical areas (Portland, OR; Pittsburgh; Minneapolis; San Diego; Palo Alto; and Birmingham), and will be followed for an average of three years. Baseline assessments will include BMD and bone geometry, vertebral morphometry, OA, neuromuscular and visual function, anthropometrics, nutrition, medical history, medication use, serum/urine/DNA collections, and functional status. Repeat measures of BMD and health/functional status will be obtained at two follow-up visits. The final exam will include repeat radiographs of the spine, hips and knees to determine incident vertebral fracture rate, and incidence and progression of OA. Participants will be followed every 4 months by postcard to determine the rates of non-vertebral fracture, falls, and prostate cancer. Data analysis will utilize proportional hazards and logistic regression models, depending on the type of outcome being analyzed. The study will have 90% power to detect RR of 1.35 for vertebral fractures and OR of 1.22 for non-spine fractures. MR.OS will provide unique information concerning osteoporosis and other common disorders, and will provide a basis for the construction of crucial preventative and treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPOROSIS IN OLDER MEN AND WOMEN Principal Investigator & Institution: Greenspan, Susan L. Professor of Medicine; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 30-NOV-2007 Summary: (provided by applicant): Susan Greenspan, M.D., Professor of Medicine at University of Pittsburgh, is applying for the K24 Midcareer Investigator Award in Patient-Oriented Research to advance her career in clinical investigations of osteoporosis in older men and women. Her immediate career objectives are 1) to establish herself as a leading national authority on osteoporosis in the elderly with a new focus on older men, and 2) to serve as a mentor for medical trainees, including medical students, fellows, and junior faculty members pursuing patient-oriented research in osteoporosis and related geriatric fields. Her long-term objectives are 1) to apply the expertise and skills in patient-oriented osteoporosis research to clinical research in other fields involving common endocrine or geriatric syndromes, and 2) to actively participate in the institutional commitment to promote clinical research at the University of Pittsburgh through mentoring and teaching activities. Dr. Greenspan's research will center on two areas. First, she will explore novel treatments with combination therapy with antiresorptive and anabolic agents for postmenopausal osteoporosis.. New techniques assessing outcomes of trabecular vs. cortical bone density and markers of bone turnover will be utilized. Secondly, a model of male osteoporosis will be examined-that of bone loss following androgen deprivation therapy in men with prostate cancer. She will examine the pathophysiology of this bone loss and its prevention. Dr. Greenspan has a strong track record in mentoring junior investigators. This award would ensure protected time for mentoring activities that

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provide appropriate direction, resources, and educational programs for her trainees. Furthermore, this proposal will allow protected time for the candidate's self education for additional training in statistical analysis, the essentials of mentoring, involvement of African American subjects in clinical research, and leadership in academic medicine for women. The clinical research and mentoring program will be conducted at the University of Pittsburgh, which has a strong institutional commitment to the professional development of the candidate and a mission to support patient-oriented activities of its faculty members. The General Clinical Research Center (Dr. Greenspan's clinical laboratory), the Center for Minority Health, and the recently funded Clinical Research Training Award (K30) will help facilitate this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPOROSIS IN THALASSEMIA Principal Investigator & Institution: Cohen, Alan;; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, PA 19104 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OSTEOPOROSIS PREVENTION IN EARLY STAGE BREAST CANCER Principal Investigator & Institution: Hershman, Dawn; Epidemiology; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): In the United States, more than 2 million women are living with a history of breast cancer. Because of past advances in chemotherapy, the vast majority of women diagnosed with breast cancer will survive for many years, but they will also have increased risk for long-term complications related to estrogen deficiency, lymph node dissection, and other effects of chemotherapy on health tissue Evidence suggests that women who survive breast cancer have an increased risk for osteoporosis.. This risk is highest for premenopausal women who become menopausal with chemotherapy. However, controversy exists regarding the extent of bone loss, and only a few studies have evaluated mechanisms to prevent it. A double- blind randomized control trial of weekly alendronate in premenopausal women treated with adjuvant chemotherapy for breast cancer will be performed to define and compare the changes in BMD and bone turnover that occur during and after adjuvant chemotherapy for breast cancer. We expect to characterize the natural history of bone loss during chemotherapy and define risk factors that contribute to this loss in newly diagnosed premenopausal breast cancer patients. By defining factors that predict accelerated bone loss we hope to help guide preventive therapy. With the results of this trial, costeffectiveness of bisphosphonate treatment will be modeled. We expect that bisphosphonates will significantly reduce the rate of bone loss in this patient population and that bisphosphonate use for the prevention of osteoporosis and its related complications will be cost-effective. The training portion of this proposal includes regular mentoring with Dr. Karen Antman and Dr. Elizabeth Shane; extensive interaction with Dr. Alfred Neugut, Dr. Victor Grann, and Dr. Richard Gralla; and continued formal coursework at the Mailman School of Public Health at Columbia University. My goal as an independent investigator is to conduct clinical research that will identify approaches to cancer treatment that will minimize toxic effects, prevent long- term complications, and maximize survival, quality of life, and cost- effectiveness.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPOROSIS PREVENTION IN PREADOLESCENT GIRLS (BE A STAR! BANK ON YOUR BONES!) Principal Investigator & Institution: Kwoh, Kent;; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: We have developed an innovate behavioral/education intervention designed to decrease modifiable risk factors for osteoporosis in preadolescent girls. The objective of the proposed study is to demonstrate the efficacy of this intervention in increasing levels of dietary calcium intake and weight-bearing exercise within an at-risk population in a stage of rapid accrual of bone mass--specifically, premenarchal Girl Scouts between the ages of 10 and 12. Cluster randomization will be used to randomize Girl Scout troops to either the intervention or a program of education only. Eighteen Girl Scout troops (144 girls) will be randomized into each arm (i.e., an estimated 8 girls participating per troop). The intervention consists of 3 interactive sessions utilizing various media (i.e., overhead transparencies, graphics, and three-dimensional demonstrations) to present instructional material. Topics include an explanation of osteoporosis and its modifiable and non-modifiable risk factors, prevention of osteoporosis via healthy food choice (i.e., high calcium, low fat foods), and prevention of osteoporosis via weight-bearing exercise (specifically, jumping rope.) Each girl is given a "3-day Star Chart" with colorful graphics for easy self-monitoring of her progress toward the goal of 1350 to 100 mg of calcium per day. Star stickers represent serving sizes of foods that contain either 150 mg (1 star) or 300 mg (2 stars) of calcium. The "Star Exercise Pyramid" similarly allows simple self monitoring of weight-bearing activity to be recorded with stars representing 5-, 10- or 15-minutes blocks of weight bearing exercise per week. Incentives are given to the girls to reinforce the content of the intervention sessions-- i.e., a food pyramid magnet, a mug with markings for 1 and 2 cup serving sizes, jump ropes, a booklet of jump rope games. The intervention program is reinforced via monthly self monitoring for 18 months. The education only program consists of three generic sessions on healthy eating, physical fitness, and healthy lifestyle choices. The primary outcomes of interest are higher calcium intake and higher levels of weight bearing exercise. A secondary outcome of interest is increased broadband ultrasound attenuation of the os calcis assessed using quantitative ultrasound. In summary, the group of girls targeted is ideal for this intervention since they are at a stage of rapid accrual of bone mass. We postulate that the intervention will maximize their opportunity for attaining potential peak bone mass, thus serving to further the ultimate goal of osteoporosis prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OSTEOPOROSIS PREVENTION IN SEDENTARY ADOLESCENT FEMALES Principal Investigator & Institution: Jamner, Margaret S. Urban and Regional Planning; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001; Project Start 19-JUN-2000; Project End 31-MAY-2005 Summary: Description (adapted from the investigator's abstract): The goal of this research is to implement a novel behavioral program designed to increase physical activity and enhance bone mineralization. The study focuses on sedentary adolescent females, a population at particularly high risk for developing osteoporosis later in life.

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The investigators hypothesize that the intervention will increase physical activity, that these increases in activity will be associated with changes in specific psychosocial characteristics, and that they will lead to increases in bone formation and bone mineral density over 10 months. The proposed research intends to: (1) test the intervention designed to increase female adolescents' physical activity; (2) evaluate the efficacy of one component of the intervention consisting of an Internet-based exercise diary linked with motivational role model stories; (3) evaluate the respective roles of specific psychosocial characteristics that may predispose toward the adoption and maintenance of physical activity; (4) determine whether positive changes in psychosocial characteristics over time are associated with increased participation in physical activity; and (5) test the hypothesis that increased physical activity enhances bone mineralization. Sedentary adolescent females will be assigned to full intervention (n=100), modified intervention (n=100), or comparison group (n=100) for 10 months. All participants will receive daily calcium supplementation. Bone formation will be assessed at baseline (DEXA), 5 wks and 5 mo. (serum and urinary measures), and 10 mo. (DEXA). Psychosocial characteristics and physical activity participation will be measure at all four intervals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPOROSIS, COLLAGEN CROSS-LINKS & BIOMECHANICS Principal Investigator & Institution: Paschalis, Eleftherios P. Associate Scientist; Hospital for Special Surgery 535 E 70Th St New York, NY 10021 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant): During studies of the variation in mineral properties in osteoporotic bone, an apparent alteration in the quality of the organic matrix as a function of anatomical location within the same individual was observed. The overall goal of this proposal is to test the hypothesis that there are consistent alterations in the organic matrix of osteoporotic patients compared with normals, which are dependent on the anatomical site, and are due to differences in collagen properties. This will be accomplished through the investigation of three specific aims: Aim 1: To test the hypothesis that there are significant differences in collage/matrix properties between normal and osteoporotic human bones. Furthermore, that these differences are evident in actively bone forming surfaces. This hypothesis will be addressed by comparison of iliac crest biopsies from individuals in whom osteoporosis has been determined based on histologic/histomorphometric parameters, with biopsies from those without morphometric evidence of osteopenia. These studies will be based on histology, and FTIR Imaging (FTIRI) techniques. Aim 2: To test the hypothesis that the observed differences are a function of variations in the biochemical properties of collagen, primarily cross-linking pattern (extent, maturity, origin). This will be verified by a comparison of biochemical and FTIR analyses of a series of highly purified collagen peptides. Additionally. quantitation of the spectroscopic parameters describing collagen cross-links will be achieved utilizing well-established chemical methods to modify predentin. Aim 3: To test the hypothesis that variation in the mechanical properties of bone is dependent part on the quality of the organic matrix. This aim will document the effect of changes in collagen-cross linking pattern observed by FTIRI on the mechanical properties of bone in a well-documented animal model system. Bulk collagen quality will be analyzed by chemical means, and geometric/anatomical variations by FTIRI. These studies will be performed using bones from the beta-aminoproprionitrile rat animal model in which collagen/structure is known to be modified, and for which both geometric and structural properties will be determined. The proposed studies will be

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based on histology, FTIR Imaging (FTIRI), biomechanical, and biochemical techniques and represent a novel approach to evaluating the organic matrix inosteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPOROTIC BIOPSIES ASSESSED BY MICROCT Principal Investigator & Institution: Myers, Elizabeth R. Associate Scientist; Hospital for Special Surgery 535 E 70Th St New York, NY 10021 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Osteoporosis has been defined traditionally as porous bone structure that is reduced in quantity but has normal bone material or quality. A decrease in bone density is considered the hallmark of osteoporosis, but bone fracture is the critical clinical outcome. Moreover, although bone density is associated with the mechanical characteristics of bone, it does not fully account for bone mechanical response. There is a growing body of evidence that bone turnover contributes to changes in bone strength by affecting not only quantity but also architecture, mineral, and matrix quality. Quantitative micro-computed tomography (microCT) has the potential to characterize the quantity and quality of cancellous bone in three dimensions and to explore the effects of osteoporosis and bone turnover. The goal of this exploratory & developmental grant proposal (R21) is to analyze human biopsies using quantitative microCT. Iliac crest biopsies characterized as normal, lowturnover osteoporosis, and high-turnover osteoporosis will be examined to test the following research question: Do cancellous volume fraction, trabecular threedimensional architecture, and patterns of material inhomogeneity differ among normal, low-turnover, and high-turnover osteoporotic bone? Human iliac crest biopsies of lowturnover or high-turnover osteoporosis will be compared with normal biopsies by quantitative microCT. Bone volume fraction and trabecular architecture will be characterized. Quantitative CT x-ray attenuation values will be used to provide tissue mineral density within trabeculae. The variation in tissue mineral density will be assessed as a function of depth from the trabecular surface by a distance transformation approach. Comparisons will be made among the three groups to investigate whether substantial differences exist between low- and high-turnover bone and between osteoporotic and control specimens. The main goal is to detect differences in trabecular architecture and material properties with turnover state. These results should lead to specific hypotheses about the effects of turnover rate on bone quality in osteoporosis and possibly under therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OSTEOPOROTIC FRACTURES IN MEN (MR.OS) Principal Investigator & Institution: Lewis, Cora Elizabeth. Associate Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 30-JUN-2006 Summary: There has long been an appreciation of the importance of osteoporosis in women, and decades of research have yielded a strong foundation of mechanistic and practical knowledge that underlies clinical decision- making. On the other hand, very little information is available to direct the management of osteoporosis in men. The primary goal of this study (MR.OS) is to determine the extent to which fracture risk in order men is related to bone mass, bone geometry, lifestyle factors, biochemical measures, fall propensity, and other variables. This information is essential for understanding the genesis of fractures, and for the formulation of clinical algorithms for

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detection and treatment of osteoporosis in men. A second goal is to determine the relationships between osteoporotic fracture and two common chronic conditions in older men prostate cancer and osteoarthritis (OA). This will be a multicenter, prospective study of risk factors for vertebral and all non- vertebral fractures in older men (> 65 years). A total of 5,700 men will be recruited in six diverse geographical areas (Portland, OR; Pittsburgh; Minneapolis; San Diego; Palo Alto; and Birmingham), and will be followed for an average of three years. Baseline assessments will include BMD and bone geometry, vertebral morphometry, OA, neuromuscular and visual function, anthropometrics, nutrition, medical history, medication use, serum/urine/DNA collections, and functional status. Repeat measures of BMD and health/functional status will be obtained at two follow-up visits. The final exam will include repeat radiographs of the spine, hips and knees to determine incident vertebral fracture rate, and incidence and progression of OA. Participants will be followed every 4 months by postcard to determine the rates of non-vertebral fracture, falls, and prostate cancer. Data analysis will utilize proportional hazards and logistic regression models, depending on the type of outcome being analyzed. The study will have 90% power to detect RR of 1.35 for vertebral fractures and OR of 1.22 for non-spine fractures. MR.OS will provide unique information concerning osteoporosis and other common disorders, and will provide a basis for the construction of crucial preventative and treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARY INTACT MURINE MODEL FOR MENOPAUSE Principal Investigator & Institution: Hoyer, Patricia B. Professor; Physiology; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-MAR-2008 Summary: (provided by applicant): By the year 2025, 19.5% of the population of the U.S. will be post-menopausal aged women. Many health risks are associated with menopause, thus, research into menopause and aging in women is of prime interest. Investigations of menopause-associated disorders in a relevant animal model would be particularly useful. The occupational chemical 4-vinylcyclohexene diepoxide (VCD) has been well characterized and found to induce pre-mature ovarian failure in mice and rats by accelerating the natural process of atresia (apoptosis). More recently, preliminary data have demonstrated that VCD-induced follicle loss in mice can cause depletion of primordial follicles within 15 days of daily dosing. This results in complete ovarian failure within 46 days of the onset of dosing, and the animals retain residual ovarian tissue. Physiological end points related to several menopause-associated disorders, including osteoporosis, cardiovascular disease, and ovarian cancer have been observed in VCD-treated mice. The majority of women enter menopause by a gradual depletion of ovarian function and they retain residual ovarian tissue. Thus, a follicle-deplete, ovary-intact animal would most closely mimic the natural progression through perimenopause and into the post-menopausal stage of life. It is proposed here to conduct studies to more completely characterize the physiological end points that have already been seen. The hypothesis to be tested is that the VCD-treated mouse will serve as a highly relevant animal model for studies aimed at understanding many of the facets of menopause. Four Specific Aims have been proposed: Specific Aim 1: To determine events surrounding the period of impending ovarian failure (model for perimenopause) Specific Aim 2: To investigate mechanisms by which osteocalcin levels are elevated (model for osteoporosis) Specific Aim 3: To characterize the development of aortic lesions (model for cardiovascular disease) Specific Aim 4: To evaluate changes resulting from proliferation of the ovarian surface epithelium (model for ovarian

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cancer). The studies proposed here will provide evidence in the follicle-deplete, ovaryintact mouse as to what aspects of menopausal physiology and pathology are particularly relevant for designing future studies aimed at mechanistic or therapeutic issues. Characterization of the VCD-treated mouse will, therefore, make a profound contribution to the study of menopause-related pathologies and, therefore, to women's health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: P01-PATHOGENESIS AND PREVENTION OF OSTEOPOROSIS Principal Investigator & Institution: Kream, Barbara E. Professor; Medicine; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2001; Project Start 30-SEP-1987; Project End 31-JUL-2005 Summary: OF THE OVERALL PROGRAM (taken from the application): This program project application represents a coordinated, collaborative and multidisciplinary approach that utilizes common resources, facilities and instrumentation to support scientific investigators related to the pathogenesis of osteoporosis.. This application is comprised of four highly integrated scientific projects and three supporting core facilities (Administration, Molecular Histology and Transgenic Animal and Molecular Cores). The central theme of the ?program project is that the pathogenesis of osteoporosis is due both to the interaction of catabolic factors that increase bone resorption and to the loss of anabolic activities. These factors, both systemic hormones and local cytokines, modulate the differentiation of osteoclast and osteoblast lineage cells and the biological function of these cells. An understanding of these factors and their actions on bone remodeling will help elucidate the pathogenesis of osteoporosis.. Moreover, intervention with molecules that block pathogenic factors or enhance anabolic activities will have therapeutic implications. This could be accomplished by somatic gene therapy once the cellular and molecular steps required to develop such a strategy are developed. The scientific projects of this application are: (1) Glucocorticoids and osteoblast apoptosis, (2) Estrogen regulation of cytokine responsiveness in bone: osteoclastogenesis, (3) The roles of insulin-like growth factor and glucocorticoids on bone remodeling, and (4) Engraftment of osteoprogenitor cells in bone. We believe that interactions among our investigators, research productivity towards the central theme and new collaborations will be facilitated greatly by the program project mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARATHYROID HORMONE SIGNALING IN BONE CELLS Principal Investigator & Institution: Bisello, Alessandro; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): Osteoporosis is the most common human bone disorder. It is estimated that more than 10 million women and men in the United States have osteoporosis and 20 million more are at risk for osteoporotic fractures. Animal and human studies have shown that, when administered intermittently at low doses, both PTH and PTH-related protein (PTHrP) effectively stimulate bone formation. The bone anabolic activity of PTH and PTHrP is associated with their capacity to stimulate the type 1 PTH/PTHrP receptor (PTHI Rc), expressed in both osteoblasts and bone marrow stromal cells. PTH1 Rc is coupled to several signaling pathways, leading to activation of protein kinase A (PKA), PKC and mitogen-activated protein kinases ERK1 and ERK2. While the Gs/cAMP/PKA signaling pathway seems to be necessary, and possibly

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sufficient, to stimulate an anabolic response in the skeleton, recent studies have established the combined actions of PKC and beta-arrestin2 in the desensitization of PTH 1 Rc function. The central hypothesis of this research proposal is that the cellular responses to PTH and PTHrP depend not only on PTH1 Rc-mediated signal transduction, but also on additional interactions with arrestins, endocytosis and cellular trafficking of ligand/receptor beta-arrestin2 complexes. Specifically, we hypothesize that continuous and selective activation of the Gs/camp/PKA pathway will induce expression of genes, proteins and cellular responses associated with the anabolic activity on bone. The development of non-desensitizing PTHrP analogs displaying selective and sustained CAMP signaling permits the direct testing of this hypothesis. We therefore propose to: 1) identify specific interactions between PTH1 Rc and beta-arrestin2; 2) determine the role of beta-arrestin2 in mediating PTH 1Rc signal transduction and cellular trafficking in osteoblasts and stromal cells; 3) determine the effect of selective and continuous stimulation of cAMP signaling on gene/protein expression by osteoblasts and stromal cells; 4) determine the effect of selective and continuous stimulation of cAMP signaling on osteoblasts and stromal cells proliferation and apoptosis. These studies will advance the understanding of the molecular mechanisms underlying the cellular actions of PTH and PTHrP and may lead to the development of novel PTH/PTHrP-based anabolic compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOPHYSIOLOGY OF OSTEOPOROSIS Principal Investigator & Institution: Riggs, B L.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001 Summary: Our central hypothesis is that estrogen (E) deficiency acts through various tissue-specific mechanisms to account for most of the bone loss in aging women and for a substantial part of it in aging men. Specific Aim 1 will define possible direct versus indirect effects of E on parathyroid hormone (PTH) secretion, leading to a better understanding of the pathogenesis of the secondary hyperparathryoidism of elderly women by assessing PTH secretory dynamics in elderly women in whom E status has been experimentally altered. Protocol 2 will determine id osteoprotegrin (OPG), a newly discovered potent inhibitor of bone resorption and its cognitive ligand, (OPGL), are major paracrine mediators of E action on bone by measuring their bone marrow plasma levels in women followed transmenopausally with and without E therapy. Specific Aim 2 will determine if impaired OPG or excessive OPGL secretion predisposes some, but not other E deficient women to develop osteoporosis by measuring marrow plasma levels in untreated osteoporotic and non-osteoporotic postmenopausal women (Protocol 3). Specific Aim 3 will define the comparative roles for E. testosterone (T), and PTH in regulation bone turnover in elderly men. Protocol 4 will test directly for a causal role for the age-related increase in serum PTH levels in men in mediating increases in bone resorption. Protocol 5 will compare thje effects of E, T + E in preventing increased bone resorption induced by acute induction of hypogonadism with GnRH agonist administration in elderly men, and Protocol 6 will assess the effects of 6 month treatment of elderly men with placebo or raloxifene (which has an E agonist effect on bone but is not feminizing) on biochemical markers of bone turnover. These state-of-theart studies will elucidate the role of E deficiency on the pathophysiology of bone loss and osteoporosis in postmenopausal and aging women and its contribution to bone loss in aging men and may lead to innovative types of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOPHYSIOLOGY OF PTH-RELATED PROTEIN (1-36) IN HUMANS Principal Investigator & Institution: Stewart, Andrew F. Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-JUL-1996; Project End 31-MAR-2003 Summary: (Adapted from the Applicant's Abstract): This application is a hormonerelated protein (PTHrP) in the syndrome of humoral hypercalcemia of malignancy (HHM) and its potential therapeutic role in osteoporosis.. PThrP is responsible for HHM. Patients with HHM resemble those with primary hyperparathyroidism (HPT) in that both groups are hypercalcemic, both display increases in osteoclastic bone resorption, both display renal phosphorus wasting and hypophosphatemia, and increases in nephrogenous cydic AMP excretion. Both HPT and HHM are humoral syndromes. The two syndromes differ with regard to regulation of 1,25(OH)2D (in that this vitamin D metabolite is increased in HPT and reduced in HHM) and in renal calcium handling (with some groups reporting that renal calcium reabsorption is increased, while others suggest that the syndrome is associated with increased renal calcium excretion). In the prior period of funding, we have shown that PTHrP(1-36) stimulates renal calcium conservation in normal human volunteers, and appears to transiently up-regulate, then down regulate, 1,25(OH)2D production. Moreover, we have demonstrated in rats that daily subcutaneous administration of PTHrP is markedly anabolic for the skeleton, leading to increases in bone mass as well as in biomechanical strength. Preliminary studies in humans demonstrate that PTHrP may be a pure anabolic agent," selectively stimulating bone formation without stimulating bone resorption. The studies in this proposal, then, have two Specific Aims: 1. To further define the relative potencies and mechanisms of action of PThrP vs. PTH in humans as regulators of renal calcium reabsorption and 1,25(OH)2D biosynthesis. 2. To complete a pilot study, currently in progress, designed to determine the efficacy of PTHrP(1-36) in the treatment of postmenopausal osteoporosis.. These studies represent an extension of an ongoing, longstanding research program in humans, targeted at understanding the physiology and pathophysiology of PTHrP, and at developing strategies which might employ PTHrP as an anabolic agent in the treatment of osteoporosis.. The studies described in the application strongly suggest that PTHrP may have a unique role as an anabolic agent in the treatment of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEDIATRIC BONE GROWTH, DENSITY, AND METABOLISM Principal Investigator & Institution: Henderson, Richard C. Professor; Orthopaedics; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 30-JUN-2004 Summary: Diminished growth, deformity, osteopenia noted on plain radiographs, and frequent osteoporosis-related fractures are evidence of problems with bone growth and metabolism in many children with an assortment of medical and physical conditions. Although these very late consequences are clinically apparent, the problems are usually initially silent during the important years of skeletal growth and development. The Midcareer Award is requested to support the Research Plan of Dr. Richard Henderson, MD, PhD. He is Professor of Orthopaedics and Pediatrics at the University of North Carolina, and in this capacity is a clinically active pediatric orthopaedic surgeon. Dr. Henderson also has a long-standing commitment to clinical research, with proven

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productivity. His primary research focus is on the issues of osteoporosis, fractures, and bone growth and metabolism in various pediatric conditions such as cerebral palsy, cystic fibrosis, milk allergy, chemotherapuetically treated malignancies, and muscular dystrophy. In the first phase of his Research Plan techniques for assessing bone growth, density, and metabolism are adapted to the unique features of handicapped children. The first phase also includes several single-site, observational, cross-sectional and longitudinal studies with the specific aim of assessing the potential impact of these assorted conditions on mineralization of the immature skeleton. This phase of the Research Plan has just been completed. The second phase includes projects designed to better characterize bone growth and metabolism in children with cerebral palsy, and to assess in greater detail the prevalence, causes, and outcomes of osteoporosis in this population. The utility of this information depends in great part on the availability of prevention and/or treatment alternatives. The bisphosphonates are a class of medications used for the treatment of osteoporosis in elderly adults, and limited anecdotal data suggest that these drugs are also effective in children. The second phase of the Research Plan includes the first controlled clinical trial assessing the safety and efficacy of these drugs in a pediatric population. Extensive collaboration with other research centers brings greater statistical power and expertise in nutrition to studies in the second phase. The second phase consists of 5 closely inter-related projects over a 2-3 year time span, and data collection recently began in April 1998. The third phase planned for the years 2001-2004 will involve larger-scale clinical trials assessing bisphosphonates for the treatment of osteoporosis in multiple pediatric conditions. The practicalities of drug treatment in clinical practice and the dose-response relationship are important issues that will be addressed in this phase. The Midcareer Award is requested to support the second and third phases of the Research Plan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHONING FOR FUNCTION--PROMOTING HEALTH AFTER CANCER Principal Investigator & Institution: Demark-Wahnefried, Wendy; Associate Professor; Duke University Durham, NC 27706 Timing: Fiscal Year 2001 Summary: This year, nearly 1 million older Americans will be diagnosed with cancer. Given improvements in early detection and treatment, most of these individuals will be "cured." However, they may be left with significant morbidity, either from the cancer itself or from its treatment. Furthermore, this population either because of genetic, treatment or lifestyle factors is at increased risk for developing secondary cancers, as well as diabetes, osteoporosis, & cardiovascular disease. Therefore, the older cancer survivor is at even greater risk for developing secondary cancers, as well as diabetes, osteoporosis, & cardiovascular disease. Therefore, the older cancer survivor is at even greater risk of functional decline than the average older adult. However, while cancer may bring a greater risk for functional decline, it may also bring a greater risk for functional decline, it also may bring a "teachable moment." Major lifestyle events, such as a cancer diagnosis, often increase receptivity toward positive lifestyle change. To date, however, little has been done among older cancer survivors to capitalize on this opportunity. Given increased cure rates coupled with the ever growing numbers of elderly, there is significant public health potential for interventions that can reorient the functional decline trajectory of this high risk population. A multi-disciplinary team of investigators in the fields of aging, nutrition, physical activity, behavioral psychology & biostatistics at Duke University Medical Center proposes to test whether a telephone

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counseling program is effective in improving diet & physical activity behaviors among elderly cancer patients with early stage disease-behavior changes which should ultimately improve their physical function. The specific aims of this study are to determine 1) the efficacy of a diet- physical activity telephone counseling program in improving physical function among elders who are newly diagnosed with early stage breast or prostate cancer in both the short and longer term, 2) differences between experimental & control groups with regard to secondary endpoints (diet quality, physical activity, depression, quality of life, etc.) &3) factors that interact with program efficacy (social support, comorbidity, etc.) We will recruit 420 early stage, breast & prostate cancer patients greater than 65 years throughout North Carolina and randomize them into 1 of 2 arms: 1) EXPERIMENTAL ARM-a group that receives a 6month telephone counseling program tailored to stage of readiness to improve dietary & physical activity behaviors; & 2) ATTENTION CONTROL ARM- a group that receives telephone counseling in unrelated areas (e.g, cancer screening). Results will increase our knowledge of the use of telephone counseling to deliver multiple risk factor interventions to elderly with early state-cancers-a rapidly growing population that may be highly receptive, where health promotion is greatly needed & where historically little research has been done. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYSIOLOGY POPULATION

OF

BONE

METABOLISM

IN

AN

AGING

Principal Investigator & Institution: Riggs, B. Lawrence. Professor of Medicine; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-SEP-1984; Project End 30-JUN-2004 Summary: This is a competitive renewal application for funding of years 16-20 of P-01 AG 04875 "Physiology of Bone Metabolism in an Aging Population." Osteoporosis is one of the most important diseases associated with aging and one of the most important issues affecting women's health. Fractures due to osteoporosis exact a staggering toll in disability and expense. The lifetime risk of having one or more fractures associated with osteoporosis is 40%-50% for a White women and is one third of this for a Black woman or a White man. Each year osteoporosis causes at least 1.5 million fractures and costs the health care system $14 billion in the United States. Our overall goal is to understand the causes of age-related bone loss and osteoporosis better so as to develop more effective strategies for their treatment and prevention. This program grant application comprises projects employing different investigative disciplines and an administrative/statistical core that interact synergistically two permit more rapid progress than could be achieved by each alone. "Pathophysiology of Osteoporosis," is the clinical investigative component. Among the novel hypotheses that will be tested are whether the newly discovered anti-resorptive and pro-resorptive cytokines-osteoprotegrin and its cognate ligand-are the paracrine mediators of estrogen (E) action on bone and abnormalities in their secretion contribute to postmenopausal osteoporosis and whether E deficiency plays a major causal role in bone loss in aging men. "Risk Factors for Hip Fractures," the epidemiology component, features a series of unique, population-based retrospective (non-current, historical) cohort studies designed to assess the effects of certain diseases, drugs, and lifestyle differences on the incidence of fractures. "Sex Steroids, Growth Factors, and Bone Cell Function," the basic science component, focuses on sex steroid regulation of bone cell function. It will address two of the most important current issues in bone cell biology- the effect of changes in the concentration of the alpha and beta

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species of estrogen receptors on bone cell function and the identify of the major paracrine mediator of E on bone cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT--GENDER/ BONE MINERAL DENSITY IN PULMONARY DISEASE Principal Investigator & Institution: Covey, Margaret K.; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: (from applicant's Abstract) Patients with Chronic Obstructive Pulmonary Disease (COPD) have risk factors for the development of osteoporosis including: heavy smoking history, corticosteroid use, sedentary life style. Few studies have examined the incidence of bone loss in these patients and no studies have compared bone mass in men and women with COPD. The purpose of this study is to examine the relationship of variables that potentially influence bone mass with current bone compared between men and women with COPD, and healthy men and healthy women. The sample will consist of 45 patients with COPD, and 45 healthy subjects. In order to control for the effects of smoking history vs. disease state on BMD, the healthy group will be divided into those with a significant smoking history (>20 pack-years) versus those with minimal or no smoking history (<20 pack years). Bone mineral density will be measured using dual energy x-ray absorptiometry (DXA) at the following sites: PA lumbar spine, proximal femur, and whole body. Variables potentially influencing BMD will be measured: 1. calcium and ethanol intake as measured by the Bloc' '98 Food Frequency Questionnaire, historical and current physical activity as measured by the Historical Liesur Time Activity Questionnaire and the Physical Activity Scale for the Elderly respectively, cumulative smoking: history as measured by the number of pack-years, gonadal hormones as measured by serum testosterone and serum estradiol levels, corticosteroid use as measured by clinical questionnaire, body mass as measured by body weigh and whole body DXA scan. Statistical analysis will include: 1. univariate linear regression with lumbar spine BMI and proximal femur BMD as dependent variables and smoking history, disease state, calcium intake, ethanol intake physical activity, gonadal hormone levels, corticosteroid use, body mass as independent variables; and 2. analysis of variance with lumbar spine BMD and proximal femur BMD as dependent variables. Results of this study will provide improved understanding of the nature of bone loss in COPD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ASSESSMENT

PORTABLE

ULTRASONOMETER

FOR

OSTEOPOROSIS

Principal Investigator & Institution: Sarvazyan, Armen; Chief Scientist; Artann Laboratories, Inc. 1753 Linvale Harbourton Rd Lambertville, NJ 08530 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 30-JUN-2003 Summary: (Provided by Applicant): The aim of this project is to develop a portable, low cost, fast and easy-to-use device for the quantitative assessment of bone quality that is suitable for mass screening and early identification of those at risk for osteoporosis.. The device will detect changes in the composition and micro-architectural properties of bone by measuring the ultrasound velocity, attenuation, spectral, and non-linear acoustic (NLA) parameters of bone at multiple sites along the skeleton with varied proportion of spongy and compact bone components. The manual scanning probe operating in surface

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pulse transmission mode will be used to obtain ultrasonic profiles in tested skeletal area. The diagnostic potential of NLA spectroscopy as a novel method for detecting the accumulation of microdamage in living bone will be evaluated. The feasibility of the proposed methods and devices has been proven in laboratory model studies and in pilot clinical trials. In Phase II of the project designed during Phase I will be developed into a fully functional and compact bone ultrasonometer with the manual scanning and NLA modes of operation, and clinically tested. Indexes of bone quality composed of several ultrasonic parameters will be developed for differential diagnostics of osteoporosis and mixed osteopenia. PROPOSED COMMERCIAL APPLICATIONS: Early evaluation and monitoring of osteoporosis is imperative for timely and effective treatment of the disease. According to the National Osteoporosis Foundation [1998 Report] the current economic burden associated with osteoporosis-related fractures is estimated at about $13.8 billion annually. There is an urgent need for advancement of the existing diagnostic techniques. The Proposed multi-site ultrasonometer offers higher diagnostic efficacy and specificity, lower cost, portability, and ease of operation. Developed device is ideally suited for the mass screening of osteoporosis and primary monitoring of population with high fracture risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POTENTIAL MECHANISMS OF AGE DEPENDENT BONE LOSS Principal Investigator & Institution: Williams, John P. Associate Professor; Medicine; University of Kentucky 109 Kinkead Hall Lexington, KY 40506 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: Osteoporosis is the most common debilitating bone disease affecting 24 million people in the U.S. An estimated 50 percent of women over 45 and 90 percent of women over 75 years of age have osteoporosis, of which approximately half will suffer osteoporotic fractures. The estimated cost of osteoporosis and related fractures is 7-10 billion dollars per year. Bone resorption by osteoclasts is an energy intensive process, requiring ATP hydrolysis by an H+-ATPase to drive proton secretion. Age-dependent changes in bone mass are accompanied by age-dependent changes in other parameters, including glucose intolerance. Osteoclasts are glucose responsive cells that resorb bone in a glucose concentration dependent manner with a Km of 3 mM. The data presented here indicate that osteoclasts have glucose concentration dependent changes in 1) ATP synthesis, 2) phosphate uptake, 3) tyrosine phosphorylation, and 4) phosphatidylinositol 3-kinase activity. In view of the high metabolic demands of bone resorption, I hypothesize that glucose directly alters the activity of osteoclasts by modulating critical signal transduction processes in these cells. The proposed research will define the molecular mechanisms and metabolic requirements responsible for regulating these signal transduction processes. The Specific Aims are to: I: Characterize The Expression Of Glucose Transport Protein (S) In Osteoclasts. A. Determine the effect of bone attachment on GLUT2 expression in osteoclasts. B. Determine whether glucose transporters are translocated to the plasma membrane in response to bone attachment. II: Characterize Metabolic Elements That Govern Osteoclast Activity. A. Determine the rate limiting steps in glucose metabolism by osteoclasts. B. Characterize the glucose dependence of metabolic pathways. III: Identify Ket Signaling Pathways That Regulate Osteoclast Metabolism. A. Determine and characterize the role of glucose in osteoclastic phosphatidylinositol-dependent signaling pathways. B. Determine the role of glucose in modulating changes in tyrosine phosphorylation of specific proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PRECISE 3D QCT TO MONITOR OSTEOPOROSIS THERAPY Principal Investigator & Institution: Lang, Thomas F. Associate Professor; Image Analysis, Inc. 1380 Burkesville St Columbia, KY 42728 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 30-JUN-2004 Summary: (provided by applicant):The growing number of women receiving drug treatment for osteoporosis underscores the need for sensitive methods to monitor therapy. Because it permits selective assessment of the trabecular and cortical bone, which may respond differently to disease and therapy, quantitative computed tomography (QCT) is well-suited to this purpose. However, the ability of QCT to resolve therapy- or disease-induced changes in bone mineral density (BMD) is limited by variable precision errors. These precision errors mostly relate to the operatordependence of current techniques, which involve manual slice selection and region of interest placement. In our Phase I Grant, we have addressed this problem by developing and demonstrating the feasibility of an image registration algorithm which aligns serial images and uses the resulting 3D transformation to map a baseline region into the same volume of the follow-up image. As we have documented in the Phase I Final Report, this fast and automated approach yields precision errors in vivo of 1.0 mg/cc and 0.9 mg/cc for spinal and proximal femoral trabecular BMD measurements respectively. In this application, we propose to develop and commercialize a prototype software package which will combine diagnostic 3D QCT BMD measurements with our new approach for highly reproducible longitidunal measurements. PROPOSED COMMERCIAL APPLICATION: We will provide commercial CT imaging centers with a powerful set of tools which they can use to compete in the bone mineral density measurement market. The diagnostic measurement component will allow CT scanners to measure bone mineral density in the spine and hip in bone regions comparable to those measured by DXA. Moreover, the high reproducibility of our technique will permit CT centers to offer a method for monitoring therapy effects which will be superior to DXA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREVENTION TRANSPLANTATION

OF

OSTEOPOROSIS

AFTER

ORGAN

Principal Investigator & Institution: Shane, Elizabeth J. Professor of Clinical Medicine; Medicine; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2002 Summary: Osteoporosis and fragility fractures affect 40-50 percent of patients who have had organ transplantation. Improved survival of transplant recipients and expansion of transplantation programs make it likely that the incidence of transplantation osteoporosis will grow substantially. Over the past five years, new insights have been gained into the natural history, demographic and biochemical features of bone loss and fracture after cardiac transplantation, many of which are applicable to other types of organ transplantation. It is now known that the significant declines in lumbar spine and hip bone density (8-10 percent) and fractures (25-40 percent) occur primarily during the initial 6-12 months after transplantation. Although women, older patients and those with low pretransplant bone mass are at increased risk, men also fracture frequently. Moreover, many patients fracture despite normal pretransplant bone density. The early post-transplant period is characterized by increases in markers of bone resorption and decreases in both serum 1,25(OH)2vitamin D and osteocalcin, a marker of bone formation, all of which are associated with more rapid rates of cancelleous bone loss..

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The purpose of this proposal is to use these data to design a rational approach to the prevention of bone loss and fractures after transplantation. The specific aims of the proposal are to evaluate the efficacy and safety of the active metabolite of vitamin D, 1,25(OH)2D (calcitriol) and the antiresorptive bisphosphonate drug, alendronate, in the prevention of bone loss at the spine and hip after cardiac transplantation; to characterize the effects of these drugs on biochemical indices of bone and mineral metabolism during the first year after cardiac transplantation; and to establish the incidence of vertebral fracture during the first year after cardiac transplantation in patients treated with either calcitriol or alendronate. These specific aims will be addressed in a prospective, double-blind, design in which approximately 120 cardiac recipients at Columbia-Presbyterian Medical Center will be randomized shortly after transplantation to receive either A. active alendronate and placebo calcitriol or B. placebo alendronate and active calcitriol for the duration of the first post-transplant year. The goals of the study will be accomplished using timed serial measurements of bone density (spine and hip; by DEXA), spine radiographs and biochemical assays of calciotropic hormones and bone turnover markers. It is expected that this research will lead to rational programs for prevention of this crippling form of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURVIVORS

PREVENTION

OF

OSTEOPOROSIS

IN

BREAST

CANCER

Principal Investigator & Institution: Waltman, Nancy L. Adult Health and Illness; University of Nebraska Medical Center Omaha, NE 681987835 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-DEC-2006 Summary: Osteoporosis can be a major debilitating, expensive, long term, irreversible condition, and breast cancer survivors are particularly at risk for osteoporosis.. As a result of some chemotherapy agents, many of these women experience premature ovarian failure. At least 60% of women with breast cancer have estrogen receptor positive tumor status; thus, they are not candidates for hormone replacement therapy. Without estrogen, bone loss occurs rapidly the first five years of menopause and continues over time but at a slower rate. The purpose of this study is to test whether strength/weight training exercises enhance the effectiveness of risedronate (5 mg/day), calcium (1200 mg/day), and vitamin D (400 IU/day) in improving bone mineral density (BMD) in post-menopausal breast cancer survivors. The sample will be 218 subjects recruited within a 100 mile radius of r sites across Nebraska (Omaha, Lincoln, Kearney and Scottsbluff). Post-menopausal women with a history of stage O (in situ), stage I or II breast cancer, with a BMD DEXA T-score of -1.0 SD or lower at any of 3 sites (hip, spine, forearm) will be stratified by time since menopause (5 yrs or less: > 5 years) and randomly assigned to one of two treatment groups (G1 and G2), with approximately 109 per group. Differences in tamoxifen, smoking, intake of calcium, and body mass index (BMI) between the two groups at baseline will be examined; if differences exist they will be controlled statistically. Both groups will receive risedronate, calcium and vitamin D; G1 also will receive strength/weight training exercises for upper and lower extremities and spine. Facilitative strategies based on Bandura's (1997) Self-Efficacy Theory are designed and used to encourage long-term adherence for both groups. The multicomponent intervention is 24 months with follow-up at 30 and 36 months. The primary outcome measure is BMD of the hip, spine and forearm (via DEXA): secondary outcome measures are muscle strength and fractures. The impact of the multi-component intervention on outcomes will be assessed using General Estimating Equation methodology Measurement of outcomes will occur at 6 and/or 12 month intervals

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through 36 months. In addition, relationships will be examined between level of confidence in goal accomplishment and adherence to intervention components over time. This study may provide evidence of an effective alternative to HRT for treatment of osteoporosis in breast cancer survivors who are not candidates for HRT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF POSTMENOPAUSAL BONE LOSS WITH NITRIC OXIDE Principal Investigator & Institution: Wimalawansa, Sunil J. Professor; Medicine; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, NJ 08854 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: Osteoporosis is a debilitating bone disease predominantly affecting postmenopausal women. Despite recent advances, therapeutic options available for its prevention and treatment are limited. The available FDA approved therapies for osteoporosis are expensive, and some are associated with significant adverse effects. The goal of this proposed research is to establish the role of nitric oxide (NO) in the prevention of postmenopausal osteoporosis.. Others and we have conducted several in vivo and in vitro studies that suggest that NO play an important role in bone homeostasis. Furthermore, administration of nitroglycerin (NG) not only prevented bone loss, but also restored lost BMD following ovariectomy in rats. Once a day administration in rats for up to 6-months, and in humans up to 1 year, did not result in tachyphylaxis. Taking together these in vitro and in vivo data, we hypothesized that NG might exert a similar beneficial effect in preventing postmenopausal bone loss.. The data compelled us to carry out an intervention study to assess the efficacy of NG in humans. To effectively address this issue, we plan to conduct a randomized, double blinded, controlled clinical trial in postmenopausal women. We will screen pre-selected -1,000 postmenopausal women who fulfill clinical criteria, and recruit 195 women for this study, and then follow them up for a period of 3 years. The primary end-point of the study is the lumbar BMD, and secondary end-points are hip BMD, biomarkers and bone histomorphometry. We will randomize these patients (block randomization method) into three groups: calcium and vitamin D (control), prempro (positive control), and 22 mg of NG ointment applied once daily to skin (n=65/group). Patients will be reviewed at six-month intervals at our GCRC clinical facility and additional telephone contacts with patients will be made every two months to optimize compliance and to assess adverse effects. We have constructed a stringent safety net to protect these women's health. All variables will be assessed at the beginning and then at yearly intervals for the 3-years. We believe that this study should provide definitive data on whether NO donor, NG treatment, would be beneficial in preventing bone loss in postmenopausal women. It should, therefore, help in devising a novel cost-effective alternative therapy for estrogen to prevent postmenopausal bone loss.. The study will also pave the way for the future for providing more acceptable affordable and costeffective therapies for the prevention of postmenopausal osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROBE OF ANTIGEN STRUCT & ANTIBODY INTERACTIONS W/ SYNCHN RADIATION & MASS SPEC Principal Investigator & Institution: Downard, Kevin M.; Yeshiva University 500 W 185Th St New York, NY 10033

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Timing: Fiscal Year 2001 Summary: We are examining the chemical composition of bone from the knee joints of cynomolgus monkeys. A comparison is being made between  intact monkeys (Shamovariectomized) and ovariectomized monkeys. An extensive clinical database is available for all animals, including bone densitometry, CT scan, and bone biomarker data. The ovariectomized monkeys show a marked reduction in bone mass, consistent with osteoporosis.. Although it is clear that bone mass is significantly reduced in osteoporosis, and the subchondral bone is thickened in osteoarthritis, it is unclear whether bone that is formed differs from  normal bone. This issue is extremely important because the chemical composition of bone not only affects its strength and flexibility, but also influences the process of remodeling because it affects hydroxyapatite crystal size, density, and solubility. Infrared microspectroscopy is being used to compare variations in bone Hmorphology with bone compositional features such as protein/mineral Hratios, mineral crystallinity, protein composition, and mineral Hcomposition. Comparisons are made between (1) normal vs. osteoporotic Hand osteoarthritic bone, (2) cortical vs. cancellous bone, and (3) H old bone vs.  new bone. Cortical bone will be mapped with the osteon Hmethod and cancellous bone, including trabecular bone, will be mapped Husing the transverse method. The osteon method involves collection of Hline scans from the four orthogonal directions of an osteon. The Htransverse method involves collection of line scans that transverse Hregions of cancellous bone. For subchondral bone, maps begin at the Hmarrow space and end in the cartilage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROPOSAL VERTEBROPLASTY

TO

PLAN

A

RANDOMIZED

TRIAL

OF

Principal Investigator & Institution: Birkmeyer, Nancy J. Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 29-SEP-2003 Summary: (provided by applicant): The broad objective of the proposed planning process is to solicit early peer review of the rationale and design for a randomized, double-blind, placebo-controlled clinical trial of percutaneous vertebroplasty for the treatment of osteoporotic compression fractures. The potential impact of the proposed study might be substantial because it involves a new and largely uninvestigated approach to the treatment of osteoporotic compression fractures of the spine, which are a prevalent, serious, and costly health problem. Large, multicenter clinical trials in general require extensive planning. The proposed clinical trial will require especially careful planning because, as it is currently performed, percutaneous vertebroplasty involves the off-label use of acrylic bone cement and radiographic contrast materials. For this reason, the proposed trial involves complex operational relationships between the public and private sectors, science, and clinical practice. The specific aims are: 1. To further refine specific aspects of the study design and protocol for the development of the trial operations manual including: study interventions, outcome measures, size of the study population, number of recruiting sites, the study inclusion and exclusion criteria, statistical data and cost-effectiveness analysis plans, the development of standardized study procedures for bone mineral density measurement, spine imaging and fracture assessment, medical management of pain and osteoporosis, trial interventions, and the development of data collection instruments.. 2. To develop relationships with the relevant Federal regulatory and insurance agencies (Food and Drug Administration and Health Care Financing Administration) and industry

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(manufacturer of an appropriate radiopaque bone cement) as well as academic and clinical medicine (Dartmouth and the participating clinical sites) required to perform a study of this rapidly spreading investigational treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RACIAL DIFFERENCES IN CIRCULATING SEX STEROIDS Principal Investigator & Institution: Bohler, Henry;; Meharry Medical College 1005-D B Todd Blvd Nashville, TN 37208 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2008 Summary: The overall hypothesis of this proposal is that elevated sex steroid levels may account for some of the hormone related conditions that follow throughout life in African American females, including leiomyomas, endocrine related cancers, and protection from osteoporosis.. If so, we may then begin to understand their contribution to these processes, both protective and additive in Black females. This will form the basis for better understanding these conditions in all females, and also will allow us to amend our preventive strategies to prevent these morbidities. We propose to both quantify differences in sex steroid levels in the normal menstrual cycle, as well as to identify mechanisms. We further propose to examine the effects of sex steroids on an end organ-in this case bone mineral density and architecture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RALIOXIFENE OSTEOPOROSIS

TREATMENT

OF

POSTMENOPAUSAL

Principal Investigator & Institution: Favus, Murray J.; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RALOXIFENE EFFECTS ON COGNITION IN EARLY MENOPAUSE Principal Investigator & Institution: Upchurch, Margaret B. Professor; Psychology; Transylvania University 300 N Broadway Lexington, KY 40508 Timing: Fiscal Year 2001; Project Start 15-MAY-2001; Project End 30-APR-2004 Summary: Applicant?s Hormone replacement therapy (HRT) in women is commonly used to diminish the physical symptoms of menopause and to reduce the risk of disorders such as osteoporosis, heart disease, and atherosclerosis. HRT may have by its own risks, in particular, an increased chance of developing endometrial or breast cancer. In an effort to reduce these risks, some physicians are prescribing the selective estrogen receptor modulator (SERM) raloxifene (trade name Evista) for the prevention of osteoporosis.. Estrogen also has cognition-enhancing capabilities in postmenopausal women and may serve to prevent or delay the onset of Alzheimer?s disease. Because raloxifene can function as either an agonist or antagonist at estrogen receptors, it is not known whether it too may affect cognitive function. The goals of this study are to examine the cognitive function of women in the perimenopausal period and to compare the effects of estrogen replacement and raloxifene treatment on cognitive function. The women in the two replacement groups will be compared with same-aged women who are still menstruating and to same-aged postmenopausal women who are not on HRT. The research will therefore compare the function of age-matched women with cyclic

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variation in estrogen levels (premenopausal), consistently high estrogen levels (postmenopausal, HRT-estrogen), consistently high SERM levels (postmenopausal, HRT-raloxifene), and consistently low estrogen levels (postmenopausal, no HRT). The tests will assess verbal recall and mental rotation skills, cognitive abilities that are influenced by estrogen levels. Digit span and Trail-Making Test performance, skills for which there is little evidence of an estrogen effect, will also be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RANDOMIZED CONTROLLED TESTING OF OSTEOPOROSIS EDUCATION Principal Investigator & Institution: Solomon, Daniel H.; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 17-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant):Over one-third of women over 65 and 15% of older men have osteoporosis.. Untreated it can result in substantial morbidity, mortality, and costs, but there are effective pharmacologic and lifestyle interventions for preventing falls and fractures. There is evidence that these interventions are not reaching those most at risk. It is a critical public health issue to develop strategies to bring evidencebased interventions to widespread use in at-risk patients. To further his training in patient-oriented research, the candidate has proposed a research project with 3 aims. In the first aim, he will develop and pilot test osteoporosis fracture prevention behaviorchange programs that target both patients and physicians. The growing public interest in osteoporosis and the potential to target patient communication based on prescribing and clinical data suggests the possibility for innovative interventions for fracture prevention. Additionally, interventions directed towards physicians that use patientspecific data and oneon-one academic detailing have proven successful at improving physician prescribing in many chronic medical conditions. Thus, he will develop and pilot test two osteoporosis prevention interventions: one targeting patients and another targeting doctors. In the second Aim, he will supervise a randomized controlled trial to compare the effects of the patient and physician intervention programs on prescribing patterns for osteoporosis.. Over 20,000 patients and 200 physicians will be included in the trial through a collaboration developed with the Pennsylvania Department of Aging. Pharmacy claims data and information from Medicare will be used to target patient communications and to assess the effects of the program on prescribing. In the third Aim, he will examine the interventions effects on osteoporosis prevention behaviors other than medication use, including gait and strength training, home safety, vision care, and calcium and vitamin D intake. This will help determine whether differences in osteoporosis prevention behavior were mediated through the interventions effect on patient and/or physician attitudes, perceived behavioral control, and/or social norms regarding osteoporosis prevention. In addition to active involvement in these studies, the candidate has developed a coordinated training program in epidemiology, biostatistics, bone and mineral metabolism, and rheumatology. A multi-disciplinary Training Advisory Board will review the applicants progress regularly to ensure that the proposed training goals are met. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RANK LIGAND IS A BONE ANABOLIC AGENT Principal Investigator & Institution: Teitelbaum, Steven L. Messing Professor of Pathology; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, MO 63110

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Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (provided by applicant): Treatment of osteopenic disorders has relied, todate, on anti-resorptive drugs such as estrogens and bisphosphonates. While these agents often retard progressive bone loss, they are not effective in reversing the established osteoporotic lesion, nor are they typically capable of curing patients already afflicted with the disease. The dramatic effect of parathyroid hormone as a potential clinical bone anabolic drug underscores the hypothesis that substantial enhancement of skeletal mass requires stimulation of bone formation. Thus, identification of molecules, which promote systemic osteogenesis, is a major focus of anti-osteoporosis research. We have made the surprising observation that the key osteoclastogenic cytokine, RANK ligand (RANKL), when administered subcutaneously as a GST-fusion protein, is a potent bone anabolic agent. This compound dramatically enhances osteoblastogenesis and, within one week, stimulates exuberant bone formation, as detected radiographically, histologically and densitometrically. Importantly, GST-RANKL, at doses inducing as much as a 25-fold increase in osteoblast (OB) number, does not promote osteoclastogenesis in vivo. We also have established that OBs, and their precursors, are direct targets of GST-RANKL and have shown that collagen type I synthesis, by these cells, is greatly accelerated when they are exposed to the fusion protein. These data position GST-RANKL, or its derivatives, as potential bone anabolic, anti-osteoporosis agents. We therefore hypothesize that (1) GST-RANKL enhances OBs function by distinct signal pathways; (2) GST-RANKL, transcriptionally and/or posttranscriptionally, induces collagen type I synthesis by OBs; and (3) GST-RANKL prevents and/or reverses osteoporosis.. Our Specific Aims are therefore to: (1) identify the signal pathways by which GST-RANKL enhances OB function; (2) identify the mechanism by which GST-RANKL induces collagen type I synthesis by OBs; and (3) determine if GST-RANKL prevents and/or reverses osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RANK-ASSOCIATED INHIBITOR (RAIN) IN OSTEOCLAST FORMATION Principal Investigator & Institution: Darnay, Bryant G. Bioimmunotherapy; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 29-MAR-2008 Summary: (provided by applicant): Receptor activator of NF-kappaB (RANK) and its ligand (RANKL, also known as TRANCE/ODF/OPGL) are essential mediators of osteoclastogenesis and have been implicated in various diseases, which include rheumatoid arthritis, osteoporosis, giant cell tumor of bone, Paget's disease, metastatic breast cancer, multiple myeloma, and familial expansile osteolysis. Osteoprotegerin (OPG, also known as OCIF/TR1) is a soluble, decoy receptor that inhibits RANKL from binding to its cell surface receptor RANK. Activation of signaling pathways by RANK is mediated through its interaction with tumor necrosis factor receptor-associated factors (TRAFs). Mice deleted of RANKL, RANK, or TRAF6 lack osteoclasts and develop severe osteopetrosis while mice lacking OPG develop osteoporosis.. Thus, RANKL and OPG are the governing factors that regulate normal bone homeostasis. The cytoplasmic domain of RANK interacts with TRAF1, 2, 3, 5, and 6, and our laboratory described the distinct regions of RANK that interact with TRAF2, 5, and 6. In an effort to identify other factors that interact with the cytoplasmic domain of RANK, we used a yeast twohybrid approach and identified a novel protein, which we termed RAIN, for RANKAssociated Inhibitor, for its ability to inhibit RANKL-mediated osteoclast formation Both mouse and human cDNAs were cloned and contain an open reading frame of 241

Studies 129

and 242 residues, respectively. RAIN is a novel protein with no identifiable domains or motifs. RAIN coprecipitates with endogenous RANK in RAW264.7 (RAW) cells. Furthermore, RAIN interacts with TRAF2, TRAF5, and TRAF6 in RAW cells. To understand the function of RAIN, RAW cells stably expressing RAIN did not interfere with early RANKL signaling such as NF-kappaB, JNK, ERK, or p38 MAPK activation. However, RAIN expressing cells did not form multinucleated osteoclasts when stimulated with RANKL, although the cells were TRAP+ and the cell cycle inhibitor p27 was upregulated. Thus, it appears RAIN acts as a negative regulator of the fusion event during osteoclast differentiation. In support of this model, we established RAW cells stably expressing anti-sense RAIN. Surprisingly, we observed increased osteoclast number, which was observed as early as day 2. Additionally, RANKL treatment of RAW cells caused induction of RAIN mRNA and protein, which begins on day 2 and continues through day 5. Biochemical evidence suggests that RAIN may function by sequestering or preventing F-actin polymerizatio. Thus, we have identified a novel protein that interacts with RANK and TRAFs, and presumably controls the formation multi-nucleated osteoclasts. We propose to extend these studies to further our understanding of RAIN's function in osteoclastogenesis by pursing the following specific aims: (1) define the molecular interactions of RAIN and TRAFs; (2) determine the biochemical proteins of RAIN with respect to actin polymerization; and (3) determine the physiological role of RAIN by targeted gene disruption and transgenic mice expressing RAIN. The identification of RAIN and it function in controlling osteoclast formation will provide new insights into the mechanism of osteoclast formation and may provide a novel target for the development of pharmaceutical agents aimed at preventing unwanted bone destruction associated with metabolic bone disorders and cancers associated with osteolytic lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REDUCED GI TOXICITY OF PC-BISPHOSPHONATES Principal Investigator & Institution: Sanduja, Sudershan K.; Natural Therapeutics, Inc. 16406 Ash Point Sugar Land, TX 77478 Timing: Fiscal Year 2001; Project Start 15-MAY-2001; Project End 14-NOV-2002 Summary: Osteoporosis is the most common metabolic bone disease, afflicting 8-10 million Americans and placing another 25 million individuals at risk. Bisphosphonates represent a class of drugs that have proven quite effective in the treatment of osteoporosis and related diseases. Unfortunately, bisphosphonate consumption is associated with GI inflammation, erosions and ulceration, by topically injuring the tissue. Our preliminary results indicate that these drugs rapidly attenuate the hydrophobic phospholipidic barrier of the stomach of rats. Based upon these observations, Natural Therapeutics is developing unique formulations of bisphosphonates and phosphatidylcholine (PC) that have a significantly lower gastric toxicity than the unmodified dtug(s) in an established rodent model system 1n this Phase I application we propose to build upon our encouraging preliminary data in the evaluation and comparison of gastric macroscopic and microscopic injury/inflammation, bleeding (hematocrit and intraluminal hemoglobin), surface hydrophobicity and apoptotic index in rats administered one of three commercially available bisphosphonates (pamidronate, alendronate and risedronate) alone and in combination with PC. We will also compare different grades of PC, ranging from 15% to 93% purity, as well as different bisphosphonate: PC ratios to determine the optimum and least costly formulation to limit the GI sideeffects of these powerful drugs. PROPOSED COMMERCIAL APPLICATION: The market for GI-safe Bisphosphonates,

130 Osteoporosis

such as pamidronate, alendronate, and risedronate, to treat osteoporosis will be enormous. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF T CELL TNF PRODUCTION Principal Investigator & Institution: Pacifici, Roberto;; Barnes-Jewish Hospital Ms 90-94212 St. Louis, MO 63110 Timing: Fiscal Year 2002; Project Start 08-AUG-2002; Project End 24-DEC-2002 Summary: (provided by applicant): Estrogen (E2) has multiple and complex regulatory effects on T cell function which may be relevant for the pathogenesis of postmenopausal osteoporosis.. However, a cause-effect relationship between T cell alterations and postmenopausal bone loss remains to be established. We found that ovariectomy (ovx) failed to induce bone loss in T cell deficient nude mice. The capacity of ovx to induce bone loss was restored by T cell reconstitution with Wild type T cells but not by constitution with T cells from TNF-/- mice. Moreover, ovx increased T cell TNF production by enhancing T cell proliferation and decreasing T cell apoptosis. These events led to an increase in the number of TNF producing T cells in the bone marrow. These findings demonstrated that T cells and T cell produced TNF are essential mediators of the bone-wasting effects of E2 deficiency in vivo. However, the specific phenotype of the E2 regulated TNF producing T cell remains to be characterized. Equally enigmatic are the mechanisms by which E2 down regulates the number of TNF producing T cells in the bone marrow. Therefore, our first Specific Aim will be to identify the specific T cell population (CD4+ CD8+ and/or gamma-delta T cells) that produces increased amounts of TNF and cause bone loss in ovx mice. The relevance of the candidate T cell population will be demonstrate by determining if ovx induces bone loss in mice lacking either CD4+, CD8+ and/or gamma-delta lymphocytes. In Specific Aim 2 we will determine if E2 blocks T cell dependent bone loss via a direct targeting of T cells or via effects on bone marrow accessory cells. This will be accomplished by analyzing the effects of ovx and E2 replacement on bone density, T cell proliferation, T cell apoptosis and T cell TNF production in nude mice reconstituted with T cell harvested from E2 receptor alpha and beta deficient donors. Our experimental evidence suggests that E2 blocks T cell TNF production by repressing IL-7, a cytokine which regulates T cell proliferation and induces bone loss.. Therefore, we will evaluate the contribution of IL-7 by determining if in vivo neutralization of IL- 7 prevents the increase in T cell TNF production and the bone loss induced by ovx. Our data also suggest that E2 represses T cell TNF production by blunting IFN-gamma induced macrophage antigen presenting cell (A PC) activity, through down regulation of CIITA gene expression. Therefore, we will conclude Aim 2 by using IFN-gamma neutralization and IFN-gR1 -/- mice to determine the effects of CIITA silencing on T cell TNF production and bone loss.. In specific Aim 3 we will investigate the mechanism which E2 represses CIITA gene expression. This will be accomplished by analyzing the effects of E2 on the transcription and the translation of CIIT A and by determining the Cisregulating factors that confer E2 responsiveness to the CIITA promoter. The significance of this project is high, as it may shed light on the pathogenesis of postmenopausal osteoporosis and identify novel target of E2 in bone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RESPONSE OF THE OSTEOPOROTIC SKELETON TO IN VIVO LOADING Principal Investigator & Institution: Silva, Matthew J. Associate Professor; Orthopaedic Surgery; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 13-JUL-2001; Project End 30-JUN-2005 Summary: Senile osteoporosis increasingly affects the aging population of the United States and, along with post- menopausal osteoporosis, impacts more than 20 million women and men with an annual estimated cost of 14 billion dollars. Increased skeletal loading and exercise may be helpful in preventing senile osteoporosis, but clinical studies have not demonstrated a consistent benefit, perhaps because a reduction in the number of bone marrow osteoprogenitor cell renders the osteoporotic skeleton unable to respond to loading. Our overall goal is to test the hypothesis that the vigor of the osteogenic response following increased mechanical loading depends in part on the number of bone marrow osteoprogenitor cells. To address this question we will utilize a unique animal model of senile osteoporosis, the senescene accelerated mouse (SAM). For Aim 1 we will use femurs and tibias from control SAMRI and osteoporotic SAMP6 mice at three ages to quantify mechanical properties ex vivo (using four-point bending and nanoindentation) and marrow osteogenic potential in vitro (using bone marrow cell cultures). We will determine whether or not to relative differences in mechanical properties between SAMR1 and SAMP6 correlate with differences in marrow osteogenesis in vitro. For Aim 2 we will develop validated computed tomographybased finite element models of tibias from SAM mice and use them to predict strain distributions in the cortical diaphysis during in vivo four-point bending. These models will allow us to deliver prescribed strain magnitudes to the endosteal bone surface and to establish conditions for subsequent in vivo experiments. Finally, for Aim 3 we will cyclically load the tibias of SAM mice in vivo at three prescribed strain magnitudes and evaluate the skeletal response using peripheral computed tomography and dynamic histomorphometry and the bone marrow response using in vitro cell culture. We will determine whether or not loading increases the number of osteoprogenitor cells in the bone marrow and whether or not the magnitude of the osteogenic response correlates with changes in the bone marrow and is proportional to the number of osteoprogenitor cells. Finding from these studies will represent an important first step toward our longterm goal of determining the role of marrow osteoprogenitor cells in maintaining skeletal integrity and in mediating the response of bone to mechanical loading. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RISK FACTORS FOR AGE RELATED BONE LOSS Principal Investigator & Institution: Kiel, Douglas P. Associate Professor; Hebrew Rehabilitation Center for Aged 1200 Centre St, Roslindale Boston, MA 02131 Timing: Fiscal Year 2002; Project Start 30-SEP-1991; Project End 31-MAY-2007 Summary: (provided by applicant): The Framingham Osteoporosis Study (FOS) is a prospective study that is part of the Framingham Heart Study, one of the longest running cohort studies in the world. FOS involves participants from the Original Cohort (1948-present) and the Offspring Cohort (2nd generation and spouses). Both cohorts have comprehensive data about osteoporosis risk factors, as well as having stored DNA, relevant genotyping being performed by other groups, and large numbers of extended families in whom a genome wide scan has been carried out. We propose to continue the FOS. Our preliminary findings suggest that patterns of food consumption, dietary silicon and phosphoric acid intake have influences on bone mineral density (BMD). We

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will study these dietary factors as they relate to changes in BMD and fractures in both Cohorts. Findings from these studies may offer potential dietary approaches to preventing osteoporosis.. We have recently completed a genome wide scan on some of the extended families in FOS who have completed BMD and quantitative calcaneal ultrasound (QUS), and found several loci with suggestive linkage. In some cases, loci differed between the BMD and QUS phenotypes. The results of this linkage analysis will be used to suggest potential gene candidates for association studies in addition to the ones that we will investigate in this project: interleukin-6 (IL-6), transforming growth factor beta (TGF-Beta), and estrogen receptors alpha and beta (ERa and ERBeta). We recently discovered that women with bone loss or low BMD have greater severity of vascular calcification, suggesting that the two processes may have a common etiology. We will test the hypothesis that this common etiology is related to estrogen and the estrogen receptors by using electron beam computed tomography to quantify vascular calcification, by measuring serum estradiol and sex-hormone binding globulin, and by genotyping women for ERa and ERBeta. This will advance our understanding of two of the most common chronic diseases affecting older persons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RISK FACTORS FOR HIP FRACTURES AMONG THE ELDERLY Principal Investigator & Institution: Melton, Joseph L.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001 Summary: This project complements studies of pathophysiology by addressing fractures, the principle clinical manifestation of osteoporosis.. Through the unique data resources of the Rochester Epidemiology Project, we can identify large inception cohorts of Rochester and/or Olmsted County, Minnesota., residents with specific medical and surgical conditions and conduct a series of retrospective (=historical) cohort studies to estimate the long-term risk of age-related fractures associated with secondary osteoporosis, an important contributor to bone loss in the elderly. Secondary, osteoporosis is an important area of research because new therapies are being developed for affected men and older women who are not candidates for estrogen replacement. We previously determined the risk of fracture among cohorts with diabetes mellitus, hyperparathryoidism, thyroidectomy, gastrectomy, pernicious anemia, oophorectomy, urolithiasis, anticoagulant therapy, anorexia nervosa, dementia, parkinsonism, epilepsy, poliomyelitis, rheumatoid arthritis, ankylosing spondylitis and breast cancer. We now proposed to extend this work by quantifying the fracture risk associated with conditions that might impair peak bone mass (endometriosis, infertility), induce hypogonadism (orchiectomy), disturb extraskeletal bone metabolism in the kidney (chronic renal failure) and gut (inflammatory bowel disease) or cause a generalized increase in bone resorbing cytokine (multiple myeloma). Each condition represents a natural experiment with respect to the pathogenesis of osteoporosis, several of which parallel the concerns of other projects. These will be the first assessments of fracture risk among cohorts of unselected patients from the community, and the results should be more valid and more precise than any previous estimates. Our overall goal is to develop new information that will lead to effective strategies for preventing osteoporosis-related fractures among the elderly. This project contributes by demonstrating the public health importance of specific risk factors and, by identifying high risk groups within each cohort, allowing future control programs to be designed and conducted more efficiently. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RISK OF OSTEOPOROSIS ASSOCIATED WITH INHALED GLUCOCORTICOIDS Principal Investigator & Institution: Apter, Andrea J. Associate Professor of Medicine; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE FOR IL6 IN PTH INDUCED BONE RESORPTION Principal Investigator & Institution: Insogna, Karl L. Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 15-AUG-1998; Project End 31-JUL-2002 Summary: (Adapted from the Applicant's Abstract): Osteoporosis is an important disease of aging. The age-specific incidence of the disease is stable or increasing, and when this is coupled with the greater number of older Americans in the at risk population, it is clear that the prevalence of this disease will rise for the foreseeable future. Already nearly one million fractures occur annually in persons over the age of 65 and the vast majority of these are due to osteoporosis.. Osteoporosis is due to the permanent loss of otherwise normal bone from the skeleton. Of the various subtypes of this disease, postmenopausal osteoporosis is by far the most common. Increased bone resorption is the principal mechanism for bone loss in postmenopausal osteoporosis, and recent evidence indicates that rates of bone resorption are important predictors of bone mass in older individuals. Parathyroid hormone (PTH) is the principal regulator of bone resorption on a day-to-day basis and increased sensitivity to PTH may underlie the increased bone resorption seen in osteoporosis.. The applicant group has demonstrated that the pro-resorptive cytokine, IL-6, is regulated by PTH in vitro and in vivo, and plays a crucial role in mediating the resorptive actions of PTH. Thus, they have recently shown that circulating levels of IL-6 are elevated in states of parathyroid excess, are low in hypoparathyroidism, and correlate strongly with markers of bone resorption in patients with primary hyperparathyroidism. In experimental animals, they have demonstrated that PTH infusions cause serum IL-6 levels to rise, and neutralizing antisera to IL-6 block PTH-induced increases in bone resorption. They hypothesize that IL-6 is an important mediator of PTH's resorptive actions in bone and that, in the estrogen-deficient state, PTH-dependent IL-6 production increases. To test these hypotheses the investigators will: (1) conduct a prospective clinical trial in patients with primary hyperparathyroidism to determine if serum IL-6 levels correlate with rates of bone loss, as determined by dual energy x-ray densitometry; (2) examine the response of postmenopausal women to an infusion of PTH, before and after estrogen replacement, to determine if estrogen affects PTH-induced changes in IL-6; (3) determine whether neutralizing IL-6, in vivo, blocks PTH-induced bone loss in mice, and whether IL-6 knock-out mice do not lose bone in response to PTH; (4) explore the effect of ovariectomy on PTH-induced increases in circulating IL-6 in mice; and (5) use the isolated perfused rat liver system to begin to examine the role of the liver in the PTH-induced increases in circulating levels of IL-6. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RXR ALPHA: SCREENING A CANDIDATE FOR LATE LIFE DISEASE Principal Investigator & Institution: Beamer, Brock A. Medicine; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218

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Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2003 Summary: While changes in body composition-and often disastrous sequelae thereofuniversally accompany old age, there is tremendous variability in their onset, pattern and severity. The long term objective of this project is to better understand the molecular basis for this heterogeneity, and thereby the pathways which underlie such changes. The immediate focus is whether some variability is due to genetic heterogeneity in the nuclear receptor RXRalpha (9-cis retinoic acid receptor). RXRalpha is essential for the action of many nuclear receptors (e.g. PPAR, THR, RAR) and lays significant roles in development and maintenance of bone, muscle and skin tissue (among other tissues). Ligand and artificial mutation suggest that alterations in RXRalpha activity or interactivity could have a variety of phenotypic consequences. We hypothesize that mutations in genes such as RXRalpha could contribute to (or protect against) severe or early onset declines in bone, muscle or skin. Specific aim #1 is to recruit small cohorts of well-characterized older individuals free of confounding conditions (e.g. glucocorticoid use) selected for severe and/or early onset: (i) osteoporosis, (ii) muscle weakness, (iii) decreased skin integrity, or (iv) absence of these at extreme old age. Specific Aim #2 is to perform SSCP analysis of RXRalpha on genomic DNA from 15 individuals of each cohort, and begin characterization of any variants identified. Beyond the scope of this pilot project is (i) screening these cohorts for variation in other genes that may influence musculoskeletal or dermatologic changes with age; (ii) performing functional analyses of large definitive association studies with any variants found from this screen; or (iii) assessing other conditions potentially influenced by variation in RXRalpha (e.g. thyroid function, vision). However, this project should form bases from which such questions could be explored. Within its scope, it may help to elucidate general pathways underlying age-related changes in body composition/function, which ultimately will lead to improved means of preventing and treating their sequelae (perhaps with the RXRalpha agonists/antagonists now being developed). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SAFETY OF ESTROGEN IN LUPUS ERYTHEMATOSUS Principal Investigator & Institution: Buyon, Jill P. Professor; Hospital for Joint Diseases Ortho Inst Orthopaedic Institute New York, NY 10003 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-AUG-2006 Summary: (provided by applicant): The Safety of Estrogens in Lupus Erythematosus, National Assessment (SELENA) consists of two randomized double blind placebocontrolled equivalence trials. The first examines the effect of hormonal replacement therapy (HRT) on disease activity in postmenopausal women with SLE, the primary outcome being severe flare. Current enrollment is 314 patients and should reach the target of 350 by April 2001. The second trial, initiated in April 1997, examines the effect of oral contraceptive pills (OCP) on disease activity. To date, 159 subjects have been enrolled at an average rate of month. This application seeks an additional 5 years of enrollment for the OCP trial to achieve adequate power for assessing equivalence in severe flare rates across treatment arms; determining potential salutary effects of estrogens on two clinical concerns in SLE, osteoporosis and atherosclerosis; and studying two research themes often linked to estrogen use, autoimmunity and thrombosis. Three new investigations have been added to the proposal, each of which optimally utilizes the unique resources of this prospective clinical trial. These complementary projects have a dual purpose: to evaluate hormonal effects in vitro with respect to fundamental pathophysiologic questions, and to determine whether

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laboratory markers can be established to select subsets of patients who may either benefit from OCP or be at increased risk for exacerbation of 1upus or cardiovascular sequelae. Accordingly, 4 specific aims are proposed in this application. Specific Aim 1: To evaluate the safety of OCP by assessing whether the rates of severe flare in the OCP and placebo groups are clinically equivalent. Specific Aim 2: To assess protection from and risk of osteoporosis and atherosclerosis by pre- and post-study evaluation of DEXA scans, fasting lipids, fibrinogen, CRP, plasminogen activator inhibitor, homocysteine, lipoprotein(a), and carotid duplex. Specific Aim 3: To understand whether there is a change in B cell subsets in the peripheral blood of SLE patients receiving OCP; whether there are changes in expression of candidate autoimmunity genes in peripheral blood B cells (including SHP-1, VCAM-1, Bcl-2, and CD22); and whether there are changes in the number or phenotype of B cells spontaneously secreting anti-DNA antibody. Specific Aim 4: To address the hemostatic effects of estrogen (with focus on the protein S system) which may increase the risk for thrombosis even in patients screened out by virtue of high levels of anticardiolipin antibodies or a lupus anticoagulant. The SELENA-OCP trial offers the best (and perhaps only) opportunity to firmly answer the concerns of clinical safety and potential cardiovascular and skeletal efficacy of exogenous hormones in women with SLE. Moreover, this translational research trial, at least with regard to the estrogen and progesterone load imposed by OCP, will facilitate answers to the everpressing basic biologic issues of the effect of female hormones on autoimmunity and thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SODIUM EFFECTS ON BONE METABOLISM Principal Investigator & Institution: Carbone, Laura D. Medicine; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-AUG-2003 Summary: The candidate, Laura Carbone M.D., is a new investigator in the field of metabolic bone diseases. Immediate goals include acquiring expertise in study design. This will be provided on a ongoing basis by the co-mentors Dr. Genaro Palmieri, a well known expert in metabolic bone disease, and Dr. William B. Applegate, an expert in large multi-center clinical trials. Long term goals include obtaining the skills necessary to do clinical trials in metabolic bone diseases. This will be provided at this center by weekly classes in statistics and epidemiology, seminars in nutrition and osteoporosis and a program leading to a master of science degree in epidemiology. The specific research plan is detailed below: Racial differences in bone metabolism, bone mineral density and fracture rates have been reported between Caucasians and African Americans with Caucasians generally having increased biochemical markers of bone metabolism, decreased bone mineral density and higher fracture rats than African Americans. More recent data, however, suggests that the incidence of osteoporosis and osteoporotic fractures may be increasing in African Americans. Environmental factors, specifically salt intake, have been shown to influence bone metabolism in Caucasians, but have not been studied in African Americans, despite the fact that the African American diet may be high in sodium. This study proposes to examine the effects of sodium load and then a sodium restriction diet of calciotropic hormones and biochemical markers of bone metabolism in African American and Caucasian women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SOLID STATE MR OF BONE MINERAL Principal Investigator & Institution: Ackerman, Jerome L. Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-JUN-1994; Project End 31-JUL-2003 Summary: (Adapted from Applicant's abstract): The central idea of this project is that solid state magnetic resonance (SSMR) imaging and spectroscopy can provide unique solutions to problems related to the chemistry of biomineralization. In this continuation of the development of SSMR methodology for bone mineral characterization, in vivo and high resolution SSMR techniques are applied to study the remodeling of synthetic calcium phosphate biomaterials in vivo, and to elucidate the structural chemical properties of bone mineral crystals. The work focused on measurements that can be made in no other way with existing technology. In Specific Aim 1, the conversion of a non-proprietary beta-tricalcium phosphate (TCP) implant into the host bone in a rabbit bone defect model is follow with in vivo and high resolution SSMR. Although much effort has been expended in the study of this and similar increasingly used calcium phosphate based materials, these materials have rarely been studied by solid state MR, and never in vivo by this method. Forty-five rabbits will be implanted, and the time course of the remodeling of the implant material will be characterized by in vivo SSMR imaging, and by high field high resolution cross polarization/magic angle spinning (CP/MAS) spectroscopy, chemical analysis and histomorphometry on harvested specimens. This study is expected to elucidate details of the chemistry of the remodeling process that have so far remained obscure. In Specific Aim 2, specialized CP/MAS and other solid state MR techniques in conjunction with computer modeling are applied to characterize bone mineral crystals in order to develop detailed model of the structural chemistry of the crystal interior as well as the surface. Specimens of trabecular bone from normal and ovariectomized rats, treated and not treated with alendronate, a typical diphosphonate anti-resorptive pharmaceutical of rapidly increasing importance in the treatment of osteoporosis, will be analyzed. Because the action of diphosphonates includes physicochemical effects involving binding to bone mineral crystals, enhanced understanding of the structural chemistry of bone mineral crystals and their diphosphonate binding properties will be important in the design of improved antiresorptive drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SPECIALIZED CENTER FOR RESEARCH IN OSTEOPOROSIS Principal Investigator & Institution: Kronenberg, Henry M.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 22-SEP-1997; Project End 31-AUG-2005 Summary: (Taken from the application): Despite impressive advances in understanding of osteoporosis, the cure of osteoporosis remains an elusive goal. When patients present with fractures, the loss of bone has already been quite substantial. An important goal must be to increase the strength of such bone to normal. Since currently available treatments all focus on inhibiting resorption of bone, these treatments cannot restore bone mass to normal. A safe and effective agent that increases bone formation in osteoporotic patients, therefore, is required for the cure of osteoporosis.. Parathyroid hormone (PTH), administered by once daily injection to humans or to a variety of animal species, increases bone mass and bone strength by increasing bone formation, and prevents fractures. Consideration of the complicated actions of parathyroid hormone on bone leads to the realization that very little is understood about the basic

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mechanisms of PTH action. Greater understanding of these basic mechanisms will facilitate the design of strategies for clinical use of PTH. The goal of this proposed SCOR (a continuation of funding begun in October 1997) is to learn how to use parathyroid hormone to treat patients with osteoporosis in the most effective manner. Achievement of this goal will require a combined approach that both evaluates the effects parathyroid hormone in humans and studies the basic mechanisms of parathyroid hormone action in animal models. The SCOR has as its centerpiece a patient-based project that explores the effects of administering PTH to osteoporotic men and women. The goals are to understand the mechanisms of the anabolic action of PTH and, thereby, to determine how best to use PTH in the treatment of osteoporosis.. Three projects then explore the cellular and molecular basis of the actions of parathyroid hormone on bone. Each of these three projects studies the actions of PTH on bone in vivo and uses precise genetic manipulations in mice to probe mechanisms without abandoning the complexity of the intact animal. A Bone Analysis Core Facility will provide skills efficiencies in the analysis of samples of blood, urine, and bone that will aid each of the four scientific projects. An Administrative Core will assure that communication between the various projects is optimal and will monitor the progress of each project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPECIALIZED CENTER OF RESEARCH IN OSTEOPOROSIS Principal Investigator & Institution: Lindsay, Robert; Chief of Internal Medicine; Helen Hayes Hospital Rt 9 W West Haverstraw, NY 10993 Timing: Fiscal Year 2001; Project Start 30-SEP-1987; Project End 31-AUG-2003 Summary: Osteoporosis is recognized has a major public health problem in the USA today, with the likelihood of increased societal impact as "baby boomers" age. Therapeutic options are currently limited to "anti-resorptive" therapies which reduce bone turnover. Therapeutic options are currently limited to "anti-resorptive" therapies which reduce bone turnover, stabilize bone mass and reduce but not eliminate fracture risk, in part because many treated individuals are left with a bone mass that remains less than optimal. Thus, there is a clear need for agents that stimulate new bone formation. Our Specialized Center of Research has assembled a panoply of basic and clinical scientists to focus on this issue. Over the past 9 years we have investigated interactions of parathyroid hormone and sex steroids in the development and treatment of osteoporosis.. Our cohesive and integrated approach has generated a significant base of knowledge, culminating in the demonstration that PTH (superimposed on standard HRT) not only increases bone mass but may also reduce vertebral fracture risk. In our current application, in four inter-related and integrated projects, we will examine aspects of PTH action at both basic and clinical levels. In Project 1 we will use novel techniques to isolate functional human osteoclasts and transgenic murine models to examine the mechanisms underlying osteoclast differentiation and death. In Project 2 the ovariectomized rat model will be used to evaluate morphological, biochemical, and mechanical responses to PTH, comparing a model of primary hyperparathyroidism (continuous PTH infusion) with intermittent PTH administration, in both estrogen replete and depleted states. The next project uses the paradigm of endogenous primary hyperparathyroidism in post-menopausal women to characterize the effects of chronically increased PTH, and its reduction (after parathyroidectomy) on skeletal homeostasis. The last project focusses on the mechanism underlying the initial period of new bone formation that occurs in the early months of PTH therapy, as well as the effects of withdrawal of treatment. Each of these projects relies heavily on the support of "Core" units,: Administration/Statistics; Biochemistry; Histomorphometry; and Bone

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Mass Measurement, with integration of all Projects and Cores with regard to protocols, investigators and data interpretation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STATISTICAL METHODS FOR UTILITY OF MULTIPLE TESTS Principal Investigator & Institution: Lu, Ying; Associate Professor; Radiology; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-JAN-2004 Summary: Osteoporosis is a major health problem in our aging society. As a silent disease, diagnosis and risk assessment of osteoporosis rely on diagnostic tests. In the past decade, a great number of diagnostic techniques have been developed and used to assess bone density and quality. The accuracy and cost of these tests vary greatly. With such a variety of diagnostic tests, the clinicians must determine the best diagnostic strategy for specific patient populations, both for screening and for selecting and monitoring treatment. Because of the lack of appropriate statistical tools to assess diagnostic utility of combining multiple tests in their accuracy in predicting osteoporotic fractures and cost-effectiveness, it is difficult to identify the optimum combination of tests. The specific aims of our study are the following: 1. Development of receiver operating characteristics (ROC) region analysis for parallel tests. 2. Development of recursive partitioning trees for test series using cost criteria. 3. Development of costeffectiveness models of optimal decision thresholds for sequential tests. We will study theoretical properties, develop computer software for above statistical tools and apply them to examine the combinations of DXA, SXA, QCT, QUS, biomarkers, and epidemiological risk factors such as age, weight, fall rate, family and fracture history, etc., based on data from the Study of Osteoporotic Fractures (SOF) and simulation models using cost-effectiveness and population distribution parameters published in literature. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRENGTH AND MICROSTRAIN IN VERTEBRAL TRABECULAR BONE Principal Investigator & Institution: Fyhrie, David P. Professor; Bone and Joint Center; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, MI 48202 Timing: Fiscal Year 2001; Project Start 01-JUL-1991; Project End 31-AUG-2004 Summary: (Adapted from the investigator's Abstract): Osteoporosis is a severe health problem that is associated with aging and caused, in part, by age-related changes in the normal processes of bone maintenance. The process of bone tissue turnover, or bone remodeling, is a highly regulated process where a packet of either trabecular or cortical calcified bone matrix is removed by osteoclasts and subsequently replaced by osteoblasts. As a step in the formation of the collagenous matrix of the bone, a fraction of the osteoblasts are buried in the matrix and become osteocytes. The osteocytes partially regulate mineralization and are the key candidates as the mechanosensory cells of bone. Understanding the cycle of remodeling and the signals that control it is important to determining the underlying causes of the universal age-related loss of bone mass that can cause osteoporosis, debilitating fracture and death. The remodeling process is intimately associated with angiogenesis and can be initiated and is regulated by mechanical loading. Each site of remodeling, both for cortical and cancellous tissue, is associated with the growth of a sinusoid (capillary). The sinusoids are formed, in part,

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of endothelial cells and serve as channels to transport nutrients, cells, and in particular, osteoclast precursors (monocytes to appropriate locations. The coordination of remodeling includes components of control resulting from: a) direct communication between osteoclasts and osteoblasts, b) vascular ingrowth, c) activation and release of growth factors sequestered in the calcified matrix and d) a collection of signals caused by mechanical loading, sex hormones or damage associated with osteocytes. The interaction between mechanical loading, osteocyte morphology and the concentration of matrix-sequestered growth factors are the potential control mechanisms to be investigated in the proposed research. The Principal Investigator proposes to determine the associations between mechanical strain at the trabecular level, osteocyte lacunar density, remodeling rate and matrix sequestered growth factors (in particular TGFbeta1, TGF-beta2, VEGF and IGF-1). The investigators have demonstrated gender related differences in osteocyte lacunar density of human vertebral cancellous bone. This is similar to the gender related difference in matrix TGF-beta1 concentration in human vertebral cancellous bone. Studies are proposed to determine the quantitative relationship between these independent findings of gender differences and to determine the association of trabecular level strain and remodeling rate to these novel results. As a further test, it will be determined whether the gender related differences noted for the vertebra are also present in tibial cancellous bone. This will help to determine whether the differences noted for the vertebra are systemic or site-specific. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL ANALYSIS OF DEXA SCANS: OSTEOPOROSIS STUDIES Principal Investigator & Institution: Beck, Thomas J. Associate Professor; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES OSTEOPOROSIS

IN

SCLERODERMA

AND

CYSTIC

FIBROSIS

Principal Investigator & Institution: Merkel, Peter A. Assistant Professor; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 18-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): To provide support for research projects in the field of rheumatology that will form the basis of a structured mentoring program for young investigators pursuing careers in patient-oriented clinical research. This application has two major specific research aims: 1) Develop new outcome measures for skin assessment in scleroderma for use in clinical trials and 2) Determine the prevalence and progression of osteoporosis in patients with cystic fibrosis (CF). Both projects will have direct relevance to furthering the health of the populations under study. Clinical research in scleroderma, including therapeutic trials, is greatly hampered by a lack of reliable and precise outcome measurements of disease activity. Skin thickening and fibrosis are major causes of morbidity and dysfunction for patients with scleroderma. The great success in extending the life expectancy of patients with CF gained in the last 20 years has resulted in patients now experiencing diseases as adults not formerly encountered in this population. Among these diseases is osteoporosis.. Patients with CF appear to be at high risk for osteoporosis due to nutritional, pharmacologic, and genetic factors but

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the pathophysiology and extent of the problem is not known. Patients with scleroderma will be followed prospectively and evaluated for skin disease activity by skin scoring, durometer readings (thickness), light-based technologies, skin biopsies, selfassessments, and functional status instruments. These data will be analyzed to determine a core set of outcome measures for scleroderma. and validated by an expert panel of national researchers in this disease. An observational cohort of patients with CF will be studied. Baseline and 2-year measurements of bone density, nutritional status, and biochemical markers of bone turnover will performed. A comprehensive program for training new clinical investigators by the principal investigator is proposed. This program includes trainees taking an active and integral role in the research studies described. Additionally, trainees will be enrolled in formal coursework in biostatistics, epidemiology, and clinical research techniques leading to a master degree. A unique seminar and a series of support services at the host institution will further complement the training program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDIES OF METABOLIC BONE DISEASE Principal Investigator & Institution: Avioli, Louis V.; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001 Summary: Adults and children with generalized skeletal abnormalities or abnormalities in mineral metabolism have been studied. Included were metabolic, radiographic, genetic and pathological studies to define the pathogenesis of a variety of disorders of bone and mineral metabolism, particularly osteoporosis, osteomalacia and Paget's disease. Several new disorders have been characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES OF THE FATE OF THE OSTEOCLAST Principal Investigator & Institution: Boyce, Brendan F. Professor; Pathology and Lab Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2001; Project Start 01-JUN-1995; Project End 31-AUG-2003 Summary: Osteoclasts are required for the normal development of bone during endochondral osification and for the resorption of worn-out bone in the adult skeleton during normal bone remodeling. They also mediate the increased bone loss that occurs in association with inflammation in bone and estrogen deficiency following menopause. Recent studies indicate that expression of M-CSF and RANK (receptor activation of NFkappaB) ligand is required for osteoclast formation and that activation of genes regulated by the transcription factors, c-fos, PU.1 and NF-kappaB is also necessary. NFkappaB regulates the expression of the osteoclastogenic cytokines, IL-6, IL-1, and TNF whose expression is up-regulated in inflammatory bone diseases and in response to estrogen deficiency. These cytokines also prevent osteoclast apoptosis, and the increased bone resorption seen after the menopause may in part be due to prolongation of osteoclast life spans on bone surfaces. NF-kappaB has also been shown to prevent TNFand FAS ligand-induced apoptosis of some cell types and therefore may be involved in the regulation of osteoclast life span. Thus, NF-kappaB may regulate not only the formation of osteoclasts in normal bone remodeling, but also the increased production and prolonged life spans after the menopause. However, the molecular mechanisms whereby NF-kappaB mediates these activities in osteoclasts in osteoclasts are largely unknown and are likely to involve multiple signaling pathways in osteoclasts and their

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precursors and osteoblasts. We propose to use a combination of in vitro and in vitro approaches to study the role of NF- kappaB in osteoclast formation, activity and survival. Our specific aims are to determine the role of NF-kappaB in 1) osteoclast formation 2) the up- regulation of osteoclastogenesis induced by cytokines and estrogen deficiency and 3) the regulation of osteoclast apoptosis Our underlying hypothesis is that NF-kappaB is required for the activation of genes encoding cytokines which are essential for 1) the progression of osteoclast precursors along a differentiation pathway to form mature osteoclasts; 2) the up-regulation of osteoclastogenesis following estrogen withdrawal; and 3) for the survival of osteoclasts by preventing them from undergoing apoptosis. Understanding the role of NF-kappaB in osteoclastogenesis and survival could lead to the development of new therapeutic agents designed specifically to inhibit bone resorption in conditions, such as postmenopausal osteoporosis, in which it is increased. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDY OF OSTEOPOROTIC FRACTURES Principal Investigator & Institution: Cauley, Jane A. Professor; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-FEB-1986; Project End 31-JUL-2006 Summary: (provided by applicant): The Study of Osteoporotic Fractures (SOF) is a multi-center longitudinal study in a cohort of 9,704 older women. SOF has comprehensive data about risk factors for osteoporosis and other diseases, along with an archive of serum, buffy coat and urine specimens. Data from SOF have served for: (1) developing osteoporosis guidelines, (2) estimating the cost-effectiveness of screening for osteoporosis, and (3) planning trials of osteoporosis therapies. They propose to renew SOF to sustain this unique resource and to pursue several new hypotheses. Osteoporosis is a chronic disease and prevention of fractures must be considered over the very long-term, not just the 3-5 year duration of most studies in the field. As the study of osteoporosis and aging with the longest (nearly 15 years) follow-up, SOF will provide the foundation for describing ways to identify people at greatest risk of osteoporosis and fractures decades in advance. They envision a new generation of clinical guidelines based on long-term prediction of risk of fractures and disability. Because they have enriched the cohort with African-American women, SOF will also provide unique information on risk factors for osteoporosis and non-spine fractures in older African American women. SOF was the first study to show a link between low BMD and risk of stroke and this has helped to fuel the interest and new investigations about the links between arterial calcification and osteoporosis.. If they demonstrate, and can begin to explain, the link between these two diseases, this may lead to screening tools and treatments that simultaneously decrease the risk of both of these disabling conditions. Preliminary results from SOF suggest that impaired sleep may be a major cause of fractures, disability and decline in cognition in older women. If the next phase of SOF confirms these relationships using more objective measures of insomnia and other sleep disorders, then this might change current clinical policies and practices toward more aggressive screening and better coverage for treatment of sleep disorders. Finally, the value of SOF could be magnified by recruiting other scientists to work on SOF data and samples. They propose to make the database easily accessible to investigators outside of SOF and assist them in making productive use of a database that represents one of the most comprehensive prospective sources of information about the health of older women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TESTOSTERONE THERAPY FOR MEN WITH OSTEOPOROSIS Principal Investigator & Institution: Kenny, Anne M. Professor; Medicine; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (verbatim from application) Attention to osteoporosis has largely emphasized women's health, and little attention has focused on the diagnosis and prevention of osteoporotic fractures in men. And yet the disease is also an important problem in men. Tesosterone levels decline with advancing age, and severe testosterone deficiency is associated with low bone mass and fracture. Several epidemiologic studies suggest that low testosterone is associated with low bone mass in older men, but this finding is not consistent. Men with hip fracture are found to be testosterone deficient more often than control subjects. Among men over age 70 with testosterone levels below young normal range, we found differences in bioavailable testosterone accounted for 20 percent of the variance in femoral next bone mineral density (FN BMD) values. Based on these data, testosterone supplementation may be important for bone health in older men. We will test the hypothesis that testosterone supplementation can decrease the risk of subsequent vertebral and non-vertebral fractures in older men with recent hip fracture. We will also evaluate the effects of testosterone on general health and wellbeing in this group. The specific aims of the proposed study will be to determine the effect of testosterone supplementation on vertebral and non-vertebral fractures incidence in men, age 60 years and older, who have sustained a recent hip fracture. Two hundred men, age 60 years and older, who have sustained a hip fracture following mild to moderate trauma (such as a fall from a standing height in the previous 2-6 months) will be randomly assigned to receive either long-acting testosterone or placebo injections in a double-blind study. We will ascertain new, non vertebral fracture incidence by structured questionnaire and follow-up radiographic confirmation every 6 months for 36 months, as well as vertebral fracture rates with baseline lateral spine films and yearly follow-up lateral spine films. In addition, bone mineral density (BMD) of the proximal femur, lumbar spine, distal radius and total body by dual x-ray absorptiometry (DXA) will be performed at baseline and yearly for 3 years to assess changes in BMD. In addition, we will determine the effect of testosterone on general health, including physical and cognitive function, cardiovascular risk, body composition and prostate parameters. Various physical and cognitive measures will be assessed, cardiovascular risk will be assessed by lipid profile and body composition from the whole body DXA and prostate parameters will include prostate specific antigen levels, American Urologic Association Prostate Symptom Score and digital rectal examination of the prostate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE EFFECT OF DELAYED MENARCHE ON PEAK BONE MASS IN RATS Principal Investigator & Institution: Yingling, Vanessa R. Biology; Brooklyn College 2900 Bedford Ave New York, NY 11210 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): This project will provide a foundation for future investigations regarding the optimization of peak bone mass obtained during adolescence. Osteoporosis, once thought to be a natural part of aging among women, is no longer considered age- or gender-dependent. Low bone mass in young women has emerged as a crucial factor that may contribute to the development of osteoporosis.. Studies have reported bone densities in young athletic women similar to 51-year-old

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women. In a recent study, 72% of amenorrheic athletes had bone densities that met the diagnostic criterion for osteopenia or osteoporosis.. Multiple factors have been found to correlate with low bone mass in young women including low estrogen scores and increased age at menarche. Therefore, the effect of delayed estrogen levels during bone development may decrease the peak bone mass in young adults and lead to an increase risk of fractures later in life. Few studies have been focused on the relationship between delayed menarche and peak bone mass. The aim of this research is to develop an animal model that will delay menarche and, in turn, alter peak bone mass. Rats will be injected with GnRH antagonists to delay the increase of estrogen levels prior to reproductive maturation. GnRH antagonists will be withdrawn at age 8 weeks. Bone slices of rat tibiae and lumbar spine will be analyzed using histomorphometric measurements and compared between groups. Cross-sectional slices of the tibia midshaft will be analyzed. Specifically, cross-sectional area and the polar moment of inertia will be measured. Ash content values of bones will be measured to assess bone quality (mineral content). Blood will be taken from the tail vein bi-weekly and serum estrogen levels (pg/mL) will be measured using an estradiol ultra-sensitive double antibody RIA. LH and FSH measures will be measured using ELISA kits. All groups will be sacrificed by anesthesia overdose at 24 weeks of age. A one-way ANOVA will be used for this study with a significance level of 0.05. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE EFFECTS OF JUMPING ON GROWING BONES Principal Investigator & Institution: Snow, Christine M. Associate Professor; Exercise and Sport Sciences; Oregon State University Corvallis, OR 973391086 Timing: Fiscal Year 2002; Project Start 18-SEP-1998; Project End 30-JUN-2007 Summary: Fractures related to osteoporosis continue to grow at an alarming rate, despite advances in bone biology and pharmaceutical treatment. The situation suggests the need for bold, new strategies for both the treatment and the prevention of osteoporosis.. To be successful, such strategies must be based in a sound understanding of the relevant biological mechanisms and sufficiently simple and low cost to be applicable on a national scale to a broad segment of the population. Given that: 1) peak bone mass is an important determinant of fracture risk in later life; 2) up to 40 percent of peak bone mass can be influenced by environmental factors such as exercise and diet; and 3) childhood and prepubescence are the most critical time periods for skeletal mineralization, we conducted during the previous funding period what we believe to be the first randomized controlled study investigating the effects of a highly specific jumping program on bone mass in pre-pubertal children. We showed that 7 months of high-impact loading from jumping off two foot boxes was both safe and effective and resulted in 4.5 percent and 3.1 percent (p less than 0.01) increases compared to controls in bone mineral content (BMC) at the hip and spine, respectively. Moreover, after an additional 7 months of detraining, jumpers maintained a 4 percent greater femoral neck BMC (p less than 0.05). After detraining, the group differences at the spine, although positive, were not statistically significant. The exercise program was simple, practical and low cost enough so that it could be incorporated into elementary school physical education curricula. In this competitive renewal, we now propose to build on and extend these findings by determining: 1) if two sequential, 7-month high- impact jumping interventions can be used to increase bone mass even further; 2) if the increases in bone mass are again maintained after detraining; and 3) if the increases in bone mass observed in the subjects studied during the previous funding period continue to be maintained through puberty and into adolescence. As we have done previously, we will

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measure ground impact forces from jumping in individual subjects both early and late in the intervention, with the advantage now that dual force plates can be used to determine forces in each leg. Given the relatively stable nature of the Corvallis population, we believe that our program represents a valuable and unique resource for the long-term study of exercise effects in the developing skeleton. We also believe our program can serve as a model for exercise-based interventions that might be implemented successfully on regional and even national levels. Thus, if we continue to produce and maintain practically important and structurally significant increases in bone mass at the hip and spine in growing children, we believe we will have taken an important step toward the bold new strategies that are needed if we are to reverse the continued increases in the numbers of age- related fractures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF ESTROGEN IN BONE METABOLISM Principal Investigator & Institution: Oz, Orhan K. Radiology; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: The candidate, Dr. Orhan K. Oz, is a diagnostic radiologist with previous scientific training in biophysics and tumor biology who seeks to become an independent investigator in the field of bone biology. To make this transition additional training will be necessary under the auspices of a career development award. His long-term career goals are to improve understanding of the pathophysiology of osteoporosis and to use this understanding as the basis for new therapeutic and diagnostic modalities for this disease. A development plan has been developed in which the candidate will conduct research on the role of estrogen in bone metabolism under the guidance of Drs. Zerwekh and Sakhaee experienced investigators in the field of bone biology. They will direct the basic science and clinical activities necessary for this project. Dr. Oz will become an active participant in data conferences and the local Bone Research Society - activities and an environment designed to enhance the candidate's transition to the field of bone science. The broad, long-term objective of the research is to elucidate the mechanisms of estrogen's effect on bone growth and metabolism and to use that information to develop new therapeutic and diagnostic modalities for osteoporosis.. The enzyme aromatase synthesizes estrogen from its androgen precursors. Estrogen withdrawal in postmenopausal women is associated with an increase of bone turnover and acceleration of bone loss, that leads to an increased susceptibility to bone fractures and clinically relevant osteoporosis in one third of all women. The recent observation of a phenotype in men with aromatase deficiency or estrogen receptor deficiency comprising failure of epiphyseal fusion closure leading to excessive height together with osteopenia, is indicative of an important role of estrogen in bone growth and metabolism of males, as well as females. This leads to the issue of the origin of the estrogen involved in the bone metabolism and points to the possibility that local formation of estrogen within bone tissues may play an important role in bone mineral metabolism in both sexes. The central hypothesis is that estrogen is an important regulator of growth and metabolism which effects its regulatory function by influencing bone cell differentiation and the differentiated function of bone cells. A model of estrogen deficiency has recently been created, namely the aromatase-deficient (ArKO) mouse. Specific aims designed to test this hypothesis are: 1) To study the cellular distribution of aromatase in sections of bone tissue from mice of various ages; 2) To study bone metabolism in the ArKO knock-out mouse; 3) To determine whether aromatase deficiency affects bone cell differentiation

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and proliferation and; 4) To study expression of cytokines, critical to bone growth and metabolism, in bone marrow cells from aromtase deficient mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THEE FFECTS OF CA AND VIT D3 SUPPLEMENT ON CORTICOSTEROID INDUCED OSTEOPOROSIS Principal Investigator & Institution: Buckley, Lenore;; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001 Summary: To examine rates of bone loss during moderate to high dose corticosteroid treatment and determine whether 2,000 mg of calcium and 750 IU of vitamin D3 can reduce bone loss as compared to treatment with calcium carbonate (500mg/d) during moderate to high dose corticosteroid treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THERAPY OF OSTEOPOROSIS IN MEN WITH PARATHYROID HORMONE Principal Investigator & Institution: Bilezikian, John P.; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSGENIC MODELS OF ESTROGEN RECEPTOR ACTIVITY IN BONE Principal Investigator & Institution: Alexander, Joseph M.; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2002; Project Start 17-MAY-2002; Project End 30-APR-2005 Summary: The efficacy of hormone replacement therapy (HRT) in preventing postmenopausal bone loss is well-known. However, the relative roles of the two known estrogen receptors (ERs), alpha and beta, and their bone-specific mechanisms of action continue to be debated. For example, biochemical studies outlined below agree that ERalpha has profound inhibitory effects on osteoclast-mediated bone resorption by tonically down-regulating osteoblast cytokine production. Yet, recently reported 'double knock-out' mouse animal models for both ERalpha and ERbeta so far have shown no osteoporotic phenotype, despite clear effects of estrogen (E2)-deficiency in the uterus and gonads. The inability to reconcile data from in vitro cell culture experiments and the mouse double ERalpha/beta knockout studies have made it difficult to formulate a hypothesis regarding ER mechanism of action in bone. This is especially true since the established animal model for post-menopausal osteoporosis (OP)-the rat- is not yet accessible to genetic manipulation by transgenic and knock-out technologies. Thus, while the rat model can continue to test the efficacy of new therapies, it cannot be adapted to functionally characterize the molecular mechanisms of ERalpha and ERbeta action and their role in OP. In an effort to shed light on ERalpha and ERbeta function in bone, re report implementation of a mouse model of ovariectomy (OVX)-induced OP as a system for further elucidating the molecular mechanisms in hormone-dependent bone homeostasis. As a 'proof of principle' experiment for testing this model system, we propose to introduce characterized, constitutively action mutant ER alpha isoform

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(CAM-ERalpha) as transgenes into our mice. These two ERalpha isoforms, L536P and Y537S encode adjacent single residue changes in the ERalpha ligand-binding domain, and have been previously shown to confer full gene activation to ERalpha in the absence of E2 using in vitro cell-based assays. We will confirm the activity the CAM-ERalpha (L536P) and (Y537S) on MC-3T3-E1 osteoblastic cells. We then will determine whether these receptors can prevent bone loss in the absence of HRT in vivo by expressing CAM-ERalpha transgenes under the transcriptional control of an inducible 'Tet On/Off promoter system designed for regulating mammalian gene expression. If this pilot transgenic study demonstrates CAM-ERalpha isoforms can rescue the OP phenotype from OVX mice in the absence of HRT, it will be a key initial experiment in: 1) elucidating the molecular mechanisms of ERalpha in bone homeostasis in an in vivo assay, and 2) developing a mouse model system for OVX-induced OP that can be manipulated to add, delete, or alter specific gene targets that are active in bone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT CROSSOVER STUDY

OF

SENILE

OSTEOPOROSIS--OPEN

LABEL

Principal Investigator & Institution: Rubin, Craig D.; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001 Summary: The aim of this two year extension project is to go beyond the 40 month duration of the Randomized controlled trial that precedes this study in senile osteoporosis and ascertain the long term safety and efficacy (up to five years) of a novel pharmacologic approach in the treatment of elderly individuals with established osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UAB CERT OF MUSCULOSKELETAL DISORDERS Principal Investigator & Institution: Saag, Kenneth G. Associate Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2003 Summary: Musculoskeletal disorders (MSDs) affect over 40 million Americans and are the leading cause of activity limitations. Health care costs for arthritis and osteoporosis alone exceed 75 billion dollars per year. In the past 5 years, there has been a dramatic rise in the number of new FDA approved therapies for MSD treatment. Society faces difficult questions of how best to use new versus existing therapies in an equitable, efficient and cost-effective fashion. The long-term objective of this proposal is to establish a self-sustaining Center for Education and Research on Therapeutics (CERT) of MSDs. The CERT will combine substantial UAB clinical and health services research expertise with private sector collaborations to evaluate the effectiveness and safety of new MSD therapeutics and to guide changes in the practice community. The specific aims of the CERT are to establish a core facility that will be utilized to: 1) In collaboration with AHCPR/FDA, conduct outcomes and effectiveness research on high profile MSD projects that are generated internally, from our partners in managed care organizations and in the pharmaceutical industry, and from other CERTs. Our CERT will use both private and public national data sources and will build on the diverse resources of UAB Schools, Centers, and Programs; 2) Identify variations in the use of MSD therapeutics and explore the causes of these variations in practices by examining their association with scientific evidence, provider, care system, patient and community

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characteristics; 3) Using previously well-tested methodology, effectively disseminate new knowledge about MSD therapeutics to practitioners, insurers, policy makers, and the general public. Emphasis will be placed on altering provider behavior via education on evidence-based guidelines, quality of care indicators, and peer performance. A study of glucocorticoid-induced osteoporosis, an endemic problem that is currently inadequately treated, highlights selected CERT capabilities. Other demonstration studies addressing arthritis and osteoporosis problems of high current interest are also proposed. The UAB CERT, a cooperative agreement with AHCPR, will encompass broad and rapidly emerging therapeutic areas in all MSDs that affect predominantly older and other high-risk populations. We demonstrate that future viability of the CERT will follow form our broad-base of public and private sector support. Our findings and interventions will address health care policy concerns of significant National importance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: 'UPREGULATED STATES' OF THE VITAMIN D RECEPTOR Principal Investigator & Institution: Heller, Howard J.; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001 Summary: It is hypothesisized that a major subset of patients with absorptive hypercalciuria (AH) oridiopathic osteoporosis (IO) will demonstrate an upregulated state of the vitamin D receptor (increased fibroblast VDR number or VDR-complex activity).The aims of this study are 1) to carefully characterize both stone-formers and those with idiopathic osteoporosis who demonstrate an absorptive hypercalciuria pattern 2) to determine if these patients have an upregulated state of the 1,25- (OH)2D receptor in skin fibroblasts and 2) to determine by bone biopsy if the vitamin D receptor is upregulated in those subjects with low bone mass. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UROPHOS-K OSTEOPOROSIS

FOR

THE

TREATMENT

OF

IDIOPATHIC

Principal Investigator & Institution: Sakhaee, Khashayar;; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001 Summary: The objective of this project is to determine whether UroPhos-K would be useful in the treatment of bone disease in patients with hypercalciuric idiopathic osteoporosis.. The hypotheses to be tested are that hypercalciuric idiopathic osteoporosis may be caused by calcitriol excess or sensitivity, and that UroPhos-K would lower serum 1,25 vitamin D, reduce urinary calcium, inhibit bone resorption and stimulate bone formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: USE OF DHEA TO PREVENT OSTEOPOROSIS IN ANOREXIA NERVOSA Principal Investigator & Institution: Gordon, Catherine;; Children's Hospital (Boston) Boston, MA 021155737 Timing: Fiscal Year 2001

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Summary: The proposed clinical study will test the hypothesis that 12 months of DHEA therapy will increase bone mineral density, as well as increase markers of bone formation and decrease markers of bone resorption in young women with anorexia nervosa. The investigators will examine whether augmenting the low adrenal androgen DHEA level back to the level seen in young adults will increase bone formation and decrease bone resorption, trends reflected in the pilot data, thereby attenuating the bone loss associated with this disease. A double-blinded, randomized controlled trial will include two treatment arms of 30 patients each. Group 1 will receive daily doses of 50mg of DHEA while group 2 will receive a standard regimen of estrogen cycled with progesterone. According to data obtained in the pilot study, a dose of 50mg restores DHEA levels to a range characteristic of the second decade of life. Bone mineral density and bone composition will be measured at baseline and after completion of the study, by dual x-ray absorptiometry (DEXA). The determination of body compostition will permit the investigators to assess the effects of DHEA on fat and lean body mass. Fasting bloods will be obtained to follow other laboratory parameters, although no signs of toxicity were noted (physical or biochemical) during the pilot study. Levels of specific circulating hormones will also be monitored. Determination of the effects of DHEA on markers of bone formation and on indices of bone resorption will be made. Measurement of parameters of bone turnover will provide data as to the effects of DHEA and other androgens on bone formation and resorption. This model will address the longitudinal effects of DHEA on markers of bone turnover and to determine whether restoring the DHEA levels of young women with anorexia nervosa to the normal range of early adulthood will be beneficial in the prevention of bone loss.. The investigators anticipate that these studies will enable them to evaluate the efficacy of oral DHEA as a treatment strategy to optimize peak bone mass and to prevent development of osteoporosis in patients with eating disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VANGUARD CENTER FOR WOMENS HEALTH INITIATIVE Principal Investigator & Institution: Beresford, Shirley a A. Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, WA 98109 Timing: Fiscal Year 2001; Project Start 15-MAR-1993; Project End 14-SEP-2005 Summary: The Women's Health Initiative is a randomized controlled clinical trial conducted in 40 clinical centers across the United States addressing some of the most common causes of death, disability, and impaired quality of life in postmenopausal women ages 50-79: cardiovascular disease; breast and colon cancer; and osteoporosis.. The three components of this disease prevention trial are: (1) hormone replacement therapy with a primary outcomes of coronary heart disease and stroke and secondary outcomes of hip and other fractures; (2) low fat dietary intervention with primary outcomes of breast cancer and colorectal cancer and a secondary outcome of coronary heart disease; and (3) calcium and vitamin D supplementation with a primary outcome of hip fractures and secondary outcomes of colorectal cancer and combined fractures. A concurrent observational study will provide estimates of health effects of known risk factors and new predictors for disease. Each clinical center will collect data through questionnaires and biological specimens over 8-12 years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VERTEBRAL FRACTURE: TRABECULAR BONE STRUCTURE ASSESSMENT Principal Investigator & Institution: Majumdar, Sharmila; Professor; Radiology; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Osteoporosis is a condition characterized by a reduction in the bone mineral density, impaired bone quality and frequent occurrence of fractures resulting from minor trauma. Current assessment of osteoporotic fracture risk is based on bone densitometry techniques that do not entirely predict fracture risk or the impact of a particular intervention. Bone quality encompasses bone geometry and macro-architecture, trabecular bone structure, matrix calcification, bone turnover. The quantitative analysis of bone structure and the elucidation of relationships between structural parameters and bone strength may have a major impact upon the prediction of fracture risk and evaluation of different therapies. In this application, we are proposing to extend our previous work and make use of recent advances in hardware and software, to obtain three-dimensional (3-D) magnetic resonance (MR) images with resolutions of approximately 100x 100x300 microns so as to accurately quantify the 3-D architecture of the trabecular bone network in the radius, calcaneus and proximal femur, and perform a rigorous evaluation of the impact of these data on the pathophysiological changes in skeletal bone and trabecular micro-architecture in aging, osteoporosis and fracture susceptibility. The specific aims of this study will be to establish non-invasive, reproducible imaging surrogates that can be used to assess bone quality in vivo. MR image derived parameters of trabecular micro-architecture at the different measurement sites will be related to age, menopause status and osteoporotic status in a cohort of 250 subjects. The primary question that will be addressed is whether MR assessment of trabecular micro-architecture at the radius, calcaneus and proximal femur, combined with bone mineral density, provide a means to explain the discrepancy between bone mineral density and fracture occurrence. We will assess whether using MR derived measures of trabecular bone at the different skeletal sites show site specific differences, relationship between structure and bone mineral density at these sites, and whether these measures may be used to complement bone mineral density measurements in the study of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VITAMIN D RECEPTOR AND REGULATION OF HORMONE RESPONSE Principal Investigator & Institution: Feldman, David; Medicine; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 01-JUN-1991; Project End 30-JUN-2005 Summary: (provided by applicant): This grant proposal is a competitive renewal of a project we have pursued for 10 years directed at understanding the mechanism of action of the vitamin D receptor (VDR) as the mediator of 1,25-dihydroxyvitamin D (1,25D) action. The project has supported the publication of many original research papers as well as reviews of the field, editorials, chapters and the editing of two multi-authored books. The next support period will continue our investigation into the role of the VDR in clinically relevant situations in which 1,25D activity is enhanced or suppressed by either genetic factors (mutations or polymorphisms) or physiologic factors (regulators of VDR abundance or action). The clinical diseases most relevant to the project are: Aim I, rickets; Aim II, osteoporosis;; and Aim III, prostate cancer. Specific Aim I will

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investigate Hereditary Vitamin D Resistant Rickets (HVDRR) and elucidate loss of function mutations causing rickets and a gain of function mutation causing hypercalcemia. An additional project will study the use of 1,25D analogs to activate mutant VDRs and treat HVDRR patients. Specific Aim II will focus on the structure of the VDR and will examine factors that regulate the abundance of receptors and the capacity of the VDR to mediate 1,25D actions. Sub-Aim 1 will investigate the VDR promoter. Sub-Aim 2 will investigate the VDR promoter variants leading to N-terminal isoforms and evaluate their differential functional potency and tissue distribution. SubAim 3 will investigate VDR polymorphisms and the ability of the variant receptors to respond to 1,25D and analogs with target gene activation. Specific Aim III will focus on 1,25D actions. The sub-Aims will involve cDNA microarray analysis to identify new target genes in prostate cancer and bone; a further analysis of IGFBP-3 as a target gene that mediates some of the anti-prostate cancer activity of 1,25D; and an analysis of the negative vitamin D response element (nVDRE) in new target genes including the estrogen receptor and IGFBP-3. Many of the projects will be carried out in collaboration with leading researchers in their respective fields. Comprehensive preliminary data and an extensive track record support our ability to successfully conduct this large, multiphasic study. The long-term goals of the grant proposal are to provide further insight into the mechanism of 1,25D action and to understand the role of the VDR in affecting disease risk, pathogenesis and treatment of rickets, osteoporosis and prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN D SUPPLEMENTATION IN POSTMENOPAUSAL BLACK WOMEN Principal Investigator & Institution: Nieves, Jeri W. Assistant Professor; Helen Hayes Hospital Rt 9 W West Haverstraw, NY 10993 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-AUG-2003 Summary: Osteoporosis is a major public health problem throughout the world. Although black women are believed to be at lower risk of osteoporotic fracture than white women, the risk of fracture in postmenopausal black women is still substantial. Blacks have consistently lower 25- hydroxy-vitamin D levels and an elevation in parathyroid hormone level compared to white women. These findings are consistent with vitamin D insufficiency, or in some, true deficiency. Vitamin D insufficiency has been implicated in bone loss with aging in the white female population. furthermore, in white elderly women and men, treatment with vitamin D has resulted in a lower rate of bone loss and fractures. The effect of vitamin D supplementation has never been evaluated in black women. We hypothesize that the presence of relative 25(OH)D insufficiency that exists among black postmenopausal women may exacerbate loss of bone among aging black women. To test this hypothesis, we propose to conduct a randomized clinical trial to compare vitamin D supplementation (1000 IU/ day) with placebo during a two year study in a population of 150 black postmenopausal (>5 years) women, who are shown to be 25(OH)D insufficient. We propose to determine whether supplemental vitamin D (1000 IU) improves mineral metabolism, increases calcium absorption, reduces bone turnover and reduces the rate of bone loss in black postmenopausal women. In addition, we intend to determine whether biochemical and bone density responses to vitamin D supplementation in black women are related to allelic variation in the vitamin D receptor. The fact that black women fracture less frequently than white woman and tend to have higher bone mass has virtually excluded this ethnic group from studies of osteoporosis treatment and prevention. However, the fracture rate in black women is still substantial. It is possible that a simple, safe

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nutritional supplement, vitamin D, could reduce the rate of bone loss and risk of osteoporotic fracture in black women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN D SUPPLEMENTATION IN POSTMENOPAUSAL WOMEN Principal Investigator & Institution: Aloia, John F.; Winthrop-University Hospital 259 1St St Mineola, NY 11501 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-JUL-2003 Summary: (Adapted from the Applicant's Abstract): The long-term goal of this project is to develop strategies for the prevention of osteoporotic fractures in black women. Most studies have excluded black women because of the mistaken belief that osteoporosis is not a major health problem in this population. It is true that black women have a higher bone density, protective anatomic geometry of the femur, and a larger muscle mass compared to white women. Nonetheless, the incidence of hip fracture in black women is as great as 40% of that in white women. As the black population ages, osteoporosis will become even a greater health problem for this ethnic minority. Black women have lower levels of calcidiol and higher levels of parathyroid hormone (PTH) than white women. Since black women have lower indices of bone turnover, they also appear to have a relative resistance to the effect of PTH. Dietary supplementation with vitamin D3 has been shown to safely reduce bone loss and prevent hip fractures in postmenopausal white women. The strategy of vitamin D3 supplementation to prevent osteoporosis is even more cogent in black postmenopausal women compared to white women because (a) they have lower calcidiol levels, (b) they have evidence of secondary hyperparathyroidism, (c) the long-term effects and risks of hormonal replacement therapy have not been evaluated in black women, and (d) because of their higher bone mass, low risk strategies are more appropriate. There are less black women with osteoporosis at menopause, so that a modest reduction in bone loss could have a great impact on prevention of osteoporosis.. The specific aim of this project is to determine if daily dietary supplementation with 800 IU (20 ug) of vitamin D3 will reduce bone loss in postmenopausal black women. A secondary aim is to evaluate the changes in the vitamin D-endocrine system and indices of bone turnover that result from long term vitamin D3 augmentation. A positive response would provide a safe, inexpensive and acceptable strategy for prevention of osteoporotic fractures in black women. If this randomized clinical trial demonstrates a positive effect on prevention of bone loss, a large scale multi-centered trial with fracture prevention as an endpoint will have merit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VITAMIN OSTEOPOROSIS

K

INSUFFICIENCY--A

RISK

FACTOR

FOR

Principal Investigator & Institution: Booth, Sarah L. None; Tufts University Boston Boston, MA 02111 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-JUL-2004 Summary: This application proposes to extend ongoing investigations in the Framingham Offspring Study which is examining biological and behavioral risk factors for bone loss and related fractures to include measures of serum osteocalcin (total and degree of carboxylation) and plasma vitamin K (phylloquinone) concentrations to assess the influence of vitamin K status on BMD. Plasma 25-hydroxyvitamin D also will be assayed to evaluate whether the relationship between vitamin K status and bone health is influenced by vitamin D status. These biochemical measurements will be compared to

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BMD measurements of the spine and hip collected at the 6th consecutive physical examination. From the Original Framingham Cohort of 3800 participants, 2000 males and females, ages 28-84 years will be studied. Covariates in addition to 25(OH) D concentrations include: age, anthropometric data, physical activity, medication use, smoking and diet including energy, protein, calcium, alcohol, and caffeine. The proposed studies will identify factors that lead to bone loss and help clarify the role of vitamin K status in the development of osteoporosis.. Results of the studies proposed could lead to effective intervention programs that reduce bone loss resulting in a decreased risk and incidence of osteoporosis.. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “osteoporosis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for osteoporosis in the PubMed Central database: •

2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. by Brown JP, Josse RG. 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=134653

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A crucial role for thiol antioxidants in estrogen-deficiency bone loss. by Lean JM, Davies JT, Fuller K, Jagger CJ, Kirstein B, Partington GA, Urry ZL, Chambers TJ. 2003 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193670

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Be careful with the term "bone loss". by Donaldson MG, Khan KM, McKay HA, Wark JD. 2001 Aug 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81318

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Bone loss: Epidemiology of bone loss. by Hunter DJ, Sambrook PN. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128872

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Bone loss: Factors that regulate osteoclast differentiation - an update. by Roux S, Orcel P. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128874

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Bone loss: Quantitative imaging techniques for assessing bone mass in rheumatoid arthritis. by Njeh CF, Genant HK. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128873

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Bone loss: Therapeutic approaches for preventing bone loss in inflammatory arthritis. by Rehman Q, Lane NE. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128900

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Clinical nutrition: 2. The role of nutrition in the prevention and treatment of adult osteoporosis. by Atkinson SA, Ward WE. 2001 Nov 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81671

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Community-based exercise program reduces risk factors for falls in 65- to 75-year-old women with osteoporosis: randomized controlled trial. by Carter ND, Khan KM, McKay HA, Petit MA, Waterman C, Heinonen A, Janssen PA, Donaldson MG, Mallinson A, Riddell L, Kruse K, Prior JC, Flicker L. 2002 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134175

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CRA endorsement of osteoporosis guidelines. by Pope J. 2003 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154902

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Effect of vitamin D on bone mineral density of elderly patients with osteoporosis responding poorly to bisphosphonates. by Heckman GA, Papaioannou A, Sebaldt RJ, Ioannidis G, Petrie A, Goldsmith C, Adachi JD. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65678

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Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. by Wu XB, Li Y, Schneider A, Yu W, Rajendren G, Iqbal J, Yamamoto M, Alam M, Brunet LJ, Blair HC, Zaidi M, Abe E. 2003 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193662

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Influence of bone densitometry results on the treatment of osteoporosis. by Fitt NS, Mitchell SL, Cranney A, Gulenchyn K, Huang M, Tugwell P. 2001 Mar 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80872

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Investigation and treatment of osteoporosis in patients with fragility fractures. by Hajcsar EE, Hawker G, Bogoch ER. 2000 Oct 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80503

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Mechanisms of bone loss in inflammatory arthritis: diagnosis and therapeutic implications. by Goldring SR, Gravallese EM. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129989

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Mutation in a Gene for Type I Procollagen (COL1A2) in a Woman with Postmenopausal Osteoporosis: Evidence for Phenotypic and Genotypic Overlap with Mild Osteogenesis Imperfecta. by Spotila LD, Constantinou CD, Sereda L, Ganguly A, Riggs BL, Prockop DJ. 1991 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51885

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New evidence of a link between inhaled corticosteroid use and osteoporosis. by Myers KA. 2000 Nov 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80359

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Oral contraceptive use and bone mineral density in premenopausal women: crosssectional, population-based data from the Canadian Multicentre Osteoporosis Study. by Prior JC, Kirkland SA, Joseph L, Kreiger N, Murray TM, Hanley DA, Adachi JD, Vigna YM, Berger C, Blondeau L, Jackson SA, Tenenhouse A. 2001 Oct 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81536

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Osteoporosis guidelines. by Laupacis A. 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161603

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Osteoporosis guidelines. by Yendt ER. 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161602

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Osteoporosis guidelines. by Brown JP. 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161604

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Osteoporosis in Canadian adult cystic fibrosis patients: A descriptive study. by Brenckmann C, Papaioannou A, Freitag A, Hennessey R, Hansen S, Ioannidis G, Webber C, Adachi J. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=198278

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Osteoporosis in children: 2002 guidelines do not apply. by Taback SP. 2003 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154909

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Osteoporosis in children: 2002 guidelines do not apply. by Brown JP. 2003 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154910

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Osteoporosis Induced in Mice by Overproduction of Interleukin 4. by Lewis DB, Liggitt HD, Effmann EL, Motley ST, Teitelbaum SL, Jepsen KJ, Goldstein SA, Bonadio J, Carpenter J, Perlmutter RM. 1993 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48035

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Ovariectomy Selectively Reduces the Concentration of Transforming Growth Factor [beta] in Rat Bone: Implications for Estrogen Deficiency-Associated Bone Loss. by Finkelman RD, Bell NH, Strong DD, Demers LM, Baylink DJ. 1992 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50724

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Quantitative ultrasound and risk factor enquiry as predictors of postmenopausal osteoporosis: comparative study in primary care. by Hodson J, Marsh J. 2003 Jun 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161556

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Rheumatology: 15. Osteoporosis. by Wade JP. 2001 Jul 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81245

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Stimulation of bone formation and prevention of bone loss by prostaglandin E EP4 receptor activation. by Yoshida K, Oida H, Kobayashi T, Maruyama T, Tanaka M, Katayama T, Yamaguchi K, Segi E, Tsuboyama T, Matsushita M, Ito K, Ito Y, Sugimoto Y, Ushikubi F, Ohuchida S, Kondo K, Nakamura T, Narumiya S. 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123690

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Systematic assessment of the quality of osteoporosis guidelines. by Cranney A, Waldegger L, Graham ID, Man-Son-Hing M, Byszewski A, Ooi DS. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126217

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The association between iliocostal distance and the number of vertebral and nonvertebral fractures in women and men registered in the Canadian Database For Osteoporosis and Osteopenia (CANDOO). by Olszynski WP, Ioannidis G, Sebaldt RJ, Hanley DA, Petrie A, Brown JP, Josse RG, Murray TM, Goldsmith CH, Stephenson GF, Papaioannou A, Adachi JD. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130045

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The design of a valid and reliable questionnaire to measure osteoporosis knowledge in women: the Osteoporosis Knowledge Assessment Tool (OKAT). by Winzenberg TM, Oldenburg B, Frendin S, Jones G. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=183834

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Up-regulation of TNF-producing T cells in the bone marrow: A key mechanism by which estrogen deficiency induces bone loss in vivo. by Roggia C, Gao Y, Cenci S, Weitzmann MN, Toraldo G, Isaia G, Pacifici R. 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61149

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with osteoporosis, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “osteoporosis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for osteoporosis (hyperlinks lead to article summaries): •

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A case of march fracture in a patient with osteoporosis on long-term HAART. Author(s): Forsyth SF, Gazzard BG, Nelson MR. Source: International Journal of Std & Aids. 2002 September; 13(9): 645-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230930&dopt=Abstract

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A comparison of the effect of risedronate and etidronate on lumbar bone mineral density in Japanese patients with osteoporosis: a randomized controlled trial. Author(s): Fukunaga M, Kushida K, Kishimoto H, Shiraki M, Taketani Y, Minaguchi H, Inoue T, Morita R, Morii H, Yamamoto K, Ohashi Y, Orimo H; Risedronate Phase III Research Group. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 December; 13(12): 971-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459940&dopt=Abstract

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A comprehensive review of treatments for postmenopausal osteoporosis. Author(s): Hauselmann HJ, Rizzoli R. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 January; 14(1): 2-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577179&dopt=Abstract

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A crossover comparison of four peripheral bone-site measurements to identify central osteopenia and osteoporosis in women. Author(s): Rosenthall L. Source: International Orthopaedics. 2002; 26(6): 328-33. Epub 2002 July 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466863&dopt=Abstract

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A fresh approach to osteoporosis. Interview by Carol Davis. Author(s): Sutcliffe A. Source: Nurs Times. 2003 July 15-21; 99(28): 40-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889311&dopt=Abstract

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A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. Author(s): Lips P, Duong T, Oleksik A, Black D, Cummings S, Cox D, Nickelsen T. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 March; 86(3): 121221. Erratum In: J Clin Endocrinol Metab 2001 July; 86(7): 3008. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11238511&dopt=Abstract

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A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis. Author(s): Cranney A, Guyatt G, Krolicki N, Welch V, Griffith L, Adachi JD, Shea B, Tugwell P, Wells G; Osteoporosis Research Advisory Group (ORAG). Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(2): 140-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303715&dopt=Abstract

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A new approach to the development of assessment guidelines for osteoporosis. Author(s): Kanis JA, Black D, Cooper C, Dargent P, Dawson-Hughes B, De Laet C, Delmas P, Eisman J, Johnell O, Jonsson B, Melton L, Oden A, Papapoulos S, Pols H, Rizzoli R, Silman A, Tenenhouse A; International Osteoporosis Foundation; National Osteoporosis Foundation. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 July; 13(7): 527-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111012&dopt=Abstract

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A pharmacokinetic and pharmacodynamic model for intravenous bisphosphonate (pamidronate) in osteoporosis. Author(s): Cremers S, Sparidans R, den HJ, Hamdy N, Vermeij P, Papapoulos S. Source: European Journal of Clinical Pharmacology. 2002 February; 57(12): 883-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936708&dopt=Abstract

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A potential role for the mast cell in the pathogenesis of idiopathic osteoporosis in men. Author(s): Brumsen C, Papapoulos SE, Lentjes EG, Kluin PM, Hamdy NA. Source: Bone. 2002 November; 31(5): 556-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477568&dopt=Abstract

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A prospective evaluation of the awareness, knowledge, risk factors and current treatment of osteoporosis in a cohort of elderly subjects. Author(s): Juby AG, Davis P. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(8): 617-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11580074&dopt=Abstract

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A prospective study of discordance in diagnosis of osteoporosis using spine and proximal femur bone densitometry. Author(s): O'Gradaigh D, Debiram I, Love S, Richards HK, Compston JE. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 January; 14(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577180&dopt=Abstract

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A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: effects on bone mineral density and bone markers. Author(s): Trovas GP, Lyritis GP, Galanos A, Raptou P, Constantelou E. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 March; 17(3): 521-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874243&dopt=Abstract

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A regional audit of the prevention and treatment of corticosteroid-induced osteoporosis in patients with rheumatic diseases in the West Midlands. Author(s): Erb N, Duncan RC, Raza K, Rowe IF, Kitas GD, Situnayake RD; West Midlands Rheumatology Services and Training Committee. Source: Rheumatology (Oxford, England). 2002 September; 41(9): 1021-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209036&dopt=Abstract

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A review of combination regimens for osteoporosis--prevention and treatment. Author(s): Miller E, Kalin MF. Source: Int J Fertil Womens Med. 2002 September-October; 47(5): 198-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469706&dopt=Abstract

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A review of the female athlete triad (amenorrhea, osteoporosis and disordered eating). Author(s): Golden NH. Source: Int J Adolesc Med Health. 2002 January-March; 14(1): 9-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467202&dopt=Abstract

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A role for sarcopenia in late-life osteoporosis. Author(s): Ferrucci L, Russo CR, Lauretani F, Bandinelli S, Guralnik JM. Source: Aging Clin Exp Res. 2002 February; 14(1): 1-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027146&dopt=Abstract

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A strategy for identifying osteoporosis risk genes. Author(s): Rowe D, Lichtler A. Source: Endocrine. 2002 February; 17(1): 67-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014707&dopt=Abstract

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A systematic review of health state utility values for osteoporosis-related conditions. Author(s): Brazier JE, Green C, Kanis JA; Committee Of Scientific Advisors International Osteoporosis Foundation. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 October; 13(10): 768-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378365&dopt=Abstract

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A whole-genome linkage scan suggests several genomic regions potentially containing quantitative trait Loci for osteoporosis. Author(s): Deng HW, Xu FH, Huang QY, Shen H, Deng H, Conway T, Liu YJ, Liu YZ, Li JL, Zhang HT, Davies KM, Recker RR. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 November; 87(11): 5151-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414886&dopt=Abstract

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About soft and hard endpoints in osteoporosis research. Author(s): Muskiet FA, Schaafsma A, Van der Veer E. Source: European Journal of Clinical Nutrition. 2001 April; 55(4): 305-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11360136&dopt=Abstract

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ACOG Committee opinion #270. Bone density screening for osteoporosis. American College of Obstetricians and Gynecologists. Author(s): Committee on Gynecologic Practice, American College of Obstetricians and Gynecologists. Source: Obstetrics and Gynecology. 2002 March; 99(3): 523-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11864698&dopt=Abstract

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Acro-osteolysis and osteoporosis as manifestations of the Hajdu-Cheney syndrome. Author(s): Blumenauer BT, Cranney AB, Goldstein R. Source: Clin Exp Rheumatol. 2002 July-August; 20(4): 574-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175120&dopt=Abstract

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Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: a randomized controlled trial. Author(s): Biermasz NR, Hamdy NA, Janssen YJ, Roelfsema F. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 July; 86(7): 3079-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11443170&dopt=Abstract

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Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. Author(s): Johnell O, Scheele WH, Lu Y, Reginster JY, Need AG, Seeman E. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 March; 87(3): 98592. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889149&dopt=Abstract

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Adenoviral delivery of osteoprotegerin ameliorates bone resorption in a mouse ovariectomy model of osteoporosis. Author(s): Bolon B, Carter C, Daris M, Morony S, Capparelli C, Hsieh A, Mao M, Kostenuik P, Dunstan CR, Lacey DL, Sheng JZ. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2001 February; 3(2): 197-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11237676&dopt=Abstract

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Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Author(s): Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Source: Biogerontology. 2001; 2(3): 165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708718&dopt=Abstract

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Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis. Author(s): Verma S, Rajaratnam JH, Denton J, Hoyland JA, Byers RJ. Source: Journal of Clinical Pathology. 2002 September; 55(9): 693-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195001&dopt=Abstract

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Adrenal incidentalomas and subclinical Cushing's syndrome: is there evidence for glucocorticoid-induced osteoporosis? Author(s): Angeli A, Osella G, Reimondo G, Terzolo M. Source: Frontiers of Hormone Research. 2002; 30: 73-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892272&dopt=Abstract

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Advances in osteoporosis therapy. 2003 update of practical guidelines. Author(s): Khan A. Source: Can Fam Physician. 2003 April; 49: 441-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729240&dopt=Abstract

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Advances in the treatment of osteoporosis. Author(s): Bell NH. Source: Current Drug Targets. Immune, Endocrine and Metabolic Disorders. 2001 May; 1(1): 93-102. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476784&dopt=Abstract

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Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study. Author(s): Goldstein SR, Nanavati N. Source: American Journal of Obstetrics and Gynecology. 2002 September; 187(3): 521-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237621&dopt=Abstract

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AGA technical review on osteoporosis in gastrointestinal diseases. Author(s): Bernstein CN, Leslie WD, Leboff MS. Source: Gastroenterology. 2003 March; 124(3): 795-841. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612917&dopt=Abstract

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AGA technical review on osteoporosis in hepatic disorders. Author(s): Leslie WD, Bernstein CN, Leboff MS; American Gastroenterological Association Clinical Practice Commitee. Source: Gastroenterology. 2003 September; 125(3): 941-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949738&dopt=Abstract

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Age-related bone mineral density, accumulated bone loss rate and prevalence of osteoporosis at multiple skeletal sites in chinese women. Author(s): Liao EY, Wu XP, Deng XG, Huang G, Zhu XP, Long ZF, Wang WB, Tang WL, Zhang H. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 August; 13(8): 669-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181627&dopt=Abstract

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Age-specific values and cutoff levels for the diagnosis of osteoporosis in quantitative ultrasound measurements at the calcaneus with SAHARA in healthy Japanese women: Japanese population-based osteoporosis (JPOS) study. Author(s): Ikeda Y, Iki M, Morita A, Aihara H, Kagamimori S, Kagawa Y, Matsuzaki T, Yoneshima H, Marumo F; JPOS Study Group. Source: Calcified Tissue International. 2002 July; 71(1): 1-9. Epub 2002 June 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200654&dopt=Abstract

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Aging, chronic illness and self-concept: a study of women with osteoporosis. Author(s): Wilkins S. Source: J Women Aging. 2001; 13(1): 73-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217187&dopt=Abstract

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Alcohol and other factors affecting osteoporosis risk in women. Author(s): Sampson HW. Source: Alcohol Research & Health : the Journal of the National Institute on Alcohol Abuse and Alcoholism. 2002; 26(4): 292-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875040&dopt=Abstract

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Alendronate and male osteoporosis. Author(s): Alkhenizan A, Almarri S, Evans MF. Source: Can Fam Physician. 2001 March; 47: 509-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281083&dopt=Abstract

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Alendronate for the treatment of osteoporosis in men. Author(s): Adami S, Prizzi R, Colapietro F. Source: Calcified Tissue International. 2001 October; 69(4): 239-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730259&dopt=Abstract

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Alendronate in the treatment of primary hyperparathyroid-related osteoporosis: a 2year study. Author(s): Parker CR, Blackwell PJ, Fairbairn KJ, Hosking DJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 October; 87(10): 4482-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364423&dopt=Abstract

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Alendronate treatment for osteoporosis in patients infected with human immunodeficiency virus. Author(s): Guaraldi G, Ventura P, Albuzza M, Orlando G, Bedini A, Esposito R. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 August 1; 33(3): 414-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438917&dopt=Abstract

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Alendronate: an update of its use in osteoporosis. Author(s): Sharpe M, Noble S, Spencer CM. Source: Drugs. 2001; 61(7): 999-1039. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434454&dopt=Abstract

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Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency. Author(s): Sato Y, Honda Y, Kaji M, Asoh T, Hosokawa K, Kondo I, Satoh K. Source: Bone. 2002 July; 31(1): 114-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110423&dopt=Abstract

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American Gastroenterological Association medical position statement: osteoporosis in hepatic disorders. Author(s): American Gastroenterological Association. Source: Gastroenterology. 2003 September; 125(3): 937-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949737&dopt=Abstract

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An analysis of osteoporosis-related hip fractures using hospital discharge data. Author(s): Rubin BR, Rene AA, Mains DA, Marshall MA. Source: J Am Osteopath Assoc. 2003 April; 103(4): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733546&dopt=Abstract

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An Asian perspective to the problem of osteoporosis. Author(s): Koh LK. Source: Ann Acad Med Singapore. 2002 January; 31(1): 26-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885491&dopt=Abstract

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An assessment of the new “SCORE” index as a predictor of osteoporosis in women. Author(s): Russell AS, Morrison RT. Source: Scandinavian Journal of Rheumatology. 2001; 30(1): 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11252690&dopt=Abstract

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An osteoporosis clinical pathway for the medical management of patients with lowtrauma fracture. Author(s): Chevalley T, Hoffmeyer P, Bonjour JP, Rizzoli R. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002; 13(6): 450-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107657&dopt=Abstract

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An update on glucocorticoid-induced osteoporosis. Author(s): Lane NE. Source: Rheumatic Diseases Clinics of North America. 2001 February; 27(1): 235-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285998&dopt=Abstract

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Anabolic agents to treat osteoporosis in older people: is there still place for fluoride? Fluoride for treating postmenopausal osteoporosis. Author(s): Duque G. Source: Journal of the American Geriatrics Society. 2001 October; 49(10): 1387-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890501&dopt=Abstract

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Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: histomorphometric evidence in a longitudinal study. Author(s): Khastgir G, Studd J, Holland N, Alaghband-Zadeh J, Fox S, Chow J. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 January; 86(1): 28995. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232014&dopt=Abstract

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Anabolic effect of long-term estrogen replacement on bone collagen in elderly postmenopausal women with osteoporosis. Author(s): Khastgir G, Studd J, Holland N, Alaghband-Zadeh J, Sims TJ, Bailey AJ. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(6): 465-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446562&dopt=Abstract

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Analgesic effect of calcitonin in osteoporosis. Author(s): Gennari C. Source: Bone. 2002 May; 30(5 Suppl): 67S-70S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12008161&dopt=Abstract

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Analgesic efficacy of flupirtine in primary care of patients with osteoporosis related pain. A multivariate analysis. Author(s): Ringe JD, Miethe D, Pittrow D, Wegscheider K. Source: Arzneimittel-Forschung. 2003; 53(7): 496-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918215&dopt=Abstract

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Analysis of 1-year vertebral fracture risk reduction data in treatments for osteoporosis. Author(s): Miller P. Source: Southern Medical Journal. 2003 May; 96(5): 478-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911187&dopt=Abstract

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Analysis of polymorphism of the interleukin-6 gene in Thai subjects with osteoporosis. Author(s): Weerakulwattana L, Tirawanchai N, Bunyaratavej N. Source: J Med Assoc Thai. 2001 October; 84 Suppl 2: S547-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11853279&dopt=Abstract

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Androgen receptor (AR) gene microsatellite polymorphism in postmenopausal women: correlation to bone mineral density and susceptibility to osteoporosis. Author(s): Chen HY, Chen WC, Wu MC, Tsai FJ, Tsai CH. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2003 March 26; 107(1): 52-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593895&dopt=Abstract

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Animal models for osteoporosis. Author(s): Turner RT, Maran A, Lotinun S, Hefferan T, Evans GL, Zhang M, Sibonga JD. Source: Reviews in Endocrine & Metabolic Disorders. 2001 January; 2(1): 117-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704974&dopt=Abstract

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Antioxidants and bone turnover in involutional osteoporosis. Author(s): Maggio D, Barabani M, Pierandrei M, Macchiarulo MC, Cecchetti R, Pedrazzoni M, Senin U, Cherubini A. Source: J Endocrinol Invest. 2002; 25(10 Suppl): 101-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508937&dopt=Abstract

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Antipsychotic drugs, menstrual regularity and osteoporosis risk. Author(s): Zhang-Wong JH, Seeman MV. Source: Archives of Women's Mental Health. 2002 November; 5(3): 93-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510211&dopt=Abstract

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Antiresorptive treatment of postmenopausal osteoporosis: comparison of study designs and outcomes in large clinical trials with fracture as an endpoint. Author(s): Marcus R, Wong M, Heath H 3rd, Stock JL. Source: Endocrine Reviews. 2002 February; 23(1): 16-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844743&dopt=Abstract

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Are Wisconsin physicians knowledgeable about male osteoporosis? Author(s): Binkley N, Krueger D, Li Z, Gangnon RE, Drezner MK. Source: Wmj. 2003; 102(2): 51-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754910&dopt=Abstract

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Are women with premenstrual dysphoric disorder prone to osteoporosis? Author(s): Halbreich U, Kahn LS. Source: Psychosomatic Medicine. 2001 May-June; 63(3): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382263&dopt=Abstract

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Ask the doctor. I take a statin because of high cholesterol. Now that I'm past menopause, my doctor thinks I need to take a medication to protect my bones. I've read that statins prevent osteoporosis, so do I really need another pill? Author(s): Lee TH. Source: Harvard Heart Letter : from Harvard Medical School. 2003 June; 13(10): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835155&dopt=Abstract

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Assessing the risk of vertebral osteoporosis. Author(s): Kanis JA. Source: Singapore Med J. 2002 February; 43(2): 100-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11993900&dopt=Abstract

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Assessment of four biochemical markers of bone metabolism in postmenopausal osteoporosis. Author(s): Majkic-Singh N, Ilic M, Ignjatovic S, Aleksandra-Postic-Grujin. Source: Clin Lab. 2002; 48(7-8): 407-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12146575&dopt=Abstract

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Assessment of periodontal conditions and systemic disease in older subjects. I. Focus on osteoporosis. Author(s): Persson RE, Hollender LG, Powell LV, MacEntee MI, Wyatt CC, Kiyak HA, Persson GR. Source: Journal of Clinical Periodontology. 2002 September; 29(9): 796-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423291&dopt=Abstract

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Assessment of prevalent and incident vertebral fractures in osteoporosis research. Author(s): Genant HK, Jergas M. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003; 14 Suppl 3: S43-55. Epub 2003 March 12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730798&dopt=Abstract

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Assessment of the relationship between dynamic pattern of nighttime levels of melatonin and chosen biochemical markers of bone metabolism in a rat model of postmenopausal osteoporosis. Author(s): Ostrowska Z, Kos-Kudla B, Swietochowska E, Marek B, Kajdaniuk D, Gorski J. Source: Neuroendocrinol Lett. 2001 April; 22(2): 129-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11335889&dopt=Abstract

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Association between long-term acitretin therapy and osteoporosis: no evidence of increased risk. Author(s): McMullen EA, McCarron P, Irvine D, Dolan OM, Allen GE. Source: Clinical and Experimental Dermatology. 2003 May; 28(3): 307-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780720&dopt=Abstract

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Association between pharmacokinetics of oral ibandronate and clinical response in bone mass and bone turnover in women with postmenopausal osteoporosis. Author(s): Ravn P, Neugebauer G, Christiansen C. Source: Bone. 2002 January; 30(1): 320-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792604&dopt=Abstract

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Association of birth weight with osteoporosis and osteoarthritis in adult twins. Author(s): Antoniades L, MacGregor AJ, Andrew T, Spector TD. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 791-6. Epub 2003 April 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730541&dopt=Abstract

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Association of the C-509-->T polymorphism, alone of in combination with the T869-->C polymorphism, of the transforming growth factor-beta1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women. Author(s): Yamada Y, Miyauchi A, Takagi Y, Tanaka M, Mizuno M, Harada A. Source: Journal of Molecular Medicine (Berlin, Germany). 2001 April; 79(2-3): 149-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357939&dopt=Abstract

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Atypical pityriasis rubra pilaris associated with arthropathy and osteoporosis: a case report with 15-year follow-up. Author(s): Behr FD, Bangert JL, Hansen RC. Source: Pediatric Dermatology. 2002 January-February; 19(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11860571&dopt=Abstract

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Audit of the diagnosis, assessment, and treatment of osteoporosis in patients with ankylosing spondylitis. Author(s): Bessant R, Harris C, Keat A. Source: The Journal of Rheumatology. 2003 April; 30(4): 779-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672199&dopt=Abstract

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Barriers to osteoporosis identification and treatment among primary care physicians and orthopedic surgeons. Author(s): Simonelli C, Killeen K, Mehle S, Swanson L. Source: Mayo Clinic Proceedings. 2002 April; 77(4): 334-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936928&dopt=Abstract

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Barriers to postfracture osteoporosis care in postmenopausal women. Author(s): Cuddihy MT. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2003 January; 18(1): 70-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534768&dopt=Abstract

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Beliefs, perceptions, and practices related to osteoporosis risk reduction among women with multiple sclerosis. Author(s): Sharts-Hopko NC, Sullivan MP. Source: Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses. 2002 November-December; 27(6): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432671&dopt=Abstract

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Beta-2 microglobulins in postmenopausal osteoporosis. Author(s): Akinci A, Ozcakar L. Source: Rheumatology International. 2002 August; 22(4): 173-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418487&dopt=Abstract

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Beyond bone mineral density-navigating the laboratory assessment of patients with osteoporosis. Author(s): Wagman RB, Marcus R. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 October; 87(10): 4429-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364412&dopt=Abstract

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Bilateral retinal detachments at birth: the osteoporosis pseudoglioma syndrome. Author(s): Wilson G, Moore A, Allgrove J. Source: The British Journal of Ophthalmology. 2001 September; 85(9): 1139. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561553&dopt=Abstract

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Bilateral transient osteoporosis of the knee in pregnancy. Author(s): Stamp L, McLean L, Stewart N, Birdsall M. Source: Annals of the Rheumatic Diseases. 2001 July; 60(7): 721-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11436862&dopt=Abstract

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Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study. Author(s): Szulc P, Munoz F, Claustrat B, Garnero P, Marchand F, Duboeuf F, Delmas PD. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 January; 86(1): 1929. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232000&dopt=Abstract

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Biochemical markers in glucocorticoid-induced osteoporosis. Author(s): Bruyere O, Stephaniak N, Reginster JY. Source: Frontiers of Hormone Research. 2002; 30: 49-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892270&dopt=Abstract

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Biochemical markers of bone formation in patients with plasma cell dyscrasias and benign osteoporosis. Author(s): Woitge HW, Horn E, Keck AV, Auler B, Seibel MJ, Pecherstorfer M. Source: Clinical Chemistry. 2001 April; 47(4): 686-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11274019&dopt=Abstract

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Biology of the basic multicellular unit and the pathophysiology of osteoporosis. Author(s): Jilka RL. Source: Medical and Pediatric Oncology. 2003 September; 41(3): 182-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868116&dopt=Abstract

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Birthweight, vitamin D receptor genotype and the programming of osteoporosis. Author(s): Dennison EM, Arden NK, Keen RW, Syddall H, Day IN, Spector TD, Cooper C. Source: Paediatric and Perinatal Epidemiology. 2001 July; 15(3): 211-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11489147&dopt=Abstract

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Bisphosphonate treatment of osteoporosis. Author(s): Watts NB. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 395-414. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916293&dopt=Abstract

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Bisphosphonates and osteoporosis. Author(s): Jenny-Avital ER. Source: The New England Journal of Medicine. 2002 June 27; 346(26): 2088-9; Author Reply 2088-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087149&dopt=Abstract

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Bisphosphonates and osteoporosis. Author(s): Treloar V. Source: The New England Journal of Medicine. 2002 June 27; 346(26): 2088-9; Author Reply 2088-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088019&dopt=Abstract

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Bisphosphonates and osteoporosis. Author(s): Solomon CG. Source: The New England Journal of Medicine. 2002 February 28; 346(9): 642. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870240&dopt=Abstract

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Bisphosphonates for osteoporosis in people with cystic fibrosis. Author(s): Brenckmann C, Papaioannou A. Source: Cochrane Database Syst Rev. 2001; (4): Cd002010. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687132&dopt=Abstract

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Bisphosphonates for prevention of postmenopausal osteoporosis. Author(s): Ravn P. Source: Dan Med Bull. 2002 February; 49(1): 1-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894721&dopt=Abstract

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Bisphosphonates for the prevention and treatment of corticosteroid-induced osteoporosis. Author(s): Miller PD. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001 December; 12 Suppl 3: S3-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846338&dopt=Abstract

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Bisphosphonates for the treatment of postmenopausal osteoporosis: clinical studies of etidronate and alendronate. Author(s): Harris ST. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001 December; 12 Suppl 3: S11-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846336&dopt=Abstract

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Bisphosphonates in bone diseases other than osteoporosis. Author(s): Orcel P, Beaudreuil J. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 January; 69(1): 19-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858352&dopt=Abstract

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Bisphosphonates in the treatment of glucocorticoid-induced osteoporosis. Author(s): Doga M, Bonadonna S, Burattin A, Carpinteri R, Manelli F, Giustina A. Source: Frontiers of Hormone Research. 2002; 30: 150-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892263&dopt=Abstract

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Bisphosphonates in the treatment of thalassemia-induced osteoporosis. Author(s): Morabito N, Lasco A, Gaudio A, Crisafulli A, Di Pietro C, Meo A, Frisina N. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 August; 13(8): 644-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181623&dopt=Abstract

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Bisphosphonates to prevent osteoporosis in men receiving androgen deprivation therapy for prostate cancer. Author(s): Smith MR. Source: Drugs & Aging. 2003; 20(3): 175-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578398&dopt=Abstract

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Bisphosphonates, a new treatment for glucocorticoid-induced osteoporosis in children. Author(s): Noguera A, Ros JB, Pavia C, Alcover E, Valls C, Villaronga M, Gonzalez E. Source: J Pediatr Endocrinol Metab. 2003 April-May; 16(4): 529-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793604&dopt=Abstract

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Bisphosphonates, statins, osteoporosis, and atherosclerosis. Author(s): Watts N. Source: Southern Medical Journal. 2002 June; 95(6): 578-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081213&dopt=Abstract

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Bone builders: preventing and treating osteoporosis. Author(s): Chan HW. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2001 August; 15(10): 1677. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481213&dopt=Abstract

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Bone builders: the discoveries behind preventing and treating osteoporosis. Author(s): Patlak M. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2001 August; 15(10): 1677E-E. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481214&dopt=Abstract

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Bone densitometry and the diagnosis of osteoporosis. Author(s): Blake GM, Fogelman I. Source: Semin Nucl Med. 2001 January; 31(1): 69-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11200207&dopt=Abstract

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Bone densitometry, steroids and osteoporosis. Author(s): Blake GM, Fogelman I. Source: Current Opinion in Nephrology and Hypertension. 2002 November; 11(6): 641-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394611&dopt=Abstract

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Bone density measurement techniques in the diagnosis and management of osteoporosis. Author(s): Chausmer AB. Source: J S C Med Assoc. 2001 March; 97(3): 106-10. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285881&dopt=Abstract

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Bone density screening for osteoporosis. Author(s): Committee on Gynecologic Practice. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 June; 77(3): 299-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150146&dopt=Abstract

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Bone histomorphometry in untreated and treated glucocorticoid-induced osteoporosis. Author(s): Dalle Carbonare L, Chavassieux PM, Arlot ME, Meunier PJ. Source: Frontiers of Hormone Research. 2002; 30: 37-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892269&dopt=Abstract

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Bone loss and recovery in regional migratory osteoporosis. Author(s): Trevisan C, Ortolani S. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 November; 13(11): 901-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415438&dopt=Abstract

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Bone matrix proteins: their function, regulation, and relationship to osteoporosis. Author(s): Young MF. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003; 14 Suppl 3: S35-42. Epub 2003 March 12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730768&dopt=Abstract

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Bone microstructure in osteoporosis: transilial biopsy and histomorphometry. Author(s): Barger-Lux MJ, Recker RR. Source: Topics in Magnetic Resonance Imaging : Tmri. 2002 October; 13(5): 297-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464743&dopt=Abstract

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Bone mineral density and dietary patterns in older adults: the Framingham Osteoporosis Study. Author(s): Tucker KL, Chen H, Hannan MT, Cupples LA, Wilson PW, Felson D, Kiel DP. Source: The American Journal of Clinical Nutrition. 2002 July; 76(1): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081842&dopt=Abstract

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Bone mineral density and grip strength in postmenopausal Turkish women with osteoporosis: site specific or systemic? Author(s): Sahin G, Duce MN, Milcan A, Bagis S, Cimen OB, Cimen B, Erdogan C. Source: Int J Fertil Womens Med. 2002 September-October; 47(5): 236-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469710&dopt=Abstract

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Bone mineral density and osteoporosis in rural and urban women. Epidemiological study of the Lublin region (Eastern Poland). Author(s): Filip RS, Zagorski J. Source: Annals of Agricultural and Environmental Medicine : Aaem. 2001; 8(2): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748880&dopt=Abstract

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Bone mineral density in acromegaly: does growth hormone excess protect against osteoporosis? Author(s): Chiodini I, Trischitta V, Carnevale V, Liuzzi A, Scillitani A. Source: J Endocrinol Invest. 2001 April; 24(4): 288-91. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383916&dopt=Abstract

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Bone mineral density of the spine, hip and distal forearm in representative samples of the Japanese female population: Japanese Population-Based Osteoporosis (JPOS) Study. Author(s): Iki M, Kagamimori S, Kagawa Y, Matsuzaki T, Yoneshima H, Marumo F. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(7): 529-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527049&dopt=Abstract

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Bone mineral density screening: assessment of influence on prevention and treatment of osteoporosis. Author(s): Anastasopoulou C, Rude RK. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2002 May-June; 8(3): 199-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113632&dopt=Abstract

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Bone scan manifestation of transient osteoporosis of the hip. Author(s): Moreno AJ, Ward DL. Source: Clinical Nuclear Medicine. 2001 October; 26(10): 872-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564932&dopt=Abstract

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Bone turnover markers and sex hormones in men with idiopathic osteoporosis. Author(s): Pietschmann P, Kudlacek S, Grisar J, Spitzauer S, Woloszczuk W, Willvonseder R, Peterlik M. Source: European Journal of Clinical Investigation. 2001 May; 31(5): 444-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380597&dopt=Abstract

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Bone-specific antibodies in sera from patients with celiac disease: characterization and implications in osteoporosis. Author(s): Sugai E, Chernavsky A, Pedreira S, Smecuol E, Vazquez H, Niveloni S, Mazure R, Mauriro E, Rabinovich GA, Bai JC. Source: Journal of Clinical Immunology. 2002 November; 22(6): 353-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462335&dopt=Abstract

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Branemark implants and osteoporosis: a clinical exploratory study. Author(s): Friberg B, Ekestubbe A, Mellstrom D, Sennerby L. Source: Clinical Implant Dentistry and Related Research. 2001; 3(1): 50-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11441543&dopt=Abstract

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Breaking bones. Prehospital care of the osteoporosis patient. Author(s): Peck B, Bruce ML. Source: Emerg Med Serv. 2003 April; 32(4): 79-80, 83-7; Quiz 96. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705223&dopt=Abstract

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By the way, doctor. I recently heard that I can take Fosamax once a week for osteoporosis, rather than every day. Is it really effective when taken this way? Is there a downside? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 May; 8(9): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410457&dopt=Abstract

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By the way, doctor. I recently read that the new osteoporosis drug Forteo is better than any available alternative. Since so many of us who are postmenopausal are at risk for osteoporosis, shouldn't we be taking it? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2003 March; 10(7): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654595&dopt=Abstract

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By the way, doctor. I recently saw a TV ad for a product called “coral calcium,” which is supposed to prevent osteoporosis and other diseases. What do you know about it? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2003 August; 10(12): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12936861&dopt=Abstract

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By the way, doctor...I'm a few years past menopause, and I take a statin because of high cholesterol. My doctor has broached the subject of whether I might need to take something else to lower my risk for osteoporosis, but I've read that statins help prevent that problem. Can't I tell the doctor I don't need another pill? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2001 May; 26(7): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11424275&dopt=Abstract

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Calcitonin for the long-term prevention and treatment of postmenopausal osteoporosis. Author(s): Body JJ. Source: Bone. 2002 May; 30(5 Suppl): 75S-79S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12008163&dopt=Abstract

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Calcitonin in glucocorticoid-induced osteoporosis. Author(s): Roux C, Dougados M. Source: Frontiers of Hormone Research. 2002; 30: 145-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892262&dopt=Abstract

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Calcitonin in osteoporosis. Author(s): Kanis JA. Source: Bone. 2002 May; 30(5 Suppl): 65S-66S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12008160&dopt=Abstract

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Calcitriol treatment of glucocorticoid-induced osteoporosis in subjects with pemphigus vulgaris. Author(s): Sivri A, Karaduman A, Gokce-Kutsal Y, Atakan N. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 January; 16(1): 89-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952306&dopt=Abstract

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Calcium and vitamin D in osteoporosis. Author(s): Morgan SL. Source: Rheumatic Diseases Clinics of North America. 2001 February; 27(1): 101-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285990&dopt=Abstract

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Calcium and vitamin D in osteoporosis: chairman's introduction to proceedings. Author(s): Francis RM. Source: Calcified Tissue International. 2002 February; 70(2): 69. Epub 2002 January 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870409&dopt=Abstract

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Calcium effects on phosphorus absorption: implications for the prevention and cotherapy of osteoporosis. Author(s): Heaney RP, Nordin BE. Source: Journal of the American College of Nutrition. 2002 June; 21(3): 239-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074251&dopt=Abstract

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Calcium, vitamin D and etidronate for the prevention and treatment of corticosteroidinduced osteoporosis in patients with rheumatic diseases. Author(s): Loddenkemper K, Grauer A, Burmester GR, Buttgereit F. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 19-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673885&dopt=Abstract

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Can biochemical markers be used to screen patients with inflammatory bowel disease for osteoporosis? Author(s): Compston JE. Source: European Journal of Gastroenterology & Hepatology. 2002 June; 14(6): 587-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072590&dopt=Abstract

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Can DHEA be used to prevent bone loss and osteoporosis? Author(s): Marcelli C. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2003 February; 70(1): 1-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639609&dopt=Abstract

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Can metacarpal cortical area predict the occurrence of hip fracture in women and men over 3 decades of follow-up? Results from the Framingham Osteoporosis Study. Author(s): Kiel DP, Hannan MT, Broe KE, Felson DT, Cupples LA. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 December; 16(12): 2260-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11760840&dopt=Abstract

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Can practitioners use the WHO definition for osteoporosis? Author(s): Roux C. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2001 February; 68(1): 10-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235774&dopt=Abstract

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Candidate genes for osteoporosis. Therapeutic implications. Author(s): Niu T, Xu X. Source: American Journal of Pharmacogenomics : Genomics-Related Research in Drug Development and Clinical Practice. 2001; 1(1): 11-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173309&dopt=Abstract

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Cardiovascular disease and osteoporosis: is there a link between lipids and bone? Author(s): Burnett JR, Vasikaran SD. Source: Annals of Clinical Biochemistry. 2002 May; 39(Pt 3): 203-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12038594&dopt=Abstract

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Case of the month. Osteoporosis in a postmenopausal woman. Author(s): Chaudhry MU. Source: J Ark Med Soc. 2002 January; 98(7): 232-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778301&dopt=Abstract

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Case studies in osteoporosis management and prevention. Author(s): Bolognese CJ. Source: Nurs Clin North Am. 2001 September; 36(3): 491-7, Ix-X. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532663&dopt=Abstract

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Cathepsin K, osteoclastic resorption, and osteoporosis therapy. Author(s): Zaidi M, Troen B, Moonga BS, Abe E. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 October; 16(10): 1747-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585336&dopt=Abstract

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Causal analysis of exercise and calcium intake behaviors for osteoporosis prevention among young women in Thailand. Author(s): Piaseu N, Schepp K, Belza B. Source: Health Care for Women International. 2002 June; 23(4): 364-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148914&dopt=Abstract

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Challenges for model-based economic evaluations of postmenopausal osteoporosis interventions. Author(s): Tosteson AN, Jonsson B, Grima DT, O'Brien BJ, Black DM, Adachi JD. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(10): 849-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716188&dopt=Abstract

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Challenges in the care of adults with osteoporosis. Author(s): Wishnia G. Source: Geriatric Nursing (New York, N.Y.). 2001 May-June; 22(3): 160-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410769&dopt=Abstract

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Changes in biochemical parameters of bone turnover and bone mineral density in post-pregnancy osteoporosis. Author(s): Honjo S, Mizunuma H. Source: American Journal of Obstetrics and Gynecology. 2001 July; 185(1): 246-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483939&dopt=Abstract

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Choosing our view of osteoporosis. Author(s): Hamdy RC. Source: Southern Medical Journal. 2001 June; 94(6): 558-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440322&dopt=Abstract

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Claims by charity exaggerate dangers of osteoporosis. Author(s): Moynihan R. Source: Bmj (Clinical Research Ed.). 2003 August 16; 327(7411): 358. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919972&dopt=Abstract

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Classification of osteoporosis based on bone mineral densities. Author(s): Lu Y, Genant HK, Shepherd J, Zhao S, Mathur A, Fuerst TP, Cummings SR. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 May; 16(5): 901-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11341335&dopt=Abstract

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Clinical challenges in osteoporosis. Case 1: screening for osteoporosis in early menopause. Author(s): Watts NB. Source: Seminars in Arthritis and Rheumatism. 2002 February; 31(4): 284-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836662&dopt=Abstract

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Clinical characteristics and etiologic factors of premenopausal osteoporosis in a group of Spanish women. Author(s): Peris P, Guanabens N, Martinez de Osaba MJ, Monegal A, Alvarez L, Pons F, Ros I, Cerda D, Munoz-Gomez J. Source: Seminars in Arthritis and Rheumatism. 2002 August; 32(1): 64-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12219322&dopt=Abstract

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Clinical decision rules in rheumatoid arthritis: do they identify patients at high risk for osteoporosis? Testing clinical criteria in a population based cohort of patients with rheumatoid arthritis recruited from the Oslo Rheumatoid Arthritis Register. Author(s): Haugeberg G, Orstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK. Source: Annals of the Rheumatic Diseases. 2002 December; 61(12): 1085-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429540&dopt=Abstract

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Clinical evaluation for osteoporosis. Author(s): Becker C. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 299-320. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916288&dopt=Abstract

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Clinical evaluation of patients with idiopathic juvenile osteoporosis. Author(s): Chlebna-Sokol D, Loba-Jakubowska E, Sikora A. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 2001 July; 10(3): 259-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497372&dopt=Abstract

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Clinical management of childhood osteoporosis. Author(s): Chan YY, Bishop NJ. Source: Int J Clin Pract. 2002 May; 56(4): 280-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074211&dopt=Abstract

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Clinical review 123: Anabolic therapy for osteoporosis. Author(s): Rosen CJ, Bilezikian JP. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 March; 86(3): 95764. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11238469&dopt=Abstract

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Clinical review 151: The role of parathyroid hormone in the pathogenesis of glucocorticoid-induced osteoporosis: a re-examination of the evidence. Author(s): Rubin MR, Bilezikian JP. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 September; 87(9): 4033-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213840&dopt=Abstract

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Clinical risk factors as predictors of postmenopausal osteoporosis in general practice. Author(s): Versluis RG, Papapoulos SE, de Bock GH, Zwinderman AH, Petri H, van de Ven CM, Springer MP. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2001 October; 51(471): 806-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11677703&dopt=Abstract

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Clinical role of quantitative ultrasound in the assessment of osteoporosis in individual patients. Author(s): Nguyen TV, Sambrook PN. Source: The Medical Journal of Australia. 2001 March 19; 174(6): 310-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297129&dopt=Abstract

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Clinical update on osteoporosis. Author(s): Koh LK. Source: Ann Acad Med Singapore. 2002 January; 31(1): 71-4; Quiz 75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885500&dopt=Abstract

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Combination therapy for postmenopausal osteoporosis. Author(s): Compston JE, Watts NB. Source: Clinical Endocrinology. 2002 May; 56(5): 565-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030903&dopt=Abstract

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Combination treatment of osteoporosis: a clinical review. Author(s): Crandall C. Source: Journal of Women's Health & Gender-Based Medicine. 2002 April; 11(3): 211-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11988132&dopt=Abstract

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Commentary on clinical safety of recombinant human parathyroid hormone 1-34 in the treatment of osteoporosis in men and postmenopausal women. Author(s): Tashjian AH Jr, Chabner BA. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 July; 17(7): 1151-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096828&dopt=Abstract

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Community-based exercise program reduces risk factors for falls in 65- to 75-year-old women with osteoporosis: randomized controlled trial. Author(s): Carter ND, Khan KM, McKay HA, Petit MA, Waterman C, Heinonen A, Janssen PA, Donaldson MG, Mallinson A, Riddell L, Kruse K, Prior JC, Flicker L. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 October 29; 167(9): 997-1004. Erratum In: Cmaj. 2003 January 21; 168(2): 152. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403738&dopt=Abstract

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Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy. Author(s): Cortet B, Bera-Louville A, Gauthier P, Gauthier A, Marchandise X, Delcambre B. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2001 October; 68(5): 410-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707007&dopt=Abstract

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Comparative safety of bone remodeling agents with a focus on osteoporosis therapies. Author(s): Kleerekoper M, Schein JR. Source: Journal of Clinical Pharmacology. 2001 March; 41(3): 239-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11269564&dopt=Abstract

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Comparing screening methods for osteoporosis. Author(s): Placide J, Martens MG. Source: Curr Womens Health Rep. 2003 June; 3(3): 207-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734031&dopt=Abstract

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Comparing therapies for postmenopausal osteoporosis prevention and treatment. Author(s): Eichner SF, Lloyd KB, Timpe EM. Source: The Annals of Pharmacotherapy. 2003 May; 37(5): 711-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708951&dopt=Abstract

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Comparison of alendronate, calcitonin and calcium treatments in postmenopausal osteoporosis. Author(s): Dursun N, Dursun E, Yalcin S. Source: Int J Clin Pract. 2001 October; 55(8): 505-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11695068&dopt=Abstract

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Comparison of calcaneal ultrasound and DXA to assess the risk of corticosteroidinduced osteoporosis: a cross-sectional study. Author(s): Javaid MK, McCrudden PR, Taylor P, Petley GW, Stroud M, Fine DR, Cooper C, Arden NK. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(9): 788-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605746&dopt=Abstract

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Comparison of heel ultrasound and finger DXA to central DXA in the detection of osteoporosis. Implications for patient management. Author(s): Bachman DM, Crewson PE, Lewis RS. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002 Summer; 5(2): 131-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110756&dopt=Abstract

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Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis. Author(s): Kawana K, Takahashi M, Hoshino H, Kushida K. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 February; 316(1-2): 109-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750280&dopt=Abstract

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Comparison of trabecular bone microarchitecture and remodeling in glucocorticoidinduced and postmenopausal osteoporosis. Author(s): Dalle Carbonare L, Arlot ME, Chavassieux PM, Roux JP, Portero NR, Meunier PJ. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 January; 16(1): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149495&dopt=Abstract

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Computed tomography image analysis of the calcaneus in male osteoporosis. Author(s): Cortet B, Dubois P, Boutry N, Palos G, Cotten A, Marchandise X. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 January; 13(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11878453&dopt=Abstract

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Consensus statement on the modern therapy of Paget's disease of bone from a Western Osteoporosis Alliance symposium. Biannual Foothills Meeting on Osteoporosis, Calgary, Alberta, Canada, September 9-10, 2000. Author(s): Drake WM, Kendler DL, Brown JP. Source: Clinical Therapeutics. 2001 April; 23(4): 620-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11354395&dopt=Abstract

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COPD and osteoporosis. Author(s): Biskobing DM. Source: Chest. 2002 February; 121(2): 609-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834678&dopt=Abstract

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Correct regimen of fluoride and calcium reduces the risk of vertebral fractures in postmenopausal osteoporosis. Author(s): Reginster JY, Rovati LC, Setnikar I. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(9): 800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605748&dopt=Abstract

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Correlates of osteoporosis among Jewish and Arab women aged 45-74 in Israel: national women's health interview survey. Author(s): Nitzan-Kaluski D, Chinich A, Ifrah A, Merom D, Green MS. Source: J Gend Specif Med. 2003; 6(1): 17-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661173&dopt=Abstract

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Corticosteroid induced osteoporosis. Guidelines for treatment. Author(s): Sambrook PN, Diamond T, Ferris L, Fiatarone-Singh M, Flicker L, MacLennan A, Nowson C, O'Neill S, Greville H; Osteoporosis Australia; National Asthma Campaign. Source: Aust Fam Physician. 2001 August; 30(8): 793-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11681155&dopt=Abstract

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Corticosteroid osteoporosis. Author(s): Sambrook P, Lane NE. Source: Best Practice & Research. Clinical Rheumatology. 2001 July; 15(3): 401-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485337&dopt=Abstract

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Corticosteroid-induced osteoporosis in patients with uveitis. Author(s): Jones NP, Anderton LC, Cheong FM, Whallett A, Stanford MR, Murray PI, Lesnik-Oberstein S, Pavesio C. Source: Eye (London, England). 2002 September; 16(5): 587-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194074&dopt=Abstract

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Corticosteroid-induced osteoporosis. Author(s): Lucasey B. Source: Nurs Clin North Am. 2001 September; 36(3): 455-66, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532660&dopt=Abstract

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Corticosteroid-induced osteoporosis. Author(s): Legerton CW 3rd. Source: J S C Med Assoc. 2001 March; 97(3): 111-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285882&dopt=Abstract

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Corticosteroid-induced osteoporosis. Author(s): Adachi JD. Source: Int J Fertil Womens Med. 2001 July-August; 46(4): 190-205. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563829&dopt=Abstract

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Corticosteroid-induced osteoporosis: does it occur in patients with Crohn's disease? Author(s): de Jong DJ, Corstens FH, Mannaerts L, van Rossum LG, Naber AH. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2011-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190169&dopt=Abstract

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Cost effectiveness of alendronate (fosamax) for the treatment of osteoporosis and prevention of fractures. Author(s): Johnell O, Jonsson B, Jonsson L, Black D. Source: Pharmacoeconomics. 2003; 21(5): 305-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627984&dopt=Abstract

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Costs and strategies in minority recruitment for osteoporosis research. Author(s): Marquez MA, Muhs JM, Tosomeen A, Riggs BL, Melton LJ 3rd. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 January; 18(1): 3-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510799&dopt=Abstract

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Counseling female athletes: application of the stages of change model to avoid disordered eating, amenorrhea, and osteoporosis. Author(s): Bass M, Turner L, Hunt S. Source: Psychological Reports. 2001 June; 88(3 Pt 2): 1153-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11597070&dopt=Abstract

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CRA endorsement of osteoporosis guidelines. Author(s): Pope J. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 March 18; 168(6): 672. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642415&dopt=Abstract

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Cross-sectional and longitudinal study of osteoporosis in patients with rheumatoid arthritis. Author(s): Shibuya K, Hagino H, Morio Y, Teshima R. Source: Clinical Rheumatology. 2002 May; 21(2): 150-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086167&dopt=Abstract

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Current and emerging therapies in osteoporosis. Author(s): DeSantis A, Buchman A. Source: Expert Opinion on Pharmacotherapy. 2002 July; 3(7): 835-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083984&dopt=Abstract

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Current approaches to the prevention and treatment of postmenopausal osteoporosis. Author(s): Follin SL, Hansen LB. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 May 1; 60(9): 883-901; Quiz 903-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756940&dopt=Abstract

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Current consensus recommendations for rheumatoid arthritis therapy: a blind spot for osteoporosis prevention and treatment. Author(s): Jolles BM, Bogoch ER. Source: The Journal of Rheumatology. 2002 September; 29(9): 1814-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233871&dopt=Abstract

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Cybernetic aspects of bone modeling and remodeling, with special reference to osteoporosis and whole-bone strength. Author(s): Frost HM. Source: American Journal of Human Biology : the Official Journal of the Human Biology Council. 2001 March-April; 13(2): 235-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11460869&dopt=Abstract

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Daily oral pamidronate in women and men with osteoporosis: a 3-year randomized placebo-controlled clinical trial with a 2-year open extension. Author(s): Brumsen C, Papapoulos SE, Lips P, Geelhoed-Duijvestijn PH, Hamdy NA, Landman JO, McCloskey EV, Netelenbos JC, Pauwels EK, Roos JC, Valentijn RM, Zwinderman AH. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 June; 17(6): 1057-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054161&dopt=Abstract

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Daily treatment with parathyroid hormone is associated with an increase in vertebral cross-sectional area in postmenopausal women with glucocorticoid-induced osteoporosis. Author(s): Rehman Q, Lang TF, Arnaud CD, Modin GW, Lane NE. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 January; 14(1): 77-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577188&dopt=Abstract

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Decreased bone density in carriers and patients of an Israeli family with the osteoporosis-pseudoglioma syndrome. Author(s): Lev D, Binson I, Foldes AJ, Watemberg N, Lerman-Sagie T. Source: Isr Med Assoc J. 2003 June; 5(6): 419-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841014&dopt=Abstract

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Deficient acquisition of bone during maturation underlies idiopathic osteoporosis in men: evidence from a three-generation family study. Author(s): Van Pottelbergh I, Goemaere S, Zmierczak H, De Bacquer D, Kaufman JM. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 February; 18(2): 303-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568407&dopt=Abstract

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Defining the genetics of osteoporosis: using the mouse to understand man. Author(s): Rosen CJ, Beamer WG, Donahue LR. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(10): 803-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716182&dopt=Abstract

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Delayed vertebral collapse with neurological deficits secondary to osteoporosis. Author(s): Kim KT, Suk KS, Kim JM, Lee SH. Source: International Orthopaedics. 2003; 27(2): 65-9. Epub 2003 March 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700926&dopt=Abstract

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Densitometric diagnosis of osteoporosis in men: effect of measurement site and normative database. Author(s): Vallarta-Ast N, Krueger D, Binkley N. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002 Winter; 5(4): 383-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665639&dopt=Abstract

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Depression: a major, unrecognized risk factor for osteoporosis? Author(s): Cizza G, Ravn P, Chrousos GP, Gold PW. Source: Trends in Endocrinology and Metabolism: Tem. 2001 July; 12(5): 198-203. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11397644&dopt=Abstract

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Depressive disorder as possible risk factor of osteoporosis. Author(s): Vrkljan M, Thaller V, Lovricevic I, Gacina P, Resetic J, Bekic M, Sonicki Z. Source: Coll Antropol. 2001 December; 25(2): 485-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11811278&dopt=Abstract

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Design and methodology of the phase 3 trials for the clinical development of strontium ranelate in the treatment of women with postmenopausal osteoporosis. Author(s): Meunier PJ, Reginster JY. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003; 14 Suppl 3: S66-76. Epub 2003 March 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730769&dopt=Abstract

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Detection of osteoporosis by dual energy X-ray absorptiometry (DXA) of the calcaneus: is the WHO criterion applicable? Author(s): Pacheco EM, Harrison EJ, Ward KA, Lunt M, Adams JE. Source: Calcified Tissue International. 2002 June; 70(6): 475-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960208&dopt=Abstract

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Determinants of fracture risk in osteoporosis. Author(s): Harvey N, Cooper C. Source: Curr Rheumatol Rep. 2003 February; 5(1): 75-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590888&dopt=Abstract

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Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS). Author(s): Roy DK, O'Neill TW, Finn JD, Lunt M, Silman AJ, Felsenberg D, Armbrecht G, Banzer D, Benevolenskaya LI, Bhalla A, Bruges Armas J, Cannata JB, Cooper C, Dequeker J, Diaz MN, Eastell R, Yershova OB, Felsch B, Gowin W, Havelka S, Hoszowski K, Ismail AA, Jajic I, Janott I, Johnell O, Kanis JA, Kragl G, Lopez Vaz A, Lorenc R, Lyritis G, Masaryk P, Matthis C, Miazgowski T, Gennari C, Pols HA, Poor G, Raspe HH, Reid DM, Reisinger W, Scheidt-Nave C, Stepan JJ, Todd CJ, Weber K, Woolf AD, Reeve J; European Prospective Osteoporosis Study (EPOS). Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 January; 14(1): 19-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577181&dopt=Abstract

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Determinants of osteoporosis prevention in low-income Mexican-American women. Author(s): Orces CH, Casas C, Lee S, Garci-Cavazos R, White W. Source: Southern Medical Journal. 2003 May; 96(5): 458-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911184&dopt=Abstract

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Developing profiles of postmenopausal women being prescribed estrogen therapy to prevent osteoporosis. Author(s): Amonkar MM, Mody R. Source: Journal of Community Health. 2002 October; 27(5): 335-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12238732&dopt=Abstract

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Development and assessment of the Osteoporosis Index of Risk (OSIRIS) to facilitate selection of women for bone densitometry. Author(s): Sedrine WB, Chevallier T, Zegels B, Kvasz A, Micheletti MC, Gelas B, Reginster JY. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 June; 16(3): 245-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192897&dopt=Abstract

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Development and pilot testing of a decision aid for postmenopausal women with osteoporosis. Author(s): Cranney A, O'Connor AM, Jacobsen MJ, Tugwell P, Adachi JD, Ooi DS, Waldegger L, Goldstein R, Wells GA. Source: Patient Education and Counseling. 2002 July; 47(3): 245-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088603&dopt=Abstract

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Development and validation of a specific quality of life module in post-menopausal women with osteoporosis: the QUALIOST. Author(s): Marquis P, Cialdella P, De la Loge C. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2001; 10(6): 555-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789555&dopt=Abstract

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Development of a short osteoporosis quality of life questionnaire by equating items from two existing instruments. Author(s): Badia X, Prieto L, Roset M, Diez-Perez A, Herdman M. Source: Journal of Clinical Epidemiology. 2002 January; 55(1): 32-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781120&dopt=Abstract

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Diabetes mellitus a risk for osteoporosis? Author(s): Leidig-Bruckner G, Ziegler R. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2001; 109 Suppl 2: S493514. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11460594&dopt=Abstract

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Diagnosing osteoporosis in Japanese American women. Author(s): Rice MM, Larson EB, LaCroix AZ, Drinkwater BL. Source: The American Journal of Medicine. 2001 February 15; 110(3): 241-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221637&dopt=Abstract

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Diagnosis and management of treatment-related osteoporosis in men with prostate carcinoma. Author(s): Smith MR. Source: Cancer. 2003 February 1; 97(3 Suppl): 789-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548577&dopt=Abstract

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Diagnosis and treatment of osteoporosis in patients with vertebral compression fractures. Author(s): Neuner JM, Zimmer JK, Hamel MB. Source: Journal of the American Geriatrics Society. 2003 April; 51(4): 483-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657067&dopt=Abstract

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Diagnosis and treatment of osteoporosis. Author(s): Wilson A. Source: British Journal of Community Nursing. 2001 October; 6(10): 535-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832812&dopt=Abstract

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Diagnosis of osteoporosis and assessment of fracture risk. Author(s): Kanis JA. Source: Lancet. 2002 June 1; 359(9321): 1929-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12057569&dopt=Abstract

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Diagnosis of osteoporosis and fracture threshold in men. Author(s): Kanis JA, Johnell O, Oden A, De Laet C, Mellstrom D. Source: Calcified Tissue International. 2001 October; 69(4): 218-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730254&dopt=Abstract

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Diagnosis of postmenopausal osteoporosis: reviews in endocrine and metabolic disorders. Author(s): Shields AT, Chesnut CH 3rd. Source: Reviews in Endocrine & Metabolic Disorders. 2001 January; 2(1): 23-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704977&dopt=Abstract

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Diagnosis, treatment and management of osteoporosis in the orthopaedic setting. Author(s): Murphy D, Rice J, McElwain JP. Source: Ir Med J. 2001 October; 94(9): 262-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11820514&dopt=Abstract

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Diagnostic challenges in osteoporosis. Indications for bone densitometry and establishing secondary causes. Author(s): Karsh J. Source: Can Fam Physician. 2001 June; 47: 1244-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421053&dopt=Abstract

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Diagnostic criteria for primary osteoporosis: year 2000 revision. Author(s): Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujiwara S, Shiraki M, Kushida K, Miyamoto S, Soen S, Nishimura J, Oh-Hashi Y, Hosoi T, Gorai I, Tanaka H, Igai T, Kishimoto H; Osteoporosis Diagnostic Criteria Review Committee: Japanese Society for Bone and Mineral Research. Source: Journal of Bone and Mineral Metabolism. 2001; 19(6): 331-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685647&dopt=Abstract

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Diethylstilbesterol revisited: androgen deprivation, osteoporosis and prostate cancer. Author(s): Scherr D, Pitts WR Jr, Vaughn ED Jr. Source: The Journal of Urology. 2002 February; 167(2 Pt 1): 535-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792913&dopt=Abstract

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Different effects of antiresorptive therapies on vertebral and nonvertebral fractures in postmenopausal osteoporosis. Author(s): Delmas PD. Source: Bone. 2002 January; 30(1): 14-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792559&dopt=Abstract

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Differential diagnosis of osteoporosis. Author(s): Freitag A, Barzel US. Source: Gerontology. 2002 March-April; 48(2): 98-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867932&dopt=Abstract

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Digital topological analysis of in vivo magnetic resonance microimages of trabecular bone reveals structural implications of osteoporosis. Author(s): Wehrli FW, Gomberg BR, Saha PK, Song HK, Hwang SN, Snyder PJ. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 August; 16(8): 1520-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499875&dopt=Abstract

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Directions of drug discovery in osteoporosis. Author(s): Mundy GR. Source: Annual Review of Medicine. 2002; 53: 337-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818478&dopt=Abstract

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Direct-to-consumer marketing of osteoporosis drugs and bone densitometry. Author(s): Hollon MF, Larson EB, Koepsell TD, Downer AE. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 976-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841803&dopt=Abstract

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Discordance between changes in bone mineral density measured at different skeletal sites in perimenopausal women--implications for assessment of bone loss and response to therapy: The Danish Osteoporosis Prevention Study. Author(s): Abrahamsen B, Stilgren LS, Hermann AP, Tofteng CL, Barenholdt O, Vestergaard P, Brot C, Nielsen SP. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 July; 16(7): 1212-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450696&dopt=Abstract

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Discrimination of changes in osteoporosis outcomes. Author(s): Cranney A, Welch V, Wells G, Adachi J, Shea B, Simon L, Tugwell P. Source: The Journal of Rheumatology. 2001 February; 28(2): 413-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11246689&dopt=Abstract

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Discriminatory ability of quantitative ultrasound parameters and bone mineral density in a population-based sample of postmenopausal women with vertebral fractures: results of the Basel Osteoporosis Study. Author(s): Hartl F, Tyndall A, Kraenzlin M, Bachmeier C, Guckel C, Senn U, Hans D, Theiler R. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 February; 17(2): 321-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11811563&dopt=Abstract

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Distal forearm fracture history in an older community-dwelling population: the Nottingham Community Osteoporosis (NOCOS) study. Author(s): Masud T, Jordan D, Hosking DJ. Source: Age and Ageing. 2001 May; 30(3): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11443028&dopt=Abstract

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Distinguishing transient osteoporosis of the hip from avascular necrosis. Author(s): Balakrishnan A, Schemitsch EH, Pearce D, McKee MD. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 2003 June; 46(3): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812240&dopt=Abstract

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Disuse osteoporosis as evidence of brachial plexus palsy due to intrauterine fetal maladaptation. Author(s): Jennett RJ, Tarby TJ. Source: American Journal of Obstetrics and Gynecology. 2001 July; 185(1): 236-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483934&dopt=Abstract

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Disuse osteoporosis. Author(s): Takata S, Yasui N. Source: J Med Invest. 2001 August; 48(3-4): 147-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694954&dopt=Abstract

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Do the COL1A1 and Taq 1 vitamin D receptor polymorphisms have a role in identifying individuals at risk of developing osteoporosis? Author(s): McClean E, Archbold GP, Taggart HM. Source: Ulster Med J. 2003 May; 72(1): 26-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868700&dopt=Abstract

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Documentation of preventive education and screening for osteoporosis. Author(s): De Villers MJ. Source: Outcomes Management. 2003 January-March; 7(1): 28-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593123&dopt=Abstract

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Does milk intake in childhood protect against later osteoporosis? Author(s): Tucker KL. Source: The American Journal of Clinical Nutrition. 2003 January; 77(1): 10-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499317&dopt=Abstract

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Does osteoporosis classification using heel BMD agree across manufacturers? Author(s): Grigorian M, Shepherd JA, Cheng XG, Njeh CF, Toschke JO, Genant HK. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 August; 13(8): 613-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181618&dopt=Abstract

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Does patient partnership in continuing medical education (CME) improve the outcome in osteoporosis management? Author(s): Pazirandeh M. Source: The Journal of Continuing Education in the Health Professions. 2002 Summer; 22(3): 142-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227236&dopt=Abstract

Studies 193

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Does raloxifene reduce risk of vertebral fractures? Is this another, brighter way to treat osteoporosis? Author(s): Hathirat S, Evans MF. Source: Can Fam Physician. 2001 October; 47: 1982-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723592&dopt=Abstract

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Dose-response of physical activity and low back pain, osteoarthritis, and osteoporosis. Author(s): Vuori IM. Source: Medicine and Science in Sports and Exercise. 2001 June; 33(6 Suppl): S551-86; Discussion 609-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427782&dopt=Abstract

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Dual-energy X-ray absorptiometry in diagnosis of osteoporosis: basic principles, indications, and scan interpretation. Author(s): Theodorou DJ, Theodorou SJ, Sartoris DJ. Source: Compr Ther. 2002 Fall; 28(3): 190-200. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360631&dopt=Abstract

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DXA in the diagnosis of glucocorticoid-induced osteoporosis. Author(s): Bianchi G, Girasole G, Sinigaglia L. Source: Frontiers of Hormone Research. 2002; 30: 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892260&dopt=Abstract

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DXA scanning to diagnose osteoporosis: do you know what the results mean? Author(s): Richmond B. Source: Cleve Clin J Med. 2003 April; 70(4): 353-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701991&dopt=Abstract

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Dynamic pattern of IGF-I and chosen biochemical markers of bone metabolism in a rat model of postmenopausal osteoporosis. Author(s): Ostrowska Z, Kos-Kudla B, Marek B, Kajdaniuk D, Ciesielska-Kopacz N. Source: Endocrine Regulations. 2002 March; 36(1): 9-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971746&dopt=Abstract

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Early discontinuation of treatment for osteoporosis. Author(s): Tosteson AN, Grove MR, Hammond CS, Moncur MM, Ray GT, Hebert GM, Pressman AR, Ettinger B. Source: The American Journal of Medicine. 2003 August 15; 115(3): 209-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947959&dopt=Abstract

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Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with osteoporosis. Author(s): Maricic M, Adachi JD, Sarkar S, Wu W, Wong M, Harper KD. Source: Archives of Internal Medicine. 2002 May 27; 162(10): 1140-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020184&dopt=Abstract

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Early response to alendronate after treatment with etidronate in postmenopausal women with osteoporosis. Author(s): Iwamoto J, Takeda T, Ichimura S, Uzawa M. Source: Keio J Med. 2003 June; 52(2): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862363&dopt=Abstract

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Economic evaluation of interventions for osteoporosis. Author(s): Kanis JA, Jonsson B. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 October; 13(10): 765-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378364&dopt=Abstract

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Effect of alendronate on bone mineral density in male idiopathic osteoporosis. Author(s): Weber TJ, Drezner MK. Source: Metabolism: Clinical and Experimental. 2001 August; 50(8): 912-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474478&dopt=Abstract

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Effect of daily and intermittent use of ibandronate on bone mass and bone turnover in postmenopausal osteoporosis: a review of three phase II studies. Author(s): Schimmer RC, Bauss F. Source: Clinical Therapeutics. 2003 January; 25(1): 19-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637110&dopt=Abstract

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Effect of estrogen replacement plus low-dose alendronate treatment on bone density in surgically postmenopausal women with osteoporosis. Author(s): Palomba S, Orio F Jr, Colao A, di Carlo C, Sena T, Lombardi G, Zullo F, Mastrantonio P. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 April; 87(4): 1502-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932272&dopt=Abstract

Studies 195

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Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis. Author(s): Iwamoto J, Takeda T, Ichimura S. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2001; 6(2): 128-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11484097&dopt=Abstract

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Effect of high doses of oral risedronate (20 mg/day) on serum parathyroid hormone levels and urinary collagen cross-link excretion in postmenopausal women with spinal osteoporosis. Author(s): Zegels B, Eastell R, Russell RG, Ethgen D, Roumagnac I, Collette J, Reginster JY. Source: Bone. 2001 January; 28(1): 108-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165950&dopt=Abstract

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Effect of intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis. Author(s): Shiota E, Tsuchiya K, Yamaoka K, Kawano O. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2001; 6(2): 133-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11484098&dopt=Abstract

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Effect of low-dose of recombinant human growth hormone on bone metabolism in elderly women with osteoporosis. Author(s): Sugimoto T, Kaji H, Nakaoka D, Yamauchi M, Yano S, Sugishita T, Baylink DJ, Mohan S, Chihara K. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 September; 147(3): 339-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213671&dopt=Abstract

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Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate. Author(s): Iwamoto J, Takeda T, Ichimura S. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2001; 6(6): 487-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793169&dopt=Abstract

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Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. Author(s): Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Source: The New England Journal of Medicine. 2001 May 10; 344(19): 1434-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11346808&dopt=Abstract

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Effect of pregnancy on bone mineral density and biochemical markers of bone turnover in a patient with juvenile idiopathic osteoporosis. Author(s): Black AJ, Reid R, Reid DM, MacDonald AG, Fraser WD. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 January; 18(1): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510820&dopt=Abstract

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Effect of raloxifene on sexual function in older postmenopausal women with osteoporosis. Author(s): Modugno F, Ness RB, Ewing S, Cauley JA. Source: Obstetrics and Gynecology. 2003 February; 101(2): 353-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576261&dopt=Abstract

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Effect of transplantation on bone: osteoporosis after liver and multivisceral transplantation. Author(s): Hommann M, Abendroth K, Lehmann G, Patzer N, Kornberg A, Voigt R, Seifert S, Hein G, Scheele J. Source: Transplantation Proceedings. 2002 September; 34(6): 2296-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270405&dopt=Abstract

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Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes. Author(s): Palomba S, Numis FG, Mossetti G, Rendina D, Vuotto P, Russo T, Zullo F, Nappi C, Nunziata V. Source: Clinical Endocrinology. 2003 March; 58(3): 365-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608943&dopt=Abstract

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Effects of 5-year treatment with elcatonin and alfacalcidol on lumbar bone mineral density and the incidence of vertebral fractures in postmenopausal women with osteoporosis: a retrospective study. Author(s): Iwamoto J, Takeda T, Ichimura S, Uzawa M. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2002; 7(6): 637-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486466&dopt=Abstract

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Effects of an osteoporosis prevention program incorporating tailored educational materials. Author(s): Blalock SJ, DeVellis BM, Patterson CC, Campbell MK, Orenstein DR, Dooley MA. Source: Am J Health Promot. 2002 January-February; 16(3): 146-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11802260&dopt=Abstract

Studies 197

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Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study. Author(s): Ebeling PR, Wark JD, Yeung S, Poon C, Salehi N, Nicholson GC, Kotowicz MA. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 September; 86(9): 4098-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11549632&dopt=Abstract

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Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis. Author(s): McCloskey E, Selby P, de Takats D, Bernard J, Davies M, Robinson J, Francis R, Adams J, Pande K, Beneton M, Jalava T, Loyttyniemi E, Kanis JA. Source: Bone. 2001 March; 28(3): 310-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11248662&dopt=Abstract

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Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. Author(s): Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L, Shane E, Plavetic K, Muller R, Bilezikian J, Lindsay R. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 October; 16(10): 1846-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585349&dopt=Abstract

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Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. Author(s): Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 11506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629098&dopt=Abstract

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Effects of long-term risedronate on bone quality and bone turnover in women with postmenopausal osteoporosis. Author(s): Eriksen EF, Melsen F, Sod E, Barton I, Chines A. Source: Bone. 2002 November; 31(5): 620-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477578&dopt=Abstract

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Effects of oral alendronate in elderly patients with osteoporosis and mild primary hyperparathyroidism. Author(s): Rossini M, Gatti D, Isaia G, Sartori L, Braga V, Adami S. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 January; 16(1): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149474&dopt=Abstract

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Effects of osthole on postmenopausal osteoporosis using ovariectomized rats; comparison to the effects of estradiol. Author(s): Li XX, Hara I, Matsumiya T. Source: Biological & Pharmaceutical Bulletin. 2002 June; 25(6): 738-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081139&dopt=Abstract

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Effects of projective bone area size of the spine on bone density and the diagnosis of osteoporosis in healthy pre-menopausal women in China. Author(s): Wu XP, Liao EY, Dai RC, Luo XH, Zhang H. Source: The British Journal of Radiology. 2003 July; 76(907): 452-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857704&dopt=Abstract

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Effects of raloxifene on fracture severity in postmenopausal women with osteoporosis: results from the MORE study. Multiple Outcomes of Raloxifene Evaluation. Author(s): Siris E, Adachi JD, Lu Y, Fuerst T, Crans GG, Wong M, Harper KD, Genant HK. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 November; 13(11): 907-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415439&dopt=Abstract

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Effects of the combined use of calcitonin and 1 alpha-hydroxycholecalciferol on vertebral bone loss and bone turnover in women with postmenopausal osteopenia and osteoporosis: a prospective study of long-term and continuous administration with low dose calcitonin. Author(s): Ushiroyama T, Ikeda A, Sakai M, Higashiyama T, Ueki M. Source: Maturitas. 2001 December 14; 40(3): 229-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731184&dopt=Abstract

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Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children. Author(s): Stuart M. Source: Clinical Pediatrics. 2002 June; 41(5): 362-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086205&dopt=Abstract

Studies 199

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Efficacy of HMG-CoA reductase inhibitors in treating osteoporosis. Author(s): Richard AA, Harrison TM. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 February 15; 59(4): 372-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885403&dopt=Abstract

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Efficacy of low-intensity pulsed ultrasound in the prevention of osteoporosis following spinal cord injury. Author(s): Warden SJ, Bennell KL, Matthews B, Brown DJ, McMeeken JM, Wark JD. Source: Bone. 2001 November; 29(5): 431-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704494&dopt=Abstract

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Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. Author(s): Delmas PD, Ensrud KE, Adachi JD, Harper KD, Sarkar S, Gennari C, Reginster JY, Pols HA, Recker RR, Harris ST, Wu W, Genant HK, Black DM, Eastell R; Mulitple Outcomes of Raloxifene Evaluation Investigators. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 August; 87(8): 3609-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161484&dopt=Abstract

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EMEA guidelines for trials in osteoporosis: design implications. Author(s): Boers M. Source: The Netherlands Journal of Medicine. 2002 September; 60(8): 310-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481877&dopt=Abstract

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Emerging anabolic treatments for osteoporosis. Author(s): Rosen CJ, Rackoff PJ. Source: Rheumatic Diseases Clinics of North America. 2001 February; 27(1): 215-33, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285997&dopt=Abstract

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Emerging therapies in osteoporosis. Author(s): MacDonald BR, Gowen M. Source: Best Practice & Research. Clinical Rheumatology. 2001 July; 15(3): 483-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485342&dopt=Abstract

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Endocrine causes of age-related bone loss and osteoporosis. Author(s): Riggs BL. Source: Novartis Found Symp. 2002; 242: 247-59; Discussion 260-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855691&dopt=Abstract

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Epidemiology of glucocorticoid-induced osteoporosis. Author(s): Dennison E, Cooper C. Source: Frontiers of Hormone Research. 2002; 30: 121-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892258&dopt=Abstract

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Epidemiology of osteoporosis. Author(s): Jordan KM, Cooper C. Source: Best Practice & Research. Clinical Rheumatology. 2002 December; 16(5): 795-806. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473274&dopt=Abstract

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Epidemiology of osteoporosis. Author(s): Lau EM. Source: Best Practice & Research. Clinical Rheumatology. 2001 July; 15(3): 335-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485333&dopt=Abstract

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Epidemiology of osteoporosis. Author(s): Boyle P, Leon ME, Autier P. Source: Journal of Epidemiology and Biostatistics. 2001; 6(2): 185-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434498&dopt=Abstract

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Epidemiology of osteoporosis. Author(s): Walker-Bone K, Dennison E, Cooper C. Source: Rheumatic Diseases Clinics of North America. 2001 February; 27(1): 1-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285989&dopt=Abstract

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Estimation of the rate of osteogenesis by tetracycline double labeling in intertrochanteric fractures of the femur in different age groups and its correlation with radiological grading of osteoporosis. Author(s): Singh S, Jain AK, Arora A, Khanna J, Bhargava SK, Kumar S. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2002; 7(2): 226-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956983&dopt=Abstract

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Estrogen therapy for prevention and treatment of osteoporosis. Author(s): Doren M. Source: Maturitas. 2002 August 30; 43 Suppl 1: S53-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361888&dopt=Abstract

Studies 201

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Etidronate for treating and preventing postmenopausal osteoporosis. Author(s): Cranney A, Welch V, Adachi JD, Guyatt G, Krolicki N, Griffith L, Shea B, Tugwell P, Wells G. Source: Cochrane Database Syst Rev. 2001; (4): Cd003376. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687195&dopt=Abstract

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Evaluating and managing osteoporosis in men. Author(s): Lawson MT. Source: The Nurse Practitioner. 2001 May; 26(5): 26, 29-36, 43-4 Passim; Quiz 49-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383493&dopt=Abstract

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Evaluation and management of osteoporosis following hospitalization for low-impact fracture. Author(s): Simonelli C, Chen YT, Morancey J, Lewis AF, Abbott TA. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2003 January; 18(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534759&dopt=Abstract

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Evaluation and treatment of postmenopausal osteoporosis. Author(s): Wang CY, Bruder JM, Rubin CD. Source: Am J Manag Care. 2001 September 25; 7 Spec No: Sp5-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599675&dopt=Abstract

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Evaluation of a fully automated serum assay for C-terminal cross-linking telopeptide of type I collagen in osteoporosis. Author(s): Garnero P, Borel O, Delmas PD. Source: Clinical Chemistry. 2001 April; 47(4): 694-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11274020&dopt=Abstract

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Evaluation of an osteoporosis workshop for women. Author(s): Ribeiro V, Blakeley JA. Source: Public Health Nursing (Boston, Mass.). 2001 May-June; 18(3): 186-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359620&dopt=Abstract

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Evaluation of calcaneus bone densitometry against hip and spine for diagnosis of osteoporosis. Author(s): Williams ED, Daymond TJ. Source: The British Journal of Radiology. 2003 February; 76(902): 123-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642281&dopt=Abstract

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Evaluation of osteoporosis in orthopedic practice: a review of current diagnostic modalities. Author(s): Theodorou SJ, Theodorou DJ, Sartoris DJ. Source: Am J Orthop. 2003 April; 32(4): 178-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723769&dopt=Abstract

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Evaluation of osteoporosis in thalassemia by quantitative computed tomography: is it reliable? Author(s): Akpek S, Canatan D, Arac M, Ilgit ET. Source: Pediatric Hematology and Oncology. 2001 March; 18(2): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255728&dopt=Abstract

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Evaluation of osteoporosis treatment in seniors after hip fracture. Author(s): Juby AG, De Geus-Wenceslau CM. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 March; 13(3): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991439&dopt=Abstract

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Evaluation of the simple calculated osteoporosis risk estimation (SCORE) in a sample of white women from Belgium. Author(s): Ben Sedrine W, Devogelaer JP, Kaufman JM, Goemaere S, Depresseux G, Zegels B, Deroisy R, Reginster JY. Source: Bone. 2001 October; 29(4): 374-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595621&dopt=Abstract

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Examination, prevention and treatment of osteoporosis in patients with inflammatory bowel disease: recommendations and reality. Author(s): Kirchgatterer A, Wenzl HH, Aschl G, Hinterreiter M, Stadler B, Hinterleitner TA, Petritsch W, Knoflach P. Source: Acta Medica Austriaca. 2002; 29(4): 120-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424936&dopt=Abstract

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Exercise and osteoporosis. Author(s): O'Brien M. Source: Ir J Med Sci. 2001 January-March; 170(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440416&dopt=Abstract

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Exercise for preventing and treating osteoporosis in postmenopausal women. Author(s): Bonaiuti D, Shea B, Iovine R, Negrini S, Robinson V, Kemper HC, Wells G, Tugwell P, Cranney A. Source: Cochrane Database Syst Rev. 2002; (3): Cd000333. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137611&dopt=Abstract

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Exercise in the prevention and treatment of osteoporosis: the role of physical therapy and nursing. Author(s): Hertel KL, Trahiotis MG. Source: Nurs Clin North Am. 2001 September; 36(3): 441-53, Viii-Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532659&dopt=Abstract

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Expanding the role of the orthopaedic surgeon in the treatment of osteoporosis. Author(s): Rosier RN. Source: Clinical Orthopaedics and Related Research. 2001 April; (385): 57-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302327&dopt=Abstract

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Expressing effects of osteoporosis interventions in terms of postponing of fractures. Author(s): Christensen PM, Brosen K, Brixen K, Kristiansen IS. Source: European Journal of Clinical Pharmacology. 2002 December; 58(9): 629-33. Epub 2002 November 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483456&dopt=Abstract

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Factors affecting long-term adherence to hormone replacement therapy after screening for osteoporosis. Author(s): Steel SA, Albertazzi P, Howarth EM, Purdie DW. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 96-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841879&dopt=Abstract

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Failure of intertrochanteric fracture fixation with a dynamic hip screw in relation to pre-operative fracture stability and osteoporosis. Author(s): Kim WY, Han CH, Park JI, Kim JY. Source: International Orthopaedics. 2001; 25(6): 360-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11820441&dopt=Abstract

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Failure of operative treatment in a child with osteoporosis-pseudoglioma syndrome. Author(s): Kasten P, Bastian L, Schmid H, Coull R, Wippermann BW, Krettek C. Source: Clinical Orthopaedics and Related Research. 2003 May; (410): 262-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771838&dopt=Abstract

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Falls' guidelines and osteoporosis assessment. Author(s): Kamel HK, Zablocki CJ. Source: Journal of the American Geriatrics Society. 2002 June; 50(6): 1167; Author Reply 1168. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110088&dopt=Abstract

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Falls, fractures, and osteoporosis after stroke: time to think about protection? Author(s): Poole KE, Reeve J, Warburton EA. Source: Stroke; a Journal of Cerebral Circulation. 2002 May; 33(5): 1432-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11988628&dopt=Abstract

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Familial severe congenital neutropenia associated with infantile osteoporosis: a new entity. Author(s): Elhasid R, Hofbauer LC, Ish-Shalom S, Ben-Arush M, Koc O, Rowe JM, Etzioni A. Source: American Journal of Hematology. 2003 January; 72(1): 34-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508266&dopt=Abstract

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Family physicians and osteoporosis. Meeting the challenge. Author(s): McKercher HG. Source: Can Fam Physician. 2003 April; 49: 405-7, 412-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729232&dopt=Abstract

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FDG-PET findings of vertebral compression fractures in osteoporosis: preliminary results. Author(s): Schmitz A, Risse JH, Textor J, Zander D, Biersack HJ, Schmitt O, Palmedo H. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 September; 13(9): 755-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195540&dopt=Abstract

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Finance issue brief: women's health: osteoporosis coverage requirements: year end report-2002. Author(s): Plaza CI. Source: Issue Brief Health Policy Track Serv. 2002 December 31; : 1-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901353&dopt=Abstract

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Fluoride and anabolic steroids in the treatment of glucocorticoid-induced osteoporosis. Author(s): Marcocci C, Bevilacqua M. Source: Frontiers of Hormone Research. 2002; 30: 165-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892264&dopt=Abstract

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For osteoporosis, are two antiresorptive drugs better than one? Author(s): Ettinger B, Bilezikian JP. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 March; 87(3): 983-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889148&dopt=Abstract

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Fracture rates lower in rural than urban communities: the Geelong Osteoporosis Study. Author(s): Sanders KM, Nicholson GC, Ugoni AM, Seeman E, Pasco JA, Kotowicz MA. Source: Journal of Epidemiology and Community Health. 2002 June; 56(6): 466-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011207&dopt=Abstract

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Fracture risks for women in long-term care: high prevalence of calcaneal osteoporosis and hypovitaminosis D. Author(s): Elliott ME, Binkley NC, Carnes M, Zimmerman DR, Petersen K, Knapp K, Behlke JM, Ahmann N, Kieser MA. Source: Pharmacotherapy. 2003 June; 23(6): 702-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820811&dopt=Abstract

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Fracture thresholds revisited. Geelong Osteoporosis Study. Author(s): Henry MJ, Pasco JA, Seeman E, Nicholson GC, Sanders KM, Kotowicz MA. Source: Journal of Clinical Epidemiology. 2002 July; 55(7): 642-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160911&dopt=Abstract

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Fragility fractures in dialysis and transplant patients. Is it osteoporosis, and how should it be treated? Author(s): Hodsman AB. Source: Perit Dial Int. 2001; 21 Suppl 3: S247-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887831&dopt=Abstract

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Frequency and causes of osteoporosis in men. Author(s): Pye SR, Adams KR, Halsey JP, Klimiuk P, Knight SM, Pal B, Selby PL, Stewart IM, Swinson DR, O'Neill TW. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 811-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771448&dopt=Abstract

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Gender and osteoporosis: similarities and sex-specific differences. Author(s): Boling EP. Source: J Gend Specif Med. 2001; 4(2): 36-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480096&dopt=Abstract

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Gene therapy for osteoporosis: evaluation in a murine ovariectomy model. Author(s): Baltzer AW, Whalen JD, Wooley P, Latterman C, Truchan LM, Robbins PD, Evans CH. Source: Gene Therapy. 2001 December; 8(23): 1770-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11803396&dopt=Abstract

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General and oral aspects of osteoporosis: a review. Author(s): von Wowern N. Source: Clinical Oral Investigations. 2001 June; 5(2): 71-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480813&dopt=Abstract

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Genetic and environmental factors affect bone density variances of families of men and women with osteoporosis. Author(s): Baudoin C, Cohen-Solal ME, Beaudreuil J, De Vernejoul MC. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 May; 87(5): 2053-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994340&dopt=Abstract

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Genetic control of susceptibility to osteoporosis. Author(s): Ralston SH. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 June; 87(6): 2460-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050200&dopt=Abstract

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Genetic polymorphisms and clinical practice: the example of osteoporosis. Author(s): Pols HA, Uitterlinden AG. Source: Acta Clin Belg. 2002 September-October; 57(5): 266-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534134&dopt=Abstract

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Genetic polymorphisms of estrogen receptor-alpha: possible implications for targeted osteoporosis therapy. Author(s): Ongphiphadhanakul B. Source: American Journal of Pharmacogenomics : Genomics-Related Research in Drug Development and Clinical Practice. 2003; 3(1): 5-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562211&dopt=Abstract

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Genetics of male osteoporosis. Author(s): Gennari L, Brandi ML. Source: Calcified Tissue International. 2001 October; 69(4): 200-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730250&dopt=Abstract

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Genetics of osteoporosis. Author(s): Ralston SH. Source: Reviews in Endocrine & Metabolic Disorders. 2001 January; 2(1): 13-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704976&dopt=Abstract

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Genetics of osteoporosis. Author(s): Peacock M, Turner CH, Econs MJ, Foroud T. Source: Endocrine Reviews. 2002 June; 23(3): 303-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050122&dopt=Abstract

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Genetics of osteoporosis: role of steroid hormone receptor gene polymorphisms. Author(s): Gennari L, Becherini L, Falchetti A, Masi L, Massart F, Brandi ML. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 May; 81(1): 124. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127038&dopt=Abstract

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Global assessment of risk factors for osteoporosis. Author(s): Fujita T. Source: Journal of Bone and Mineral Metabolism. 2001; 19(3): 131-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11368296&dopt=Abstract

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Glucocorticoid decreases circulating osteoprotegerin (OPG): possible mechanism for glucocorticoid induced osteoporosis. Author(s): Sasaki N, Kusano E, Ando Y, Yano K, Tsuda E, Asano Y. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 March; 16(3): 479-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11239019&dopt=Abstract

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Glucocorticoid osteoporosis. Author(s): Sambrook PN. Source: Current Pharmaceutical Design. 2002; 8(21): 1877-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171526&dopt=Abstract

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Glucocorticoid-induced osteoporosis in asthma and respiratory diseases. Author(s): Malerba M, Romanelli G, Grassi V. Source: Frontiers of Hormone Research. 2002; 30: 86-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892273&dopt=Abstract

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Glucocorticoid-induced osteoporosis. Author(s): Weinstein RS. Source: Reviews in Endocrine & Metabolic Disorders. 2001 January; 2(1): 65-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708295&dopt=Abstract

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Glucocorticoid-induced osteoporosis. Author(s): Clowes JA, Peel N, Eastell R. Source: Current Opinion in Rheumatology. 2001 July; 13(4): 326-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555737&dopt=Abstract

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Glucocorticoid-induced osteoporosis. Author(s): Kumar R. Source: Current Opinion in Nephrology and Hypertension. 2001 September; 10(5): 58995. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11496051&dopt=Abstract

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Glucocorticoid-induced osteoporosis: pathogenesis, diagnosis, and management. Author(s): McIlwain HH. Source: Preventive Medicine. 2003 February; 36(2): 243-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591000&dopt=Abstract

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Glucocorticoid-induced osteoporosis: summary of a workshop. Author(s): Canalis E, Giustina A. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 December; 86(12): 5681-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739419&dopt=Abstract

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Graphic trace analysis of ultrasound at the phalanges may differentiate between subjects with primary hyperparathyroidism and with osteoporosis: a pilot study. Author(s): Montagnani A, Gonnelli S, Cepollaro C, Bruni D, Franci MB, Lucani B, Gennari C. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 March; 13(3): 222-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991442&dopt=Abstract

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Growth hormone in glucocorticoid-induced osteoporosis. Author(s): Manelli F, Carpinteri R, Bossoni S, Burattin A, Bonadonna S, Agabiti Rosei E, Giustina A. Source: Frontiers of Hormone Research. 2002; 30: 174-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892265&dopt=Abstract

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Growth hormone secretion and sensitivity in men with idiopathic osteoporosis. Author(s): Gillberg P, Johansson AG, Blum WF, Groth T, Ljunghall S. Source: Calcified Tissue International. 2001 February; 68(2): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310349&dopt=Abstract

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Guidelines for prevention of falls in people aged over 65. Health improvement plans must incorporate falls and osteoporosis strategies. Author(s): Chakravarty M, Sorman A. Source: Bmj (Clinical Research Ed.). 2001 March 3; 322(7285): 554-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263455&dopt=Abstract

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Guidelines for the treatment of postmenopausal osteoporosis for general practitioners. Author(s): O'Neill S, Sambrook P, Diamond T, Ebeling P, Ferris L, Flicker L, Findlay D, Singh MF, Lord S, MacLennan A, Markwell A, Nowson C, Pocock N, Williamson M; Osteoporosis Australia. Source: Aust Fam Physician. 2002 October; 31(10): 921-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404830&dopt=Abstract

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Guidelines for treatment of osteoporosis in men. Author(s): Diamond T, Sambrook P, Williamson M, Flicker L, Nowson C, FiataroneSingh M, Lord S, Ferris L, O'Neil S, MacLennan A. Source: Aust Fam Physician. 2001 August; 30(8): 787-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11681154&dopt=Abstract

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Guidelines on the use of biochemical markers of bone turnover in osteoporosis (2001). Author(s): Nishizawa Y, Nakamura T, Ohata H, Kushida K, Gorai I, Shiraki M, Fukunaga M, Hosoi T, Miki T, Nakatsuka K, Miura M; Committee on the Guidelines for the Use of Biochemical Markers of Bone Turnover in Osteoporosis: Japan Osteoporosis Society. Source: Journal of Bone and Mineral Metabolism. 2001; 19(6): 338-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685648&dopt=Abstract

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Haptoglobin genotype as a risk factor for postmenopausal osteoporosis. Author(s): Pescarmona GP, D'Amelio P, Morra E, Isaia GC. Source: Journal of Medical Genetics. 2001 September; 38(9): 636-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11565553&dopt=Abstract

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Heads up on osteoporosis. Author(s): Gray K. Source: J S C Med Assoc. 2001 February; 97(2): 53-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235116&dopt=Abstract

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Health beliefs and attitudes toward the prevention of osteoporosis in older women. Author(s): Hsieh C, Novielli KD, Diamond JJ, Cheruva D. Source: Menopause (New York, N.Y.). 2001 September-October; 8(5): 372-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528365&dopt=Abstract

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Health professional's guide to rehabilitation of the patient with osteoporosis. Author(s): Bonner FJ Jr, Sinaki M, Grabois M, Shipp KM, Lane JM, Lindsay R, Gold DT, Cosman F, Bouxsein ML, Weinstein JN, Gallagher RM, Melton LJ 3rd, Salcido RS, Gordon SL. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003; 14 Suppl 2: S1-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759719&dopt=Abstract

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Heparin and osteoporosis during pregnancy: 2002 update. Author(s): Ruiz-Irastorza G, Khamashta MA, Hughes GR. Source: Lupus. 2002; 11(10): 680-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413068&dopt=Abstract

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Hepatocyte growth factor: a possible mediator of heparin-induced osteoporosis? Author(s): Borawski J, Naumnik B, Mysliwiec M. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2003 April; 9(2): 171-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812389&dopt=Abstract

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High concentrations of dexamethasone suppress the proliferation but not the differentiation or further maturation of human osteoblast precursors in vitro: relevance to glucocorticoid-induced osteoporosis. Author(s): Walsh S, Jordan GR, Jefferiss C, Stewart K, Beresford JN. Source: Rheumatology (Oxford, England). 2001 January; 40(1): 74-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157145&dopt=Abstract

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High density lipoproteins (HDL) in women with postmenopausal osteoporosis: a preliminary study. Author(s): D'Amelio P, Pescarmona GP, Gariboldi A, Isaia GC. Source: Menopause (New York, N.Y.). 2001 November-December; 8(6): 429-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723416&dopt=Abstract

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High prevalence of osteoporosis in patients with chronic liver disease prior to liver transplantation. Author(s): Ninkovic M, Love SA, Tom B, Alexander GJ, Compston JE. Source: Calcified Tissue International. 2001 December; 69(6): 321-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11800228&dopt=Abstract

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Hip fracture patients are not treated for osteoporosis: a call to action. Author(s): Harrington JT, Broy SB, Derosa AM, Licata AA, Shewmon DA. Source: Arthritis and Rheumatism. 2002 December 15; 47(6): 651-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522840&dopt=Abstract

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HIV infection--a risk factor for osteoporosis. Author(s): Thomas J, Doherty SM. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 July 1; 33(3): 281-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843738&dopt=Abstract

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Hormone replacement therapy (oestradiol-only preparations): can the laboratory recommend a concentration of plasma oestradiol to protect against osteoporosis? Author(s): Armston A, Wood P. Source: Annals of Clinical Biochemistry. 2002 May; 39(Pt 3): 184-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12038591&dopt=Abstract

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Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study. Author(s): Jensen LB, Vestergaard P, Hermann AP, Gram J, Eiken P, Abrahamsen B, Brot C, Kolthoff N, Sorensen OH, Beck-Nielsen H, Nielsen SP, Charles P, Mosekilde L. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 February; 18(2): 333-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568411&dopt=Abstract

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Hormone replacement therapy for postmenopausal osteoporosis. Author(s): Cranney A, Wells GA. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 361-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916291&dopt=Abstract

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Hospital care of osteoporosis-related vertebral fractures. Author(s): Gehlbach SH, Burge RT, Puleo E, Klar J. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 January; 14(1): 53-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577185&dopt=Abstract

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How are family physicians managing osteoporosis? Qualitative study of their experiences and educational needs. Author(s): Jaglal SB, Carroll J, Hawker G, McIsaac WJ, Jaakkimainen L, Cadarette SM, Cameron C, Davis D. Source: Can Fam Physician. 2003 April; 49: 462-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729242&dopt=Abstract

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How reliable is a radiological report in osteoporosis in diagnosing low bone density? Author(s): McCullagh CD, McCoy K, Crawford VL, Taggart H. Source: Ulster Med J. 2003 May; 72(1): 34-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868701&dopt=Abstract

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How reliable is the ultrasound densitometer for community screening to diagnose osteoporosis in spine, femur, and forearm? Author(s): Kim KI, Han IK, Kim H, Cho NH. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2001 Summer; 4(2): 159-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486785&dopt=Abstract

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How should clinicians manage osteoporosis in ankylosing spondylitis? Author(s): Bessant R, Keat A. Source: The Journal of Rheumatology. 2002 July; 29(7): 1511-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136913&dopt=Abstract

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How to diagnose the presence of osteoporosis and assess the risk of fracture. Author(s): Prince RL. Source: Best Practice & Research. Clinical Rheumatology. 2001 July; 15(3): 345-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485334&dopt=Abstract

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How to grow bone to treat osteoporosis and mend fractures. Author(s): Whitfield JF. Source: Curr Rheumatol Rep. 2003 February; 5(1): 45-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590885&dopt=Abstract

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How to prevent fractures in the individual with osteoporosis. Author(s): Javaid MK, Cooper C. Source: Best Practice & Research. Clinical Rheumatology. 2001 July; 15(3): 497-515. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485343&dopt=Abstract

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How well are community-living people treated for osteoporosis after hip fracture? Author(s): Wilkinson TJ, Sainsbury R, Gilchrist NL. Source: Journal of the American Geriatrics Society. 2002 November; 50(11): 1914. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410924&dopt=Abstract

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How well are community-living women treated for osteoporosis after hip fracture? Author(s): Bellantonio S, Fortinsky R, Prestwood K. Source: Journal of the American Geriatrics Society. 2001 September; 49(9): 1197-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559379&dopt=Abstract

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Hydroxymethylglutaryl-coenzyme A reductase inhibitors in osteoporosis management. Author(s): Coons JC. Source: The Annals of Pharmacotherapy. 2002 February; 36(2): 326-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847956&dopt=Abstract

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Hypogonadism and osteoporosis in men. Author(s): Mikhail N. Source: Archives of Internal Medicine. 2003 May 26; 163(10): 1237; Author Reply 1237-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767963&dopt=Abstract

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Hypothalamic digoxin and hemispheric chemical dominance--relation to the pathogenesis of senile osteoporosis, degenerative osteoarthritis, and spondylosis. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 March; 113(3): 341-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803138&dopt=Abstract

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Ibandronate: a comparison of oral daily dosing versus intermittent dosing in postmenopausal osteoporosis. Author(s): Riis BJ, Ise J, von Stein T, Bagger Y, Christiansen C. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 October; 16(10): 1871-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585352&dopt=Abstract

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Ibandronate: a potent new bisphosphonate in the management of postmenopausal osteoporosis. Author(s): Papapoulos SE. Source: Int J Clin Pract. 2003 June; 57(5): 417-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846348&dopt=Abstract

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Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. Author(s): Siris ES, Miller PD, Barrett-Connor E, Faulkner KG, Wehren LE, Abbott TA, Berger ML, Santora AC, Sherwood LM. Source: Jama : the Journal of the American Medical Association. 2001 December 12; 286(22): 2815-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11735756&dopt=Abstract

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Identification and treatment of osteoporosis in fractures. Author(s): McLellan AR. Source: Curr Rheumatol Rep. 2003 February; 5(1): 57-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590886&dopt=Abstract

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Identification of vertebral fractures in osteoporosis. Author(s): Guermazi A, Mohr A, Grigorian M, Taouli B, Genant HK. Source: Seminars in Musculoskeletal Radiology. 2002 September; 6(3): 241-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541202&dopt=Abstract

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Idiopathic juvenile osteoporosis. Author(s): Lorenc RS. Source: Calcified Tissue International. 2002 May; 70(5): 395-7. Epub 2002 April 29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973603&dopt=Abstract

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Idiopathic osteoporosis: an evolutionary dys-adaptation? Author(s): Alexander C. Source: Annals of the Rheumatic Diseases. 2001 June; 60(6): 554-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11350841&dopt=Abstract

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Images in clinical medicine. Osteoporosis circumscripta. Author(s): Leu KM, Kalemkerian GP. Source: The New England Journal of Medicine. 2002 August 1; 347(5): E2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151465&dopt=Abstract

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Imaging modalities in the assessment of osteoporosis. Author(s): Theodorou DJ, Theodorou SJ, Sartoris DJ. Source: Compr Ther. 2002 Winter; 28(4): 189-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12506488&dopt=Abstract

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Impact of degenerative radiographic abnormalities and vertebral fractures on spinal bone density of women with osteoporosis. Author(s): Paiva LC, Filardi S, Pinto-Neto AM, Samara A, Marques Neto JF. Source: Sao Paulo Medical Journal = Revista Paulista De Medicina. 2002 January 3; 120(1): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836546&dopt=Abstract

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Implications in the use of T-scores for the diagnosis of osteoporosis in men. Author(s): Faulkner KG, Orwoll E. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002 Spring; 5(1): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940733&dopt=Abstract

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Improvement in the undertreatment of osteoporosis following hip fracture. Author(s): Gardner MJ, Flik KR, Mooar P, Lane JM. Source: The Journal of Bone and Joint Surgery. American Volume. 2002 August; 84-A(8): 1342-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177263&dopt=Abstract

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Improving risk assessment: hip geometry, bone mineral distribution and bone strength in hip fracture cases and controls. The EPOS study. European Prospective Osteoporosis Study. Author(s): Crabtree NJ, Kroger H, Martin A, Pols HA, Lorenc R, Nijs J, Stepan JJ, Falch JA, Miazgowski T, Grazio S, Raptou P, Adams J, Collings A, Khaw KT, Rushton N, Lunt M, Dixon AK, Reeve J. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 January; 13(1): 48-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883408&dopt=Abstract

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Incidence and costs of osteoporosis-associated hip fractures in Austria. Author(s): Koeck CM, Schwappach DL, Niemann FM, Strassmann TJ, Ebner H, Klaushofer K. Source: Wiener Klinische Wochenschrift. 2001 May 15; 113(10): 371-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11432126&dopt=Abstract

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Incidence of limb fracture across Europe: results from the European Prospective Osteoporosis Study (EPOS). Author(s): Ismail AA, Pye SR, Cockerill WC, Lunt M, Silman AJ, Reeve J, Banzer D, Benevolenskaya LI, Bhalla A, Bruges Armas J, Cannata JB, Cooper C, Delmas PD, Dequeker J, Dilsen G, Falch JA, Felsch B, Felsenberg D, Finn JD, Gennari C, Hoszowski K, Jajic I, Janott J, Johnell O, Kanis JA, Kragl G, Lopez Vaz A, Lorenc R, Lyritis G, Marchand F, Masaryk P, Matthis C, Miazgowski T, Naves-Diaz M, Pols HA, Poor G, Rapado A, Raspe HH, Reid DM, Reisinger W, Scheidt-Nave C, Stepan J, Todd C, Weber K, Woolf AD, O'Neill TW. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 July; 13(7): 565-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111017&dopt=Abstract

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Influence of bone densitometry results on the treatment of osteoporosis. Author(s): Fitt NS, Mitchell SL, Cranney A, Gulenchyn K, Huang M, Tugwell P. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 March 20; 164(6): 777-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11276543&dopt=Abstract

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Initiation of osteoporosis treatment after bone mineral density testing. Author(s): Pressman A, Forsyth B, Ettinger B, Tosteson AN. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(5): 337-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444079&dopt=Abstract

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Instant vertebral assessment: a noninvasive dual X-ray absorptiometry technique to avoid misclassification and clinical mismanagement of osteoporosis. Author(s): Greenspan SL, von Stetten E, Emond SK, Jones L, Parker RA. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2001 Winter; 4(4): 373-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748342&dopt=Abstract

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Insufficiency fracture of the femoral neck during osteoporosis treatment: a case report. Author(s): Iwamoto J, Takeda T. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2002; 7(6): 707-12. Erratum In: J Orthop Sci. 2003; 8(1): 125. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486478&dopt=Abstract

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Intensive and prolonged health promotion strategy may increase awareness of osteoporosis among postmenopausal women. Author(s): Tellier V, De Maeseneer J, De Prins L, Sedrine WB, Gosset C, Reginster JY. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(2): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303713&dopt=Abstract

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Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphism in postmenopausal women: correlation to bone mineral density and susceptibility to osteoporosis. Author(s): Chen HY, Chen WC, Wu MC, Tsai FJ, Lin CC. Source: Maturitas. 2003 January 30; 44(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568735&dopt=Abstract

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Intermittent cyclic tiludronate in the treatment of osteoporosis. Author(s): Reginster JY, Christiansen C, Roux C, Fechtenbaum J, Rouillon A, Tou KP. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(3): 169-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315234&dopt=Abstract

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Internal fracture fixation in patients with osteoporosis. Author(s): Cornell CN. Source: J Am Acad Orthop Surg. 2003 March-April; 11(2): 109-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670137&dopt=Abstract

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Interplay of pregnancy, lactation, and hyperthyroidism leading to severe osteoporosis in a young woman. Author(s): Sekhar RV, Vassilopoulou-Sellin R. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2001 July-August; 7(4): 2626. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497477&dopt=Abstract

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Intervention thresholds for osteoporosis. Author(s): Kanis JA, Johnell O, Oden A, De Laet C, Oglesby A, Jonsson B. Source: Bone. 2002 July; 31(1): 26-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110408&dopt=Abstract

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Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study. Author(s): Krieg MA, Seydoux C, Sandini L, Goy JJ, Berguer DG, Thiebaud D, Burckhardt P. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(2): 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303710&dopt=Abstract

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Intravenous pamidronate compared with oral alendronate for the treatment of postmenopausal osteoporosis. Author(s): Heijckmann AC, Juttmann JR, Wolffenbuttel BH. Source: The Netherlands Journal of Medicine. 2002 September; 60(8): 315-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481878&dopt=Abstract

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Intravenous pamidronate in the treatment of transient osteoporosis of the hip. Author(s): Varenna M, Zucchi F, Binelli L, Failoni S, Gallazzi M, Sinigaglia L. Source: Bone. 2002 July; 31(1): 96-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110419&dopt=Abstract

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Inverse relation between osteoporosis and spondylosis in postmenopausal women as evaluated by bone mineral density and semiquantitative scoring of spinal degeneration. Author(s): Miyakoshi N, Itoi E, Murai H, Wakabayashi I, Ito H, Minato T. Source: Spine. 2003 March 1; 28(5): 492-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616163&dopt=Abstract

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Involvement of interleukin-6 and prostaglandin E2 in periarticular osteoporosis of postmenopausal women with rheumatoid arthritis. Author(s): Sugiyama T. Source: Journal of Bone and Mineral Metabolism. 2001; 19(2): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281165&dopt=Abstract

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Is absorptiometry useful for monitoring osteoporosis treatment? Author(s): Pouilles JM, Ribot C, Tremollieres F. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2001 October; 68(5): 367-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707000&dopt=Abstract

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Is distal forearm fracture in men due to osteoporosis? Author(s): Tuck SP, Raj N, Summers GD. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 August; 13(8): 630-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181621&dopt=Abstract

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Is hormone therapy still an option for the management of osteoporosis? Author(s): MacLennan A, Sturdee D. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 89-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848151&dopt=Abstract

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Is osteoporosis screening in postmenopausal women effective? Author(s): Phillips J, Krist A, Wilder L. Source: The Journal of Family Practice. 2003 April; 52(4): 331-3; Discussion 333. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681096&dopt=Abstract

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Is osteoporosis undertreated after minimal trauma fracture? Author(s): Zochling JM, Schwarz JM, March L, Sambrook PN. Source: The Medical Journal of Australia. 2001 June 18; 174(12): 663-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480694&dopt=Abstract

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Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study. European Prospective Osteoporosis Study. Author(s): Vergnaud P, Lunt M, Scheidt-Nave C, Poor G, Gennari C, Hoszowski K, Vaz AL, Reid DM, Benevolenskaya L, Grazio S, Weber K, Miazgowski T, Stepan JJ, Masaryk P, Galan F, Armas JB, Lorenc R, Havelka S, Perez Cano R, Seibel M, Armbrecht G, Kaptoge S, O'Neill TW, Silman AJ, Felsenberg D, Reeve J, Delmas PD. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 August; 322(1-2): 121-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12104091&dopt=Abstract

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Is the Sp1 polymorphism in the COL1A1 gene a risk factor for postmenopausal osteoporosis? Comment on the article by Keen et al. Author(s): Zajickova K, Zofkova I, Hill M. Source: Arthritis and Rheumatism. 2002 October; 46(10): 2828-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384955&dopt=Abstract

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Is there a potential therapeutic value of copper and zinc for osteoporosis? Author(s): Lowe NM, Lowe NM, Fraser WD, Jackson MJ. Source: The Proceedings of the Nutrition Society. 2002 May; 61(2): 181-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133199&dopt=Abstract

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Is vitamin K deficiency a risk factor for osteoporosis in Crohn's disease? Author(s): Szulc P, Meunier PJ. Source: Lancet. 2001 June 23; 357(9273): 1995-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438129&dopt=Abstract

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Isolating the cost of osteoporosis-related fracture for postmenopausal women. A population-based study. Author(s): Martin BC, Chisholm MA, Kotzan JA. Source: Gerontology. 2001 January-February; 47(1): 21-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244288&dopt=Abstract

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Knee extension strength is a significant determinant of static and dynamic balance as well as quality of life in older community-dwelling women with osteoporosis. Author(s): Carter ND, Khan KM, Mallinson A, Janssen PA, Heinonen A, Petit MA, McKay HA; Fall-Free BC Research Group. Source: Gerontology. 2002 November-December; 48(6): 360-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393951&dopt=Abstract

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Knowledge of osteoporosis in a Swedish municipality--a prospective study. Author(s): Waller J, Eriksson O, Foldevi M, Kronhed AC, Larsson L, Lofman O, Toss G, Moller M. Source: Preventive Medicine. 2002 April; 34(4): 485-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914055&dopt=Abstract

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Knowledge of, attitudes toward, and activity to prevent osteoporosis among middleaged and elderly women. Author(s): Yu S, Huang YC. Source: The Journal of Nursing Research : Jnr. 2003 March; 11(1): 65-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695981&dopt=Abstract

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Knowledge, beliefs, and risk factors for osteoporosis among African-American and Hispanic women. Author(s): Geller SE, Derman R. Source: Journal of the National Medical Association. 2001 January; 93(1): 13-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653376&dopt=Abstract

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Laboratory workup for osteoporosis. Which tests are most cost-effective? Author(s): Crandall C. Source: Postgraduate Medicine. 2003 September; 114(3): 35-8, 41-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14503399&dopt=Abstract

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Lack of diagnosis and treatment of osteoporosis in men and women after hip fracture. Author(s): Follin SL, Black JN, McDermott MT. Source: Pharmacotherapy. 2003 February; 23(2): 190-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587808&dopt=Abstract

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Lactose intolerance: a self-fulfilling prophecy leading to osteoporosis? Author(s): Savaiano D. Source: Nutrition Reviews. 2003 June; 61(6 Pt 1): 221-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903833&dopt=Abstract

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Lactose maldigestion, calcium intake and osteoporosis in African-, Asian-, and Hispanic-Americans. Author(s): Jackson KA, Savaiano DA. Source: Journal of the American College of Nutrition. 2001 April; 20(2 Suppl): 198S-207S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349943&dopt=Abstract

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Lacunarity analysis of spatial pattern in CT images of vertebral trabecular bone for assessing osteoporosis. Author(s): Dougherty G, Henebry GM. Source: Medical Engineering & Physics. 2002 March; 24(2): 129-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886832&dopt=Abstract

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Lifestyle factors are associated with osteoporosis in lean women but not in normal and overweight women: a population-based cohort study of 1222 women. Author(s): Korpelainen R, Korpelainen J, Heikkinen J, Vaananen K, KeinanenKiukaanniemi S. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 January; 14(1): 34-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577183&dopt=Abstract

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Lifestyle risk factors for osteoporosis in Asian and Caucasian girls. Author(s): Mackelvie KJ, McKay HA, Khan KM, Crocker PR. Source: Medicine and Science in Sports and Exercise. 2001 November; 33(11): 1818-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689730&dopt=Abstract

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Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis. Author(s): Ohmori H, Makita Y, Funamizu M, Hirooka K, Hosoi T, Orimo H, Suzuki T, Ikari K, Nakajima T, Inoue I, Hata A. Source: Journal of Human Genetics. 2002; 47(8): 400-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181640&dopt=Abstract

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Long-term estrogen and hormone replacement therapy for the prevention and treatment of osteoporosis. Author(s): Levine JP. Source: Curr Womens Health Rep. 2003 June; 3(3): 181-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734027&dopt=Abstract

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Long-term tolerability of the bisphosphonates in postmenopausal osteoporosis: a comparative review. Author(s): Kherani RB, Papaioannou A, Adachi JD. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2002; 25(11): 781-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222989&dopt=Abstract

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Loss of bone mass and vitamin D deficiency after hematopoietic stem cell transplantation: standard prophylactic measures fail to prevent osteoporosis. Author(s): Massenkeil G, Fiene C, Rosen O, Michael R, Reisinger W, Arnold R. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 November; 15(11): 1701-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11681410&dopt=Abstract

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Low circulating estradiol and adrenal androgens concentrations in men on glucocorticoids: a potential contributory factor in steroid-induced osteoporosis. Author(s): Hampson G, Bhargava N, Cheung J, Vaja S, Seed PT, Fogelman I. Source: Metabolism: Clinical and Experimental. 2002 November; 51(11): 1458-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404198&dopt=Abstract

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Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease? Author(s): Schoon EJ, Muller MC, Vermeer C, Schurgers LJ, Brummer RJ, Stockbrugger RW. Source: Gut. 2001 April; 48(4): 473-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11247890&dopt=Abstract

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Lupus pregnancy: is heparin a risk factor for osteoporosis? Author(s): Ruiz-Irastorza G, Khamashta MA, Nelson-Piercy C, Hughes GR. Source: Lupus. 2001; 10(9): 597-600. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678446&dopt=Abstract

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Lymphoplasmacytoid lymphoma presenting as severe osteoporosis. Author(s): Atoyebi W, Brown M, Wass J, Littlewood TJ, Hatton C. Source: American Journal of Hematology. 2002 May; 70(1): 77-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994987&dopt=Abstract

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Maintenance of osteoblastic and adipocytic differentiation potential with age and osteoporosis in human marrow stromal cell cultures. Author(s): Justesen J, Stenderup K, Eriksen EF, Kassem M. Source: Calcified Tissue International. 2002 July; 71(1): 36-44. Epub 2002 June 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200657&dopt=Abstract

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Male osteoporosis associated with longterm cyproterone treatment. Author(s): Vasireddy S, Swinson DR. Source: The Journal of Rheumatology. 2001 July; 28(7): 1702-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469484&dopt=Abstract

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Management of childhood osteoporosis. Author(s): Shaw NJ. Source: Archives of Disease in Childhood. 2003 January; 88(1): 91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495983&dopt=Abstract

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Management of corticosteroid-induced osteoporosis. Author(s): Yeap SS, Hosking DJ. Source: Rheumatology (Oxford, England). 2002 October; 41(10): 1088-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364625&dopt=Abstract

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Management of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis: rates and predictors of care in an academic rheumatology practice. Author(s): Solomon DH, Katz JN, Jacobs JP, La Tourette AM, Coblyn J. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483716&dopt=Abstract

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Management of osteoporosis due to ovarian failure. Author(s): Eastell R. Source: Medical and Pediatric Oncology. 2003 September; 41(3): 222-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868123&dopt=Abstract

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Management of osteoporosis in an orthopaedic department: audit improves practice. Author(s): Charalambous CP, Kumar S, Tryfonides M, Rajkumar P, Hirst P. Source: Int J Clin Pract. 2002 October; 56(8): 620-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425375&dopt=Abstract

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Management of patients with osteoporosis. Author(s): Grajower MM. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2001 September-October; 7(5): 409. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585381&dopt=Abstract

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Management of postmenopausal osteoporosis: position statement of the North American Menopause Society. Author(s): North American Menopause Society.. Source: Menopause (New York, N.Y.). 2002 March-April; 9(2): 84-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875327&dopt=Abstract

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Management of primary osteoporosis. Author(s): Body JJ. Source: Acta Clin Belg. 2002 September-October; 57(5): 277-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534136&dopt=Abstract

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Management of the patient after an osteoporotic fracture: Guidelines for orthopedic surgeons--consensus conference on Treatment of Osteoporosis for Orthopedic Surgeons, Nordic Orthopedic Federation, Tampere, Finland 2000. Author(s): Johnell O, Kannus P, Obrant KJ, Jarvinen M, Parkkari J; Nordic Orthopedic Federation. Source: Acta Orthopaedica Scandinavica. 2001 August; 72(4): 325-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11580118&dopt=Abstract

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Management of treatment-related osteoporosis in men with prostate cancer. Author(s): Smith MR. Source: Cancer Treatment Reviews. 2003 June; 29(3): 211-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787715&dopt=Abstract

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Management quandary: osteoporosis in teenagers. Author(s): Harel Z. Source: Journal of Pediatric and Adolescent Gynecology. 2002; 15(4): 241-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459232&dopt=Abstract

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Managing osteoporosis. Author(s): Stevens R, Cutts S. Source: Practitioner. 2003 June; 247(1647): 525-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822321&dopt=Abstract

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May is osteoporosis month. Author(s): Hamdy RC. Source: Southern Medical Journal. 2003 May; 96(5): 419-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911176&dopt=Abstract

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Measuring quality of life in osteoporosis. Author(s): Morris R, Masud T. Source: Age and Ageing. 2001 September; 30(5): 371-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709372&dopt=Abstract

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Measuring quality of life in women with vertebral fractures due to osteoporosis: a comparison of the OQLQ and QUALEFFO. Author(s): Badia X, Diez-Perez A, Alvarez-Sanz C, Diaz-Lopez B, Diaz-Curiel M, Guillen F, Gonzalez-Macias J; Spanish GRECO Study Group. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2001; 10(4): 307-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763244&dopt=Abstract

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Mechanisms of bone loss and gain in untreated and treated osteoporosis. Author(s): Compston J. Source: Endocrine. 2002 February; 17(1): 21-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014699&dopt=Abstract

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Medical management of osteoporosis. Author(s): Lane JM, Garfin SR, Sherman PJ, Poynton AR. Source: Instr Course Lect. 2003; 52: 785-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690902&dopt=Abstract

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Medical treatment of male osteoporosis. Author(s): Fonderico F, Fittipaldi MR, Vitale G, Ciccarelli A, Lupoli GA, Panico A, Cascella T, Lupoli G. Source: J Endocrinol Invest. 2002; 25(10 Suppl): 103-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508938&dopt=Abstract

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Men and osteoporosis. Author(s): Diamond T, Sambrook P, Williamson M, Flicker L, Nowson C, FiataroneSingh M, Lord S, Ferris L, O'Neil S, MacLennan A. Source: Aust Fam Physician. 2001 August; 30(8): 781-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11681153&dopt=Abstract

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Men and osteoporosis. Preventing fracture and disability. Author(s): Wildauer JM. Source: Adv Nurse Pract. 2001 April; 9(4): 30-4; Quiz 34-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420433&dopt=Abstract

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Men with osteoporosis: are they being treated fairly? Author(s): Legrand E. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2001 May; 68(3): 191-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11394617&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. I. Systematic reviews of randomized trials in osteoporosis: introduction and methodology. Author(s): Cranney A, Tugwell P, Wells G, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 496-507. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202464&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Author(s): Cranney A, Wells G, Willan A, Griffith L, Zytaruk N, Robinson V, Black D, Adachi J, Shea B, Tugwell P, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 508-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202465&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Author(s): Cranney A, Tugwell P, Adachi J, Weaver B, Zytaruk N, Papaioannou A, Robinson V, Shea B, Wells G, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 517-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202466&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis. Author(s): Cranney A, Tugwell P, Zytaruk N, Robinson V, Weaver B, Adachi J, Wells G, Shea B, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 524-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202467&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of metaanalyses of therapies for postmenopausal osteoporosis. Author(s): Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 570-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202472&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Author(s): Wells G, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, Robinson V, Henry D, O'Connell D, Cranney A; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 529-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202468&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis. Author(s): Cranney A, Tugwell P, Zytaruk N, Robinson V, Weaver B, Shea B, Wells G, Adachi J, Waldegger L, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 540-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202469&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Author(s): Papadimitropoulos E, Wells G, Shea B, Gillespie W, Weaver B, Zytaruk N, Cranney A, Adachi J, Tugwell P, Josse R, Greenwood C, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 560-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202471&dopt=Abstract

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Metabolic characteristics and prevalence of osteoporosis among women in Tae-An area. Author(s): Yoon HK, Kim SW, Yim CH, Chung HY, Oh HJ, Han KO, Jang HC, Cho DH, Han IK. Source: Journal of Korean Medical Science. 2001 June; 16(3): 323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410694&dopt=Abstract

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Missed opportunities in physician management of glucocorticoid-induced osteoporosis? Author(s): Ramsey-Goldman R. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3115-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483714&dopt=Abstract

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Models for assessing the cost-effectiveness of the treatment and prevention of osteoporosis. Author(s): Zethraeus N, Ben Sedrine W, Caulin F, Corcaud S, Gathon HJ, Haim M, Johnell O, Jonsson B, Kanis JA, Tsouderos Y, Reginster JY. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 November; 13(11): 841-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415431&dopt=Abstract

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Modifiable and nonmodifiable factors associated with osteoporosis in postmenopausal women: results from the Third National Health and Nutrition Examination Survey, 1988-1994. Author(s): Snelling AM, Crespo CJ, Schaeffer M, Smith S, Walbourn L. Source: Journal of Women's Health & Gender-Based Medicine. 2001 January-February; 10(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11224945&dopt=Abstract

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Molecular mechanisms of glucocorticoid-induced osteoporosis. Author(s): Patschan D, Loddenkemper K, Buttgereit F. Source: Bone. 2001 December; 29(6): 498-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728918&dopt=Abstract

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Molecular studies of identification of genes for osteoporosis: the 2002 update. Author(s): Liu YZ, Liu YJ, Recker RR, Deng HW. Source: The Journal of Endocrinology. 2003 May; 177(2): 147-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740006&dopt=Abstract

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Monitoring treatment for osteoporosis by using bone densitometry. Author(s): Blake GM, Fogelman I. Source: Semin Nucl Med. 2001 July; 31(3): 212-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430528&dopt=Abstract

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Monofluorophosphate combined with hormone replacement therapy in postmenopausal osteoporosis. An open-label pilot efficacy and safety study. Author(s): Ringe JD, Setnikar I. Source: Rheumatology International. 2002 May; 22(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120908&dopt=Abstract

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Month 3 and month 6 measurements of bone mineral density predict the annual outcome in postmenopausal women with osteoporosis in whom alendronate was added to long-term HRT. Author(s): Pines A, Eckstein N, Kopernik G, Ayalon D, Comaneshter D, Frenkel Y. Source: Maturitas. 2003 April 25; 44(4): 287-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697369&dopt=Abstract

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Mortality, morbidity, and assessment of fracture risk in male osteoporosis. Author(s): Johnell O, Kanis J, Gullberg G. Source: Calcified Tissue International. 2001 October; 69(4): 182-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730245&dopt=Abstract

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Multiple imputation to account for missing data in a survey: estimating the prevalence of osteoporosis. Author(s): Kmetic A, Joseph L, Berger C, Tenenhouse A. Source: Epidemiology (Cambridge, Mass.). 2002 July; 13(4): 437-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094099&dopt=Abstract

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Myasthenia gravis, corticosteroids and osteoporosis prophylaxis. Author(s): Smith GD, Stevens DL, Fuller GN. Source: Journal of Neurology. 2001 February; 248(2): 151. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11284137&dopt=Abstract

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Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. Author(s): Prie D, Huart V, Bakouh N, Planelles G, Dellis O, Gerard B, Hulin P, BenqueBlanchet F, Silve C, Grandchamp B, Friedlander G. Source: The New England Journal of Medicine. 2002 September 26; 347(13): 983-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324554&dopt=Abstract

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Nephrolithiasis, osteoporosis, and mutations in the type 2a sodium-phosphate cotransporter. Author(s): Scheinman SJ, Tenenhouse HS. Source: The New England Journal of Medicine. 2003 January 16; 348(3): 264-5; Author Reply 264-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529474&dopt=Abstract

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New anabolic therapies in osteoporosis. Author(s): Rubin MR, Bilezikian JP. Source: Current Opinion in Rheumatology. 2002 July; 14(4): 433-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118181&dopt=Abstract

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New criteria for female athlete triad syndrome? As osteoporosis is rare, should osteopenia be among the criteria for defining the female athlete triad syndrome? Author(s): Khan KM, Liu-Ambrose T, Sran MM, Ashe MC, Donaldson MG, Wark JD. Source: British Journal of Sports Medicine. 2002 February; 36(1): 10-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867483&dopt=Abstract

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New possibilities for diagnosis and treatment of osteoporosis. Author(s): Miller PD. Source: Int J Fertil Womens Med. 2001 July-August; 46(4): 215-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563832&dopt=Abstract

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NIH releases statement on osteoporosis prevention, diagnosis, and therapy. Author(s): Hellekson KL. Source: American Family Physician. 2002 July 1; 66(1): 161-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126031&dopt=Abstract

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No association between the TGF-beta 1 Leu10Pro polymorphism and osteoporosis among white women in the United States. Author(s): Ziv E, Kahn A, Cauley J, Morin P, Saiz R, Browner W. Source: The American Journal of Medicine. 2003 February 15; 114(3): 227-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637138&dopt=Abstract

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No major effect of estrogen receptor beta gene RsaI polymorphism on bone mineral density and response to alendronate therapy in postmenopausal osteoporosis. Author(s): Arko B, Prezelj J, Komel R, Kocijancic A, Marc J. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 June; 81(2): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137804&dopt=Abstract

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Non-participants differ from participants as regards risk factors for vertebral deformities: a source of misinterpretation in the European Vertebral Osteoporosis Study. Author(s): Hasserius R, Karlsson MK, Nilsson BE, Redlund-Johnell I, Johnell O. Source: Acta Orthopaedica Scandinavica. 2002 August; 73(4): 451-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358120&dopt=Abstract

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Novel therapeutic targets in osteoporosis. Author(s): Tobias JH, Flanagan AM, Scutt AM. Source: Expert Opinion on Therapeutic Targets. 2002 February; 6(1): 41-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901480&dopt=Abstract

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Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis. Author(s): Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 June; 16(6): 1120-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393789&dopt=Abstract

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Occult bilateral acetabular fractures associated with high-energy trauma and osteoporosis. Author(s): Schachter AK, Roberts CS, Seligson D. Source: Journal of Orthopaedic Trauma. 2003 May; 17(5): 386-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759646&dopt=Abstract

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Occurrence of new vertebral body fracture after percutaneous vertebroplasty in patients with osteoporosis. Author(s): Uppin AA, Hirsch JA, Centenera LV, Pfiefer BA, Pazianos AG, Choi IS. Source: Radiology. 2003 January; 226(1): 119-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511679&dopt=Abstract

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Once-weekly treatment for osteoporosis. Author(s): Stone M. Source: Hosp Med. 2002 April; 63(4): 230-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995275&dopt=Abstract

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Optimal age for preventing osteoporosis after menopause depends on effects of stopping treatment. Author(s): Caulin F, Kanis JA, Johnell O, Oden A. Source: Bone. 2002 May; 30(5): 754-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996915&dopt=Abstract

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Optimizing bone metabolism in osteoporosis: insight into the pharmacologic profile of strontium ranelate. Author(s): Marie PJ. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003; 14 Suppl 3: S9-12. Epub 2003 March 18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730801&dopt=Abstract

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Oral administration of ketotifen in a patient with eosinophilic colitis and severe osteoporosis. Author(s): Katsinelos P, Pilpilidis I, Xiarchos P, Christodoulou K, Papagiannis A, Tsolkas P, Capelidis P, Vasiliadis I. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 1072-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003402&dopt=Abstract

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Oral radiographic predictors of osteoporosis. Author(s): White SC. Source: Dento Maxillo Facial Radiology. 2002 March; 31(2): 84-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076061&dopt=Abstract

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Organ transplantation and glucocorticoid-induced osteoporosis. Author(s): Giannini S, Nobile M, Sartori L. Source: Frontiers of Hormone Research. 2002; 30: 94-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892274&dopt=Abstract

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Orthopedic management of vertebral and long bone fractures in patients with osteoporosis. Author(s): Cornell CN, Lane JM, Poynton AR. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 433-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916295&dopt=Abstract

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Osteoclast formation from circulating precursors in osteoporosis. Author(s): Jevon M, Hirayama T, Brown MA, Wass JA, Sabokbar A, Ostelere S, Athenasou NA. Source: Scandinavian Journal of Rheumatology. 2003; 32(2): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737328&dopt=Abstract

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Osteonecrosis and transient osteoporosis of the hip: diagnostic and treatment dilemmas. Author(s): Harvey EJ. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 2003 June; 46(3): 168-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812235&dopt=Abstract

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Osteopenia and osteoporosis in anorexia nervosa. Author(s): Golden NH. Source: Adolescent Medicine (Philadelphia, Pa.). 2003 February; 14(1): 97-108. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529194&dopt=Abstract

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Osteoporosis 2002: headline news. Author(s): Watts N. Source: Southern Medical Journal. 2002 June; 95(6): 570-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081212&dopt=Abstract

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Osteoporosis after renal transplantation. Author(s): Trabulus S, Apaydin S, Altiparmak MR, Seyahi N, Sariyar M, Serdengecti K, Erek E. Source: Nefrologia. 2003; 23 Suppl 2: 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778869&dopt=Abstract

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Osteoporosis and anterior femoral notching in periprosthetic supracondylar femoral fractures: a biomechanical analysis. Author(s): Shawen SB, Belmont PJ Jr, Klemme WR, Topoleski LD, Xenos JS, Orchowski JR. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 January; 85-A(1): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533581&dopt=Abstract

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Osteoporosis and bisphosphonates. Author(s): Rodan GA, Reszka AA. Source: The Journal of Bone and Joint Surgery. American Volume. 2003; 85-A Suppl 3: 812. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925603&dopt=Abstract

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Osteoporosis and bone marrow mastocytosis: dissociation of skeletal responses and mast cell activity during long-term bisphosphonate therapy. Author(s): Brumsen C, Hamdy NA, Papapoulos SE. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 April; 17(4): 567-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924571&dopt=Abstract

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Osteoporosis and diabetes. Author(s): Chau DL, Edelman SV, Chandran M. Source: Curr Diab Rep. 2003 February; 3(1): 37-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643144&dopt=Abstract

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Osteoporosis and exercise. Author(s): Todd JA, Robinson RJ. Source: Postgraduate Medical Journal. 2003 June; 79(932): 320-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840119&dopt=Abstract

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Osteoporosis and fractures: the size of the problem. Author(s): Theodorou SJ, Theodorou DJ, Sartoris DJ. Source: Hosp Med. 2003 February; 64(2): 87-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619335&dopt=Abstract

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Osteoporosis and liver disease: additional reasons for coeliac disease screening. Author(s): Marignani M, Angeletti S, Morini S. Source: Gut. 2003 March; 52(3): 452. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584234&dopt=Abstract

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Osteoporosis and periodontal disease progression. Author(s): Geurs NC, Lewis CE, Jeffcoat MK. Source: Periodontology 2000. 2003; 32: 105-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756036&dopt=Abstract

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Osteoporosis and prevention of fractures: practical approaches for orthopaedic surgeons. Author(s): Kaufman JD, Cummings SR. Source: Instr Course Lect. 2002; 51: 559-65. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064147&dopt=Abstract

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Osteoporosis and quality of life psychosocial outcomes and interventions for individual patients. Author(s): Gold DT. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 271-80, Vi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916286&dopt=Abstract

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Osteoporosis associated with gastrointestinal diseases. Author(s): Compston J. Source: European Journal of Gastroenterology & Hepatology. 2003 August; 15(8): 841-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867791&dopt=Abstract

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Osteoporosis associated with the treatment of paraphilias: a clinical review of seven case reports. Author(s): Grasswick LJ, Bradford JM. Source: J Forensic Sci. 2003 July; 48(4): 849-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877306&dopt=Abstract

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Osteoporosis awareness: implications for improving the care of patients with hip fracture. Author(s): Kaufman JD. Source: The Journal of Bone and Joint Surgery. American Volume. 2002 April; 84-A(4): 683; Author Reply 683. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940637&dopt=Abstract

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Osteoporosis before lung transplantation: association with low body mass index, but not with underlying disease. Author(s): Tschopp O, Boehler A, Speich R, Weder W, Seifert B, Russi EW, Schmid C. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2002 February; 2(2): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099519&dopt=Abstract

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Osteoporosis coverage in selected women's magazines and newspapers, 1998-2001. Author(s): Wallace LS, Ballard JE. Source: American Journal of Health Behavior. 2003 January-February; 27(1): 75-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500954&dopt=Abstract

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Osteoporosis following chronic constriction injury of sciatic nerve in rats. Author(s): Suyama H, Moriwaki K, Niida S, Maehara Y, Kawamoto M, Yuge O. Source: Journal of Bone and Mineral Metabolism. 2002; 20(2): 91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862530&dopt=Abstract

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Osteoporosis guidelines. Author(s): Yendt ER. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 June 24; 168(13): 1644; Author Reply 1645-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821611&dopt=Abstract

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Osteoporosis guidelines. Author(s): Laupacis A. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 June 24; 168(13): 1644-5; Author Reply 1645-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821610&dopt=Abstract

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Osteoporosis imaging. Author(s): Link TM, Majumdar S. Source: Radiologic Clinics of North America. 2003 July; 41(4): 813-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899494&dopt=Abstract

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Osteoporosis in 5 elderly women with pubic osteolysis. Author(s): Takada J, Yamashita T, Takebayashi T, Nagoya S, Ishii S, Katahira G. Source: Acta Orthopaedica Scandinavica. 2003 February; 74(1): 59-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635795&dopt=Abstract

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Osteoporosis in aging--challenges and opportunities. Author(s): Kim I. Source: J Okla State Med Assoc. 2003 March; 96(3): 143-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688228&dopt=Abstract

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Osteoporosis in anorexia nervosa: a brittle future? Author(s): Katzman DK. Source: Current Drug Targets. Cns and Neurological Disorders. 2003 February; 2(1): 115. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769808&dopt=Abstract

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Osteoporosis in anorexia nervosa: prevention and treatment. Author(s): Mehler PS. Source: The International Journal of Eating Disorders. 2003 March; 33(2): 113-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616577&dopt=Abstract

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Osteoporosis in children: 2002 guidelines do not apply. Author(s): Taback SP. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 March 18; 168(6): 675-6; Author Reply 676. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642419&dopt=Abstract

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Osteoporosis in Cushing's syndrome. Author(s): Kaltsas G, Manetti L, Grossman AB. Source: Frontiers of Hormone Research. 2002; 30: 60-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892271&dopt=Abstract

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Osteoporosis in inflammatory bowel disease. Author(s): Compston J. Source: Gut. 2003 January; 52(1): 63-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477761&dopt=Abstract

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Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride. Author(s): Abitbol V, Mary JY, Roux C, Soule JC, Belaiche J, Dupas JL, Gendre JP, Lerebours E, Chaussade S; Groupe D'etudes Therapeutiques des Affections Inflammatoires Digestives (GETAID). Source: Alimentary Pharmacology & Therapeutics. 2002 May; 16(5): 919-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966500&dopt=Abstract

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Osteoporosis in men treated with androgen deprivation therapy for prostate cancer. Author(s): Ross RW, Small EJ. Source: The Journal of Urology. 2002 May; 167(5): 1952-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956415&dopt=Abstract

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Osteoporosis in men. Author(s): Campion JM, Maricic MJ. Source: American Family Physician. 2003 April 1; 67(7): 1521-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722852&dopt=Abstract

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Osteoporosis in men: pathophysiology, evaluation, and therapy. Author(s): Burgess E, Nanes MS. Source: Current Opinion in Rheumatology. 2002 July; 14(4): 421-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118179&dopt=Abstract

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Osteoporosis in men: suspect secondary disease first. Author(s): Licata A. Source: Cleve Clin J Med. 2003 March; 70(3): 247-54. Review. Erratum In: Cleve Clin J Med. 2003 June; 70(6): 501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678216&dopt=Abstract

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Osteoporosis in patients with inflammatory bowel disease. Author(s): Arden NK, Cooper C. Source: Gut. 2002 January; 50(1): 9-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772958&dopt=Abstract

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Osteoporosis in pediatrics. Author(s): Hartman C, Hochberg Z, Shamir R. Source: Isr Med Assoc J. 2003 July; 5(7): 509-15. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901249&dopt=Abstract

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Osteoporosis in postmenopausal women (Mexico City): 1. Risk factors. Author(s): Carranza-Lira S, Rosas M, Murillo A, Martinez N, Santos J. Source: Int J Fertil Womens Med. 2002 January-February; 47(1): 22-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900271&dopt=Abstract

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Osteoporosis in postmenopausal women (Mexico City): 2. Validation of a predictive clinical index. Author(s): Carranza-Lira S, Rosas M, Murillo A, Martinez N, Santos J. Source: Int J Fertil Womens Med. 2002 January-February; 47(1): 26-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900272&dopt=Abstract

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Osteoporosis in postmenopausal women. Author(s): Harvey M, De Lusignan S. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 June; 52(479): 496-7; Author Reply 497-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051217&dopt=Abstract

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Osteoporosis in postmenopausal women. Author(s): Pluskiewicz W, Drozdzowska B, Halaba Z. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 June; 52(479): 496; Author Reply 497-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051218&dopt=Abstract

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Osteoporosis in pulmonary clinic patients: does point-of-care screening predict central dual-energy X-ray absorptiometry? Author(s): Adler RA, Funkhouser HL, Petkov VI, Elmore BL, Via PS, McMurtry CT, Adera T. Source: Chest. 2003 June; 123(6): 2012-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796183&dopt=Abstract

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Osteoporosis in relation to menopause. Author(s): Choo WL, Loh FH, Ng SC. Source: Ann Acad Med Singapore. 2002 January; 31(1): 30-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885493&dopt=Abstract

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Osteoporosis intervention following distal forearm fractures: a missed opportunity? Author(s): Cuddihy MT, Gabriel SE, Crowson CS, Atkinson EJ, Tabini C, O'Fallon WM, Melton LJ 3rd. Source: Archives of Internal Medicine. 2002 February 25; 162(4): 421-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863474&dopt=Abstract

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Osteoporosis is not a specific complication of primary biliary cirrhosis (PBC). Author(s): Floreani A. Source: Gut. 2002 June; 50(6): 898; Author Reply 898-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12010900&dopt=Abstract

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Osteoporosis options. Choose medication based on age, health, and family history. Author(s): Cosman F. Source: Health News. 2003 July; 9(7): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838920&dopt=Abstract

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Osteoporosis prevention in primary care. Author(s): Schrager S. Source: Wmj. 2003; 102(3): 52-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822291&dopt=Abstract

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Osteoporosis prevention project: a model multidisciplinary educational intervention. Author(s): Brecher LS, Pomerantz SC, Snyder BA, Janora DM, Klotzbach-Shimomura KM, Cavalieri TA. Source: J Am Osteopath Assoc. 2002 June; 102(6): 327-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090650&dopt=Abstract

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Osteoporosis prevention: pediatricians' knowledge, attitudes, and counseling practices. Author(s): Fleming R, Patrick K. Source: Preventive Medicine. 2002 April; 34(4): 411-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914047&dopt=Abstract

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Osteoporosis prophylaxis during corticosteroid treatment: failure to prescribe. Author(s): Hart SR, Green B. Source: Postgraduate Medical Journal. 2002 April; 78(918): 242-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930029&dopt=Abstract

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Osteoporosis recognition: correcting Gehlbach et al. Author(s): Ann Intern Med. 2002 Dec 3;137(11):I31 Source: American Journal of Public Health. 2002 December; 92(12): 1885. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12459003

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Osteoporosis risk factor assessment and bone densitometry--current status and future trends. Author(s): Koh LK, Ng DC. Source: Ann Acad Med Singapore. 2002 January; 31(1): 37-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885494&dopt=Abstract

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Osteoporosis risks. A comparative study of Asian Australian and Caucasian Australian women. Author(s): Liew YL, Mann D, Piterman L. Source: Aust Fam Physician. 2002 March; 31(3): 291-3, 297. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926162&dopt=Abstract

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Osteoporosis screening by community pharmacists: use of National Osteoporosis Foundation resources. Author(s): Elliott ME, Meek PD, Kanous NL, Schill GR, Weinswig PA, Bohlman JP, Zimpel CL, Jensen BC, Walters DR, Sutter SL, Peterson AN, Peterson RM, Binkley NC. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2002 January-February; 42(1): 101-10; Quiz 110-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833500&dopt=Abstract

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Osteoporosis with underlying connective tissue disease: an unusual case. Author(s): Prasad R, De Silva M. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 474-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114306&dopt=Abstract

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Osteoporosis, the deafening silent epidemic. Author(s): Hamdy RC. Source: Southern Medical Journal. 2002 June; 95(6): 567-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081211&dopt=Abstract

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Osteoporosis. Author(s): Curry LC, Hogstel MO. Source: The American Journal of Nursing. 2002 January; 102(1): 26-32; Quiz 33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839904&dopt=Abstract

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Osteoporosis: a review. Author(s): Iqbal MM, Sobhan T. Source: Mo Med. 2002 January; 99(1): 19-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11816351&dopt=Abstract

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Osteoporosis: a treatable disease. Author(s): Leong KH, Koh LK, Ng DC. Source: Ann Acad Med Singapore. 2002 January; 31(1): 1-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885482&dopt=Abstract

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Osteoporosis: alternatives to estrogen treatment. Author(s): Fitzpatrick LA. Source: Minn Med. 2003 January; 86(1): 36-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585558&dopt=Abstract

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Osteoporosis: important knowledge for the ophthalmic healthcare provider. Author(s): Webb CS. Source: Insight (American Society of Ophthalmic Registered Nurses). 2002 JanuaryMarch; 27(1): 15-9; Quiz 20-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11962060&dopt=Abstract

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Osteoporosis: What a clinician expects to learn from a patient's bone density examination. Author(s): Lentle BC, Prior JC. Source: Radiology. 2003 September; 228(3): 620-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954887&dopt=Abstract

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Osteoporosis: what are the implications of DEXA scanning 'high risk' women in primary care? Author(s): Thomas E, Richardson JC, Irvine A, Hassell AB, Hay EM. Source: Family Practice. 2003 June; 20(3): 289-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738698&dopt=Abstract

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Osteoporosis--a worldwide problem and the implications in Asia. Author(s): Lau EM. Source: Ann Acad Med Singapore. 2002 January; 31(1): 67-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885498&dopt=Abstract

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Osteoporosis--the disease of the 21st century? Author(s): Clark S. Source: Lancet. 2002 May 18; 359(9319): 1714. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049857&dopt=Abstract

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p38 kinase inhibitors for the treatment of arthritis and osteoporosis: thienyl, furyl, and pyrrolyl ureas. Author(s): Redman AM, Johnson JS, Dally R, Swartz S, Wild H, Paulsen H, Caringal Y, Gunn D, Renick J, Osterhout M, Kingery-Wood J, Smith RA, Lee W, Dumas J, Wilhelm SM, Housley TJ, Bhargava A, Ranges GE, Shrikhande A, Young D, Bombara M, Scott WJ. Source: Bioorganic & Medicinal Chemistry Letters. 2001 January 8; 11(1): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11140741&dopt=Abstract

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Parathyroid hormone for treatment of osteoporosis. Author(s): Crandall C. Source: Archives of Internal Medicine. 2002 November 11; 162(20): 2297-309. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418944&dopt=Abstract

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Parathyroid hormone in the treatment of osteoporosis. Author(s): Fujita T. Source: Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. 2001; 15(11): 721-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707147&dopt=Abstract

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Parathyroid hormone: an anabolic treatment for osteoporosis. Author(s): Morley P, Whitfield JF, Willick GE. Source: Current Pharmaceutical Design. 2001 May; 7(8): 671-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375775&dopt=Abstract

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Pathogenesis of postmenopausal osteoporosis. Author(s): Raisz LG. Source: Reviews in Endocrine & Metabolic Disorders. 2001 January; 2(1): 5-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704980&dopt=Abstract

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Pathological fractures in AIDS patients with osteopenia and osteoporosis induced by antiretroviral therapy. Author(s): Guaraldi G, Ventura P, Albuzza M, Orlando G, Bedini A, Amorico G, Esposito R. Source: Aids (London, England). 2001 January 5; 15(1): 137-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192861&dopt=Abstract

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Pathophysiology of osteoporosis and fracture. Author(s): Lappe JM. Source: Nurs Clin North Am. 2001 September; 36(3): 393-400, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532654&dopt=Abstract

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Patient barriers to osteoporosis interventions after fracture. Author(s): Cuddihy MT, Amadio PC, Melton LJ 3rd. Source: Mayo Clinic Proceedings. 2002 August; 77(8): 875; Author Reply 875-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173724&dopt=Abstract

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Patterns of pharmacotherapy and counseling for osteoporosis management in visits to US ambulatory care physicians by women. Author(s): Lee E, Zuckerman IH, Weiss SR. Source: Archives of Internal Medicine. 2002 November 11; 162(20): 2362-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418951&dopt=Abstract

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Performance of the Osteoporosis Self-assessment Screening Tool for osteoporosis in American men. Author(s): Adler RA, Tran MT, Petkov VI. Source: Mayo Clinic Proceedings. 2003 June; 78(6): 723-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934782&dopt=Abstract

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Periodontal conditions in 70-year-old women with osteoporosis. Author(s): Lundstrom A, Jendle J, Stenstrom B, Toss G, Ravald N. Source: Swed Dent J. 2001; 25(3): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813450&dopt=Abstract

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Periodontal diseases and osteoporosis: association and mechanisms. Author(s): Wactawski-Wende J. Source: Ann Periodontol. 2001 December; 6(1): 197-208. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887465&dopt=Abstract

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Perspectives on osteoporosis in pediatric inflammatory bowel disease. Author(s): Harpavat M, Keljo DJ. Source: Current Gastroenterology Reports. 2003 June; 5(3): 225-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734045&dopt=Abstract

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Pharmacogenetics of the vitamin D receptor and osteoporosis. Author(s): Eisman JA. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 April; 29(4 Pt 2): 505-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11259341&dopt=Abstract

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Pharmacologic therapy for the treatment and prevention of osteoporosis. Author(s): McClung B, McClung M. Source: Nurs Clin North Am. 2001 September; 36(3): 433-40, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532658&dopt=Abstract

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Pharmacotherapeutics for osteoporosis prevention and treatment. Author(s): Davidson MR. Source: Journal of Midwifery & Women's Health. 2003 January-February; 48(1): 39-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589304&dopt=Abstract

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Pharmacotherapy of osteoporosis in postmenopausal women: focus on safety. Author(s): Reid IR. Source: Expert Opinion on Drug Safety. 2002 May; 1(1): 93-107. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904164&dopt=Abstract

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Pharmacy-based bone mass measurement to assess osteoporosis risk. Author(s): Elliott ME, Meek PD, Kanous NL, Schill GR, Weinswig PA, Bohlman JP, Zimpel CL, Jensen BC, Walters DR, Sutter SL, Peterson AN, Peterson RM, Binkley NC. Source: The Annals of Pharmacotherapy. 2002 April; 36(4): 571-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918501&dopt=Abstract

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Physical activity and bone development during childhood and adolescence. Implications for the prevention of osteoporosis. Author(s): Janz K. Source: Minerva Pediatr. 2002 April; 54(2): 93-104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981524&dopt=Abstract

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Physical activity and osteoporosis: disparities between knowledge and practice. Author(s): Gordon PM, Newcomer RR, Krummel DA. Source: W V Med J. 2001 May-June; 97(3): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11471464&dopt=Abstract

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Physician treatment of osteoporosis in response to heel ultrasound bone mineral density reports. Author(s): Boyd JL, Holcomb JP, Rothenberg RJ. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002 Winter; 5(4): 375-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665638&dopt=Abstract

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Plasma lipids and osteoporosis in postmenopausal women. Author(s): Yamaguchi T, Sugimoto T, Yano S, Yamauchi M, Sowa H, Chen Q, Chihara K. Source: Endocr J. 2002 April; 49(2): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081241&dopt=Abstract

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Population-based osteoporosis education for older women. Author(s): Curry LC, Hogstel MO, Davis GC, Frable PJ. Source: Public Health Nursing (Boston, Mass.). 2002 November-December; 19(6): 460-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406180&dopt=Abstract

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Possible pathogenetic role of new cytokines in postmenopausal osteoporosis and changes during calcitonin plus calcium therapy. Author(s): Gur A, Denli A, Nas K, Cevik R, Karakoc M, Sarac AJ, Erdogan F. Source: Rheumatology International. 2002 September; 22(5): 194-8. Epub 2002 July 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215865&dopt=Abstract

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Post-liver transplantation osteoporosis. Author(s): Cheung AM. Source: Journal of Hepatology. 2001 February; 34(2): 337-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281566&dopt=Abstract

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Postmenopausal breast cancer survivors at risk for osteoporosis: physical activity, vigor, and vitality. Author(s): Gross GJ, Ott CD, Lindsey AM, Twiss JJ, Waltman N. Source: Oncology Nursing Forum. 2002 October; 29(9): 1295-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370699&dopt=Abstract

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Postmenopausal hormone replacement therapy and major clinical outcomes: a focus on cardiovascular disease, osteoporosis, dementia, and breast and endometrial neoplasia. Author(s): Dick SE, DeWitt DE, Anawalt BD. Source: Am J Manag Care. 2002 January; 8(1): 95-104; Quiz 105-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11814176&dopt=Abstract

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Postmenopausal osteoporosis and celiac disease. Author(s): Chiechi LM, Valerio T, Loizzi P. Source: Clin Exp Obstet Gynecol. 2002; 29(3): 187-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519039&dopt=Abstract

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Postmenopausal osteoporosis and estrogen. Author(s): Nelson HD. Source: American Family Physician. 2003 August 15; 68(4): 606, 610, 612. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952379&dopt=Abstract

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Postmenopausal osteoporosis as a failure of bone's adaptation to functional loading: a hypothesis. Author(s): Lanyon L, Skerry T. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 November; 16(11): 1937-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11697789&dopt=Abstract

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Postmenopausal osteoporosis risk management in primary care: how well does it adhere to national practice guidelines? Author(s): Wei GS, Jackson JL, O'Malley PG. Source: J Am Med Womens Assoc. 2003 Spring; 58(2): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744423&dopt=Abstract

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Post-menopausal osteoporosis. Author(s): Marcus R. Source: Best Practice & Research. Clinical Obstetrics & Gynaecology. 2002 June; 16(3): 309-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099665&dopt=Abstract

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Postmenopausal survivors of breast cancer at risk for osteoporosis: nutritional intake and body size. Author(s): Lindsey AM, Gross G, Twiss J, Waltman N, Ott C, Moore TE. Source: Cancer Nursing. 2002 February; 25(1): 50-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838720&dopt=Abstract

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Postnatal growth failure, microcephaly, mental retardation, cataracts, large joint contractures, osteoporosis, cortical dysplasia, and cerebellar atrophy. Author(s): Shotelersuk V, Desudchit T, Suwanwela N. Source: American Journal of Medical Genetics. 2003 January 15; 116A(2): 164-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494436&dopt=Abstract

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Postpartal sacral fracture without osteoporosis. Author(s): Rousiere M, Kahan A, Job-Deslandre C. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2001 February; 68(1): 71-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235785&dopt=Abstract

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Potential use of HMG-CoA reductase inhibitors for osteoporosis. Author(s): Cushenberry LM, de Bittner MR. Source: The Annals of Pharmacotherapy. 2002 April; 36(4): 671-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918519&dopt=Abstract

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Practice pattern variation in the prevention and treatment of osteoporosis. Author(s): Casebeer L, James N. Source: Current Opinion in Rheumatology. 2002 July; 14(4): 453-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118184&dopt=Abstract

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Prediction of fracture risk in postmenopausal white women with peripheral bone densitometry: evidence from the National Osteoporosis Risk Assessment. Author(s): Miller PD, Siris ES, Barrett-Connor E, Faulkner KG, Wehren LE, Abbott TA, Chen YT, Berger ML, Santora AC, Sherwood LM. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 December; 17(12): 2222-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469916&dopt=Abstract

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Prediction of psychological reactions to bone density screening for osteoporosis using a cognitive-behavioral model of health anxiety. Author(s): Rimes KA, Salkovskis PM. Source: Behaviour Research and Therapy. 2002 April; 40(4): 359-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002895&dopt=Abstract

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Predictors of bone mineral density and osteoporosis in patients attending a rheumatology outpatient clinic. Author(s): Lee YH, Rho YH, Choi SJ, Ji JD, Song GG. Source: Rheumatology International. 2003 March; 23(2): 67-9. Epub 2002 October 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634938&dopt=Abstract

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Predictors of postmenopausal osteoporosis: study methods and analysis require clarification. Author(s): Wong J, Wong V, Fahey T, Brindle P, Hay A. Source: Bmj (Clinical Research Ed.). 2003 August 16; 327(7411): 392; Author Reply 392-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919999&dopt=Abstract

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Pregnancy associated osteoporosis: the familial effect. Author(s): Peris P, Guanabens N, Monegal A, Pons F, Martinez de Osaba MJ, Ros I, Munoz-Gomez J. Source: Clin Exp Rheumatol. 2002 September-October; 20(5): 697-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412203&dopt=Abstract

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Pregnancy, heparin and osteoporosis. Author(s): Schulman S, Hellgren-Wangdahl M. Source: Thrombosis and Haemostasis. 2002 February; 87(2): 180-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858474&dopt=Abstract

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Pregnancy-associated osteoporosis with hypercalcaemia. Author(s): Tran HA, Petrovsky N. Source: Internal Medicine Journal. 2002 September-October; 32(9-10): 481-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380703&dopt=Abstract

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Prenatal and childhood influences on osteoporosis. Author(s): Javaid MK, Cooper C. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2002 June; 16(2): 349-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064897&dopt=Abstract

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Prevalence and determinants of osteoporosis drug prescription among patients with high exposure to glucocorticoid drugs. Author(s): Ettinger B, Chidambaran P, Pressman A. Source: Am J Manag Care. 2001 June; 7(6): 597-605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439733&dopt=Abstract

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Prevalence of long term steroid treatment and the frequency of decision making to prevent steroid induced osteoporosis in daily clinical practice. Author(s): Gudbjornsson B, Juliusson UI, Gudjonsson FV. Source: Annals of the Rheumatic Diseases. 2002 January; 61(1): 32-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779755&dopt=Abstract

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Prevalence of osteopenia and osteoporosis in Thai women. Author(s): Limpaphayom KK, Taechakraichana N, Jaisamrarn U, Bunyavejchevin S, Chaikittisilpa S, Poshyachinda M, Taechamahachai C, Havanond P, Onthuam Y, Lumbiganon P, Kamolratanakul P. Source: Menopause (New York, N.Y.). 2001 January-February; 8(1): 65-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11201518&dopt=Abstract

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Prevalence rate of osteoporosis in the mid - aged and elderly in selected parts of China. Author(s): Li N, Ou P, Zhu H, Yang D, Zheng P. Source: Chin Med J (Engl). 2002 May; 115(5): 773-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133555&dopt=Abstract

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Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: a 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study. Author(s): Hasserius R, Karlsson MK, Nilsson BE, Redlund-Johnell I, Johnell O; European Vertebral Osteoporosis Study. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 January; 14(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577186&dopt=Abstract

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Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study. Author(s): Ismail AA, Cockerill W, Cooper C, Finn JD, Abendroth K, Parisi G, Banzer D, Benevolenskaya LI, Bhalla AK, Armas JB, Cannata JB, Delmas PD, Dequeker J, Dilsen G, Eastell R, Ershova O, Falch JA, Felsch B, Havelka S, Hoszowski K, Jajic I, Kragl U, Johnell O, Lopez Vaz A, Lorenc R, Yriti GL, Marchand F, Masary P, Matthis C, Miazgowski T, Pols HA, Poor G, Rapado A, Raspe HH, Reid DM, Reisinger W, Janott J, Scheidt-Nave C, Stepan J, Todd C, Weber K, Woolf AD, Ambrecht G, Gowin W, Felsenberg D, Lunt M, Kanis JA, Reeve J, Silman AJ, O'Neill TW. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(2): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303719&dopt=Abstract

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Prevent corticosteroid-induced osteoporosis. Author(s): Kessenich CR. Source: The Nurse Practitioner. 2002 April; 27(4): 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984415&dopt=Abstract

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Preventing and treating osteoporosis: strategies at the millennium. Author(s): Sherman S. Source: Annals of the New York Academy of Sciences. 2001 December; 949: 188-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795353&dopt=Abstract

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Preventing osteoporosis naturally. Author(s): Henderson NK, Prince RL. Source: The Medical Journal of Australia. 2001 September 3; 175(5): 239-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587251&dopt=Abstract

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Preventing osteoporosis. Lifelong nutrition and exercise habits are the most powerful weapons. Author(s): Motszko M. Source: Adv Nurse Pract. 2002 July; 10(7): 41-3, 76. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420550&dopt=Abstract

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Preventing osteoporosis: outcomes of the Australian Fracture Prevention Summit. Author(s): Sambrook PN, Seeman E, Phillips SR, Ebeling PR; Osteoporosis Australia; National Prescribing Service. Source: The Medical Journal of Australia. 2002 April 15; 176 Suppl: S1-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049064&dopt=Abstract

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Preventing osteoporosis: outcomes of the Australian Fracture Prevention Summit. Author(s): Carey RP, Plehwe WE. Source: The Medical Journal of Australia. 2002 August 5; 177(3): 167; Author Reply 167. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149096&dopt=Abstract

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Prevention and treatment of osteoporosis in postmenopausal women. Author(s): French L, Smith M, Shimp L. Source: The Journal of Family Practice. 2002 October; 51(10): 875-82. Review. Erratum In: J Fam Pract 2002 November; 51(11): 968. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401161&dopt=Abstract

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Prevention and treatment of osteoporosis in primary care offices. Author(s): Gill JM, Hoffman MK. Source: Journal of Women's Health (2002). 2003 June; 12(5): 473-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869294&dopt=Abstract

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Prevention and treatment of osteoporosis in the cystic fibrosis population. Author(s): Robinson RF, Nahata MC. Source: Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners. 2001 November-December; 15(6): 308-15; Quiz 316-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717688&dopt=Abstract

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Prevention and treatment of osteoporosis. Author(s): Lloyd M. Source: Clinical Medicine (London, England). 2001 March-April; 1(2): 155-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11333463&dopt=Abstract

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Prevention and treatment of osteoporosis: where are we today? Author(s): Maby JI. Source: J Am Osteopath Assoc. 2003 February; 103(2 Suppl 2): S9-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625633&dopt=Abstract

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Prevention for the older woman. A practical guide to prevention and treatment of osteoporosis. Author(s): Messinger-Rapport BJ, Thacker HL. Source: Geriatrics. 2002 April; 57(4): 16-8, 21-4, 27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11974387&dopt=Abstract

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Prevention of corticosteroid induced osteoporosis in inpatients recently discharged from a tertiary teaching hospital. Author(s): Smith MD, Cheah SP, Taylor K, Ahern MJ. Source: The Journal of Rheumatology. 2001 March; 28(3): 566-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296960&dopt=Abstract

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Prevention of glucocorticoid-induced osteoporosis: experience in a managed care setting. Author(s): Yood RA, Harrold LR, Fish L, Cernieux J, Emani S, Conboy E, Gurwitz JH. Source: Archives of Internal Medicine. 2001 May 28; 161(10): 1322-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11371261&dopt=Abstract

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Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years. Author(s): Jolly EE, Bjarnason NH, Neven P, Plouffe L Jr, Johnston CC Jr, Watts SD, Arnaud CD, Mason TM, Crans G, Akers R, Draper MW. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 337-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851517&dopt=Abstract

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Prevention of osteoporosis in cardiac transplant recipients. Author(s): Pisani B, Mullen GM. Source: Current Opinion in Cardiology. 2002 March; 17(2): 160-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981248&dopt=Abstract

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Prevention of osteoporosis. Author(s): Slawson DC, Shaughnessy AF, Schwartz K. Source: The Journal of Family Practice. 2002 March; 51(3): 287; Author Reply 287. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978245&dopt=Abstract

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Prevention of secondary osteoporosis postmenopause in hemiplegia. Author(s): Ikai T, Uematsu M, Eun SS, Kimura C, Hasegawa C, Miyano S. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2001 March; 80(3): 169-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11237270&dopt=Abstract

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Primary prevention of glucocorticoid-induced osteoporosis with intravenous pamidronate and calcium: a prospective controlled 1-year study comparing a single infusion, an infusion given once every 3 months, and calcium alone. Author(s): Boutsen Y, Jamart J, Esselinckx W, Devogelaer JP. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 January; 16(1): 104-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149473&dopt=Abstract

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Progression of coronary artery calcification in patients taking alendronate for osteoporosis. Author(s): Hill JA, Goldin JG, Gjertson D, Emerick AM, Greaser LD, Yoon HC, Khorrami S, Aziz D, Adams JS. Source: Academic Radiology. 2002 October; 9(10): 1148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385509&dopt=Abstract

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Pros and cons of existing treatment modalities in osteoporosis: a comparison between tibolone, SERMs and estrogen (+/-progestogen) treatments. Author(s): Kloosterboer HJ, Ederveen AG. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 December; 83(1-5): 157-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650712&dopt=Abstract

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PTH in the pathogenesis and treatment of glucocorticoid-induced osteoporosis. Author(s): Gennari C, Gonnelli S, Bruni D, Gennari L, Brandi ML. Source: Frontiers of Hormone Research. 2002; 30: 184-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892266&dopt=Abstract

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PTH revisited for osteoporosis treatment. Author(s): Kessenich CR. Source: The Nurse Practitioner. 2003 June; 28(6): 51-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796623&dopt=Abstract

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Pulmonary function tests, respiratory muscle strength, and endurance of patients with osteoporosis. Author(s): Cimen OB, Ulubas B, Sahin G, Calikoglu M, Bagis S, Erdogan C. Source: Southern Medical Journal. 2003 May; 96(5): 423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911178&dopt=Abstract

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Quality indicators for management of osteoporosis. Author(s): Bauer DC, Orwoll E. Source: Annals of Internal Medicine. 2002 October 1; 137(7): 621-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353958&dopt=Abstract

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Quality of life in osteoporosis. Author(s): Ioannidis G, Gordon M, Adachi JD. Source: Nurs Clin North Am. 2001 September; 36(3): 481-9, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532662&dopt=Abstract

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Quality-of-life assessment in osteoporosis: health-status and preference-based measures. Author(s): Tosteson AN, Hammond CS. Source: Pharmacoeconomics. 2002; 20(5): 289-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994039&dopt=Abstract

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Quantitative ultrasound and bone mineral density are equally strongly associated with risk factors for osteoporosis. Author(s): Frost ML, Blake GM, Fogelman I. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 February; 16(2): 406-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204441&dopt=Abstract

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Quantitative ultrasound and risk factor enquiry as predictors of postmenopausal osteoporosis: comparative study in primary care. Author(s): Hodson J, Marsh J. Source: Bmj (Clinical Research Ed.). 2003 June 7; 326(7401): 1250-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791742&dopt=Abstract

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Quantitative ultrasound in osteoporosis. Author(s): Stewart A, Reid DM. Source: Seminars in Musculoskeletal Radiology. 2002 September; 6(3): 229-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541200&dopt=Abstract

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Quantitative ultrasound of bone in male osteoporosis. Author(s): Mulleman D, Legroux-Gerot I, Duquesnoy B, Marchandise X, Delcambre B, Cortet B. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 May; 13(5): 388-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086349&dopt=Abstract

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Racial disparities in osteoporosis prevention in a managed care population. Author(s): Mudano AS, Casebeer L, Patino F, Allison JJ, Weissman NW, Kiefe CI, Person S, Gilbert D, Saag KG. Source: Southern Medical Journal. 2003 May; 96(5): 445-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911182&dopt=Abstract

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Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associated with generalised osteoporosis. Author(s): Forsblad D'Elia H, Larsen A, Waltbrand E, Kvist G, Mellstrom D, Saxne T, Ohlsson C, Nordborg E, Carlsten H. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 617-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810422&dopt=Abstract

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Radiologic bone assessment in the evaluation of osteoporosis. Author(s): Brunader R, Shelton DK. Source: American Family Physician. 2002 April 1; 65(7): 1357-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996418&dopt=Abstract

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Radiology of osteoporosis. Author(s): Quek ST, Peh WC. Source: Seminars in Musculoskeletal Radiology. 2002 September; 6(3): 197-206. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541197&dopt=Abstract

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Raloxifene administration in post-menopausal women with osteoporosis: effect of different BsmI vitamin D receptor genotypes. Author(s): Palomba S, Numis FG, Mossetti G, Rendina D, Vuotto P, Russo T, Zullo F, Nappi C, Nunziata V. Source: Human Reproduction (Oxford, England). 2003 January; 18(1): 192-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525466&dopt=Abstract

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Rapid increase in bone mineral density in a child with osteoporosis and autoimmune hypoparathyroidism treated with PTH 1-34. Author(s): Koch CA. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2001; 109(6): 350-4. Retraction In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571675&dopt=Abstract

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Rationale for active vitamin D and analogs in the treatment of osteoporosis. Author(s): Nishii Y. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 381-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520540&dopt=Abstract

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Re: Diethylstilbesterol revised: androgen deprivation, osteoporosis and prostate cancer. Author(s): Pitts WR Jr. Source: The Journal of Urology. 2002 November; 168(5): 2131-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394735&dopt=Abstract

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Re: Diethylstilbesterol revisited: androgen deprivation, osteoporosis an prostate cancer. Author(s): Pitts WR Jr. Source: The Journal of Urology. 2002 July; 168(1): 201; Author Reply 201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050534&dopt=Abstract

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Re: Diethylstilbestrol revisited: androgen deprivation, osteoporosis and prostate cancer. Author(s): Pitts WR Jr. Source: The Journal of Urology. 2002 October; 168(4 Pt 1): 1506-7. Erratum In: J Urol 2003 January; 169(1): 295. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352441&dopt=Abstract

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Re: Skeletal fracture associated with androgen suppression induced osteoporosis: the clinical incidence and risk factors for patients with prostate cancer. Author(s): Miro C, De Cobelli O, Orecchia R, Sancho G, Villavicencio H, Craven-Bartle J. Source: The Journal of Urology. 2002 August; 168(2): 662-3; Author Reply 663. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131341&dopt=Abstract

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Recent developments in the epidemiology of osteoporosis. Author(s): Walker-Bone K, Walter G, Cooper C. Source: Current Opinion in Rheumatology. 2002 July; 14(4): 411-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118177&dopt=Abstract

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Recognition of osteoporosis since 1997. Author(s): Simon M. Source: American Journal of Public Health. 2002 November; 92(11): 1707. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406786&dopt=Abstract

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Recombinant human PTH 1-34 (Forteo): an anabolic drug for osteoporosis. Author(s): Deal C, Gideon J. Source: Cleve Clin J Med. 2003 July; 70(7): 585-6, 589-90, 592-4 Passim. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882381&dopt=Abstract

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Recommendations for the prevention of osteoporosis and fragility fractures. International comparison and synthesis. Author(s): Rossignol M, Moride Y, Perreault S, Boivin JF, Ste-Marie LG, Robitaille Y, Poulin de Courval L, Fautrel B. Source: International Journal of Technology Assessment in Health Care. 2002 Summer; 18(3): 597-610. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391952&dopt=Abstract

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Recovery from severe glucocorticoid-induced osteoporosis in an adolescent boy. Author(s): Geusens P, Menten J, Vosse D, Vanhoof J, van der Linden S. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2001 Winter; 4(4): 389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748345&dopt=Abstract

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Reduced bone formation and increased bone resorption: rational targets for the treatment of osteoporosis. Author(s): Seeman E. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003; 14 Suppl 3: S2-8. Epub 2003 March 19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730770&dopt=Abstract

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Regional migratory osteoporosis: a pathogenetic hypothesis based on three cases and a review of the literature. Author(s): Trevisan C, Ortolani S, Monteleone M, Marinoni EC. Source: Clinical Rheumatology. 2002 September; 21(5): 418-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223996&dopt=Abstract

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Regional osteoporosis in women who have a complete spinal cord injury. Author(s): Garland DE, Adkins RH, Stewart CA, Ashford R, Vigil D. Source: The Journal of Bone and Joint Surgery. American Volume. 2001 August; 83-A(8): 1195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11507128&dopt=Abstract

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Regression to the mean: what does it mean? Using bone density results to monitor treatment of osteoporosis. Author(s): Lenchik L, Watts NB. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2001 Spring; 4(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11309514&dopt=Abstract

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Relation of BsmI vitamin D receptor gene polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal Chinese women in Taiwan. Author(s): Chen HY, Chen WC, Hsu CD, Tsai FJ, Tsai CH, Li CW. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001 December; 12(12): 1036-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846330&dopt=Abstract

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Relation of polymorphism in the promotor region for the human osteocalcin gene to bone mineral density and occurrence of osteoporosis in postmenopausal Chinese women in Taiwan. Author(s): Chen HY, Tsai HD, Chen WC, Wu JY, Tsai FJ, Tsai CH. Source: Journal of Clinical Laboratory Analysis. 2001; 15(5): 251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574953&dopt=Abstract

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Relation of the estrogen receptor alpha gene microsatellite polymorphism to bone mineral density and the susceptibility to osteoporosis in postmenopausal Chinese women in Taiwan. Author(s): Chen HY, Chen WC, Tsai HD, Hsu CD, Tsai FJ, Tsai CH. Source: Maturitas. 2001 November 30; 40(2): 143-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716992&dopt=Abstract

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Relation of vitamin D receptor FokI start codon polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal women in Taiwan. Author(s): Chen HY, Chen WC, Hsu CD, Tsai FJ, Tsai CH. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 February; 81(2): 93-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942896&dopt=Abstract

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Relationship between serum leptin concentrations and bone mineral density as well as biochemical markers of bone turnover in women with postmenopausal osteoporosis. Author(s): Shaarawy M, Abassi AF, Hassan H, Salem ME. Source: Fertility and Sterility. 2003 April; 79(4): 919-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749431&dopt=Abstract

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Reliability and validity of the self-efficacy and outcome expectations for osteoporosis medication adherence scales. Author(s): Resnick B, Wehren L, Orwig D. Source: Orthopaedic Nursing / National Association of Orthopaedic Nurses. 2003 March-April; 22(2): 139-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703398&dopt=Abstract

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Reproducibility of DXA: potential impact on serial measurements and misclassification of osteoporosis. Author(s): Phillipov G, Seaborn CJ, Phillips PJ. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305083&dopt=Abstract

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Resistance training prevents vertebral osteoporosis in lung transplant recipients. Author(s): Mitchell MJ, Baz MA, Fulton MN, Lisor CF, Braith RW. Source: Transplantation. 2003 August 15; 76(3): 557-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923444&dopt=Abstract

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Results of a 10 week community based strength and balance training programme to reduce fall risk factors: a randomised controlled trial in 65-75 year old women with osteoporosis. Author(s): Carter ND, Khan KM, Petit MA, Heinonen A, Waterman C, Donaldson MG, Janssen PA, Mallinson A, Riddell L, Kruse K, Prior JC, Flicker L, McKay HA. Source: British Journal of Sports Medicine. 2001 October; 35(5): 348-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11579072&dopt=Abstract

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Results of a home exercise program for patients with osteoporosis resulting from neurological disorders. Author(s): Shimizu ME, Ishizaki F, Nakamura S. Source: Hiroshima J Med Sci. 2002 March; 51(1): 15-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999456&dopt=Abstract

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Retinal detachment and cataract, facial dysmorphism, generalized osteoporosis, immobile spine and platyspondyly in a consanguinous kindred--a possible new syndrome. Author(s): Schmidt H, Rudolph G, Hergersberg M, Schneider K, Moradi S, Meitinger T. Source: Clinical Genetics. 2001 February; 59(2): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11260210&dopt=Abstract

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Reversible migratory osteoporosis in renal oncocytoma mimicking renal cell carcinoma with bone metastases. Author(s): Peters FP, Verhoeven MA, Anten HW, Erdkamp FL, van der Pol H. Source: The Netherlands Journal of Medicine. 2002 November; 60(10): 411-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607593&dopt=Abstract

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Review of ibandronate in the treatment of osteoporosis. Author(s): Chapurlat RD, Delmas PD. Source: Expert Opinion on Pharmacotherapy. 2003 March; 4(3): 391-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614191&dopt=Abstract

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Review of raloxifene and its clinical applications in osteoporosis. Author(s): Maricic M, Gluck O. Source: Expert Opinion on Pharmacotherapy. 2002 June; 3(6): 767-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036416&dopt=Abstract

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Review of risedronate in the treatment of osteoporosis. Author(s): Geusens P, McClung M. Source: Expert Opinion on Pharmacotherapy. 2001 December; 2(12): 2011-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11825332&dopt=Abstract

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Revision of the Facts on Osteoporosis Quiz. Author(s): Ailinger RL, Lasus H, Braun MA. Source: Nursing Research. 2003 May-June; 52(3): 198-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792261&dopt=Abstract

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Rheumatic disorders and glucocorticoid-induced osteoporosis. Author(s): Dequeker J, Westhovens R, Luyten FP. Source: Frontiers of Hormone Research. 2002; 30: 107-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892257&dopt=Abstract

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Risedronate for the prevention and treatment of corticosteroid-induced osteoporosis. Author(s): Dougherty JA. Source: The Annals of Pharmacotherapy. 2002 March; 36(3): 512-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895066&dopt=Abstract

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Risedronate for the prevention and treatment of postmenopausal osteoporosis: results from recent clinical trials. Author(s): Watts NB. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001 December; 12 Suppl 3: S17-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846337&dopt=Abstract

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Risedronate for the prevention of fractures in postmenopausal osteoporosis. Author(s): Sickels JM, Nip CS. Source: The Annals of Pharmacotherapy. 2002 April; 36(4): 664-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918518&dopt=Abstract

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Risk factors for hip fracture in Asian men and women: the Asian osteoporosis study. Author(s): Lau EM, Suriwongpaisal P, Lee JK, Das De S, Festin MR, Saw SM, Khir A, Torralba T, Sham A, Sambrook P. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 March; 16(3): 572-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11277276&dopt=Abstract

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Risk factors for osteoporosis in a subgroup of elderly men in a Veterans Administration nursing home. Author(s): Yeh SS, Phanumas D, Hafner A, Schuster MW. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2002 November; 50(6): 452-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425432&dopt=Abstract

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Risk factors for osteoporosis in Alaska Native women: a cross-sectional survey. Author(s): Filner JJ, Krohn KD, Lapidus JA, Becker TM. Source: Alaska Med. 2002 January-March; 44(1): 8-13, 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11969140&dopt=Abstract

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Risk factors for osteoporosis in Asia. Author(s): Suzuki T. Source: Journal of Bone and Mineral Metabolism. 2001; 19(3): 133-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11368297&dopt=Abstract

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Risk factors for osteoporosis in Europe. Author(s): Lau EM, Cooper C. Source: Journal of Bone and Mineral Metabolism. 2001; 19(3): 142-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11368298&dopt=Abstract

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Risk factors for osteoporosis related to their outcome: fractures. Author(s): van der Voort DJ, Geusens PP, Dinant GJ. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(8): 630-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11580076&dopt=Abstract

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Risk factors for proximal femur osteoporosis in men aged 50 years or older. Author(s): Tanaka T, Latorre MR, Jaime PC, Florindo AA, Pippa MG, Zerbini CA. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(11): 942-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11804021&dopt=Abstract

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Risk factors for proximal humerus, forearm, and wrist fractures in elderly men and women: the Dubbo Osteoporosis Epidemiology Study. Author(s): Nguyen TV, Center JR, Sambrook PN, Eisman JA. Source: American Journal of Epidemiology. 2001 March 15; 153(6): 587-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257067&dopt=Abstract

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Risk indices and osteoporosis screening: scope and limits. Author(s): Ben Sedrine W, Reginster JY. Source: Mayo Clinic Proceedings. 2002 July; 77(7): 622-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108598&dopt=Abstract

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Risk status related to knowledge of osteoporosis in older women. Author(s): Curry LC, Hogstel MO. Source: J Women Aging. 2001; 13(2): 71-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11569595&dopt=Abstract

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Role of alendronate and risedronate in preventing and treating osteoporosis. Author(s): Peters ML, Leonard M, Licata AA. Source: Cleve Clin J Med. 2001 November; 68(11): 945-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11718433&dopt=Abstract

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Role of biochemical markers in the management of osteoporosis. Author(s): Ebeling PR, Akesson K. Source: Best Practice & Research. Clinical Rheumatology. 2001 July; 15(3): 385-400. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485336&dopt=Abstract

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Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis. Author(s): Woo T, Adachi JD. Source: Best Practice & Research. Clinical Rheumatology. 2001 July; 15(3): 469-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485341&dopt=Abstract

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Role of calcium, vitamin D, and other essential nutrients in the prevention and treatment of osteoporosis. Author(s): Dowd R. Source: Nurs Clin North Am. 2001 September; 36(3): 417-31, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532657&dopt=Abstract

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Role of exercise in preventing and treating osteoporosis. Author(s): Marcus R. Source: Rheumatic Diseases Clinics of North America. 2001 February; 27(1): 131-41, Vi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285991&dopt=Abstract

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Role of genetic factors in the pathophysiology and management of osteoporosis. Author(s): Hobson EE, Ralston SH. Source: Clinical Endocrinology. 2001 January; 54(1): 1-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11167918&dopt=Abstract

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Role of genetics in osteoporosis. Author(s): Recker RR, Deng HW. Source: Endocrine. 2002 February; 17(1): 55-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014706&dopt=Abstract

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Role of the vitamin D-endocrine system in the pathophysiology of postmenopausal osteoporosis. Author(s): Riggs BL. Source: Journal of Cellular Biochemistry. 2003 February 1; 88(2): 209-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520516&dopt=Abstract

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Role of vascular factors in osteoporosis. Author(s): Alagiakrishnan K, Juby A, Hanley D, Tymchak W, Sclater A. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 April; 58(4): 362-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663699&dopt=Abstract

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Screening for celiac disease in idiopathic osteoporosis. Author(s): Di Stefano M, Veneto G, Corazza GR. Source: The American Journal of Gastroenterology. 2001 November; 96(11): 3205-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721778&dopt=Abstract

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Screening for osteoporosis and colon cancer under Medicare. Author(s): Adler GS, Shatto A. Source: Health Care Financing Review. 2002 Summer; 23(4): 189-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500479&dopt=Abstract

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Screening for osteoporosis in patients with inflammatory bowel disease by using urinary N-telopeptides. Author(s): Bregenzer N, Erban P, Albrich H, Schmitz G, Feuerbach S, Scholmerich J, Andus T. Source: European Journal of Gastroenterology & Hepatology. 2002 June; 14(6): 599-605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072593&dopt=Abstract

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Screening for osteoporosis in postmenopausal women: recommendations and rationale. Author(s): Berg AO. Source: The American Journal of Nursing. 2003 January; 103(1): 73-80; Discussion 81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544063&dopt=Abstract

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Screening for osteoporosis in postmenopausal women: recommendations and rationale. Author(s): U.S. Preventive Services Task Force. Source: American Family Physician. 2002 October 15; 66(8): 1430-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408417&dopt=Abstract

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Screening for osteoporosis in postmenopausal women: recommendations and rationale. Author(s): Ann Intern Med. 2002 Sep 17;137(6):I59 Source: Annals of Internal Medicine. 2002 September 17; 137(6): 526-8. Summary for Patients In: /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12230384

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Screening for postmenopausal osteoporosis. Author(s): Daniell HW. Source: Annals of Internal Medicine. 2003 April 15; 138(8): 689; Author Reply 389-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693905&dopt=Abstract

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Screening for postmenopausal osteoporosis: a review of the evidence for the U.S. Preventive Services Task Force. Author(s): Nelson HD, Helfand M, Woolf SH, Allan JD. Source: Annals of Internal Medicine. 2002 September 17; 137(6): 529-41. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230356&dopt=Abstract

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Search for occult secondary osteoporosis: impact of identified possible risk factors on bone mineral density. Author(s): Deutschmann HA, Weger M, Weger W, Kotanko P, Deutschmann MJ, Skrabal F. Source: Journal of Internal Medicine. 2002 November; 252(5): 389-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528756&dopt=Abstract

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Secondary causes of osteoporosis in men. Author(s): Compston J. Source: Calcified Tissue International. 2001 October; 69(4): 193-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730248&dopt=Abstract

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Secondary causes of osteoporosis. Author(s): Fitzpatrick LA. Source: Mayo Clinic Proceedings. 2002 May; 77(5): 453-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004995&dopt=Abstract

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Secondary osteoporosis and the risk of distal forearm fractures in men and women. Author(s): Melton LJ 3rd, Achenbach SJ, O'fallon WM, Khosla S. Source: Bone. 2002 July; 31(1): 119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110424&dopt=Abstract

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Secondary osteoporosis in women. A retrospective analysis. Author(s): Cakir B, Odabasi E, Turan M, Guler S, Kutlu M. Source: Archives of Gynecology and Obstetrics. 2002 August; 266(4): 214-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192482&dopt=Abstract

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Secondary prevention of osteoporosis: when should a non-vertebral fracture be a trigger for action? Author(s): Eastell R, Reid DM, Compston J, Cooper C, Fogelman I, Francis RM, Hay SM, Hosking DJ, Purdie DW, Ralston SH, Reeve J, Russell RG, Stevenson JC. Source: Qjm : Monthly Journal of the Association of Physicians. 2001 November; 94(11): 575-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704688&dopt=Abstract

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Secreting ovarian tumors may protect women from osteoporosis. Author(s): Castelo-Branco C, Gomez O, Pons F, Martinez de Osaba MJ, Balasch J, Antonio Vanrell J. Source: Gynecologic Oncology. 2003 February; 88(2): 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586594&dopt=Abstract

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Seeking genetic causes of “osteoporosis:” insights of the Utah paradigm of skeletal physiology. Author(s): Frost HM. Source: Bone. 2001 November; 29(5): 407-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704489&dopt=Abstract

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Selective estrogen receptor modulation and reduction in risk of breast cancer, osteoporosis, and coronary heart disease. Author(s): Jordan VC, Gapstur S, Morrow M. Source: Journal of the National Cancer Institute. 2001 October 3; 93(19): 1449-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11584060&dopt=Abstract

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Semiquantitative evaluation of prevalent vertebral deformities in men and their relationship with osteoporosis: the MINOS study. Author(s): Szulc P, Munoz F, Marchand F, Delmas PD. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(4): 302-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420780&dopt=Abstract

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Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis. Author(s): Arko B, Prezelj J, Komel R, Kocijancic A, Hudler P, Marc J. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 September; 87(9): 4080-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213850&dopt=Abstract

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Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis. Author(s): Shaarawy M, Hasan M. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2001; 61(7): 51321. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763409&dopt=Abstract

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Serum bone specific alkaline phosphatase and urinary deoxypyridinoline in postmenopausal osteoporosis. Author(s): Nawawi HM, Yazid TN, Ismail NM, Mohamad AR, Nirwana SI, Khalid BA. Source: Malays J Pathol. 2001 December; 23(2): 79-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166596&dopt=Abstract

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Serum insulin/like growth factor I, bone mineral density and biochemical markers of bone metabolism in children with idiopathic osteoporosis. Author(s): Chlebna-Sokol D, Rusinska A. Source: Endocrine Regulations. 2001 December; 35(4): 201-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858767&dopt=Abstract

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Serum interleukin-6 reflects disease severity and osteoporosis in mastocytosis patients. Author(s): Theoharides TC, Boucher W, Spear K. Source: International Archives of Allergy and Immunology. 2002 August; 128(4): 344-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218373&dopt=Abstract

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Serum prolidase activity as a marker of osteoporosis in type 2 diabetes mellitus. Author(s): Erbagci AB, Araz M, Erbagci A, Tarakcioglu M, Namiduru ES. Source: Clinical Biochemistry. 2002 June; 35(4): 263-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135686&dopt=Abstract

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Severe hypertension and massive osteoporosis as presenting symptoms of Cushing's syndrome. Author(s): Endemann DH, Fischereder M, Leingartner T, Stubanus M, Zietz B, Riegger GA, Kramer BK. Source: American Journal of Nephrology. 2001 May-June; 21(3): 245-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11423697&dopt=Abstract

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Severe osteoporosis and autonomous hyperparathyroidism: making the numbers add up. Author(s): Weis U, Meeking DR, Cummings MH. Source: Qjm : Monthly Journal of the Association of Physicians. 2002 April; 95(4): 255-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937656&dopt=Abstract

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Severe symptomatic osteoporosis in patients on androgen deprivation therapy for prostatic carcinoma. Author(s): Paterson CR, Mole PA. Source: Scandinavian Journal of Urology and Nephrology. 2002; 36(4): 314-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201927&dopt=Abstract

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Severe transient osteoporosis of the hip during pregnancy. Successful treatment with intravenous biphosphonates. Author(s): Schapira D, Braun Moscovici Y, Gutierrez G, Nahir AM. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 107-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673900&dopt=Abstract

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Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial. Author(s): Greenspan SL, Emkey RD, Bone HG, Weiss SR, Bell NH, Downs RW, McKeever C, Miller SS, Davidson M, Bolognese MA, Mulloy AL, Heyden N, Wu M, Kaur A, Lombardi A. Source: Annals of Internal Medicine. 2002 December 3; 137(11): 875-83. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458987&dopt=Abstract

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Simulation of osteoporosis bone changes: effects on the degree of anisotropy. Author(s): Pothuaud L, Levitz P, Benhamou CL. Source: Advances in Experimental Medicine and Biology. 2001; 496: 111-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783613&dopt=Abstract

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Six and twelve month changes in bone turnover are related to reduction in vertebral fracture risk during 3 years of raloxifene treatment in postmenopausal osteoporosis. Author(s): Bjarnason NH, Sarkar S, Duong T, Mitlak B, Delmas PD, Christiansen C. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(11): 922-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808544&dopt=Abstract

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Skeletal adaptations to alterations in weight-bearing activity: a comparison of models of disuse osteoporosis. Author(s): Giangregorio L, Blimkie CJ. Source: Sports Medicine (Auckland, N.Z.). 2002; 32(7): 459-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12015807&dopt=Abstract

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Skeletal fracture associated with androgen suppression induced osteoporosis: the clinical incidence and risk factors for patients with prostate cancer. Author(s): Oefelein MG, Ricchuiti V, Conrad W, Seftel A, Bodner D, Goldman H, Resnick M. Source: The Journal of Urology. 2001 November; 166(5): 1724-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586210&dopt=Abstract

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Smokeless tobacco and osteoporosis: a new relationship? Author(s): Spangler JG, Quandt S, Bell RA. Source: Medical Hypotheses. 2001 May; 56(5): 553-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388768&dopt=Abstract

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Social support, knowledge, and self-efficacy as correlates of osteoporosis preventive behaviors among preadolescent females. Author(s): Ievers-Landis CE, Burant C, Drotar D, Morgan L, Trapl ES, Kwoh CK. Source: Journal of Pediatric Psychology. 2003 July-August; 28(5): 335-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808010&dopt=Abstract

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Spinal performance and functional impairment in postmenopausal women with osteoporosis and osteopenia without vertebral fracture. Author(s): Tsauo JY, Chien MY, Yang RS. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002; 13(6): 456-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107658&dopt=Abstract

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Spondylo-ocular syndrome: a new entity with crystalline lens malformation, cataract, retinal detachment, osteoporosis, and platyspondyly. Author(s): Rudolph G, Kalpadakis P, Bettecken T, Lichtner P, Haritoglou C, Hergersberg M, Meitinger T, Schmidt H. Source: American Journal of Ophthalmology. 2003 May; 135(5): 681-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719077&dopt=Abstract

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Statin use, bone mineral density, and fracture risk: Geelong Osteoporosis Study. Author(s): Pasco JA, Kotowicz MA, Henry MJ, Sanders KM, Nicholson GC; Geelong Osteoporosis Study. Source: Archives of Internal Medicine. 2002 March 11; 162(5): 537-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11871921&dopt=Abstract

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Statins and osteoporosis: can these lipid-lowering drugs also bolster bones? Author(s): Cruz AC, Gruber BL. Source: Cleve Clin J Med. 2002 April; 69(4): 277-8, 280-2, 287-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996199&dopt=Abstract

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Statins and their potential for osteoporosis. Author(s): Mundy GR. Source: Bone. 2001 December; 29(6): 495-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728917&dopt=Abstract

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Statins as novel therapies for osteoporosis? Author(s): Galloway P, Greer IA, Sattar N. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2002 February 10; 101(1): 4-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11803091&dopt=Abstract

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Statins, hormones, and women: benefits and drawbacks for atherosclerosis and osteoporosis. Author(s): Herrington DM, Potvin Klein K. Source: Current Atherosclerosis Reports. 2001 January; 3(1): 35-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11123846&dopt=Abstract

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Statins: new drugs for treating osteoporosis? Author(s): Whitfield JF. Source: Expert Opinion on Investigational Drugs. 2001 March; 10(3): 409-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11424897&dopt=Abstract

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Steroid-induced osteoporosis. Author(s): Sambrook PN. Source: Ann Acad Med Singapore. 2002 January; 31(1): 48-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885496&dopt=Abstract

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Steroids cause osteoporosis. Author(s): Paget S. Source: Annals of the Rheumatic Diseases. 2002 January; 61(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779746&dopt=Abstract

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Sticks and stones. Osteoporosis can break your bones, even if you are a man. This disease is not for women only. Author(s): Smith IK. Source: Time. 2001 February 12; 157(6): 90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216229&dopt=Abstract

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Stress fracture of the foot secondary to osteoporosis: an atypical presentation. Author(s): Freeman D, Randall DB. Source: Journal of the American Podiatric Medical Association. 2001 February; 91(2): 99101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11266487&dopt=Abstract

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Strontium ranelate in osteoporosis. Author(s): Reginster JY. Source: Current Pharmaceutical Design. 2002; 8(21): 1907-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171530&dopt=Abstract

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Strontium ranelate: a new paradigm in the treatment of osteoporosis. Author(s): Reginster JY, Deroisy R, Jupsin I. Source: Drugs Today (Barc). 2003 February; 39(2): 89-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698204&dopt=Abstract

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Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis--a 2-year randomized placebo controlled trial. Author(s): Meunier PJ, Slosman DO, Delmas PD, Sebert JL, Brandi ML, Albanese C, Lorenc R, Pors-Nielsen S, De Vernejoul MC, Roces A, Reginster JY. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 May; 87(5): 2060-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994341&dopt=Abstract

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Structure-based development of cathepsin L inhibitors and therapeutic applications for prevention of cancer metastasis and cancer-induced osteoporosis. Author(s): Katunuma N, Tsuge H, Nukatsuka M, Fukushima M. Source: Advances in Enzyme Regulation. 2002; 42: 159-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12123713&dopt=Abstract

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Subchondral changes in transient osteoporosis of the hip. Author(s): Miyanishi K, Yamamoto T, Nakashima Y, Shuto T, Jingushi S, Noguchi Y, Iwamoto Y. Source: Skeletal Radiology. 2001 May; 30(5): 255-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407716&dopt=Abstract

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Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis. Author(s): Conover CA, Johnstone EW, Turner RT, Evans GL, John Ballard FJ, Doran PM, Khosla S. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2002 June; 12(3): 178-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162999&dopt=Abstract

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Summary of meta-analyses of therapies for postmenopausal osteoporosis and the relationship between bone density and fractures. Author(s): Guyatt GH, Cranney A, Griffith L, Walter S, Krolicki N, Favus M, Rosen C. Source: Endocrinology and Metabolism Clinics of North America. 2002 September; 31(3): 659-79, Xii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227126&dopt=Abstract

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Sunscreen and risk of osteoporosis in the elderly: a two-year follow-up. Author(s): Farrerons J, Barnadas M, Lopez-Navidad A, Renau A, Rodriguez J, Yoldi B, Alomar A. Source: Dermatology (Basel, Switzerland). 2001; 202(1): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244224&dopt=Abstract

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Superficial gyrate erythema as a cutaneous reaction to alendronate for osteoporosis. Author(s): High WA, Cohen JB, Wetherington W, Cockerell CJ. Source: Journal of the American Academy of Dermatology. 2003 June; 48(6): 945-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789190&dopt=Abstract

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Suppressed levels of serum cortisol following high-dose oral dexamethasone administration differ between healthy postmenopausal females and patients with established primary vertebral osteoporosis. Author(s): Kann P, Laudes M, Piepkorn B, Heintz A, Beyer J. Source: Clinical Rheumatology. 2001; 20(1): 25-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254236&dopt=Abstract

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Sustained-release sodium fluoride in the treatment of the elderly with established osteoporosis. Author(s): Rubin CD, Pak CY, Adams-Huet B, Genant HK, Li J, Rao DS. Source: Archives of Internal Medicine. 2001 October 22; 161(19): 2325-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11606148&dopt=Abstract

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Synthesis and biological evaluation of prostaglandin-F alkylphosphinic acid derivatives as bone anabolic agents for the treatment of osteoporosis. Author(s): Soper DL, Milbank JB, Mieling GE, Dirr MJ, Kende AS, Cooper R, Jee WS, Yao W, Chen JL, Bodman M, Lundy MW, De B, Stella ME, Ebetino FH, Wang Y, deLong MA, Wos JA. Source: Journal of Medicinal Chemistry. 2001 November 22; 44(24): 4157-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708917&dopt=Abstract

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The ALUI calcitonin receptor gene polymorphism (TT) is associated with low bone mineral density and susceptibility to osteoporosis in postmenopausal women. Author(s): Tsai FJ, Chen WC, Chen HY, Tsai CH. Source: Gynecologic and Obstetric Investigation. 2003; 55(2): 82-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771454&dopt=Abstract

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The bone formation defect in idiopathic juvenile osteoporosis is surface-specific. Author(s): Rauch F, Travers R, Norman ME, Taylor A, Parfitt AM, Glorieux FH. Source: Bone. 2002 July; 31(1): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110417&dopt=Abstract

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The burden of osteoporosis in California, 1998. Author(s): Max W, Sinnot P, Kao C, Sung HY, Rice DP. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002; 13(6): 493-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107664&dopt=Abstract

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The characteristics of bone turnover in the second decade in relation to age and puberty development in healthy Japanese male and female subjects--Japanese Population-based Osteoporosis Study. Author(s): Matsukura T, Kagamimori S, Nishino H, Yamagami T, Iki M, Kajita E, Kagawa Y, Yoneshima H, Matsuzaki T, Marumo F. Source: Annals of Human Biology. 2003 January-February; 30(1): 13-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519652&dopt=Abstract

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The comparative efficacy of drug therapies used for the management of corticosteroid-induced osteoporosis: a meta-regression. Author(s): Amin S, Lavalley MP, Simms RW, Felson DT. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 August; 17(8): 1512-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162505&dopt=Abstract

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The cost of osteoporosis in men: the French situation. Author(s): Levy P, Levy E, Audran M, Cohen-Solal M, Fardellone P, Le Parc JM. Source: Bone. 2002 April; 30(4): 631-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934657&dopt=Abstract

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The cost utility of bisphosphonate treatment in established osteoporosis. Author(s): Iglesias CP, Torgerson DJ, Bearne A, Bose U. Source: Qjm : Monthly Journal of the Association of Physicians. 2002 May; 95(5): 305-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978902&dopt=Abstract

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The decision to accept treatment for osteoporosis following hip fracture: exploring the woman's perspective using a stage-of-change model. Author(s): Mauck KF, Cuddihy MT, Trousdale RT, Pond GR, Pankratz VS, Melton LJ 3rd. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 July; 13(7): 560-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111016&dopt=Abstract

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The design and synthesis of selective prostaglandin analogs as bone anabolic agents for the potential treatment of osteoporosis. Author(s): Soper DL, Wang Y, De B, deLong MA, Dirr MJ, Soehner ME, Lundy MW, Mieling GE, Wos JA. Source: Advances in Experimental Medicine and Biology. 2002; 507: 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664601&dopt=Abstract

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The diagnosis of osteoporosis: attitudes and knowledge of Israeli physicians. Author(s): Werner P, Vered I. Source: Aging Clin Exp Res. 2002 February; 14(1): 52-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027154&dopt=Abstract

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The diagnostic criteria for primary osteoporosis and the incidence of osteoporosis in China. Author(s): Liu Z, Piao J, Pang L, Qing X, Nan S, Pan Z, Guo Y, Wang X, Li F, Liu J, Cheng X. Source: Journal of Bone and Mineral Metabolism. 2002; 20(4): 181-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115062&dopt=Abstract

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The effectiveness of blood tests in detecting secondary osteoporosis or mimicking conditions in postmenopausal women. Author(s): Cooper A, Brew S, de Lusignan S. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 April; 52(477): 311-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942449&dopt=Abstract

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The effects of alendronate and calcitonin on cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study. Author(s): Gur A, Denli A, Cevik R, Nas K, Karakoc M, Sarac AJ. Source: Yonsei Medical Journal. 2003 February; 44(1): 99-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619182&dopt=Abstract

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The effects of alendronate in postmenopausal women with osteoporosis. Author(s): Yaniv I. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 January; 14(1): 90-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577190&dopt=Abstract

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The effects of osteoporosis on distraction osteogenesis: an experimental study in an ovariectomised rabbit model. Author(s): Arslan H, Ketani A, Gezici A, Kapukaya A, Necmioglu S, Kesemenli C, Subasi M. Source: Acta Orthop Belg. 2003; 69(1): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666293&dopt=Abstract

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The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. Author(s): Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ; PaTH Study Investigators. Source: The New England Journal of Medicine. 2003 September 25; 349(13): 1207-15. Epub 2003 Sep 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500804&dopt=Abstract

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The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. Author(s): Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. Source: The New England Journal of Medicine. 2003 September 25; 349(13): 1216-26. Epub 2003 Sep 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500805&dopt=Abstract

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The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis. Author(s): Brown JP, Kendler DL, McClung MR, Emkey RD, Adachi JD, Bolognese MA, Li Z, Balske A, Lindsay R. Source: Calcified Tissue International. 2002 August; 71(2): 103-11. Epub 2002 June 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085156&dopt=Abstract

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The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Author(s): van Staa TP, Leufkens HG, Cooper C. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 October; 13(10): 777-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378366&dopt=Abstract

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The epidemiology of osteoporosis and fractures in geriatric medicine. Author(s): Wehren LE. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 245-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916284&dopt=Abstract

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The Erlangen Fitness Osteoporosis Prevention Study: a controlled exercise trial in early postmenopausal women with low bone density-first-year results. Author(s): Kemmler W, Engelke K, Weineck J, Hensen J, Kalender WA. Source: Archives of Physical Medicine and Rehabilitation. 2003 May; 84(5): 673-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736880&dopt=Abstract

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The hemorheological effects of raloxifene in postmenopausal women with osteoporosis. Results of a 3-year placebo-controlled clinical trial. Author(s): Shand B, Gilchrist N, Blackwell T, March R. Source: Clinical Hemorheology and Microcirculation. 2002; 26(4): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122230&dopt=Abstract

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The impact of osteoporosis continuing education on nurses' knowledge and attitudes. Author(s): Berarducci A, Lengacher CA, Keller R. Source: Journal of Continuing Education in Nursing. 2002 September-October; 33(5): 210-6; Quiz 238-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269759&dopt=Abstract

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The impact of osteoporosis on quality-of-life: the OFELY cohort. Author(s): Martin AR, Sornay-Rendu E, Chandler JM, Duboeuf F, Girman CJ, Delmas PD. Source: Bone. 2002 July; 31(1): 32-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110409&dopt=Abstract

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The influence of back pain on balance and functional mobility in 65- to 75-year-old women with osteoporosis. Author(s): Liu-Ambrose T, Eng JJ, Khan KM, Mallinson A, Carter ND, McKay HA. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 November; 13(11): 868-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415433&dopt=Abstract

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The menopause and HRT. Prevention and management of osteoporosis. Author(s): McClung MR. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 53-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763512&dopt=Abstract

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The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Author(s): Boivin G, Meunier PJ. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003; 14 Suppl 3: S19-24. Epub 2003 March 18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730799&dopt=Abstract

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The nursing home crack. Even the best care will be challenged by osteoporosis. Author(s): Olson JK. Source: Contemporary Longterm Care. 2002 September; 25(9): 30, 32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12298102&dopt=Abstract

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The osteoporosis risk assessment tool: establishing content validity through a panel of experts. Author(s): Wynd CA, Schaefer MA. Source: Applied Nursing Research : Anr. 2002 August; 15(3): 184-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173169&dopt=Abstract

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The pathogenesis of osteoporosis in older women and men: a review. Author(s): Enriori PJ, Enriori CL. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 September; 82(1): 1-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429134&dopt=Abstract

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The patients with incidentally discovered adrenal adenoma (incidentaloma) are not at increased risk of osteoporosis. Author(s): Osella G, Reimondo G, Peretti P, Ali A, Paccotti P, Angeli A, Terzolo M. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 February; 86(2): 604-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158016&dopt=Abstract

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The pharmaceutical industry and disease mongering. Article was insulting to people with osteoporosis. Author(s): Edwards L. Source: Bmj (Clinical Research Ed.). 2002 July 27; 325(7357): 216; Author Reply 216. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143857&dopt=Abstract

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The pharmaceutical industry and disease mongering. Authors were incorrect in their comments about Osteoporosis Australia. Author(s): Sambrook P, Stenmark J. Source: Bmj (Clinical Research Ed.). 2002 July 27; 325(7357): 216; Author Reply 216. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143859&dopt=Abstract

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The pleiotropic effects of HMG-CoA reductase inhibitors: their role in osteoporosis and dementia. Author(s): Waldman A, Kritharides L. Source: Drugs. 2003; 63(2): 139-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515562&dopt=Abstract

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The potential of parathyroid hormone as a therapy for osteoporosis. Author(s): Rubin MR, Bilezikian JP. Source: Int J Fertil Womens Med. 2002 May-June; 47(3): 103-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081255&dopt=Abstract

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The psychometric properties of patient preferences in osteoporosis. Author(s): Cranney A, Coyle D, Pham BA, Tetroe J, Wells G, Jolly E, Tugwell P. Source: The Journal of Rheumatology. 2001 January; 28(1): 132-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11196515&dopt=Abstract

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The relationship among history of falls, osteoporosis, and fractures in postmenopausal women. Author(s): Geusens P, Autier P, Boonen S, Vanhoof J, Declerck K, Raus J. Source: Archives of Physical Medicine and Rehabilitation. 2002 July; 83(7): 903-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098147&dopt=Abstract

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The reliability and validity of the Turkish version of Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Author(s): Kocyigit H, Gulseren S, Erol A, Hizli N, Memis A. Source: Clinical Rheumatology. 2003 February; 22(1): 18-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605312&dopt=Abstract

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The risk of osteoporosis in Caucasian men and women with obstructive airways disease. Author(s): Sin DD, Man JP, Man SF. Source: The American Journal of Medicine. 2003 January; 114(1): 10-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543283&dopt=Abstract

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The role of bone density measurements in the evaluation of new treatments for osteoporosis. Author(s): Blake GM, Fogelman I. Source: Current Pharmaceutical Design. 2002; 8(21): 1885-1905. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171529&dopt=Abstract

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The role of serial bone mineral density testing for osteoporosis. Author(s): Crandall C. Source: Journal of Women's Health & Gender-Based Medicine. 2001 November; 10(9): 887-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747684&dopt=Abstract

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The role of the primary care physician in diagnosis and management of osteoporosis. Author(s): Wehren LE. Source: Int J Fertil Womens Med. 2002 May-June; 47(3): 116-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081256&dopt=Abstract

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The role of trace minerals in the pathogenesis of postmenopausal osteoporosis and a new effect of calcitonin. Author(s): Gur A, Colpan L, Nas K, Cevik R, Sarac J, Erdogan F, Duz MZ. Source: Journal of Bone and Mineral Metabolism. 2002; 20(1): 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11810415&dopt=Abstract

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The role of ultrasound in osteoporosis evaluation. Author(s): Ferenczy G, Meuleman J. Source: Journal of the American Geriatrics Society. 2002 February; 50(2): 401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028235&dopt=Abstract

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The serologic screening for celiac disease in the general population (blood donors) and in some high-risk groups of adults (patients with autoimmune diseases, osteoporosis and infertility) in the Czech republic. Author(s): Vancikova Z, Chlumecky V, Sokol D, Horakova D, Hamsikova E, Fucikova T, Janatkova I, Ulcova-Gallova Z, Stepan J, Limanova Z, Dvorak M, Kocna P, Sanchez D, Tuckova L, Tlaskalova-Hogenova H. Source: Folia Microbiol (Praha). 2002; 47(6): 753-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630332&dopt=Abstract

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The sheep as a model for osteoporosis in humans. Author(s): Turner AS. Source: Veterinary Journal (London, England : 1997). 2002 May; 163(3): 232-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090765&dopt=Abstract

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The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and prevalent vertebral fractures in postmenopausal women with osteoporosis. Author(s): Marcus R, Wang O, Satterwhite J, Mitlak B. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2003 January; 18(1): 18-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510801&dopt=Abstract

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The use of placebo-controlled and non-inferiority trials for the evaluation of new drugs in the treatment of postmenopausal osteoporosis. Author(s): Delmas PD, Calvo G, Boers M, Abadie E, Avouac B, Kahan A, Kaufman JM, Laslop A, Lekkerkerker JF, Nilsson P, Van Zwieten-Boot B, Kreutz G, Reginster JY; Group for the Respect of Ethics and Excellence in Science (GREES). Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 January; 13(1): 1-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11878450&dopt=Abstract

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The use of quantitative ultrasonometry in patients with glucocorticoid-induced osteoporosis. Author(s): Wuster C. Source: Frontiers of Hormone Research. 2002; 30: 20-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892268&dopt=Abstract

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Therapeutic equivalence of alendronate 35 milligrams once weekly and 5 milligrams daily in the prevention of postmenopausal osteoporosis. Author(s): Luckey MM, Gilchrist N, Bone HG, Davie MW, de Villiers TJ, Wu M, Daifotis AG, Santora AC, Orloff JJ. Source: Obstetrics and Gynecology. 2003 April; 101(4): 711-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681875&dopt=Abstract

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Therapeutic interventions in osteoporosis. Author(s): Sutcliffe A. Source: Nurs Times. 2002 March 7-13; 98(10): 52-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11921627&dopt=Abstract

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Therapeutic options: an evidence-based approach to prevention and treatment of osteoporosis. Author(s): Miller E. Source: Int J Fertil Womens Med. 2003 May-June; 48(3): 122-6; Discussion 137-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839143&dopt=Abstract

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Therapeutic potentials of androgens, estrogen and SERMs in glucocorticoid-induced osteoporosis. Author(s): Agnusdei D, Isaia GC, Iori N. Source: Frontiers of Hormone Research. 2002; 30: 136-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892261&dopt=Abstract

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Therapy of osteoporosis in patients with Crohn's disease: a randomized study comparing sodium fluoride and ibandronate. Author(s): von Tirpitz C, Klaus J, Steinkamp M, Hofbauer LC, Kratzer W, Mason R, Boehm BO, Adler G, Reinshagen M. Source: Alimentary Pharmacology & Therapeutics. 2003 March 15; 17(6): 807-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641503&dopt=Abstract

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Three-monthly ibandronate bolus injection offers favourable tolerability and sustained efficacy advantage over two years in established corticosteroid-induced osteoporosis. Author(s): Ringe JD, Dorst A, Faber H, Ibach K, Preuss J. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 743-9. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730532&dopt=Abstract

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Tolerability of once-weekly alendronate in patients with osteoporosis: a randomized, double-blind, placebo-controlled study. Author(s): Greenspan S, Field-Munves E, Tonino R, Smith M, Petruschke R, Wang L, Yates J, de Papp AE, Palmisano J. Source: Mayo Clinic Proceedings. 2002 October; 77(10): 1044-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374248&dopt=Abstract

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Trabecular bone structure of the calcaneus: preliminary in vivo MR imaging assessment in men with osteoporosis. Author(s): Boutry N, Cortet B, Dubois P, Marchandise X, Cotten A. Source: Radiology. 2003 June; 227(3): 708-17. Epub 2003 April 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676974&dopt=Abstract

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Transdermal estrogen therapy improves lipid profile and osteoporosis in postmenopausal liver transplant patients. Author(s): Isoniemi H, Appelberg J, Nilsson C, Makela P, Risteli J, Hockerstedt K. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1472-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267379&dopt=Abstract

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Transdermal fentanyl for the treatment of back pain caused by vertebral osteoporosis. Author(s): Ringe JD, Faber H, Bock O, Valentine S, Felsenberg D, Pfeifer M, Minne HW, Schwalen S. Source: Rheumatology International. 2002 September; 22(5): 199-203. Epub 2002 July 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215866&dopt=Abstract

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Transient bilateral osteoporosis of the hip in pregnancy. A case report and review of the literature. Author(s): Axt-Fliedner R, Schneider G, Seil R, Friedrich M, Mink D, Schmidt W. Source: Gynecologic and Obstetric Investigation. 2001; 51(2): 138-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11223710&dopt=Abstract

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Transient osteoporosis of the femoral condyle: a case report. Author(s): Komatsu T, Kadoya Y, Minoda Y, Masada T, Yamano Y. Source: The Knee. 2002 September; 9(3): 241-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126686&dopt=Abstract

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Transient osteoporosis of the talus followed by migration to the tibia. Author(s): Matsumoto T, Tsurumoto T, Shindo H. Source: The Journal of Rheumatology. 2003 April; 30(4): 860-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672214&dopt=Abstract

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Transient osteoporosis with bilateral fracture of the neck of the femur during pregnancy: a case report. Author(s): Wattanawong T, Wajanavisit W, Laohacharoensombat W. Source: J Med Assoc Thai. 2001 October; 84 Suppl 2: S516-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11853274&dopt=Abstract

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Treating osteoporosis without hormones. Author(s): Turkoski B. Source: Orthopaedic Nursing / National Association of Orthopaedic Nurses. 2002 September-October; 21(5): 80-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432704&dopt=Abstract

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Treatment for patients with postmenopausal osteoporosis who have been placed on HRT and show a decrease in bone mineral density: effects of concomitant administration of vitamin K(2). Author(s): Hidaka T, Hasegawa T, Fujimura M, Sakai M, Saito S. Source: Journal of Bone and Mineral Metabolism. 2002; 20(4): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115070&dopt=Abstract

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Treatment of established osteoporosis: a systematic review and cost-utility analysis. Author(s): Kanis JA, Brazier JE, Stevenson M, Calvert NW, Lloyd Jones M. Source: Health Technology Assessment (Winchester, England). 2002; 6(29): 1-146. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654239&dopt=Abstract

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Treatment of glucocorticoid-induced osteoporosis with calcium, vitamin D and Dmetabolites. Author(s): Ringe JD. Source: Frontiers of Hormone Research. 2002; 30: 127-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892259&dopt=Abstract

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Treatment of male osteoporosis: recent advances with alendronate. Author(s): Ringe JD, Orwoll E, Daifotis A, Lombardi A. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 March; 13(3): 195-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991437&dopt=Abstract

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Treatment of osteoporosis among older adults discharged from hospital in Italy. Author(s): Onder G, Pedone C, Gambassi G, Landi F, Cesari M, Bernabei R; Investigators of the GIFA Study. Source: European Journal of Clinical Pharmacology. 2001 October; 57(8): 599-604. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11758639&dopt=Abstract

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Treatment of osteoporosis and osteopenia in long-term renal transplant patients with alendronate. Author(s): Cruz DN, Brickel HM, Wysolmerski JJ, Gundberg CG, Simpson CA, Kliger AS, Lorber MI, Basadonna GP, Friedman AL, Insogna KL, Bia MJ. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2002 January; 2(1): 62-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095058&dopt=Abstract

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Treatment of osteoporosis in men using dehydroepiandrosterone sulfate. Author(s): Sun Y, Mao M, Sun L, Feng Y, Yang J, Shen P. Source: Chin Med J (Engl). 2002 March; 115(3): 402-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940375&dopt=Abstract

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Treatment of osteoporosis: combination therapies. Author(s): Simon JA, Mack CJ. Source: Int J Fertil Womens Med. 2003 May-June; 48(3): 127-31; Discussion 137-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839144&dopt=Abstract

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Treatment of osteoporosis: current status and recent advances. Author(s): Theodorou DJ, Theodorou SJ, Sartoris DJ. Source: Compr Ther. 2002 Summer; 28(2): 109-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085458&dopt=Abstract

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Treatment of postmenopausal osteoporosis. Author(s): Delmas PD. Source: Lancet. 2002 June 8; 359(9322): 2018-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076571&dopt=Abstract

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Treatment of postmenopausal osteoporosis. Author(s): Cranney A. Source: Bmj (Clinical Research Ed.). 2003 August 16; 327(7411): 355-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919968&dopt=Abstract

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Treatment of symptomatic pediatric osteoporosis with cyclic single-day intravenous pamidronate infusions. Author(s): Steelman J, Zeitler P. Source: The Journal of Pediatrics. 2003 April; 142(4): 417-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712060&dopt=Abstract

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Two polymorphisms in the vitamin D receptor gene--association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish Osteoporosis Prevention Study. Author(s): Tofteng CL, Jensen JE, Abrahamsen B, Odum L, Brot C. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 August; 17(8): 1535-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162507&dopt=Abstract

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Two years of treatment with recombinant human growth hormone increases bone mineral density in men with idiopathic osteoporosis. Author(s): Gillberg P, Mallmin H, Petren-Mallmin M, Ljunghall S, Nilsson AG. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 November; 87(11): 4900-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414848&dopt=Abstract

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Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis. Author(s): Rizzoli R, Greenspan SL, Bone G 3rd, Schnitzer TJ, Watts NB, Adami S, Foldes AJ, Roux C, Levine MA, Uebelhart B, Santora AC 2nd, Kaur A, Peverly CA, Orloff JJ; Alendronate Once-Weekly Study Group. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 November; 17(11): 1988-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412806&dopt=Abstract

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Ultrasonic backscatter and transmission parameters at the os calcis in postmenopausal osteoporosis. Author(s): Roux C, Roberjot V, Porcher R, Kolta S, Dougados M, Laugier P. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 July; 16(7): 1353-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450712&dopt=Abstract

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Unbalanced diet to lower serum cholesterol level is a risk factor for postmenopausal osteoporosis and distal forearm fracture. Author(s): Varenna M, Binelli L, Zucchi F, Ghiringhelli D, Sinigaglia L. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001; 12(4): 296-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420779&dopt=Abstract

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Uncertain future of trials in osteoporosis. Author(s): Kanis JA, Oden A, Johnell O, Caulin F, Bone H, Alexandre JM, Abadie E, Lekkerkerker F. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002; 13(6): 443-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107656&dopt=Abstract

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Underdiagnosis and undertreatment of osteoporosis. Author(s): Westesson PL, Lee RK, Ketkar MA, Lin EP. Source: Lancet. 2002 December 7; 360(9348): 1891. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480407&dopt=Abstract

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Undertreatment of osteoporosis following hip fracture. Author(s): Fisher AA, Davis MW, Smith PN. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 July; 85-A(7): 1394-5; Author Reply 1395-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851373&dopt=Abstract

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Undertreatment of osteoporosis in men who have had a hip fracture. Author(s): Abraham A. Source: Archives of Internal Medicine. 2003 May 26; 163(10): 1236; Author Reply 1236-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767962&dopt=Abstract

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Undertreatment of osteoporosis in men with hip fracture. Author(s): Kiebzak GM, Beinart GA, Perser K, Ambrose CG, Siff SJ, Heggeness MH. Source: Archives of Internal Medicine. 2002 October 28; 162(19): 2217-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390065&dopt=Abstract

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Underuse of procedures for diagnosing osteoporosis and of therapies for osteoporosis in older nursing home residents. Author(s): Gupta G, Aronow WS. Source: Journal of the American Medical Directors Association. 2003 July-August; 4(4): 200-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837141&dopt=Abstract

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Unresolved issues in osteoporosis in men. Author(s): Seeman E. Source: Reviews in Endocrine & Metabolic Disorders. 2001 January; 2(1): 45-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704979&dopt=Abstract

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Unusual presentation of primary hyperparathyroidism with osteoporosis, hypercalcemia, and normal parathyroid hormone level. Author(s): Perez JB, Pazianos AG. Source: Southern Medical Journal. 2001 March; 94(3): 339-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11284524&dopt=Abstract

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Update on alendronate for osteoporosis: once-weekly dosing. Author(s): Schnitzer TJ. Source: Expert Opinion on Pharmacotherapy. 2001 September; 2(9): 1461-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585024&dopt=Abstract

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Use of a peripheral dexa measurement for osteoporosis screening. Author(s): Kirk JK, Nichols M, Spangler JG. Source: Family Medicine. 2002 March; 34(3): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922536&dopt=Abstract

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Use of bisphosphonate therapy for osteoporosis in childhood and adolescence. Author(s): Batch JA, Couper JJ, Rodda C, Cowell CT, Zacharin M. Source: Journal of Paediatrics and Child Health. 2003 March; 39(2): 88-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603794&dopt=Abstract

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Use of quantitative ultrasound densitometry (QUS) in male osteoporosis. Author(s): Wuster C, Hadji P. Source: Calcified Tissue International. 2001 October; 69(4): 225-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730256&dopt=Abstract

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Usefulness of bone quantitative ultrasound in management of osteoporosis in men. Author(s): Montagnani A, Gonnelli S, Cepollaro C, Mangeri M, Monaco R, Gennari L, Gennari C. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2001 Fall; 4(3): 231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740065&dopt=Abstract

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Using bone densitometry to monitor therapy in treating osteoporosis: pros and cons. Author(s): Deal CL. Source: Curr Rheumatol Rep. 2001 June; 3(3): 233-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11352792&dopt=Abstract

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Validation of Web-based questionnaires regarding osteoporosis prevention in young British women. Author(s): Marsden J, Jones RB. Source: Health Bull (Edinb). 2001 July; 59(4): 254-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664736&dopt=Abstract

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Value of vertebral X-rays in osteoporosis. Author(s): Gordon L, Pope TL, Monen S. Source: J S C Med Assoc. 2001 March; 97(3): 102-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285880&dopt=Abstract

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Variations in glucocorticoid induced osteoporosis prevention in a managed care cohort. Author(s): Mudano A, Allison J, Hill J, Rothermel T, Saag K. Source: The Journal of Rheumatology. 2001 June; 28(6): 1298-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11409123&dopt=Abstract

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Vascular calcification and osteoporosis: inflammatory responses to oxidized lipids. Author(s): Demer LL. Source: International Journal of Epidemiology. 2002 August; 31(4): 737-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177011&dopt=Abstract

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Vertebral fracture and cortical bone changes in corticosteroid-induced osteoporosis. Author(s): Tsugeno H, Tsugeno H, Fujita T, Goto B, Sugishita T, Hosaki Y, Ashida K, Mitsunobu F, Tanizaki Y, Shiratori Y. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 August; 13(8): 650-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181624&dopt=Abstract

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Vertebral fractures: a hidden problem of osteoporosis. Author(s): Haczynski J, Jakimiuk A. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2001 September-October; 7(5): 1108-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535963&dopt=Abstract

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Vertebroplasty in osteoporosis. Author(s): Deramond H, Mathis JM. Source: Seminars in Musculoskeletal Radiology. 2002 September; 6(3): 263-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541204&dopt=Abstract

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Vitamin D status, trunk muscle strength, body sway, falls, and fractures among 237 postmenopausal women with osteoporosis. Author(s): Pfeifer M, Begerow B, Minne HW, Schlotthauer T, Pospeschill M, Scholz M, Lazarescu AD, Pollahne W. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2001; 109(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11341304&dopt=Abstract

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Vitamin K administration to elderly patients with osteoporosis induces no hemostatic activation, even in those with suspected vitamin K deficiency. Author(s): Asakura H, Myou S, Ontachi Y, Mizutani T, Kato M, Saito M, Morishita E, Yamazaki M, Nakao S. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2001 December; 12(12): 996-1000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846334&dopt=Abstract

Studies 289

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Vitamins D and K in the treatment of osteoporosis secondary to graft-versus-host disease following bone-marrow transplantation. Author(s): Hattori M, Morita N, Tsujino Y, Yamamoto M, Tanizawa T. Source: J Int Med Res. 2001 July-August; 29(4): 381-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675913&dopt=Abstract

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Water fluoridation, osteoporosis, fractures--recent developments. Author(s): Demos LL, Kazda H, Cicuttini FM, Sinclair MI, Fairley CK. Source: Aust Dent J. 2001 June; 46(2): 80-7; Quiz 143. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491235&dopt=Abstract

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Weekly dose of osteoporosis drug. Author(s): Casale JA. Source: The American Journal of Nursing. 2002 May; 102(5): 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006843&dopt=Abstract

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What are effective strategies for reducing the risk of steroid-induced osteoporosis? Author(s): Koval PG, Hutton SF, Thering A. Source: The Journal of Family Practice. 2002 December; 51(12): 1076. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540335&dopt=Abstract

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What are the criteria by which a densitometric diagnosis of osteoporosis can be made in males and non-Caucasians? Author(s): Binkley NC, Schmeer P, Wasnich RD, Lenchik L; International Society for Clinical Densitometry Position Development Panel and Scientific Advisory Committee. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002; 5 Suppl: S19-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464708&dopt=Abstract

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What are the standards by which bone mass measurement at peripheral skeletal sites should be used in the diagnosis of osteoporosis? Author(s): Miller PD, Njeh CF, Jankowski LG, Lenchik L; International Society for Clinical Densitometry Position Development Panel and Scientific Advisory Committee. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002; 5 Suppl: S39-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464710&dopt=Abstract

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What is osteoporosis? Author(s): Christodoulou C, Cooper C. Source: Postgraduate Medical Journal. 2003 March; 79(929): 133-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697910&dopt=Abstract

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What is the best approach to prevention and treatment of osteoporosis? Author(s): Schwartz K. Source: The Journal of Family Practice. 2001 December; 50(12): 1024-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742601&dopt=Abstract

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What is the impact of osteoporosis education and bone mineral density testing for postmenopausal women in a managed care setting? Author(s): Rolnick SJ, Kopher R, Jackson J, Fischer LR, Compo R. Source: Menopause (New York, N.Y.). 2001 Summer; 8(2): 141-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256875&dopt=Abstract

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What role would thiazide diuretics have in the prevention of postmenopausal osteoporosis? Author(s): Kamel H. Source: The American Journal of Medicine. 2001 August; 111(2): 161-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11501547&dopt=Abstract

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When should a gynecologist refer a patient for specialty care in osteoporosis? Author(s): Bilezikian JP. Source: Int J Fertil Womens Med. 2003 May-June; 48(3): 132-6; Discussion 137-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839145&dopt=Abstract

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When should densitometry be repeated in healthy peri- and postmenopausal women: the Danish osteoporosis prevention study. Author(s): Abrahamsen B, Nissen N, Hermann AP, Hansen B, Barenholdt O, Vestergaard P, Tofteng CL, Pors Nielsen S. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 November; 17(11): 2061-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412814&dopt=Abstract

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When tiny glands cause big problems. Kidney stones or osteoporosis may signal hyperparathyroidism, a disease that disrupts the distribution of calcium in the body. Author(s): Utiger RD. Source: Health News. 2003 January; 9(1): 5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545949&dopt=Abstract

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When to measure BMD in patients being treated for osteoporosis. Author(s): Crandall C. Source: Postgraduate Medicine. 2001 March; 109(3): 191-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11265357&dopt=Abstract

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Which central dual X-ray absorptiometry skeletal sites and regions of interest should be used to determine the diagnosis of osteoporosis? Author(s): Hamdy RC, Petak SM, Lenchik L; International Society for Clinical Densitometry Position Development Panel and Scientific Advisory Committee. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002; 5 Suppl: S11-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464707&dopt=Abstract

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Who should be screened for osteoporosis? Author(s): Weinstein L. Source: Jama : the Journal of the American Medical Association. 2001 October 24-31; 286(16): 1970; Author Reply 1971. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11667922&dopt=Abstract

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Who should be screened for osteoporosis? Author(s): Russo CR, Lauretani F, De Marco F, Ferrucci L. Source: Jama : the Journal of the American Medical Association. 2001 October 24-31; 286(16): 1970-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11667923&dopt=Abstract

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Women with osteoporosis: strategies for managing aging and chronic illness. Author(s): Wilkins S. Source: J Women Aging. 2001; 13(3): 59-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722007&dopt=Abstract

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Women's knowledge of new regulations about publicly funded medications for osteoporosis. Author(s): Werner P, Vered I. Source: Health Policy (Amsterdam, Netherlands). 2002 June; 60(3): 275-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965335&dopt=Abstract

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Women's willingness to pay out-of-pocket for drug treatment for osteoporosis before and after the enactment of regulations providing public funding: evidence from a natural experiment in Israel. Author(s): Werner P, Vered I. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 March; 13(3): 228-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991443&dopt=Abstract

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Yield of laboratory testing to identify secondary contributors to osteoporosis in otherwise healthy women. Author(s): Tannenbaum C, Clark J, Schwartzman K, Wallenstein S, Lapinski R, Meier D, Luckey M. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 October; 87(10): 4431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364413&dopt=Abstract

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Zoledronate once-yearly increases bone mineral density--implications for osteoporosis. Author(s): Doggrell SA. Source: Expert Opinion on Pharmacotherapy. 2002 July; 3(7): 1007-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083999&dopt=Abstract

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Zoledronic acid: an advance in tumour bone disease therapy and a new hope for osteoporosis. Author(s): Body JJ. Source: Expert Opinion on Pharmacotherapy. 2003 April; 4(4): 567-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667119&dopt=Abstract

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CHAPTER 2. NUTRITION AND OSTEOPOROSIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and osteoporosis.

Finding Nutrition Studies on Osteoporosis The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “osteoporosis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on osteoporosis: •

Lysinuric protein intolerance: a rare cause of childhood osteoporosis. Source: Nutrition-reviews (USA). (March 1986). volume 44(3) page 110-113. children osteodystrophy nutritional disorders proteins lysine amino acids diagnosis therapy case studies 0029-6643

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Preventing bone loss with trace minerals and calcium supplementation. Author(s): University of California, La Jolla, CA Source: Strause, L.G. Saltman, P.D. Nutrition-and-the-M.D (USA). (June 1993). volume 19(6) page 1-3. osteodystrophy disease control minerals trace element deficiencies calcium copper zinc manganese biological rhythms diet nutrient uptake ash content density bones women elderly 0732-0167

Additional consumer oriented references include: •

Bone loss in amenorrheic athletes. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. November 1986. volume 44 (11) page 361-363. 0029-6643

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Boning up on osteoporosis. Source: Kurtzweil, P. FDA-consum. Rockville, Md. : Food and Drug Administration, Department of Health & Human Services. Sept 1996. volume 30 (7) page 16-20. 03621332

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By the way, doctor. I am 70 years old and have taken estrogen (Premarin 1.25 mg) for 14 years. Recently, my bone density test showed osteopenia, which my doctor says is the beginning of osteoporosis. Why would I still get osteoporosis after taking large doses of estrogen for so long? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1999 July; 6(11): 8 1070-910X

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By the way, doctor. My doctor prescribed Fosamax to me for osteoporosis prevention, but it upsets my stomach. Are there any other proven medications for osteoporosis prevention? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 2000 August; 7(12): 8 1070910X

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By the way, doctor. Recently, you advocated taking 800 IU of vitamin D as part of osteoporosis prevention. However, during the summer, I get a lot of vitamin D from sunlight. Am I in danger of getting too much vitamin D? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1999 August; 6(12): 8 1070910X

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Calcium intake and bone loss. Source: Anonymous Nutr-Revolume 1988 March; 46(3): 123-5 0029-6643

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Calcium, skeletal aging, and osteoporosis. Source: Marcus, R. Nutrition-and-the-M.D (USA). (Mar 1985). volume 11(3) page 1-3. calcium bone formation osteodystrophy additives physical activity 0732-0167

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Excess retinol intake may explain the high incidence of osteoporosis in northern Europe. Author(s): College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada. Source: Whiting, S J Lemke, B Nutr-Revolume 1999 June; 57(6): 192-5 0029-6643

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Fit but fragile: are elite sportswomen at an increased risk of osteoporosis. Source: Poulter, J. BNF-nutr-bull. London : The British Nutrition Foundation. Winter 1998. volume 23 (85) page 211-215. 0141-9684

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How reliable are high-tech tests for osteoporosis, diabetes, cholesterol. Source: Environ-Nutr. New York, N.Y. : Environmental Nutrition, Inc. October 1987. volume 10 (10) page 1, 8. 0893-4452

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How soy fares in fight against cancer, heart disease, osteoporosis. Source: Walsh, J. Environ-nutr. New York : Environmental Nutrition, Inc.,. May 2002. volume 25 (5) page 1, 6. 0893-4452

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How to build better bones: overview of all the new osteoporosis options. Source: Antinoro, L. Environ-nutr. New York : Environmental Nutrition, Inc.,. Sept 2001. volume 24 (9) page 1, 4-5. 0893-4452

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I am 51 years old, perimenopausal, have irritable bowel syndrome and a family history of breast cancer, and am told my bones are thinning. These conditions would seem to rule out my use of estrogen or Fosamax. I weight train and take 1,500 mg of calcium a day to stave off osteoporosis. What's left? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1998 November; 6(3): 8 1070910X

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I just read about a recent report, which concluded that high consumption of milk was associated with an increased risk of osteoporosis. This flies in the face of everything I've heard about calcium. Is it really true? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1999 February; 6(6): 8 1070910X

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In an article last summer, you mentioned that a 0.3 milligram daily dose of estrogen is effective in preventing osteoporosis. Is a dose that low also effective for preventing heart disease? Author(s): Indiana University School of Medicine, USA. Source: Walsh, M N Health-News. 2000 March; 6(3): 10 1081-5880

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It is true that drinking soda increases my risk of osteoporosis? Source: Anonymous Johns-Hopkins-Med-Lett-Health-After-50. 1998 April; 10(2): 8 10421882

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It's never too late to prevent osteoporosis. Source: Borra, S.T. Nutr-News. Rosemont, Ill. : National Dairy Council. Spring 1992. volume 55 (1) page 2-3. 0369-6464

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Low-dose estrogen for bone loss. Source: Anonymous Harv-Womens-Health-Watch. 1998 May; 5(9): 7 1070-910X

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Manganese and vegetarianism: new factors in osteoporosis. Source: Hudnall, M. Environ-Nutr. New York : Environmental Nutrition, Inc. February 1987. volume 10 (2) page 1, 4. 0195-4024

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Osteoporosis and calcium balance. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. March 1983. volume 41 (3) page 83-85. 0029-6643

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Osteoporosis and calcium supplementation. Source: Conning, D.M. B-N-F-Nutr-Bull-Br-Nutr-Found. London : The Foundation. May 1989. volume 14 (2) page 126-134. ill. 0141-9684

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Osteoporosis and coeliac disease. Source: Rochford, L. Nutr-food-sci. Bradford, West Yorkshire, England : MCB University Press. Nov/December 1999. (6) page 285-287. 0034-6659

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Osteoporosis followed by primary hyperparathyroidism. Source: Anonymous Nutr-Revolume 1989 March; 47(3): 82-4 0029-6643

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Osteoporosis--summary of the 19th Steenbock Symposium. Source: Roe, D.A. Nutr-Today. Baltimore, Md. : Williams & Wilkins. October 1989. volume 24 (5) page 30-34. 0029-666X

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Osteoporosis--the treatment controversy. Source: Liebman, B. Hurley, J. Nutr-Today. Baltimore, Md. : Williams & Wilkins. August 1992. volume 27 (4) page 6-12. 0029-666X

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Preventing wintertime bone loss: effects of vitamin D supplementation in healthy postmenopausal women. Source: Anonymous Nutr-Revolume 1992 February; 50(2): 52-4 0029-6643

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Reducing osteoporosis risk. Source: Anonymous Harv-Womens-Health-Watch. 2001 March; 8(7): 3-4 1070-910X

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Sodium-calcium inter-relationships with specific reference to osteoporosis. Source: Williams, C.M. Dickerson, J.W.T. Nutr-Res-Rev. Cambridge [England] : Cambridge University Press. 1990. volume 3 page 101-115. 0954-4224

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Steps men should take to avoid osteoporosis. Source: Tufts-Univ-diet-nutr-lett. New York, N.Y. : Tufts University Diet and Nutrition Letter, 1983-c1997. November 1996. volume 14 (9) page 7-8. 0747-4105

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The complicated research field of nutrients and osteoporosis. Source: Michaelsson, K Nutr-Revolume 2000 August; 58(8): 249-50 0029-6643

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What's the score on osteoporosis. Source: Lustgarden, S. Veg-Times. Mt. Morris, Ill. : Vegetarian Times. November 1992. (183) page 64-71. 0164-8497

The following information is typical of that found when using the “Full IBIDS Database” to search for “osteoporosis” (or a synonym): •

A comparison of the effect of risedronate and etidronate on lumbar bone mineral density in Japanese patients with osteoporosis: a randomized controlled trial. Author(s): Department of Nuclear Medicine, Kawasaki Medical School, Okayama, Japan. Source: Fukunaga, M Kushida, K Kishimoto, H Shiraki, M Taketani, Y Minaguchi, H Inoue, T Morita, R Morii, H Yamamoto, K Ohashi, Y Orimo, H Osteoporos-Int. 2002 December; 13(12): 971-9 0937-941X

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A comprehensive review of treatments for postmenopausal osteoporosis. Author(s): Center for Rheumatology and Bone Diseases, Klinik im Park, Zurich, Switzerland. Source: Hauselmann, H J Rizzoli, R Osteoporos-Int. 2003 January; 14(1): 2-12 0937-941X

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Bisphosphonates in the treatment of thalassemia-induced osteoporosis. Author(s): Department of Internal Medicine, University of Messina, Italy. [email protected] Source: Morabito, N Lasco, A Gaudio, A Crisafulli, A Di Pietro, C Meo, A Frisina, N Osteoporos-Int. 2002 August; 13(8): 644-9 0937-941X

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Bone growth stimulators. New tools for treating bone loss and mending fractures. Author(s): Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6. Source: Whitfield, J F Morley, P Willick, G E Vitam-Horm. 2002; 65: 1-80 0083-6729

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Bone mineral density screening: assessment of influence on prevention and treatment of osteoporosis. Author(s): University of Southern California, Keck School of Medicine and Orthopaedic Hospital, Los Angeles, California 90089-9317, USA. Source: Anastasopoulou, C Rude, R K Endocr-Pract. 2002 May-June; 8(3): 199-201 1530891X

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Current and emerging therapies in osteoporosis. Author(s): Division of Endocrinology, Molecular Medicine and Metabolism, Northwestern University Medical School, Tarry Building 14-759, 303 East Chicago Avenue, Chicago, Illinois 60611, USA. [email protected] Source: DeSantis, A Buchman, A Expert-Opin-Pharmacother. 2002 July; 3(7): 835-43 1465-6566

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Diagnosis, prevention, and treatment of osteoporosis in men. Author(s): Family Practice Residency of Idaho, 777 North Raymond, Boise, ID 83704. [email protected] Source: Epperly, T D Moore, K E J-Gend-Specif-Med. 2002 Nov-December; 5(6): 33-8 1523-7036

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Documentation of preventive education and screening for osteoporosis. Author(s): University of Wisconsin, Green Bay, USA. [email protected] Source: De Villers, M J Outcomes-Manag. 2003 Jan-March; 7(1): 28-32 1535-2765

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Effects of osthole on postmenopausal osteoporosis using ovariectomized rats; comparison to the effects of estradiol. Author(s): Department of Pharmacology, Intractable Diseases Research Center, Tokyo Medical University, Japan. [email protected] Source: Li, X X Hara, I Matsumiya, T Biol-Pharm-Bull. 2002 June; 25(6): 738-42 0918-6158

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Effects of Siberian ginseng extract and ipriflavone on the development of glucocorticoid-induced osteoporosis. Author(s): Department of Pharmacology, Vladivostok State Medical University. Source: Kropotov, A V Kolodnyak, O L Koldaev, V M Bull-Exp-Biol-Med. 2002 March; 133(3): 252-4 0007-4888

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Histopathological changes in the tissues under a denture base in experimental osteoporosis with a non-pressure covering or bearing continuous pressure. Author(s): Department of Removable Prosthodontics, Okayama University Dental School, Okayama City, Japan. [email protected] Source: Oki, K Sato, T Hara, T Minagi, S J-Oral-Rehabil. 2002 June; 29(6): 594-603 0305182X

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How soy fares in fight against cancer, heart disease, osteoporosis. Source: Walsh, J. Environ-nutr. New York : Environmental Nutrition, Inc.,. May 2002. volume 25 (5) page 1, 6. 0893-4452

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How to build better bones: overview of all the new osteoporosis options. Source: Antinoro, L. Environ-nutr. New York : Environmental Nutrition, Inc.,. Sept 2001. volume 24 (9) page 1, 4-5. 0893-4452

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Influence of normal ageing on mechanism of bone loss in women and men in Bangkok. Author(s): Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Source: Chailurkit, L O Piaseu, N Rajatanavin, R J-Med-Assoc-Thai. 2002 August; 85(8): 915-21 0125-2208

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Lifestyle factors are associated with osteoporosis in lean women but not in normal and overweight women: a population-based cohort study of 1222 women. Author(s): Department of Sports Medicine, Deaconess Institute of Oulu, Isokatu 43, 90100 Oulu, Finland. [email protected] Source: Korpelainen, R Korpelainen, J Heikkinen, J Vaananen, K Keinanen Kiukaanniemi, S Osteoporos-Int. 2003 January; 14(1): 34-43 0937-941X

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Mechanisms of bone loss and gain in untreated and treated osteoporosis. Author(s): Department of Medicine, University of Cambridge School of Clinical Medicine, UK. [email protected] Source: Compston, J Endocrine. 2002 February; 17(1): 21-7 0969-711X

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Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis. Source: Cranney, A Tugwell, P Zytaruk, N Robinson, V Weaver, B Adachi, J Wells, G Shea, B Guyatt, G Endocr-Revolume 2002 August; 23(4): 524-8 0163-769X

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Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of metaanalyses of therapies for postmenopausal osteoporosis. Source: Cranney, A Guyatt, G Griffith, L Wells, G Tugwell, P Rosen, C EndocrRevolume 2002 August; 23(4): 570-8 0163-769X

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Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Source: Wells, G Tugwell, P Shea, B Guyatt, G Peterson, J Zytaruk, N Robinson, V Henry, D O'Connell, D Cranney, A Endocr-Revolume 2002 August; 23(4): 529-39 0163769X

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Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of calcitonin for the treatment of postmenopausal osteoporosis. Source: Cranney, A Tugwell, P Zytaruk, N Robinson, V Weaver, B Shea, B Wells, G Adachi, J Waldegger, L Guyatt, G Endocr-Revolume 2002 August; 23(4): 540-51 0163769X

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Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis. Source: Shea, B Wells, G Cranney, A Zytaruk, N Robinson, V Griffith, L Ortiz, Z Peterson, J Adachi, J Tugwell, P Guyatt, G Endocr-Revolume 2002 August; 23(4): 552-9 0163-769X

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Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Source: Papadimitropoulos, E Wells, G Shea, B Gillespie, W Weaver, B Zytaruk, N Cranney, A Adachi, J Tugwell, P Josse, R Greenwood, C Guyatt, G Endocr-Revolume 2002 August; 23(4): 560-9 0163-769X

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Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases. Author(s): Craniofacial and Skeletal Diseases Branch, Building 30 Room 225, NIDCR, NIH, Bethesda, MD 20892, USA. Source: Ameye, L Young, M F Glycobiology. 2002 September; 12(9): 107R-16R 0959-6658

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Monofluorophosphate combined with hormone replacement therapy in postmenopausal osteoporosis. An open-label pilot efficacy and safety study. Author(s): Department of Internal Med. IV, Klinikum Leverkusen, Teaching Hospital of the University of Cologne, Germany. [email protected] Source: Ringe, J D Setnikar, I Rheumatol-Int. 2002 May; 22(1): 27-32 0172-8172

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New anabolic therapies in osteoporosis. Author(s): Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Source: Rubin, M R Bilezikian, J P Curr-Opin-Rheumatol. 2002 July; 14(4): 433-40 10408711

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Nonmedical management of osteoporosis. Author(s): Metabolic Bone Disease/Spine and Sports Medicine, Department of Rehabilitation Medicine, The New York-Presbyterian Hospital/Hospital for Special Surgery, New York, New York 10021, USA. [email protected] Source: Lin, J T Lane, J M Curr-Opin-Rheumatol. 2002 July; 14(4): 441-6 1040-8711

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Nutriments and osteoporosis: is calcium enough? Author(s): (University Hospital of Geneva (Suisse). Division of Bone Diseases) Source: Bonjour, J.P. Ammann, P. Chevalley, T. Bertiere, M.C. Rizzoli, R. Sciences-desAliments (France). (2002). volume 22(4) page 409-414. Numero special: Dairy Products, Nutrition and Health. P11. calcium mineral nutrients human nutrition bone diseases 0240-8813

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Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis. Author(s): Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK. Source: Hirayama, T Danks, L Sabokbar, A Athanasou, N A Rheumatology-(Oxford). 2002 November; 41(11): 1232-9 1462-0324

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Osteoporosis and anorexia nervosa: relative role of endocrine alterations and malnutrition. Author(s): Department of Internal Medicine, University of Tor Vergata, Rome, Italy. Source: Jacoangeli, F Zoli, A Taranto, A Staar Mezzasalma, F Ficoneri, C Pierangeli, S Menzinger, G Bollea, M R Eat-Weight-Disord. 2002 September; 7(3): 190-5 1124-4909

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Osteoporosis before lung transplantation: association with low body mass index, but not with underlying disease. Author(s): Division of Pulmonary Medicine, University Hospital, Zurich, Switzerland. Source: Tschopp, O Boehler, A Speich, R Weder, W Seifert, B Russi, E W Schmid, C AmJ-Transplant. 2002 February; 2(2): 167-72 1600-6135

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Osteoporosis during androgen deprivation therapy for prostate cancer. Author(s): Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [email protected] Source: Smith, M R Urology. 2002 September; 60(3 Suppl 1): 79-85; discussion 86 15279995

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Osteoporosis in childhood rheumatic diseases: prevention and therapy. Author(s): Department of Paediatrics, ICP, Milano, Italy. Source: Cimaz, R Best-Pract-Res-Clin-Rheumatol. 2002 July; 16(3): 397-409 1521-6942

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Osteoporosis in elderly: prevention and treatment. Author(s): Section of Geriatric Medicine, A91 Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Source: Srivastava, M Deal, C Clin-Geriatr-Med. 2002 August; 18(3): 529-55 0749-0690

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Osteoporosis in juvenile idiopathic arthritis. Author(s): Pediatric Rheumatology, Institute of Child Health, Birmingham Children's Hospital, Birmingham, United Kingdom. [email protected] Source: McDonagh, J E Curr-Opin-Rheumatol. 2001 September; 13(5): 399-404 1040-8711

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Osteoporosis--Part I: Risk factors and screening. Author(s): University of Michigan Medical Center, Department of Urology, Ann Arbor, MI, USA. Source: Moyad, M A Urol-Nurs. 2002 August; 22(4): 276-9 1053-816X

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Osteoporosis--Part II: Dietary and/or supplemental calcium and vitamin D. Author(s): University of Michigan Medical Center, Department of Urology, Ann Arbor, MI, USA. Source: Moyad, M A Urol-Nurs. 2002 December; 22(6): 405-9 1053-816X

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Osteoprotegerin abrogates chronic alcohol ingestion-induced bone loss in mice. Author(s): Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, USA. Source: Zhang, J Dai, J Lin, D L Habib, P Smith, P Murtha, J Fu, Z Yao, Z Qi, Y Keller, E T J-Bone-Miner-Res. 2002 July; 17(7): 1256-63 0884-0431

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Population-based osteoporosis education for older women. Author(s): Texas Christian University, Fort Worth, Texas 76129, USA. [email protected] Source: Curry, L C Hogstel, M O Davis, G C Frable, P J Public-Health-Nurs. 2002 NovDecember; 19(6): 460-9 0737-1209

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Possible pathogenetic role of new cytokines in postmenopausal osteoporosis and changes during calcitonin plus calcium therapy. Author(s): Department of Physical Medicine and Rehabilitation, Dicle University School of Medicine, Diyarbakir, Turkey. [email protected] Source: Gur, A Denli, A Nas, K Cevik, R Karakoc, M Sarac, A J Erdogan, F RheumatolInt. 2002 September; 22(5): 194-8 0172-8172

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Preventing osteoporosis. Lifelong nutrition and exercise habits are the most powerful weapons. Author(s): Franciscan Skemp Healthcare, Arcadia, Wis., USA. Source: Motszko, M Adv-Nurse-Pract. 2002 July; 10(7): 41-3, 76 1096-6293

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Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome. Author(s): Division of Reproductive Sciences, Department of Obstetrics and Gynecology, Samuel Lunenfeld Research Institute and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. Source: Mitwally, M F Gotlieb, L Casper, R F Menopause. 2002 Jul-August; 9(4): 236-41 1072-3714

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Prevention of bone loss in ovariectomized rats by combined treatment with risedronate and 1alpha,25-dihydroxyvitamin D3. Author(s): Institute of Physiology, Physiological Chemistry, and Animal Nutrition, Ludwig Maximilians University, Munich, Germany. Source: Erben, R G Mosekilde, L Thomsen, J S Weber, K Stahr, K Leyshon, A Smith, S Y Phipps, R J-Bone-Miner-Res. 2002 August; 17(8): 1498-511 0884-0431

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Serum alkaline phosphatase and bone mineral density: to assess bone loss in oral contraceptive pill user. Author(s): Department of Pharmacology, Mymensingh Medical College. Source: Sultana, S Choudhury, S Choudhury, S A Mymensingh-Med-J. 2002 July; 11(2): 107-9 1022-4742

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Severe symptomatic osteoporosis in patients on androgen deprivation therapy for prostatic carcinoma. Author(s): Department of Medicine, University of Dundee, UK. [email protected] Source: Paterson, C R Mole, P A Scand-J-Urol-Nephrol. 2002; 36(4): 314-6 0036-5599

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Strontium ranelate in osteoporosis. Author(s): WHO Collaborating Center for Public Health Aspects of Rheumatic Diseases, Liege, Belgium. [email protected] Source: Reginster, J Y Curr-Pharm-Des. 2002; 8(21): 1907-16 1381-6128

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Structure-based development of cathepsin L inhibitors and therapeutic applications for prevention of cancer metastasis and cancer-induced osteoporosis. Author(s): Institute for Health Sciences, Tokushima Bunri University, Yamashiro-chi, Tokushima-city, 770-8514, Japan. Source: Katunuma, N Tsuge, H Nukatsuka, M Fukushima, M Adv-Enzyme-Regul. 2002; 42: 159-72 0065-2571

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The comparative efficacy of drug therapies used for the management of corticosteroid-induced osteoporosis: a meta-regression. Author(s): Department of Medicine, Boston Medical Center, Massachusetts, USA. Source: Amin, S Lavalley, M P Simms, R W Felson, D T J-Bone-Miner-Res. 2002 August; 17(8): 1512-26 0884-0431

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The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Author(s): MRC Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK. Source: van Staa, T P Leufkens, H G Cooper, C Osteoporos-Int. 2002 October; 13(10): 777-87 0937-941X

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The nursing home crack. Even the best care will be challenged by osteoporosis. Source: Olson, J K Contemp-Longterm-Care. 2002 September; 25(9): 30, 32 8750-9652

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The present state and perspective in treatment of primary osteoporosis by acupuncture and moxibustion. Author(s): Anatomical Department, Shanghai University of Traditional Chinese Medicine, Shanghai 200032. Source: Zhao, Y J-Tradit-Chin-Med. 2002 March; 22(1): 67-72 0254-6272

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The role of bone density measurements in the evaluation of new treatments for osteoporosis. Author(s): Department of Nuclear Medicine, Guy's Hospital, St Thomas Street, London, SE1 9RT, UK. [email protected] Source: Blake, G M Fogelman, I Curr-Pharm-Des. 2002; 8(21): 1885-1905 1381-6128

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Therapeutic effect of in vivo sustained estradiol release from poly (lactide-coglycolide) microspheres on bone mineral density of osteoporosis rats. Author(s): Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyama-Kitamachi 4-19-1, Higashi-Nada, Kobe 658-8558, Japan. [email protected] Source: Otsuka, M Uenodan, H Matsuda, Y Mogi, T Ohshima, H Makino, K BiomedMater-Eng. 2002; 12(2): 157-67 0959-2989

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Treating osteoporosis without hormones. Author(s): Kent State University College of Nursing, Kent, Ohio, USA. Source: Turkoski, B Orthop-Nurs. 2002 Sep-October; 21(5): 80-5 0744-6020

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Treatment for patients with postmenopausal osteoporosis who have been placed on HRT and show a decrease in bone mineral density: effects of concomitant administration of vitamin K(2). Author(s): Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. Source: Hidaka, T Hasegawa, T Fujimura, M Sakai, M Saito, S J-Bone-Miner-Metab. 2002; 20(4): 235-9 0914-8779

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Two polymorphisms in the vitamin D receptor gene--association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish Osteoporosis Prevention Study. Author(s): Department 545, The Osteoporosis Research Clinic, Hvidovre Hospital, Denmark. Source: Tofteng, C L Jensen, J E Abrahamsen, B Odum, L Brot, C J-Bone-Miner-Res. 2002 August; 17(8): 1535-44 0884-0431

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

The following is a specific Web list relating to osteoporosis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Folic Acid Source: Healthnotes, Inc. www.healthnotes.com Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Pyridoxine Source: Integrative Medicine Communications; www.drkoop.com Vitamin A Source: Healthnotes, Inc. www.healthnotes.com Vitamin A Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B12 Source: Healthnotes, Inc. www.healthnotes.com Vitamin B12 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B6 Source: Healthnotes, Inc. www.healthnotes.com

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Vitamin B6 (Pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B9 (Folic Acid) Alternative names: Folate, Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html Vitamin D Source: Healthnotes, Inc. www.healthnotes.com Vitamin D Alternative names: Calciferol, Calcitrol, Cholecalciferol, Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin D Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,905,00.html Vitamin K Source: Healthnotes, Inc. www.healthnotes.com Vitamin K Alternative names: Menadione, Menaphthone, Menaquinone, Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin K Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10068,00.html •

Minerals Aluminum, Calcium, and Magnesium-Containing Preparations Source: Integrative Medicine Communications; www.drkoop.com Boron Source: Healthnotes, Inc. www.healthnotes.com

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Boron Source: Prima Communications, Inc.www.personalhealthzone.com Boron Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,909,00.html Calcium Source: Healthnotes, Inc. www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Calcium Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Calcium/magnesium Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,937,00.html Calcium: Which Form is Best? Source: Healthnotes, Inc. www.healthnotes.com Chondroitin Alternative names: chondroitin sulfate, sodium chondroitin sulfate Source: Integrative Medicine Communications; www.drkoop.com Chromium Source: Integrative Medicine Communications; www.drkoop.com Copper Source: Healthnotes, Inc. www.healthnotes.com Copper Source: Prima Communications, Inc.www.personalhealthzone.com Copper Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,886,00.html

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Folate Source: Integrative Medicine Communications; www.drkoop.com Folate Source: Prima Communications, Inc.www.personalhealthzone.com Magnesium Source: Healthnotes, Inc. www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Magnesium Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Manganese Source: Healthnotes, Inc. www.healthnotes.com Manganese Source: Integrative Medicine Communications; www.drkoop.com Manganese Source: Prima Communications, Inc.www.personalhealthzone.com Potassium-Sparing Diuretics Source: Integrative Medicine Communications; www.drkoop.com Sodium Fluoride Source: Healthnotes, Inc. www.healthnotes.com Vanadium Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Healthnotes, Inc. www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com

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Zinc Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html Zinc/copper Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,938,00.html •

Food and Diet Atkins Diet Source: Healthnotes, Inc. www.healthnotes.com Barley Source: Healthnotes, Inc. www.healthnotes.com Coffee Source: Healthnotes, Inc. www.healthnotes.com Low Back Pain Source: Healthnotes, Inc. www.healthnotes.com Low-Salt Diet Source: Healthnotes, Inc. www.healthnotes.com Milk Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,95,00.html Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Omega-6 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Rye Source: Healthnotes, Inc. www.healthnotes.com Salmon Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,102,00.html Soy Source: Healthnotes, Inc. www.healthnotes.com

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Soy products Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,135,00.html Soybeans Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,105,00.html Tea Source: Healthnotes, Inc. www.healthnotes.com Weight Loss and Obesity Source: Healthnotes, Inc. www.healthnotes.com Wheat Source: Healthnotes, Inc. www.healthnotes.com Whey Protein Source: Healthnotes, Inc. www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND OSTEOPOROSIS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to osteoporosis. At the conclusion of this chapter, we will provide additional sources.

The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “osteoporosis” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •

Soybeans: Good for Your Heart. Patient Education Source: Advance for Nurse Practitioners. 10(5): 85. May 2002. Summary: This article provides information on the health benefits of soybeans and foods made from soybeans. The possible benefits that soy proteins may have on certain diseases, such as coronary heart disease, menopause, This article, cancer, allergies, diabetes, and kidney disease, are briefly noted. The article also describes the soy products currently available, including edamame, miso, tofu, soy nuts, tempeh, soy milk, soy sauce, and natto. It lists two Web sites for additional information on soybeans.

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National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to osteoporosis and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “osteoporosis” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to osteoporosis: •

2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. Author(s): Brown JP, Josse RG; Scientific Advisory Council of the Osteoporosis Society of Canada. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 November 12; 167(10 Suppl): S1-34. Review. Erratum In: Cmaj. 2003 February 18; 168(4): 400. Cmaj. 2003 March 18; 168(6): 676. Cmaj. 2003 Mar 4; 168(5): 544. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427685&dopt=Abstract

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Active vitamin D and its analogs as drugs for the treatment of osteoporosis: advantages and problems. Author(s): Nishii Y. Source: Journal of Bone and Mineral Metabolism. 2002; 20(2): 57-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862526&dopt=Abstract

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Age-related changes in cortical bone content of insulin-like growth factor binding protein (IGFBP)-3, IGFBP-5, osteoprotegerin, and calcium in postmenopausal osteoporosis: a cross-sectional study. Author(s): Ueland T, Brixen K, Mosekilde L, Mosekilde L, Flyvbjerg A, Bollerslev J. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 10148. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629078&dopt=Abstract

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Alendronate improves bone mineral density in elderly women with osteoporosis residing in long-term care facilities. A randomized, double-blind, placebo-controlled trial. Author(s): Greenspan SL, Schneider DL, McClung MR, Miller PD, Schnitzer TJ, Bonin R, Smith ME, DeLucca P, Gormley GJ, Melton ME. Source: Annals of Internal Medicine. 2002 May 21; 136(10): 742-6. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020142&dopt=Abstract

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American Association of Clinical Endocrinologists 2001 Medical Guidelines for Clinical Practice for the Prevention and Management of Postmenopausal Osteoporosis.

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Author(s): Hodgson SF, Watts NB, Bilezikian JP, Clarke BL, Gray TK, Harris D W, Johnston CC, Kleerekoper M, Lindsay R, Luckey MM, McClung MR, Nankin HR, Petak SM, Recker RR; American Association of Clinical Endocrinologists. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2001 July-August; 7(4): 293312. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11508261&dopt=Abstract •

Asian and Asian-American college students' awareness of osteoporosis. Author(s): Nguyen DN, O'Connell MB. Source: Pharmacotherapy. 2002 August; 22(8): 1047-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173790&dopt=Abstract

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Biomarkers of bone health appropriate for evaluating functional foods designed to reduce risk of osteoporosis. Author(s): Weaver CM, Liebman M. Source: The British Journal of Nutrition. 2002 November; 88 Suppl 2: S225-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495464&dopt=Abstract

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Bone metabolism and the perimenopause overview, risk factors, screening, and osteoporosis preventive measures. Author(s): Sayegh RA, Stubblefield PG. Source: Obstetrics and Gynecology Clinics of North America. 2002 September; 29(3): 495-510. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353670&dopt=Abstract

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Bones and nutrition: common sense supplementation for osteoporosis. Author(s): Advani S, Wimalawansa SJ. Source: Curr Womens Health Rep. 2003 June; 3(3): 187-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734028&dopt=Abstract

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Breastfeeding and postmenopausal osteoporosis. Author(s): Grimes JP, Wimalawansa SJ. Source: Curr Womens Health Rep. 2003 June; 3(3): 193-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734029&dopt=Abstract

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By the way, doctor. I am 70 years old and have taken estrogen (Premarin 1.25 mg) for 14 years. Recently, my bone density test showed osteopenia, which my doctor says is the beginning of osteoporosis. Why would I still get osteoporosis after taking large doses of estrogen for so long? Author(s): Robb-Nicholson C.

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Source: Harvard Women's Health Watch. 1999 July; 6(11): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10454850&dopt=Abstract •

Calcium and vitamin D in osteoporosis: supplementation or treatment? Author(s): Burckhardt P. Source: Calcified Tissue International. 2002 February; 70(2): 74-7. Epub 2002 January 29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870411&dopt=Abstract

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Calcium intake in midlife women: one step in preventing osteoporosis. Author(s): Marchigiano G. Source: Orthopaedic Nursing / National Association of Orthopaedic Nurses. 1999 September-October; 18(5): 11-8; Quiz 19-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11052048&dopt=Abstract

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Calcium, dairy products and osteoporosis. Author(s): Heaney RP. Source: Journal of the American College of Nutrition. 2000 April; 19(2 Suppl): 83S-99S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10759135&dopt=Abstract

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Calcium, vitamin D and vitamin K in the prevention of fractures due to osteoporosis. Author(s): Meunier PJ. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 1999; 9 Suppl 2: S48-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10525726&dopt=Abstract

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Can calcium and vitamin D supplementation adequately treat most patients with osteoporosis? Author(s): Deal C. Source: Cleve Clin J Med. 2000 October; 67(10): 696-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060955&dopt=Abstract

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Carcinoma of the breast and hormone replacement therapy for osteoporosis. Author(s): Crawshaw A. Source: Int J Clin Pract. 2000 March; 54(2): 99-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10824364&dopt=Abstract

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Chronotherapy with active vitamin D3 in aged stroke-prone spontaneously hypertensive rats, a model of osteoporosis. Author(s): Tsuruoka S, Nishiki K, Sugimoto K, Fujimura A.

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Source: European Journal of Pharmacology. 2001 October 5; 428(2): 287-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675047&dopt=Abstract •

Clinical nutrition: 2. The role of nutrition in the prevention and treatment of adult osteoporosis. Author(s): Atkinson SA, Ward WE. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 November 27; 165(11): 1511-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762578&dopt=Abstract

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Clinical observation on treatment with the kidney-tonifying prescription in 25 cases of postmenopausal osteoporosis. Author(s): Zhao G, Cai D, Dong S, Fan Y. Source: J Tradit Chin Med. 2003 June; 23(2): 103-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875064&dopt=Abstract

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Complementary therapies for reducing the risk of osteoporosis in patients receiving luteinizing hormone-releasing hormone treatment/orchiectomy for prostate cancer: a review and assessment of the need for more research. Author(s): Moyad MA. Source: Urology. 2002 April; 59(4 Suppl 1): 34-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937434&dopt=Abstract

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Conference report--scientific and clinical developments in osteoporosis. Author(s): Lindsay R. Source: Medscape Women's Health [electronic Resource]. 1999 November; 4(6): 1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10629069&dopt=Abstract

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Diagnosis, prevention, and treatment of osteoporosis in men. Author(s): Epperly TD, Moore KE. Source: J Gend Specif Med. 2002 November-December; 5(6): 33-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503224&dopt=Abstract

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Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Author(s): Scheiber MD, Liu JH, Subbiah MT, Rebar RW, Setchell KD. Source: Menopause (New York, N.Y.). 2001 September-October; 8(5): 384-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528367&dopt=Abstract

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Dietary needs for bone health and the prevention of osteoporosis. Author(s): Love C.

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Source: British Journal of Nursing (Mark Allen Publishing). 2003 January 9-22; 12(1): 1221. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574721&dopt=Abstract •

Effect of calcium supplementation on bone dynamics of the maxilla, mandible and proximal tibia in experimental osteoporosis. Author(s): Shirai H, Sato T, Oka M, Hara T, Mori S. Source: Journal of Oral Rehabilitation. 2002 March; 29(3): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896847&dopt=Abstract

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Effect of omega 3 polyunsaturated fatty acid ingestion on bone metabolism and osteoporosis. Author(s): Terano T. Source: World Review of Nutrition and Dietetics. 2001; 88: 141-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11935946&dopt=Abstract

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Effects of Siberian ginseng extract and ipriflavone on the development of glucocorticoid-induced osteoporosis. Author(s): Kropotov AV, Kolodnyak OL, Koldaev VM. Source: Bulletin of Experimental Biology and Medicine. 2002 March; 133(3): 252-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360344&dopt=Abstract

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Effects of the selective oestrogen receptor modulator-raloxifene-on calcium and PTH secretory dynamics in women with osteoporosis. Author(s): Oleksik A, Duong T, Popp-Snijders C, Pliester N, Asma G, Lips P. Source: Clinical Endocrinology. 2001 May; 54(5): 575-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380487&dopt=Abstract

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Efficacy of a soy rich diet in preventing postmenopausal osteoporosis: the Menfis randomized trial. Author(s): Chiechi LM, Secreto G, D'Amore M, Fanelli M, Venturelli E, Cantatore F, Valerio T, Laselva G, Loizzi P. Source: Maturitas. 2002 August 30; 42(4): 295-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12191852&dopt=Abstract

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Essential fatty acids and osteoporosis. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11279685

Author(s): Cochrane Database Syst Rev. 2001;(1):CD000227 Source: Nutrition (Burbank, Los Angeles County, Calif.). 2000 May; 16(5): 386-90. Review. <Title>Evaluating

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postmenopausal osteoporosis. Author(s): Sagraves R. Source: The Annals of Pharmacotherapy. 2003 May; 37(5): 744-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708956&dopt=Abstract •

Glucocorticoid-induced osteoporosis in patients with sarcoidosis. Author(s): Adler RA, Funkhouser HL, Petkov VI, Berger MM. Source: The American Journal of the Medical Sciences. 2003 January; 325(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544077&dopt=Abstract

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Guidelines for the diagnosis of osteoporosis by densitometric methods. Author(s): Diez F. Source: Journal of Manipulative and Physiological Therapeutics. 2002 July-August; 25(6): 403-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183698&dopt=Abstract

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Guidelines on the management of osteoporosis associated with chronic liver disease. Author(s): Collier JD, Ninkovic M, Compston JE. Source: Gut. 2002 February; 50 Suppl 1: I1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788576&dopt=Abstract

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Investigation and treatment of osteoporosis in patients with fragility fractures. Author(s): Hajcsar EE, Hawker G, Bogoch ER. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2000 October 3; 163(7): 819-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11033708&dopt=Abstract

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Ipriflavone and osteoporosis. Author(s): Schelonka EP, Usher A. Source: Jama : the Journal of the American Medical Association. 2001 October 17; 286(15): 1836-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11597279&dopt=Abstract

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Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. Author(s): Alexandersen P, Toussaint A, Christiansen C, Devogelaer JP, Roux C, Fechtenbaum J, Gennari C, Reginster JY; Ipriflavone Multicenter European Fracture Study. Source: Jama : the Journal of the American Medical Association. 2001 March 21; 285(11): 1482-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255425&dopt=Abstract

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Low-frequency acoustic sweep monitoring of bone integrity and osteoporosis. Author(s): Panteliou SD, Abbasi-Jahromi H, Dimarogonas AD, Kohrt W, Civitelli R. Source: Journal of Biomechanical Engineering. 1999 August; 121(4): 423-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10464697&dopt=Abstract

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Management of glucocorticoid-induced osteoporosis in male veterans. Author(s): Elliott ME, Farrah RM, Binkley NC, Carnes ML, Gudmundsson A. Source: The Annals of Pharmacotherapy. 2000 December; 34(12): 1380-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144692&dopt=Abstract

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Management of male osteoporosis. Author(s): Cortet B, Vasseur J, Grardel B, Catanzariti L, Marchandise X, Delcambre B. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2001 May; 68(3): 252-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11394626&dopt=Abstract

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Management of osteoporosis in patients with gastrointestinal diseases. Author(s): von Tirpitz C, Reinshagen M. Source: European Journal of Gastroenterology & Hepatology. 2003 August; 15(8): 869-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867796&dopt=Abstract

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Management of osteoporosis in the new millennium. Author(s): Cavalieri TA. Source: J Am Osteopath Assoc. 2000 January; 100(1 Suppl): S16-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10705680&dopt=Abstract

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Medical treatment of osteoporosis--increasing options. Author(s): Leong KH. Source: Ann Acad Med Singapore. 2002 January; 31(1): 43-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885495&dopt=Abstract

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Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis. Author(s): Shea B, Wells G, Cranney A, Zytaruk N, Robinson V, Griffith L, Ortiz Z, Peterson J, Adachi J, Tugwell P, Guyatt G; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Source: Endocrine Reviews. 2002 August; 23(4): 552-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202470&dopt=Abstract

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Natural remedies for osteoporosis in postmenopausal women. Author(s): Del Mar Christopher B, Glasziou PP, Spinks AB, Sanders SL.

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Source: The Medical Journal of Australia. 2002 February 18; 176(4): 182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913921&dopt=Abstract •

Nonmedical management of osteoporosis. Author(s): Lin JT, Lane JM. Source: Current Opinion in Rheumatology. 2002 July; 14(4): 441-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118182&dopt=Abstract

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Novel therapeutic options for osteoporosis. Author(s): Biskobing DM, Novy AM, Downs R Jr. Source: Current Opinion in Rheumatology. 2002 July; 14(4): 447-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118183&dopt=Abstract

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Novel therapies for osteoporosis. Author(s): Biskobing DM. Source: Expert Opinion on Investigational Drugs. 2003 April; 12(4): 611-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665416&dopt=Abstract

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Nutritional factors in osteoporosis. Author(s): Swaminathan R. Source: Int J Clin Pract. 1999 October-November; 53(7): 540-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10692741&dopt=Abstract

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Osteopathic physicians should raise awareness of osteoporosis. Author(s): Cole RE. Source: J Am Osteopath Assoc. 2000 August; 100(8): 483. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979251&dopt=Abstract

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Osteoporosis and beta-thalassemia major: role of the IGF-I/IGFBP-III axis. Author(s): Lasco A, Morabito N, Gaudio A, Crisafulli A, Meo A, Denuzzo G, Frisina N. Source: J Endocrinol Invest. 2002 April; 25(4): 338-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030605&dopt=Abstract

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Osteoporosis and fractures. Author(s): van Zandt KB. Source: American Family Physician. 2000 February 15; 61(4): 960. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10706152&dopt=Abstract

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Osteoporosis and nutrition. Author(s): Eldridge R.

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Source: Pract Midwife. 2003 April; 6(4): 23-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715502&dopt=Abstract •

Osteoporosis and the aging male. Author(s): Stein B, Ashok S. Source: Medicine and Health, Rhode Island. 2002 May; 85(5): 160-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048750&dopt=Abstract

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Osteoporosis in childhood rheumatic diseases: prevention and therapy. Author(s): Cimaz R. Source: Best Practice & Research. Clinical Rheumatology. 2002 July; 16(3): 397-409. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387807&dopt=Abstract

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Osteoporosis in juvenile idiopathic arthritis. Author(s): McDonagh JE. Source: Current Opinion in Rheumatology. 2001 September; 13(5): 399-404. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11604595&dopt=Abstract

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Osteoporosis in men treated with androgen suppression therapy for prostate cancer. Author(s): Gholz RC, Conde F, Rutledge DN. Source: Clinical Journal of Oncology Nursing. 2002 March-April; 6(2): 88-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889683&dopt=Abstract

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Osteoporosis prevention in college women: application of the expanded health belief model. Author(s): Wallace LS. Source: American Journal of Health Behavior. 2002 May-June; 26(3): 163-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018752&dopt=Abstract

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Osteoporosis prevention: knowledge and behavior in a southwestern community. Author(s): Larkey LK, Day SH, Houtkooper L, Renger R. Source: Journal of Community Health. 2003 October; 28(5): 377-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535602&dopt=Abstract

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Osteoporosis. Author(s): Cimaz R, Biggioggero M. Source: Curr Rheumatol Rep. 2001 October; 3(5): 365-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564366&dopt=Abstract

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Osteoporosis: diagnosis, prevention, and treatment of established disease. Author(s): Dunlop MB, Lane NE.

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Source: Bulletin on the Rheumatic Diseases. 1999; 48(6): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10544524&dopt=Abstract •

Osteoporosis: evaluation and treatment. Author(s): Milott JL, Green SS, Schapira MM. Source: Compr Ther. 2000 Fall; 26(3): 183-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984823&dopt=Abstract

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Osteoporosis: pathophysiology and non-pharmacological management. Author(s): Mundy GR. Source: Best Practice & Research. Clinical Rheumatology. 2001 December; 15(5): 727-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11812018&dopt=Abstract

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Osteoporosis: prevention and treatment. 1. Author(s): Sutcliffe A. Source: Nurs Times. 2001 November 1-7; 97(44): 53-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966176&dopt=Abstract

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Osteoporosis--Part II: Dietary and/or supplemental calcium and vitamin D. Author(s): Moyad MA. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2002 December; 22(6): 405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593233&dopt=Abstract

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Patterns of bone diseases in transfusion-dependent homozygous thalassaemia major: predominance of osteoporosis and desferrioxamine-induced bone dysplasia. Author(s): Chan YL, Pang LM, Chik KW, Cheng JC, Li CK. Source: Pediatric Radiology. 2002 July; 32(7): 492-7. Epub 2002 April 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107582&dopt=Abstract

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Pharmacological activities of Genistein, an isoflavone from soy (Glycine max): part II-anti-cholesterol activity, effects on osteoporosis & menopausal symptoms. Author(s): Suthar AC, Banavalikar MM, Biyani MK. Source: Indian J Exp Biol. 2001 June; 39(6): 520-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562012&dopt=Abstract

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Phyto-oestrogens and osteoporosis: what is a safe dose? Author(s): Barnes S. Source: The British Journal of Nutrition. 2003 June; 89 Suppl 1: S101-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725659&dopt=Abstract

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Polyunsaturated fatty acids. Is there a role in postmenopausal osteoporosis prevention? Author(s): Albertazzi P, Coupland K. Source: Maturitas. 2002 May 20; 42(1): 13-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020975&dopt=Abstract

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Postmenopausal osteoporosis treatment guidelines. Author(s): Sambrook P, O'Neill S, Diamond T, Flicker L, MacLennan A. Source: Aust Fam Physician. 2000 August; 29(8): 751-3, 756-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10958021&dopt=Abstract

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Prevention and treatment of osteoporosis. Author(s): Prestwood KM, Raisz LG. Source: Clinical Cornerstone. 2002; 4(6): 31-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739329&dopt=Abstract

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Prevention of postmenopausal osteoporosis with oestrogen replacement therapy and associated compounds: update on clinical trials since 1995. Author(s): Doren M, Samsioe G. Source: Human Reproduction Update. 2000 September-October; 6(5): 419-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11045872&dopt=Abstract

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Protective role of n-3 lipids and soy protein in osteoporosis. Author(s): Fernandes G, Lawrence R, Sun D. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2003 June; 68(6): 361-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798656&dopt=Abstract

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Quality indicators for the management of osteoporosis in vulnerable elders. Author(s): Grossman JM, MacLean CH. Source: Annals of Internal Medicine. 2001 October 16; 135(8 Pt 2): 722-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11601955&dopt=Abstract

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Recognition of osteoporosis by primary care physicians. Author(s): Gehlbach SH, Fournier M, Bigelow C. Source: American Journal of Public Health. 2002 February; 92(2): 271-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818304&dopt=Abstract

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Rheumatology: 15. Osteoporosis. Author(s): Wade JP.

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Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 July 10; 165(1): 45-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468955&dopt=Abstract •

Risks and benefits of soy phytoestrogens in cardiovascular diseases, cancer, climacteric symptoms and osteoporosis. Author(s): Walsh PC. Source: The Journal of Urology. 2002 October; 168(4 Pt 1): 1637. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356048&dopt=Abstract

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Risks and benefits of soy phytoestrogens in cardiovascular diseases, cancer, climacteric symptoms and osteoporosis. Author(s): Sirtori CR. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2001; 24(9): 665-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522120&dopt=Abstract

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Role of Ca(2+) and vitamin D in the prevention and treatment of osteoporosis. Author(s): Rodriguez-Martinez MA, Garcia-Cohen EC. Source: Pharmacology & Therapeutics. 2002 January; 93(1): 37-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916540&dopt=Abstract

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Sex steroids, ANGELS and osteoporosis. Author(s): Moggs JG, Deavall DG, Orphanides G. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 2003 March; 25(3): 195-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596222&dopt=Abstract

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Short-term effects of a chicken egg shell powder enriched dairy-based products on bone mineral density in persons with osteoporosis or osteopenia. Author(s): Schaafsma A, Pakan I. Source: Bratisl Lek Listy. 1999 December; 100(12): 651-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10758743&dopt=Abstract

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Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. Author(s): Horwitz MJ, Tedesco MB, Gundberg C, Garcia-Ocana A, Stewart AF. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 February; 88(2): 569-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574182&dopt=Abstract

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Supplementation of vitamin D plus calcium is effective in corticosteroid-induced osteoporosis management. Author(s): Bijlsma JW. Source: Clin Exp Rheumatol. 2000 January-February; 18(1): 3-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10777337&dopt=Abstract

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The beneficial effect of OST-6 (OsteoCare), a herbomineral formulation, in experimental osteoporosis. Author(s): Mitra SK, Venkataranganna MV, Udupa UV, Gopumadhavan S, Seshadri SJ, Rafiq M, Anturlikar SD, Sundaram R, Tripathi M. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2001 May; 8(3): 195-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417912&dopt=Abstract

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The periodontal-systemic connection: implications for treatment of patients with osteoporosis and periodontal disease. Author(s): Krall EA. Source: Ann Periodontol. 2001 December; 6(1): 209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887467&dopt=Abstract

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The present state and perspective in treatment of primary osteoporosis by acupuncture and moxibustion. Author(s): Zhao Y. Source: J Tradit Chin Med. 2002 March; 22(1): 67-72. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11977527&dopt=Abstract

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The psychosocial aspects of osteoporosis in women. Author(s): Bayles CM, Cochran K, Anderson C. Source: Nurs Clin North Am. 2000 March; 35(1): 279-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10673581&dopt=Abstract

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The role of phytoestrogens in the prevention and treatment of osteoporosis in ovarian hormone deficiency. Author(s): Arjmandi BH. Source: Journal of the American College of Nutrition. 2001 October; 20(5 Suppl): 398S402S; Discussion 417S-420S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11603649&dopt=Abstract

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Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Author(s): Gillespie WJ, Avenell A, Henry DA, O'Connell DL, Robertson J.

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Source: Cochrane Database Syst Rev. 2001; (1): Cd000227. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279685&dopt=Abstract •

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Author(s): Gillespie WJ, Henry DA, O'Connell DL, Robertson J. Source: Cochrane Database Syst Rev. 2000; (2): Cd000227. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796331&dopt=Abstract

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Vitamin D status of women in the Geelong Osteoporosis Study: association with diet and casual exposure to sunlight. Author(s): Pasco JA, Henry MJ, Nicholson GC, Sanders KM, Kotowicz MA. Source: The Medical Journal of Australia. 2001 October 15; 175(8): 401-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700831&dopt=Abstract

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Vitamin K replacement in osteoporosis associated with cirrhosis: another reason to “eat your vegetables”? Author(s): Lipkin EW, Kowdley KV. Source: The American Journal of Gastroenterology. 2002 April; 97(4): 786-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003410&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

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The following is a specific Web list relating to osteoporosis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Amenorrhea Source: Healthnotes, Inc. www.healthnotes.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Arthritis, OsteoSource: Integrative Medicine Communications; www.drkoop.com Back Pain, Low Source: Integrative Medicine Communications; www.drkoop.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Bone loss Source: Integrative Medicine Communications; www.drkoop.com Celiac Disease Source: Healthnotes, Inc. www.healthnotes.com Cough Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Healthnotes, Inc. www.healthnotes.com Eating Disorders, Anorexia Source: Integrative Medicine Communications; www.drkoop.com High Homocysteine Source: Healthnotes, Inc. www.healthnotes.com Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Kidney Stones Source: Healthnotes, Inc. www.healthnotes.com Liver Cirrhosis Source: Healthnotes, Inc. www.healthnotes.com Low Back Pain Source: Integrative Medicine Communications; www.drkoop.com Menopausal Symptoms (Other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com

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Menopause Source: Healthnotes, Inc. www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Healthnotes, Inc. www.healthnotes.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com Parathyroid, Overactive Source: Integrative Medicine Communications; www.drkoop.com Parkinson's Disease Source: Healthnotes, Inc. www.healthnotes.com Periodontal Disease Alternative names: Gum Disease Source: Prima Communications, Inc.www.personalhealthzone.com •

Alternative Therapy Aston-patterning Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10118,00.html Chiropractic Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,681,00.html Macrobiotics Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,714,00.html Osteopathy Source: Integrative Medicine Communications; www.drkoop.com

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Osteopathy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,724,00.html Tai Chi Source: Integrative Medicine Communications; www.drkoop.com •

Homeopathy Calcarea carbonica Source: Healthnotes, Inc. www.healthnotes.com Calcarea phosphorica Source: Healthnotes, Inc. www.healthnotes.com Silicea (Silica) Source: Healthnotes, Inc. www.healthnotes.com Symphytum Source: Healthnotes, Inc. www.healthnotes.com

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Herbs and Supplements 7-KETO Source: Healthnotes, Inc. www.healthnotes.com Alendronate Source: Healthnotes, Inc. www.healthnotes.com Amino Acids Overview Source: Healthnotes, Inc. www.healthnotes.com Aminoglycosides Source: Integrative Medicine Communications; www.drkoop.com Androstenedione Source: Healthnotes, Inc. www.healthnotes.com Antituberculosis Agents Source: Integrative Medicine Communications; www.drkoop.com Barbiturates Source: Integrative Medicine Communications; www.drkoop.com Betaine (Trimethylglycine) Source: Healthnotes, Inc. www.healthnotes.com Bile Acid Sequestrants Source: Integrative Medicine Communications; www.drkoop.com

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Bisphosphonate Derivatives Source: Integrative Medicine Communications; www.drkoop.com Bisphosphonates Source: Healthnotes, Inc. www.healthnotes.com Black Cohosh Alternative names: Cimicifuga racemosa Source: Healthnotes, Inc. www.healthnotes.com Black Cohosh Source: Prima Communications, Inc.www.personalhealthzone.com Black cohosh Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10009,00.html Bone-building formula Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,838,00.html Brewer's Yeast Alternative names: Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com Caffeine Source: Healthnotes, Inc. www.healthnotes.com Calciferol Source: Integrative Medicine Communications; www.drkoop.com Calcitonin Source: Healthnotes, Inc. www.healthnotes.com Calcitrol Source: Integrative Medicine Communications; www.drkoop.com Cardiac Glycosides Source: Integrative Medicine Communications; www.drkoop.com Cholecalciferol Source: Integrative Medicine Communications; www.drkoop.com Corticosteroids Source: Prima Communications, Inc.www.personalhealthzone.com Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc. www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com

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DHEA Source: Integrative Medicine Communications; www.drkoop.com DHEA Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10022,00.html DHEA (Dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com Diclofenac Source: Healthnotes, Inc. www.healthnotes.com Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.drkoop.com EPA Source: Integrative Medicine Communications; www.drkoop.com Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Estradiol Source: Healthnotes, Inc. www.healthnotes.com Estrogen Source: Prima Communications, Inc.www.personalhealthzone.com Estrogens Source: Healthnotes, Inc. www.healthnotes.com Estrogens (Combined) Source: Healthnotes, Inc. www.healthnotes.com Estropipate Source: Healthnotes, Inc. www.healthnotes.com Felodipine Source: Healthnotes, Inc. www.healthnotes.com Gamma-Linolenic Acid (GLA) Source: Integrative Medicine Communications; www.drkoop.com GLA Source: Integrative Medicine Communications; www.drkoop.com

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GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Green Tea Source: Prima Communications, Inc.www.personalhealthzone.com Heparin Source: Healthnotes, Inc. www.healthnotes.com Heparin Alternative names: Hep-Lock Source: Prima Communications, Inc.www.personalhealthzone.com Histamine H2 Antagonists Source: Integrative Medicine Communications; www.drkoop.com Horsetail Alternative names: Equisetum arvense Source: Healthnotes, Inc. www.healthnotes.com Horsetail Source: Prima Communications, Inc.www.personalhealthzone.com Horsetail Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10105,00.html Humulus Alternative names: Hops; Humulus lupulus L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Hydantoin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Inhalant, Systemic, and Topical Corticosteroids Source: Integrative Medicine Communications; www.drkoop.com Inhaled Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com Ipriflavone Source: Healthnotes, Inc. www.healthnotes.com Ipriflavone Source: Prima Communications, Inc.www.personalhealthzone.com Ipriflavone Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10039,00.html

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Isoflavones Source: Prima Communications, Inc.www.personalhealthzone.com Lactase Source: Healthnotes, Inc. www.healthnotes.com Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com Lubricant Laxatives Source: Integrative Medicine Communications; www.drkoop.com Lysine Source: Healthnotes, Inc. www.healthnotes.com Medroxyprogesterone Source: Healthnotes, Inc. www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com Menadione Source: Integrative Medicine Communications; www.drkoop.com Menaphthone Source: Integrative Medicine Communications; www.drkoop.com Menaquinone Source: Integrative Medicine Communications; www.drkoop.com Miscellaneous Preparations Source: Integrative Medicine Communications; www.drkoop.com Monophasic, Biphasic, and Triphasic Preparations Source: Integrative Medicine Communications; www.drkoop.com Natural progesterone cream Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10099,00.html Oral Contraceptives Source: Prima Communications, Inc.www.personalhealthzone.com Oral Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com Phenobarbital Alternative names: Bellatal, Solfoton Source: Prima Communications, Inc.www.personalhealthzone.com

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Phosphorus Source: Integrative Medicine Communications; www.drkoop.com Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com Primidone Alternative names: Mysoline Source: Prima Communications, Inc.www.personalhealthzone.com Progesterone Source: Healthnotes, Inc. www.healthnotes.com Raloxifene Source: Healthnotes, Inc. www.healthnotes.com Red Clover Alternative names: Trifolium pratense , beebread, cow clover, cow grass, meadow clover, purple clover Source: Integrative Medicine Communications; www.drkoop.com Reverse Transcriptase Inhibitors Source: Integrative Medicine Communications; www.drkoop.com Silicon Source: Healthnotes, Inc. www.healthnotes.com Soy isoflavones Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10057,00.html Strontium Source: Healthnotes, Inc. www.healthnotes.com Thiazide Diuretics Source: Integrative Medicine Communications; www.drkoop.com Trace minerals Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10061,00.html Valproic Acid Derivatives Source: Integrative Medicine Communications; www.drkoop.com Vasodilators Source: Integrative Medicine Communications; www.drkoop.com

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Warfarin Alternative names: Coumadin Source: Prima Communications, Inc.www.personalhealthzone.com Wild yam Alternative names: Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON OSTEOPOROSIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to osteoporosis. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “osteoporosis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on osteoporosis, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Osteoporosis ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to osteoporosis. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Age-associated Bone Loss in an Imperial Roman Population: an Historical Analysis of Inter-skeletal and Intra-skeletal Variability by Cho, Helen; Phd from University of Missouri - Columbia, 2002, 237 pages http://wwwlib.umi.com/dissertations/fullcit/3052164

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Aging, Chronic Illness and Self-concept: a Study of Older Women with Osteoporosis by Wilkins, Mary Seanne; Phd from University of Toronto (canada), 1998, 221 pages http://wwwlib.umi.com/dissertations/fullcit/NQ41531

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Cellular Mechanisms of Vascular Calcification and Osteoporosis by Mody, Nilam; Phd from University of California, Los Angeles, 2002, 191 pages http://wwwlib.umi.com/dissertations/fullcit/3040255

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Effect of Web-based Computer-tailoring on Women's Intention to Continue or Begin to Use Hormone Replacement Therapy to Lower Their Risk for Osteoporosis by Mcginley, Anne Marie; Phd from University of Pennsylvania, 2002, 166 pages http://wwwlib.umi.com/dissertations/fullcit/3043913

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Lumbar Bone Density in Adolescent Female Runners (osteoporosis) by Moen, Susan Margaret, Phd from Texas Woman's University, 1990, 156 pages http://wwwlib.umi.com/dissertations/fullcit/9106745

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Mechanism of Impaired Bone Formation in Hypokinetic Osteopenia (osteoporosis) by Kidder, Louis Scott, Phd from Washington University, 1995, 164 pages http://wwwlib.umi.com/dissertations/fullcit/9606101

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Osteoporosis in Patients with End-stage Liver Cirrhosis: Evolution after Liver Transplantation. Study of the Mechanisms of Osteopenia and Their Correlation with Igf-i Synthesis by Pego Reigosa, Jose Maria; Dr from Universidad De Navarra (spain), 2002, 174 pages http://wwwlib.umi.com/dissertations/fullcit/f661809

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Osteoporosis: an Overview of Prevention, Genetics, and Treatment by Khaled, Hana Hassan; Ms from University of Louisville, 2002, 117 pages http://wwwlib.umi.com/dissertations/fullcit/1410580

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Postmenopausal Osteoporosis Characterisation of an Animal Model and the Effects of Dietary Calcium by Lazowski, Darien-alexis; Phd from The University of Western Ontario (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL51751

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Skeletal Adaptation to Disuse: Longitudinal and Cross-sectional Study of the Response of the Femur and Spine to Immobilization (paralysis) (osteoporosis) by Kiratli, Beatrice Jenny, Phd from The University of Wisconsin - Madison, 1989, 142 pages http://wwwlib.umi.com/dissertations/fullcit/8923333

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The Effectiveness of an Osteoporosis Health Education Program on Subsequent Behaviors of College Students by Okeson, Diane Lavon (minks); Edd from Oklahoma State University, 2001, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3023944

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The Relationship between Cortical Bone Involution and Fracture Occurrence in an Affluent Aging American White Population (osteoporosis) by Harrington, Richard James, Phd from The University of Arizona, 1992, 239 pages http://wwwlib.umi.com/dissertations/fullcit/9225194

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The Relationship between Exercise Knowledge and Exercise Self-efficacy for the Prevention of Osteoporosis by Leclaire, Suzanne Marguerite; Msn from Grand Valley State University, 2002, 80 pages http://wwwlib.umi.com/dissertations/fullcit/1407787

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Towards a Rational Definition of Osteoporosis by Homminga, Jasper Johan; Dr from Technische Universiteit Eindhoven (the Netherlands), 2003, 104 pages http://wwwlib.umi.com/dissertations/fullcit/f85585

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Women's Health: with a Focus on Hrt and Osteoporosis by Shirley, Andrea Beatrice; Phd from Queen's University of Belfast (northern Ireland), 2002, 370 pages http://wwwlib.umi.com/dissertations/fullcit/f692753

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND OSTEOPOROSIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning osteoporosis.

Recent Trials on Osteoporosis The following is a list of recent trials dedicated to osteoporosis.8 Further information on a trial is available at the Web site indicated. •

Bone Loss in Premenopausal Women with Depression Condition(s): Depression; Healthy; Osteopenia; Osteoporosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine whether women with major depression lose bone mass at a faster rate than women without depression. This study will also determine if the drug alendronate can maintain or increase bone mass in premenopausal women with major depression and osteoporosis.. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006180

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Calcium With or Without Estrogen and/or Risedronate in Preventing Osteoporosis in Patients with Prostate Cancer Condition(s): Osteoporosis; stage I prostate cancer; stage II prostate cancer; stage III prostate cancer Study Status: This study is currently recruiting patients.

8

These are listed at www.ClinicalTrials.gov.

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Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Preventing bone loss in patients who are undergoing androgen ablation for prostate cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without estrogen and/or risedronate in preventing osteoporosis. PURPOSE: Randomized phase III trial to compare the effectiveness of two forms of calcium with or without estrogen and/or risedronate in preventing osteoporosis in patients with prostate cancer who are receiving androgen ablation therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00043069 •

Combination Osteogenic Therapy in Established Osteoporosis Condition(s): Osteoporosis, Post-Menopausal Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This study is designed to determine if combining parathyroid (PTH 1-34) with fluoride (MFPSR) therapy in a cyclic treatment regimen will: (1) produce a greater increase in bone density of the spine than would be produced by either treatment alone; (2) prevent the resistance (i.e., decreased bone formation and no further increase in bone density) that is observed within 18-24 months of PTH therapy; (3) eliminate the calcium deficiency and osteomalacia that can occur with fluoride; (4) prevent excessive bone fluoride content; and (5) result in an increase in bone density which is maintained after treatment is discontinued. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018447

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Comparison of Study Drug With Alendronate on How it Effects GlucocorticoidInduced Osteoporosis Condition(s): Osteoporosis Study Status: This study is currently recruiting patients. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: Osteoporosis is a condition in which the amount of bone is reduced, the bones are weak, and there is an increased risk for fractures. Glucocorticoids (a type of cortisone such as prednisone) are prescribed to treat a large number of conditions such as arthritis and asthma. When taken for several months or longer, glucocorticoids can cause bone loss and lead to a form of osteoporosis called "glucocorticoid-induced osteoporosis." This study will be comparing the effects of the study drug to an available drug called alendronate on glucocorticoid-induced osteoporosis. Phase(s): Phase III Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051558 •

Lead Exposure, Genetics, and Osteoporosis Epidemiology Condition(s): Osteoporosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: This study's primary objective is to assess the effects of environmental lead exposures and genetic risk factors on the development of osteoporosis in middle-aged women. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00013637

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Osteoporosis in children and adults following liver transplantation Condition(s): Osteoporosis; liver transplantation Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: This pilot project aims to 1) estimate the prevalence of osteoporosis in adults having undergone liver transplantation in childhood, and 2) identify risk factors for osteoporosis in this group. We aim to study 40 individuals. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00008788

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Preventing Osteoporosis in Adolescent Girls Condition(s): Osteoporosis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Physical activity in adolescents is an important part of bone health. Good bone health in adolescents can decrease the risk of osteoporosis. This study will evaluate a program designed to increase the level of physical activity in adolescent girls. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069173

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Prevention of Osteoporosis in Men with Prostate Cancer Condition(s): Prostate Cancer; Osteoporosis; Hypogonadism Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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Purpose - Excerpt: The purpose of this two year study is to examine the safety and effectiveness of alendronate (Fosamax) for the prevention of bone loss in men with prostate cancer who are on therapy to lower their testosterone levels. All men will receive appropriate calcium and vitamin D supplements and one to two years of alendronate therapy. Bone density tests will be done every six months. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048841 •

Prevention of Postmenopausal Bone Loss with Nitric Oxide Condition(s): Osteoporosis; Osteopenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Imbalance in the activities of osteoclasts (cells responsible for bone loss) and osteoblasts (cells responsible for bone formation) may lead to osteoporosis and fractures in postmenopausal women. The postmenopausal status is associated with decreased estrogen levels and nitric oxide production. Estrogen replacement therapy has been shown to restore serum nitric oxide levels to normal. Reversing nitric oxide deficiency may be one othe mechanisms of the beneficial effect of bitroglycerin on bone. This study will test the safety and efficacy of nitroglycerin ointment for the treatment of decreased spine bone mineral density (osteopenia) in postmenopausal women. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00043719

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Randomized Study of Alendronate in Adult Patients With Cystic Fibrosis Related Osteoporosis Condition(s): Osteoporosis; Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; University of North Carolina Purpose - Excerpt: Objectives: I. Determine the bioavailability and biologic effect of alendronate on bone metabolism in patients with cystic fibrosis. II. Assess the safety and efficacy of this treatment regimen in improving osteoporosis in this patient population. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004489

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Randomized Study of Human Parathyroid Hormone in Middle-Aged Men with Idiopathic Osteoporosis Condition(s): Osteoporosis

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Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development; Columbia University Purpose - Excerpt: Objectives: I. Determine the effect of human parathyroid hormone (134) on bone mass in middle-aged men with idiopathic osteoporosis. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004406 •

Risedronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy for Primary Breast Cancer Condition(s): Osteoporosis; stage I breast cancer; stage II breast cancer; stage IIIA breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Preventing bone loss in patients who are receiving chemotherapy for breast cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without risedronate in preventing bone loss.. PURPOSE: Randomized phase III trial to compare the effectiveness of two forms of calcium with or without risedronate in preventing bone loss in premenopausal women who are receiving chemotherapy for primary stage I, stage II, or stage IIIA breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054418

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Sequential Use of Study Drug and Raloxifene HCI in the Treatment of Postmenopausal Women with Osteoporosis Condition(s): Osteoporosis, Postmenopausal Study Status: This study is currently recruiting patients. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: The purpose of this study is to determine whether the increase in spine bone mineral density that has been generally observed in previous clinical studies involving the study drug can be maintained or even increased if followed with raloxifene HCI. All qualifying study participants will receive the study drug followed by treatment with raloxifene HCI or placebo. All study participants will receive raloxifene HCI in the third phase of the study. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035256

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Tamoxifen to Prevent Bone Loss and Heart Disease in Premenopausal Women Receiving Chemotherapy for Stage I or Stage II Breast Cancer Condition(s): Osteoporosis; stage I breast cancer; stage II breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Tamoxifen may be able to increase bone density and decrease cholesterol in women who are undergoing chemotherapy for breast cancer. PURPOSE: Clinical trial to study the effectiveness of tamoxifen in preventing bone loss and heart disease caused by chemotherapy treatment in premenopausal women who have stage I or stage II breast cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005605

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The Effect of Zometa on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy Condition(s): Prostate Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Novartis Pharmaceuticals Purpose - Excerpt: The purpose of this study is to compare the effect of an investigational drug used intravenously and placebo administered every three months for one year, on bone loss associated with initial androgen deprivation) in men with prostate cancer without metastasis. In order to participate in this trial male patients must be 18 years of age or older and have been diagnosed with prostate cancer without metastasis and within one year of starting their androgen deprivation therapy at the day of randomization onto this trial. In addition, patients who have undergone a recent orchiectomy (or"ke-ek'te-me) (removal of one or two testes) are eligible to participate. Patients who received any prior bisphosphonate therapy or prior treatment with systemic corticosteroids within in the past 12 months are not eligible to participate. Also patients who are receiving treatment for osteoporosis are not eligible to participate. Inclusion into this clinical trial with this investigational drug is based on the protocol entry criteria and evaluation from a participating trial investigator. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063609

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To evaluate the ability of an investigational drug to reduce the rate of all subsequent skeletal fractures after a hip fracture. Condition(s): Osteoporosis; Hip Fracture Study Status: This study is currently recruiting patients. Sponsor(s): Novartis Pharmaceuticals Purpose - Excerpt: To evaluate that an investigational drug given once yearly for two years to men and women after surgical repair of a recent hip fracture will significantly

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reduce the rate of all re-occurring (new) skeletal fractures. All patients will receive vitamin D and calcium. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046254 •

Zoledronate and Estradiol in Preventing Bone Loss in Patients With Prostate Cancer Condition(s): Osteoporosis; stage III prostate cancer; stage IV prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Zoledronate and estradiol may be effective in preventing bone loss.. It is not yet known whether zoledronate and estradiol are more effective alone or in combination in preventing bone loss in patients who are receiving hormone therapy for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of zoledronate and estradiol alone to that of zoledronate combined with estradiol in preventing bone loss in patients who are receiving hormone therapy for prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049491

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Zoledronate in Preventing Bone Loss Caused By Long-Term Androgen Deprivation Therapy in Patients With Stage III or Stage IV Prostate Cancer Condition(s): Hypercalcemia; stage III prostate cancer; stage IV prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Zoledronate may prevent bone loss associated with long term androgen deprivation therapy. It is not yet known whether zoledronate combined with calcium is more effective than calcium alone in preventing bone loss.. PURPOSE: Randomized phase III trial to compare the effectiveness of zoledronate combined with calcium with that of calcium alone in preventing bone loss in patients with stage III or stage IV prostate cancer who have received long-term androgen deprivation therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058188

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Zoledronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy After Surgery For Early Stage Breast Cancer Condition(s): Osteoporosis; stage I breast cancer; stage II breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: It is not yet known whether zoledronate is effective in preventing bone loss in premenopausal women who are receiving adjuvant chemotherapy after undergoing surgery for early stage breast cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of zoledronate in preventing bone loss in premenopausal women who are receiving chemotherapy after surgery for early stage breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049452

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Zoledronate, Calcium, and Vitamin D in Preventing Bone Loss in Women Receiving Adjuvant Chemotherapy for Breast Cancer Condition(s): Osteoporosis; stage I breast cancer; stage II breast cancer; stage IV breast cancer; stage IIIA breast cancer; stage IIIB breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Zoledronate plus calcium and vitamin D may prevent bone loss in patients receiving adjuvant chemotherapy for breast cancer. It is not yet known which regimen is most effective for treating breast cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of zoledronate plus calcium and vitamin D in preventing bone loss in women who are receiving adjuvant chemotherapy for breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022087

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Zometa - Femara Adjuvant Synergy Trial (ZFAST) - Cancer Treatment Related Bone Loss in Postmenopausal Women with Estrogen Receptor Positive and/or Progesterone Receptor Positive Breast Cancer Receiving Adjuvant Hormonal Therapy Condition(s): Breast Neoplasms; Osteoporosis Study Status: This study is currently recruiting patients. Sponsor(s): Novartis Pharmaceuticals Purpose - Excerpt: This protocol is designed to compare the effect on bone of Zometa 4 mg every 6 months when given upfront versus delayed start ( based on a post-baseline BMD T- Score below -2.0 SD at either the lumbar spine or total hip, or any clinical fracture unrelated to trauma, or an asymptomatic fracture discovered at the month 36

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scheduled visit) in stage I-IIIa postmenopausal women with hormone receptor positive breast cancer who will receive Femara 2.5 mg daily as an adjuvant therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050011 •

Alendronate and/or Parathyroid Hormone for Osteoporosis Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study looks at the effects of two medications, alendronate and parathyroid hormone, on bone mass and on bone formation and bone breakdown in women with osteoporosis. We will randomly select postmenopausal women who have osteoporosis to receive laboratory-produced human parathyroid hormone (hPTH), or alendronate, or both for 2.5 years. Study participants will return to the study center periodically to have their bone mass measured and to give blood and urine samples for tests of bone formation and breakdown and for other laboratory tests. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000400

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Combined Use of Study Drug and a marketed SERM (Selective Estrogen Receptor Modulator) in Postmenopausal Women with Osteoporosis Condition(s): Osteoporosis, Postmenopausal Study Status: This study is no longer recruiting patients. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: The purpose of this study is to compare treatment with both Study Drug and a SERM to treatment with Study Drug alone. The study will evaluate any side effects that may be associated with the two drugs and may help to determine whether Study Drug and a SERM together can help patients with osteoporosis more than Study Drug alone. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046137

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Effect of Androgen Suppression on Bone Loss in Patients With or Without Bone Metastases Secondary to Prostate Cancer Condition(s): stage I prostate cancer; stage II prostate cancer; stage III prostate cancer; stage IV prostate cancer; Osteoporosis

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Study Status: This study is no longer recruiting patients. Sponsor(s): James P. Wilmot Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Assessing the effect of androgen suppression on bone loss in prostate cancer patients may improve the ability to plan treatment, may decrease the risk of fractures and bony pain, and may help patients live more comfortably. PURPOSE: Clinical trial to determine the effect of androgen suppression on bone loss in patients who have prostate cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003903 •

Effects of Parathyroid Hormone in Men with Osteoporosis Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will compare the effects of parathyroid hormone (PTH) alone, alendronate alone, and PTH plus alendronate in men with osteoporosis over a period of 2.5 years. Alendronate is a drug that blocks or reduces bone loss, whereas PTH stimulates the formation of new bone. All men in the study will receive some form of treatment for osteoporosis. The main results we will look for are changes in bone density measured at multiple places in the skeleton and changes in chemicals in the body that indicate bone breakdown and bone formation. The study should allow us to understand whether some breakdown of bone is required for PTH to have an overall bone-building effect in men. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000427

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Efficacy and safety study of intravenous ibandronate to treat postmenopausal osteoporosis as compared to daily oral ibandronate Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): Hoffmann-La Roche Purpose - Excerpt: The purpose of this study is to compare the effectiveness and safety of two doses of intravenous (given through the veins) ibandronate, 2 mg every 2 months or 3 mg every 3 months, with 2.5 mg daily oral ibandronate in the treatment of postmenopausal osteoporosis Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048074

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Efficacy and safety study of oral ibandronate to treat postmenopausal osteoporosis Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): Hoffmann-La Roche Purpose - Excerpt: The purpose of the study is to compare the effectiveness and safety of two monthly doses of oral ibandronate, 100 mg every month or 150 mg every month, with 2.5 mg daily oral ibandronate in the treatment of postemenopausal osteoporosis Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048061

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HORIZON-PFT: Pivotal Fracture Trial Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): Novartis Pharmaceuticals Purpose - Excerpt: HORIZON-PFT (Pivotal Fracture Trial) will study the effect of zoledronic acid, given once per year, on the treatment of osteoporosis in women past menopause. Hip and vertebral fractures are the most devastating consequences of osteoporosis.. HORIZON-PFT is designed to determine the benefits of zoledronic acid in fracture reduction at both the hip and spine. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049829

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Improving Bone Health in Adolescent Girls: The Youth Osteoporosis and Understanding Total Health (YOUTH) Study Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Osteoporosis affects nearly half of all American women over age 50. During the teenage years, girls can increase bone growth to decrease their risk of osteoporosis later in life. This study will test whether girls can change their food intake and physical activity patterns in ways that will increase their bone growth during the mid-teen years. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067600

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Low-Dose Hormone Replacement Therapy and Alendronate for Osteoporosis Condition(s): Osteopenia; Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Osteoporosis, a condition in which bones are fragile and break easily, is a major health problem for postmenopausal women. Research studies have shown that both estrogen/progestin replacement therapy (hormone replacement therapy, or HRT) and alendronate are effective in preventing and treating osteoporosis. However, because these drugs work in somewhat different ways, a combination of the two drugs might protect women from osteoporosis better than either drug alone. In this study we will test whether HRT and alendronate given together for 3.5 years to postmenopausal women with low bone mass will have a greater effect on bone than either HRT or alendronate given alone. We will also give every participant in this study calcium and vitamin D supplements. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000430

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Osteoporosis Prevention After Heart Transplant Condition(s): Osteoporosis; Cardiac transplantation Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Merck Research Laboratories Purpose - Excerpt: During the first year after a heart transplant, people often rapidly lose bone from their spine and hips. About 35 percent of people who receive heart transplants will suffer broken bones during the first year after transplantation. This study will compare the safety and effectiveness of the drug alendronate (Fosamax) and the active form of vitamin D (calcitriol) in preventing bone loss at the spine and hip after a heart transplant. In this study, people who have had a successful heart transplant will receive either active alendronate and a "dummy pill" instead of calcitriol, or active calcitriol and a dummy pill instead of alendronate for the first year after their transplant, starting within 1 month after transplant surgery. We will measure bone density in the hip and spine at the start of the study and after 6 and 12 months, and will also check for broken bones in the spine. This research should lead to ways of preventing this crippling form of osteoporosis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000412

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Osteoporosis Prevention: Changes to Exercise and Diet in Children Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients.

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Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: The purpose of this study is to determine whether educating parents about health and behavior management techniques will increase physical activity, calcium intake, fitness, and bone density in their children. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063050 •

Parathyroid Hormone (PTH) with Alendronate for Osteoporosis Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study investigates the effectiveness of parathyroid hormone (PTH) in combination with alendronate, a standard treatment for osteoporosis that blocks or reduces bone loss. We are using alendronate because it may help protect patients against any possible harmful effects of PTH in cortical bone such as the long bones or hip. We are testing two different treatment schedules of PTH-one in which we give PTH daily and one in which we give PTH for 3 out of every 6 months in a cyclical fashion. The entire study is 21 months long; the active treatment period is 18 months with a 6-month followup period. The main effects we will look for in this study are changes in body chemicals that are signs of bone formation or bone breakdown, and changes in bone density throughout the skeleton. We will randomly assign all study participants, who are women aged 50 and over, to either stay on alendronate alone, receive daily continuous PTH plus alendronate, or receive daily PTH for 3 months out of every 6 for a total of three separate 3-month cycles of PTH plus daily alendronate. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005006

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PaTH Study: Parathyroid Hormone and Alendronate for Osteoporosis Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This 2-year study will test the effectiveness of combining parathyroid hormone (PTH) and alendronate for treating osteoporosis in postmenopausal women. Alendronate is a drug used to treat osteoporosis and primarily prevents bone loss, whereas PTH increases bone formation. We will treat the study participants either with PTH and alendronate, alendronate alone, or PTH alone. We will determine the effects of these treatments by looking for changes in bone mineral density in the hip and spine. Phase(s): Phase II

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005005 •

Program to Prevent Osteoporosis in Girls Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Osteoporosis is a condition defined by decreased bone mass. Osteoporosis generally affects older women and can lead to bone fractures. One way to prevent osteoporosis is to build strong, healthy bones during childhood. This study will evaluate a program designed to improve girls' bones. The program encourages eating foods rich in calcium and participating in physical activity. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063024

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The BONES Project: Building Healthy Bones in Children Condition(s): Osteoporosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: The Beat Osteoporosis: Nourish and Exercise Skeletons (BONES) Project is an after-school program that includes weight loading physical activity, nutrition and bone health education, and calcium-rich snacks. The program is designed to improve bone health in early elementary school children. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065247

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A School-Based Osteoporosis Prevention Program for Adolescent Girls Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: The Incorporating More Physical Activity and Calcium in Teens (IMPACT) study was a behaviorally-based middle school nutrition and physical activity program for the prevention of osteoporosis. The goal of IMPACT was to increase calcium intake and physical activity to help build bone mass in girls. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067925

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Calcium and Bone Mass in Young Females Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: We originally suggested that calcium in the diet is important in determining the amount of bone (bone mass) that builds up in young adults. We are testing the effect of calcium on bone mass in 354 Caucasian (white) girls. At the start of this 7-year study, the average age of the girls was 11 years, and they had not yet reached puberty. The study will also provide information about the effect of calcium on body composition (body fat) and blood pressure in young women. We have been giving calcium to one group of participants in this study and giving a placebo (an inactive pill, or "sugar pill") to the other group. The results of this research will be important in preventing osteoporosis, because building more bone as a young person should reduce a woman's chances of developing osteoporosis later in life. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000402

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Can parathyroid hormone injections reverse glucocorticoid-induced osteoporosis Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose Excerpt: Glucocorticoids are potent anti-inflammatory and immunosuppressive agents. However, prolonged use of these potent agents results in severe bone loss and osteoporotic fractures. Parathyroid hormone (1-34), when given as a daily injection has been found to dramatically increase bone mass in osteoporotic animals and postmenopausal women. The purpose of this study is to determine whether 2 years of daily PTH (1-34) injections will increase bone mass and reduce the development of new fractures. In addition, we will follow the study subjects for 2 more years to determine which type of anti-resorptive agent is required to maintain the newly formed bone. We are enrolling postmenopausal women that are on chronic corticosteroid therapy (prednisone etc.) and have bone loss (osteopenia by DXA) to be a part of this four-year-long study. The patients will receive two-year therapy with either PTH (1-34) or placebo, and for the second part of the study subjects receive either estrogen and placebo or alendronate and placebo. We will measure bone gain by standard bone densitometry, special x-rays of the spine and hip, and serum and urine bone markers. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004993

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Determining the risk factors such as smoking, alcohol, and caffeine and their association with osteoporosis in men. Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program Purpose - Excerpt: The goals of this project are to establish a new cohort of male veterans and describe associations between potential risk factors and baseline bone mineral density (BMD) as well as rates of BMD loss. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011323

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Diagnostic Pilot Study of Dual Energy Absorptiometry in the Detection of Osteopenia or Osteoporosis in Patients With Thalassemia Major Condition(s): Osteoporosis; Thalassemia Major; Osteopenia Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Children's Hospital of Philadelphia Purpose - Excerpt: Objectives: I. Determine the frequency and severity of osteopenia and osteoporosis in patients with thalassemia major who undergo dual energy x-ray absorptiometry, and correlate these findings with other relevant endocrinologic measurements. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006138

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Electromagnetic Treatment For Bone Loss After Fractures Condition(s): Bone Disease, Metabolic; Osteopenia; Osteoporosis, Post-Traumatic Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will determine the usefulness of pulsing electromagnetic field (PEMF) technology to reverse or reduce the bone loss (osteopenia) that occurs in the forearm after fracture or surgery. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067834

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Once Weekly Parathyroid Hormone for Osteoporosis Condition(s): Osteopenia; Osteoporosis

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Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Daily parathyroid hormone (PTH) is approved by the FDA for the treatment of osteoporosis. This study will evaluate the safety and effectiveness of PTH when given once a week. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065637 •

Osteoporosis Prevention in Preadolescent Girls Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will test an osteoporosis prevention program aimed at preadolescent girls between the ages of 10 and 12 who have not yet started their menstrual periods. Girls in this age group are adding large amounts of new bone to their skeletons. Adding more bone at this time of life can reduce a person's chances of developing osteoporosis (thinning bones) in later years. We will look at how this osteoporosis prevention program affects the amount of calcium in the girls' diets, the amount of weight-bearing exercise they do, and their bone mass measured using ultrasound testing of the heel. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000413

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Phase II Study of Alendronate Sodium in Children With High-Turnover Idiopathic Juvenile Osteoporosis Condition(s): Osteoporosis Study Status: This study is not yet open for patient recruitment. Sponsor(s): FDA Office of Orphan Products Development; Medical University of South Carolina Purpose - Excerpt: Objectives: I. Determine the effects of alendronate sodium on skeletal remodeling and bone mineral density of the hip and spine in children with highturnover idiopathic juvenile osteoporosis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010439

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Phase III Randomized Study of the Effect of Postmenopausal Estrogen Replacement Therapy on Alveolar Bone Loss Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Dental and Craniofacial Research (NIDCR); Washington University School of Medicine Purpose - Excerpt: Objectives: I. Quantify periodontal alveolar bone loss rates in postmenopausal women. II. Evaluate the effects of estrogen on alveolar bone loss rates in these patients. III. Determine whether changes in periodontal bone mass relate to bone mass changes in other skeletal sites in these patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004650

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Prevention of Steroid-Induced Osteoporosis in Children Condition(s): Osteoporosis Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The purpose of this study is to determine whether the drug pamidronate can safely and effectively improve bone mineral density in growing children who have bone disease caused by taking steroid medications. People who take steroid medications called glucocorticoids, like prednisone or dexamethasone, for long periods almost always have decreased bone density and are at increased risk of breaking a bone. Research has shown that pamidronate improves bone density in adults who take glucocorticoids. However, use of pamidronate is not approved in children because it has not been extensively tested in children. It is possible that children will have a different response or unique problems with the medication because their bones are still growing. We will assign all study participants to one of two groups. One group will recieve pamidronate intravenously (through a vein) every 3 months in addition of daily oral calcium and vitamin D and the other group will receive calcium and vitamin D. The study is scheduled to run for 36 months, with visits to the study center once every 3 months. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022841

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PTHrP and Osteoporosis Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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Purpose - Excerpt: PTH-related protein, or ''PTHrP'', is a hormone which was discovered in 1987. As its name implies, it is closely related to another hormone discovered in the 1920's named parathyroid hormone or ''PTH''. PTH has been shown to be effective in treating osteoporosis in both animals and humans. PTHrP has been shown to be effective in treating osteoporosis in laboratory animals, and there are strong scientific reasons to think that it may be effective in humans as well. However, no human trials with PTHrP in the treatment of osteoporosis have been performed. The studies in this trial are focussed on determining whether PTHrP can indeed increase bone mass in postmenopausal women with osteoporosis, when administered daily by subcutaneous injection for three months. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021827 •

Treatment of Childhood Osteoporosis with Alendronate (Fosamax) Condition(s): Osteoporosis Study Status: This study is completed. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Bones grow and stay strong through a continuous process of formation (building) and resorption (break down). When more bone is formed than resorbed, the density (level of calcium) in bone increases and the bones become stronger. However, if more bone is resorbed than formed the density of bone decreases and the bones become weak. This condition is called osteoporosis. Osteoporosis is a rare but serious condition in children. Childhood osteoporosis can occur without a known cause (idiopathic juvenile osteoporosis). Children with osteoporosis suffer from pain, inability to stay active, and increased amounts of broken bones, including fractures of the spine. Even mild childhood osteoporosis may have long-term consequences since individuals who achieve a less than normal bone composition (peak bone mass) during the first 2030 years of life may be at an increased risk for osteoporosis as adults. Alendronate (Fosamax) is a drug that works by stopping bone resorption (break down). It has been used to treat post-menopausal osteoporosis, male osteoporosis and adults with osteoporosis due to long-term steroid therapy. The goal of this study is to determine the effectiveness of alendronate in children with idiopathic juvenile osteoporosis. Researchers believe that children treated with alendronate will improve bone strength and decrease the amount of fractures caused by osteoporosis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001720

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Vertebroplasty for the Treatment of Fractures Due to Osteoporosis Condition(s): Spinal Fractures; Osteoporosis Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

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Purpose - Excerpt: Vertebroplasty is a procedure used to stabilize broken vertebrae, the bones that form the spine. This study will evaluate the effectiveness of vertebroplasty for the treatment of fractures due to osteoporosis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068822

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “osteoporosis” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON OSTEOPOROSIS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “osteoporosis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on osteoporosis, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Osteoporosis By performing a patent search focusing on osteoporosis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on osteoporosis: •

(-)-hydroxycitric acid for the prevention of osteoporosis Inventor(s): Clouatre; Dallas L. (555 Bryant St. #357, Palo Alto, CA 94301-1704), Dunn; James M. (3236 Hinsdale Pl., Littleton, CO 80112) Assignee(s): none reported Patent Number: 6,441,041 Date filed: June 20, 2001 Abstract: (-)-Hydroxycitrate (HCA) supplementation constitutes a novel means of reducing the loss in bone mineral content such as that usually found in osteoporosis and the related loss in bone quality (protection against the corticoid-induced loss in nonmineral bone components). Similarly, HCA supplementation constitutes a novel means of reducing stress-induced bone loss and of reducing other forms of bone loss induced by glucocorticoid-related mechanisms. The discovery that HCA has bone lossmoderating effects allows for the creation of novel and more efficacious approaches to preventing osteoporosis and for maintaining normal bone metabolic functioning even in the face of diet and exercise habits which are less than ideal and in the face of chronic stress. Furthermore, this discovery makes possible the development of adjuvant modalities which can be used to improve the results realized through the employment of conventional anti-osteoporosis/bone protective remedies. Controlled release can be used to provide a sustained and modulated amount of the active to the body as desired and therefore to regulate the use of the compound. Excerpt(s): This invention relates to pharmaceutical compositions containing (-)hydroxycitric acid useful for preventing osteoporosis and other forms of bone loss.... Osteoporosis is Latin for "porous bones." It is a progressive condition in which the bones gradually lose their strength and density. As a living tissue, the bone is continuously "remodeled" as it renews itself, responds to damage, and so forth. It constantly is both releasing and absorbing new calcium. As is true of all other tissues, the bone renews itself with a turnover of its cells over time. Bone loss results when the balance of the constructive and destructive processes is tipped from equilibrium towards a loss of calcium and other bone components. An estimated 1.3 million older Americans suffer broken bones every year because of osteoporosis. Wrists, hips, and spinal vertebrae are the most susceptible areas. Women are far more susceptible than are men and suffer about 80% of the injuries caused by this condition. Nevertheless, as this number indicates, a substantial number of men also suffer from osteoporosis. At least in part, this gender-based disproportion in injuries appears to reflect the fact that males begin with larger and denser bones, hence can lose more bone mass and yet still not suffer damage. Still, there is more to it than this. By the age of 65, men on average have lost approximately 9% of their bone mass, whereas women have lost 26% of their bone mass on reaching this age.... More successful in preventing bone loss, at least in the short term, than hormone replacement therapy (HRT) is treatment with bisphosponates. Randomized clinical trials have demonstrated that vertebral fractures in postmenopausal women are reduced by treatment with the bisphosphonates alendronate, risedronate or raloxifene, and also with nasal calcitonin. The bisphosphonates also reduce the incidence of hip fractures in postmenopausal women and have an additive benefit in subjects receiving calcium and vitamin D supplements. (Black DM, et al. Randomised trial of effect of alendronate on risk of fracture in women

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with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348:1535-1541; Ettinger B, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA. 1999;282:637-645; Harris S T, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA. 1999;282:1344-1352; Chesnut CH 3rd, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med. 2000;109:267-276). Web site: http://www.delphion.com/details?pn=US06441041__ •

Agent for anti-osteoporosis Inventor(s): Arai; Shigeyuki (Okayama, JP), Nishizaki; Yasushi (Okayama, JP), Kurimoto; Masashi (Okayama, JP), Yoshizane; Chiyo (Okayama, JP) Assignee(s): Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo (Okayama, JP) Patent Number: 6,440,446 Date filed: April 16, 1999 Abstract: An orally or parenterally administrable agent for anti-osteoporosis, comprising trehalose as an effective ingredient and optionally another ingredients, that exerts a satisfactory therapeutic/prophylactic effect on osteoporosis with lesser side effects. Excerpt(s): This application claims priority from JP 126657/98 filed Apr. 22, 1998, JP 153696/98 filed May 20, 19998filed 164468/98 filed May 29, 1998, JP 316706/98 filed Nov. 6, 1998, and JP 316709/98 filed Nov. 6, 1998.... The present invention relates to an agent for anti-osteoporosis, and more particularly to an agent for anti-osteoporosis, comprising trehalose as- an effective ingredient.... Osteoporosis, alias Scalier's disease, is a symptom of the bone where the absolute quantity of bone lowers without qualitative change. In living bodies, osteogenesis by osteoblasts and bone resorption by osteoclasts are continued ceaselessly. osteogenesis is induced by an imbalance between the rates of osteogenesis and bone resorption, caused by some factors, that is inclined to a negative equilibrium side. The major causatives of osteoporosis are classified into environmentaland genetic-factors; the former may be ageing and endocrine diseases such as hyperthyroidism, hypogonadism, Cushing syndrome, etc. and the latter may be abnormality in an estrogen receptor gene, osteogenesis imperfecta tarda, homocysteinuria, etc. Once osteoporosis is caused, the following occurs successively to make bone porous; the width of cortical bone narrows, the cavity of bone marrow enlarges, and the trabecula of cancellous bone lowers. As osteoporosis progresses, the physical strength of bone lowers, and this makes patients complain frequently about their lumbago and arthralgia and makes their bone broken easily with only a slight shock. Web site: http://www.delphion.com/details?pn=US06440446__

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Analogs of parathyroid hormone and parathyroid hormone related peptide: synthesis and use for the treatment of osteoporosis Inventor(s): Nestor, Jr. John J. (Cupertino, CA), Krstenansky; John L. (Palo Alto, CA), Vickery; Brian H. (Mountain View, CA) Assignee(s): Syntex (U.S.A.) Inc. (Palo Alto, CA) Patent Number: 5,693,616 Date filed: May 23, 1995 Abstract: Synthetic polypeptide analogs of parathyroid hormone PTH, parathyroid hormone related peptide PTHrp, and of the physiologically active truncated homologs and analogs of PTH and PTHrp, in which amino acid residues (22-31) form an amphipathic.alpha.-helix, said residues (22-31) selected from hydrophilic amino acids (Haa) and lipophilic amino acids (Laa) ordered in the sequence:Haa (Laa Laa Haa Haa).sub.2 Laaand their pharmaceutically acceptable salts are useful for the prophylaxis and treatment of osteoporosis in mammals. Processes for the production of the polypeptides via solid phase and recombinant methods are provided. Excerpt(s): This invention relates to novel analogs of parathyroid hormone and parathyroid hormone related peptide, their synthesis by solid phase and recombinant techniques, and their use for increasing bone mass in mammalian subjects.... Osteoporosis is the most common form of metabolic bone disease and may be considered the symptomatic, fracture stage of bone loss (osteopenia). Although osteoporosis may occur secondary to a number of underlying diseases, 90% of all cases appear to be idiopathic. Postmenopausal women are particularly at risk for idiopathic osteoporosis (postmenopausal or Type I osteoporosis). Another high risk group for idiopathic osteoporosis is the elderly of either sex (senile or Type II osteoporosis). Osteoporosis has also been related to corticosteroid use, immobilization or extended bed rest, alcoholism, diabetes, gonadotoxic chemotherapy, hyperprolactinemia, anorexia nervosa, primary and secondary amenorrhea, and oophorectomy.... In the various forms of osteoporosis, bone fractures, which are the result of bone loss that has reached the point of mechanical failure, frequently occur. Postmenopausal osteoporosis is characterized by fractures of the wrist and spine, while femoral neck fractures seem to be the dominant feature of senile osteoporosis. Web site: http://www.delphion.com/details?pn=US05693616__

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Antiestrogens and their use in treatment of menopause and osteoporosis Inventor(s): Young; Ronald L. (Houston, TX) Assignee(s): BCM Technologies, Inc. (Houston, TX) Patent Number: 4,894,373 Date filed: January 12, 1988 Abstract: Disclosed is a method for treating menopausal symptoms and treating and preventing osteoporosis, wherein a true antiestrogen is administered and estrogen is not. This treatment is effective for female osteoporosis and can also be used to treat male osteoporosis. Examples of true antiestrogens are clomiphene, and its isomers, citrates and derivatives, as well as several other compounds which appear in the specification. Excerpt(s): The invention relates to the use of antiestrogens in treatment of menopausal symptoms and treatment and prevention of osteoporosis.... In the United States alone,

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there are approximately 40 million women who have entered their post-menopausal years. The life expectancy of a woman who attains her last menstrual period is about 28 years. A recent study indicates that 75 to 85% of these post-menopausal women will develop symptoms of estrogen deficiency. C. Hammond, M.D., et al., "Current Status of Estrogen Therapy for the Menopause," Fertil. Steril., 37(1): 5-25 (1982).... A common complaint of patients following ovarian failure is the "hot flash" or vasomotor symptom complex. This is described as a sudden onset of warmth in the face and neck, often progressing to the chest. It generally lasts several minutes, and is often evidenced by a visible red flush. These episodes may be uncomfortable. They are often accompanied by dizziness, nausea, headaches, palpitations and diaphoresis. Estrogen supplementation provides relief to over 90% of such patients. Web site: http://www.delphion.com/details?pn=US04894373__ •

Apparatus and method for diagnosing osteoporosis Inventor(s): Kubota; Yasuyuki (Kyoto, JP), Ishii; Tetsuya (Kyoto, JP), Kuriwaki; Masashi (Kyoto, JP) Assignee(s): Sekisui Kagaku Kogyo Kabushiki Kaisya (Osaka, JP) Patent Number: 5,817,020 Date filed: July 29, 1997 Abstract: The apparatus for diagnosing osteoporosis in the present invention radiates repeated ultrasonic pulses Ai toward cortical bone Mb in a subject and receives echoes Ae from the bone Mb. The received signal is converted to a digital echo signal by an A/D converter 8, and the echo level is detected by a CPU 11. The CPU 11 extracts the maximum echo level from the echo levels detected during the measurement period and calculates the acoustic impedance Zb of the cortical bone based on the maximum echo level which has been extracted. The bone density of the subject is calculated from the detected acoustic impedance Zb of the cortical bone using a predetermined recurrence formula. The acoustic impedance of bone is given by the square root of ›the elastic modulus.times.density! of bone, and since the elastic modulus of bone increases (or decreases) as bone density increases (or decreases), the elastic modulus of bone and bone density play a synergistic role in the acoustic impedance. The acoustic impedance Zb of bone is thus a good index for assessing bone density. Excerpt(s): This invention relates to an ultrasonic reflection type of apparatus and method for diagnosing osteoporosis by emitting ultrasonic pulses toward predetermined cortical bone in a subject so as to measure the echo levels from the surface of the cortical bone.... With the advent of an ageing society in recent years, the bone disease referred to as osteoporosis has become a problem. This is a disease in which the loss of bone calcium results in brittleness and susceptibility to fractures with minimal trauma, and can cause the elderly to become bedridden. The physical diagnosis of osteoporosis is managed by the precise measurement of bone density using a diagnostic apparatus featuring the use of X-rays such as DXA, but problems involved in physical diagnosis with X-rays are that the equipment is large and expensive, and its use is limited in many ways in the interests of protecting against harm caused by radiation exposure.... Diagnostic apparatuses featuring the use of transmitted ultrasonic waves or reflected ultrasonic waves have begun to enjoy more popularity as simple devices which do not suffer from such drawbacks. Web site: http://www.delphion.com/details?pn=US05817020__

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Benzo [B] thiophene compounds, and compositions for treating bone loss, and hyperlipidemia Inventor(s): Yong Cho; Stephen Sung (Palo Alto, CA), Pennington; Lewis Dale (Irvine, CA), Grese; Timothy Alan (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,998,442 Date filed: August 27, 1997 Abstract: The invention provides benzo[b]thiophene compounds, formulations, and methods of inhibiting bone loss or bone resorption, particularly osteoporosis, and cardiovascular-related pathological conditions including hyperlipidemia and related cardiovascular pathologies. Excerpt(s): Osteoporosis describes a group of diseases which arises from diverse etiologies, but which are characterized by the net loss of bone mass per unit volume. The consequence of this loss of bone mass and resulting bone fracture is the failure of the skeleton to provide adequate support for the body. One of the most common types of osteoporosis is associated with menopause. Most women lose from about 20% to about 60% of the bone mass in the trabecular compartment of the bone within 3 to 6 years after the cessation of menses. This rapid loss is generally associated with an increase of bone resorption and formation. However, the resorptive cycle is more dominant and the result is a net loss of bone mass. Osteoporosis is a common and serious disease among postmenopausal women.... There are an estimated 25 million women in the United States alone who are afflicted with this disease. The results of osteoporosis are personally harmful, and also account for a large economic loss due to its chronicity and the need for extensive and long term support (hospitalization and nursing home care) from the disease sequelae. This is especially true in more elderly patients. Additionally, although osteoporosis is generally not thought of as a life threatening condition, a 20% to 30% mortality rate is related to hip fractures in elderly women. A large percentage of this mortality rate can be directly associated with postmenopausal osteoporosis.... The most vulnerable tissue in the bone to the effects of postmenopausal osteoporosis is the trabecular bone. This tissue is often referred to as spongy or cancellous bone and is particularly concentrated near the ends of the bone (near the joints) and in the vertebrae of the spine. The trabecular tissue is characterized by small osteoid structures which interconnect with each other, as well as the more solid and dense cortical tissue which makes up the outer surface and central shaft of the bone. This interconnected network of trabeculae gives lateral support to the outer cortical structure and is critical to the biomechanical strength of the overall structure. In postmenopausal osteoporosis, it is primarily the net resorption and loss of the trabeculae which leads to the failure and fracture of bone. In light of the loss of the trabeculae in the postmenopausal woman, it is not surprising that the most common fractures are those associated with bones which are highly dependent on trabecular support, for example, the vertebrae, the neck of the weight-bearing bones such as the femur and the forearm. Indeed, hip fracture, collies fractures, and vertebral crush fractures are hallmarks of postmenopausal osteoporosis. Web site: http://www.delphion.com/details?pn=US05998442__

Patents 363

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Bisphosphonates prevent bone loss associated with immunosuppressive therapy Inventor(s): Yates; Ashley J. (Westfield, NJ), Daifotis; Anastasia G. (Westfield, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,616,571 Date filed: June 6, 1995 Abstract: Bisphosphonate, particularly alendronate, can prevent or treat bone loss associated with immunosuppressive therapy, whether or not the immunosuppressive therapy is associated with an organ transplant. Excerpt(s): This invention relates to the use of bisphosphonates, particularly alendronate, to prevent bone loss associated with immunosuppressive therapy, and in particular when such therapy is used in conjunction with organ transplantation.... Patients suffering fom various medical conditions which require an organ or bone marrow transplant, need a variety of drugs in order to suppress the body's tendency to reject the organ. This generally requires that the patient take one or more immunosuppressive agents, such as cyclosporine or the like, often in combination with adrenal corticosteriods, such as methylprednisolone. Unfortunately, the combination of the underlying condition, immobility or decreased mobility, and drug therapy causes these patients to experience a high degree of bone loss.... Further, various immunosuppressive agents are being tried as therapeutic agents in treating various conditions which do not necessarily involve organ transplantation, such as in rheumatoid arthritis, psoriasis, inflammatory bowel disease and nephrotic syndrome. These patients also are at high risk for bone loss. Web site: http://www.delphion.com/details?pn=US05616571__

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Combination therapy for osteoporosis Inventor(s): Ke; Hua Zhu (Ledyard, CT), Thompson; David D. (Gales Ferry, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,323,232 Date filed: August 11, 1998 Abstract: Pharmaceutical combination compositions including certain estrogen agonists/antagonists and prostaglandins or prostaglandin agonists/antagonists. The compositions are useful for the treatment of bone disorders including osteoporosis. Excerpt(s): This invention relates to a pharmaceutical combination of estrogen agonists/antagonists and agents that stimulate bone formation and increase bone mass, kits containing such combinations and the use of such combinations to treat conditions which present with low bone mass in mammals, including humans.... Osteoporosis is a systemic skeletal disease, characterized by low bone mass and deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In the U.S., the condition affects more than 25 million people and causes more than 1.3 million fractures each year, including 500,000 spine, 250,000 hip and 240,000 wrist fractures annually. Hip fractures are the most serious, with 5-20% of patients dying within one year, and over 50% of survivors being incapacitated.... The elderly are at greatest risk of osteoporosis, and the problem is therefore predicted to increase significantly with the aging of the population. Worldwide fracture incidence is forecast to increase three-fold

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over the next 60 years, and one study estimates that there will be 4.5 million hip fractures worldwide in 2050. Web site: http://www.delphion.com/details?pn=US06323232__ •

Combination therapy for the prevention and treatment of osteoporosis Inventor(s): Patchett; Arthur A. (Westfield, NJ), Rodan; Gideon A. (Bryn Mawr, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,043,026 Date filed: May 1, 1998 Abstract: The combination of an estrogen receptor modulator and a growth hormone secretagogue is useful in the treatment or prevention of diseases involving bone resorption, especially osteoporosis. Excerpt(s): The present invention provides a combination therapy for the treatment and prevention of osteoporosis. More particularly, the combination of the present invention comprises an estrogen receptor modulator and a growth hormone secretogogue.... Osteoclasts are multinucleated cells of up to 400.mu.m in diameter that resorb mineralized tissue, chiefly calcium phosphate, in vertebrates. They are actively motile cells that migrate along the surface of bone. They can bind to bone, secrete necessary acid and proteases and thereby cause the actual resorption of mineralized tissue from the bone.... More specifically, osteoclasts are believed to exist in at least two physiological states. In the secretory state, osteoclasts are flat, attach to the bone matrix via a tight attachment zone (sealing zone), become highly polarized, form a ruffled border, and secrete lysosomal enzymes and acid to resorb bone. The adhesion of osteoclasts to bone surfaces is an important initial step in bone resorption. In the migratory or motile state, the osteoclasts migrate across bone matrix and do not take part in resorption until they attach again to bone. Web site: http://www.delphion.com/details?pn=US06043026__

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Composition and method for the treatment of osteoporosis in mammals Inventor(s): Burk; Robert Roland (Bottmingen, CH) Assignee(s): Novartis Corporation (New York, NY) Patent Number: 6,174,857 Date filed: December 30, 1996 Abstract: Pharmaceutical compositions and methods for the treatment of osteoporosis in mammals are disclosed. The compositions are suitable for parenteral administration and comprise Insulin-Like Growth Factor I (IGF-I) and a pharmaceutically acceptable carrier. The compositions for use in the methods may also include bone antiresorptive compounds. Excerpt(s): The present invention concerns a method for the treatment of patients having osteoporosis in which such patients exhibit decreased bone mineral density and patients substantially at risk of developing such decreased bone mineral density through the administration of insulin-like growth factor I (IGF-I) and pharmaceutical compositions therefor.... Osteoporosis encompasses a broad range of clinical syndromes having

Patents 365

varving etiologies. In postmenopausal women, for example, two distinct types of osteoporosis have been identified. Type I osteoporosis occurs mainly in the early postmenopausal period from about age 50-65. It is characterized by excessive resorption, primarily in trabecular bone. Vertebral fractures are common and if given prior to significant bone loss, treatment which decreases or prevents bone resorption (such as estrogen or calcitonin) is considered effective therapy.... Type II osteoporosis (a.k.a. senile osteoporosis) occurs essentially in all aging women and, to a lesser extent, in men. It is characterized by proportionate loss of cortical and trabecular bone. Here decreased bone formation plays a major role, if not a more important role than increased bone resorption. Fractures of the hip are characteristic of this type. Web site: http://www.delphion.com/details?pn=US06174857__ •

Composition comprising fluriprofen and effectively non-antibacterial tetracycline to reduce bone loss Inventor(s): Greenwald; Robert A. (Melville, NY), Ramamurthy; Nangavarum S. (Smithtown, NY), McNamara; Thomas F. (Port Jefferson, NY), Golub; Lorne M. (Smithtown, NY) Assignee(s): The Research Foundation of State University of New York (Albany, NY) Patent Number: 5,321,017 Date filed: August 12, 1991 Abstract: A method for treating mammals suffering from rheumatoid arthritis and other tissue-destructive (chronic inflammatory or other) conditions associated with excess metalloproteinase activity comprising administering to the mammal an amount of a tetracycline that is effectively anti-metalloproteinase, but that is not effectively antimicrobial, and an amount of non-steroidal anti-inflammatory agent which, when combined with the effectively anti-metalloproteinase amount of tetracycline, results in a significant reduction of tissue destruction and/or bone loss. Excerpt(s): The present invention relates to an anti-collagenolytic composition useful in the treatment of rheumatoid arthritis and other tissue-destructive conditions associated with excess collagenolytic activity as well as a method for using such formulations.... Tetracycline as well as the 5-0H (terramycin) and 7-C1 (Aureomycin) derivatives exist in nature, and are well known antibiotics. Natural tetracyclines may be modified without losing their antibiotic properties, although certain elements of the structure must be retained. The modifications that may and may not be made to the basic tetracycline structure have been reviewed by Mitscher in The Chemistry of Tetracyclines, Chapter 6. According to Mitscher, the substituents at positions 5-9 of the tetracycline ring system may be modified without the complete loss of antibiotic properties. Changes to the basic ring system or replacement of the substituents at positions 1-4 and 10-12, however, generally lead to synthetic tetracyclines with substantially less or effectively no antibacterial activity. For example, 4-dedimethylaminotetracycline is commonly considered to be a non-antibacterial tetracycline.... The use of tetracycline antibiotics, while effective, may lead to undesirable side effects. For example, the long term administration of antibiotic tetracyclines may reduce or eliminate healthy flora, such as intestinal flora, and may lead to the production of antibiotic resistant organisms or the overgrowth of yeast and fungi. Web site: http://www.delphion.com/details?pn=US05321017__

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Composition comprising indomethacin [non-steroidal anti-inflammatory agent] and effectively non-antibacterial tetracycline to reduce bone loss Inventor(s): Golub; Lorne M. (Smithtown, NY), McNamara; Thomas F. (Port Jefferson, NY), Ramamurthy; Nangavarum S. (Smithtown, NY), Greenwald; Robert A. (Melville, NY) Assignee(s): The Research Foundation of State University of New York (Albany, NY) Patent Number: 5,459,135 Date filed: February 23, 1994 Abstract: A method for treating mammals suffering from rheumatoid arthritis and other tissue-destructive (chronic inflammatory or other) conditions associated with excess metalloproteinase activity comprising administering to the mammal an amount of a tetracycline that is effectively anti-metalloproteinase, but that is not effectively antimicrobial, and an amount of non-steroidal anti-inflammatory agent which, when combined with the effectively anti-metalloproteinase amount of tetracycline, results in a significant reduction of tissue destruction and/or bone loss. Excerpt(s): The present invention relates to an anti-collagenolytic composition useful in the treatment of rheumatoid arthritis and other tissue-destructive conditions associated with excess collagenolytic activity as well as a method for using such formulations.... Tetracycline as well as the 5-OH (terramycin) and 7-Cl (Aureomycin) derivatives exist in nature, and are well known antibiotics. Natural tetracyclines may be modified without losing their antibiotic properties, although certain elements of the structure must be retained. The modifications that may and may not be made to the basic tetracycline structure have been reviewed by Mitscher in The Chemistry of Tetracyclines, Chapter 6. According to Mitscher, the substituents at positions 5-9 of the tetracycline ring system may be modified without the complete loss of antibiotic properties. Changes to the basic ring system or replacement of the substituents at positions 1-4 and 10-12, however, generally lead to synthetic tetracyclines with substantially less or effectively no antibacterial activity. For example, 4-dedimethylaminotetracycline is commonly considered to be a non-antibacterial tetracycline.... The use of tetracycline antibiotics, while effective, may lead to undesirable side effects. For example, the long term administration of antibiotic tetracyclines may reduce or eliminate healthy flora, such as intestinal flora, and may lead to the production of antibiotic resistant organisms or the overgrowth of yeast and fungi. Web site: http://www.delphion.com/details?pn=US05459135__

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Composition for the prevention and/or treatment of osteoporosis and alterations due to menopause syndrome Inventor(s): Cavazza; Claudio (Rome, IT) Assignee(s): Sigma-Tau Healthscience S.p.A. (Pomezia, IT) Patent Number: 6,335,038 Date filed: December 22, 2000 Abstract: A composition that may take the form of a dietary supplement or of a medicament is disclosed which comprises as active ingredients propionyl L-carnitine and the isoflavone genistein for the therapeutic treatment of osteoporosis and menopause syndrome.

Patents 367

Excerpt(s): The present invention relates to a composition for the prevention and/or treatment of osteoporosis and alterations due to menopause syndrome.... Accordingly the composition may take the form and exert the action of a dietary supplement or of an actual medicine, depending upon the support or preventive action, or the strictly therapeutic action, which the composition is intended to exert in relation to the particular individuals it is to be used in.... (b) 4',5,7-trihydroxyisoflavone (genistein) optionally in combination with at least another isoflavone selected from the group comprising 4',7-dihidroxyisoflavone (daidzein), its 7-glucoside (daidzin) and its 4,7diglucoside. Web site: http://www.delphion.com/details?pn=US06335038__ •

Compositions for inhibiting bone loss Inventor(s): Neubauer; Blake L. (Indianapolis, IN), Audia; James E. (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,670,514 Date filed: March 28, 1996 Abstract: The present invention provides methods of inhibiting bone loss in mammals via the administration to a mammal in need of such treatment an effective amount of a compound from a series of benzoquinolin-3-ones. Such compounds also are sequentially or concurrently coadministered with a bone antiresorptive agent or a bone anabolic agent. Excerpt(s): The present invention relates to the fields of pharmacology and pharmaceutical chemistry, and provides methods for inhibiting the loss of bone in humans.... The mechanism of bone loss is not well understood, but in practical effect, the disorder arises from an imbalance in the formation of new healthy bone and the resorption of old bone, skewed toward a net loss of bone tissue. This bone loss includes a decrease in both mineral content and protein matrix components of the bone, and leads to an increased fracture rate of, predominantly, femoral bones and bones in the forearm and vertebrae. These fractures, in turn, lead to an increase in general morbidity, a marked loss of stature and mobility, and, in many cases, an increase in mortality resulting from complications.... Bone loss occurs in a wide range of subjects including post-menopausal women, patients who have undergone hysterectomy, patients who are undergoing or have undergone long-term administration of corticosteroids, patients suffering from Cushing's syndrome, and patents having gonadal dysgenesis. Web site: http://www.delphion.com/details?pn=US05670514__

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Densitometer for scanning os calcis for predicting osteoporosis Inventor(s): Manly; Philip J. (c/o Osteon Incorporated, 649 California Ave., Wahiawa, HI 96786), Vogel; John M. (c/o University of California-Davis Medical Center, Sacramento, CA 95817), Wasnich; Richard D. (c/o Kuakini Medical Center, 347 N. Kaukini, Honolulu, HI 96817) Assignee(s): none reported Patent Number: 4,829,549 Date filed: November 30, 1987

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Abstract: The level of relative risk of osteoporosis in human subjects can be quickly determined by: measuring the bone mineral content of the os calcis (heel)--which is highly trabecular--and; assessing relative non-violent fracture risk at substantially all skeletal sites (both spinal and non-spinal) due to osteoporosis of the subject from the os calcis mineral content determination. The bone mineral content of a cortical bone site, such as the proximal radius (forearm), can also be determined. The densitometer apparatus includes a heel holding structure, or a forearm holding structure, which may be placed between a low energy source of gamma and/or x-rays, and a detector. The source and detector are mounted on a C-shaped yoke, which yoke can be moved horizontally and vertically during a rectilinear scan, and which can be rotated about a vertical axis when computed tomography (CT) capabilities are necessary. Excerpt(s): Osteoporosis has been increasingly recognized as a prevalent debilitating condition. However when osteopenia is discovered at early stages, a variety of treatments can be prescribed which can effectively prevent progress to clinically significant osteoporosis. Exercise (particularly by weight loading bones), calcium supplements, estrogen, and estrogen thiazide combinations, can each be effective at different stages in progression. Even when there has been significant progression to clinically significant osteoporosis, some treatment strategies are available, including the administering of sodium fluoride. In view of the available treatment strategies, it has been widely recognized that techniques for the accurate, safe, and relatively inexpensive determination of the level of risk for osteoporosis are highly desirable.... Indiscriminant treatment of all postmenopausal women (who have by far by the highest propensity to osteoporosis in the population, irrespective of actual risk) is not cost-effective and is limited by low patient compliance. Bone mineral content (BMC), which has been demonstrated to correlate with skeletal strength, can be precisely measured by a variety of techniques, and at many different skeletal sites, however no prospective data has been available relating BMC to fracture incidence. Conventional understanding suggests that the prediction of fracture risk at a given site, such as the spine, necessarily requires direct BMC measurements of that site, and since it is not feasible to measure all potential fracture sites, and since it is not known ahead of time for any given individual which skeletal site might be at greatest risk, prediction of fracture risks by prefracture BMC measurements has not been implemented.... According to the present invention, an accurate, safe, and relatively inexpensive method has been developed for determining the level of risk for osteoporosis in humans. According to the present invention it has been surprisingly found that it is possible to predict fracture risk at multiple skeletal sites (substantially all skeletal sites), both spinal and non-spinal (including the hip) by screening individuals utilizing a single BMC measurement site. The word "fracture" as used herein means non-violent fractures incident to the osteoporotic syndrome. Web site: http://www.delphion.com/details?pn=US04829549__ •

Detecting genetic predisposition for osteoporosis Inventor(s): Eastell; Richard (289 Ringinglow Road, Sheffield, S11 7PZ, GB2), Duff; Gordon W. (18 Ashgate Road, Sheffield, S10 3BZ, S Yorks, GB2), Russell; Graham (Ronksley Farm Hollow Meadows, Sheffield, South Yorks S6 6GH, GB2) Assignee(s): none reported Patent Number: 5,698,399 Date filed: April 5, 1996

Patents 369

Abstract: The present invention relates to methods of predicting the risk of osteoporosis. Specifically, the methods comprise isolating genomic DNA from an individual and determining an allelic pattern for IL-1 receptor antagonist (IL-1ra) in the genomic DNA. The identification of at least one copy of allele 2 indicates increased susceptibility to osteoporosis. Excerpt(s): This invention relates to a method of detecting a predisposition for osteoporosis.... In 1993, osteoporosis was identified as "one of the leading diseases of women" by Bernadine Healy, MD, then director of the National Institutes of Health. Complications following osteoporosis fractures are the fourth leading cause of death for women over the age of 65, following heart disease, cancer and stroke. It is the leading cause of disability in the United States and the most common cause of hip fracture. For reviews see in general "A Women Doctor's Guide to Osteoporosis" (Sherrer and Levinson, 1995); "150 Most Asked Questions About Osteoporosis" (Jacobowitz, 1993); and "Osteoporosis: Etiology, Diagnosis, and Management" (Raven Press, 1988), as well as Peel and Eastell (1995) and Eastell and Riggs (1988, 1987a,b).... Twenty-five million Americans suffer from osteoporosis, of which 85% are women. Type 1 osteoporosis, which is postmenopausal osteoporosis stemming from loss of estrogen, affects more than half of all women over 65 and has been detected in as many as 90 percent of women over age 75. Type II or senile osteoporosis which is strictly age related, affects both men and women usually over the age of seventy. Another form of osteoporosis affecting both sexes, is drug-induced, for example, by long-term steroid therapy, known to accelerate bone loss (Eastell, 1995). Patient groups that receive long term steroid therapy include asthmatics (7 million over the age of 18 in the United States) as well as patients with rheumatoid arthritis or other autoimmune diseases. Osteoporosis can also occur in association with an underlying disease such as rheumatoid arthritis (prevalence of 1-2% in the population). Web site: http://www.delphion.com/details?pn=US05698399__ •

Diagnosis of osteoporosis using acoustic emissions Inventor(s): Aldrich; John E. (North Vancouver, CA), Akhtar; Ainul (Vancouver, CA), Lentle; Brian C. (West Vancouver, CA) Assignee(s): The University of British Columbia (Vancouver, CA) Patent Number: 6,024,711 Date filed: March 12, 1998 Abstract: Osteoporosis may be detected in-vivo by applying an acoustic sensor in contact with the skin of the patient while subjecting the patient to stress, for example, by lifting light weights and measuring the acoustic emissions sensed by the acoustic sensor to provide an indication of the degree of osteoporosis damage incurred by the bones of the patient being diagnosed. Excerpt(s): The present invention relates to a test method for diagnosing osteoporosis, more particularly, the present invention comprises a method of detecting osteoporosis by sensing acoustic emissions.... Osteoporosis is a disease involving considerable socioeconomic implications in that it leads to hip fractures, vertebral fractures which cause severe pain and immobility and often result in surgery. The diagnostic test of choice for determining osteoporosis (prior to the present invention) is bone densitometry using a dual x-ray beam device, though it is also possible to use tests such as computed tomography CT and magnetic resonance imaging and/or ultra-sound measurements.

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None of these processes is of wide spread use due to the associated high cost of testing.... Dual energy x-ray absorption (DXA) and quantitative computed tomography (QCT) measure the electron density of bone which is almost entirely due to its calcium content. These procedures provide a measure of bone mass and thus an indication of whether the patient is suffering from osteoporosis since in osteoporosis there is a proportional loss of both matrix and material. Web site: http://www.delphion.com/details?pn=US06024711__ •

Diagnosis of predisposition to osteoporosis Inventor(s): Ralston; Stuart Hamilton (Aberdeen, GB), Grant; Struan Frederick Airth (Sydney, AU) Assignee(s): Gemini International Holdings Limited (MC) Patent Number: 5,922,542 Date filed: February 28, 1997 Abstract: Diagnostic means that determines the genotype of a collagen gene of an individual is described. A polymorphism in the collagen gene correlates with predisposition to osteoporosis, so diagnosis of a predisposition is achieved using the diagnostic means. An isolated gene comprising the nucleotide substitution of the polymorphism is also described, as is a method of diagnosis based on the presence or absence of the polymorphism. Excerpt(s): This invention relates to diagnostic method and apparatus based upon a polymorphism in a collagen gene. More specifically, this invention relates to method and apparatus for diagnosis of pre-disposition to certain disease states, by screening for the presence of this polymorphism, and more specifically to diagnosis of predisposition to osteoporosis. The invention further relates to a collagen gene containing the polymorphism.... Hormone replacement therapy is an established treatment for osteoporosis and has proved successful in halting further decline in bone density that is characteristic in women suffering from this disease. Hormone replacement therapy is generally not, however, able to bring about a reversal of osteoporosis, that is to say it is not capable of inducing an increase in the bone density of sufferers.... It would, accordingly, be of particular advantage to be able to identify with increased accuracy those individuals having a predisposition or increased susceptibility to osteoporosis. Suitable therapy could then be put into place before the effects of osteoporosis set in. Web site: http://www.delphion.com/details?pn=US05922542__

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Diagnostics and therapeutics for osteoporosis Inventor(s): van Dijk; Simon (San Antonio, TX), Duff; Gordon W. (Sheffield, GB) Assignee(s): Interleukin Genetics, Inc. (Waltham, MA) Patent Number: 6,558,905 Date filed: August 30, 2000 Abstract: Diagnostics and therapeutics for osteoporosis, which are based on the identification of the subject's IL-1 haplotype pattern are described.

Patents 371

Excerpt(s): In 1993, osteoporosis was identified as "one of the leading diseases of women" by Bernadine Healy, MD, then director of the National Institutes of Health. Complications following osteoporosis fractures are the fourth leading cause of death for women over the age of 65, following heart disease, cancer and stroke. It is the leading cause of disability in the United States and the most common cause of hip fracture.... Twenty-five million Americans suffer from osteoporosis, of which 85% are women. Type 1 osteoporosis, which is postmenopausal osteoporosis stemming from loss of estrogen, affects more than half of all women over 65 and has been detected in as many as 90 percent of women over age 75. Type II or senile osteoporosis which is strictly age related, affects both men and women usually over the age of seventy. Type III, the newest classification affecting both sexes, is drug-induced, for example, by long-term steroid therapy, known to accelerate bone loss. Patient groups that receive long term steroid therapy include asthmatics (7 million over the age of 18 in the United States) as well a patients with rheumatoid arthritis or other autoimmune diseases. Type IV is caused by an underlying disease such as rheumatoid arthritis (prevalence of 1-2% in the population).... Osteoporosis is responsible for a majority of the 1.5 million bone fractures each year leading to disabilities costing 10 billion dollars in medical, social and nursinghome costs. Even in the best hands, 40% of patients 65 years of age or older will not survive two years following a hip fracture. Web site: http://www.delphion.com/details?pn=US06558905__ •

Dibenzoazulene derivatives for treating thrombosis, osteoporosis, arteriosclerosis Inventor(s): Goodman; Simon (Griesheim, DE), Gottschlich; Rudolf (Reinheim, DE), Stahle; Wolfgang (Ingelheim, DE) Assignee(s): Merck Patent GmbH (Darmstadt, DE) Patent Number: 6,521,646 Date filed: October 15, 2001 Abstract: Compounds of the formula (I) and their physiologically acceptable salts and solvates are useful as integrin-inhibiting substances. They are especially useful in the prophylaxis and treatment of cardiovascular disorders, of thrombosis, cardiac infarction, coronary heart diseases, arteriosclerosis, osteoporosis, in pathological conditions that are caused or propagated by angiogenesis and in tumor therapy. Excerpt(s): and their physiologically acceptable salts and solvates.... Similar compounds are disclosed, for example, in WO 97/01540.... The invention is based on the object of finding novel compounds having valuable properties, in particular those which can be used for the production of medicaments. Web site: http://www.delphion.com/details?pn=US06521646__

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Dietary supplement derived from fermented milks for the prevention of osteoporosis Inventor(s): Weissmahr; Joseph A. (Zurich, CH) Assignee(s): Sigma-Tau Healthscience S.p.A. (Pomezia, IT) Patent Number: 6,511,685 Date filed: December 13, 2000

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Abstract: A process is described for manufacturing dietary supplements (food integrators) by means of a natural fermentation, including the following steps: a) preparation of a "mix" at a 18.degree. Centigrade temperature, containing one or more types of pasteurized milk from animal origin; b) introduction in such a "basic material" of a 1.5-4.5% in weight of polysaccharide "grains" mainly formed "friendly bacteria"; c) maintenance of the previous substance at a 18-25.degree. Centigrade temperature for a first period of 6-12 hours then adding a quantity of 1-3 % in weight of a second pool of polysaccharide "grains", mainly formed by yeasts; d) maintenance of the substance at 1825.degree. C. during a second period of 6-12 hours, by adding again 2.5-65% in weight of "grains" mainly formed by yeasts, then adding some minerals (calcium, magnesium, etc.) in proportion 0.2-1.2% of weight; e) separation, by filtration, of different components of the substance, among whose a "residual matrix" composed by grains of polysaccharides containing bacteria and yeasts; f) drying of the substance, after filtration, for obtaining a fine powder, g) preparation of various dietary supplements, presented in tablets or "sachets" or other formulations, useful in the treatment of osteoporosis and other degenerative conditions. Excerpt(s): The present invention relates to products used as dietary supplements or nutritional supplements for the supplementation of nutrition and diets by taking substances, mainly of natural origin, which supply elements necessary for nutrition and thus for good maintenance of essential body functions (such as the formation and preservation of the bones, muscles, skin, its related tissues and the like).... More particularly, the present invention relates to a process for obtaining a natural dietary supplement which has proved very effective in the prevention and treatment of osteoporosis and of other diseases mainly due to calcium, magnesium and potassium deficiencies in the body.... At the present state of our technical and scientific knowledge, it is well known that an adequate supply of a number of nutritional substances, commonly called "nutrients" (such as minerals, vitamins, proteins, and others) is of fundamental importance for the proper development of body tissues and for the body's vital functions and that deficiencies or imbalances of such nutrients are often concomitant with actual pathological conditions (particularly those of a "degenerative" and/or chronic type which may affect various parts of the body, e.g. the skeleton and blood vessels, interalia. Web site: http://www.delphion.com/details?pn=US06511685__ •

Diphosphonic acid salts for the treatment of osteoporosis Inventor(s): VanGulik; Fred (Laan Copes van Cattenburch, NL), Parente; Antonio (Sant Just Desvern, ES) Assignee(s): Eurodrug Ltd. (Hong Kong, CN), Lipotec SA (De Llobregat, ES), Geange Ltd. (Dublin, IE) Patent Number: 6,410,782 Date filed: April 3, 2000 Abstract: Diphosphonates or their salts between acids and linear, branch substituted and non-substituted, cyclic, heterocyclic and aromatic amino alcohols are used to treat osteoporosis. Pharmaceutical compositions and therapeutic methods of treating osteoporosis are described. Excerpt(s): Object of the present invention are salts of diphosphonic acids or diphosphonates and a procedure for their preparation.... Object of the present invention

Patents 373

is also the use of mentioned salts of diphosphonic acids or diphosphonates for treatment of osteoporosis.... Object of the present invention are again pharmaceutical compositions which contain, as active principle, the mentioned salts of diphosphonic acids or diphosphonates and the use of these compositions in the treatment of osteoporosis. Web site: http://www.delphion.com/details?pn=US06410782__ •

Electromagnetic non-invasive measurement and monitoring system for osteoporosis Inventor(s): Ko; Harvey W. (Columbia, MD), Skura; Joseph P. (Ellicott City, MD) Assignee(s): The Johns Hopkins University (Baltimore, MD) Patent Number: 4,850,372 Date filed: August 25, 1987 Abstract: A method for noninvasively sensing bone mass loss associated with osteoporosis is disclosed. The method uses an electromagnetic field to measure impedance (or conductivity) changes in the bone. A decrease in conductivity is indicative of osteoporosis. Excerpt(s): The invention relates to a method and apparatus for measuring and monitoring osteoporosis in an animal or human patient. More particularly, the invention uses an electromagnetic field to non-invasively measure impedance changes in a bone as a monitor of osteoporosis.... Osteoporosis is a condition characterized by a loss of bone mass. It can result because of a variety of causes that include chronically restricted calcium intake, hyperparathyroidism, hypersteroidism, immobilization, and weightlessness. Lay people also associate osteoporosis with the aging process. Various prior art x-ray techniques are of some assistance in detecting a loss of bone mass. However, no safe, inexpensive, non-invasive technique is taught by the prior art to regularly monitor osteoporosis.... The present invention uses an electromagnetic field to non-invasively measure impedance changes in a bone as a monitor of osteoporosis. As will be discussed in detail subsequently in this application, Applicants have related the impedance change in a bone with bone mass loss associated with osteoporosis. U.S. Pat. No. 3,735,245 entitled "Method and Apparatus for Measuring Fat Content in Animal Tissue Either in Vivo or in Slaughtered and Prepared Form", invented by Wesley H. Harker, teaches that the fat content in meat can be determined by measuring the impedance difference between fat and meat tissue. The Harker apparatus determines gross impedance change and does not provide adequate spatial resolution for the present use. U.S. Pat. No. 4,240,445 teaches the use of an electromagnetic field responsive to the dielectric impedance of water to detect the presence of water in a patient's lungs. However, such an apparatus does not detect the conductivity variations required in the present invention. U.S. Pat. No. 3,789,834 relates to measurement of body impedance by using a transmitter and receiver and computing transmitted wave impedance from the electrical or magnetic field generated. However, the antenna pickup would receive extraneous noise rendering it inappropriate for the present use. None of the above-cited references contemplate measuring the loss of bone mass associated with osteoporosis by measuring the impedance of the bone and none of the references teach an apparatus capable of specifically detecting such impedance. Web site: http://www.delphion.com/details?pn=US04850372__

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Estimation of change in bone mineral density and diagnosis of osteoporosis Inventor(s): Chen; Jui-Tung (Minato-ku, JP), Morita; Ikuo (Itabashi-ku, JP), Maruo; Naoko (Yokohama, JP), Shiraki; Masataka (Minamiazumi-gun, JP) Assignee(s): Tosoh Corporation (Shinnanyo, JP) Patent Number: 6,258,552 Date filed: February 20, 1996 Abstract: A method for estimation of change in bone mineral density or a method for diagnosis of osteoporosis, comprising the step of measuring change in a concentration of soluble interleukin-6 receptor in a blood sample, by for example, sandwich assay or competition assay; and a kit for carrying out the methods, comprising:(1) an anti-sIL-6R antibody immobilized to a solid carrier, and(2) an anti-sIL-6R antibody bound to a detectable marker or capable of binding to a detectable marker. Excerpt(s): The present invention relates a method for estimation of change in bone mineral density and a method for diagnosis of osteoporosis as well as a kit used for said methods.... Interleukin-6 (IL-6) is reported to be a multifunctional cytokine, and it has recently become known that one of the functions of IL-6 is stimulation of bone absorption. On the other hand, it is also known that a decrease in the secretion of estradiol in the post-menopausal phase results in an increase of the production of IL-6, and on the basis of these findings, it has been pointed out that there is a possibility that IL-6 is involved in causing osteoporosis.... Interleukin-6 receptor (IL-6R) is a protein which has a molecular weight of about 80 kDa and binds with IL-6 resulting in formation of a ligand-receptor complex. The complex of IL-6 and IL-6R, in turn, binds with a protein called gp130 protein, having a molecular weight of about 130 kDa, so as to be responsible for IL-6-mediated signal transduction (Japanese Unexamined Patent Publication (Kokai) No. 4-29997). Web site: http://www.delphion.com/details?pn=US06258552__

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Formulation containing S(+) enantiomer of flurbiprofen or ketoprofen and method of use for oral administration for prevention and treatment of bone loss associated with periodontal disease Inventor(s): Wechter; William J. (Redlands, CA) Assignee(s): Sepracor Inc. (Marlborough, MA) Patent Number: 5,190,981 Date filed: May 28, 1991 Abstract: A method of reducing bone loss and promoting bone regrowth, once loss has occurred, particularly alveolar bone loss associated wtih periodontal disease, and a composition useful in the method. The method comprises applying to buccal membranes a therapeutically effective quantity of at least one S enantiomer, generally an S(+) enantiomer, of a nonsteroidal anti-inflammatory drug, such as S(+) flurbiprofen or S(+) ketoprofen. The composition is a formulation which is a toothpaste or which is a mouthwash. Excerpt(s): Periodontal disease, which includes any abnormality, whether inflammatory or degenerative, of tissue around a tooth, is very common worldwide. For example, the World Health Organization has estimated that even if there were no new periodontal disease, it would take 45 years to treat those people who are affected. In addition, the

Patents 375

Journal of Public Health Dentistry concluded in 1985 that "more than two out of three patients were affected by periodontal disease." Moos, W.F., Medical Marketing & Media, 52-54 (1985). Chronic gingivitis (i.e., inflammation of the gingiva or gums) and chronic destructive periodontitis (i.e., a disease of the connective tissue which attaches a tooth to the alveolar bone, which results in alveolar bone resorption, increasing mobility of the tooth and, ultimately, tooth loss) are two common types of periodontal disease.... Although chronic periodontal disease is so common and known to be caused ultimately by bacteria accumulated on the teeth and under the gingiva, progress in its prevention and treatment has been limited and therapy is still largely unsuccessful. Preventive techniques rely heavily on establishing and maintaining good oral hygiene and therapy of existing periodontal disease includes expensive and ongoing treatments, such as periodontal surgery, which, in many cases, must be carried out often and has not been clearly shown to be effective in arresting alveolar bone loss and preserving teeth. Alveolar bone loss or resorption, which occurs after tooth extraction, is also a serious dental problem which cannot, to date, be successfully treated. A more effective method of preventing or treating alveolar bone loss would be of great value, particularly because of the prevalence of its occurrence.... The present invention is a method of reducing (decreasing or preventing) bone loss and/or promoting bone regrowth, to replace previously destroyed or lost bone, as well as a composition useful in the method. The present method and composition are particularly useful in the case of alveolar bone loss associated with periodontal disease, bone loss associated with osteoporosis and fracture repair. In the method of the present invention, at least one S enantiomer of a nonsteroidal anti-inflammatory drug, such as S(+)flurbiprofen or S(+) ketoprofen, is administered by application to the buccal membranes to an individual, in whom bone loss is to be prevented, reduced or reversed, in sufficient quantities to produce a systemic effect (adequate blood levels of the drug). In the case in which an individual with periodontal disease is being treated, the present method is also useful in reducing (decreasing or preventing) inflammation or gingivitis. Particularly suitable for use in the present method is a composition which can be used to provide a means by which the S enantiomer of one or more nonsteroidal anti-inflammatory drugs can be applied to make sufficient contact with an individual's buccal membranes to result in adequate blood levels of the drug to produce the desired effect. Typically, the composition will be a formulation, referred to as a toothpaste, but which can be any form (gel, powder, foam) or a mouthwash. The toothpaste is used as is any other toothpaste (typically, it is applied by brushing), as is the mouthwash, with which an individual gargles, rinses his or her mouth, etc. Web site: http://www.delphion.com/details?pn=US05190981__ •

Formulation for treatment of osteoporosis Inventor(s): Ungell; Anna-Lena (Vastra Frolunda, SE) Assignee(s): AstraZeneca AB (Sodertalje, SE) Patent Number: 6,372,728 Date filed: October 29, 1998 Abstract: The present invention provides pharmaceutical formulations comprising at least one bisphosphonate and an absorption enhancing agent essentially consisting of a medium chain glyceride or a mixture of medium chain glycerides. The said pharmaceutical formulations are useful for the inhibition of bone resorption and for the treatment and prevention of osteoporosis.

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Excerpt(s): The present invention relates to pharmaceutical formulations comprising bisphosphonates. The invention also relates to a process for preparing such pharmaceutical formulations, to the use of such pharmaceutical formulations for inhibition of bone resorption and for the treatment and prevention of osteoporosis.... The oral bioavailability of bisphosphonates (etidronate; clodronate; pamidronate; alendronate) in humans lies between 1% and 10% according to Lin (Bone 18, 75-85, 1996) and absorption is diminished when given with meals, especially in the presence of calcium. Therefore bisphosphonates should never be given at mealtime and never together with milk or diary products according to Fleisch (Bisphosphonates in bone disease, Stampli & Co., Bern 1993, p.50, and references cited therein).... The oral bioavailability of alendronate has been studied by Gertz et al. (Clinical Pharmacology & Therapeutics, vol. 58, pp. 288-298, 1995). It was found that taking alendronate either 60 or 30 minutes before breakfast reduced bioavailability by 40% relative to a 2-hour wait before a meal. Taking alendronate either concurrently with or 2 hours after breakfast drastically (>85%) impaired availability. A practical dosing recommendation, derived from these findings was that patients should take the drug with water after an overnight fast and at least 30 min before any other food or beverage. Web site: http://www.delphion.com/details?pn=US06372728__ •

Human osteoporosis gene Inventor(s): Styrkarsdottir; Unnur (Reykjavik, IS), Johannsdottir; Vala Drofn (Reykjavik, IS) Assignee(s): deCODE genetics ehf. (Reykjavik, IS) Patent Number: 6,630,304 Date filed: September 14, 2000 Abstract: A role of the human BMP2 gene in osteoporosis is disclosed. Methods for diagnosis, prediction of clinical course and treatment for osteoporosis using polymorphisms in the BMP2 gene are also disclosed. Excerpt(s): Osteoporosis is a debilitating disease characterized by low bone mass and deterioration of bone tissue, as defined by decreased bone mineral density (BMD). A direct result of the experienced microarchitectural deterioration is susceptibility to fractures and skeletal fragility, ultimately causing high mortality, morbidity and medical expenses worldwide. Postmenopausal woman are at greater risk than others because the estrogen deficiency and corresponding decrease in bone mass experienced during menopause increase both the probability of osteoporotic fracture and the number of potential fracture sites. Yet aging women are not the only demographic group at risk. Young woman who are malnourished, ammenorrheic, or insufficiently active are at risk of inhibiting bone mass development at an early age. Furthermore, androgens play a role in the gain of bone mass during puberty, so elderly or hypogonadal men face the risk of osteoporosis if their bones were insufficiently developed.... The need to find a cure for this disease is complicated by the fact that there are many contributing factors that cause osteoporosis. Nutrition (particularly calcium, vitamin D and vitamin K intake), hormone levels, age, sex, race, body weight, activity level, and genetic factors all account for the variance seen in bone mineral density among individuals. Currently, the drugs approved to treat osteoporosis act as inhibitors of bone reabsorption, and include methods such as hormone replacement therapy (HRT), selective estrogen receptor modulators, calcitonin, and biophosphonates. However, these treatments may not individually reduce risk with consistent results and while some therapies improve BMD

Patents 377

when coadministered, others show no improvement or even lose there efficacy when used in combination. Clearly, as life expectancy increases and health and economic concerns of osteoporosis grow, a solution for the risks associated with this late-onset disease is in great demand. Early diagnosis of the disease or predisposition to the disease would be desirable.... As described herein, it has been discovered that polymorphisms in the gene for human bone morphogenetic protein 2 (BMP2) have been correlated through human linkage studies to a number of osteoporosis phenotypes. In particular, it has been discovered that one or more single nucleotide polymorphisms within the nucleotide sequence encoding the BMP2 gene product is correlated to osteoporosis. Accordingly, this invention pertains to an isolated nucleic acid molecule containing the BMP2 gene of SEQ ID NO:1 (Table 1) having at least one altered nucleotide and to gene products encoded thereby (referred to herein as a "variant BMP2 gene" or "variant BMP2 gene product"). Web site: http://www.delphion.com/details?pn=US06630304__ •

Inhibiting bone loss with equilenin Inventor(s): Dodge; Jeffrey A. (Indianapolis, IN), Bryant; Henry U. (Indianapolis, IN), Yang; Na N. (Indianapolis, IN), Sato; Masahiko (Carmel, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,545,635 Date filed: May 23, 1995 Abstract: The present invention provides methods of inhibiting bone loss in humans comprising administering to a patient in need of treatment an effective amount of dequilenin, 17.beta.-dihydroequilenin, and 17.alpha.-dihydroequilenin, and pharmaceutical formulations thereof. Excerpt(s): The present invention relates to the fields of pharmacology and pharmaceutical chemistry, and provides methods for inhibiting the loss of bone in humans.... The current major diseases or conditions of bone which would benefit from the present invention include post-menopausal osteoporosis, hysterectomy patients, senile osteoporosis, patients undergoing long-term treatment of corticosteroids, side effects from glucocorticoid or steroid treatment, patients suffering from Cushings's syndrome, gonadal dysgensis, periarticular erosions in rheumatoid arthritis, osteoarthritis, Paget's disease, osteohalisteresis, osteomalacia, hypercalcemia of malignancy, osteopenia due to bone metastases, periodontal disease, and hyperparathyroidism.... All of these conditions are characterized by net bone loss, resulting from an imbalance between the degradation of bone (bone resorption) and the formation of new healthy bone. Web site: http://www.delphion.com/details?pn=US05545635__

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Inhibition of bone loss by (-)-N-[[(5-chloro-2-benzothiazolyl)thio]phenylacetyl]-Lcysteine Inventor(s): Hayward; Marshall (Lawrenceville, NJ), Schmid; Jean (Yardley, PA) Assignee(s): American Home Products Corporation (New York, NY) Patent Number: 4,866,082 Date filed: April 6, 1988 Abstract: A method for modifying the balance between bone production and bone resorption in a host animal by administration of (-)-N-[[(5-chloro-benzothiazolyl)thio]phenylacetyl]-L-cysteine to inhibit bone loss. Excerpt(s): This invention relates to a process for modifying the balance between bone production and bone resorption in a host animal, including man, and more specifically to the use f (-)-N-[[(5-chloro-2-benzothiazolyl)thio]phenylacetyl]-L-cysteine for the inhibition of bone loss.... Osteoporosis is a skeletal disorder which is evidenced by a decrease in bone density throughout the body. In fact, both the bone mineral (calcium phosphate called "hydroxyapatite") and the matrix (major protein called "collagen") are slowly lost. This condition may begin to occur in humans as early as age 30. In general, the process is more rapid in postmenopausal women than in men. However, after age 80 there is no sex difference in the incidence of osteoporosis. In the course of 10 to 20 years of bone loss there may be symptoms of back pain and X-ray evidence of deformation of the back bine. At older ages, the brittleness of the bones becomes evident by the ease in which the proximal femur ("hip") fractures. Osteoporosis is the most common cause of fractures in people over age 45.... Although the cause of osteoporosis is poorly understood, it is believed that there is an imbalance between bone production and bone resorption (bone breakdown). Bone remains a dynamic tissue throughout the life of an animal. That is, new bone is continuously being formed and old bone is continuously being resorbed. However, in animals suffering from an osteoporotic condition, net bone resorption exceeds bone formation. Web site: http://www.delphion.com/details?pn=US04866082__

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Kit for use in the treatment of osteoporosis Inventor(s): Uchtman; Vernon A. (Cincinnati, OH) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 4,812,311 Date filed: September 12, 1986 Abstract: A kit for use in the treatment of osteoporosis is disclosed. The kit comprises a bone cell activating compound, a bone resorption inhibiting polyphosphonate, and a nutrient supplement or placebo, for sequential administration. Excerpt(s): The present invention relates to a kit for use in a regimen for treatment or prevention of osteoporosis. Specifically, the present invention relates to a kit for use in a regimen whereby a bone cell activating compound, a bone resorption inhibiting polyphosphonate, and a placebo or a nutrient supplement is administered sequentially to a subject afflicted with or at risk to osteoporosis.... Osteoporosis is the most common form of metabolic bone disease. Although it may occur secondary to a number of underlying diseases, 90% of all cases appear to be idiopathic.... Idiopathic osteoporosis is most commonly observed in postmenopausal women (postmenopausal osteoporosis)

Patents 379

but it may also occur in elderly males and females (senile osteoporosis) or occasionally in younger individuals of both sexes. The disease which develops in postmenopausal women is characterized primarily by fractures of the wrist and spine, while femoral fractures seem to be the dominant feature of senile osteoporosis. Web site: http://www.delphion.com/details?pn=US04812311__ •

Marker at the estrogen receptor gene for determination of osteoporosis predisposition Inventor(s): Rousseau; Fran.cedilla.ois (Ste-Foy, CA) Assignee(s): Universite Laval, Cite Universitaire (Quebec, CA) Patent Number: 5,834,200 Date filed: July 14, 1997 Abstract: The present invention relates to a method of determining predisposition to low or high bone mineral density and to development of osteoporosis of a patient, which comprises determining estrogen receptor polymorphism in linkage disequilibrium in a biological sample of said patient, wherein heterozygosity is associated with high bone density and homozygosity is associated with low bone density. Excerpt(s): The invention relates to a method of determining genetic predisposition to low or high bone mineral density of a patient, wherein low bone density is indicative of a predisposition to osteoporosis and high bone density is indicative of resistance to osteoporosis.... Osteoporosis, a reduction of bone mineral density (BMD), is a multifactorial disease that leads to an increasing risk of fracture and is becoming a major public health problem, especially in post-menopausal women. Its major consequence, hip fracture, has major health consequences with serious social, medical and economical implications in increasingly aging populations. Research on osteoporosis emphasizes at either finding new therapeutic approaches or at the characterization of the major determinants of bone mineral density (BMD) in the hope to find markers useful in identification of women at risk of osteoporosis and its complications. Since therapy of established osteoporosis remains far from satisfactory, prevention is the best choice.... Heredity has always been considered an important risk factor for osteoporosis, but its role was still poorly understood, at least until recently. Indeed, several studies of monozygotic (MZ) and dizygotic (DZ) twins have shown that BMD was better correlated between MZ than DZ twins, indicating that BMD is genetically determined and that heredity could account for up to 80 to 90% of the variability in BMD. Intra and intergeneration correlations were more contradictory, two studies showing significantly lower BMD in daughters of women with osteoporosis while another mother/daughter pairs study found no such difference. Since a decrease of one standard deviation in BMD within normal range approximately doubles the risk of fracture at different skeletal sites, the search for a marker likely to identify women at risk of postmenopausal osteoporotic fractures is becoming more and more relevant. Web site: http://www.delphion.com/details?pn=US05834200__

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Material for prevention and treatment of osteoporosis Inventor(s): Takizawa; Toshio (Saitama, JP), Ohta; Atsutane (Saitama, JP), Adachi; Takashi (Saitama, JP) Assignee(s): Meiji Seika Kaisha, Ltd. (Tokyo, JP) Patent Number: 5,900,255 Date filed: October 20, 1997 Abstract: A material for the prevention and treatment of osteoporosis characterized by containing minerals and indigestible oligosaccharides. The material for the prevention and treatment of osteoporosis according to the present invention is excellent in the absorption of calcium and the reduction in a bone salt amount which is observed in the osteoporosis can be depressed. Accordingly, by taking the material for the prevention and treatment of osteoporosis according to the present invention, the osteoporosis which often occurs particularly in postmenopausal women is effectively prevented and its progress can be retarded. Excerpt(s): This invention relates to a material for the prevention and treatment of osteoporosis which is excellent in absorbability of calcium and is capable of suppressing the reduction of a bone-salt amount and a bone density observed in the osteoporosis.... Recently, various geriatric diseases have been increased with coming of an era of the advanced age society and now become to be a serious social problem. A typical example of these diseases is osteoporosis which is often observed in persons of advanced age, in particular, postmenopausal women. In bones, salts of calcium as well as phosphorus, magnesium and sodium are present in large amounts. In a recent national nutritional investigation, insufficient intake of calcium was pointed out, and this is assumed to be one of reasons for the increase of osteoporosis. From such a background, a number of calcium-enriched foods has been developed and is now commercially available. Further, an effect of the calcium replenishment on the therapy or the suppression of symptom of osteoporosis has been extensively studied.... However, there are not a few reports in which a mere replenishment of calcium is confirmed to be ineffective to the treatment or the suppression of symptom. The reason therefor is considered that, in persons of advanced age, it is highly possible that an absorption of calcium decreases, and that not only calcium but also minerals which constitute the bone are required to be adsorbed in a well-balanced manner. Web site: http://www.delphion.com/details?pn=US05900255__

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Method and apparatus for diagnosing osteoporosis Inventor(s): Wehrli; Felix W. (Bala Cynwyd, PA) Assignee(s): The Trustees of The University of Pennsylvania (Philadelphia, PA) Patent Number: 5,270,651 Date filed: May 21, 1991 Abstract: A method for noninvasively detecting osteoporosis in human subjects by means of NMR imaging is described. In the preferred embodiment, a series of images are acquired whereby the echo time TE is incremented until a predefined number of images, each differing in echo time, has been acquired. The images are then displayed, a region of interest (ROI) is selected and mean signal amplitudes are computed (block 46). The mean signal amplitude values are then used as inputs for the curve fitting

Patents 381

procedure that computes T2* (block 48). The final step of the process compares the computed value of T2* with a normal baseline (block 50), which permits the subject to be classified as either normal or osteoporotic (block 52). Excerpt(s): The present invention generally relates to the field of characterizing bone and particularly relates to characterizing trabecular bone with nuclear magnetic resonance (NMR). The invention more particularly relates to a method and apparatus for noninvasively diagnosing osteoporosis with NMR interferometry.... Trabecular bone consists of a three-dimensional gridwork whose individual components (the trabeculae) are plates and struts 100-300.mu.m thick with the mean intertrabecular space varying between about 500 and 1500.mu.m. The function of the trabecular structure is to provide the skeleton with mechanical strength. Trabeculation is reduced with a concomitant loss in bone strength as a result of normal aging and disease processes such as osteoporosis.... The most common method of assaying bone density is based on a measurement of the X-ray attenuation coefficient using either a projection technique (Xray dual photon absorptiometry) or its tomographic analog, quantitative computed tomography (QCT). Although these techniques are capable of providing bone mineral densities, they do not provide information on trabecular microstructure (i.e., the geometry, thickness, orientation and density of the trabecular plates), which is commonly obtained by optical stereology, whereby thin sections of transiliac bone biopsy specimens are microscopically analyzed. There is currently no known noninvasive method for obtaining detailed information on trabecular microstructure. Web site: http://www.delphion.com/details?pn=US05270651__ •

Method and apparatus for diagnosing osteoporosis with MR imaging Inventor(s): Kugelmass; Steven D. (Teaneck, NJ), Wehrli; Felix W. (Bala Cynwyd, PA) Assignee(s): Trustees of the University of Pennsylvania (Philadelphia, PA) Patent Number: 5,247,934 Date filed: August 9, 1991 Abstract: Methods are provided for detecting and diagnosing osteoporosis using highresolution NMR imaging of trabecular bone. One such method comprises the steps of obtaining high-resolution NMR imaging data indicative of the trabecular microstructure of a mass of bone, analyzing the imaging data to determine the density of the trabeculae of the bone, comparing the density thus obtained with reference trabecular density data, and determining on the basis of the comparison whether the subject is osteoporotic or normal. To determine trabecular density, bone volume can be computed as the area fraction of those pixels that by virtue of their characteristic pixel intensity can be assigned to bone. Trabecular thickness can be computed from the relative bone area in a region of interest divided by half the perimeter length, the perimeter length being the circumference of all bone islands observed in the region of interest. Trabecular density can be expressed as the mean number of intercepts of parallel search lines perpendicular to the orientation of the trabeculae or as the ratio of mean trabecular thickness divided by the bone area within the region of interest. Excerpt(s): The present invention generally relates to the field of characterizing bone and particularly relates to characterizing trabecular bone with nuclear magnetic resonance (NMR) imaging. The invention more particularly relates to a method and apparatus for diagnosing diseases that affect trabecular bone, such as osteoporosis, with NMR imaging.... Bone in vertebrates has both a structural and metabolic function. Its

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major structural function is to provide support for the body against gravity and to act as a lever system for muscular action. Bone consists of a mineralized phase (essentially calcium hydroxy apatite, approximately 50% by volume) and an organic phase (osteoid) mainly composed of collagen. In addition, bone may be organizationally and functionally subdivided into trabecular (cancellous) and cortical bone. Trabecular bone consists of a three-dimensional gridwork whose individual components (the trabeculae) are plates and struts 100-300.mu.m thick with the mean intertrabecular space varying between about 500 and 1500.mu.m. The function of the trabecular structure is to provide the skeleton with mechanical strength. Trabeculation is reduced with a concomitant loss in bone strength as a result of normal aging and disease processes such as osteoporosis.... Aging is associated with a progressive decrease in bone mass that is more prominent in women than in men. For example, most women have lost 40-50% of their peak trabecular mass by the time they are 90 years old while men have lost 10-20% by that age. In addition, symptomatic osteoporosis affects more than 15 million postmenopausal American women. Moreover 25% of all women over the age of 60 years have had at least one spinal compression fracture. The biomechanical and structural aspects of osteoporosis therefore assume exceptional practical importance in clinical medicine. Its diagnosis is similarly of great significance. Web site: http://www.delphion.com/details?pn=US05247934__ •

Method and apparatus for evaluating the progress of osteoporosis by ultrasonic signals Inventor(s): Nogata; Fumio (Himeji, JP), Matsui; Kazuyuki (Neagari-machi, JP), Higashi; Kohji (Kanazawa, JP), Nakahashi; Akio (Matto, JP) Assignee(s): Kabushiki Kaisha Ishikawa Seisakusho, Ltd. (Kanazawa, JP) Patent Number: 5,535,750 Date filed: September 30, 1994 Abstract: An ultrasonic signal is transmitted to a heel bone or patella of a person being examined to obtain data of velocity of transmission propagation. The data which is obtained is computerized through calculation to compute a two-dimensional ratio of a compact bone to a bone structure (Au) from a one-dimensional ratio of a compact bone to a bone structure (Eu). Then, a chart is drawn to suffice an Au for which a fractal geometry is utilized to compare the chart with an image of an Au of a healthy person who is under the same condition in sex and age. The portions different from each other are then sorted by color for evaluating the progress of osteoporosis. Excerpt(s): The present invention relates to a method and apparatus for evaluating the progress of osteoporosis by utilizing ultrasonic signals.... With an increase in population of aged people, there is a rapid increase in number of patients who suffer from a disease called osteoporosis, which causes fractures of bones, and it is becoming a great concern in the medical field. With a decrease in the calcium content in a bone structure, cracking and damage of bones are easily caused by deterioration in the strength of bone. About 30% of women and about 10% of men who are more than 60 years old are said to be suffering from osteoporosis. If a symptom of osteoporosis is discovered at an early stage, it may be possible to effectively prevent the progress of the disease with a variety of medical treatments. It is, therefore, very important to undergo a medical examination at regular intervals in order to detect the disease in its early stages. Heretofore, it has been practiced to preestimate the degree of progress of the osteoporosis by measuring bone mineral content (BMC) by roentgen irradiation (D-ray) or by gamma radiation....

Patents 383

However, the radiation is very harmful to the living body, and people ranging from about 50 to over 60 years old who might have osteoporosis and post-menopausal women have had to undergo such a hazardous medical examination by the use of radiation. In order to avoid such a hazardous treatment, there have been proposed apparatuses for evaluating osteoporosis by utilizing ultrasonic signals which are not harmful to the human body. Web site: http://www.delphion.com/details?pn=US05535750__ •

Method and apparatus for osteoporosis diagnosis Inventor(s): Nakamori; Yuichi (Kyoto, JP), Kubota; Yasuyuki (Kyoto, JP), Kuriwaki; Masashi (Kyoto, JP), Ishii; Tetsuya (Kyoto, JP) Assignee(s): Sekisui Kagaku Kogyo Kabushiki Kaisya (Osaka, JP) Patent Number: 5,902,240 Date filed: October 21, 1997 Abstract: An osteoporosis diagnosis yapparatus provided with a two-dimensional ultrasonic transducer array (3) comprising a number of cells (1.sub.1, 1.sub.2,... ). The ultrasonic transducer array (3) is applied to the skin covering a predetermined bone of a subject, and the individual cells sequentially emit a predetermined number of ultrasonic pulses through the skin while receiving echoes from the bone. The received echo data are processed so that they can be handled in a planewave problem, from which the information on the reflection from the bone is determined. This information is processed to obtain the acoustic impedance of a cortical bone and a cancellous bone, so as to check for the presence of osteoporosis. The information on the reflection from the bone can also be handled as an eigen-value problem, and, when the information is handled in such a manner, the shape determination of a bone becomes un necessary. Excerpt(s): This invention relates to an ultrasonic pulse-echo type osteoporosis diagnosing apparatus and method, which diagnoses osteoporosis by emitting ultrasonic pulses towards a certain bone of an examinee and detecting the echoes from the bone.... With the emergence of a more aged society in recent years, the bone disease termed osteoporosis has been becoming a problem. In this disease the calcium is withdrawn from the bones leaving them friable and prone to fracture at the slightest impact; and it is one motive for concern in old people. Physical diagnosis is performed mainly by determining the density of bone precisely by means of diagnostic apparatus employing X-rays, typified by DXA and DCT; however, physical diagnosis by means of X-rays is beset by various problems such as the fact that the apparatus is large, and that its use is restricted by the need to prevent harmful radiation exposure.... Accordingly, diagnostic apparatus employing ultrasound has started to become popular because the equipment is simple and does not cause such problems. Diagnostic apparatus employing ultrasound measures the speed and attenuation of ultrasound waves propagated inside bony tissues, and uses this to estimate the density and elastic modulus (elastic strength) of the bone. If a low estimated value is obtained it can be deduced that this is because of withdrawal of calcium from the bone, and hence osteoporosis is diagnosed. Web site: http://www.delphion.com/details?pn=US05902240__

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Method and apparatus particularly useful for treating osteoporosis Inventor(s): Spector; Avner (Savyon, IL) Assignee(s): Medispec Ltd. (Rockville, MD) Patent Number: 5,529,572 Date filed: July 13, 1994 Abstract: A method and apparatus for increasing the density and strength of bone, particularly for preventing or treating osteoporosis, by subjecting the bone to unfocussed compressional shock waves. Excerpt(s): The present invention relates to a method and apparatus particularly useful for treating osteoporosis.... Osteoporosis is a bone disorder which affects middle and old age people, especially women. It is characterized by an abnormal loss of bone tissue, and consequently by a decrease in the density of the bone. The reduction in bone density reduces the strength of the bone such as to make the afflicted person susceptible to easy fracture, particularly of the pelvis (hip), spine, femoral neck, and forearm.... Osteoporosis affects millions of elderly people. In the USA, it affects about one out of every four women over the age of 45, and half of all women over the age of 60. Each year approximately 200,000 persons break a hip because of osteoporosis. It is therefore one of the major causes for prolonged hospitalization of the elderly; and resulting complications, particularly from hip fracture, constitute a frequent cause of death in the USA. Web site: http://www.delphion.com/details?pn=US05529572__

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Method and composition for the treatment of osteoporosis Inventor(s): Bhatia; Satish (Summit, NJ), Guler; Hans-Peter (Chatham Township, NJ) Assignee(s): Novartis Corp. (New York, NY) Patent Number: 6,358,925 Date filed: November 1, 2000 Abstract: A method for the treatment or prevention of osteoporosis in higher mammals is disclosed, the method comprising administering Insulin-like Growth Factor I (IGF-I) in an effective amount thereof to said mammal, said mammal being in need of said treatment or prevention. Compositions for pharmaceutical use in the above method are also described. Excerpt(s): The present invention concerns a method for the treatment of higher mammals having or being at substantial risk of developing osteoporosis in cortical bone, the treatment comprising the administration of insulin-like growth factor I (IGF-I). Hence, the invention is directed to the fields of bone growth and degeneration, to IGF-I, and to compositions thereof for use as pharmaceuticals.... Osteoporosis encompasses a broad range of clinical syndromes having varying etiologies. In postmenopausal women, for example, two distinct types of osteoporsis have been identified. Type I osteoporosis occurs mainly in the early postmenopausal period from about age 50-65. It is characterized by excessive resorption, primarily in trabecular bone. Vertebral fractures are common. If given prior to significant bone loss, treatment which decreases or prevents bone resorption (such as with estrogen or calcitonin) is considered effective therapy.... Type II osteoporosis (a.k.a. senile osteoporosis) occurs essentially in all aging women and, to a lesser extent, in men. It is characterized by proportionate loss of

Patents 385

cortical bone as well as trabecular bone. Here decreased bone formation plays a major role, if not a more important role than increased bone resorption. Fractures of the hip are characteristic of this type of osteoporosis. Web site: http://www.delphion.com/details?pn=US06358925__ •

Method and composition for treating or preventing osteoporosis Inventor(s): Valliere; Charles R. (Madison, WI), Bishop; Charles W. (Verona, WI), Knutson; Joyce C. (Madison, WI) Assignee(s): Bone Care International, Inc. (Madison, WI) Patent Number: 6,150,346 Date filed: June 7, 1995 Abstract: Method of treating or preventing osteoporosis by administering orally a 1.alpha.-hydroxyprevitamin D. This previtamin D form increases vitamin D blood level without significant risk of hypercalcemia associated with other oral dosing of vitamin D forms. The 1.alpha.-hydroxyprevitamin is compounded into a pharmaceutical composition in combination with a pharmaceutically acceptable excipient. Excerpt(s): This invention relates to a method for increasing the blood level of active vitamin D compounds. More specifically, the invention relates to orally administering the 1.alpha.-hydroxylated previtamin form of vitamin D compounds in order to increase the blood level of the corresponding active vitamin D compound.... Vitamin D is known to be important in the regulation of calcium metabolism in animals and man. See, Harrison's Principals of Internal Medicine: Part Eleven, "Disorders of Bone and Mineral Metabolism," Chapter 335, E. Braunwald et al., (eds.), McGraw-Hill, New York (1987) pp. 1860-1865.... It is known that vitamin D.sub.3 must be hydroxylated in the carbon-1 and the carbon-25 position before it is activated, i.e., before it will produce a biological response. A similar metabolism appears to be required to activate the other forms of vitamin D, e.g., vitamin D.sub.2 and vitamin D.sub.4. As is generally understood and used herein, the term "vitamin D" is intended to include vitamins D.sub.3, D.sub.2, and D.sub.4. The term "activated vitamin D," as used herein, is intended to refer to vitamin D which has been hydroxylated in at least the carbon-1 position of the A ring, e.g., 1.alpha.-hydroxyvitamin D.sub.3. Web site: http://www.delphion.com/details?pn=US06150346__

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Method and composition for treating with a vasodilator inflammation, bone loss and detachment of teeth as associated with periodontal Inventor(s): Hennessey; Richard K. (803 Cottonwood Dr., Severna Park, MD 21146) Assignee(s): none reported Patent Number: 5,665,731 Date filed: June 7, 1995 Abstract: A process is provided which is useful in alleviating inflammation of gums, bone loss and detachment of teeth in a patient in need of such treatment. The process comprises administering a vasodilator to the inflamed gum tissue and other affected tissue, either topically or by injection. Advantageously, the vasodilator is papaverine or a pharmaceutically acceptable salt thereof such as papaverine hydrochloride.

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Advantageously, the papaverine hydrochloride may be administered topically in a composition comprising a carrier such as an aqua based transparent gel dental vehicle. The carrier dissolves the papaverine hydrochloride and enables it to penetrate the soft tissue of the gums and be absorbed into the inflamed tissue. Excerpt(s): This invention relates to methods of treating inflammation of gums, bone loss and detachment of teeth in a patient in need of such treatment. The process comprises administering a vasodilator to the inflamed gum tissue, either topically or by injection. This invention also relates to methods of treating inflammation of such tissue by administering a composition comprising papaverine or a pharmaceutically acceptable salt thereof to the affected tissue.... Periodontal disease is characterized by gingival inflammation and swelling of soft gum tissue, loss of bone structure and attachment loss of the affected teeth. The pockets caused by loss of bone are areas of maximum bacteria attack and gum inflammation both of which increases bone loss and destroys the micro ligaments that attach the teeth in the bone sockets.... There currently are many accepted methods of treatment for this ailment, including bactericides added to toothpaste, mouth washes, STIM-U-DENT.TM. stimulation with baking soda, and other anti-inflammatory preparations. In some cases, surgery of the diseased soft tissue is required. If the disease progresses to the extent that surgery is required, however, the treatment may not be effective enough to prevent future tooth loss. Web site: http://www.delphion.com/details?pn=US05665731__ •

Method for anticipating sensitivity to medicine for osteoporosis Inventor(s): Kusaba; Nobutaka (Osaka, JP), Ouchi; Yasuyoshi (Tokyo-to, JP), Hosoi; Takayuki (Tokyo-to, JP), Shiraki; Masataka (Misato-mura, JP), Baba; Toshiaki (Osaka, JP), Yoshida; Hiroshi (Osaka, JP) Assignee(s): Nipro Corporation (Osaka, JP) Patent Number: 6,566,064 Date filed: May 18, 2000 Abstract: A method for anticipating sensitivity to a medicine for osteoporosis is provided which is characterized by analyzing respective genetic polymorphisms of a vitamin D receptor gene, an estrogen receptor gene, and an apolipoprotein E gene from a genome DNA contained in a sample obtained from a human, and anticipating, based on the analyzed combination of the genetic polymorphisms, that the sample is derived from an individual who shows a specific priority to sensitivities to a plurality of remedies for osteoporosis. A reagent for simultaneously detecting genetic polymorphisms is also provided which contains amplification primers and/or detection probes specific to respective genes of the vitamin D receptor gene, apolipoprotein E gene, and estrogen receptor gene. Further, a method for simultaneously detecting these genes, and a method for selecting remedies for bone disease based on the genetic polymorphisms are provided. According to the method of the present invention, a diagnosis as to which remedy, or medicine, for osteoporosis a subject patient has higher sensitivity can be made before the administration of the medicine so that selection of an appropriate medicine is possible and the QOL (quality of life) of the patient can be improved. Excerpt(s): The present invention relates to a novel method for the analysis of humanderived samples that can provide information useful in the therapy of osteoporosis. Specifically, the present invention relates to a method for the analysis of genetic

Patents 387

polymorphism of genome DNA in human-derived samples in order to anticipate which is the most effective remedy for osteoporosis, in particular, among vitamin D, estrogen, and vitamin K2. Also, the present invention relates to a method for anticipating, based on a combination of genetic polymorphisms of genome DNA in a human-derived sample, that the sample is derived from an individual who shows specified priority in sensitivity to the above medicines. Further, the present invention relates to a kit for the analysis of genetic polymorphisms that can be used in the above method.... Osteoporosis is the state of a disease in which bone mass (the amount of minerals, mainly calcium contained in bone) decreases and the fine structure of bone tissue changes so that the bone becomes brittle and tends to be broken. It occurs mostly in females after menopause and in senior males. It is said that the number of patients with osteoporosis is presumably 10,000,000 in Japan. It is anticipated that as the ratio of elderly persons in the population increases, the number of patients will henceforth inevitably increase.... At present, various medicines such as bone activators, e.g., calcium preparations, vitamin D, etc., bone resorption depressants, e.g., estrogen, etc., and osteogenesis accelerators, e.g., vitamin K, etc., are used to treat osteoporosis. However, their therapeutical effects vary randomly depending on the patient and there have been made almost no study as to how to use a right medicine with a right patient. Since it has been taken as a rule that these remedies are administered singly, there is currently no way other than actually administering a single medicine to patients for several years and obtaining results before it can be judged based on the results which medicine is most effective. This is extremely inefficient. Web site: http://www.delphion.com/details?pn=US06566064__ •

Method for diagnosing and monitoring osteoporosis Inventor(s): Timonen; Jussi (Soidintie 5 C, Fin-40630 Jyv.ang.skyl.ang., FI), Cheng; Shu Lin (7927 Farnifold, #2, Germantown, TN 38138), Suominen; Harri (Soidintie 1, #3, Fin40630 Jyv.ang.skyl.ang., FI) Assignee(s): none reported Patent Number: 5,800,363 Date filed: March 27, 1996 Abstract: A method for diagnosing and monitoring osteoporosis includes the steps of:stimulating the tibia of a patient, to create a pulse that progresses in the bone, which can be registered as a function of time;measuring accelerations of the pulse at at least two spaced locations, at an interval from the point of stimulation and at an interval from one another, as a temporal function, both measurement points being at a distance of at least 1/6 of the length of the tibia from its nearest end;measuring the diameter of the bone to provide a quantity depicting the geometry of the bone, at a predetermined point on the tibia and estimating the density of the bone tissue at the same point,measuring the velocity V of a pulse in the bone to provide a quantity depicting the condition of the bone, over at least one measurement interval;calculating at least one of the following factors over at least one measurement interval:a coefficient R, dependent on the variation of the bone tissue,a coefficient K, dependent on changes in the cross-sectional surface area of the bone, anda coefficient P, dependent on changes in the modulus of elasticity of the bone, andquantifying the condition of the bone tissue of the patient as a function of the quantities V and at least one of R/K/P. Excerpt(s): This invention relates to a method for diagnosing and monitoring osteoporosis.... Osteoporosis, the increase in the brittleness of bones, is a health problem

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of aging people--particularly women. Osteoporotic fractures and the complications associated with them have caused a significant increase in health care costs as the age structure of the population grows older.... Osteoporosis has generally been investigated by examining the mineral content and/or density of bones. Generally it is not possible to determine the real density of bones by conventional methods. These methods include periodic X-ray imaging, photon absorption and computed tomography, none of which can provide detailed information about the mechanical properties of bone, such as elasticity and strength. In fact, the loss with age of the biomechanical strength of bone is more pronounced than the loss of bone mass, and, at any given age, there is greater inter-individual variation in the mechanical properties of bone than in the bone mass. Therefore, it is desirable to develop a clinically relevant method for determining the mechanical properties of bone. Additional drawbacks of the methods are radiationpredisposition caused by exposure to ionizing radiation and considerable equipment costs. Web site: http://www.delphion.com/details?pn=US05800363__ •

Method for inhibiting bone loss using centchroman derivatives Inventor(s): Labroo; Virender M. (Mill Creek, WA), Bain; Steven D. (Seattle, WA), Piggott; James R. (Bothell, WA) Assignee(s): ZymoGenetics, Inc. (Seattle, WA) Patent Number: 5,464,862 Date filed: January 13, 1994 Abstract: Methods and pharmaceutical compositions for reducing bone loss are disclosed. 3,4-diarylchromans and their pharmaceutically acceptable salts are formulated into medicaments for the treatment of bone loss due to osteoporosis or other conditions. An exemplary 3,4-diarylchroman is centchroman (3,4-trans-2,2-dimethyl-3phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-me thoxychroman). Formulations include tablets and other forms suitable for oral administration and controlled-release subdermal implants. Excerpt(s): Bone remodeling is the dynamic process whereby skeletal mass and architecture are renewed and maintained. This renewal and maintenance is a balance between bone resorption and bone formation, with the osteoclast and the osteoblast considered the two key participants in the remodeling process. The osteoclast initiates the remodeling cycle by resorbing a cavity in the bone which is subsequently refilled when the osteoblast synthesizes and deposits new bone matrix into the excavation. The activities of osteoclast and osteoblast are regulated by complex interactions between systemic hormones and the local production of growth factors and cytokines at active remodeling sites.... Imbalances in bone remodeling are associated with such conditions as osteoporosis, Paget's disease, and hyperparathyroidism. Osteoporosis, characterized by a decrease in the skeletal mass, is one of the most common diseases of postmenopausal women and is often the cause of debilitating and painful fractures of the spine, hip and wrist.... Approximately 25% of all postmenopausal women suffer from osteoporosis, and it is generally accepted that the etiology of the disease involves the reduction of circulating estrogens (Komm et al., Science 241:81-84, 1988). Komm et al. further report that the proportion of caucasian women in the United States who are at risk for a hip fracture is 15%, or 247,000 hip fractures per year in women over the age of 45.

Patents 389

Web site: http://www.delphion.com/details?pn=US05464862__ •

Method for preventing and treating osteoporosis in a living body by using electrical stimulation non-invasively Inventor(s): Pollack; Solomon R. (Dresher, PA), Brighton; Carl T. (Malvern, PA) Assignee(s): Biolectron, Inc. (Hackensack, NJ) Patent Number: 4,467,808 Date filed: September 17, 1982 Abstract: Osteoporosis in a living body prevented and/or treated by applying electrodes non-invasively to a body and supplying to the electrodes an AC signal of about 5-15 volts peak-to-peak at a frequency of about 20-100 KHz to cause a treatment current to flow in a body region affected or likely to be affected by osteoporosis. Excerpt(s): This invention relates to a method of preventing and treating osteoporosis in a living body using non-invasive techniques, and more particularly to treating a region affected by osteoporosis by inducing a current to flow in the region affected.... Bones comprise an organic component (cells and matrix), and an inorganic or mineral component. The cells and matrix comprise a framework of collagenous fibers which is impregnated with the mineral component, chiefly calcium phosphate (85%) and calcium carbonate (10%), which imparts the quality of rigidity to bone. In a disease commonly known as osteoporosis, the bone demineralizes and becomes abnormally rarefied. While osteoporosis in general predominantly afflicts the elderly, a specific form of osteoporosis known as disuse or immobilization osteoporosis has been identified with immobilized persons of all ages whose bones are not subject to functional stress. In these cases, some patients will experience significant loss of cortical and cancellous bone during prolonged periods of immobilization. Quite often, an elderly patient immobilized after a fracture of a long bone may experience bone loss due to disuse, which may ultimately lead to secondary fractures in an already osteoporotic skeleton. Diminished bone density may lead to verterbrae collapse, fractures of the hips, lower arms, wrists, ankles and incapacitating pain.... Attempts at treating and/or preventing osteoporosis by means of electrical signals include the work of McElhaney and Stalnaker who in 1967 reported that a 200 V and 30 Hz field applied between two parallel plates to a castimmobilized femur of the rat could reduce the bone weight loss and bone cortical area reduction associated with immobilization. However the number of animals was too small to yield results of statistical significance. Web site: http://www.delphion.com/details?pn=US04467808__

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Method for reducing development of osteoporosis Inventor(s): Hausheer; Frederick H. (Boerne, TX) Assignee(s): BioNumerik Pharmaceuticals, Inc. (San Antonio, TX) Patent Number: 6,468,993 Date filed: October 4, 1999 Abstract: This invention relates to a method of treating patients afflicted with osteoporosis. The method includes administering to a patient in need of treatment an

390 Osteoporosis

effective amount of a thiol or reducible disulfide compound according to the formula set forth in the specification. Excerpt(s): This invention relates to a method for reducing or preventing osteoporosis in patients at risk. The method involves administering an effective amount of a disulfide or thiol-containing compound to a patient at risk of developing osteoporosis.... Osteoporosis is by definition a loss of bone material, and results in a progressive weakening of bones. It predominantly occurs in post-menopausal women, but there are numerous other factors that can mediate the loss of bone tissue, in both men and women. The exact cause of the disease is not clear and is thought to be multifaceted.... Current treatments for both regression and prevention of osteoporosis include calcium and hormonal therapy, as well as administration of hormonal blockers. Many of these treatments involve highly undesirable side effects, namely increased risk of certain cancers, dyspnea, venous thrombosis, hot flashes, night sweats, leg cramps, and others. Many of these treatments are not indicated for premenopausal women. Web site: http://www.delphion.com/details?pn=US06468993__ •

Method for screening anti-osteoporosis agents Inventor(s): Yang; Na N. (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,445,941 Date filed: June 21, 1993 Abstract: The present invention relates to methods for the identification of therapeutic agents for the treatment of osteoporosis and serum lipid lowering agents. The invention relates to isolating cloning, and using nucleic acids from the promoter regions of transforming growth factor.beta. genes comprising novel regulatory elements designated "raloxifene responsive elements". The invention also encompasses eukaryotic cells containing such raloxifene responsive elements operably linked to reporter genes such that the raloxifene responsive elements modulate the transcription of the reporter genes. The invention provides methods for identifying anti-osteoporosis agents that induce transcription of genes operably linked to such raloxifene responsive elements without inducing deleterious or undesirable side effects associated with current antiosteoporosis therapy regimens. Excerpt(s): The invention relates to methods for identifying therapeutic agents for the treatment of osteoporosis and as serum lipid lowering agents. The invention relates to isolating, cloning and using nucleic acids comprising the promoter regions of mammalian transforming growth factor B genes that are novel regulatory elements designated "raloxifene responsive elements". The invention also encompasses genetically engineered eukaryotic cells containing the recombinant expression constructs wherein the raloxifene responsive elements are operably linked to reporter genes. In such cells the raloxifene responsive elements are capable of modulating transcription of the reporter genes and response to treatment with certain compounds. The invention also relates to methods for identifying anti-osteoporosis agents that induce transcription of certain genes via raloxifene responsive elements and that specifically do not induce deleterious or undesirable side effects that have been associated with estrogen replacement therapy, such as increased risk with uterine and breast cancer. The nucleic acids, cells and methods of the invention provide effective methods for screening putative sources of anti-osteoporosis agents or serum lipid

Patents 391

lowering agents and identifying those that advantageously lack the undesirable side effects associated with current anti-osteoporosis agents.... In 1991, U.S. pharmaceutical companies spent an estimated $7.9 billion on research and development devoted to identifying new therapeutic agents (Pharmaceutical Manufacturer's Association). The magnitude of this amount is due, in part, to the fact that the hundreds, if not thousands, of chemical compounds must be tested in order to identify a single effective therapeutic agent that does not engender unacceptable levels of undesirable or deleterious side effects. There is an increasing for economical methods of testing large numbers of testing large number of chemical compounds to quickly identify those compounds that are likely to be effective in treating disease. At present, few such economical systems exist.... One disease that conspicuously lacks a rapid method of potential therapeutic agents is bone loss. Bone loss occurs in a wide variety of patients, including those who have undergone hysterectomy, who are undergoing or have undergone long-term administration of corticosteroids, who suffer from Cushing's syndrome or have gonadal dysgenesis, as well as post-menopausal women. Web site: http://www.delphion.com/details?pn=US05445941__ •

Method for screening for osteoporosis Inventor(s): Enomoto; Koichi (Sayama, JP), Tanaka; Shigeaki (Tsurugashima, JP), Akita; Mikio (Kawagoe, JP), Otawara-Hamamoto; Yoko (Kamifukuoka, JP) Assignee(s): Hoechst Japan Limited (Tokyo, JP) Patent Number: 5,545,534 Date filed: September 19, 1994 Abstract: A method for screening for osteoporosis comprising bone sialoprotein of mammals. Osteoporosis can be screened by bringing the body fluid sample collected from a living body into contact with the above-mentioned diagnostic agent to immunochemically detect the antibody which is present in the said sample and specifically reacts with the said diagnostic agent. Excerpt(s): This invention relates to a diagnostic agent for osteoporosis which comprises a mammalian bone sialoprotein and a method for diagnosis of osteoporosis using the same. More particularly, this invention is concerned with a new immunochemical diagnostic agent and a new method for diagnosis, which can make pathogenetic classification of osteoporosis feasibility. Moreover, there may be suggested a different therapy from the prior ones, e.g., utilization of an immunosuppressing agent, to osteoporotic patients classified according to the present method.... Degenerative osteoporosis is a syndrome showing a reduced amount of bone owing to unknown causes with aging after growth period and subsequent clinical pictures such as easy fractures of bones, lumbago and dorsalgia and the like. As the diagnostic methods for osteoporosis presently applied, there may be mentioned X-ray photographing of bones (MD method), DPA (Dual Photon Absorptiometry), DEXA (Dual Energy X-ray Absorptiometry), CXD (Computed X-ray Densitometry) and determination of a bone mineral amount, a bone density and the like by means of a physical apparatus for determining a bone amount using a low-frequency ultrasonic wave and the like. To determine a bone amount of an individual at a certain age according to such diagnostic methods makes it feasible to judge a person of his or her any future possibility of fractures. More specifically, a remarkable reduction in bone density could suggest a high risk of fractures in the future.... It has been considered, however, that a reduced bone density is only one of dangerous factors for possible fractures and a fracture risk would

392 Osteoporosis

be also increased owing to phenomena with aging such as a lowered elasticity of collagen fibers, qualitative deterioration of the bone structure, lowered muscular power and so on. These dangerous factors other than lowered muscular power could not presently be determined noninvasively, which remains as an important problem to be solved in the future. Web site: http://www.delphion.com/details?pn=US05545534__ •

Method for treating osteoporosis Inventor(s): Vickery; Brian Henry (Mountain View, CA), Uskokovic; Milan Radoje (Upper Montclair, NJ), Nestor, Jr. John Joseph (Cupertino, CA) Assignee(s): Syntex (U.S.A.) Inc. (Palo Alto, CA), Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 5,696,103 Date filed: November 17, 1995 Abstract: A method for treating osteoporosis via administration of a compound of the formula, 1.alpha.-fluoro-25-hydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol, in an amount therapeutically effective to restore bone density to an asymptomatic level, without inducing hypercalciuria, hypercalcemia, or nephrotoxicity is provided. Excerpt(s): This invention relates to a method for treating osteoporosis with an analog of Vitamin D.... Osteoporosis is the most common form of metabolic bone disease and may be considered the symptomatic, fracture stage of bone loss (osteopenia). Although osteoporosis may occur secondary to a number of underlying diseases, 90% of all cases appear to be idiopathic. Postmenopausal women are at risk for idiopathic osteoporosis (postmenopausal or Type I osteoporosis); another particularly high risk group for idiopathic osteoporosis is the elderly of either sex (senile or Type II osteoporosis). Osteoporosis has also been related to corticosteroid use, immobilization or extended bed rest, alcoholism, diabetes, gonadotoxic chemotherapy, hyperprolactinemia, anorexia nervosa, primary and secondary amenorrhea, transplant immunosuppression, and oophorectomy. Postmenopausal osteoporosis is characterized by fractures of the spine, while femoral neck fractures are the dominant features of senile osteoporosis.... The mechanism by which bone is lost in osteoporotics is believed to involve an imbalance in the process by which the skeleton renews itself. This process has been termed bone remodeling. It occurs in a series of discrete pockets of activity. These pockets appear spontaneously within the bone matrix on a given bone surface as a site of bone resorption. Osteoclasts (bone dissolving or resorbing cells) are responsible for the resorption of a portion of bone of generally constant dimension. This resorption process is followed by the appearance of osteoblasts (bone forming cells) which then refill with new bone the cavity left by the osteoclasts. Web site: http://www.delphion.com/details?pn=US05696103__

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Method for treating osteoporosis in castrated prostatic cancer patients Inventor(s): Bell; Robert G. (Palm Harbor, FL) Assignee(s): Barr Laboratories, Inc. (Pomona, NY) Patent Number: 6,613,758 Date filed: April 2, 1999

Patents 393

Abstract: The present invention provides a method for preventing or treating osteoporosis in a castrated prostatic cancer patient, by administering to the patient an amount of from 10 mg to 300 mg cyproterone acetate per day. The present therapy is compatible with the patients' anti-cancer treatment. Excerpt(s): The present invention relates to a treatment for slowing or preventing the progression of osteoporosis in surgically or chemically castrated prostatic cancer patients.... Osteoporosis is generally the occurrence of a reduction in the quantity of bone, or the atrophy of skeletal tissue. This disorder is evidenced by a decrease in bone density throughout the body. Although the mechanism of osteoporosis is not entirely understood, it is believed that there is an imbalance between bone production and bone resorption, resulting in net bone resorption or breakdown. The condition can begin to occur as early as age 30. The process is typically more rapid in postmenopausal women than in men. Bone loss in males can be recognized at about 65 years of age. A significant bone loss is seen in men at about 80 years of age, and is accompanied by increased hip, spine and wrist fractures.... Surgical and chemical (e.g., LH-RH agonists) castration are widely used for the treatment of patients with prostate cancer. A number of side effects occur as a result of such therapy. Impotence and the occurrence of hot flashes are among the more distressing side effects to patients. Web site: http://www.delphion.com/details?pn=US06613758__ •

Method for treatment of osteoporosis Inventor(s): Matsuyama; Toshikatsu (Sapporo, JP), Konishi; Jin-emon (Tokyo, JP) Assignee(s): Nippon Zoki Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 6,165,515 Date filed: June 18, 1998 Abstract: A therapeutic agent for osteoporosis brought about by a decrease in estrogen comprises an extract from inflammatory rabbit skin inoculated with vaccinia virus as an effective component. In ovariectomized rats, a model animal for osteoporosis brought about by a decrease in estrogen, the extract from inflammatory rabbit skin inoculated with vaccinia virus has an excellent action for maintaining bone volume and bone strength. The therapeutic agent containing the extract as an active component is very useful for treatment and prevention of osteoporosis brought about by a decrease in estrogen which is frequently caused by menopause or ovariectomy in women. The extract from inflammatory rabbit skin inoculated with vaccinia virus has a high safety profile even when administered for a long term. Excerpt(s): The present invention relates to a therapeutic agent for osteoporosis brought about by a decrease in estrogen, which has a high safety profile even when administered for a prolonged period of time.... As the segment of the population advanced in age increases in society, the number of patients with osteoporosis is rapidly increasing. The diagnostic criteria and therapy for osteoporosis have been earnestly investigated. Bones become friable and weak in the osteoporosis patient. Pressure fracture of the spine and limb fracture causing pain or dysfunction to the patient easily occur by a trifle action or weak impact. Osteoporosis not only imparts pain to the patient but often makes the patient bedridden, leading to heavy burdens upon persons attending to the patient and to society supporting medical expenses.... Various pathophysiologies of osteoporosis have been suggested. Osteoporosis in women rapidly increases after menopause and the early onset of osteoporosis is observed in ovariectomy women. Accordingly, a decrease

394 Osteoporosis

in female hormones, especially estrogen, is thought to be the important cause of osteoporosis. In fact, the occurrence of osteoporosis in women is several times that in men. Also, osteoporosis in women occurs earlier than in men and its occurrence rapidly increases around menopause. Osteoporosis brought about by the decrease in estrogen is the leading cause of the disease and is one of the diseases for which an appropriate therapeutic agent has been sought. The first choice for the treatment of osteoporosis in Europe and America is estrogen replacement therapy to replenish estrogen. However, estrogen causes undesirable side effects such as metrorrhagia and mammary hypertrophy. Estrogen replacement therapy also has a high risk of inducing mammary carcinoma. Therefore, estrogen replacement therapy in Japan is not preferred unlike as in Europe and America. Web site: http://www.delphion.com/details?pn=US06165515__ •

Method of combatting osteoporosis in mammalian subjects, utilizing organic boron compounds Inventor(s): Spielvogel; Bernard F. (Raleigh, NC), Sood; Anup (Durham, NC), Hall; Iris H. (Carrboro, NC) Assignee(s): Boron Biologicals, Inc. (Raleigh, NC) Patent Number: 5,312,816 Date filed: September 14, 1993 Abstract: A method of combatting, e.g., preventing as well as treating, a disease state such as cystic fibrosis, neonatal hypoxemia, pulmonary hypertension, adult respiratory distress syndrome, psoriasis, spondyloarthritis, rheumatoid arthritis, gout, inflammatory bowel disease, myocardial infarctions, and/or osteoporosis in an animal subject, by administering to the animal subject an amount of an organic boron compound which is effective thereagainst. The organic boron compounds usefully employed in the method of the invention include any suitable organic boron-containing compounds, such as Lewis base-boron adducts; a preferred class of organic boron compounds useful in such method includes boron analogs of.alpha.-amino acids, and the corresponding amides and esters of such amino acids. A method is also disclosed of inhibiting enzyme activity in in vitro or in vivo systems comprising administering to such system an enzyme-inhibiting amount of an organic boron compound. Further disclosed is a method of reducing hydroxyproline, calcium, and/or inorganic phosphorous in serum and/or urine of an animal subject, by administering to the animal subject an effective amount of an organic boron compound. Excerpt(s): The present invention relates to a method for preventing and/or treating osteoporosis and other disease states in animal subjects, utilizing organic boron compounds.... The adult skeleton is composed of 80% cortical and 20% trabecular bone. Bone matrix is composed of 25% collagen, 65% inorganio material, and 10% non-cellular proteins (i.e., osteocalcin, silaoprotein, proteoglycans and osteonectin) and lipids. Osteoblasts synthesize and secrete Type 1 collagen and mucopolysaccharides to form the bone matrix which is laid down between the thin layers of osteoid. The layers are subsequently mineralized with 99% of the body's calcium found in the bone as a calcium phosphate complex with hydroxyapatite. Osteoblasts also synthesize and release PgE.sub.2, osteocalcin, osteonectin, and collagenase. These cells have membrane receptors for PTH, VitD, and glucocorticosteroids.... Osteoclasts are multi-nucleated cells which reabsorb calcium from bone and cartilage. These cells may be derived from hemopoietic stem cells, i.e., mono-nucleated phagocytic cells. These cells lie on the bone surface

Patents 395

(Howship's lacunae) and the surface becomes ruffled (motile microvilli). This area is sealed off from the neighboring cells. In these pockets, acid is produced which activates acidic hydrolytic enzymes and neutral proteases are released. Calcium is chelated by organic anions, e.g., citrate. Web site: http://www.delphion.com/details?pn=US05312816__ •

Method of preventing osteoporosis Inventor(s): Ledbetter; John C. (Billings, MT) Assignee(s): The Nyvatex Marketing Corporation (Billings, MT) Patent Number: 5,782,875 Date filed: August 1, 1997 Abstract: Disclosed herein is a method for preventing osteoporosis in a human patient by contacting the patient with an electromagnetic (EM) capture and generator device for a time effective for preventing the disease. Excerpt(s): The present invention is directed to methods of preventing the symptoms of osteoporosis in mammals.... Osteoporosis is the term used for a group of diseases of diverse etiology characterized by a reduction in the mass of bone to a level below that required for adequate mechanical support function. After the age of 40-50, skeletal mass begins to decline at a faster rate in women than in men and is particularly apparent in post-menopausal women. Osteoporosis is the commonest of the metabolic bone diseases and an important cause of morbidity in elderly patients.... Estrogens produce significant, although modest, calcium retention, decrease the difference between formation and resorption of bone, and therefore tend to retard the progress of osteoporosis. However, the use of estrogens is limited due to the known dose-related increase in the incidence of endometrial carcinoma with their use. Web site: http://www.delphion.com/details?pn=US05782875__

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Method of treating low bone turnover osteoporosis with (205) vitamin D compounds Inventor(s): Wicha; Jerzy (Warsaw, PL), DeLuca; Hector F. (Deerfield, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 5,585,369 Date filed: May 5, 1995 Abstract: The present invention is directed toward the use of 20-epi-vitamin D.sub.3 analogs to treat low bone turnover osteoporosis. The 20-epi compounds are characterized by a marked intestinal calcium transport activity while exhibiting much higher activity than 1.alpha.,25-dihydroxyvitamin D.sub.3 in their ability to mobilize calcium from bone. Excerpt(s): This invention relates to biologically active vitamin D compounds. More specifically, the invention relates to (20S) vitamin D compounds, to a general process for their preparation, and to their use in treating osteoporosis.... With the discovery of 1.alpha.,25-dihydroxyvitamin D.sub.3, as the active form of the vitamin has come an intense investigation of analogs of this hormonal form of vitamin D with the intent of finding analogs that have selective activity. By now, several compounds have been

396 Osteoporosis

discovered which carry out the differentiative role of 1,25-dihydroxyvitamin D.sub.3 while having little or no calcium activity. Additionally, other compounds have been found that have minimal activities in the mobilization of calcium from bone while having significant activities in stimulating intestinal calcium transport. Modification of the vitamin D side chain by lengthening it at the 24-carbon has resulted in loss of calcium activity and either an enhancement or undisturbed differentiative activity. Placing the 24-methyl of 1.alpha.,25-dihydroxyvitamin D.sub.2 in the epi-configuration appears to diminish activity in the mobilization of calcium from bone. On the other hand, increased hydrophobicity on the 26- and 27-carbons seems to increase the total activity of the vitamin D compounds provided the 25-hydroxyl is present.... Several of these known compounds exhibit highly potent activity in vivo or in vitro, and possess advantageous activity profiles. Thus, some of these compounds are in use, or have been proposed for use, in the treatment of a variety of diseases such as renal osteodystrophy, vitamin D-resistant rickets, osteoporosis, psoriasis, and certain malignancies. Web site: http://www.delphion.com/details?pn=US05585369__ •

Method of treating dehydropiandrosterone

or

preventing

osteoporosis

by

adminstering

Inventor(s): Labrie; Fernand (Quebec, CA) Assignee(s): Endorecherche, Inc. (Quebec, CA) Patent Number: 5,776,923 Date filed: January 18, 1994 Abstract: Sex steroid precursors such as dehydroepiandrosterone and dehydroepiandrosterone sulphate, and compounds converted in vivo to ether of the foregoing, are utilized for the treatment and/or prevention of vaginal atrophy, hyprogonadism, diminished libido, osteoporosis, urinary incontinence, ovarian cancer, uterine cancer, skin atrophy, for contraception, and, in combination with an estrogen and/or progestin, for the treatment of menopause. The precursors may be formulated for percutaneous or transmucosal administration. Gels, solutions, lotions, creams, ointments and transdermal patches for the administration of these precursors are provided, as are certain pharmaceutical compositions and kits which can be used for the prevention and treatment of a wide variety of conditions related to decreased secretion of sex steroid precursors by the adrenals. Excerpt(s): This invention relates to a method for preventing and/or treating vaginal atrophy, hypogonadism, diminished libido, osteoporosis, urinary incontinence, ovarian cancer, uterine cancer, and menopause or contraception in susceptible warm-blooded animals including humans involving administration of dehydroespiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S) or compounds converted in vivo to either and to pharmaceutical products, including kits and pharmaceutical compositions for delivery of active ingredient(s) useful to the invention.... Primates are unique in having adrenals that secrete large amounts of the precursor steroid dehydroepiandrosterone (DHEA) and especially DHEA-sulfate (DHEA-S), which are converted into androstenedione (.DELTA.4-dione) or androstene-diol (.DELTA.5-diol) and then into potent androgens and estrogens in peripheral tissues (Adams, Mol. Cell. Endocrinol. 41: 1-17, 1985; Labrie et al., in Important Advances in Oncology (de Vita S, Hellman S, Rosenberg SA, eds), J. B. Lippincott, Philadelphia, Pa., pp 193-200, 1985). DHEA-S, the major steroid present in blood of both men and women is converted into DHEA and.DELTA.5-diol in peripheral tissues, thus maintaining a close correlation

Patents 397

between the concentration of these three steroids in the blood (Adams, Mol. Cell. Endocrinol. 41: 1-17, 1985). Depending upon the relative activities of 17.beta.hydroxysteroid dehydrogenase (17.beta.-HSD), aromatase and 5.alpha.-reductase, DHEA or its derivatives will be preferentially converted into androgens and/or estrogens.... The low serum values of DHEA and DHEA-S found at birth persist up to six years of age. Usually, during the 7th year of age, serum levels of these two steroids increase and continue to rise until age 16 in both boys and girls (Orentreich et al., J. Clin. Endocr. Metab. 59: 551-555, 1984). A further increase is then seen in males, who typically reach maximal levels between 20 and 24 years of age. In women, there is usually no further increase after 16 years. DHEA and DHEA-S decrease with aging in both men and women (Vermeulen and Verdoreck, J. Steroid Biochem. 7: 1-10, 1976; Vermeulen et al., J. Clin. Endocr. Metab. 54: 187-191, 1982). In fact, at 70 years of age, serum DHEA-S levels are at approximately 20% of their peak values while they decrease by up to 95% by the age of 85 to 90 years (Migeon et al., J. Clin. Endocr. Metab. 17: 1051-1062, 1957). The 70% to 95% reduction in the formation of DHEA-S by the adrenals during aging results in a dramatic reduction in the formation of androgens and estrogens in peripheral target tissues, thus resulting in a marked decrease in the biochemical and cellular functions induced by sex steroids. Web site: http://www.delphion.com/details?pn=US05776923__ •

Method of treating osteoporosis with 1.alpha.25-dihydroxy-22(E)-dehydro-vitamin D.sub.3 Inventor(s): DeLuca; Hector F. (Deerfield, WI), Schnoes; Heinrich K. (Madison, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 5,393,749 Date filed: October 25, 1993 Abstract: A method of treating osteoporosis comprising the administration of an effective amount of 1.alpha.,25-dihydroxy-22(E)-dehydro-vitamin D.sub.3. Excerpt(s): This invention relates to a method for treating or for preventing the depletion of calcium from bones as a result of osteoporosis.... More specifically, this invention relates to a method for treating or preventing various known forms of osteoporosis, e.g. postmenopausal, senile and steroid-induced osteoporosis, one of the characteristics of which is the loss of bone mass.... It is well known that females at the time of menopause suffer a marked loss of bone mass giving rise ultimately to osteopenia, which in turn gives rise to spontaneous crash fractures of the vertebrae and fractures of the long bones. This disease is generally known as postmenopausal osteoporosis and presents a major medical problem, both in the United States and most other countries where the life-span of females reaches ages of at least 60 and 70 years. Generally, the disease which is often accompanied by bone pain and decreased physical activity, is diagnosed by one or two vertebral crush fractures with evidence of diminished bone mass. It is known that this disease is accompanied by diminished ability to absorb calcium, decreased levels of sex hormones, especially estrogen and androgen, and a negative calcium balance. Web site: http://www.delphion.com/details?pn=US05393749__

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Method of treating osteoporosis with 1.alpha.,24(R)-dihydroxy-22(E)-dehydro-vitamin D.sub.3 Inventor(s): Schnoes; Heinrich K. (Madison, WI), Deluca; Hector F. (Deerfield, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 5,395,830 Date filed: January 12, 1994 Abstract: A method of treating osteoporosis comprising the administration of an effective amount of 1.alpha.,24(R)-dihydroxy-22(E)-dehydro-vitamin D.sub.3. Excerpt(s): This invention relates to a method for treating or for preventing the depletion of calcium from bones as a result of osteoporosis.... More specifically, this invention relates to a method for treating or preventing various known forms of osteoporosis, e.g. postmenopausal, senile and steroid-induced osteoporosis, one of the characteristics of which is the loss of bone mass.... It is well known that females at the time of menopause suffer a marked loss of bone mass giving rise ultimately to osteopenia, which in turn gives rise to spontaneous crush fractures of the vertebrae and fractures of the long bones. This disease is generally known as postmenopausal osteoporosis and presents a major medical problem, both in the United States and most other countries where the life-span of females reaches ages of at least 60 and 70 years. Generally, the disease which is often accompanied by bone pain and decreased physical activity, is diagnosed by one or two vertebral crush fractures with evidence of diminished bone mass. It is known that this disease is accompanied by diminished ability to absorb calcium, decreased levels of sex hormones, especially estrogen and androgen, and a negative calcium balance. Web site: http://www.delphion.com/details?pn=US05395830__

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Method of treating post menopausal osteoporosis with hexafluro-vitamin D Inventor(s): Ogura; Yosuke (Tokyo, JP), Deluca; Hector F. (Deerfield, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 5,571,802 Date filed: February 18, 1994 Abstract: A method of treating post menopausal osteoporosis which comprises administering to a subject having the disease an effective daily dose of 26,26,26,27,27,27hexafluoro-1.alpha.,25-dihydroxycholecalciferol compound in an amount from about 0.05.mu.g to about 2.0.mu.g. Excerpt(s): The present invention relates to a novel method of treating diseases resulting from calcium metabolism disorders. More specifically, this invention relates to a method comprising the use of 26,26,26,27,27,27-hexafluoro-1.alpha.,25-dihydroxycholecalciferol, a derivative of vitamin D.sub.3.... Vitamin D.sub.3 is a well-known agent for the control calcium and phosphorous homeostasis. It is also now well known that to be effective, vitamin Da must be converted to its hydroxylated forms. For example, the vitamin is first hydroxylated in the liver to form 25-hydroxyvitamin D.sub.3 and is further hydroxylated in the kidney to produce 1.alpha.,25-dihydroxyvitamin D.sub.3 or 24,25dihydroxy vitamin D.sub.3. The 1.alpha.-hydroxylated form of the vitamin is generally considered to be the physiologically active or hormonal form of the vitamin and to be responsible for what are termed the vitamin D-like activities, such as increasing

Patents 399

intestinal absorption of calcium phosphate, mobilizing bone mineral, and reabsorbing calcium in the kidneys.... Since the discovery of biologically active metabolites of vitamin D.sub.3 there has been much interest in the preparation of structural analogs of these metabolites, because such compounds may represent useful therapeutic agents for the treatment of diseases resulting from calcium metabolism disorders. A variety of vitamin D-like compounds have been synthesized. See, for example, U.S. Pat. Nos. 3,741,996 directed to 1.alpha.-hydroxycholecalciferol; 3,907,843 directed to 1.alpha.hydroxyergocalciferol; 3,786,062 directed to 22-dehydro-25-hydroxycholecalciferol; 3,906,014 directed to 3-deoxy-1.alpha.-hydroxycholecalciferol; and 4,069,321 directed to the preparation of various side chain-fluorinated vitamin D.sub.3 derivatives and side chain-fluorinated dihydrotachysterol analogs. Web site: http://www.delphion.com/details?pn=US05571802__ •

Method of treating reduced insulin-like growth factor and bone loss associated with aging Inventor(s): Shug; Austin L. (5322 Lighthouse Bay Dr., Madison, WI 53704) Assignee(s): none reported Patent Number: 5,240,961 Date filed: July 2, 1992 Abstract: Methods of treating reduced insulin-like growth factor levels and bone loss associated with aging which include administering L-carnitine and/or its precursors thereof are disclosed. Such administration results in increased serum insulin-like growth factor-1 and osteocalcin levels. Excerpt(s): This invention relates generally to methods of improving aging phenomena, in particular, to a method of stimulating formation of insulin-like growth factor, and preventing bone loss, by administering L-carnitine and/or carnitine precursors to patients. The invention is particularly well-suited for administration to the elderly who generally suffer from decreased insulin-like growth factor levels as well as bone loss and muscle weakness.... In middle and late adulthood, all people experience a series of progressive alterations in body composition. The lean body mass shrinks and the mass of adipose tissue expands. The contraction in lean body mass reflects atrophic processes in skeletal muscle, liver, kidney, spleen, skin and bone.... These structural changes have been considered unavoidable results of the aging process. It has recently been proposed, however, that reduced availability of growth hormone in late adulthood may contribute to such changes. For example, after about the age of 30, the secretion of growth hormone by the pituitary gland tends to decline. Web site: http://www.delphion.com/details?pn=US05240961__

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Method of using triaryl-ethylene derivatives in the treatment and prevention of osteoporosis Inventor(s): Bitonti; Alan J. (Maineville, OH) Assignee(s): Hoechst Marion Roussel, Inc. (Cincinnati, OH) Patent Number: 5,693,674 Date filed: June 12, 1996

400 Osteoporosis

Abstract: The present invention relates to a method of using triaryl-ethylene derivatives in the treatment or prevention bone tissue loss or osteoporosis. Excerpt(s): The present invention relates to a method of using triaryl-ethylene derivatives in the treatment or prevention osteoporosis or bone tissue loss. Osteoporosis is a significant problem for the developed nations. The term osteoporosis is often used to describe different clinical situations. Osteoporosis was first used to describe the syndrome in which post-menopausal women tended to suffer vertebral fractures. F. Albright et al., J. Am. Med. Assoc. 116, 2465-2474 (1941). To avoid ambiguity, the terms bone tissue loss or osteopenia are used to describe the clinical situation in which loss of bone mass or density has occurred in the absence of a fracture.... Osteoporosis is most commonly associated with post-menoapuse and age related bone tissue loss. Osteoporosis or bone tissue loss can also occur secondarily to various drugs and diseases, including: corticosteroids, anticonvulsants, alcohol, malabsorption syndromes, primary biliary cirrhosis, myeloma, thalassemia, thyrotoxicosis, Cushing's syndrome, Turner's syndrome, and primary hyperparathyroidism.... The present invention relates to a method of using triaryl-ethylene derivatives in the treatment or prevention bone tissue loss or osteoporosis. Web site: http://www.delphion.com/details?pn=US05693674__ •

Methods for inhibiting bone loss Inventor(s): Audia; James E. (Indianapolis, IN), Neubauer; Blake L. (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,550,134 Date filed: May 10, 1995 Abstract: The present invention provides methods of inhibiting bone loss in mammals via the administration to a mammal in need of such treatment an effective amount of a compound from a series of benzoquinolin-3-ones. Such compounds also are sequentially or concurrently coadministered with a bone antiresorptive agent or a bone anabolic agent. Excerpt(s): The present invention relates to the fields of pharmacology and pharmaceutical chemistry, and provides methods for inhibiting the loss of bone in humans.... The mechanism of bone loss is not well understood, but in practical effect, the disorder arises from an imbalance in the formation of new healthy bone and the resorption of old bone, skewed toward a net loss of bone tissue. This bone loss includes a decrease in both mineral content and protein matrix components of the bone, and leads to an increased fracture rate of, predominantly, femoral bones and bones in the forearm and vertebrae. These fractures, in turn, lead to an increase in general morbidity, a marked loss of stature and mobility, and, in many cases, an increase in mortality resulting from complications.... Bone loss occurs in a wide range of subjects including post-menopausal women, patients who have undergone hysterectomy, patients who are undergoing or have undergone long-term administration of corticosteroids, patients suffering from Cushing's syndrome, and patents having gonadal dysgenesis. Web site: http://www.delphion.com/details?pn=US05550134__

Patents 401

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Methods for inhibiting bone loss using substituted benzothiophene Inventor(s): Grese; Timothy A. (Indianapolis, IN), Bryant; Henry U. (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,441,964 Date filed: October 15, 1993 Abstract: A method of inhibiting bone loss comprising administering to a human in need of treatment an effective amount of a substituted benzothiophene. Excerpt(s): The mechanism of bone loss is not completely understood, but in practical effect, the disorder arises from an imbalance in the formation of new healthy bone and the resorption of old bone, skewed toward a net loss of bone tissue. This bone loss includes a decrease in both mineral content and protein matrix components of the bone, and leads to an increased fracture rate of, predominantly, femoral bones and bones in the forearm and vertebrae. These fractures, in turn, lead to an increase in general morbidity, a marked loss of stature and mobility, and, in many cases, an increase in mortality resulting from complications.... Bone loss occurs in a wide range of subjects, including post-memopausal women, patients who have undergone hysterectomy, patients who are undergoing or have undergone long-term administration of corticosteroids, patients suffering from Cushing's syndrome, and patients having gonadal dysgenesis. The need for bone repair or replacement also arises locally in the case of bone fracture, non-union, defect, prosthesis implantation, and the like. Further, such need also arises in cases of systemic bone diseases, as in osteoporosis, osteroarthritis, Paget's disease, osteomalacia, osteohalisteresis, multiple myeloma and other forms of cancer and the like.... The current invention provides methods for inhibiting the loss of bone. Web site: http://www.delphion.com/details?pn=US05441964__

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Methods for inhibiting bone loss with vanadyl sulfate Inventor(s): Cullinan; George J. (Trafalgar, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,547,685 Date filed: May 16, 1995 Abstract: The present invention provides a method for inhibiting bone loss comprising administering to a human in need of treatment an effective amount of vanadyl sulfate, or a pharmaceutically acceptable solvate or hydrate thereof, and pharmaceutical compositions thereof. Excerpt(s): The present invention relates to the fields of pharmacology and pharmaceutical chemistry, and provides methods for inhibiting the loss of bone in humans.... The mechanism of bone loss is not well understood, but in practical effect, the disorder arises from an imbalance in the formation of new healthy bone and the resorption of old bone, skewed toward a net loss of bone tissue. This bone loss includes a decrease in both mineral content and protein matrix components of the bone, and leads to an increased fracture rate of, predominantly, femoral bones and bones in the forearm and vertebrae. These fractures, in turn, lead to an increase in general morbidity, a marked loss of stature and mobility, and, in many cases, an increase in mortality resulting from complications.... Bone loss occurs in a wide range of subjects including

402 Osteoporosis

postmenopausal women, patients who have undergone hysterectomy, patients who are undergoing or have undergone long-term administration of corticosteroids, patients suffering from Cushing's syndrome, and patents having gonadal dysgenesis. Web site: http://www.delphion.com/details?pn=US05547685__ •

Methods for preventing and treating osteoporosis with low dose non-masculinizing androgenic compounds Inventor(s): Labrie; Fernand (Quebec, CA) Assignee(s): Endorecherche, Inc. (Quebec, CA) Patent Number: 5,846,960 Date filed: June 7, 1995 Abstract: A method of treatment or prevention of breast and endometrial cancer, osteoporosis and endometriosis in susceptible warm-blooded animals comprising administering a low dose of a progestin or other steroid derivative having androgenic activity and low masculinizing activity. Pharmaceutical compositions useful for such treatment and pharmaceutical kits containing such compositions are disclosed. An in vitro assay permitting specific measurements of androgenic activity of potentially useful compounds is also disclosed. Excerpt(s): This invention relates to a method for treating or preventing breast and endometrial cancer, bone loss, and for treating endometriosis in susceptible warmblooded animals including humans involving administration of a compound possessing androgenic activity, and to kits containing active ingredients to be used in the therapy.... Various investigators have been studying hormonal therapy for breast and endometrial cancer as well as for the prevention and treatment of bone loss and for treatment of endometriosis. The main approaches for the treatment of already developed breast cancer are related to the inhibition of estrogen action and/or formation. The role of estrogens in promoting the growth of estrogen-sensitive breast cancer is well recognized (Lippman, Semin. Oncol. 10 (suppl. 4): 11-19, 1983; Sledge and McGuire, Cancer Res. 38: 61-75, 1984; Wittliff, Cancer 53: 630-643, 1984; Poulin and Labrie, Cancer Res. 46: 49334937,1986).... Estrogens are also known to promote the proliferation of normal endometrium. Chronic exposure to estrogens unopposed by progesterone can lead to the development of endometrial hyperplasia which predisposes to endometrial carcinoma (Lucas, Obstet. Gynecol. Surv. 29: 507-528, 1974). The incidence of endometrial cancer increases after menopause, especially in women receiving estrogen therapy without simultaneous treatment with progestins (Smith et al., N. Engl. J. Med. 293: 1164-1167, 1975; Mack et al., N. Engl J. Med. 294:1262-1267,1976). Web site: http://www.delphion.com/details?pn=US05846960__

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Methods for reducing bone loss using centchroman derivatives Inventor(s): Labroo; Virender M. (Mill Creek, WA), Piggott; James R. (Bothell, WA), Bain; Steven D. (Seattle, WA) Assignee(s): ZymoGenetics, Inc. (Seattle, WA) Patent Number: 5,280,040 Date filed: March 11, 1993

Patents 403

Abstract: Methods and pharmaceutical compositions for reducing bone loss are disclosed. 3,4-diarylchromans and their pharmaceutically acceptable salts are formulated into medicaments for the treatment of bone loss due to osteoporosis or other conditions. An exemplary 3,4-diarylchroman is centchroman (3,4-trans-2,2-dimethyl-3phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-me thoxy-chroman). Formulations include tablets and other forms suitable for oral administration and controlled-release subdermal implants. Excerpt(s): Bone remodeling is the dynamic process whereby skeletal mass and architecture are renewed and maintained. This renewal and maintenance is a balance between bone resorption and bone formation, with the osteoclast and the osteoblast considered the two key participants in the remodeling process. The osteoclast initiates the remodeling cycle by resorbing a cavity in the bone which is subsequently refilled when the osteoblast synthesizes and deposits new bone matrix into the excavation. The activities of osteoclast and osteoblast are regulated by complex interactions between systemic hormones and the local production of growth factors and cytokines at active remodeling sites.... Imbalances in bone remodeling are associated with such conditions as osteoporosis, Paget's disease, and hyperparathyroidism. Osteoporosis, characterized by a decrease in the skeletal mass, is one of the most common diseases of postmenopausal women and is often the cause of debilitating and painful fractures of the spine, hip and wrist.... Approximately 25% of all postmenopausal women suffer from osteoporosis, and it is generally accepted that the etiology of the disease involves the reduction of circulating estrogens (Komm et al., Science 241:81-84, 1988). Komm et al. further report that the proportion of caucasian women in the United States who are at risk for a hip fracture is 15%, or 247,000 hip fractures per year in women over the age of 45. Web site: http://www.delphion.com/details?pn=US05280040__ •

Methods for the treatment of bone resorption disorders, including osteoporosis Inventor(s): Chapman; Harold (Newton, MA), Desnick; Robert J. (New York, NY), Gelb; Bruce D. (Dobbs Ferry, NY) Assignee(s): Mount Sinai School of Medicine of the City of New York (New York, NY), Brigham and Women's Hospital (Boston, MA) Patent Number: 5,830,850 Date filed: August 28, 1996 Abstract: The present invention relates to methods and compositions for the amelioration of symptoms caused by bone resorption disorders, including but not limited to osteoporosis, arthritides and periodontal disease, and damage caused by macrophage-mediated inflammatory processes. In one embodiment, the methods and compositions of the invention include methods and compositions for the specific inhibition of cathepsin K activity. In an additional embodiment, the methods and compositions of the invention include methods and compositions for the specific inhibition of cathepsin K activity coupled with specific inhibition of at least a second activity involved in the bone resorption and/or macrophage-mediated inflammatory processes. In a particular embodiment, the methods and compositions of the invention include methods and compositions for the specific inhibition of cathepsin K and cathepsin S activity.

404 Osteoporosis

Excerpt(s): The present invention relates to methods and compositions for the amelioration of symptoms caused by bone resorption disorders, including but not limited to osteoporosis, arthritides and periodontal disease, and damage caused by macrophage-mediated inflammatory processes.... In one embodiment, the methods and compositions of the invention include methods and compositions for the specific inhibition of cathepsin K activity. In an additional embodiment, the methods and compositions of the invention Include methods and compositions for the specific inhibition of cathepsin K activity coupled with specific inhibition of at least a second activity involved in the bone resorption and/or macrophage-mediated inflammatory processes. In a particular embodiment, the methods and compositions of the invention include methods and compositions for the specific inhibition of cathepsin K and cathepsin S activity.... Bone remodeling is a dynamic process which does not cease when longitudinal growth ceases, but continues throughout an individual's lifetime. Remodeling is required to preserve the mechanical strength of bone and involves both bone resorption and deposition. In order to maintain a constant adult skeletal mass, the rates of bone resorption and formation must be equal. (For a review, see, e.g., Rasmussen, H. & Bordier, P., 1974, The Physiological and Cellular Basis of Metabolic Bone Disease, Williams & Wilkins Co., Baltimore). Web site: http://www.delphion.com/details?pn=US05830850__ •

Methods for the treatment of osteoporosis Inventor(s): McOsker; Jocelyn Elaine (Norwich, NY) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 6,329,354 Date filed: January 25, 1993 Abstract: Methods of treatment for osteoporosis in a human or other animal subject, comprising: administering a bone-active phosphonate to said subject, at a level of at least about 0.1 LED per day of said treatment; and administering an estrogen hormone to said subject at a level of from about 0.2 to about 0.8 LED per day of said treatment. The bone-active phosphonate is preferably a bisphosphonate, or a phosphonoalkyl phosphonate. Excerpt(s): This invention relates to methods of building bone in humans and other animals, i.e., for the treatment of osteoporosis and related disorders. In particular, this invention relates to such methods of treatment by administration of bone-active phosphonates and estrogen.... The most common metabolic bone disorder is osteoporosis. Osteoporosis can be generally defined as the reduction in the quantity of bone, or the atrophy of skeletal tissue. In general, there are two types of osteoporosis: primary and secondary. "Secondary osteoporosis" is the result of an identifiable disease process or agent. However, approximately 90% of all osteoporosis cases is idiopathic "primary osteoporosis". Such primary osteoporosis includes postmenopausal osteoporosis, age-associated osteoporosis (affecting a majority of individuals over the age of 70 to 80), and idiopathic osteoporosis affecting middle-aged and younger men and women.... For some osteoporotic individuals the loss of bone tissue is sufficiently great so as to cause mechanical failure of the bone structure. Bone fractures often occur, for example, in the hip and spine of women suffering from postmenopausal osteoporosis. Kyphosis (abnormally increased curvature of the thoracic spine) may also result.

Patents 405

Web site: http://www.delphion.com/details?pn=US06329354__ •

Methods for the treatment of osteoporosis using bisphosphonates and parathyroid hormone Inventor(s): Geddes; Ann D. (Norwich, NY), Boyce; Rogely W. (Pottstown, PA) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 5,616,560 Date filed: March 20, 1996 Abstract: The present invention provides methods of increasing bone mass in a human or other animal subject afflicted with osteoporosis, comprising a thirty(30)-day treatment period, comprised of a parathyroid hormone administration regimen and a bisphosphonate administration regimen, wherein(a) said parathyroid hormone administration regimen comprises the administration to said subject of parathyroid hormone at one or more level of from about 4 IU/kg per day to about 15 IU/kg per day that said parathyroid hormone is administered, provided that said parathyroid hormone is administered at least one day every seven days of every said thirty(30)-day treatment periods; and wherein(b) said bisphosphonate administration regimen comprises the administration to said subject of a bisphosphonate at a level of from about 0.0005 mgP/kg to about 1.0 mgP/kg per day that said bisphosphonate is administered, provided that said bisphosphonate is administered at least 1 day of every said thirty(30)day treatment period. Excerpt(s): This invention relates to methods of increasing bone mass in humans and other animals, i.e., for the treatment of osteoporosis and related bone metabolic disorders. In particular, this invention relates to such methods of treatment by the administration of a bone-active phosphonate and parathyroid hormone.... The most common metabolic bone disorder is osteoporosis. Osteoporosis can be generally defined as the reduction in the quantity of bone, or the atrophy of skeletal tissue. In general, there are two types of osteoporosis: primary and secondary. "Secondary osteoporosis" is the result of an identifiable disease process or agent. However, approximately 90% of all osteoporosis cases is "primary osteoporosis". Such primary osteoporosis includes postmenopausal osteoporosis, age-associated osteoporosis (affecting a majority of individuals over the age of 70 to 80), and idiopathic osteoporosis affecting middle-aged and younger men and women.... For some osteoporotic individuals the loss of bone tissue is sufficiently great so as to cause mechanical failure of the bone structure. Bone fractures often occur, for example, in the hip and spine of women suffering from postmenopausal osteoporosis. Kyphosis (abnormally increased curvature of the thoracic spine) may also result. Web site: http://www.delphion.com/details?pn=US05616560__

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Methods for treatment and prevention of bone loss using 2,3-benzopyrans Inventor(s): Labroo; Virender M. (Mill Creek, WA) Assignee(s): ZymoGenetics, Inc. (Seattle, WA) Patent Number: 5,389,646 Date filed: December 30, 1993

406 Osteoporosis

Abstract: Methods and pharmaceutical compositions for reducing bone loss are disclosed. 2,3-diaryl-1-benzopyrans and their pharmaceutically acceptable salts are formulated into medicaments for the treatment of bone loss due to osteoporosis or other conditions. Formulations include tablets and other forms suitable for oral administration and controlled-release subdermal implants. Excerpt(s): Bone remodeling is the dynamic process whereby skeletal mass and architecture are renewed and maintained. This renewal and maintenance is a balance between bone resorption and bone formation, with the osteoclast and the osteoblast considered the two key participants in the remodeling process. The osteoclast initiates the remodeling cycle by resorbing a cavity in the bone which is subsequently refilled when the osteoblast synthesizes and deposits new bone matrix into the excavation. The activities of osteoclast and osteoblast are regulated by complex interactions between systemic hormones and the local production of growth factors and cytokines at active remodeling sites.... Imbalances in bone remodeling are associated with such conditions as osteoporosis, Paget's disease, and hyperparathyroidism. Osteoporosis, characterized by a decrease in the skeletal mass, is one of the most common diseases of postmenopausal women and is often the cause of debilitating and painful fractures of the spine, hip and wrist.... Approximately 25% of all postmenopausal women suffer from osteoporosis, and it is generally accepted that the etiology of the disease involves the reduction of circulating estrogens (Komm et al., Science 241:81-84, 1988). Komm et al. further report that the proportion of caucasian women in the United States who are at risk for a hip fracture is 15% , or 247 000 hip fractures per year in women over the age of 45. Web site: http://www.delphion.com/details?pn=US05389646__ •

Methods of inhibiting bone loss Inventor(s): Grese; Timothy A. (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,637,598 Date filed: May 2, 1995 Abstract: The instant invention provides methods for inhibiting bone loss comprising adminstering to a mammal in need of treatment a compound as provided in formula I. Excerpt(s): The mechanism of bone loss is not completely understood, but bone loss disorders arise from an imbalance in the formation of new healthy bone and the resorption of old bone, skewed toward a net loss of bone tissue. This bone loss involves a decrease in both mineral content and protein matrix components of the bone. Ultimately, such bone loss leads to an increased fracture rate of, predominantly, femoral bones and bones in the forearm and vertebrae. These fractures, in turn, lead to an increase in general morbidity, a marked loss of stature and mobility, and, in many cases, an increase in mortality resulting from complications.... Bone loss occurs in a wide range of subjects, including post-menopausal women, patients who have undergone hysterectomy, patients who are undergoing or have undergone long-term administration of corticosteroids, patients suffering from Cushing's syndrome, and patients having gonadal dysgenesis. The need for bone repair or replacement also arises locally in the case of bone fracture, non-union, defect, prosthesis implantation, and the like. Further, such need also arises in cases of systemic bone diseases, as in osteoporosis, osteoarthritis, Paget's disease, osteomalacia, osteohalisteresis, multiple myeloma and

Patents 407

other forms of cancer and the like.... Unfortunately, there exists a need for effective pharmaceutical agents which would inhibit bone loss in mammals while having negligible or non-existent side effects. Web site: http://www.delphion.com/details?pn=US05637598__ •

Methods of reducing bone loss with CD40 ligand Inventor(s): Bonewald; Lynda F. (San Antonio, TX), Ahuja; Seema A. (San Antonio, TX) Assignee(s): Board of Regents, The University of Texas System (Austin, TX) Patent Number: 6,482,411 Date filed: August 24, 2000 Abstract: Provided are methods and compositions using one or more CD40 agonists, such as CD40 ligands and/or agonistic anti-CD40 antibodies, to reduce or prevent cell death, or apoptosis, in bone cells. Methods of treating or preventing bone loss, including osteoporosis, as well as methods of reducing or eliminating the bone loss associated with steroid administration are particularly provided. Further disclosed are a variety of therapeutic kits and cocktails. Excerpt(s): The present invention relates generally to the fields of cell biology and bone metabolism. More particularly, it concerns the use of compositions containing one or more CD40 agonists, such as CD40 ligands and/or agonistic anti-CD40 antibodies, to reduce or prevent cell death or apoptosis, in bone cells, such as osteocytes and osteoblasts. Methods of treating or preventing bone loss, including osteoporosis, and methods of reducing or eliminating the bone loss associated with steroid administration are also included. Further provided are a variety of therapeutic kits and cocktails.... In the body, bone is remodeled continuously through the process of resorption by osteoclasts, followed by bone formation by osteoblasts. Normally, the activity of these two types of cells is balanced through the action of hormones and other signaling mechanisms. During the resorption phase, sites for remodeling are targeted by osteoclasts that form pits in bone, releasing organic matrix and minerals into the circulation. Resorption at a single site can last as long as about three weeks. As resorption progresses, osteoblasts begin filling in the resorbed region with new mineralized bone.... Peak bone mass is reached at about age 30. After pe tne mass is reached, there is a gradual age-related loss of bone mass in both males and females due to a slight imbalance in resorption and formation. However, as estrogen production declines in women around the time of menopause, bone resorption increases dramatically, which can lead to rapid bone loss. Premenopausal women have been shown to turnover bone at a rate of about one-third to one-half gram of bone per day, while the turnover is double to triple that in early postmenopausal women. Although bone loss can be especially elevated in the five to seven years immediately following menopause, this process continues throughout life. The rate of bone loss can vary dramatically from woman to woman. Web site: http://www.delphion.com/details?pn=US06482411__

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Methods of treating osteoporosis prophylactically or therapeutically Inventor(s): Knutson; Joyce C. (Madison, WI), Moriarty; Robert M. (Oak Park, IL), Bishop; Charles W. (Verona, WI) Assignee(s): Bone Care International, Inc. (Madison, WI) Patent Number: 5,801,164 Date filed: June 7, 1995 Abstract: Methods of treating osteoporosis prophylactically or therapeutically are disclosed. The method of treating osteoporosis includes administering to a patient suffering therefrom an effective amount to treat the osteoporosis of novel 1.alpha.hydroxyvitamin D.sub.4 and novel analogues 1,25-dihydroxyvitamin D.sub.4 and 1,24dihydroxyvitamin D.sub.4, the aforementioned compounds having lower toxicity as measured by an LD.sub.50 test in rats when compared to a corresponding vitamin D.sub.3 compound. The method of administering the compound is substantially without occurrence of hypercalcemia. Excerpt(s): This invention relates to biologically active vitamin D.sub.4 compounds. More specifically, this invention relates to novel 1.alpha.-hydroxy vitamin D.sub.4 and novel intermediates used in its synthesis, novel 1,25 dihydroxy vitamin D.sub.4, and novel 1,24 dihydroxy vitamin D.sub.4.... This invention also relates to a pharmaceutical composition which includes a pharmaceutically effective amount of the novel 1.alpha.hydroxy vitamin D.sub.4 compounds, and to a method of controlling abnormal calcium metabolism by administering a pharmaceutically effective amount of the novel compounds.... Vitamin D is known to be important in the regulation of calcium metabolism in animals and man. See, Harrison's Principals of Internal Medicine: Part Eleven, "Disorders of Bone and Mineral Metabolism, Chapter 335," E. Braunwald, et al., (eds.), McGraw-Hill, New York, 1987, pp. 1860-1865. The two most commonly known, useful forms of vitamin D are vitamin D.sub.3 and vitamin D.sub.2. Vitamin D.sub.3 is synthesized endogenously in the skin of animals and man, whereas vitamin D.sub.2 is the form of vitamin D supplied by plants. Vitamin D.sub.2 differs from vitamin D.sub.3 in that it contains a double bond between C22 and C23 and further contains a C24methyl group. In man and rats, vitamin D.sub.3 and vitamin D.sub.2 have equivalent biopotency. Web site: http://www.delphion.com/details?pn=US05801164__

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Methods of treating osteoporosis, increasing bone mineral content and preventing the occurrence of compression fractures in a mammal Inventor(s): Margolis; David J. (Philadelphia, PA) Assignee(s): Trustees of the University of Pennsylvania (Philadelphia, PA) Patent Number: 5,070,108 Date filed: October 12, 1990 Abstract: Methods of treating osteoporosis, increasing bone mineral content and preventing the occurrence of compression fractures are provided comprising administering to a mammal in need of such treatment a retinoid such as etretinate. Excerpt(s): This invention relates to a method of treating osteoporosis. More particularly, methods of treating osteoporosis, increasing bone mineral content and preventing the occurrence of compression fractures with retinoids are provided....

Patents 409

Osteoporosis is considered to be one of the most debilitating diseases of the adult population in the industrialized nations. Osteoporosis is the general term used for diseases of diverse etiology that are characterized by a reduction in the mass of bone per unit volume to a level below that required for adequate mechanical support (Krane, S. M., et al., "Metabolic Bone Disease," in Harrison's Principles of Internal Medicine, pg. 1889 edition 11 (1987)). One form of osteoporosis is senile osteoporosis which is responsible for a large portion of the health dollars spent on the geriatric population (Resnick, N. M., et al., "Senile Osteoporosis Reconsidered," JAMA 261:1025-1029 (1989)). The two other most common forms of osteoporosis are peri- or postmenopausal osteoporosis and corticosteroid induced osteoporosis. The most devastating consequence of osteoporosis is the occurrence of a pathologic fracture in trabecular bone, such as the vertebral spine or the hip. No current medical regimen is effective in fully preventing this common malady and no treatments are capable of reversing this affliction.... The pathophysiology of osteoporosis is poorly understood. It probably is related to an interplay of osteoblasts, osteoclasts, and other hormonally mediated events that alter calcium homeostasis. Most current treatment strategies attempt to reduce the bone loss of calcium in order to retard the onset of osteoporosis (Dawon-Hughes, B. et al., "A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women," NEJM 323:878-83 (1990)); Storm, T. et al., "Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis," NEJM 322:1264-1271 (1990)). Attempts to produce new and structurally functional bone have not been successful (Riggs, B. L. et al., "Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis," NEJM 322:802-809 (1990)). Web site: http://www.delphion.com/details?pn=US05070108__ •

Minimal orthesis for the treatment of osteoporosis Inventor(s): Minne; Helmut W. (Bad Pyrmont, DE) Assignee(s): Medi Bayreuth Weihermuller and Voigtmann GmbH & Co. KG (Bayreuth, DE) Patent Number: 6,063,047 Date filed: November 18, 1998 Abstract: Minimal orthesis for the treatment of osteoporosis comprising a rigid brace propping the spine as well as fastening structure for the brace guided around the truncus whereas the brace extends in a supporting manner essentially along the whole length of the spine, wherein the brace is provided with lower fastening belts for encompassing the truncus, the fastening belts being arranged at a height where they are not hindering abdominal respiration and the brace is provided with upper fastening belts which are guided in the way of rucksack straps over the shoulders and back underneath the arm pits so that they do not hinder thoracic respiration. Excerpt(s): The present invention relates to an orthesis for the treatment of osteoporosis comprising a rigid brace propping the spine as well as fastening structure for brace guided around the truncus.... Different types of orthesis for the treatment of osteoporosis are known. For example, German patent DE-C-39 28 628 which is sold under the name medi 3C, discloses a hyperextension orthesis with a basic plate, an abdominal rod extending from the basic plate downwards and which is provided with a padding for the symphysis, with webs extending laterally on both sides and provided with closing elements and with a breast rod extending upwards and provided with a

410 Osteoporosis

slidable sternal padding. Another hyperextension orthesis is sold under the name medi 4C and does without abdominal and sternal rod and achieves an axial stabilization of thoracic and lumbar spine by means of a stable frame construction, whereas the truncus is kept from leaning forward underneath the clavicula. German patent DE-A-27 51 608 discloses an orthopedic support corset propping elastically the spine, wherein a brace comprising elastic members snuggles the spine and is fastened on the shoulders and the thighs by means of fastening structure.... The caving in of a vertebra is a typical late complication of osteoporosis. The deformation of the vertebra leads to misalignments of the facet articulations of the vertebrae, malfunctions of tendons, ligaments and muscles. They are the origin of chronic pain and disability in every day life. Web site: http://www.delphion.com/details?pn=US06063047__ •

Osteoporosis compounds Inventor(s): Rosati; Robert L. (Stonington, CT), Lefker; Bruce A. (Gales Ferry, CT), Cameron; Kimberly O. (East Lyme, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,376,502 Date filed: February 22, 2000 Abstract: This invention relates to prostaglandin agonists, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits containing such prostaglandin agonists. The prostaglandin agonists are useful for the treatment of bone disorders including osteoporosis. Excerpt(s): This invention relates to prostaglandin agonists, pharmaceutical compositions containing such agonists and the use of such agonists to prevent bone loss or restore or augment bone mass and to enhance bone healing including the treatment of conditions which present with low bone mass and/or bone defects in vertebrates, and particularly mammals, including humans.... Osteoporosis is a systemic skeletal disease, characterized by low bone mass and deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In the U.S., the condition affects more than 25 million people and causes more than 1.3 million fractures each year, including 500,000 spine, 250,000 hip and 240,000 wrist fractures annually. Hip fractures are the most serious consequence of osteoporosis, with 5-20% of patients dying within one year, and over 50% of survivors being incapacitated.... The elderly are at greatest risk of osteoporosis, and the problem is therefore predicted to increase significantly with the aging of the population. Worldwide fracture incidence is forecasted to increase three-fold over the next 60 years, and one study estimated that there will be 4.5 million hip fractures worldwide in 2050. Web site: http://www.delphion.com/details?pn=US06376502__

Patents 411

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Osteoporosis diagnosing apparatus and method Inventor(s): Kuriwaki; Masashi (Kyoto, JP), Ishii; Tetsuya (Kyoto, JP), Kubota; Yasuyuki (Kyoto, JP) Assignee(s): Sekisui Kagaku Kogyo Kabushiki Kaisya (Osaka, JP) Patent Number: 5,749,363 Date filed: October 21, 1996 Abstract: The osteoporosis diagnosing apparatus of the invention radiates repeatedly an ultrasonic impulse Ai toward the bone Mb of an examinee and receives an echo Ae from the bone Mb. The received signal is converted into a digital echo signal through an A/D converter (8), and the echo level is detected by a CPU (11). The CPU (11) extracts maximum echo level from among the echo levels detected in a given period of measurement to thereby calculate a bone acoustic impedance Zb based on the extracted maximum echo level, and then calculate the bone density of the examinee based on the calculated acoustic impedance Zb. As the impedance Zb is expressed in the square root of the product of modulus of elasticity and density of a bone, decreased in both the modulus of elasticity and the density synergistically affect the impedance to remarkably decrease the same. Thus the bone acoustic impedance serves as a good index in judging the bone density Excerpt(s): With the emergence of an ageing society in recent years the bone disease termed osteoporosis has been becoming a problem. In this disease the calcium is withdrawn from the bones leaving them friable and prone to fracture at the slightest shock. Physical diagnosis is performed mainly by determining the density of bone precisely by means of diagnostic apparatus employing X-rays, typified by DXA apparatus; however, physical diagnosis by means of X-rays is beset by various problems such as the fact that the apparatus is large, and its use is restricted by the need to prevent damage due to radiation exposure.... Accordingly, diagnostic apparatus employing ultrasound have started to become popular as simple apparatus which do not cause such problems. In diagnostic apparatus employing ultrasound the speed and attenuation of ultrasound waves propagated inside the bony tissues are measured and used to estimate the density and elastic modulus (elastic strength) of the bone, and if a low estimated value is obtained it can be deduced that this is because of withdrawal of calcium from the bone, and hence osteoporosis is diagnosed.... For example, in the diagnostic apparatus recorded in Japanese Unexamined Patent 2-104337 and U.S. patent application Ser. No. 193,295 the speed of sound in bony tissue is measured by radiating ultrasonic pulses towards the bony tissue of an examinee which is the measurement site from an ultrasound transducer on one side and receiving the ultrasonic pulses transmitted by the bone tissue at an ultrasound transducer on the other side, and progress in osteoporosis is diagnosed when the speed of sound inside the bony tissue is slow. This is because this diagnostic apparatus acts on the premise that in experience the speed of sound in bony tissue is proportional to bone density. Web site: http://www.delphion.com/details?pn=US05749363__

412 Osteoporosis

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Osteoporosis inhibition by dietary calcium supplementation Inventor(s): Pak; Charles Y. C. (Dallas, TX) Assignee(s): Board of Regents, U T Systems (Austin, TX) Patent Number: 4,772,467 Date filed: December 11, 1985 Abstract: A process for dietary calcium supplementation. Oral dosage of a composition comprising calcium citrate is utilized to provide an efficiently absorbable chemical form of calcium, while raising urinary level of citrate. Because of improved absorption of calcium, osteoporosis development is precluded. Since citrate retards precipitation of stone-forming calcium stones, the risk of calcium nephrolithiasis (resulting from calcium supplementation) is reduced. Excerpt(s): The mineral calcium is an important human dietary component. Calcium is required for adequate bone formation and maintenance, as well as for diverse metabolic functions. These diverse metabolic functions of calcium are incompletely understood but likely to involve, at least in part, the alteration and functional control of proteins such as enzymes, and of hormones that regulate bone metabolism.... An assurance of adequate dietary calcium intake is thus important for normal development, metabolism and maintenance. Dietary calcium intake alone however is insufficient to assure that adequate calcium levels are available for required body functions. Dietary calcium must be absorbed from the digestive tract before it may be utilized. The efficiency of calcium absorption is determined by several factors, including the physiological status of the patient and the particular chemical form of ingested calcium. However, a part of the absorbed calcium is eliminated in urine, which poses a problem for certain subjects who are prone to the formation of calcium-containing kidney stones (calcium nephrolithiasis).... Thus, the amount of calcium intake and efficiency of calcium absorption could influence two clinical conditions, osteoporosis and calcium nephrolithiasis. Web site: http://www.delphion.com/details?pn=US04772467__

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Osteoporosis-relief device Inventor(s): Varner; Lawrence Norman (5277 S. Boston St., Englewood, CO 80111) Assignee(s): none reported Patent Number: 5,792,209 Date filed: April 1, 1996 Abstract: An apparatus provides relief from osteoporosis, through either prevention of its development or reversal of its presence, by utilizing a light-weight portable low intensity, low frequency electrical field specifically targeted for osteoporotic of hips and spine, thereby reducing the growing numbers of hip and vertebral fractures in our aging population. The apparatus is simple to utilize, safe, of inexpensive construction, convenient to use, and may be incorporated permanently within a specific designer line of clothing made for this purpose, or the device may be portable and adaptable to a variety of clothing which the wearer may choose, as that person's fashion preferences may dictate. The hip areas of the official pants are padded to absorb energy if the wearer accidentally falls onto either hip, decreasing the likelihood of a hip fracture. Electrode placements are discussed, for proper positioning of the electromagnetic fields; also

Patents 413

addressed are the design of the clothing incorporating this osteoporosis-relief system, and the design of the spine electrode "envelopes". Excerpt(s): A) Field of the Invention.... This invention relates in general to reversal and prevention of osteoporosis and prevention of osteoporosis-related spine fractures and hip fractures, and in particular, to low-frequency, low-voltage electromagnetic fields conveniently placed, in relationship to the bones at risk for fracture, to slow the progress of osteoporosis or reverse its development.... B) Description of Related Art and Prior Art. Web site: http://www.delphion.com/details?pn=US05792209__ •

Parathyroid hormone analogues for the treatment of osteoporosis Inventor(s): Neugebauer; Witold (Ottawa, CA), Willick; Gordon E. (Orleans, CA), Whitfield; James F. (Ottawa, CA), Sung; Wing L. (Gloucester, CA), Surewicz; Witold (Orleans, CA) Assignee(s): National Research Council of Canada (Ottawa, CA) Patent Number: 5,556,940 Date filed: June 20, 1994 Abstract: Certain analogues of human parathyroid hormone (hPTH) have been found to be effective for the treatment of osteoporosis, while showing decreased side effects. Analogues showing this effect include all sequences from hPTH-(1-28)-NH.sub.2 to hPTH-(1-31)-NH.sub.2 and all sequences from [Leu.sup.27 ]-hPTH-(1-28)-NH.sub.2 to [Leu.sup.27 ]-hPTH-(1-33)-NH.sub.2. Also included are cyclic analogues cyclo(Lys.sup.26 -Asp.sup.30) [Leu.sup.27 ]-hPTH-(1-34)NH.sub.2 and cyclo (Lys.sup.27 -Asp.sup.30 )-hPTH-(1-34)-NH.sub.2. Analogues in the form of the carboxyl terminal amide are particularly effective. Excerpt(s): This invention relates to analogues of human parathyroid hormone, which have been found to be effective in the treatment of osteoporosis and will reverse the loss of bone and increase bone mass and density specifically without undesirable side effects.... Osteoporosis is a leading cause of disability in the elderly, particularly elderly women. It is well known that human parathyroid hormone (hPTH) and certain analogues are useful in the treatment of osteoporosis.... Parathyroid hormone (PTH) is produced by the parathyroid gland and is involved in the control of calcium levels in blood. It is a hypercalcemic hormone, elevating blood calcium levels. PTH is a polypeptide and synthetic polypeptides containing the first thirty-four residues of PTH may be prepared using the method disclosed by Erickson and Merrifield, The Proteins, Neurath et al., Eds., Academic Press, New York, 1976, page 257, preferably as modified by the method of Hodges et al., Peptide Research, 1, 19 (1988). Web site: http://www.delphion.com/details?pn=US05556940__

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Parathyroid hormone analogues substituted at AA 25, 26, 27, and use in osteoporosis treatment Inventor(s): Pang; Peter K. T. (University of Alberta, Dept. of Physiology, 7-55 Medical Science Bldg., Edmonton, CA), Shan; Jie (Edmonton, CA) Assignee(s): Pang; Peter K. T. (Edmonton, CA) Patent Number: 5,317,010 Date filed: October 10, 1991 Abstract: Analogues of bovine and human parathyroid hormone, wherein twenty-fifth, twenty-six and twenty-seventh positions of the natural hormone, Arg-Lys-Lys- each have been substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val have been found to retain bone cell effect with minimal effects on blood pressure and smooth muscle, including cardiac muscle. It has further been found that this effect can be obtained by using a synthetic PTH containing only the first 34 amino acids of PTH, with substitution at the twenty-fifth, twenty-sixth and twenty-seventh amino acids as described. These analogues of PTH also are effective in the treatment of osteoporosis and other bone diseases. Excerpt(s): This invention relates to analogues of parathyroid hormone which, by substitution at the twenty-fifth, twenty-six and twenty-seventh positions of natural parathyroid hormone, have been found to affect calcium change in bone cells without producing the typical effects of parathyroid hormone on systolic and diastolic blood pressure, the effects on smooth muscle relaxation, vascular smooth muscle calcium change as well as positive chronotropic and inotropic effects on the heart.... Parathyroid hormone (hereinafter, PTH) is produced by the parathyroid gland and is involved in the control of calcium levels in blood. It is a hypercalcemic hormone, elevating blood calcium levels. PTH is a polypeptide and the amino acid sequences of bovine and human PTH are closely related. Only the residues at locations one, seven and sixteen differ between the two. Synthetic polypeptides containing the first thirty-four residues of PTH may be prepared using the method disclosed by Erickson and Merrifield, The Proteins, Neurath et al. , Eds., Academic Press, New York, 1976, page 257, preferably as modified by the method of Hodges et al., Peptide Research, 1, 19 (1988).... When serum calcium is reduced to below a "normal" level, the parathyroid gland releases PTH and resorption of bone calcium and increased absorption of calcium from the intestine, as well as renal reabsorption of calcium, occur. Web site: http://www.delphion.com/details?pn=US05317010__

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Parathyroid hormone analogues useful for treatment of osteoporosis and disorders of calcium meatabolism in mammals Inventor(s): Strewler; Gordon J. (San Francisco, CA), Nissenson; Robert A. (Burlingame, CA), Cohen; Fred E. (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 5,849,695 Date filed: January 13, 1993 Abstract: The present invention relates polypeptide analogs which have agonist or antagonist or tissue selection properties relative to parathyroid hormone (PTH), parathyroid hormone-like protein (PLP) or parathyroid-related protein (PTHrP). The

Patents 415

serine amino acid at position 3, the glutamine amino acid at position 6, the histidine amino acid at position 9 or combinations thereof are substituted by other natural or synthetic amino acids. Preferably, a human PTH fragment of about 34 amino acids is sufficient for pharmacological activity. These polypeptides are useful as agonists or antagonists in the treatment of a human being for disease conditions of cancer, osteoporosis, hypercalcemia, or hyperparathyroid disease conditions. The invention also concerns a method of performing certain assays using the modified peptides, and based on the results of the assays falling within preset limits, selecting those modified peptides which shall be useful in the treatment of disease conditions. Excerpt(s): The present invention relates to polypeptide analogs which have agonist or antagonist properties relative to parathyroid hormone, (PTH), parathyroid hormone-like protein (PLP) or parathyroid-related protein (PTHrP). The serine amino acid at position 3, the glutamine amino acid at position 6, or the histidine amino acid at position 9, or combinations thereof, are substituted by other natural or synthetic amino acids. Preferably, a human PTH fragment of about 34 amino acids is sufficient for useful pharmacological activity. These polypeptides are useful in the treatment of a human being for conditions of cancer, osteoporosis, hypercalcemia, or hyperparathyroid disease.... The search for potent PTH agonists and/or antagonists has been intensive. The availability of potent and specific antagonists would provide a powerful research tool for the study of the mechanism of action and physiological and/or pathological role for PTH. Some research efforts have resulted in in vitro PTH antagonists. However, during in vivo evaluation of these polypeptides, they often did not have any clear antagonist properties.... For a number of polypeptide hormones, discrete, localized structural modifications are sufficient to convert a receptor agonist to a competitive receptor antagonist. Underlying this observation is the idea that the distinct functions of receptor-binding of hormone and initiation of biologic action, are signalled by distinct structural domains within the polypeptide hormone sequence. Parathyroid hormone (PTH) is a well-studied example of such a polypeptide hormone. PTH(1-34) is a full agonist of the native 84 amino-acid hormone with respect to adenylate cyclase activation in canine renal membranes (See Ref. 1 below. The letters used are the conventional ones to describe an amino acid sequence). Amino-terminal truncation results in polypeptides that are competitive antagonists of PTH-stimulated adenylate cyclase. Thus ›Tyr.sup.34 !bPTH(7-34)amide retains moderate affinity for renal PTH receptors, but does not have any agonist activity. Specific weak receptor binding activity is retained in a fragment as small as PTH(25-34) (Ref. 2). On the other hand, carboxyl-terminal truncations of PTH(134) produce agonists with progressively lower affinities. PTH(1-25) is reported to be essentially inactive (Ref. 3-5). The "receptor-binding domain" of PTH is believed to include amino acid residues 25-34 and the "activation domain" includes amino acid residues 1-6. Web site: http://www.delphion.com/details?pn=US05849695__ •

Pharmaceutical composition for treating osteoporosis Inventor(s): Komiyama; Osamu (Higashimurayama, JP), Kitamura; Kazuyuki (Sakado, JP), Tobe; Hiroyasu (Fujisawa, JP) Assignee(s): Hoechst Japan Limited (Tokyo, JP) Patent Number: 5,679,716 Date filed: September 27, 1996

416 Osteoporosis

Abstract: A therapeutic agent for osteoporosis comprising as an active ingredient xanthohumol. Xanthohumol obtained from hop extracts has a bone resorption inhibiting activity and is useful as a therapeutic agent for osteoporosis. Excerpt(s): This invention relates to a pharmaceutical composition for treating osteoporosis.... Japan is now rushing into an advanced age society which has never been experienced in the past, and simultaneously the increase in the number of osteoporotic patients now becomes a serious problem. The increased number of the aged who are bedridden due to bone fracture compels an enormous increase in medical expenditures.... As a therapeutic agent for osteoporosis, vitamin D preparations, calcitonin preparations, ipriflavone preparations and the like have been used in Japan. However, there has not been established a method for radically treating osteoporosis, but simply a symptomatic treatment is applied at this stage. Osteoporosis develops when a balance between bone formation and bone resorption is lost, and consequently it is considered feasible to prevent osteoporosis by promoting bone formation or by inhibiting bone resorption. Web site: http://www.delphion.com/details?pn=US05679716__ •

Pharmaceutical composition for treatment of osteoporosis Inventor(s): Miura; Tomoshi (Hyogo, JP), Ohara; Hiroyuki (Hyogo, JP), Aonuma; Shinichiro (Hyogo, JP) Assignee(s): Nippon Zoki Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 5,116,828 Date filed: October 25, 1990 Abstract: A pharmaceutical composition for the treatment of osteoporosis comprises an estrogen and a thyroid hormone as effective ingredients. By using the estrogen in combination with the thyroid hormone, a more excellent activity of increasing bone amount can be obtained than in the case of administering the estrogen alone. Excerpt(s): The present invention relates to pharmaceutical compositions for the treatment of osteoporosis comprising an estrogen and a thyroid hormone as effective ingredients.... Osteoporosis is a disease which has been most notably observed among senile bone diseases and refers degenerative change by aging. In osteoporosis, a small impact leads to compression fracture of the spinal cord or bone fractures of the legs and arms, which cause pain or functional disorder.... As causes for osteoporosis, endocrine factors nutritional factors, physical factors, genetic factors, etc. have been considered; inter alia, osteoporosis sharply increases in postmenopausal women occurs at an early stage in women who underwent oophorectomy. From these facts, it is suggested that there might be a serious relationship between the incidence of osteoporosis and decrease in sex hormone, especially an estrogen, accompanied by menopause. Web site: http://www.delphion.com/details?pn=US05116828__

Patents 417

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Pharmaceutical compositions and dietary soybean food products for the prevention of osteoporosis Inventor(s): Shlyankevich; Mark (Waterbury, CT) Assignee(s): Bio-Virus Research Incorporated (San Matteo, CA) Patent Number: 5,424,331 Date filed: June 10, 1994 Abstract: A composition for the treatment or prevention of osteoporosis, is disclosed, which comprises:(a) 75 to 200 parts of one or more phytoestrogen compounds;(b) 0 to 100 parts of dried licorice root extract;(c) 300 to 600 parts of calcium contained in a biologically acceptable calcium salt;(d) 70 to 280 parts of magnesium contained in a biologically acceptable magnesium salt;(e) 4 to 25 parts of zinc contained in a biologically acceptable zinc salt;(f) 5 to 20 parts of beta-carotene;(g) 0.005 to 0.010 parts of Vitamin D as cholecalciferol; and(h) 6 to 12 parts of Vitamin E,in admixture with a biologically acceptable inert carrier. The new compositions are administered to a mammalian subject as either a pharmaceutical or as a dietary supplement. Excerpt(s): This invention relates to new pharmaceutical compositions and dietary soybean food products for the prevention of osteoporosis. More particularly, the invention relates to such pharmaceutical compositions and dietary soybean food products that contain natural phytoestrogens of the isoflavone or coumestan groups.... Osteoporosis is recognized as a major public health problem in Western countries, especially among elderly white women. See Cummings, S. R. et al, Epidemiol. Rev., 7:178 to 208 (1985). Postmenopausal osteoporotic fractures affect 1.5 million people each year. About 300,000 new cases of osteoporotic hip, 650,000 of vertebrae, and 200,000 of distal forearm fractures are reported annually in the USA. Mortality in the first year after hip fractures reaches 20%. See Cooper, C. et al, Amer. J. Epidem., 1001 to 1005 (1993) and Riggs, B. L., West. J. Med., 154:63 to 67 (1991). The estimated direct cost for treatment of these patients in the USA exceeds $6 to $10 billion annually. See Holbrook, T. L. et al, Lancet, 2:1046 to 1049 (1988) and the Riggs, B. L. reference cited above. Half of the survivors are unable to walk unassisted and 25% are confined to long term care in a nursing home.... Epidemiological and clinical observations strongly indicate that osteoporosis and fractures are related to aging. See once again Cummings, S. R. et al, Epidemiol. Rev., 7:178 to 208 (1985) and also Cummings, S. R. et al, Arch. Intern. Med., 149:2445 to 2448 (1989) and Ross, P. D. et al, Am. J. Epidem., 133:801 to 809 (1991). Particularly rapid loss of bone mass is noted in the first decade after menopause, and implicates estrogen deficiency as an etiological factor. Web site: http://www.delphion.com/details?pn=US05424331__

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Pharmaceutical compositions for the nasal delivery of compounds useful for the treatment of osteoporosis Inventor(s): Krstenansky; John Leonard (3401 Hillview Ave., P.O. Box 10850, Palo Alto, CA 94303), Radomsky; Michael Lloyd (3401 Hillview Ave., P.O. Box 10850, Palo Alto, CA 94303), Piazza; Christin Teresa (3401 Hillview Ave., P.O. Box 10850, Palo Alto, CA 94303), Nestor, Jr. John Joseph (3401 Hillview Ave., P.O. Box 10850, Palo Alto, CA 94303), Vickery; Brian Henry (3401 Hillview Ave., P.O. Box 10850, Palo Alto, CA 94303) Assignee(s): none reported Patent Number: 5,977,070 Date filed: August 29, 1995 Abstract: A pharmaceutical composition for the nasal delivery of compounds useful for treating osteoporosis, comprising an effective amount of a physiologically active truncated analog of PTH or PTHrp, or salt thereof, in which amino acid residues (22-31) form an amphipathic.alpha.-helix, said residues (22-31) selected from (SEQ ID NOS: 85, 86, 26, 27, 28, 29, and 30); an absorption enhancer selected from the group consisting of dimethyl-.beta.-cyclodextrin and the bile acid surfactants; and water is provided. Excerpt(s): This invention relates to pharmaceutical compositions for the treatment of osteoporosis via the nasal administration of therapeutically effective amounts of certain novel analogs of parathyroid hormone and parathyroid hormone related peptide.... Osteoporosis is the most common form of metabolic bone disease and may be considered the symptomatic, fracture stage of bone loss (osteopenia). Although osteoporosis may occur secondary to a number of underlying diseases, 90% of all cases appear to be idiopathic. Postmenopausal women are particularly at risk for idiopathic osteoporosis (postmenopausal or Type I osteoporosis). Another high risk group for idiopathic osteoporosis is the elderly of either sex (senile or Type II osteoporosis). Osteoporosis has also been related to corticosteroid use, immobilization or extended bed rest, alcoholism, diabetes, gonadotoxic chemotherapy, hyperprolactinemia, anorexia nervosa, primary and secondary amenorrhea, and oophorectomy.... In the various forms of osteoporosis, bone fractures, which are the result of bone loss that has reached the point of mechanical failure, frequently occur. Postmenopausal osteoporosis is characterized by fractures of the wrist and spine, while femoral neck fractures seem to be the dominant feature of senile osteoporosis. Web site: http://www.delphion.com/details?pn=US05977070__

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Predicting predisposition to osteoporosis Inventor(s): Hodgen; Gary D. (Norfolk, VA) Assignee(s): Eastern Virginia Medical Authority (Norfolk, VA) Patent Number: 4,740,364 Date filed: September 27, 1985 Abstract: A method of providing a diagnostic indicia which is predictive of the risk of a non-osteoporotic human being contracting osteoporosis as a consequence of being in a long-term hormonally agonadal state, which comprises the steps of determining the average ratio of calcium to creatinine in the urine or in the blood of that person, during a period when the person is ingesting only foodstuff sources of calcium and vitamin D, while in a hormonally gonadal state, and also while in a hormonally agonadal state;

Patents 419

determining the magnitude of the difference in the ratio obtained in the latter state compared to the former state, a large difference being predictive of a high risk of that person contracting osteoporosis. Excerpt(s): This invention relates to a method of predicting the risk of a nonosteoporotic human being contracting osteoporosis as a consequence of being in a longterm hormonally agonadal state and to a test kit for practicing this method.... Osteoporosis is a predictable sequalae in primates and other mammals to a long-term hormonally agonadal condition. Although it most frequently manifests itself in postmenopausal women in association with their longevity beyond the years of gonadal activity, it can occur in castrated males and females and in pre-menopausal women on long-term GnRH agonist or antagonist therapy, e.g., for the treatment of endometriosis or precocious puberty, or in instances of protracted amenorrhea due to extremes of exercise, anorexia or irradiation with or without chemotherapy affecting ovarian or testicular functions.... Few naturally occurring diseases adversely affect the quality and longevity of so many human lives as the sequelae to severe estrogen deficiency in the post-menopausal years. The prevalence of the disease is evident from the fact that about one woman in four will experience at least one bone fracture attributable to calcium depletion of the bone by the time she reaches the age of 60 years. Web site: http://www.delphion.com/details?pn=US04740364__ •

Prophylactic implant against fracture of osteoporosis-affected bone segments Inventor(s): Thomas; Wolfram (Rome, IT), Grundei; Hans (Lubeck, DE) Assignee(s): ESKA Implants GmbH & Co. (Lubeck, DE) Patent Number: 6,319,255 Date filed: June 18, 1999 Abstract: A prophylactic implant is provided for protecting osteoporosis-affected bone segments against fractures, in particular the neck of the femur, the vertebral column and the wrist. According to a proposed solution, the implant comprises a thin-walled hollow reinforcing body (1) having such a large number of passages (2) in its outer wall (3) that the ratio of the total area of the passages (2) to the total surface area is at least 1:2. Excerpt(s): The invention relates to a prophylactic implant against fractures of osteoporosis-affected bone segments.... There are millions of osteoporotic persons in Germany alone, who most frequently have other diseases of the locomotor system.... Osteoporosis is accompanied by a loss of the bone mass, which exceeds the natural agerelated bone disintegration. In addition, the quality of the microstructure of the bone tissue degrades. The loss of the bone mass, bone structure and function leads to clinical symptoms with lasting infirmities and fractures. Femoral neck fractures, fractures of the vertebral column and of the wrist are particularly widespread. Web site: http://www.delphion.com/details?pn=US06319255__

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Prophylactic, therapeutic agent for osteoporosis Inventor(s): Ohta; Atsutane (Saitama, JP), Hirayama; Masao (Saitama, JP), Adachi; Takashi (Saitama, JP) Assignee(s): Meiji Seika Kaisha, Ltd. (Tokyo, JP) Patent Number: 6,417,224 Date filed: September 5, 2000 Abstract: The prophylactic, therapeutic agent for osteoporosis of the invention is a combination of an indigestible oligosaccharide with phytoestrogen which inhibits bone loss. The action of inhibiting the reduction of bone density can be improved remarkably by combining the indigestible oligosaccharide with phytoestrogen. Excerpt(s): This invention relates to a prophylactic, therapeutic agent capable of inhibiting bone loss which is found in osteoporosis.... In Japan, the population of aged persons is sharply increasing, and various social problems occur therewith. One of the problems is in nursing of the aged persons. Most of the aged persons who require nursing are bedridden, except for persons suffering from cranial nerve troubles, such as dementia. The greatest cause which makes aged persons bedridden is bone fracture caused by osteoporosis. Therefore, it is very important to prevent osteoporosis.... Osteoporosis is caused by trouble in the relationship between resorption and formation of the bone, and various reasons are pointed out, such as metabolic troubles and internal secretion troubles. Various medicines have already been developed. Web site: http://www.delphion.com/details?pn=US06417224__

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Regimen for treating osteoporosis Inventor(s): Flora; Lawrence (Fairfield, OH), Floyd; Benjamin F. (Cincinnati, OH) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 4,761,406 Date filed: June 6, 1985 Abstract: A method for treating or preventing osteoporosis utilizing a cyclic regimen comprising alternating for two or more cycles the administration of a bone resorption inhibiting polyphosphonate and a no treatment (rest) period. Further disclosed is a kit for use in implementing this method of treatment. Excerpt(s): The present invention relates to a method of treating or preventing osteoporosis. Specifically, the present invention relates to a well-defined regimen for the intermittent dosing, in a limited amount for a limited time, of certain polyphosphonate compounds. The present invention further relates to a kit to be used by patients for effectively implementing the method of treatment of the present invention.... Osteoporosis is the most common form of metabolic bone disease. Although it may occur secondary to a number of underlying diseases, 90% of all cases appear to be idiopathic. Postmenopausal women are particularly at risk to idiopathic osteoporosis ("postmenopausal osteoporosis"). Another high risk group for idiopathic osteoporosis are the elderly of either sex ("senile osteoporosis").... In the various forms of osteoporosis, bone fractures, which are the result of bone loss that has reached the point of mechanical failure, frequently occur. Postmenopausal osteoporosis is characterized by fractures of the wrist and spine. Femoral fractures seem to be the dominant feature of senile osteoporosis.

Patents 421

Web site: http://www.delphion.com/details?pn=US04761406__ •

Regimen for treatment or prophylaxis of osteoporosis Inventor(s): Strein; Klaus (Hemsbach, DE) Assignee(s): Boehringer Mannheim GmbH (Mannheim, DE) Patent Number: 5,366,965 Date filed: January 29, 1993 Abstract: Methods for treating or preventing osteoporosis, including regimens for intermittent dosing of bone resorption inhibiting polyphosphonate compound or a pharmaceutically acceptable salt or ester of any such compound. Excerpt(s): The present invention relates to methods for treating or preventing osteoporosis. More particularly, the present invention relates to well-defined regimens for intermittent dosing of bone resorption inhibiting polyphosphonate compounds. The present invention also relates to a kit to be used by patients for treatment in accordance with the treatment regimen.... Post menopausal osteoporosis is by far the most common form of osteoporosis. Various therapies have been approved in the United States, including the administration of oral estrogen, sodium fluoride, and, on an experimental basis, intranasal calcitonin. However, the widespread use of these agents has been limited by various factors, including expense, safety and lack of proved efficacy. A search continues in the art for an inexpensive, safe and effective treatment for osteoporosis.... Organic bisphosphonate compounds have been found to inhibit bone resorption which is mediated by osteoclasts. The earliest publication describing the administration of diphosphonates for treatment of osteoporosis was in 1979 when Frost described the "Treatment of osteoporosis by manipulation of coherent bone cell populations." Frost continued a series of publications (Frost, "The ADFR Concept and Monitoring It:" in Bone Histomorphometry 1980, 317-321; Frost, "The Evolution of Osteoporosis Therapy" in Orthopedic Clinics of North America, 12, 603-610, 1981; Frost, "Coherence Treatment of Osteoporosis," Orthopedic Clinics of North America, Vol. 12, 649-669, 1981; and others). This coherence concept has been modified by several other authors. In principle, it consists of a stimulation of bone turnover with phosphorus or parathyroid hormone, followed by blocking the resorption with intermittent therapy of blocking agents such as calcitonin or diphosphonates. This therapy, although theoretically very attractive, did not find widespread application because of the difficulty in determining a correct dose for an individual patient and the correct period of time required for stimulation and suppression of individual bone remodelling sites (without exerting an effect on formation). It appears that somewhere between three days and three weeks, most resorption sites should be suppressed. However, no exact information is available anywhere to unequivocally prove this hypothesis. Web site: http://www.delphion.com/details?pn=US05366965__

422 Osteoporosis

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Simultaneous bicarbonate

treatment

of

osteoporosis

and

hypertension

with

potassium

Inventor(s): Sebastian; Anthony (San Francisco, CA), Morris, Jr. R. Curtis (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 5,496,569 Date filed: April 2, 1993 Abstract: A method for simultaneously treating osteoporosis and hypertension in the same individual by the administration of pharmaceutically acceptable alkalinizing potassium salts, such as potassium bicarbonate, preferably in the form of a dietary supplement. Excerpt(s): This invention concerns novel methods for simultaneously treating osteoporosis and hypertension in the same individual and, more particularly, involves the administration for such purpose of pharmaceutically acceptable alkalinizing potassium salts, such as potassium bicarbonate.... Osteoporosis is a metabolic bone disease characterized pathologically by an absolute decrease in the amount of bone, and clinically by increased susceptibility to fractures. Hypertension is an insidious disease in which the blood pressure of an individual is abnormally increased.. It is clinically recognized as an elevation of systolic arterial blood pressure of 150 mm Hg or greater and/or elevation of diastolic arterial blood pressure of 90 mm Hg or higher.... Calcium bone deficiency is believed to be one of the factors which contributes to the pathogenesis of osteoporosis. Riggs, in Cecil Textbook of Medicine, Ed(s) Wyngaarden et al., (1985), p. 1456; Nordin, (1985), Lancet 2:720; Fujita, (1986), Mineral Electrolyte Metab. 12:149-156; Heaney, in Osteoporosis II Ed(s), Bonzel, (1979), p. 101; and Heaney, (1982), J. Lab. Clin. Med. 100:309. On the other hand, it has long been recognized that the blood pressure of a substantial proportion of those patients afflicted with "essential hypertension" (hypertension whose cause is not readily apparent) may be reduced by restriction of dietary sodium chloride. Simpson, F.O. in Hypertension: Pathophysiology, Diagnosis, and Management, Eds. Laragh et al. (1990), pp. 205-215. Treatment of persons suffering from both osteoporosis and hypertension is thus complicated by the need to increase calcium bone retention to ameliorate the osteoporosis and the desirability of decreasing sodium and chloride retention to ameliorate hypertension. Web site: http://www.delphion.com/details?pn=US05496569__ •

Simutaneous treatment of osteoporosis and hypertension Inventor(s): Sebastian; Anthony (San Francisco, CA), Morris, Jr. R. Curtis (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 5,766,640 Date filed: June 5, 1995 Abstract: A method for simultaneously treating osteoporosis and hypertension in the same individual by the administration of pharmaceutically acceptable alkalinizing potassium salts, such as potassium bicarbonate, preferably in the form of a dietary supplement.

Patents 423

Excerpt(s): This invention concerns novel methods for simultaneously treating osteoporosis and hypertension in the same individual and, more particularly, involves the administration for such purpose of pharmaceutically acceptable alkalinizing potassium salts, such as potassium bicarbonate.... Osteoporosis is a metabolic bone disease characterized pathologically by an absolute decrease in the amount of bone, and clinically by increased susceptibility to fractures. Hypertension is an insidious disease in which the blood pressure of an individual is abnormally increased. It is clinically recognized as an elevation of systolic arterial blood pressure of 150 mm Hg or greater and/or elevation of diastolic arterial blood pressure of 90 mm Hg or higher.... Calcium bone deficiency is believed to be one of the factors which contributes to the pathogenesis of osteoporosis. Riggs, in Cecil Textbook of Medicine, Ed(s) Wyngaarden et al., (1985), p. 1456; Nordin, (1985), Lancet 2:720; Fujita, (1986), Mineral Electrolyte Metab. 12:149-156; Heaney, in Osteoporosis II Ed(s), Bonzel, (1979), p. 101; and Heaney, (1982), J. Lab. Clin. Med. 100:309. On the other hand, it has long been recognized that the blood pressure of a substantial proportion of those patients afflicted with "essential hypertension" (hypertension whose cause is not readily apparent) may be reduced by restriction of dietary sodium chloride. Simpson, F. O. in Hypertension: Pathophysiology, Diagnosis, and Management, Eds. Laragh et al. (1990), pp. 205-215. Treatment of persons suffering from both osteoporosis and hypertension is thus complicated by the need to increase calcium bone retention to ameliorate the osteoporosis and the desirability of decreasing sodium and chloride retention to ameliorate hypertension. Web site: http://www.delphion.com/details?pn=US05766640__ •

Slow-release sodium fluoride tablet and method for treatment of osteoporosis Inventor(s): Walsdorf; Neill B. (Dallas, TX), Pak; Charles Y. C. (Dallas, TX) Assignee(s): Board of Regents, The University of Texas System (Austin, TX), Mission Pharmacal Company (San Antonio, TX) Patent Number: 4,904,478 Date filed: October 22, 1987 Abstract: A novel slow-release sodium fluoride preparation and its use. Such slowrelease sodium preparation comprises carnauba wax and talc and may be used to provide a safe but effective level of fluoride in serum, optimal for the treatment of osteoporosis. Gastrointestinal side effects are minimized by limiting the amount of fluoride released in the stomach and rheumatic complications are reduced by avoiding toxic levels of fluoride is serum. The amount of fluoride absorbed is nevertheless sufficient to stimulate bone formation and prevent fractures. Thus, the maintenance of serum fluoride as encompassed in this invention, allows for a safe and effective treatment of osteoporosis. Excerpt(s): Osteoporosis is a common disabling bone disease, particularly in postmenopausal women. Gradual loss of bone makes it porous and weak. Fracture of spine, hip and forearm frequently develop even without significant trauma.... Once the osteoporotic disease has developed, so much bone mass may already have been lost such that treatments directed at preventing further bone loss (for example, calcium supplements) would likely be of limited value. An ideal goal of therapy in patients with established osteoporosis with fracture is to provide a treatment program that will increase bone mass and restore "lost" bone. Unfortunately, most available treatment programs have failed to augment bone mass (Pak, The Menopause, Edit. J. J. Buchsbaum Springer-Verlag, 1983, pp. 35-54).... Sodium fluoride may be one agent capable of

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making more bone in osteoporosis. This possibility was first recognized in 1932, when Moller and Gudjonsson noted skeletal sclerosis in subject with overexposure with cryolite rich in fluoride (Acta Radiol., Vol. 13, 1932, pp. 269-294). It is now known that fluoride causes proliferation and increases the activity of osteoblasts, cells responsible for bone formation (Farley et al., Science, Vol. 222, 1983, pp. 330-332). When fluoride alone is given to patients with osteoporosis, the newly-formed bone is poorly mineralized (that is, deficient in calcium phosphate). However, when adequate calcium supplementation is provided along with fluoride, formation of mineralized bone may be stimulated (Jowsey et al., Amer. J. Med., Vol. 53, 1972, pp. 43-49). Using sodium fluoride (50-60 mg/day) with calcium supplement (800-1500 mg elemental calcium/day), formation of new bone has been shown on actual microscopic examination of biopsied bone (Briancon and Meunier, Orthop. Clin. North Amer., Vol. 12, 1998, pp. 629-648). Moreover, the rate of bone fracture was shown to be significantly reduced by treatment, compared to that of the untreated group (Riggs et al., N. Engl. J. Med., Vol. 306, 1982, pp. 446-450). Thus, there are sufficient references to suggest that long-term treatment with sodium fluoride could be effective in treating established osteoporosis. Web site: http://www.delphion.com/details?pn=US04904478__ •

Slow-release sodium fluoride tablet, method of making, and method of treatment of osteoporosis Inventor(s): Walsdorf; Neill B. (San Antonio, TX), Pak; Charles Y. C. (Dallas, TX) Assignee(s): Board of Regents, University of Texas System (Austin, TX), Mission Pharmacal (San Antonio, TX) Patent Number: 4,726,952 Date filed: March 21, 1986 Abstract: A novel use for a slow-release sodium fluoride preparation. Such slow-release sodium preparation is shown to provide a safe but effective level of fluoride in serum, optimal for the treatment of osteoporosis. It minimizes gastrointestinal side effects by limiting the amount of fluoride released in the stomach and it reduces rheumatic complications by avoiding toxic levels of fluoride in serum. The amount of fluoride absorbed is nevertheless sufficient to stimulate bone formation and prevent fractures. Thus, the maintenance of serum fluoride as encompassed in this invention, allows for a safe and effective treatment of osteoporosis. Excerpt(s): Osteoporosis is a common disabling bone disease, particularly in postmenopausal women. Gradual loss of bone makes it porous and weak. Fracture of spine, hip and forearm frequently develop even without significant trauma.... Once the osteoporotic disease has developed, so much bone mass may already have been lost such that treatments directed at preventing further bone loss (for example, calcium supplements) would likely be of limited value. An ideal goal of therapy is patients with established osteoporosis with fracture is to provide a treatment program that will increase bone mass and restore "lost" bone. Unfortunately, most available treatment programs have failed to augment bone mass (Pak, The Menopause, Edit. J. J. Buchsbaum Springer-Verlag, 1983, pp. 35-54).... Sodium fluoride may be one agent capable of making more bone in osteoporosis. This possibility was first recognized in 1932, when Moller and Gudjonsson noted skeletal sclerosis in subject with overexposure with cryolite rich in fluoride (Acta Radiol., Vol. 13, 1932, pp. 269-294). It is now known that fluoride causes proliferation and increases the activity of osteoblasts, cells responsible for bone formation (Farley et al., Science, Vol. 222, 1983, pp. 330-332). When fluoride

Patents 425

alone is given to patients with esteoporosis, the newly-formed bone is poorly mineralized (that is, deficient in calcium phosphate). However, when adequate calcium supplementation is provided along with fluoride, formation of mineralized bone may be stimulated (Jowsey et al., Amer. J. Med., Vol. 53, 1972, pp. 43-49). Using sodium fluoride (50-60 mg/day) with calcium supplement (800-1500 mg elemental calcium/day), formation of new bone has been shown on actual microscopic examination of biopsied bone (Briancon and Meunier, Orthop. Clin. North Amer., Vol. 12, 1981, pp. 629-648). Moreover, the rate of bone fracture was shown to be significantly reduced by treatment, compared to that of the untreated group (Riggs et al., N. Engl. J. Med., Vol. 306, 1982, pp. 446-450). Thus, there are sufficient references to suggest that long-term treatment with sodium fluoride could be effective in treating established osteoporosis. Web site: http://www.delphion.com/details?pn=US04726952__ •

System for preventing and curing osteoporosis and obesity Inventor(s): Hirano; Shinnosuke (Kanagawa, JP) Assignee(s): Kohgen Kizai Kabushiki Kaisha (Yokohama, JP) Patent Number: 5,836,997 Date filed: November 25, 1996 Abstract: A system for preventing and curing osteoporosis and obesity, which has a mat essentially consisting of a first sheet made from a semiconductive or insulating material and having a volume resistivity of less than 10.sup.4.OMEGA..cm and a second sheet made from a semiconductive or insulating material, laminated on the first sheet and having a volume resistivity of 10.sup.4.OMEGA..cm or more; an electric power source; an electrical circuit to apply DC voltage of 25-800 to the first sheet; and a control unit. A normal person or patient is made contact with the mat, so as to put his body in electrostatic field to be formed on the mat. In another embodiment, a third sheet of a material having a volume resistivity of more than 10.sup.12.OMEGA..cm is used such that the first sheet is sandwiched between the third and second sheets. Excerpt(s): The present invention relates to a system for preventing and curing osteoporosis and obesity, by putting a human body in an electrostatic field.... In recent years, medical techniques have greatly advanced to prolong the average span of human life and as a result, so-called "adult and senior diseases" tend to increase. Therefore, it has been emphasized in the medical world that so-called "Health medical science" will be required, in which each individual controls his health by himself to prevent a disease or pays his possible effort to overcome the diseases.... Among the diseases, osteoporosis has often been found in senior persons and women in menopause and it has been said that number of the patients with this disease reaches 6 million or more, even in Japan only. Web site: http://www.delphion.com/details?pn=US05836997__

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Techniques for controlling osteoporosis using non-invasive magnetic fields Inventor(s): Smith; Stephen D. (Lexington, KY), McLeod; Bruce R. (Bozeman, MT), Liboff; Abraham R. (Birmingham, MI) Assignee(s): Life Resonances, Inc. (Bozeman, MT) Patent Number: 5,267,939 Date filed: October 10, 1991 Abstract: An apparatus and method for preventing and therapeutically treating osteoporosis are provided. The apparatus includes a magnetic field generator for producing a controlled, fluctuating, directionally oriented magnetic field parallel to a predetermined axis projecting through the target bone or skeletal system. In one aspect, a field detector samples the magnetic flux density along the predetermined axis and provides a signal to a microprocessor which determines the average value of the flux density. The applied magnetic field is oscillated at predetermined frequencies to maintain a preselected ratio of frequency to average flux density which controls osteoporosis. This ratio is maintained by adjusting the frequency of the fluctuating magnetic field and/or by adjusting the intensity of the applied magnetic field as the composite magnetic flux density changes in response to changes in the local magnetic field to which the target bone is subjected. Excerpt(s): The present invention relates generally to methods and apparatus for controlling osteoporosis. More specifically, the present invention discloses the use of non-invasive magnetic fields for the prevention and treatment of osteoporosis. The present invention also relates to a method for providing an animal model for the study of osteoporosis.... It is known that in the bone disease, "osteoporosis," there is a decrease in bone density and an increase in bone porosity which significantly weakens the bone structure. More specifically, there is a progressive loss of bone mineral matrix, together with non-ossified material, such that the bones become thin and brittle. The weakened bone is susceptible to fracture upon even minor impact. While the exact etiology of osteoporosis is not fully understood, it is known that the demineralization of bone tissue is widespread throughout the skeletal system. As will be appreciated by those skilled in the art, in bone formation, osteoblasts and fibroblasts generate collagen which is then mineralized by calcium phosphate which, in turn, is converted to hydroxyapatite. It is also known that cells known as osteoclasts play an important role in the resorption of bone. Under normal conditions, bone remodeling, i.e. formation and resorption, occurs in coupled cycles to maintain equilibrium of bone mass. Bone also serves as a reservoir of calcium which is utilized in numerous cellular processes. It is believed that serum calcium regulation is mediated by the actions of parathyroid hormone, vitamin B, calcitonin, and various other local and systemic hormones. However, even if a detailed understanding of the pathways involved in bone remodeling remains unclear, it is apparent that the origin of osteoporosis is related to cell dysfunction as opposed to merely mineral imbalance.... A number of factors are known to increase an individual's predisposition to osteoporosis. It is a disease associated with aging, occurring somewhat later in men than in women. One of the most significant predisposing factors is the onset of menopause. A significant percentage of elderly women are afflicted with osteoporosis. It often leads to spinal compression fractures and collapse of vertebral bodies which may produce a dramatic change in posture. Long bone and hip fractures often lead to fatal complications. While estrogen replacement therapy has been attempted for the treatment of osteoporosis, its safety represents a problem and its efficiency is in question. Other pharmacologic treatments have also been attempted such as calcium, vitamin D and calcitonin supplements, but none have proved successful.

Patents 427

Therefore, it would be desirable to provide a method and apparatus by which osteoporosis could be treated without the need for drug therapy. Web site: http://www.delphion.com/details?pn=US05267939__ •

Tissue antigen and diagnostic method for human osteoporosis using the same Inventor(s): Watanabe; Hiroshi (Hiki, JP), Akita; Mikio (Kawagoe, JP), Gotoh; Kohsei (Higashimatsuyama, JP), Kitamura; Kazuyuki (Sakado, JP) Assignee(s): Hoechst Japan Limited (Tokyo, JP) Patent Number: 5,494,802 Date filed: March 17, 1993 Abstract: An animal tissue antigen for osteoporotic patients that reacts with antibody in a serum of human osteoporotic patients, but does not react with that in normal human serum. Preferably, a specific antigen for osteoporotic patients in rat or mouse epithelium of tongue mucous membrane, epithelium of tracheal mucous membrane, upper lip epidermis or follicular epithelium containing upper lip hair shafts, or a specific antigen for osteoporotic patients contained in cultured cells of a human squamous cell tongue carcinoma cell lines such as SCC-9 and fibroblast cell lines such as MRC-5. Osteoporosis can be both specifically and easily diagnosed by bringing the above-mentioned antigen in contact with a serum of a subject and then testing for the presence of an antigenantibody reaction. Excerpt(s): The present invention relates to a tissue antigen that reacts with an antibody particularly existing in a serum of osteoporotic patients. Moreover, the present invention also relates to a novel method for immunochemical diagnosis of osteoporosis by detection of autoantibody to the specific antigen.... Osteoporosis is a disease characterized in that bone mineral density is reduced though bone composition is normal. Osteoporosis is seen particularly and frequently in women and postmenopausal osteoporosis is observed at a high frequency accompanying menopause in women of 40 years and older. On the other hand, so-called senile osteoporosis is observed in both men and women starting at 70 years of age. Although clinical symptoms are not especially observed while reduction of bone mineral density is mild, as the extent of that depletion becomes pronounced, bone fractures and deformation begin to occur. In particular, since the predominant site of these fractures is the spinal column, pressure fractures of vertebrae and symptoms of lower back pain due to deformation of the spinal column appear. Moreover, fractures of the neck of the femur and pelvis occasionally deprive patients of movement. Therefore, the establishment of a reliable and simple diagnostic method that allows discovery of osteoporosis as early as possible while also allowing effective treatment is strongly desired.... Current methods employed for diagnosis of osteoporosis are dependent on physical techniques such as X-ray photographs. Not only is this technique both bothersome and time-consuming, it also has the shortcoming of only being able to be used during the latter stages of said disease when reduction of bone mineral density has become conspicuous. Although efforts have been made to detect factors relating to metabolic bone diseases, such as osteocalcin, parathyroid hormone (PTH), pyridinoline and C-terminal procollagen, from blood and urine for use in diagnosis, considerable problems still remain in terms of specificity and sensitivity. Web site: http://www.delphion.com/details?pn=US05494802__

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Treating osteoporosis with humulones Inventor(s): Tobe; Hiroyasu (Kanagawa, JP), Kitamura; Kazuyuki (Saitama, JP) Assignee(s): Hoechst Japan Limited (Tokyo, JP) Patent Number: 5,604,263 Date filed: April 10, 1995 Abstract: A pharmaceutical composition for treating osteoporosis which comprises as an active ingredient an effective amount of one or more compounds selected from thegroup comprising humulone, cohumulone, adhumulone, isohumulone, isocohumulone and isoadhumulone in combination with a pharmaceutically acceptable carrier or excipient. Humulone, cohumulone, adhumulone are the compounds belonging to.alpha. acids which are an ingredient extracted from hops, whilst isohumulone, isocohumulone and isoadhumulone are the compounds belonging to iso.alpha. acid derivatives which are isomers of.alpha. acids.The above described compounds have a bone resorption inhibiting activity and are useful for treating osteoporosis. Excerpt(s): This invention relates to a pharmaceutical composition for treating osteoporosis.... Japan is now rushing into an advanced age society which has never been experienced in the past, and simultaneously the increase in the number of osteoporotic patients now becomes a serious problem. The increased number of the aged who are bedridden due to bone fracture compels an enormous increase in medical expenditures.... As a therapeutic agent for osteoporosis, vitamin D preparations, calcitonin preparations, ipriflavone preparations and the like have been used in Japan. However, there has not been established a method for radically treating osteoporosis, but simply a symptomatic treatment is applied at this stage. Osteoporosis develops when a balance between bone formation and bone resorption is lost, and consequently it is considered feasible to prevent osteoporosis by promoting bone formation or by inhibiting bone resorption. Web site: http://www.delphion.com/details?pn=US05604263__

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Treatment for osteoporosis using GRF or a biologically active analog thereof Inventor(s): Recker; Robert R. (3309 S. 116th St., Omaha, NE 68144) Assignee(s): none reported Patent Number: 4,870,054 Date filed: July 31, 1987 Abstract: A method of treating osteoporosis, especially post-menopausal osteoporosis, by administering on a periodic but regular basis to a patient growth hormone releasing factor, GRF(1-44)-NH.sub.2, or a biologically active analog thereof, and continuing the administration until bone mass increases and the patient's calcium balance becomes positive and indicates a mineral accumulation in the skeleton. Excerpt(s): In the past 15 years, the physiology of pituitary function has become better understood. The pituitary gland secretes several hormones which in turn control secretion of other glands such as the adrenal, the thyroid, and the reproductive organs. In recent times, a series of pituitary releasing hormones have been discovered, and characterized. The most recent of these is growth hormone releasing factor GRF(1-44)NH.sub.2. This discovery occurred in 1982 when two investigators independently, but almost simultaneously, reported the presence of a substance occurring in a pancreatic

Patents 429

tumor which caused a clinical syndrome called acromegaly. In their respective journal articles, they reported that the tumors were found to contain a peptide consisting of 44 amino acids, which when purified and injected into animals or humans was found to stimulate growth hormone production intensively, Science, Vol. 218, Nov. 5, 1982, pp. 585-87 and Nature, Vol. 300, Nov. 18, 1982, pp. 276-78. Recently, some researchers have successfully, synthetically synthesized growth hormone releasing factor, and very recently it has been produced by genetic engineering procedures using bacterial cultures. For literature relating to synthetic production of growth hormone releasing factor see Gelato, M. C. et al., 1983, "The Effects of Growth Hormone Releasing Factor in Man," Journal of Clinical Endrocrinology and Metab., 57674.... Growth hormone releasing hormone factor is a peptide of 44 amino acids. There are analogs containing 27-40 amino acids. It is one of a group of peptides secreted by the hypothalamus, and it normally stimulates pituitary growth hormone release. It is important in normal growth and development during childhood.... Recently, it has been reported that GRF(1-44)NH.sub.2 may have some promise in the treatment of growth hormone deficiency (see Journal of Clinical Endrocrinology and Metab., 59:1, 1984 and Journal of Clinical Endrocrinology and Metab., 58:1043, 1984). However, GRF(1-44)-NH.sub.2 has not yet been marketed or suggested for any specific clinical disease treatment. It has been suggested as likely to be useful for testing pituitary function by using doses to stimulate pituitary secretion of growth hormone factor. The theory being that in the event it does not so stimulate, one knows that the pituitary gland is not functioning properly. However, when used to test pituitary function GRF(1-44)-NH.sub.2 is administered intravenously by a single bolus injection and blood levels of growth hormone are measured in serum specimens obtained at approximately half hour intervals for four hours. If growth hormone levels fail to rise, then the presumption is made that the pituitary gland is incapable of secreting growth hormone. This is a single dose for diagnostic purposes, not a periodic and regular treatment pattern. Web site: http://www.delphion.com/details?pn=US04870054__ •

Treatment for osteoporosis using growth hormone releasing factor (GRF) in combination with parathyroid hormone (PTH) Inventor(s): Recker; Robert R. (3309 S. 116th St., Omaha, NE 68144) Assignee(s): none reported Patent Number: 5,164,368 Date filed: November 4, 1991 Abstract: A method of treating osteoporosis, especially postmenopausal osteoporosis, by administering on a periodic but regular basis to a patient growth hormone releasing factor, GRF(1-44)-NH.sub.2, or a biologically active analog thereof, and concurrently administering parathyroid hormone, PTH(1-34)-NH.sub.2 and continuing the administration until bone mass increases and the patient's calcium balance becomes positive and indicates a mineral accumulation in the skeleton. Excerpt(s): In the past 20 years, the physiology of pituitary function has become better understood. The pituitary gland secretes several hormones which in turn control secretion of other glands such as the adrenal, the thyroid, and the reproductive organs. In recent times, a series of pituitary releasing hormones have been discovered, and characterized. The most recent of these is growth hormone releasing factor GRF(1-44)NH.sub.2. This discovery occurred in 1982 when two investigators independently, but almost simultaneously, reported the presence of a substance occurring in a pancreatic

430 Osteoporosis

tumor which caused a clinical syndrome called acromegaly. In their respective journal articles, they reported that the tumors were found to contain a peptide consisting of 44 amino acids, which when purified and injected into animals or humans was found to stimulate growth hormone production intensively, Science, Vol. 218, Nov. 5, 1982, pp. 585-87 and Nature, Vol. 300, Nov. 18, 1982, pp. 276-78. Recently, some researchers have successfully, synthetically synthesized growth hormone releasing factor, and very recently it has been produced by genetic engineering procedures using bacterial cultures. For literature relating to synthetic production of growth hormone releasing factor, see Gelato, M. C. et al., 1983, "The Effects of Growth Hormone Releasing Factor in Man," Journal of Clinical Endrocrinology and Metab., 57674.... Growth hormone releasing hormone factor is a peptide of 44 amino acids. There are analogs containing 27-40 amino acids. It is one of a group of peptides secreted by the hypothalamus, and it normally stimulates pituitary growth hormone release. It is important in normal growth and development during childhood.... Recently, it has been reported that GRF(1-44)NH.sub.2 may have some promise in the treatment of growth hormone deficiency (see Journal of Clinical Endrocrinoloqy and Metab., 59:1, 1984 and Journal of Clinical Endrocrinoloqy and Metab., 58:1043, 1984). However, GRF(1-44)-NH.sub.2 has not been marketed or suggested for any specific clinical disease treatment. It has been suggested as likely to be useful for testing pituitary function by using doses to stimulate pituitary secretion of growth hormone. The theory being that in the event it does not so stimulate, one knows that the pituitary gland is not functioning properly. However, when used to test pituitary function, GRF(1-44)-NH.sub.2 is administered intravenously by a single bolus injection and blood levels of growth hormone are measured in serum specimens obtained at approximately half hour intervals for four hours. If growth hormone levels fail to rise, then the presumption is made that the pituitary gland is incapable of secreting growth hormone. This is a single dose for diagnostic purposes, not a periodic and regular treatment pattern. Web site: http://www.delphion.com/details?pn=US05164368__ •

Treatment for osteoporosis using hGRF(1-40)NH.sub.2 Inventor(s): Recker; Robert R. (3309 S. 116th St., Omaha, NE 68144) Assignee(s): none reported Patent Number: 4,710,382 Date filed: September 27, 1985 Abstract: A method of treating osteoporosis, especially postmenopausal osteoporosis, by administering on a periodic but regular basis to a patient growth hormone releasing factor, GRF(1-44)--NH.sub.2, or a biologically active analog thereof, and continuing the administration until bone mass increases and the patient's calcium balance becomes positive and indicates a mineral accumulation in the skeleton. Excerpt(s): In the past 15 years, the physiology of pituitary function has become better understood. The pituitary gland secretes several homones which in turn control secretion of other glands such as the adrenal, the thyroid, and the reproductive organs. In recent times, a series of pituitary releasing hormones have been discovered, and characterized. The most recent of these is growth hormone releasing factor GRF(1-44)-NH.sub.2. This discovery occurred in 1982 when two investigators independently, but almost simultaneously, reported the presence of a substance occurring in a pancreatic tumor which caused a clinical syndrome called acromegaly. In their respective journal articles, they reported that the tumors were found to contain a peptide consisting of 44

Patents 431

amino acids, which when purified and injected into animals or humans was found to stimulate growth hormone production intensively, Science, Vol. 218, Nov. 5, 1982, pp. 585-87 and Nature, Vol. 300, Nov. 18, 1982, pp. 276-78. Recently, some researchers have successfully, synthetically synthesized growth hormone releasing factor, and very recently it has been produced by genetic engineering procedures using bacterial cultures. For literature relating to synthetic production of growth hormone releasing factor see Gelato, M.C. et al, 1983, "The Effects of Growth Hormone Releasing Factor in Man", Journal of Clinical Endrocrinology and Metab., 57..674.... Growth hormone releasing hormone factor is a peptide of 44 amino acids. There are analogs containing 27-40 amino acids. It is one of a group of peptides secreted by the hypothalamus, and it normally stimulates pituitary growth hormone release. It is important in normal growth and development during childhood.... Recently, it has been reported that GRF(1-44)-NH.sub.2 may have some promise in the treatment of growth hormone deficiency (see Journal of Clinical Endrocrinoloqy and Metab., 59:1, 1984 and Journal of Clinical Endrocrinology and Metab., 58:1043, 1984). However, GRF(1-44)--NH.sub.2 has not yet been marketed or suggested for any specific clinical disease treatment. It has been suggested as likely to be useful for testing pituitary function by using doses to stimulate pituitary secretion of growth hormone factor. The theory being that in the event it does not so stimulate, one knows that the pituitary gland is not functioning properly. However, when used to test pituitary function GRF(1-44)-NH.sub.2 is administered intravenously by a single bolus injection and blood levels of growth hormone are measured in serum specimens obtained at approximately half hour intervals for four hours. If growth hormone levels fail to rise, then the presumption is made that the pituitary gland is incapable of secreting growth hormone. This is a single dose for diagnostic purposes, not a periodic and regular treatment pattern. Web site: http://www.delphion.com/details?pn=US04710382__ •

Treatment for osteoporosis using potassium salts Inventor(s): Morris, Jr. R. Curtis (San Francisco, CA), Sebastian; Anthony (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,027,737 Date filed: October 27, 1994 Abstract: Novel methods are provided for treating osteoporosis in humans, comprising administering therapeutic amounts of pharmaceutically-acceptable alkalinizing salts of potassium. The preferred salt is potassium bicarbonate. The methods may also be used to prevent or delay the onset of osteoporosis. Dietary supplementation is a preferred and convenient method of administration. Excerpt(s): This invention concerns novel methods for treating osteoporosis in humans and, more particularly, involves the administration of pharmaceutically acceptable alkalinizing potassium salts, such as potassium bicarbonate, in a variety of dietary and pharmaceutical compositions.... Osteoporosis is a metabolic bone disease characterized pathologically by an absolute decrease in the amount of bone, and clinically by increased susceptibility to fractures. Riggs et al., N. Engl. J. Med. (1986), 314:1676; Rusbach et al., In: Textbook of Endocrinology, Ed(s) Williams, (1981), p. 922; Riggs, In: Cecil Textbook of Medicine, Ed(s) Wyngaarden et al., (1985), p. 1456; Riggs et al., Am. J. Med., (1983), 75:899.... In post-menopausal women, estrogen deficiency has been identified as a major predisposing factor. Recent studies in normal women ages 20 to 88

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years indicate, however, that substantial bone loss from the axial skeleton occurs gradually in the decades before estrogen deficiency ensues at menopause. Riggs et al., J. Clin. Invest., (1986), 77:1487. According to Riggs et al., "... factors in addition to estrogen deficiency must contribute to the pathogenesis of involutional osteoporosis in women because about half of overall vertebral bone loss occurs premenopausally." (Id.). Web site: http://www.delphion.com/details?pn=US06027737__ •

Treatment of osteoporosis Inventor(s): Flora; Lawrence (Fairfield, OH) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 4,822,609 Date filed: September 12, 1986 Abstract: A method for treating or preventing osteoporosis is disclosed. Bone cells are synchronized during a bone cell activating period; bone resorption, which normally follows activation, is inhibited using a polyphosphonate; bone formation is allowed to occur in the rest period during which nutrient supplements may be administered to the patient. The method shortens the natural cycle time of bone formation/resorption, resulting in a faster bone build-up. Excerpt(s): The present invention relates to a method for the treatment or prevention of osteoporosis. Specifically, the present invention relates to a method whereby a bone cell activating compound and a bone resorption inhibiting polyphosphonate are sequentially administered to a subject afflicted with or at risk to osteoporosis.... Osteoporosis is the most common form of metabolic bone disease. Although it may occur secondary to a number of underlying diseases, 90% of all cases appear to be idiopathic.... Idiopathic osteoporosis is most commonly observed in postmenopausal women (postmenopausal osteoporosis) but is may also occur in elderly males and females (senile osteoporosis) or occasionally in younger individuals of both sexes. The disease which develops in postmenopausal women is characterized primarily by fractures of the wrist and spine, while femoral fractures seem to be the dominant feature of senile osteoporosis. Web site: http://www.delphion.com/details?pn=US04822609__

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Treatment of osteoporosis Inventor(s): Silver; Justin (Motza Ilit, IL) Assignee(s): Hadasit Medical Research Services and Development Company Ltd. (Jerusalem, IL) Patent Number: 5,935,607 Date filed: February 15, 1996 Abstract: A method of treating osteoporosis is disclosed by administering orally a single daily dosage of phosphate in the evening in an amount, e.g., about 10 mg/kg body weight or less which is effective to raise serum parathyroid hormone levels of the subject being treated.

Patents 433

Excerpt(s): The present invention is generally in the field of endocrinology and treatment of conditions associated with impairment in normal hormone levels. More specifically, the present invention provides a composition and method for increasing the level of the parathyroid hormone (PTH) in a needy subject. In accordance with a preferred embodiment, the method and composition are used for the treatment of osteoporosis.... 1. Rodan, G. A., Mechanical loading, estrogen deficiency, and the coupling of bone formation to bone resorption, J. Bone Miner. Res., 6:527-530, 1991.... 2. Juppner, H., Abou-Samra, A. B., Freeman, M., Kong, X. F., Schipani, E., Richards, J., Kolakowski, L. F., Hock, J., Potts, J. T., Kronenberg, H. M., and Segre, G. V., A G-proteinlinked receptor for parathyroid hormone and parathyroid hormone-related peptide, Science, 254:1024-1026, 1991. Web site: http://www.delphion.com/details?pn=US05935607__ •

Treatment of osteoporosis Inventor(s): Khosla; Sundeep (Rochester, MN), Conover; Cheryl A. (Rochester, MN) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 5,998,369 Date filed: May 5, 1998 Abstract: A substantially pure complex including IGFIIE polypeptide and IGFBP2 polypeptide is described. Methods for treating an osteoporosis patient and targeting a compound to the skeletal extracellular matrix of a patient are also described. Excerpt(s): Hepatitis C-associated osteosclerosis (HCAO) is a rare syndrome characterized by a marked increase in skeletal mass in adults who are infected with the hepatitis C virus. Beyer et al., J. Bone Min. Res., 5:1257-1263 (1990); and Diamond et al., Bone, 19:679-683 (1996). Spine and hip bone mineral densities are elevated as much as two-fold in these affected individuals, who represent the most dramatic example of acquired osteosclerosis in humans. Radiographs show dense bones in the appendicular and axial skeleton, with sparing of the calvarium and facial bones. Biochemical markers of bone formation are usually elevated, and transiliac bone biopsies generally show increased bone formation rates. Nevertheless, osseous tissue from these patients appears histologically to be of good quality with intact lamellar patterns, unlike the abnormal, rapidly remodeling woven bone found in patients with Paget's bone disease.... To date, ten cases of HCAO have been reported. It is apparent, however, that only a small percentage of all patients infected with hepatitis C develop osteosclerosis, since skeletal radiographs of 107 randomly selected hepatitis C infected patients failed to show dense bones. Beyer et al., Am. J. Med., 95:660-662 (1990). Thus, although it is uncertain whether hepatitis C is the causative agent of the skeletal disease, a plausible hypothesis is that either hepatitis C or another parenterally transmitted agent increases hepatic production of a growth factor(s) that stimulate osteoblast function.... The invention is based on the discovery that insulin-like growth factor binding protein 2 (IGFBP2) facilitates targeting of insulin-like growth factors (IGFs), and in particular, IGFIIE, to skeletal tissue. Complexes of IGFIIE polypeptide and IGFBP2 polypeptide are effective in stimulating human osteoblast proliferation and can be used for increasing bone mass in patients with osteoporosis. Web site: http://www.delphion.com/details?pn=US05998369__

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•

Treatment of osteoporosis and metabolic bone disorders with nitric oxide substrate and/or donors Inventor(s): Wimalawansa; Sunil J. (Friendswood, TX), Yallampalli; Chandrasekhar (Houston, TX) Assignee(s): Board of Regents, The University of Texas System () Patent Number: 6,133,320 Date filed: October 22, 1998 Abstract: Primary and secondary osteoporosis in a female or a male mammal is treated by administering thereto a nitric oxide synthase substrate, a nitric oxide donor or both, optionally; in further combination with one or more of an estrogen, a progestin, an anabolic steroid. Nitric oxide substrate or donor also can be combined with one or more of other medications acting on bone, such as bisphosphonate, calcitonin, fluoride, androgen and other novel therapeutic agents. Either nitric oxide donor or substrate by itself or combination with other medications as described above can be used in both women and men, (preferably human) for prevention and treatment of osteoporosis and other metabolic bone disorders. Excerpt(s): This invention relates to a new method for treatment of osteoporosis and bone mineral disorders and to prevent bone loss, fractures and other abnormal clotting patterns, urogenital discomfort, prevention and treatment of cardiovascular diseases, and other conditions associated with the reduction in ovarian function in middle-aged women, with a nitric oxide synthase substrate (L-arginine), a nitric oxide donor, or both, alone or in combination with an estrogen and/or a progestin. Same compounds are also useful in men to decrease bone turnover and hence prevention and treatment of osteoporosis and for treatment of other metabolic bone disorders.... It is now well known, that hormone replacement therapy, such as estrogen treatment, improves or reverses the adverse effects of the cessation of sex steroid secretion by the ovaries during menopause. Estrogens have also been shown to prevent bone loss and improve a variety of functions including mood and psychological well-being in postmenopausal women. Estrogens have been shown to effect arterial tone and this may help to explain the reduction in hot flushes and decrease the cardiovascular mobility and mortality in postmenopausal women with estrogen replacement therapy. Unopposed estrogen therapy in postmenopausal women has been associated with endometrial hyperplasia and endometrial cancer.... Many studies have shown that the addition of progesterone to estrogen replacement therapy decreases the risk of endometrial cancer and even reverses endometrial hyperplasia. However, progestins are not without untoward side effects. Progestins may oppose the beneficial effects of estrogens on the cardiovascular system by inducing an adverse lipid profile in circulation. Progesterone may also counteract the beneficial effects of estrogen on vascular walls. Moreover, irregular or withdrawal bleedings are common with combined estrogen-progestin therapy. The current hormone replacement therapy (HRT) employs combinations of estrogen and progestins as in the case of most contraceptives. Web site: http://www.delphion.com/details?pn=US06133320__

Patents 435

•

Treatment of osteoporosis using potassium bicarbonate Inventor(s): Sebastian; Anthony (San Francisco, CA), Morris, Jr. R. Curtis (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 5,171,583 Date filed: October 17, 1989 Abstract: Novel methods are provided for treating osteoporosis in humans, comprising administering therapeutic amounts of pharmaceutically-acceptable alkalinizing salts of potassium. The preferred salt is potassium bicarbonate. The methods may also be used to prevent or delay the onset of osteoporosis. Dietary supplementation is a preferred and convenient method of administration. Excerpt(s): This invention concerns novel methods for treating osteoporosis in humans and, more particularly, involves the administration of pharmaceutically acceptable alkalinizing potassium salts, such as potassium bicarbonate, in a variety of dietary and pharmaceutical compositions.... Osteoporosis is a metabolic bone disease characterized pathologically by an absolute decrease in the amount of bone, and clinically by increased susceptibility to fractures. Riggs et al., N. Engl. J. Med. (1986), 314:1676; Rusbach et al., In: Textbook of Endocrinology, Ed(s) Williams, (1981), p. 922; Riggs, In: Cecil Textbook of Medicine, Ed(s) Wyngaarden et al., (1985), p. 1456; Riggs et al., Am. J. Med., (1983), 75:899.... In post-menopausal women, estrogen deficiency has been identified as a major predisposing factor. Recent studies in normal women ages 20 to 88 years indicate, however, that substantial bone loss from the axial skeleton occurs gradually in the decades before estrogen deficiency ensues at menopause. Riggs et al., J. Clin. Invest., (1986), 77:1487. According to Riggs et al., "... factors in addition to estrogen deficiency must contribute to the pathogenesis of involutional osteoporosis in women because about half of overall vertebral bone loss occurs premenopausally." (Id.). Web site: http://www.delphion.com/details?pn=US05171583__

•

Treatment or prevention of osteoporosis Inventor(s): Kelly; Graham E. (Northbridge, AU) Assignee(s): Novogen, Inc. (Wilmington, DE) Patent Number: 6,340,703 Date filed: June 2, 1998 Abstract: There is described a method for the treatment or prevention of menopausal symptoms or osteoporosis wherein there is administered to a subject in need of such treatment a therapeutically effective amount of the isoflavone formononetin, or a method for the treatment or prevention of menopausal symptoms wherein there is administered to a subject in need of such treatment a therapeutically effective amount of the isoflavone daidzein, the isoflavone being optionally administered with one or more pharmaceutically acceptable adjuvants, carriers and/or excipients. Therapeutic uses and compositions/foods are also described, comprising daidzeii or formononetin optionally in association with one or more pharmaceutically acceptable adjuvants, carriers, food components and/or excipients. Excerpt(s): This invention relates to compositions, therapeutic uses and methods of treatment or prevention of menopausal symptoms and osteoporosis.... Menopausal

436 Osteoporosis

symptoms and osteoporosis are significant scourges in the female population, generally affecting many women in later life.... Menopausal symptoms are very well known and are described, for example, by Greene, J. G. and Cooke, D. J. (1980) British Journal of Psychiatry Volume 136, 486-491 (incorporated herein by reference). Hot flushes are one of the principal menopausal symptoms which are uncomfortable and irritating. Greene and Cooke have developed a score in order to measure menopausal symptoms in women. This score is approved by the U.S. Department of Health and widely used in the medical community. The indicators of menopausal symptoms according to Greene and Cooke comprise hot flushes, sweating at night, heart beating quickly or strongly, feelings of tension or nervousness, difficulty in sleeping, excitability, attacks of panic, difficulties in concentrating, feelings of tiredness or lack of energy, unhappiness or depression, crying spells, irritability, feelings of dizziness or faintness, pressure or tightness in head or body, parts of the body feeling numb or tingling, dry vagina and/or dry mouth, headaches, muscle and joint pains, loss of feeling in hands or feet, breathing difficulties, and loss of interest in sex. Web site: http://www.delphion.com/details?pn=US06340703__ •

Use of calcium citrate malate for the treatment of osteoporosis and related disorders Inventor(s): Kochanowski; Barbara A. (West Chester, OH) Assignee(s): The Procter & Gamble Company (Cincinnati, OH) Patent Number: 5,128,374 Date filed: September 27, 1990 Abstract: Methods for building bone in a human or other animal subject, comprising administering to said subject a safe and effective amount of calcium citrate malate. The calcium citrate malate is preferably administered for at least about three months. A preferred method of the invention is for the treatment of osteoporosis. The calcium citrate malate comprises a complex or a mixture of calcium salts having a ratio of moles citrate to moles malate of from about 1:0.16 to about 1:13.5. The calcium citrate malate is preferably administered in an oral dosage form, containing pharmaceutically-acceptable carriers and excipients. Excerpt(s): This invention relates to methods of building bone in humans and other animals, i.e., for the treatment of osteoporosis and related disorders. In particular, this invention relates to such methods of treatment by administration of certain calcium salts.... Calcium is the fifth most abundant element in the human body. It plays an important role in many physiological processes, including nerve and muscle functions. Not surprisingly, nutritional and metabolic deficiencies of calcium can have broadranging adverse effects. Since about 90% of the body's calcium is found in bone tissues, many of these adverse effects are manifested through deficiencies in the structure, function and integrity of the skeletal system.... The most common metabolic bone disorder is osteoporosis. Osteoporosis can be generally defined as the reduction in the quantity of bone, or the atrophy of skeletal tissue. In general, there are two types of osteoporosis: primary and secondary. "Secondary osteoporosis" is the result of an identifiable disease process or agent. However, approximately 90% of all osteoporosis cases is idiopathic "primary osteoporosis". Such primary osteoporosis includes postmenopausal osteoporosis, age-associated osteoporosis (affecting a majority of individuals over the age of 70 to 80), and idiopathic osteoporosis affecting middle-aged and younger men and women.

Patents 437

Web site: http://www.delphion.com/details?pn=US05128374__ •

Use of calcium L-threonate in preventing, inhibiting and curing osteoporosis and rickets Inventor(s): Yu; Kai (Beijing, CN), Wang; Zhiwen (Beijing, CN), Kou; Fuping (Beijing, CN) Assignee(s): Beijing Jueng Asia Pacific Life Scientific Research Center (Beijing, CN) Patent Number: 6,077,872 Date filed: November 25, 1998 Abstract: The present invention relates to the use of calcium L-threonate, namely, to a method for preventing, inhibiting and curing osteoporosis and rickets using calcium Lthreonate. Excerpt(s): The present invention relates to the use of calcium L-threonate, particularly to the use of calcium L-threonate in preventing, inhibiting and curing osteoporosis and rickets.... Osteoporosis is a common metabolic bone disease. About ninety percent of osteoporosis is primary even though it may be caused by a number of other diseases. With the age increasing or menopause, the mineral substances and matrix of bone decrease which results in a change of the micro-structure of bone tissues and thus deviates the normal loading functions of bones and markedly increases the risk of fracture and also brings about systematic bone pain and changes of body attitude.... The exact cause of primary osteoporosis is not clear at present, but it is generally the cointeraction result of a number of factors and links. Most scholars regard that the occurrence of osteoporosis is associated with various factors such as increased age, decreased hormone level and calcium dysbolism, etc. As for women, particularly for menopausal women, many researchers believe that the occurrence of osteoporosis is related to their decreased estrogens and calcium dysbolism. The occurrence of osteoporosis in the aged men is also resulted from multiple factors. Like estrogens, androgens of the aged men also participate in the process of bone metabolism and play important roles in bone formation and maintenance of bone amount. The protein assimilation of androgens promotes the synthesis of collagen which provides positions for the precipitation of calcium and phosphorus. In addition, increased secretion of parathormone in the aged men reduces the bone formation but enhances the bone absorption. The kidney degeneration (kidney weakness) in the aged men will reduce the activity of hydroxylase activating vitamin D, decrease the calcium intestinal absorption and result in negative calcium balance and loss of bone matrix. A lot of attempts have been done to treat osteoporosis with a variety of pharmacological agents, such as estrogens. Owing to the complexity of the causes of osteoporosis, there is evidence to show that some therapies (such as oral administration of calcium carbonate) are not effective for preventing osteoporosis (see Recker et al, Annals of Int. Med., Vol. 87,6, pp 649-655,1977). Therefore, a more effective method of preventing and inhibiting osteoporosis is desirable. Web site: http://www.delphion.com/details?pn=US06077872__

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Use of estriol for treatment of climacteric osteoporosis Inventor(s): Ernst; Michael (Jena/Lobeda Ost, DE), Elger; Walter (Berlin, DE), Schneider; Birgitt (Jena, DE), Oettel; Michael (Jena, DE), Hubler; Doris (Schmieden, DE), Dittgen; Michael (Apolda, DE) Assignee(s): EnTec Gesellschaft fuer Endokrinologische Technologie m.b.H. (DE) Patent Number: 5,614,213 Date filed: August 31, 1994 Abstract: The invention relates to the use of estriol as the sole active ingredient for the production of a transdermal medicament which continuously releases the active ingredient for the treatment of climacteric osteoporosis. It has been shown according to the invention that estriol, which has up until now been thought ineffective for the treatment of climacteric osteoporosis, develops strong anti-osteoporotic effectiveness upon continuous transdermal application. Excerpt(s): The invention relates to the use of estriol as sole active ingredient for the production of a transdermal medicament, which continuously releases the active ingredient, for the treatment of climacteric osteoporosis.... The loss of the female sex hormone--estrogen--in the climacteric can lead to phenomena which require therapy. Estrogens are steroid hormones which are derived from the tetracyclic C.sub.18 steroid estrane. Among the natural estrogens, one differentiates between estrone (E.sub.1), estradiol (E.sub.2) and estriol (E.sub.3), estrone and estriol being the physiologically most important. Hormone replacement with both these estrogens quickly leads to an improvement in psychological consciousness and in the long term to a favourable influence on the bone and lipoid metabolism. The last-mentioned factors represent effective prevention of diseases of the skeletal system and of illnesses of the heart circulation system. It has been proved without any doubt that E.sub.1 and E.sub.2 can prevent advancing osteoporosis in the climacteric and can slow the advance of arteriosclerotic vascular changes.... Against the said favourable effects there stands a risk, which is considered tolerable, from possible stimulating effects of the estrogens on the growth of hormone-dependent tumours of the genital tract (endometrium) and of the mammary gland. The known combination of estrogens with gestagens has the aim of minimizing the corresponding risks through the anti-proliferative action of gestagens in the uterus. Web site: http://www.delphion.com/details?pn=US05614213__

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Use of tetracycline to enhance bone protein synthesis and/or treatment of osteoporosis Inventor(s): Golub; Lorne M. (Smithtown, NY), Ramamurthy; Nungavaram S. (Smithtown, NY), McNamara; Thomas F. (Port Jefferson, NY) Assignee(s): The Research Foundation of State University of New York (Albany, NY) Patent Number: 4,925,833 Date filed: December 29, 1986 Abstract: Tetracyclines, antibacterial and non-antibacterial tetracyclines, have been found to be useful in the treatment of osteoporosis in humans by administering to the human suffering from osteoporosis an effective amount of a tetracycline to enhance bone protein synthesis. Tetracyclines which have been found to be effective in the

Patents 439

treatment of osteoporosis in dedimethylaminotetracyline.

humans

include

minocycline,

doxycycline

and

Excerpt(s): In pending U.S. patent application Ser. No. 566,517, now U.S. Pat. No. 4,666,897, it is disclosed that tetracyclines, such as the antibiotic tetracyclines, e.g tetracycline, are useful as anti-collagenolytic agents or as inhibitors of collagenase. These tetracyclines and compositions containing the same are disclosed therein as being useful in the treatment of periodontal diseases, corneal ulcers, rheumatoid arthritis and the like characterized by excessive collagen destruction.... In pending U.S. patent application Ser. No. 699,048, now U.S. Pat. No. 4,704,383, it is disclosed that the non-antibiotic or non-antibacterial tetracyclines also possess anti-collagenolytic properties and are useful as inhibitors of collagenase. Additionally, these non-antibiotic or non-antibacterial tetracyclines have also been found to be useful in the treatment of periodontal diseases, corneal ulcers, bone deficiency disorders due to excess collagenase production or excessivde collagen destruction, rheumatoid arthristis and the like. A particularly useful non-antibiotic tetracycline in the practices of this invention is the tetracycline dedimethylaminotetracycline.... Tetracyclines are useful as broad spectrum antibiotics because they have the ability to inhibit protein synthesis in a wide variety of bacteria. As disclosed in the above-identified pending patent applications, it has also been discovered that tetracyclines, antibiotic tetracyclines and non-antibiotic tetracyclines, have the ability to inhibit collagen-destructive enzymes, such as collagenase, responsible for the breakdown of connective tissue in a number of diseases, such as periodontal disease, corneal ulcers and rheumatoid arthritis. Web site: http://www.delphion.com/details?pn=US04925833__ •

Use of tiludronic acid and derivatives thereof in poultry for the preparation of a medicinal product for preventing and treating osteoporosis Inventor(s): Thibaud; Dominique (Gujan Mestras, FR), Bardon; Thierry (Bouliac, FR) Assignee(s): Ceva Sante Animale (Libourne, FR) Patent Number: 6,482,809 Date filed: February 17, 2000 Abstract: The present invention relates to the use of an active substance selected from the group consisting of tiludronic acid, one of its pharmaceutically acceptable salts, one of its hydrates and mixtures thereof, in the preparation of a medicinal product for preventing and treating osteoporosis in poultry. Excerpt(s): The invention relates to the use of tiludronic acid, one of its pharmaceutically acceptable salts or one of its hydrates in the preparation of a medicinal product for preventing and treating osteoporosis in poultry, and more particularly in hens.... Female birds have a bone metabolism which is particularly stressed with the aim of producing eggshells, which are rich in minerals, the main one of which is calcium. Bones in female birds fulfil two essential functions: a mechanical function, common to all vertebrates, giving the properties of maintaining the body in space, and a physiological function which is specific to female birds, by forming a calcium reserve which can readily be mobilized for the purpose of producing eggshells. The mechanical function is provided by two types of bone: the cortical bone constituting the outer sheath of the bones, and the trabecular bone constituting bony frames oriented along the lines of force inside the bones. The physiological function is essentially provided by a third type of bone, the medullary bone which occupies the cavities of certain long bones or flat bones.

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Medullary bone develops between the frames of the trabecular bone. This bone is very fragile and thus provides no mechanical function.... During laying periods, medullary bone undergoes cycles of resorption-formation, each cycle being accompanied by the formation of an egg. On being resorbed, the medullary bone releases a large amount of calcium required for the production of the eggshell. The formation which accompanies this resorption allows the reconstitution of the medullary calcium reserve, which will be mobilized in the next cycle. Web site: http://www.delphion.com/details?pn=US06482809__ •

Use of vitamin D glycosides, vitamin D orthoester glycosides, vitamin D analog glycosides and vitamin D analog orthoester glycosides for the treatment of osteoporosis Inventor(s): Holick; Michael F. (31 Bishop La., Sudbury, MA 01776) Assignee(s): none reported Patent Number: 5,508,392 Date filed: April 20, 1994 Abstract: The present invention relates to methods for the treatment of prevention of osteoporosis by the administration of a vitamin D glycoside or vitamin D orthoester glycoside, or an analog thereof. Excerpt(s): The invention is in the field of Medical Chemistry.... It is well known that females at the time of menopause suffer a marked loss of bone mass giving rise ultimately to osteopenia, which in turn gives rise to spontaneous crush fractures of the vertebrae and fractures of the long bones. This disease is generally known as postmenopausal osteoporosis and presents a major medical problem, both in the United States and most other countries where the life-span of females reaches ages of at least 60 and 70 years. Generally the disease, which is often accompanied by bone pain and decreased physical activity, is diagnosed by one or two vertebral crush fractures with Xray evidence of diminished bone mass. It is known that this disease is accompanied by diminished ability to absorb calcium, decreased levels of sex hormones, especially estrogen and androgens, and a negative calcium balance.... Methods for treating the disease have varied considerably but to date no really satisfactory treatment is yet known. For example, calcium supplementation by itself has not been successful in preventing or curing the disease and the use of sex hormones, especially estrogen, which has been reported to be effective in preventing the rapid loss of bone mass experienced in postmenopausal women, has been complicated by the tear of its possible carcinogenicity. Other treatments, for which variable results have again been reported, have included a combination of vitamin D in large doses, calcium and fluoride. The primary problem with this approach is that fluoride induces structurally unsound bone, called woven bone, and in addition, produces a number of side effects such as increased incidence of fractures and gastrointestinal reaction to the large amounts of fluoride administered. Web site: http://www.delphion.com/details?pn=US05508392__

Patents 441

Patent Applications on Osteoporosis As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to osteoporosis: •

Apparatus and methods for diagnosing osteoporosis and other diseases with MR imaging Inventor(s): Kose, Katsumi; (Kashiwa-shi, JP) Correspondence: SHLESINGER, ARKWRIGHT & GARVEY LLP; 3000 South Eads Street; Arlington; VA; 22202; US Patent Application Number: 20020022779 Date filed: July 30, 2001 Abstract: A compact magnet and an RF probe which can accommodate a human extremity such as a heel are used to construct a compact MRI system for diagnosis and follow-up of osteoporosis and other diseases. Methods for measuring and calculating proton density in inhomogeneous static magnetic field, magnetic field gradients, and RF magnetic field are provided using 2D spin-echo image acquisitions with external reference materials and image analyses. The measured proton density of bone marrow is used for computation of trabecular bone volume fraction, which can be used for diagnosis of osteoporosis and other diseases. Excerpt(s): This invention generally relates to magnetic resonance imaging (MRI) utilizing nuclear magnetic resonance (NMR) phenomena. It more particularly relates to a specialized MRI system used for diagnosis of osteoporosis and other diseases.... Osteoporosis is a widespread disease characterized by bone loss usually associated with aging. It is a complex and chronic disease that may not be recognized until resulting fractures late in life. In many countries around 50% of women above age of 70 is osteoporosis and to overcome it has become an important social requirement. For diagnosis and follow-up of osteoporosis, measurement of bone mineral density (BMD) is indispensable. The conventional methods for the BMD measurement are based on X-ray attenuation measurements through a bone. Among them, DEXA (Dual-Energy X-ray Absorptiometry) is now the standard method, but cannot be used repeatedly nor for young women because of the ionizing radiation. Thus the X-ray BMD measurement should be replaced by some noninvasive and high precision method such as bone marrow volume measurement using MRI as described below, because MRI has no ionizing radiation and spatial localization capability is guaranteed.... The bones of a human skeletal system have a dense outer shell made of cortical bone (alternatively termed "compact" or "dense" bone). Inside the cortical bone, many regions have a mesh or network of trabecular bone (alternatively termed "spongy" or "cancellous" bone), made up of roughly the same material as the cortical bone. The regions enclosed by the cortical bone and/or trabecular network are filled with "bone marrow", of which major components are water and lipid. Since the protons (hydrogen nuclei) of the water and lipid can be measured using MRI, the bone marrow volume can be quantified using MR images. Thus quantitative bone MRI can be a complementary method for the measurement of BMD because bone is almost chemically homogeneous. Studies according to this concept are found in the following references: Jara et al., "High-

10

This has been a common practice outside the United States prior to December 2000.

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Resolution Variable Flip Angle 3D MR Imaging of Trabecular Microstructure in Vivo", Magnetic Resonance in Medicine 29: 528-539, 1993; Wehrli et al., "Cancellous Bone Volume and Structure in the Forearm: Noninvasive Assessment with MR Microimaging and Image Processing", Radiology 206: 347357, 1998; L. Hilaire et al., "High-Speed Spectroscopic Imaging for Cancellous Bone Marrow R.sub.2* mapping and Lipid Quantification", Magnetic Resonance Imaging, 18: 777-786, 2000. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Combination therapy for osteoporosis Inventor(s): Thompson, David D. (Gales Ferry, CT), Ke, Hua Zhu; (Ledyard, CT) Correspondence: Gregg C. Benson; Pfizer Inc. Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20010009920 Date filed: December 13, 2000 Abstract: Pharmaceutical combination compositions including certain estrogen agonists/antagonists and prostaglandins or prostaglandin agonists/antagonists. The compositions are useful for the treatment of bone disorders including osteoporosis. Excerpt(s): This invention relates to a pharmaceutical combination of estrogen agonists/antagonists and agents that stimulate bone formation and increase bone mass, kits containing such combinations and the use of such combinations to treat conditions which present with low bone mass in mammals, including humans.... Osteoporosis is a systemic skeletal disease, characterized by low bone mass and deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In the U.S., the condition affects more than 25 million people and causes more than 1.3 million fractures each year, including 500,000 spine, 250,000 hip and 240,000 wrist fractures annually. Hip fractures are the most serious, with 5-20% of patients dying within one year, and over 50% of survivors being incapacitated.... The elderly are at greatest risk of osteoporosis, and the problem is therefore predicted to increase significantly with the aging of the population. Worldwide fracture incidence is forecast to increase threefold over the next 60 years, and one study estimates that there will be 4.5 million hip fractures worldwide in 2050. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Combination treatment for inhibiting bone loss Inventor(s): Cullinan, George J. (Trafalgar, IN), Black, Larry J. (Indianapolis, IN) Correspondence: DAN L. WOOD; Eli Lilly And Company; Lilly Corporate Center; Patent Division/DLW; Indianapolis; IN; 46285; US Patent Application Number: 20010051636 Date filed: March 8, 2000 Abstract: The present invention provides a method for inhibiting bone loss comprising administering to a human in need thereof a first compound selected from 1) triarylethylenes; 2) 2,3-diaryl-2H-1-benzopyrans, 3) 1-aminoalkyl-2-phenylindoles; 4) 2phenyl-3-aroylbenzothiophenes, 5) 1-substituted-2-aryl-dihydronaphthalenes; or 6) benzofurans, and a second compound being a bisphosphonate: or pharmaceutically

Patents 443

acceptable salts and solvates thereof. Also encompassed by the invention are combination pharmaceutical formulations and salts. Excerpt(s): Current major diseases or conditions of bone which are of public concern include post-menopausal osteoporosis, senile osteoporosis, patients undergoing longterm treatment of corticosteroids, side effects from glucocorticoid or steroid treatment, patients suffering from Cushings's syndrome, gonadal dysgensis, periarticular erosions in rheumatoid arthritis, osteoarthritis, Paget's disease, osteohalisteresis, osteomalacia, hypercalcemia of malignancy, osteopenia due to bone metastases, periodontal disease, and hyperparathyroidism. All of these conditions are characterized by bone loss, resulting from an imbalance between the degradation of bone (bone resorption) and the formation of new healthy bone. This turnover of bone continues normally throughout life and is the mechanism by which bone regenerates. However, the conditions stated above will tip the balance towards bone loss such that the amount of bone resorbed is inadequately replaced with new bone, resulting in net bone loss.... One of the most common bone disorders is post-menopausal osteoporosis which affects an estimated 20 to 25 million women in the United States alone. Women after menopause experience an increase in the rate of bone turnover with resulting net loss of bone, as circulating estrogen levels decrease. The rate of bone turnover differs between bones and is highest in sites enriched with trabecular bone, such as the vertebrae and the femoral head. The potential for bone loss at these sites immediately following menopause is 4-5% per year. The resulting decrease in bone mass and enlargement of bone spaces leads to increased fracture risk, as the mechanical integrity of bone deteriorates rapidly.... At present, there are 20 million people with detectable vertebral fractures due to osteoporosis and 250,000 hip fractures per year attributable to osteoporosis in the U.S. The latter case is associated with a 12% mortality rate within the first two years and 30% of the patients will require nursing home care after the fracture. Therefore, bone disorders are characterized by a noticeable mortality rate, a considerable decrease in the survivor's quality of life, and a significant financial burden to families. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition for the treatment and/or the prevention of osteoporosis and/or inflammatory joint diseases Inventor(s): Buccholz, Herwig; (Frankfurt, DE), Meduski, Jerzy; (Playa Del Ray, CA) Correspondence: MILLEN, WHITE, ZELANO & BRANIGAN, P.C. 2200 CLARENDON BLVD. SUITE 1400; ARLINGTON; VA; 22201; US Patent Application Number: 20030139354 Date filed: December 2, 2002 Abstract: Compositions and pharmaceutical compositions are described which comprise: a component A comprising one or more flavonol glycosides, a component B comprising one or more tetrahydrofolic acid compounds, a component C comprising one or more calcium supplements, and a component D comprising one or more magnesium supplements. Methods of using such compositions and pharmaceutical compositions to treat and/or prevent osteoporosis and/or an inflammatory joint disease are also described. Excerpt(s): The present invention relates, e.g., to compositions and pharmaceutical compositions for the treatment and/or prevention of osteoporosis and/or inflammatory joint diseases, methods of treating and/or preventing osteoporosis and/or

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inflammatory joint diseases and the use of the aforementioned composition for the treatment and/or prevention of osteoporosis and/or inflammatory joint diseases.... 17th ed., 1999). Primary osteoporosis includes idiopathic osteoporosis, rare but occurring in children and young adults; postmenopausal osteoporosis, occurring between the ages of 50 and 75; and involutional or senile osteoporosis associated with the normal process of aging. It is characterized by a predominant osteoclast activity and a disruption of the feedback mechanism between the serum calcium level and the parathyroid hormone (PTH) secretion. It occurs mainly uniformly throughout the whole skeleton. Secondary osteoporosis, accounting for less than 5% of all osteoporosis cases, includes endocrine dysfunctions. It starts mostly at the main skeleton and progresses centrifugally. Osteoporosis is characterized by pain in the respective bones, diffuse back pain, vertebral body collapse, pathological fractures, in particular, fracture of the neck of the femur. The goal of the management of all types of osteoporosis is therefore to decrease pain, to prevent fractures and to maintain the body functions.... Osteoporosis is a common clinical feature and common complication in patients affected with chronic inflammatory diseases with joint manifestations. These include rheumatoid arthritis (RA), Juvenile Rheumatoid Arthritis (JRA), psoriatic arthritis, Reiter's syndrome (reactive arthritis), Crohn's disease, ulcerative colitis, sarcoidosis (Orcel, P. Cohen-Solal, M. de Vernejoul, M. C., and Kuntz, D. [Bone demineralization and cytokines]. Rev Rhum Mal Osteoartic. September 1992; 59(6 Pt 2):16S-22S; Brown, J. H. and Deluca, S. A. The radiology of rheumatoid arthritis. Am Fam Physician. 1995 Oct; 52(5):1372-80; De Vos, M. De Keyser, F. Mielants, H. Cuvelier, C., and Veys, E. Review article: bone and joint diseases in inflammatory bowel disease. Aliment Pharmacol Ther. 1998 May; 12(5):397-404; Falcini, F. Trapani, S. Civinini, R. Capone, A. Ermini, M., and Bartolozzi, G. The primary role of steroids on the osteoporosis in juvenile rheumatoid patients evaluated by dual energy X-ray absorptiometry. J Endocrinol Invest. March 1996; 19(3):165-9; Scutellari, P. N. and Orzincolo, C. Rheumatoid arthritis: sequences. Eur J Radiol. 1998 May; 27 Suppl 1:S31-8). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions for treating abnormalities in glomerular filtration, patent ductus arteriosus and osteoporosis Inventor(s): Peri, Krishna G. (St-Laurent, CA), Chemtob, Sylvain; (Montreal, CA) Correspondence: David A. Jackson; KLAUBER & JACKSON; 4th Floor; 411 Hackensack Street; Hackensack; NY; 07601; US Patent Application Number: 20030017988 Date filed: June 4, 2002 Abstract: The present invention relates to a composition of matter comprising novel prostaglandin E2 receptor antagonists, and their use in treatments for regulating the fluid filtration in the kidney, preventing bone mineral loss in osteoporosis and dental disease and additionally, closure of ductus arteriosus (DA) in premature infants or fetal animals. Additionally, the compositions include linear peptides, peptide analogs, and peptidomimetics. Excerpt(s): The invention relates to compounds and the use of novel peptide and peptidomimetic antagonists of a G protein coupled receptor, in treatments focused on regulating the fluid filtration in the kidney in case of acute renal failure, end stage renal disease, glomerulonephritis and other nephropathies, on decreasing resorption and bone mineral loss as in osteoporosis and dental diseases and additionally, closure of

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ductus arteriosus (DA) in premature infants or fetal animals.... Prostaglandins are derived from the oxygenation of arachidonic acid by prostaglandin (PG) synthases. Prostaglandins mediate a wide variety of physiological actions, such as vasomotricity, sleep/wake cycle, intestinal secretion, lipolysis, glomerular filtration, mast cell degranulation, neurotransmission, platelet aggregation, leuteolysis, myometrial contraction and labor, inflammation and arthritis, patent ductus arteriosus, cell growth and differentiation. Prostanoids mediate their actions through binding to distinct receptors which belong to the super family of rhodopsin-like seven transmembrane helical receptors. These receptors are coupled to heterotrimeric G-proteins comprising of.alpha.,.beta. and.gamma. subunits which, upon activation, elicit alterations in cell calcium, initiate phosphoinositide hydrolysis or promotion or repression of cyclic adenosine monophosphate synthesis.... Of the five pharmacologically-distinct prostanoid receptors for PGE.sub.2, PGI.sub.2, PGD.sub.2, PGF.sub.2.alpha. and TxA.sub.2, four subtypes of PGE.sub.2 receptor are described (Ichikawa, et al. 1996). These are EP.sub.1, EP.sub.2, EP.sub.3 which has several splice variants and EP.sub.4. Cloned human EP.sub.4 (also known as prostaglandin E2 receptor subtype EP4) is a 488 amino acid glycoprotein, linked to G.sub..alpha.s and involved in stimulation of adenylate cyclase and cAMP synthesis (Abramovitz, M. et al., U.S. Pat. Nos. 5,759,789 and 5,605,814). EP.sub.4 receptor is expressed at a high level in intestine, but at much lower levels in lung, kidney, thymus, uterus and brain (Bastien, Y. et al. 1994 J. Biol. Chem. 269 (16):11873-77). EP.sub.4 is expressed in ductus arteriosus (Bhattacharya, M. et al. 1999. Circulation. 100:1751-56). Paradoxically, EP.sub.4 knock-out mice die after birth due to insufficient closure of ductus arteriosus (Nguyen, M. et al. 1997. Nature. 390:7881; Segi, E. et al., 1998). Hence the mechanism of ductal patency and the role of EP.sub.4 remain elusive. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cyclase inhibiting parathyroid hormone antagonists or modulators and osteoporosis Inventor(s): Cantor, Thomas L. (El Cajon, CA) Correspondence: Peng Chen; Morrison & Foerster LLP; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130-2332; US Patent Application Number: 20020160945 Date filed: August 10, 2001 Abstract: The present invention relates to a novel method for treating a patient that has osteoporosis and the patient may be having administered cyclase activating parathyroid hormone (CAP) or analogues. The patient receives an administration of a cyclase inhibiting parathyroid hormone peptide (CIP) having an amino acid sequence from between (SEQ ID No.1 [PTH.sub.2-84]) and (SEQ ID No. 2 [PTH.sub.34-84]), (preferably (SEQ ID No.3 [PTH.sub.3-84]) and (SEQ ID No. 4 [PTH.sub.28-84])), or a conservatively substituted variant thereof exhibiting parathyroid hormone (PTH) antagonist activity in a therapeutically effective, but non-toxic amount that reduces the occurrence of hypercalcemia or osteosarcoma in the patient resulting from the administration of CAP, and yet, through a CAP rebound effect, is effective in itself in the treatment of osteoporosis. Excerpt(s): The present invention relates to a novel method for treating a patient that has osteoporosis and the patient may be having administered cyclase activating parathyroid hormone (CAP) or analogues. The patient receives an administration of a cyclase inhibiting parathyroid hormone peptide (CIP) having an amino acid sequence from

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between (SEQ ID No. 1 [PTH.sub.2-84]) and (SEQ ID No. 2 [PTH.sub.34-84]), (preferably (SEQ ID No.3 [PTH.sub.3-84]) and (SEQ ID No. 4 [PTH.sub.28-84])), or a conservatively substituted variant thereof exhibiting parathyroid hormone (PTH) antagonist activity in a therapeutically effective, but non-toxic amount that reduces the occurrence of hypercalcemia or osteosarcoma in the patient resulting from the administration of CAP, and yet, through a CAP rebound effect, is effective in itself in the treatment of osteoporosis.... Calcium plays an indispensable role in cell permeability, the formation of bones and teeth, blood coagulation, transmission of nerve impulse, and normal muscle contraction. The concentration of calcium ions in the blood is, along with calcitriol and calcitonin, regulated mainly by parathyroid hormone (PTH). Extracellular calcium levels are directly affected by PTH through calcium uptake in kidney tubule cells and calcium transport to or from bone. Although calcium intake and excretion may vary, PTH serves through a feedback mechanism to maintain a steady concentration of calcium in cells and surrounding fluids. When serum calcium lowers, the parathyroid glands secrete PTH, affecting the release of stored calcium. When serum calcium increases, stored calcium release is retarded through lowered secretions of PTH.... Osteoporosis is the most common form of metabolic bone disease and may be considered the symptomatic, fracture stage of bone loss (osteopenia). Although osteoporosis may occur secondary to a number of underlying diseases, 90% of all cases appear to be idiopathic. Postmenopausal women are particularly at risk for idiopathic osteoporosis (postmenopausal or Type I osteoporosis). Another high risk group for idiopathic osteoporosis is the elderly of either sex (senile or Type II osteoporosis). Osteoporosis has also been related to corticosteroid use, immobilization or extended bed rest, alcoholism, diabetes, gonadotoxic chemotherapy, hyperprolactinemia, anorexia nervosa, primary and secondary amenorrhea, and oophorectomy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Digital topological analysis of trabecular bone MR images and prediction of osteoporosis fractures Inventor(s): Wehrli, Felix W. (Bala Cynwyd, PA), Gomberg, Bryon Roos; (Philadelphia, PA), Saha, Punam K. (Philadelphia, PA) Correspondence: DILWORTH PAXSON LLP; 3200 MELLON BANK CENTER; 1735 MARKET STREET; PHILADELPHIA; PA; 19103; US Patent Application Number: 20020191823 Date filed: April 11, 2002 Abstract: The invention provides method, system and device for determining trabecular bone structure and strength by digital topological analysis, and offers, for the first time, a demonstration of superior associations between vertebral deformity and a number of architectural indices measured in the distal radius, thus permitting reliable and noninvasive detection and determination of the pathogenesis of osteoporosis. A preferred embodiment provides imaging in three dimension of a region of trabecular bone, after which the 3D image is converted into a skeletonized surface representation. Digital topological analysis is applied to the converted image, and each image voxel is identified and classified as a curve, a surface, or a junction; and then associated with microarchitectural indices of trabecular bone to quantitatively characterize the trabecular bone network. The invention is applicable in vivo, particularly on human subjects, or ex vivo.

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Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/283,270 filed on Apr. 12, 2001.... This invention relates generally to the field of digital topological analysis (DTA) to derive structural parameters from trabecular bone images obtained by magnetic resonance imaging (MRI), computed tomography (CT), or other imaging technologies, and the use of these parameters to assess trabecular bone structure in patients at risk of developing fractures from osteoporosis or those suffering from metabolic bone disorders.... Trabecular bone (TB) (also known as cancellous bone), which occurs in most of the axial skeleton and at locations toward the ends of the long bones, consists of a lattice of interconnected plates and rods that confer mechanical strength to the skeleton at minimum weight. In addition to the volume fraction of the trabecular bone (often quantified in terms of bone density), the three-dimensional (3D) arrangement of the trabecular network is a major determinant of elastic modulus (Odgaard et al.,.J Biomechan. 30:487-495 (1997)) and ultimate strength. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

EP4 receptor selective agonists in the treatment of osteoporosis Inventor(s): Cameron, Kimberly O. (East Lyme, CT), Lefker, Bruce A. (Gales Ferry, CA) Correspondence: Gregg C. Benson; Pfizer Inc. Patent Department, MS 4159,; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020065308 Date filed: November 21, 2001 Abstract: This invention is directed to EP4 receptor selective prostaglandin agonists of the Formula I, 1wherein R.sup.2, X, Z and Q are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds. This invention is also directed to methods of treating conditions which present with low bone mass, particularly osteoporosis, frailty, an osteoporotic fracture, a bone defect, childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, bone fracture, osteotomy, bone loss associated with periodontitis, or prosthetic ingrowth in a mammal comprising administering those compounds. Excerpt(s): The present application is a U.S. non-provisional application. This application claims the benefit of U.S. Ser. No. 60/253,275 filed on Nov. 27, 2000, under 35 USC 119(e).... This invention relates to EP4 receptor selective prostaglandin agonists, combinations, methods, kits and pharmaceutical compositions comprising said prostaglandin agonists which are useful to prevent bone loss, restore or augment bone mass and to enhance bone healing including the treatment of conditions which present with low bone mass and/or bone defects in vertebrates, and particularly mammals, including humans.... Osteoporosis is a systemic skeletal disease, characterized by low bone mass and deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In the U.S., the condition affects more than 25 million people and causes more than 1.3 million fractures each year, including 500,000 spine, 250,000 hip and 240,000 wrist fractures annually. Hip fractures are the most serious consequence of osteoporosis, with 5-20% of patients dying within one year, and over 50% of survivors being incapacitated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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EP4 receptor selective agonists in the treatment of osteoporosis Inventor(s): Thompson, David D. (Gales Ferry, CT), Lefker, Bruce A. (Gales Ferry, CT), Ke, HuaZhu; (Ledyard, CT), Cameron, Kimberly O. (East Lyme, CT) Correspondence: Gregg C. Benson; Pfizer Inc. Patent Department; Eastern Point Road, MS 4159; Groton; CT; 06340; US Patent Application Number: 20020040149 Date filed: November 16, 2001 Abstract: This invention is directed to methods of treating conditions which present with low bone mass, particularly osteoporosis, frailty, an osteoporotic fracture, a bone defect, childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, bone fracture, osteotomy, bone loss associated with periodontitis, or prosthetic ingrowth comprising administering prostaglandin agonists which are EP4 receptor selective prostaglandin agonists. This invention is especially directed to those methods wherein the EP4 receptor selective agonist is a compound of Formula I: 1wherein the variables are as defined in the specification. Excerpt(s): This invention relates to methods and pharmaceutical compositions comprising prostaglandin agonists which are useful to prevent bone loss, restore or augment bone mass and to enhance bone healing including the treatment of conditions which present with low bone mass and/or bone defects in vertebrates, and particularly mammals, including humans. This invention specifically relates to methods and pharmaceutical compositions comprising EP4 receptor selective prostaglandin agonists.... Osteoporosis is a systemic skeletal disease, characterized by low bone mass and deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In the U.S., the condition affects more than 25 million people and causes more than 1.3 million fractures each year, including 500,000 spine, 250,000 hip and 240,000 wrist fractures annually. Hip fractures are the most serious consequence of osteoporosis, with 5-20% of patients dying within one year, and over 50% of survivors being incapacitated.... The elderly are at greatest risk of osteoporosis, and the problem is therefore predicted to increase significantly with the aging of the population. Worldwide fracture incidence is forecasted to increase three-old over the next 60 years, and one study has estimated that there will be 4.5 million hip fractures worldwide in 2050. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Human osteoporosis gene Inventor(s): Styrkarsdottir, Unnur; (Reykjavik, IS), Johannsdottir, Vala Drofn; (Reykjavik, IS) Correspondence: HAMILTON, BROOK, SMITH & REYNOLDS, P.C. 530 VIRGINIA ROAD; P.O. BOX 9133; CONCORD; MA; 01742-9133; US Patent Application Number: 20030176344 Date filed: January 16, 2003 Abstract: A role of the human BMP2 nucleic acid in osteoporosis is disclosed. Methods for diagnosis, prediction of clinical course and treatment for osteoporosis or a susceptibility to osteoporosis using polymorphisms in the BMP2 nucleic acid, alone or in combination with other assays, are also disclosed.

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Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/952,360, filed Sep. 13, 2001, and which is also a continuation-in-part and claims priority to International Application No. PCT/IB01/01667, which designated the United States and was filed on Sep. 12, 2001, published in English, which is a continuation-inpart of U.S. application Ser. No. 09/661,887, filed Sep. 14, 2000. The entire teachings of the above applications are incorporated herein by reference.... Osteoporosis is a debilitating disease characterized by low bone mass and deterioration of bone tissue, as defined by decreased bone mineral density (BMD). A direct result of the experienced microarchitectural deterioration is susceptibility to fractures and skeletal fragility, ultimately causing high mortality, morbidity and medical expenses worldwide. Postmenopausal woman are at greater risk than others because the estrogen deficiency and corresponding decrease in bone mass experienced during menopause increase both the probability of osteoporotic fracture and the number of potential fracture sites. Yet aging women are not the only demographic group at risk. Young woman who are malnourished, ammenorrheic, or insufficiently active are at risk of inhibiting bone mass development at an early age. Furthermore, androgens play a role in the gain of bone mass during puberty, so elderly or hypogonadal men face the risk of osteoporosis if their bones were insufficiently developed.... The need to find a cure for this disease is complicated by the fact that there are many contributing factors that cause osteoporosis. Nutrition (particularly calcium, vitamin D and vitamin K intake), hormone levels, age, sex, race, body weight, activity level, and genetic factors all account for the variance seen in bone mineral density among individuals. Currently, the drugs approved to treat osteoporosis act as inhibitors of bone reabsorption, and include methods such as hormone replacement therapy (HRT), selective estrogen receptor modulators, calcitonin, and biophosphonates. However, these treatments may not individually reduce risk with consistent results and while some therapies improve BMD when co-administered, others show no improvement or even lose there efficacy when used in combination. Clearly, as life expectancy increases and health and economic concerns of osteoporosis grow, a solution for the risks associated with this late-onset disease is in great demand. Early diagnosis of the disease or predisposition to the disease would be desirable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for diagnosing osteoporosis and/or estimating risk of osteoporosis fracture Inventor(s): Ishizuka, Yasuyuki; (Kanagawa, JP), Niida, Shunpei; (Hiroshima, JP), Sanada, Mitsuhiro; (Hiroshima, JP) Correspondence: Thomas W Cole; Nixon Peabody; 8180 Greensboro Drive; Suite 800; McLean; VA; 22102; US Patent Application Number: 20030166038 Date filed: October 10, 2002 Abstract: Objects of the invention are to provide a new turnover marker and on the basis of this, to provide a method capable of diagnosis of osteoporosis and/or prediction of osteoporotic fracture risk quickly, conveniently, and accurately. To solve the problems, urine.gamma.-GTP is measured. Excerpt(s): The present invention relates to quickly-, conveniently- and accuratelyoperable method for diagnosis of osteoporosis and/or presumption of osteoporotic fracture risk.... Osteoporosis, that is characterized in that bone density decreases keeping normal bone composition, is a disease frequently occurring in a woman and a girl. Particularly, the woman of age 40s or more shows postmenopausal osteoporosis related

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to menopause in a high frequency. After 70s, senile osteoporosis occurs regardless of sex.... During decrease in bone density shows a low degree, no prominent clinical symptom appears. However, the degree of decrease becomes higher, fracture and bone deformation become easy to occur. A spine is easy to occur fracture and bone deformation and such symptoms as compressed fracture of a body of vertebra and lumbago caused by spinal deformation appear. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

METHOD FOR TREATING OSTEOPOROSIS IN CASTRATED PROSTATIC CANCER PATIENTS Inventor(s): BELL, ROBERT G. (PALM HARBOR, FL) Correspondence: MARK E WADDELL; BRYAN CAVE; 245 PARK AVENUE; NEW YORK; NY; 101670034 Patent Application Number: 20010041699 Date filed: April 2, 1999 Abstract: The present invention provides a method for preventing or treating osteoporosis in a castrated prostatic cancer patient, by administering to the patient an amount of from 10 mg to 300 mg cyproterone acetate per day. The present therapy is compatible with the patients' anticancer treatment. Excerpt(s): The present invention relates to a treatment for slowing or preventing the progression of osteoporosis in surgically or chemically castrated prostatic cancer patients.... Osteoporosis is generally the occurrence of a reduction in the quantity of bone, or the atrophy of skeletal tissue. This disorder is evidenced by a decrease in bone density throughout the body. Although the mechanism of osteoporosis is not entirely understood, it is believed that there is an imbalance between bone production and bone resorption, resulting in net bone resorption or breakdown. The condition can begin to occur as early as age 30. The process is typically more rapid in postmenopausal women than in men. Bone loss in males can be recognized at about 65 years of age. A significant bone loss is seen in men at about 80 years of age, and is accompanied by increased hip, spine and wrist fractures.... Surgical and chemical (e.g., LH-RH agonists) castration are widely used for the treatment of patients with prostate cancer. A number of side effects occur as a result of such therapy. Impotence and the occurrence of hot flashes are among the more distressing side effects to patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treatment of osteoporosis with compositions of red rice fermentation products Inventor(s): Dalin, He; (Beijing, CN), Shuren, Guo; (Beijing, CN), Yu-Fang, Zhou; (Beijing, CN), Xiu, Peng Chi; (Beijing, CN), Wen, Duan Zhen; (Beijing, CN), Liang, Zhang Mao; (Beijing, CN) Correspondence: FISH & RICHARDSON P.C. 500 ARGUELLO STREET, SUITE 500; REDWOOD CITY; CA; 94063; US Patent Application Number: 20030157068 Date filed: January 28, 2003

Patents 451

Abstract: Methods are disclosed for using red rice fermentation products for the treatment or prevention of osteoporosis and abnormal bone mass conditions. Particular Monascus strains yield fermentation products with the desired biological activities. Excerpt(s): This application is a continuation in part of U.S. Patent Application Ser. No. 09/542,438, filed Apr. 4, 2000, which is a divisional of Ser. No. 08/965,202, filed Nov. 6, 1997, now U.S. Pat. No. 6,046,022, which is a continuation-in-part of Ser. No. 08/720,548, filed Sep. 30, 1996, all of which are incorporated herein by reference in full.... The invention relates to the fields of rice fermentation and treatment of osteoporosis. More particularly, the invention relates to red rice fermentation products and use of the products to treat osteoporosis.... The invention relates to compositions comprising red rice fermentation product, that can be used to treat osteoporosis and related abnormal bone mass conditions in mammals, including humans. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for Identifying Potential Therapeutic Agents for Treatment of Osteoporosis Using Mitogenic Indices Inventor(s): ITTNER , Jochen; ( Augsburg, DE), JOSIMOVIC-ALASEVIC , Olivera; ( Berlin, DE), FRITSCH , Karl-Gerd; ( Berlin, DE) Correspondence: Birch, Stewart, Kolasch & Birch, LLP.. 8110 Gatehouse Road; PO Box 747; Falls Church; VA; 22040; US; [email protected]; 703-205-8000; 703-205-8050 Patent Application Number: 20020076730 Date filed: March 27, 1998 Abstract: A method of screening potential therapeutic substances that may be useful in the treatment of osteoporosis is provided herein utilizing primary osteoblast precursor cell cultures to determine the mitogenic effect of the tested agents. This method comprises preparation of the primary cultures from osteoporotic patients for the expression of several intracellular proteins in early and late osteoclast differentiation phases, expression of other proteins involved in matrix synthesis, and quantitative analysis of the cellular proliferation rate. The expression of such intracellular proteins and cell proliferation in the cultures derived from osteoporotic patients are quantitatively compared to primary osteoblast cell cultures from non-osteoporotic patients that are standardized for the same approximate age and sex. Excerpt(s): This application claims the benefit under 35 U.S.C..sctn.371 of prior PCT International Application No. PCT/DE96/01042 which has an International filing date of June 7, 1996 which designated the United States of America, the entire contents of which are hereby incorporated by reference.... Osteoporosis (bone atrophy) is a severe systemic disease of the skeleton, which is characterized by a reduced bone density (mass) occurring with a mosaic-like pattern, and micro-structural changes in the bone tissue. The bone tissue of a healthy adult person is subject to continuous formation and degradation even after completed development. Normally, two opposing processes are balanced. In the event of a prevailing degradation phase (bone resorption), however, the initial result will be bone atrophy (osteoporosis), i.e., reduced bone stability. The disease is accompanied by mostly lifelong pain, more frequent fractures, which may be followed by complications up to a fatal course. It is estimated that more than 200 million people worldwide, 7-8 millions in Germany, suffer from the above disease.... Therapeutic agents currently used against osteoporosis, such as estrogens, progesterones, calcitonin, di/bisphosphonates and calcium are merely capable of slowing down or reducing bone

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atrophy as a result of their effectiveness as anti-bone resorbers. Using the above, there is no success in replacing bone substance which has already been lost. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods involving the use of capG as a diagnostic marker and methods for the identification of capG modulators for the treatment and prevention of osteoporosis and related disease states Inventor(s): McAtee, C. Patrick; (Pennington, NJ) Correspondence: STEPHEN B. DAVIS; BRISTOL-MYERS SQUIBB COMPANY; PATENT DEPARTMENT; P O BOX 4000; PRINCETON; NJ; 08543-4000; US Patent Application Number: 20030017502 Date filed: March 15, 2002 Abstract: The present invention relates to the identification of capG as a critical enzyme in the process of RANKL-induced osteoclast-activation. The present invention includes modulators of capG and assays for the identification of such modulators, as well as the use of such modulators in the treatment and prevention of osteoporosis and related disease states. Excerpt(s): This application claims the benefit of provisional application U.S. Serial No. 60/276,250, filed Mar. 15, 2001.... The present invention relates to methods involving the use of capG as a diagnostic marker and methods for the identification of capG modulators. The capG modulators are useful for the treatment and prevention of osteoporosis and related disease states.... The osteoclast is a terminally differentiated cell derived from monocytic/macrophage lineage which resorbs bone as part of the normal process of skeletal modeling and remodeling. In contrast to precursor cells, only fully differentiated mature osteoclasts are able to resorb bone. Increased osteoclastic bone resorption has been linked to the pathogenesis of several skeletal disorders, most notably post-menopausal osteoporosis. As activated osteoclasts move over the bone surface to initiate new sites of bone resorption, cytoskeletal rearrangements lead to the formation of unique cell adhesion structures called podosomes which attach to the bone matrix via intermediate steps. Podosomes consist of an F-actin core surrounded by the actin-binding proteins vinculin, talin, and.alpha.-actinin (Marchisio, P. C. et al., "Cellsubstratum interactions of cultured avian osteoclasts is mediated by specific adhesion structures". J. Cell Biol., 99:1696-1705 (1984)). Osteoclasts attached to bone form a tight sealing zone resulting in an enclosed resorption lacunae. Localized membrane ruffling occurs at the cellular surface facing the bone, allowing the transport of protons and degradative enzymes within the resorption lacunae. One compound which is known to be involved with such ruffled border formation is gelsolin, although its precise function is not known. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of diagnosis and treatment of osteoporosis Inventor(s): Trantolo, Debra J. (Princeton, MA), Lewandrowski, Kai-Uwe; (Brookline, MA) Correspondence: PATREA L. PABST; HOLLAND & KNIGHT LLP; SUITE 2000, ONE ATLANTIC CENTER; 1201 WEST PEACHTREE STREET, N.E. ATLANTA; GA; 303093400; US Patent Application Number: 20020137082 Date filed: January 17, 2002 Abstract: A method of detecting osteoporosis in a mammalian is disclosed herein which includes:a) obtaining a sample of a bone related tissue or cells; andb) measuring the concentration of at least a marker which is either bacteria, bacteria produced factors, or HSPs. The method may further include comparing the concentration with concentrations from the same individual over a period of time or against a standard concentration. The marker may be a bacteria, a chaperone molecule, or a bacteria produced. Also provided herein is a method of treating or preventing osteoporosis caused by a bone disease which includes administering to a mammalian subject a therapeutically effective amount of a formulation which is either an HSP antigenic formulation or a bacterial antigenic formulation. The osteoporosis can be caused by a bone disease induced by bone infectious agents such as viruses, bacteria, fungi, protozoa and parasites. Excerpt(s): This application claims priority to U.S. Ser. No. 60/263,109 entitled "Methods of Using Heat Shock Proteins for Diagnosis and Treatment of Bone Disease" filed Jan. 19, 2001 by Kai-Uwe Lewandrowski and U.S. Ser. No. 60/304,887 entitled "Methods of Diagnosis and Treatment of Osteoporosis" filed Jul. 12, 2001 by Kai-Uwe Lewandrowski. The U.S. Government has rights to this application by virtue of a Grant from the National Institutes of Health.... The present application generally relates to methods for diagnosing bone loss. More specifically, the present application relates to identifying humoral markers for bone loss on the basis of bacterial or mammalian molecular chaperones.... Osteoporosis is a systemic disorder characterized by decreased bone mass and microarchitectural deterioration of bone tissue leading to bone fragility and increased susceptibility to fractures of hip, spine, and wrist. Osteopenia has been defined as the appearance of decreased bone mineral content on radiography, but the term more appropriately refers to a phase in the continuum from decreased bone mass to fractures and infirmity. By the time the diagnosis of osteopenia is made radiographically, significant and irreversible bone loss has already occurred. The most common cause of osteopenia is osteoporosis; other causes include osteomalacia and the bone disease of hyperparathyroidism. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of treating and preventing bone loss Inventor(s): Klein, Robert Frederick; (Portland, OR), Allard, John David; (Milpitas, CA), Peltz, Gary Allen; (Redwood City, CA) Correspondence: ROCHE PALO ALTO LLC; 3431 HILLVIEW AVENUE; PATENT DEPT., M/S A2-250; PALO ALTO; CA; 94304; US Patent Application Number: 20030175680 Date filed: February 7, 2003

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Abstract: Methods of treating and preventing bone loss and/or enhancing bone formation are disclosed. The methods utilize 15-lipoxygenase inhibitors. These molecules can be delivered alone or in combination with agents which inhibit bone resorption or additional agents that regulate calcium resorption from bone or enhances bone accumulation. The invention additionally provides methods of diagnosing a predisposition to bone loss. Excerpt(s): This application claims the priority benefit under Title 35 U.S.C. 119(e) of U.S. Provisional Application Serial No. 60/355,255, filed Feb. 8, 2002, the disclosure of which is herein incorporated by reference in its entirety.... The invention relates generally to 15-lipoxygenase inhibitors and their use in treating and preventing bone loss. Specifically, the invention relates to the use of 15-lipoxygenase inhibitors to decrease bone loss and/or increase net bone formation.... Lipoxygenases are nonheme iron-containing enzymes found in plants and animals that catalyze the oxygenation of certain polyunsaturated fatty acids, such as lipids and lipoproteins. Several different lipoxygenase enzymes are known, each having a characteristic oxidation action. Mammalian lipoxygenases are named by the position in arachidonic acid that is oxygenated. The enzyme 5-lipoxygenase converts arachidonic acid to 5hydroperoxyeicosatetraenoic acid (5-HPETE). This is the first step in the metabolic pathway which yields 5-hydroxyeicosatetraenoic acid (5-HETE) and the leukotrienes (LTs). Similarly, 12- and 15-lipoxygenase convert arachidonic acid to 12- and 15-HPETE, respectively. Biochemical reduction of 12-HPETE leads to 12-HETE, while 15-HETE is the precursor of the class of compounds known as lipoxins. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods to diagnose treat and prevent bone loss Inventor(s): Lang, Philipp; (Lexington, MA), Arnaud, Claude; (Mill Valley, CA) Correspondence: ROBINS & PASTERNAK LLP; 545 MIDDLEFIELD ROAD; SUITE 180; MENLO PARK; CA; 94025; US Patent Application Number: 20030015208 Date filed: May 28, 2002 Abstract: Methods of diagnosing and preventing bone loss and/or enhancing bone formation are disclosed. The invention additionally provides methods of diagnosing a predisposition to bone loss. The methods mathematically combine the information provided by imaging tests with the information provided by biomarkers to provide an index value. The index value is used for diagnosis of bone diseases, and to assess the progress of treatment of bone diseases. Excerpt(s): This application is related to U.S. Provisional Patent Application Serial No. 60/293,898, and U.S. Provisional Patent Application Serial No. 60/293,489, both filed on May 25, 2000, from which priority is claimed under 35 USC.sctn. 119(e)(1), and which applications are incorporated herein by reference in their entireties.... The invention relates generally to methods for diagnosing, screening, prognosing, and treating diseases. More particularly, the present invention relates to a method for diagnosing, screening or prognosing changes in bone loss, bone architecture or bone formation in humans or animals, and for determining the severity and cause of the disease by mathematically combining morphological data with metabolic data obtained using biomarkers.... Osteoporosis is a major public health issue caused by a reduction in bone mineral density in mature bone and results in fractures after minimal trauma. The most

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common fractures occur in the vertebrae, distal radius (Colles' fracture) and hip. An estimated one-third of the female population over age 65 will have vertebral fractures, caused in part by osteoporosis. Moreover, hip fractures are likely to occur in about one in every three woman and one in every six men by extreme old age. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Modulators of Bruton'sTyrosine Kinase and Bruton's Tyrosine Kinase intermediates and methods for their identification and use in the treatment and prevention of osteoporosis and related diseases states Inventor(s): McAtee, C. Patrick; (Pennington, NJ) Correspondence: STEPHEN B. DAVIS; BRISTOL-MYERS SQUIBB COMPANY; PATENT DEPARTMENT; P O BOX 4000; PRINCETON; NJ; 08543-4000; US Patent Application Number: 20030040461 Date filed: October 22, 2001 Abstract: The present invention relates to the identification of Bruton's Tyrosine Kinase as a critical intermediate in the process of osteoclast activation, modulators of Bruton's Tyrosine Kinase, and assays for the identification of such modulators. It is now found that such modulators are useful in the treatment and prevention of osteoporosis and related disease states. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/242,471, filed Oct. 23, 2000, and hereby expressly incorporated by reference in its entirety.... The present invention relates to kinase modulators and methods for their identification and use in the treatment and prevention of disease. Particularly, the present invention relates to modulators of Bruton's Tyrosine Kinase and Bruton's Tyrosine Kinase intermediates and methods for their identification and use in the treatment and prevention of osteoporosis and related disease states.... The osteoclast is a terminally differentiated cell derived from monocytic/macrophage lineage which resorbs bone as part of the normal process of skeletal modeling and remodeling. In contrast to precursor cells, only fully differentiated mature osteoclasts are able to resorb bone. Increased osteoclastic bone resorption has been linked to the pathogenesis of several skeletal disorders, most notably post-menopausal osteoporosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel use of calreticulin in modulating hormone responsiveness and new pharmaceuticals for treating cancer, osteoporosis and chronic inflammatory disease Inventor(s): Dedhar, Shoukat; (Ontario, CA) Correspondence: T. Gene Dillahunty; BURNS, DOANE, SWECKER & MATHIS, L.L.P. P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030060613 Date filed: November 29, 2001 Abstract: This invention relates to isolated and purified proteins, such as calreticulin and mimetics of calreticulin, for a novel use of modulating hormone responsiveness. These proteins are useful in gene therapy and in manufacturing pharmaceuticals for treating a variety of diseases, including cancer, osteoporosis and chronic inflammatory disease.

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The proteins include or bind to an amino acid sequence KXFFYR, wherein X is either G, A or V and Y is either K or R. This sequence is present in the DNA-binding domain, and is critical for the DNA binding activity, of a variety of hormone receptors, including glucocorticoid receptor, minerolcorticoid receptor, androgen receptor, progesterone receptor, estrogen receptor, retinoic acid receptor, thyroid hormone receptor and vitamin D receptor. Proteins which bind to this sequence may inhibit hormone receptor induced gene transcription. Proteins which include this sequence may promote hormone receptor induced gene transcription. The invention includes isolated DNA molecules for these proteins, methods of treating diseases using these proteins, synthetic peptides and their mimetics, and kits containing these proteins, synthetic peptides or their mimetics. Excerpt(s): This invention relates to isolated and purified proteins, such as calreticulin and mimetics of calreticulin, for a novel use of modulating hormone responsiveness. These proteins are useful in gene therapy and in manufacturing pharmaceuticals for treating a variety of diseases, including cancer, osteoporosis and chronic inflammatory disease. The proteins include or bind to an amino acid sequence KXFFYR, wherein X is either G, A or V and Y is either K or R. This sequence is present in the DNA-binding domain, and is critical for the DNA binding activity, of a variety of hormone receptors, including glucocorticoid receptor, minerolcorticoid receptor, androgen receptor, progesterone receptor, estrogen receptor, retinoic acid receptor, thyroid hormone receptor and vitamin D receptor. Proteins which bind to this sequence may inhibit hormone receptor induced gene transcription. Proteins which include this sequence may promote hormone receptor induced gene transcription. The invention includes isolated DNA molecules for these proteins, methods of treating diseases using these proteins, synthetic peptides and their mimetics, and kits containing these proteins, synthetic peptides or their mimetics.... The physiology of many organs in mammals is regulated by hormones. These hormones include steroid hormones, thyroid hormones, metabolites of vitamins, such as all trans retinoic acid, 9-cis retinoic acid, vitamin D and its metabolite 1,25 dihydroxyvitamin D3. These hormones are proteins and bind to intracellular receptors which regulate expression of genes (O'Malley, 1990).... There are a variety of receptors which respond to hormones. Osteoblasts and osteoclasts respond to steroid hormones, vitamin D and retinoic acid. Mammary epithelial cells and breast carcinoma cells respond to estrogens, progesterone, retinoic acid and glucocorticoids. Lymphocytes respond to glucocorticoids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Osteoporosis compounds Inventor(s): Lefker, Bruce A. (Gales Ferry, CT), Cameron, Kimberly O. (East Lyme, CT), Rosati, Robert L. (Stonington, CT) Correspondence: Gregg C. Benson; Pfizer Inc. Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020165255 Date filed: October 19, 2001 Abstract: This invention relates to prostaglandin agonists, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits containing such prostaglandin agonists. The prostaglandin agonists are useful for the treatment of bone disorders including osteoporosis.

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Excerpt(s): This invention relates to prostaglandin agonists, pharmaceutical compositions containing such agonists and the use of such agonists to prevent bone loss or restore or augment bone mass and to enhance bone healing including the treatment of conditions which present with low bone mass and/or bone defects in vertebrates, and particularly mammals, including humans.... Osteoporosis is a systemic skeletal disease, characterized by low bone mass and deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In the U.S., the condition affects more than 25 million people and causes more than 1.3 million fractures each year, including 500,000 spine, 250,000 hip and 240,000 wrist fractures annually. Hip fractures are the most serious consequence of osteoporosis, with 5-20% of patients dying within one year, and over 50% of survivors being incapacitated.... The elderly are at greatest risk of osteoporosis, and the problem is therefore predicted to increase significantly with the aging of the population. Worldwide fracture incidence is forecasted to increase three-fold over the next 60 years, and one study estimated that there Will be 4.5 million hip fractures worldwide in 2050. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Prevention and treatment of androgen-deprivation induced osteoporosis Inventor(s): Veverka, Karen A. (Cordova, TN), Steiner, Mitchell S. (Germantown, TN) Correspondence: Eitan, Pearl, Latzer & Cohen, Zedek, LLP; Suite 1001; 10 Rockefeller Plaza; New York; NY; 10020; US Patent Application Number: 20030153625 Date filed: November 27, 2002 Abstract: This invention provides: 1) a method of treating androgen-deprivation induced osteoporosis and/or bone fractures and/or loss of Bone Mineral Density (BMD) in a male subject suffering from prostate cancer; 2) a method of preventing androgendeprivation induced osteoporosis and/or bone fractures and/or loss of Bone Mineral Density (BMD) in a male subject suffering from prostate cancer; 3) a method of suppressing or inhibiting androgen-deprivation induced osteoporosis and/or bone fractures and/or loss of BMD in a male subject suffering from prostate cancer; and 4) a method of reducing the risk of developing androgen-deprivation induced osteoporosis and/or bone fractures and/or loss of BMD in a male subject suffering from prostate cancer, by administering to the subject a pharmaceutical composition comprising an anti-estrogen agent and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof as described herein. Excerpt(s): This application claims the priority of U.S. Provisional Application Serial No. 60/333,734, filed Nov. 29, 2001, which is incorporated in its entirety by reference herein.... This invention relates to reducing the incidence, inhibition, suppression, prevention and treatment of androgen-deprivation induced osteoporosis and/or bone fractures and/or loss of bone mineral density (BMD) in men suffering from prostate cancer. More particularly, this invention relates to a method of treating, preventing, suppressing, inhibiting, or reducing the risk of developing androgen-deprivation induced osteoporosis and/or bone fractures and/or loss of BMD in men suffering from prostate cancer, comprising administering to a male subject suffering from prostate cancer an anti-estrogen agent and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or any combination thereof.... It is well established that the bone mineral density of males

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decrease with age. Decreased amounts of bone mineral content and density correlates with decreased bone strength and predispose to fracture. The molecular mechanisms underlying the pleiotropic effects of sex-hormones in non-reproductive tissues are only beginning to be understood, but it is clear that physiologic concentrations of androgens and estrogens play an important role in maintaining bone homeostasis throughout the life-cycle. Consequently, when androgen or estrogen deprivation occurs, there is a resultant increase in the rate of bone remodeling that tilts the balance of resorption and formation in the favor of resorption, contributing to an overall loss of bone mass. In males, the natural decline in sex-hormones at maturity (direct decline in androgens as well as lower levels of estrogens derived from peripheral aromatization of androgens) is associated with the frailty of bones. This effect is also observed in males who have been castrated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Regulator gene and system useful for the diagnosis and therapy of osteoporosis Inventor(s): Gong, Yaoqin; (Jinan, CN), Rawadi, Georges; (Paris, FR), Roman-Roman, Sergio; (Paris, FR), Warman, Matthew L. (Shaker Heights, OH), Olsen, Bjorn R. (Milton, MA) Correspondence: HELLER EHRMAN WHITE & MCAULIFFE LLP; 1666 K STREET,NW; SUITE 300; WASHINGTON; DC; 20006; US Patent Application Number: 20030027151 Date filed: August 17, 2001 Abstract: A bone strength and mineralization regulatory ("BSMR") protein is provided that can exist in multiple forms and that affects bone density. Polymorphic gene sequences of the protein are provided that are diagnostic of predipostion to osteoporosis. Other detection tools, compositions and methods of their use also are provided for predicting, evaluating and altering bone strength and mineralization status. The invention provides new natural and synthetic pharmaceuticals that effect the BSMR regulatory pathway and improve bone status. Tools also are provided for finding new pharmaceuticals that operate by binding to BSMR and that activate and/or deactivate this protein's biological function related to osteoporosis and blood vessel formation. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/304,851, filed Jul. 13, 2001; U.S. Provisional Application No. 60/226,119, filed Aug. 18, 2000; and U.S. Provisional Application No. 60/234,337, filed Sep. 22, 2000.... The invention relates generally to polynucleic acid and polypeptide sequences associated with regulation of bone strength and mineralization and more particularly to the use of polynucleic acid, peptides, pharmaceuticals and antibodies for the diagnosis and regulation of bone strength and mineralization.... Osteoporosis is a common medical problem with major morbidity and societal cost. Individuals afflicted with this disease present diminished bone strength as a consequence of low bone mineral content. Heritable factors have been implicated as causes of osteoporosis. One osteoporosis disease that has a genetic cause is osteoporosis-pseudoglioma syndrome ("OPS"), which is characterized by severe juvenile-onset osteoporosis and congenital or juvenile-onset blindness. Because of the postulated mendelian genetic basis of this disease, patients and their families that present OPS symptoms have been studied to determine the location of the responsible gene. An early report from such studies indicated that the gene may reside within human chromosome 11 Gong et al., Am. J. Hum. Gen. 55 suppl:

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A186 (1994). A more detailed report of this localization was published subsequently by Gong et al., Amer. J. Hum. Gen. 59: 146-151 (1996). In the years since that publication, the Warman laboratory intensively has looked for further clues to the disease by studying more affected patients and their families. However data from the additional families did not suffice for a more precise localization to an interval on human chromosome 11q13. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Therapeutic agent of osteoporosis comprising an active ingredient of quercetin derivatives Inventor(s): Song, Kye-Yong; (Seoul, KR), Ha, Hye-Kyung; (Seoul, KR), Kim, ChungSook; (Seoul, KR) Correspondence: KNOBBE MARTENS OLSON & BEAR LLP; 620 NEWPORT CENTER DRIVE; SIXTEENTH FLOOR; NEWPORT BEACH; CA; 92660; US Patent Application Number: 20020165169 Date filed: February 22, 2002 Abstract: The present invention relates to a therapeutic agent for osteoporosis which comprises an active ingredient of quercetin derivatives. The quercetin derivatives of the invention can be practically applied for the treatment and prevention of osteoporosis, since they effectively inhibit osteoclast proliferation and stimulate osteoblast proliferation more than conventional therapeutic agents for osteoporosis, and increase trabecular bone area highly without changing hormone level in body and untoward effects on hematopoietic function and immune system. Excerpt(s): Osteoporosis is a disease characterized by the decrease of bone mass caused by mineral loss and the subsequent expansion of marrow cavity. Bones become brittle with the progress of the disease, and may be easily fractured by a weak impact. Bone mass is affected by various factors such as genetic factors, nutritive condition, changes of hormone level, exercise and life style, and osteoporosis is known to be caused by aging, lack of exercise, low body weight, smoking, low calcium diet, menopause, and ovariectomy. In women, decrease of bone mass begins at the age of 30, and around menopause, concentration of estrogen rapidly decreases and vast amount of Blymphocytes are accumulated by the similar mechanism to that of B-lymphocyte accumulation by IL-7(interleukin 7), and subsequent pre-B cell accumulation results in increased level of IL-6 which activates osteoclasts, thus, bone mass becomes decreased. In aged people, especially in women of postmenopause, osteoporosis is not the avoidable disease although the severity of the symptom may vary, therefore, many research groups and pharmaceutical companies have made a great deal of efforts for development of therapeutic agents for bone diseases to prevent and treat osteoporosis upon an increase of elderly population.... Therapeutic agents for osteoporosis now being used include estrogen preparations, androgenic anabolic steroid preparations, calcium supplements, phosphate preparations, fluoride preparations, ipriflavone, vitamin D3, etc. In recent years, novel drugs for osteoporosis have been developed, which include Aminobisphosphonate by Merck Co. (U.S.A.) in 1995 and Raloxifene which plays a role of selective estrogen receptor modulator(SERM) by Eli Lilly Co.(U.S.A.) in 1997.... Therapeutic agents for osteoporosis mentioned above are mostly estrogen substances which are known to cause adverse side effects such as cancer, cholelithiasis, and thrombosis. Since long term administration of drug is inevitable in the treatment of osteoporosis, there is a continuing need to develop novel effective agents which can

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replace estrogen with high safety even when administered for a prolonged period of time. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of osteoporosis Inventor(s): Ballard, Francis J. (Burnside, AU), Tapley, Peter M. (Collegeville, PA), Conover, Cheryl A. (Rochester, MN), Khosla, Sundeep; (Rochester, MN) Correspondence: MARK S. ELLINGER, PH.D. Fish & Richardson P.C., P.A. Suite 3300; 60 South Sixth Street; Minneapolis; MN; 55402; US Patent Application Number: 20020151490 Date filed: October 5, 2001 Abstract: A substantially pure complex including IGFIIE polypeptide and IGFBP2 polypeptide is described. Methods for treating an osteoporosis patient and targeting a compound to the skeletal extracellular matrix of a patient are also described. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/428,226, filed Oct. 27, 1999, which is a continuation-in-part of U.S. application Ser. No. 09/073,032, filed May 5, 1998, which in turn claims priority from U.S. Provisional Application Serial No. 60/045,607, filed May 5, 1997.... Hepatitis C-associated osteosclerosis (HCAO) is a rare syndrome characterized by a marked increase in skeletal mass in adults who are infected with the hepatitis C virus. Beyer et al., J. Bone Min. Res., 5:1257-1263 (1990); and Diamond et al., Bone, 19:679-683 (1996). Spine and hip bone mineral densities are elevated as much as two-fold in these affected individuals, who represent the most dramatic example of acquired osteosclerosis in humans. Radiographs show dense bones in the appendicular and axial skeleton, with sparing of the calvarium and facial bones. Biochemical markers of bone formation are usually elevated, and transiliac bone biopsies generally show increased bone formation rates. Nevertheless, osseous tissue from these patients appears histologically to be of good quality with intact lamellar patterns, unlike the abnormal, rapidly remodeling woven bone found in patients with Paget's bone disease.... To date, ten cases of HCAO have been reported. It is apparent, however, that only a small percentage of all patients infected with hepatitis C develop osteosclerosis, since skeletal radiographs of 107 randomly selected hepatitis C infected patients failed to show dense bones. Beyer et al., Am. J. Med., 95:660-662 (1990). Thus, although it is uncertain whether hepatitis C is the causative agent of the skeletal disease, a plausible hypothesis is that either hepatitis C or another parenterally transmitted agent increases hepatic production of a growth factor(s) that stimulate osteoblast function. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment or prevention of menopausal symptoms and osteoporosis Inventor(s): Kelly, Graham E. (Northbridge, AU) Correspondence: FINNEGAN, HENDERSON, FARABOW, GARRETT &; DUNNER LLP; 1300 I STREET, NW; WASHINGTON; DC; 20005; US Patent Application Number: 20020035074 Date filed: November 9, 2001

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Abstract: There is described a method for the treatment or prevention of menopausal symptoms or osteoporosis wherein there is administered to a subject in need of such treatment a therapeutically effective amount of the isoflavone formononetin, or a method for the treatment or prevention of menopausal symptoms wherein there is administered to a subject in need of such treatment a therapeutically effective amount of the isoflavone daidzein, the isoflavone being optionally administered with one or more pharmaceutically acceptable adjuvants, carriers and/or excipients. Therapeutic uses and compositions/foods are also described, comprising daidzein or formononetin optionally in association with one or more pharmaceutically acceptable adjuvants, carriers, food components and/or excipients. Excerpt(s): This invention relates to compositions, therapeutic uses and methods of treatment or prevention of menopausal symptoms and osteoporosis.... Menopausal symptoms and osteoporosis are significant scourges in the female population, generally affecting many women in later life.... Menopausal symptoms are very well known and are described, for example, by Greene, J. G. and Cooke, D. J. (1980) British Journal of Psychiatry Volume 136, 486-491 (incorporated herein by reference). Hot flushes are one of the principal menopausal symptoms which are uncomfortable and irritating. Greene and Cooke have developed a score in order to measure menopausal symptoms in women. This score is approved by the US Department of Health and widely used in the medical community. The indicators of menopausal symptoms according to Greene and Cooke comprise hot flushes, sweating at night, heart beating quickly or strongly, feelings of tension or nervousness, difficulty in sleeping, excitability, attacks of panic, difficulties in concentrating, feelings of tiredness or lack of energy, unhappiness or depression, crying spells, irritability, feelings of dizziness or faintness, pressure or tightness in head or body, parts of the body feeling numb or tingling, dry vagina and/or dry mouth, headaches, muscle and joint pains, loss of feeling in hands or feet, breathing difficulties, and loss of interest in sex. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of alendronate for the prevention of osteoporosis Inventor(s): Yates, Ashley J. (Westfield, NJ) Correspondence: MERCK AND CO INC; P O BOX 2000; RAHWAY; NJ; 070650907 Patent Application Number: 20020169148 Date filed: April 2, 2002 Abstract: Alendronate, an aminobisphosphonate, can prevent osteoporosis in early post menopausal women. Excerpt(s): This invention relates to the use of alendronate, an aminobisphosphonate, for the prevention of osteoporosis in early postmenopausal women.... Alendronate, 4amino-1-hydroxybutylidene-1,1-bisphosphonic acid, and its pharmaceutically acceptable salts has been found to be useful in the treatment of osteoporosis. Alendronate is a specific inhibitor of bone resorption. It has a high affinity for bone mineral and is taken up into the bone selectively where it inhibits osteoclast activity. While alendronate has been shown to be useful in restoring lost bone, there has been no indication that it can prevent the loss of bone in otherwise healthy individuals.... Peak bone mass in women is achieved at around 30-35 years of age, after which bone mass is lost progressively throughout life. The rate of loss is accelerated during the early post menopausal period, especially at sites with a high component of trabecular bone.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of harpagid-related compounds for prevention and treatment of osteoporosis, arthritis and ruptured disc and pharmaceutical composition containing the same Inventor(s): Shin, Joon Shik; (Seoul, KR), Kim, Sang Tae; (Seoul, KR), Han, Yong Nam; (Seoul, KR) Correspondence: BIRCH STEWART KOLASCH & BIRCH; PO BOX 747; FALLS CHURCH; VA; 22040-0747; US Patent Application Number: 20020183264 Date filed: November 29, 2001 Abstract: In the present invention, it is discovered that a compound of formula (I) has a potent effect for treatment of osteoporosis, arthritis and ruptured disc: 1in which R.sub.1 represents hydrogen atom or alkyl group and R.sub.2 represents hydrogen atom r cinnamoyl group. Therefore, the compound of formula (I) can be used for prevention and treatment of osteoporosis, arthritis and ruptured disc. Thus, the present invention provides a pharmaceutical preparation containing as an effective component a compound of formula (I) in combination with a pharmaceutically acceptable auxiliary, diluent, isotonic agent, preservative, lubricant and solubilizing aid, which is formulated in the form of a pharmaceutically acceptable preparation and has a potent effect for osteoporosis, arthritis and ruptured disc. Excerpt(s): The present invention relates to a use of a harpagid-related compound as an agent for treating arthritis, osteoporosis and ruptured disc, and to a pharmaceutical composition containing said harpagid-related compound as an effective component.... At present, it has been known that in Korea patients suffering from various bone diseases are on an increasing tendency annually. However, chemotherapy, operative therapy, etc. which have been currently used for the purpose of treating bone diseases have fail to realize the complete success as yet. Such bone diseases are advanced to chronic and degenerative state due to ageing, and further impose a great medical burden on a patient. Therefore, the development of novel materials which can be generally utilized in the clinical field is still urgently required.... The constituent drugs contained in the galenic composition developed by the present inventors have been described in "Dongeubogam" and "Sinnongbonchokyung" as having various pharmacological activities including hematopoiesis, tonic, diuresis, bone marrow formation, recruitment of vitality and virility, effects on pre- and post-partum joint, lumbago, stomachic, anti-inflammatory, promotion of blood circulation and removal of blood stasis, elimination of nervous disorders, detoxication, hemostasis, effect of alleviating climacteric disorders, emmenagogic effect, nutritive effect, hematic activity, etc. Further, other activities have also been disclosed in prior reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of thioamide oxazolidinones for the treatment of bone resorption and osteoporosis Inventor(s): Mesfin, Gebre-mariam; (Portage, MI), Jensen, Richard K. (Kalamazoo, MI) Correspondence: Andrew M. Solomon; Pharmacia & Upjohn Company; Global Intellectual Property; 301 Henrietta Street; Kalamazoo; MI; 49001; US Patent Application Number: 20020010341 Date filed: April 17, 2001 Abstract: The use of thioamide oxazolidinones for the treatment of bone resorption and osteoporosis is provided. Excerpt(s): The present invention is directed to a new use for known compounds. More specifically, the invention relates to the use of thioamide oxazolidinones for the treatment of bone resorption, osteoporosis and other bone diseases.... Bone is not a static tissue. It is subject to constant breakdown and resynthesis in a complex process mediated by osteoblasts, which produce new bone, and osteoblasts, which destroy bone. The activities of these cells are regulated by a large number of cytokines and growth factors, many of which have now been identified and cloned. Mundy has described the current knowledge related to these factors (Mundy, G. R. Clin Orthop 324:24-28, 1996; Mundy, G. R. J Bone Miner Res 8:S505-10, 1993).... Although there is a great deal of information available on the factors which influence the breakdown and resorption of bone, information on growth factors that stimulate the formation of new bone is more limited. Investigators have searched for sources of such activities, and have found that bone tissue itself is a storehouse for factors that have the capacity for stimulating bone cells. Thus, extracts of bovine bone tissue obtained from slaughterhouses contain not only structural proteins which are responsible for maintaining the structural integrity of bone, but also biologically active bone growth factors which can stimulate bone cells to proliferate. Among these latter factors are transforming growth factor beta., the heparinbinding growth factors (e.g., acidic and basic fibroblast growth factor), the insulin-like growth factors (e.g., insulin-like growth factor I and insulin-like growth factor II), and a recently described family of proteins called bone morphogenetic proteins (BMPs). All of these growth factors have effects on other types of cells, as well as on bone cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with osteoporosis, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “osteoporosis” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on osteoporosis. You can also use this procedure to view pending patent applications concerning osteoporosis. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON OSTEOPOROSIS Overview This chapter provides bibliographic book references relating to osteoporosis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on osteoporosis include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “osteoporosis” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on osteoporosis: •

Exercise for Osteoporosis Source: Long Island City, NY: Hatherleigh Press. 2000. 144 p. Contact: Available from Hatherleigh Press. 5-22 46th Avenue, Long Island City, NY 11101. (800) 528-2550. Fax: (800) 621-8892. Website: www.hatherleighpress.com. Email: [email protected]. Price: $14.95 plus shipping. ISBN: 1578260760. Summary: This book presents exercises that will help the osteoporosis patient strengthen their bones and improve their balance and flexibility. Osteoporosis is a disease that is characterized by abnormal loss of bone density. Although it is perceived that osteoporosis is a disease of older women, osteoporosis can affect men and women who are young or middle-aged. It is estimated that 25 million Americans suffer from osteoporosis and if preventive measures are not taken now, the incidence of this disease may double within 25 years. To prevent osteoporosis, the patient should stop smoking cigarettes, taking steroids, consuming large amounts of alcohol, and choose to eat a

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balanced diet and live an active lifestyle. Questions to determine osteoporosis risk are listed. Fractures most commonly occur at the wrist, spine, and hip. Exercise precautions are listed. The exercises in the book are divided into sections by body part: spine, hip, wrist, chest and arms, and abdominals. Each exercise is illustrated. In addition, exercises for balance and breathing are included. Suggested exercise routines are included as well as an equipment and resource list. 4 references and numerous pictures. •

Osteoporosis: A guide to prevention, early detection and treatment Source: Richmond, VA: Virginia Department of Health. ca. 1997. 43 pp. Contact: Available from Virginia Department of Health, 1500 East Main Street, Richmond, VA 23219. Summary: This document discusses the Osteoporosis Prevention Initiative in Virginia, understanding osteoporosis, early detection, treatment, prevention, and communication guidelines for educators. An osteoporosis resource list of national and state agencies is provided.

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Aging, Osteoporosis, and Dental Implants Source: Chicago, IL: Quintessence Publishing Co, Inc. 2002. 260 p. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $78.06 plus shipping and handling. ISBN: 0867154071. Summary: The book contains the proceedings of a symposium on Aging, Osteoporosis and Dental Implants, that was held at the University of Toronto (Canada) in November 2000. The proceedings attempt to reconcile the current clinical understanding of aging, with or without osteoporosis (abnormal loss of bone density), with overall dental patient management strategies, placing particular emphasis on the induction and maintenance of the osseointegrated (an induced healing process where alloplastic materials are maintained in bone) response (necessary for dental implants). The text includes 19 chapters in four sections: biologic and bioengineering considerations for prescribing prosthetic implants, the oral surgical experience, the prosthodontic experience, and biologic perspectives related to osseointegration in the elderly. Topics include mesenchymal stem cells, the concept of bone quality in osteoporosis, mechanical factors and osseointegration (the influence of implant design), choosing a prosthesis for total hip replacement, host determinants and outcome criteria for osseointegration surgery, compromised alveolar bone quality in edentulous (without teeth) jaws, compromised jawbone quantity, surgical site development, strategies for bone regeneration and osseointegration in completely edentulous patients, epidemiological considerations with oral implants for elderly patients, the significance of tooth loss in the elderly patients, the advent of osseointegration and its impact on prosthodontic management, mandibular implant-retained overdentures (load transfer, tissue reaction, oral function), implant prosthodontic treatment outcomes in elderly patients, regulation of biomineralization, the effects of postmenopausal osteoporosis on the mandible (lower jaw), and cigarette smoking and osseointegration. Each chapter concludes with a list of references. The text is illustrated with black and white and full color photographs, charts and figures. A subject index concludes the volume.

Books 467

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “osteoporosis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “osteoporosis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “osteoporosis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

150 Most-Asked Questions About Osteoporosis: What Women Really Want to Know by Ruth S. Jacobowitz; ISBN: 0688147690; http://www.amazon.com/exec/obidos/ASIN/0688147690/icongroupinterna

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A Colour Atlas of Osteoporosis by J.F. Aloia MD FACP; ISBN: 0723416915; http://www.amazon.com/exec/obidos/ASIN/0723416915/icongroupinterna

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A Discussion of the Diagnosis and Treatment of Osteoporosis by Solomon Posen (Editor) (1986); ISBN: 0920887074; http://www.amazon.com/exec/obidos/ASIN/0920887074/icongroupinterna

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A Guide to Osteoporosis (Humanatomy, 7) by Tim Peters (1994); ISBN: 1879874415; http://www.amazon.com/exec/obidos/ASIN/1879874415/icongroupinterna

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A Practical guide to Osteoporosis by Richard Eastell, et al (2002); ISBN: 185317887X; http://www.amazon.com/exec/obidos/ASIN/185317887X/icongroupinterna

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A Slide Atlas of Osteoporosis/Slides (The Encyclopedia of Visual Medicine) by J. C. Stevenson, M.S. Marsh (1994); ISBN: 1850705518; http://www.amazon.com/exec/obidos/ASIN/1850705518/icongroupinterna

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A Woman Doctor's Guide to Osteoporosis: Essential Facts and Up-To-The Minute Information on the Prevention, Treatment, and Reversal of Bone Loss (Books for Women by Women) by Yvonne R. Sherrer, Robin Karol Levinson (Contributor); ISBN: 0786880457; http://www.amazon.com/exec/obidos/ASIN/0786880457/icongroupinterna

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About Osteoporosis by Ruth S. Jacoowitz; ISBN: 0614978491; http://www.amazon.com/exec/obidos/ASIN/0614978491/icongroupinterna

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Advances in Nutritional Research: Nutrition and Osteoporosis by Harold H. Draper (Editor) (1995); ISBN: 0306448939; http://www.amazon.com/exec/obidos/ASIN/0306448939/icongroupinterna

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Advances in Some Aspects of Osteoporosis by J. L. Ambrus (Editor), et al (1985); ISBN: 0915340135; http://www.amazon.com/exec/obidos/ASIN/0915340135/icongroupinterna

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Aging and Osteoporosis in Native Americans Form Pecos Pueblo, New Mexico: Behavioral and Biomechanical Effects (The Evolution of North American Indi) by Christopher Ruff (1991); ISBN: 0824025156; http://www.amazon.com/exec/obidos/ASIN/0824025156/icongroupinterna

468 Osteoporosis

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Aging, Osteoporosis, and Dental Implants by George A. Zarb (Editor), et al; ISBN: 0867154071; http://www.amazon.com/exec/obidos/ASIN/0867154071/icongroupinterna

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American College of Physicians Home Medical Guide: Osteoporosis by David R. Goldmann (Editor), et al; ISBN: 0789441721; http://www.amazon.com/exec/obidos/ASIN/0789441721/icongroupinterna

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An Atlas of Osteoporosis, Second Edition by John C. Stevenson, et al; ISBN: 1850709874; http://www.amazon.com/exec/obidos/ASIN/1850709874/icongroupinterna

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Anabolic Treatments for Osteoporosis by James F., Ph.D. Whitfield (Editor), Paul, Ph.D. Morley (Editor); ISBN: 0849385563; http://www.amazon.com/exec/obidos/ASIN/0849385563/icongroupinterna

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Arthritis, Rheumatism and Osteoporosis by Bernard Jensen (1986); ISBN: 0932615031; http://www.amazon.com/exec/obidos/ASIN/0932615031/icongroupinterna

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Assessment and Management of Risks Associated With Hyperlipidemia, Osteoporosis, and Hepatitis B: Effectiveness of Intervention (Medical Advisory Co) by R. Gordon Douglas (Editor) (1991); ISBN: 1560530227; http://www.amazon.com/exec/obidos/ASIN/1560530227/icongroupinterna

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Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis (Who Technical Report, No 843) by Who Study Group on Assessment of Fracture Risk and Its Application to, et al (1994); ISBN: 9241208430; http://www.amazon.com/exec/obidos/ASIN/9241208430/icongroupinterna

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Atlas of Osteoporosis by Eric S. Orwoll (Editor) (2003); ISBN: 1573401986; http://www.amazon.com/exec/obidos/ASIN/1573401986/icongroupinterna

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Avoiding Osteoporosis (Positive Health Guides) by Allan Dixon, Anthony Woolf; ISBN: 0356154459; http://www.amazon.com/exec/obidos/ASIN/0356154459/icongroupinterna

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Beat Osteoporosis Special Diet Cookbook: Help Yourself to Delicious, Calcium-rich Recipes to Help Make Stronger Bones by Victor G. Ettinger MD, Judy Fredal RD; ISBN: 0722522142; http://www.amazon.com/exec/obidos/ASIN/0722522142/icongroupinterna

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Beat Your Risk Factors: A Woman's Guide to Reducing Her Risk for Cancer, Heart Disease, Stroke, Diabetes and Osteoporosis by Charlotte Libov, Lila A. Wallis; ISBN: 0452278325; http://www.amazon.com/exec/obidos/ASIN/0452278325/icongroupinterna

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Better Bones, Better Body: A Comprehensive Self-Help Program for Preventing, Halting and Overcoming Osteoporosis by Susan E. Brown, Phyllis Herman (Editor); ISBN: 0879837004; http://www.amazon.com/exec/obidos/ASIN/0879837004/icongroupinterna

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BMA Family Doctor Series: Osteoporosis (BMA Family Doctor) by Tony Smith (Editor), Family Doctor Publications ) Medical Editor (Editor); ISBN: 0751306835; http://www.amazon.com/exec/obidos/ASIN/0751306835/icongroupinterna

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Bone Ageing and Osteoporosis by Moniz; ISBN: 0340583657; http://www.amazon.com/exec/obidos/ASIN/0340583657/icongroupinterna

Books 469

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Bone Boosters: The Natural Way to Prevent Osteoporosis by Diana Moran, Helen Franks; ISBN: 1852834269; http://www.amazon.com/exec/obidos/ASIN/1852834269/icongroupinterna

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Bone Densitometry and Osteoporosis by Harry K. Genant (Editor), et al (1997); ISBN: 3540631496; http://www.amazon.com/exec/obidos/ASIN/3540631496/icongroupinterna

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Bone Loading: Exercises for Osteoporosis by Ariel Simkin, Judith Ayalon (1997); ISBN: 1853752118; http://www.amazon.com/exec/obidos/ASIN/1853752118/icongroupinterna

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Bone Loading: The New Way to Prevent and Combat the Thinning Bones of Osteoporosis by Ariel Simkin, et al; ISBN: 1853750328; http://www.amazon.com/exec/obidos/ASIN/1853750328/icongroupinterna

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Bone Loss and Osteoporosis: An Anthropological Perspective by Sabrina C. Agarwal (Editor), Sam D. Stout (Editor) (2003); ISBN: 030647767X; http://www.amazon.com/exec/obidos/ASIN/030647767X/icongroupinterna

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Bone Loss: Causes, Detection, and Therapy by Anthony August Albanese; ISBN: 0471562653; http://www.amazon.com/exec/obidos/ASIN/0471562653/icongroupinterna

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Build Bone Health: Prevent and Treat Osteoporosis by Freedolph Anderson, Linda Evans; ISBN: 1890694223; http://www.amazon.com/exec/obidos/ASIN/1890694223/icongroupinterna

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Build Strong Bones: Prevent osteoporosis and enhance bone health naturally by Mark Stengler, et al; ISBN: 1890694142; http://www.amazon.com/exec/obidos/ASIN/1890694142/icongroupinterna

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Building Stronger Bones Naturally: The Osteoporosis Diet and Exercise Plan by Xandria Williams; ISBN: 0600604578; http://www.amazon.com/exec/obidos/ASIN/0600604578/icongroupinterna

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Calcium and Osteoporosis (Evaluation of Publicly Available Scientific Evidence Regarding Certain nutrIent Series) by Robert P. Heaney (1991); ISBN: 9992239840; http://www.amazon.com/exec/obidos/ASIN/9992239840/icongroupinterna

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Calcium: Beat the Osteoporosis Epidemic by Leonard Mervyn; ISBN: 0722515790; http://www.amazon.com/exec/obidos/ASIN/0722515790/icongroupinterna

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Clinical Trials in Osteoporosis by Derek Pearson (Editor), Colin G. Miller (Editor) (2002); ISBN: 1852332298; http://www.amazon.com/exec/obidos/ASIN/1852332298/icongroupinterna

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Clinician's Manual on Male Osteoporosis by Orwoll, ES Orwoll (2001); ISBN: 1858739241; http://www.amazon.com/exec/obidos/ASIN/1858739241/icongroupinterna

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Clinicians Manual on Osteoporosis by Aviolo (1994); ISBN: 1878132083; http://www.amazon.com/exec/obidos/ASIN/1878132083/icongroupinterna

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Clinician's Manual on Osteoporosis (2nd Edition) by Avioli, LV Avioli (1997); ISBN: 1858730805; http://www.amazon.com/exec/obidos/ASIN/1858730805/icongroupinterna

470 Osteoporosis

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Clinician's Manual on Prevention and Management of Osteoporosis by Ralston, SH Ralston (2001); ISBN: 1858739225; http://www.amazon.com/exec/obidos/ASIN/1858739225/icongroupinterna

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Contemporary Diagnosis and Management of Osteoporosis by Daniel T. Baran; ISBN: 1884065481; http://www.amazon.com/exec/obidos/ASIN/1884065481/icongroupinterna

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Ct Densitometry In Osteoporosis: The Impact On Management Of The Patient by L.E.H. Duursma, S.A. and Ruys, J.H.J. Lampmann (1984); ISBN: 0898386330; http://www.amazon.com/exec/obidos/ASIN/0898386330/icongroupinterna

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Current Research in Osteoporosis and Bone Mineral Measurement V by E.F.J. Ring (Editor), et al (1998); ISBN: 0905749391; http://www.amazon.com/exec/obidos/ASIN/0905749391/icongroupinterna

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Current Research in Osteoporosis and Bone Mineral Measurement: 1992 by E.F.J. Ring (Editor); ISBN: 0905749294; http://www.amazon.com/exec/obidos/ASIN/0905749294/icongroupinterna

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Current Research in Osteoporosis and Bone Mineral Measurement: 1994 Proceedings of the 4th Bath Conference on Osteoporosis and Bone Mineral Measurement, 21-24 June, 1994 by E.F.J. Ring (Editor) (1994); ISBN: 0905749332; http://www.amazon.com/exec/obidos/ASIN/0905749332/icongroupinterna

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Current Research in Osteoporosis and Bone Mineral Measurement: Proceedings of the Second Bath Conference on Osteoporosis and Bone Mineral Measurement, Bath, 25-27 June 1990 by E.F.J. Ring (Editor); ISBN: 0905749235; http://www.amazon.com/exec/obidos/ASIN/0905749235/icongroupinterna

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Cyclical etidronate : a new dimension in therapy for osteoporosis : proceedings, April 22, 1989, Paris, France; ISBN: 0444013849; http://www.amazon.com/exec/obidos/ASIN/0444013849/icongroupinterna

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Dealing with Osteoporosis by Partha Banerjee (1988); ISBN: 0805931465; http://www.amazon.com/exec/obidos/ASIN/0805931465/icongroupinterna

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Diseases Explained: Osteoporosis Wall Chart by Lexi-Comp; ISBN: 1930598181; http://www.amazon.com/exec/obidos/ASIN/1930598181/icongroupinterna

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Dr. Linda Page's Healthy Healing Guide to Menopause & Osteoporosis by Linda Rector-Page, Linda R. Page; ISBN: 1884334903; http://www.amazon.com/exec/obidos/ASIN/1884334903/icongroupinterna

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Drugs of Tomorrow: Osteoporosis - Will Bone Building Drugs Revolutionize the Market? [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3YT; http://www.amazon.com/exec/obidos/ASIN/B00008R3YT/icongroupinterna

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Eating Well, Living Well With Osteoporosis (Eating Well Living Well) by Laura P. Svetkey, et al; ISBN: 0670866598; http://www.amazon.com/exec/obidos/ASIN/0670866598/icongroupinterna

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Effectiveness and Costs of Osteoporosis Screening and Hormone Replacement Therapy by United States; ISBN: 0160482070; http://www.amazon.com/exec/obidos/ASIN/0160482070/icongroupinterna

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Effectiveness and costs of osteoporosis screening and hormone replacement therapy; ISBN: 0160482089; http://www.amazon.com/exec/obidos/ASIN/0160482089/icongroupinterna

Books 471

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Ernst Schering Research Foundation Workshop, Supplement 4: Hormone Replacement Therapy and Osteoporosis by Junzo Kato (Editor), et al; ISBN: 3540664807; http://www.amazon.com/exec/obidos/ASIN/3540664807/icongroupinterna

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European Osteoporosis Treatment Markets: Market Driven by New Interest in Preventive Measures by Market Intelligence (1995); ISBN: 078890258X; http://www.amazon.com/exec/obidos/ASIN/078890258X/icongroupinterna

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Everything You Need to Know About Osteoporosis by Rosemary Nicol; ISBN: 085969612X; http://www.amazon.com/exec/obidos/ASIN/085969612X/icongroupinterna

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Exercise and Osteoporosis (Current Issues in Exercise Science, No 4) by Barbara Drinkwater; ISBN: 0873223292; http://www.amazon.com/exec/obidos/ASIN/0873223292/icongroupinterna

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Exercise for Strong Bones: Your Easy-to-follow Guide to Reducing Your Risk of Osteoporosis (Carroll & Brown Fitness Book) by Joan Bassey, Susie Dinan; ISBN: 1903258383; http://www.amazon.com/exec/obidos/ASIN/1903258383/icongroupinterna

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Exercise for Strong Bones: Your Easy-to-follow Stand-up Guide to Reducing Your Risk of Osteoporosis by Joan Bassey PhD, et al; ISBN: 1903258146; http://www.amazon.com/exec/obidos/ASIN/1903258146/icongroupinterna

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Exercises for Osteoporosis by Dianne Daniels, Peter Field Peck (Photographer) (2000); ISBN: 1578260760; http://www.amazon.com/exec/obidos/ASIN/1578260760/icongroupinterna

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Fast Facts: Osteoporosis (Fast Facts) by Juliet E. Compston, Clifford J. Rosen; ISBN: 1899541756; http://www.amazon.com/exec/obidos/ASIN/1899541756/icongroupinterna

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Fighting Osteoporosis by Xandria Williams (2002); ISBN: 1589230515; http://www.amazon.com/exec/obidos/ASIN/1589230515/icongroupinterna

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Food and Our Bones: The Natural Way to Prevent Osteoporosis by Annemarie Colbin (1998); ISBN: 0452278066; http://www.amazon.com/exec/obidos/ASIN/0452278066/icongroupinterna

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Generalized Bone Diseases: Osteoporosis, Osteomalacia, Ostitis Fibrosa by F. Kuhlencordt, et al (1988); ISBN: 0387187898; http://www.amazon.com/exec/obidos/ASIN/0387187898/icongroupinterna

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Generalized Bone Diseases: Osteoporosis, Osteomalacia, Ostitis Fibrosa. Proceedings of 2nd Annual Conference of the German Society for Osteology; ISBN: 3540187898; http://www.amazon.com/exec/obidos/ASIN/3540187898/icongroupinterna

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Glucocorticoid-Induced Osteoporosis (Frontiers of Hormone Research, Vol 30) by Andrea Giustina (Editor), et al (2002); ISBN: 3805572964; http://www.amazon.com/exec/obidos/ASIN/3805572964/icongroupinterna

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Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis by World Health Organization (1998); ISBN: 9241545224; http://www.amazon.com/exec/obidos/ASIN/9241545224/icongroupinterna

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Health Policy Reviews - a Public Policy for Osteoporosis: the Case of Spain: the Case of Spain by Nick Bosanquet, et al; ISBN: 1854671944; http://www.amazon.com/exec/obidos/ASIN/1854671944/icongroupinterna

472 Osteoporosis

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Health Risks/How to Test Yourself and Lower Your Chances of Cancer, Heart Disease, Stroke, Osteoporosis, Diabetes, Stress by Elliott J. Howard, et al (1987); ISBN: 0895864428; http://www.amazon.com/exec/obidos/ASIN/0895864428/icongroupinterna

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Healthy Bones & Joints: A Natural Approach to Treating Arthritis, Osteoporosis, Tendinitis, Myalgia & Bursitis by David Hoffmann, David Hoffman; ISBN: 1580172539; http://www.amazon.com/exec/obidos/ASIN/1580172539/icongroupinterna

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Healthy Bones: What You Should Know About Osteoporosis by Nancy Appleton; ISBN: 0895294621; http://www.amazon.com/exec/obidos/ASIN/0895294621/icongroupinterna

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Hormone Replacement and Its Impact on Osteoporosis by Claus Christiansen; ISBN: 0702015482; http://www.amazon.com/exec/obidos/ASIN/0702015482/icongroupinterna

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Hormone Replacement Therapy and Osteoporosis by M. Kleerekoper, Michael Kleerekoper; ISBN: 1842140302; http://www.amazon.com/exec/obidos/ASIN/1842140302/icongroupinterna

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Hormone Replacement Therapy Yes or No?: How to Make an Informed Decision About Estrogen, Progesterone, & Other Strategies for Dealing With Pms, Menopause, & Osteoporosis by Betty Kamen (1996); ISBN: 0944501109; http://www.amazon.com/exec/obidos/ASIN/0944501109/icongroupinterna

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How to Fight Osteoporosis & Win!: The Miracle of Microscrystalline Hydroxapitite (McHc) by Beth M. Ley; ISBN: 0964270358; http://www.amazon.com/exec/obidos/ASIN/0964270358/icongroupinterna

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Hrt and Osteoporosis by J.O. Drife, J.W.W. Studd (Editor); ISBN: 0387196285; http://www.amazon.com/exec/obidos/ASIN/0387196285/icongroupinterna

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Hrt and Osteoporosis (1990); ISBN: 3540196285; http://www.amazon.com/exec/obidos/ASIN/3540196285/icongroupinterna

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I'm Not Slowing Down: Winning My Battle With Osteoporosis by Ann Richards, Richard U. Levine (Contributor) (2003); ISBN: 0525946918; http://www.amazon.com/exec/obidos/ASIN/0525946918/icongroupinterna

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Key Advances in the Effective Management of Osteoporosis (Key Advances) by Juliet Compston (Editor), Ignac Fogelman (Editor); ISBN: 1853153982; http://www.amazon.com/exec/obidos/ASIN/1853153982/icongroupinterna

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Keys to Understanding Osteoporosis (Barron's Keys to Retirement Planning) by Jan Rozek; ISBN: 0812046641; http://www.amazon.com/exec/obidos/ASIN/0812046641/icongroupinterna

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Living With Osteoporosis by Joan Gomez (2001); ISBN: 0859698386; http://www.amazon.com/exec/obidos/ASIN/0859698386/icongroupinterna

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Living With Osteoporosis: Guidelines for Women Before and After Diagnosis by Mehrsheed Sinaki, et al; ISBN: 1556641281; http://www.amazon.com/exec/obidos/ASIN/1556641281/icongroupinterna

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Mayo Clinic on Osteoporosis: Keeping Bones Healthy and Strong and Reducing the Risk of Fractures by Stephen, Md. Hodges, Stephen Hodgson (Editor) (2003); ISBN: 1893005240; http://www.amazon.com/exec/obidos/ASIN/1893005240/icongroupinterna

Books 473

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Mechanobiology: Osteoarthritis and Skeletal Regeneration, and Osteoporosis and Bone Functional Adaptation by Tamara T. Sowell (Editor); ISBN: 0756705908; http://www.amazon.com/exec/obidos/ASIN/0756705908/icongroupinterna

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Menopause & osteoporosis : A-Z guide to natural healing by Brenda Beeley; ISBN: 0966224000; http://www.amazon.com/exec/obidos/ASIN/0966224000/icongroupinterna

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Menopause and Osteoporosis by Linda Rector-Page, Linda R. Page (1997); ISBN: 1884334652; http://www.amazon.com/exec/obidos/ASIN/1884334652/icongroupinterna

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Menopause and Osteoporosis: Taking Charge of Your Life Change and Preventing Bone Loss (Healthy Healing Library Ser. Vol. 1) by Linda R. Page; ISBN: 1884334237; http://www.amazon.com/exec/obidos/ASIN/1884334237/icongroupinterna

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Menopause, HRT and Osteoporosis; ISBN: 075211123X; http://www.amazon.com/exec/obidos/ASIN/075211123X/icongroupinterna

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Natural Alternatives to Hrt: Overcome Osteoporosis, Heart Disease, and Other Menopausal Conditions Without Risky Synthetic Hormone Replacement by Rita Elkins (2003); ISBN: 1580543693; http://www.amazon.com/exec/obidos/ASIN/1580543693/icongroupinterna

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New Horizons in Osteoporosis by C. Christiansen (Editor) (1988); ISBN: 1850701962; http://www.amazon.com/exec/obidos/ASIN/1850701962/icongroupinterna

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Novel Approaches to Treatment of Osteoporosis (Ernst Schering Research Foundation Workshop, 25) by R. G. G. Russell (Editor), et al (1999); ISBN: 3540648135; http://www.amazon.com/exec/obidos/ASIN/3540648135/icongroupinterna

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Nutritional Aspects of Osteoporosis (Serono Symposia) by Peter Burckhardt (Editor), et al (1998); ISBN: 0387984941; http://www.amazon.com/exec/obidos/ASIN/0387984941/icongroupinterna

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Orthopaedic Issues in Osteoporosis by Yuehuei H. An (Editor); ISBN: 0849310334; http://www.amazon.com/exec/obidos/ASIN/0849310334/icongroupinterna

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Osteomalacia, renal osteodystrophy, and osteoporosis by Brian Morgan; ISBN: 0398026025; http://www.amazon.com/exec/obidos/ASIN/0398026025/icongroupinterna

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Osteoporosis by John C. Stevenson (Editor), Robert Lindsay (Editor); ISBN: 0412488701; http://www.amazon.com/exec/obidos/ASIN/0412488701/icongroupinterna

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Osteoporosis by J. Menczel; ISBN: 0471101567; http://www.amazon.com/exec/obidos/ASIN/0471101567/icongroupinterna

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Osteoporosis by Betty Kamen; ISBN: 0523423136; http://www.amazon.com/exec/obidos/ASIN/0523423136/icongroupinterna

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Osteoporosis by Margot Joan Fromer; ISBN: 0671546872; http://www.amazon.com/exec/obidos/ASIN/0671546872/icongroupinterna

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Osteoporosis by M. S. Klempner (Editor) (1990); ISBN: 0746200862; http://www.amazon.com/exec/obidos/ASIN/0746200862/icongroupinterna

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Osteoporosis (1995); ISBN: 0881673501; http://www.amazon.com/exec/obidos/ASIN/0881673501/icongroupinterna

474 Osteoporosis

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Osteoporosis; ISBN: 0915201143; http://www.amazon.com/exec/obidos/ASIN/0915201143/icongroupinterna

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Osteoporosis by Deborah Lee (1998); ISBN: 1580540066; http://www.amazon.com/exec/obidos/ASIN/1580540066/icongroupinterna

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Osteoporosis by B. E. Nordin (Editor) (1990); ISBN: 1850703035; http://www.amazon.com/exec/obidos/ASIN/1850703035/icongroupinterna

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Osteoporosis; ISBN: 1860160794; http://www.amazon.com/exec/obidos/ASIN/1860160794/icongroupinterna

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Osteoporosis; ISBN: 1860161391; http://www.amazon.com/exec/obidos/ASIN/1860161391/icongroupinterna

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Osteoporosis by Juliet E. Compston, Clifford J. Rosen; ISBN: 1899541624; http://www.amazon.com/exec/obidos/ASIN/1899541624/icongroupinterna

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Osteoporosis by Jorge R. Talbot, Jos R. Zanchetta (2001); ISBN: 9500626179; http://www.amazon.com/exec/obidos/ASIN/9500626179/icongroupinterna

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Osteoporosis by K.K. Pun; ISBN: 9622092780; http://www.amazon.com/exec/obidos/ASIN/9622092780/icongroupinterna

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Osteoporosis (1994); ISBN: 9993026115; http://www.amazon.com/exec/obidos/ASIN/9993026115/icongroupinterna

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Osteoporosis by Wi Beck (1940); ISBN: 9998249325; http://www.amazon.com/exec/obidos/ASIN/9998249325/icongroupinterna

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Osteoporosis - Commercial and Clinical Perspectives: White: Osteoporosis by G P White, Juliet Compston; ISBN: 1860673600; http://www.amazon.com/exec/obidos/ASIN/1860673600/icongroupinterna

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Osteoporosis (2nd Edition; 2-Volume Set) by Robert Marcus (Editor), et al; ISBN: 0124708625; http://www.amazon.com/exec/obidos/ASIN/0124708625/icongroupinterna

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Osteoporosis (Bailliere's Clinical Rheumatology) by D.M. Reid; ISBN: 0702017116; http://www.amazon.com/exec/obidos/ASIN/0702017116/icongroupinterna

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Osteoporosis (Self Care Health Library) by Stephen Langer; ISBN: 0879834161; http://www.amazon.com/exec/obidos/ASIN/0879834161/icongroupinterna

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Osteoporosis (Ward Lock Family Health Guide) by Clare Dover, National Osteoporosis Society; ISBN: 0706372565; http://www.amazon.com/exec/obidos/ASIN/0706372565/icongroupinterna

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Osteoporosis : selected papers presented at the Workshop on Current Strategies in the Treatment of Osteoporosis : held during the 9th International Conference on Calcium Regulating Hormones and Bone Metabolism, Nice, 25 October-1 November 1986; ISBN: 0444808914; http://www.amazon.com/exec/obidos/ASIN/0444808914/icongroupinterna

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Osteoporosis : selected papers presented at the Workshop on Current Strategies in the Treatment of Osteoporosis : held during the 9th International Conference on Calcium Regulating Hormones and Bone Metabolism, Nice, 25 October-1 November 1986; ISBN: 0444809104; http://www.amazon.com/exec/obidos/ASIN/0444809104/icongroupinterna

Books 475

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Osteoporosis : The Complete Guide To Prevention and Treatment by John F. Aloia M.D., M.D. John F. Aloia; ISBN: 0967031001; http://www.amazon.com/exec/obidos/ASIN/0967031001/icongroupinterna

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Osteoporosis 1996 by World Congress on Osteoporosis, et al; ISBN: 0444822763; http://www.amazon.com/exec/obidos/ASIN/0444822763/icongroupinterna

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Osteoporosis and Bone Biology - the State of the Art by Juliet Compston, Stuart Ralston (Editor); ISBN: 1901769054; http://www.amazon.com/exec/obidos/ASIN/1901769054/icongroupinterna

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Osteoporosis and Bone Mineral Measurement by E.F.J. Ring, et al; ISBN: 0904181596; http://www.amazon.com/exec/obidos/ASIN/0904181596/icongroupinterna

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Osteoporosis Compendium by Nigel Arden (2002); ISBN: 1850091749; http://www.amazon.com/exec/obidos/ASIN/1850091749/icongroupinterna

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Osteoporosis Fast Facts Series by Giardino, et al; ISBN: 1878060317; http://www.amazon.com/exec/obidos/ASIN/1878060317/icongroupinterna

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Osteoporosis II; ISBN: 0808911813; http://www.amazon.com/exec/obidos/ASIN/0808911813/icongroupinterna

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Osteoporosis in Asia: Crossing the Frontiers by E. M. C. Lau (Editor), et al (1997); ISBN: 9810227302; http://www.amazon.com/exec/obidos/ASIN/9810227302/icongroupinterna

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Osteoporosis in Chronic Liver Disease (Comprehensive Summaries of Uppsala Dissertations from the Faculty of mediciNe, 1037) by Sif Ormarsdottir (2001); ISBN: 9155450210; http://www.amazon.com/exec/obidos/ASIN/9155450210/icongroupinterna

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Osteoporosis in Clinical Practice by Mark Aitken (1984); ISBN: 0723607338; http://www.amazon.com/exec/obidos/ASIN/0723607338/icongroupinterna

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Osteoporosis in Clinical Practice: A Practical Guide for Diagnosis & Treatment by P. Geusens (Editor) (2004); ISBN: 1852337575; http://www.amazon.com/exec/obidos/ASIN/1852337575/icongroupinterna

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Osteoporosis in Clinical Practice: A Practical Guide for Diagnosis and Treatment by Piet Geusens (Editor) (1998); ISBN: 354076223X; http://www.amazon.com/exec/obidos/ASIN/354076223X/icongroupinterna

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Osteoporosis in Dialogue: 100 Questions-100 Answers by Johann D. Ringe (2002); ISBN: 1588900746; http://www.amazon.com/exec/obidos/ASIN/1588900746/icongroupinterna

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Osteoporosis in Focus by Niall Ferguson, Pharmaceutical Press (2003); ISBN: 0853694834; http://www.amazon.com/exec/obidos/ASIN/0853694834/icongroupinterna

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Osteoporosis in Men by J. M. Kaufman; ISBN: 1842140337; http://www.amazon.com/exec/obidos/ASIN/1842140337/icongroupinterna

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Osteoporosis in Men: The Effects of Gender on Skeletal Health by Eric S. Orwoll (Preface); ISBN: 0125286406; http://www.amazon.com/exec/obidos/ASIN/0125286406/icongroupinterna

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Osteoporosis Management by Ian R. Reid, et al; ISBN: 0864710836; http://www.amazon.com/exec/obidos/ASIN/0864710836/icongroupinterna

476 Osteoporosis

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Osteoporosis Pocketbook (Medical Pocketbooks) by Anthony D. Woolf BsC MRCP; ISBN: 1853170453; http://www.amazon.com/exec/obidos/ASIN/1853170453/icongroupinterna

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Osteoporosis Reconsidered by William Dr Hunter; ISBN: 9996648265; http://www.amazon.com/exec/obidos/ASIN/9996648265/icongroupinterna

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Osteoporosis Research, Education & Health Promotion (1993); ISBN: 0788100637; http://www.amazon.com/exec/obidos/ASIN/0788100637/icongroupinterna

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Osteoporosis Update, 1987 by Harry K. Genant (1987); ISBN: 9991272852; http://www.amazon.com/exec/obidos/ASIN/9991272852/icongroupinterna

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Osteoporosis, La by Juliet Compston (2001); ISBN: 8440698208; http://www.amazon.com/exec/obidos/ASIN/8440698208/icongroupinterna

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Osteoporosis, Second Edition, CD by Robert Marcus, et al (2001); ISBN: 012470865X; http://www.amazon.com/exec/obidos/ASIN/012470865X/icongroupinterna

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Osteoporosis, the Silent Stalker: A Woman's Illustrated Guide to the Prevention & Treatment of Osteoporosis by Timothy J. Gray, Kathy Kaplan (Illustrator) (1994); ISBN: 096222698X; http://www.amazon.com/exec/obidos/ASIN/096222698X/icongroupinterna

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Osteoporosis: A Clinical Guide by Anthony D. Woolf, Allan St. John Dixon; ISBN: 0397583095; http://www.amazon.com/exec/obidos/ASIN/0397583095/icongroupinterna

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Osteoporosis: A Guide to Diagnosis and Treatment (Rheumatology, Vol 18) by H. Broll (Editor), et al (1996); ISBN: 3805556241; http://www.amazon.com/exec/obidos/ASIN/3805556241/icongroupinterna

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Osteoporosis: A Guide to Diagnosis, Prevention, and Treatment by Robert Lindsay; ISBN: 0881679410; http://www.amazon.com/exec/obidos/ASIN/0881679410/icongroupinterna

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Osteoporosis: A Guide to Prevention and Treatment by John F. Aloia; ISBN: 0880113545; http://www.amazon.com/exec/obidos/ASIN/0880113545/icongroupinterna

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Osteoporosis: A Multi-Disciplinary Problem by A.St.J. Russell, R.G.G. and Stamp, T.C.B. Dixon (Editor); ISBN: 0127910549; http://www.amazon.com/exec/obidos/ASIN/0127910549/icongroupinterna

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Osteoporosis: A Natural Approach to Prevention by Westeron Stephens (1995); ISBN: 0964421518; http://www.amazon.com/exec/obidos/ASIN/0964421518/icongroupinterna

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Osteoporosis: A New Concept In Treatment And Prevention by PT John Papalia; ISBN: 0970432313; http://www.amazon.com/exec/obidos/ASIN/0970432313/icongroupinterna

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Osteoporosis: A Woman Doctor's Guide by Yvonne R. Sherrer, Robin K. Levinson (Contributor); ISBN: 1575665786; http://www.amazon.com/exec/obidos/ASIN/1575665786/icongroupinterna

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Osteoporosis: An Evidence-Based Guide to Prevention and Management by Steven R. Cummings (Editor), et al; ISBN: 0943126959; http://www.amazon.com/exec/obidos/ASIN/0943126959/icongroupinterna

Books 477

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Osteoporosis: An Exercise Guide by Margie Bissinger, Cecil Byk (Illustrator); ISBN: 0966879201; http://www.amazon.com/exec/obidos/ASIN/0966879201/icongroupinterna

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Osteoporosis: Brittle Bones and the Calcium Crisis by Kathleen Mayes; ISBN: 0915201151; http://www.amazon.com/exec/obidos/ASIN/0915201151/icongroupinterna

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Osteoporosis: Contributions to Modern Management: The Proceedings of a Symposium Held at the Xviith Ilar Congress of Rheumatology, Rio De Janeiro, S by B.E.C. Nordin (Editor) (1990); ISBN: 0929858638; http://www.amazon.com/exec/obidos/ASIN/0929858638/icongroupinterna

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Osteoporosis: Critique and Practicum by Richard D. Wasnich, et al (1989); ISBN: 0962326518; http://www.amazon.com/exec/obidos/ASIN/0962326518/icongroupinterna

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Osteoporosis: Diagnosis & Management by Meunier; ISBN: 1853176133; http://www.amazon.com/exec/obidos/ASIN/1853176133/icongroupinterna

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Osteoporosis: Diagnosis and Management by Pierre J. Meunier; ISBN: 1853174122; http://www.amazon.com/exec/obidos/ASIN/1853174122/icongroupinterna

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Osteoporosis: Diagnosis and Treatment by David J. Sartoris (Editor); ISBN: 0824795075; http://www.amazon.com/exec/obidos/ASIN/0824795075/icongroupinterna

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Osteoporosis: Diagnostic and Therapeutic Principles by Clifford J. Rosen (Editor); ISBN: 0896033740; http://www.amazon.com/exec/obidos/ASIN/0896033740/icongroupinterna

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Osteoporosis: Etiology, Diagnosis, and Management by B. Lawrence Riggs, L. Joseph, III Melton (Editor); ISBN: 0781702755; http://www.amazon.com/exec/obidos/ASIN/0781702755/icongroupinterna

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Osteoporosis: Fighting the Silent Epidemic by Leonard Rose; ISBN: 1863737553; http://www.amazon.com/exec/obidos/ASIN/1863737553/icongroupinterna

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Osteoporosis: Fundamentals of Clinical Practice by Murray J. Favus (Editor), Sylvia Christakos (Editor); ISBN: 0397518234; http://www.amazon.com/exec/obidos/ASIN/0397518234/icongroupinterna

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Osteoporosis: Genetics, Prevention and Treatment (Endocrine Updates, 3) by John S. Adams (Editor), Barbara P. Lukert (Editor) (1999); ISBN: 0792383664; http://www.amazon.com/exec/obidos/ASIN/0792383664/icongroupinterna

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Osteoporosis: How to Make Your Bones Last a Lifetime (Twenty-First Century Health) by Cynthia E. Sutton, Wanda Lyon (Contributor); ISBN: 1569430055; http://www.amazon.com/exec/obidos/ASIN/1569430055/icongroupinterna

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Osteoporosis: How to Prevent It: A Comprehensive Audio Guide for Women from 1880/Audio Cassette (Bantam Audio Health Guide, No 3) by Biocom Ltd. ISBN: 055345014X; http://www.amazon.com/exec/obidos/ASIN/055345014X/icongroupinterna

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Osteoporosis: How to Prevent the Brittle Bone Disease by Wendy Smith, Stanton H. Cohn; ISBN: 067155252X; http://www.amazon.com/exec/obidos/ASIN/067155252X/icongroupinterna

478 Osteoporosis

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Osteoporosis: Medical Blunders and Treatment Strategies by William N. Taylor (1996); ISBN: 0786402296; http://www.amazon.com/exec/obidos/ASIN/0786402296/icongroupinterna

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Osteoporosis: Medical Subject Index of Progress With Reference Bibliography by Jennifer H. Houston (1987); ISBN: 0881647500; http://www.amazon.com/exec/obidos/ASIN/0881647500/icongroupinterna

•

Osteoporosis: New Medical Therapies by Lisa Henderson; ISBN: 0967302943; http://www.amazon.com/exec/obidos/ASIN/0967302943/icongroupinterna

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Osteoporosis: New Perspectives on Causes, Prevention and Treatment by Juliet E. Compston (Editor); ISBN: 1860160379; http://www.amazon.com/exec/obidos/ASIN/1860160379/icongroupinterna

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Osteoporosis: Now Under Control by R. Bartl, B. Frisch (2003); ISBN: 3540404996; http://www.amazon.com/exec/obidos/ASIN/3540404996/icongroupinterna

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Osteoporosis: Nutritional Aspects (World Review of Nutrition and Dietetics, Vol 73) by Artemis P. Simopoulos (Editor), Claudio Galli (Editor) (1993); ISBN: 3805557515; http://www.amazon.com/exec/obidos/ASIN/3805557515/icongroupinterna

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Osteoporosis: Pathogenesis and Management by R.M. Francis (Editor) (1990); ISBN: 0792389336; http://www.amazon.com/exec/obidos/ASIN/0792389336/icongroupinterna

•

Osteoporosis: Pathophysiology and Clinical Management by Eric S. Orwoll (Editor), Michael Bliziotes (Editor); ISBN: 0896039331; http://www.amazon.com/exec/obidos/ASIN/0896039331/icongroupinterna

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Osteoporosis: Physiological Basis, Assessment, and Treatment: Proc Nineteenth Steenbock Symposium Held June 5 Through June 8, 1989, Univ Wis-madison by Hector F. Deluca, Richard Mazess (Editor); ISBN: 0444015264; http://www.amazon.com/exec/obidos/ASIN/0444015264/icongroupinterna

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Osteoporosis: Pocketbook by Anthony D. Woolf; ISBN: 1853176788; http://www.amazon.com/exec/obidos/ASIN/1853176788/icongroupinterna

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Osteoporosis: Prevention & Treatment by Nancy Wiltsek (Editor), Felix Kolb (1986); ISBN: 0933161077; http://www.amazon.com/exec/obidos/ASIN/0933161077/icongroupinterna

•

Osteoporosis: Prevention & Treatment by Gloria M. Bertacchi (1988); ISBN: 0945753179; http://www.amazon.com/exec/obidos/ASIN/0945753179/icongroupinterna

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Osteoporosis: Prevention and Management in Primary Care (Clinical Series) by Colin Waine OBE FRCGP FRCPath (1997); ISBN: 0850842336; http://www.amazon.com/exec/obidos/ASIN/0850842336/icongroupinterna

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Osteoporosis: Prevention, Diagnosis and Management, Fourth Edition by Morris Notelovitz; ISBN: 1884735843; http://www.amazon.com/exec/obidos/ASIN/1884735843/icongroupinterna

•

Osteoporosis: Questions and Answers by Michael C. Ellerington, et al (1993); ISBN: 1873413556; http://www.amazon.com/exec/obidos/ASIN/1873413556/icongroupinterna

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Osteoporosis: Recent Advances in Pathogenesis and Treatment: Proceedings of the Tenth Steenbock Symposium, Held at the University of Wisconsin--madi by Hector F.

Books 479

Deluca; ISBN: 0839116306; http://www.amazon.com/exec/obidos/ASIN/0839116306/icongroupinterna •

Osteoporosis: The Aetiology and Clinical Management of Generalized Bone Loss by R Lindsay; ISBN: 0838575374; http://www.amazon.com/exec/obidos/ASIN/0838575374/icongroupinterna

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Osteoporosis: The Alternatives by Dr. Eva Lee Snead MD, Michael A. Moczygemba (2000); ISBN: 1893157008; http://www.amazon.com/exec/obidos/ASIN/1893157008/icongroupinterna

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Osteoporosis: The Brittle Bones Epidemic and How You Can Avoid It by Kathleen Mayes; ISBN: 0722525095; http://www.amazon.com/exec/obidos/ASIN/0722525095/icongroupinterna

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Osteoporosis: The Long Road Back: One Woman's Story by Pamela Horner (1989); ISBN: 0776602268; http://www.amazon.com/exec/obidos/ASIN/0776602268/icongroupinterna

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Osteoporosis: The Silent Thief by William A. Peck, Louis V. Avioli (Photographer); ISBN: 0673248372; http://www.amazon.com/exec/obidos/ASIN/0673248372/icongroupinterna

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Osteoporosis: Unmasking a Silent Thief: Your Step-By-Step Guide to Understanding, Diagnosing, Preventing, and Treating One of the Worst Dangers of Aging by Raymond E., D.O., C.C.D. Cole (2000); ISBN: 0917073037; http://www.amazon.com/exec/obidos/ASIN/0917073037/icongroupinterna

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Osteoporosis: What It Is, How to Prevent It, How to Stop It by Betty Kamen, Si Kamen (Contributor); ISBN: 1558171711; http://www.amazon.com/exec/obidos/ASIN/1558171711/icongroupinterna

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Osteoporosis: Your Head Start on the Prevention and Treatment of Brittle Bones by David F. Fardon; ISBN: 0895865602; http://www.amazon.com/exec/obidos/ASIN/0895865602/icongroupinterna

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Osteoporosis: Your Questions Answered by J. N. Fordham (2004); ISBN: 044307366X; http://www.amazon.com/exec/obidos/ASIN/044307366X/icongroupinterna

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Osteroporosis Sourcebook: Basic Consumer Health Information About Primary and Secondary Osteoporosis and Juvenile Osteoporosis and Related Conditions, Including Fibrous dysplas (Health Reference Series) by Allan R. Cook (Editor) (2001); ISBN: 078080239X; http://www.amazon.com/exec/obidos/ASIN/078080239X/icongroupinterna

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Outwitting Osteoporosis: The Smart Woman's Guide to Bone Health by Ronda Gates, Beverly, Ph.D. Whipple (2003); ISBN: 1582700990; http://www.amazon.com/exec/obidos/ASIN/1582700990/icongroupinterna

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Patient's Health Maintenance Workbook for Osteoporosis and Arthritis: A Guide to Self-Care and Healing by Brian C. Leutholtz (1999); ISBN: 0849307147; http://www.amazon.com/exec/obidos/ASIN/0849307147/icongroupinterna

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Permanent Remissions : Life-Extending Diet Stategies That Can Help Prevent and Reverse Cancer, Heart Disease, Diabets, and Osteoporosis by Robert Haas, Kristin Massey (1997); ISBN: 0671007769; http://www.amazon.com/exec/obidos/ASIN/0671007769/icongroupinterna

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Permanent Remissions: Life-Extending Diet Strategies That Can Help Prevent and Reverse Cancer, Heart Disease, Diabetes, and Osteoporosis by Robert Haas; ISBN:

480 Osteoporosis

0671007777; http://www.amazon.com/exec/obidos/ASIN/0671007777/icongroupinterna •

Preventing & Managing Osteoporosis by Sarah Hall Gueldner (Editor), et al (2002); ISBN: 1591020271; http://www.amazon.com/exec/obidos/ASIN/1591020271/icongroupinterna

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Preventing and Reversing Osteoporosis : What You Can Do About Bone Loss--A Leading Expert's Natural Approach to Increasing Bone Mass by Alan R. Gaby (1995); ISBN: 0761500227; http://www.amazon.com/exec/obidos/ASIN/0761500227/icongroupinterna

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Preventing Osteoporosis; ISBN: 0553301233; http://www.amazon.com/exec/obidos/ASIN/0553301233/icongroupinterna

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Preventing Osteoporosis with Ipriflavone: Discover the Proven, Safe Alternative to Estrogen Replacement Therapy by Andrea Girman, Carol Poole; ISBN: 0761522220; http://www.amazon.com/exec/obidos/ASIN/0761522220/icongroupinterna

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Preventing Osteoporosis: Dr. Kenneth H. Cooper's Preventive Medicine Program by Ken Cooper, Kenneth H. Cooper; ISBN: 0553053353; http://www.amazon.com/exec/obidos/ASIN/0553053353/icongroupinterna

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Prevention and Treatment of Osteoporosis; ISBN: 3456823118; http://www.amazon.com/exec/obidos/ASIN/3456823118/icongroupinterna

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Prevention and Treatment of Osteoporosis in the High-Risk Patient by Cyrus Cooper, Robert Lindsay (2004); ISBN: 1841842834; http://www.amazon.com/exec/obidos/ASIN/1841842834/icongroupinterna

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Prevention and Treatment of Osteoporosis: An International Symposium Held During the Xiith European Congress of Rheumatology, Budapest, Hungary, 1991 by B.L. Riggs (Editor), Lawrence B. Riggs (Editor); ISBN: 0889370982; http://www.amazon.com/exec/obidos/ASIN/0889370982/icongroupinterna

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Prevention of Postmenopausal Osteoporosis: Dream or Reality by W.A. Peck (Editor); ISBN: 0929858662; http://www.amazon.com/exec/obidos/ASIN/0929858662/icongroupinterna

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Primer on Corticosteroid-Induced Osteoporosis by Jonathan D. Adachi, Ioannidis (2000); ISBN: 0781724430; http://www.amazon.com/exec/obidos/ASIN/0781724430/icongroupinterna

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Proceedings of the First Middle East Congress on Osteoporosis; ISBN: 0905958500; http://www.amazon.com/exec/obidos/ASIN/0905958500/icongroupinterna

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PTH Modulation in Treatment if Osteoporosis by Arnaud; ISBN: 1841842842; http://www.amazon.com/exec/obidos/ASIN/1841842842/icongroupinterna

•

Public Information about Osteoporosis: What's Available, What's Needed? (1995); ISBN: 0788124994; http://www.amazon.com/exec/obidos/ASIN/0788124994/icongroupinterna

•

Quantitative Ultrasound: assessment of osteoporosis and bone status by Christopher F. Njeh (Editor), et al; ISBN: 1853176796; http://www.amazon.com/exec/obidos/ASIN/1853176796/icongroupinterna

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Radiology of Osteoporosis by S. Grampp (Editor), et al; ISBN: 3540668276; http://www.amazon.com/exec/obidos/ASIN/3540668276/icongroupinterna

Books 481

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Rapid Reference to Osteoporosis by Stuart H. Ralston, Michael Kleerekoper (2003); ISBN: 0723433240; http://www.amazon.com/exec/obidos/ASIN/0723433240/icongroupinterna

•

Report on Osteoporosis in the European Community: Action for Prevention; ISBN: 9282853330; http://www.amazon.com/exec/obidos/ASIN/9282853330/icongroupinterna

•

Research and Recipes on Dementia, Heart Disease, Osteoporosis and Cancer by Rosemary C. Fisher (1997); ISBN: 0875275303; http://www.amazon.com/exec/obidos/ASIN/0875275303/icongroupinterna

•

Shared Care For Osteoporosis by Cyrus Cooper, et al (1998); ISBN: 1899066268; http://www.amazon.com/exec/obidos/ASIN/1899066268/icongroupinterna

•

Solved: The Riddle of Osteoporosis by Stephen Langer, James Scheer (Contributor); ISBN: 0879837853; http://www.amazon.com/exec/obidos/ASIN/0879837853/icongroupinterna

•

Soy Smart Health: Discover the "Super Food" That Fights Breast Cancer, Heart Disease, Osteoporosis, Menopausal Discomforts, and Estrogen Dominance by Rita Elkins, et al; ISBN: 1580540449; http://www.amazon.com/exec/obidos/ASIN/1580540449/icongroupinterna

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Special Report: Osteoporosis: How to Stop It How to Prevent It How to Reverse It by Elizabeth Vierck; ISBN: 013559782X; http://www.amazon.com/exec/obidos/ASIN/013559782X/icongroupinterna

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Stand Tall! Every Woman's Guide to Preventing and Treating Osteoporosis by Morris Notelovitz, et al; ISBN: 0937404381; http://www.amazon.com/exec/obidos/ASIN/0937404381/icongroupinterna

•

Stand Tall!: Every Woman's Guide to Preventing Osteoporosis by Morris, M.D. Notelovitz, Marsha Ware; ISBN: 055334143X; http://www.amazon.com/exec/obidos/ASIN/055334143X/icongroupinterna

•

Stand Tall!: The Informed Woman's Guide to Preventing Osteoporosis by Morris Notelovitz, et al; ISBN: 0937404152; http://www.amazon.com/exec/obidos/ASIN/0937404152/icongroupinterna

•

Startling New Facts About Osteoporosis by Betty Kamen (1990); ISBN: 0944501028; http://www.amazon.com/exec/obidos/ASIN/0944501028/icongroupinterna

•

STOP HOMOCYSTEINE through the METHYLATION PROCESS: The Key to controlling homocysteine and SAM and their effect on heart disease, aging, cancer, osteoporosis, depression, AIDS and other diseases by Fred Madsen, et al; ISBN: 0965714527; http://www.amazon.com/exec/obidos/ASIN/0965714527/icongroupinterna

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Strength Training for Strong Bones: A Step-By-Step Program to Prevent Osteoporosis and Stay Fit and Active for Life [LARGE PRINT] by Susie Dinan, et al; ISBN: 0060959266; http://www.amazon.com/exec/obidos/ASIN/0060959266/icongroupinterna

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Strong Women, Strong Bones: Everything you need to know about preventing and treating osteoporosis by Dr Miriam Nelson (2000); ISBN: 0734401345; http://www.amazon.com/exec/obidos/ASIN/0734401345/icongroupinterna

482 Osteoporosis

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Strong Women, Strong Bones: Everything You Need to Know About Preventing and Treating Osteoporosis by Miriam E. Nelson; ISBN: 0749921382; http://www.amazon.com/exec/obidos/ASIN/0749921382/icongroupinterna

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Strong Women, Strong Bones: Everything You Need to Know to Prevent, Treat, and Beat Osteoporosis by Miriam E. Nelson, Sarah Wernick (Contributor); ISBN: 0399526560; http://www.amazon.com/exec/obidos/ASIN/0399526560/icongroupinterna

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Super Calcium Counter: The Essential Guide to Preventing Osteoporosis and Building Strong Bones by Harris McIlwain, Debra Fulghum Bruce (1999); ISBN: 1575663848; http://www.amazon.com/exec/obidos/ASIN/1575663848/icongroupinterna

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Super Calcium Miracle : Finally... A Proven Program to Help Reduce the Risk of Osteoporosis by Mark Andon (1998); ISBN: 0761514562; http://www.amazon.com/exec/obidos/ASIN/0761514562/icongroupinterna

•

Textbook of Osteoporosis by John A. Kanis (1996); ISBN: 0632034262; http://www.amazon.com/exec/obidos/ASIN/0632034262/icongroupinterna

•

The 2002 Official Patient's Sourcebook on Osteoporosis: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597833044; http://www.amazon.com/exec/obidos/ASIN/0597833044/icongroupinterna

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The Athletic Woman's Survival Guide: How to Win the Battle Against Eating Disorders, Amenorrhea, and Osteoporosis by Carol L. Otis, Roger Goldingay (2000); ISBN: 0736001212; http://www.amazon.com/exec/obidos/ASIN/0736001212/icongroupinterna

•

The Bible Cure for Osteoporosis (Bible Cure Series) by Don, Md. Colbert (2000); ISBN: 088419681X; http://www.amazon.com/exec/obidos/ASIN/088419681X/icongroupinterna

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The Calcium Connection: A Revolutionary Diet and Health Program to Reduce Hypertension, Prevent Osteoporosis, and Lower the Risk of Cancer by Cedric Garland, et al; ISBN: 0671671928; http://www.amazon.com/exec/obidos/ASIN/0671671928/icongroupinterna

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The Calcium Cookbook: 200 Recipes That Supply Necessary Calcium-Rich Foods to Prevent Osteoporosis by Joanne Ness, Genell Subak-Sharpe; ISBN: 0871318504; http://www.amazon.com/exec/obidos/ASIN/0871318504/icongroupinterna

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The Doctors Book of Home Remedies for Stronger Bones: Tips to Stop Osteoporosis and Reverse the Bone Loss That Affects Every Woman over 30 by Mary S. Kittel (Editor), et al (2000); ISBN: 1579542093; http://www.amazon.com/exec/obidos/ASIN/1579542093/icongroupinterna

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The Evaluation of Osteoporosis: Dual Energy X-Ray Absorptionmetry and Ultrasound in Clinical Practice by Glen M., Ph.D. Blake, et al; ISBN: 1853174726; http://www.amazon.com/exec/obidos/ASIN/1853174726/icongroupinterna

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The Genetics of Osteoporosis and Metabolic Bone Disease by Michael J. Econs (Editor); ISBN: 0896037029; http://www.amazon.com/exec/obidos/ASIN/0896037029/icongroupinterna

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The High-Calcium Low-Calorie Cookbook: 250 Delicious Recipes to Help You Beat Osteoporosis by Betty Marks, et al (2003); ISBN: 1572840595; http://www.amazon.com/exec/obidos/ASIN/1572840595/icongroupinterna

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The John Hopkins White Papers: Low Back Pain and Osteoporosis (2001); ISBN: 9990833397; http://www.amazon.com/exec/obidos/ASIN/9990833397/icongroupinterna

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The Johns Hopkins White Papers 2002, Volume 2: Hypertension and Stroke, Low Back Pain and Osteoporosis, Memory, Prostate Disorders, Vision by Simeon Margolis (Editor) (2002); ISBN: 0929661729; http://www.amazon.com/exec/obidos/ASIN/0929661729/icongroupinterna

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The Johns Hopkins White Papers: Low Back Pain and Osteoporosis by John P. Kostuik, Simeon Margolis; ISBN: 0929661273; http://www.amazon.com/exec/obidos/ASIN/0929661273/icongroupinterna

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The Market for Osteoporosis Diagnostics [DOWNLOAD: PDF] by Kalorama Information (Author); ISBN: B00005R8ZY; http://www.amazon.com/exec/obidos/ASIN/B00005R8ZY/icongroupinterna

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The market for osteoporosis diagnostics, therapeutics, and disease management; ISBN: 156241447X; http://www.amazon.com/exec/obidos/ASIN/156241447X/icongroupinterna

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The Myth of Osteoporosis by Gillian Sanson; ISBN: 0972123342; http://www.amazon.com/exec/obidos/ASIN/0972123342/icongroupinterna

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The Osteoporosis by Varios (1995); ISBN: 9580428360; http://www.amazon.com/exec/obidos/ASIN/9580428360/icongroupinterna

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The Osteoporosis Book by Nancy E. Lane (Editor) (1998); ISBN: 019511602X; http://www.amazon.com/exec/obidos/ASIN/019511602X/icongroupinterna

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The Osteoporosis Book: A Guide for Patients and Their Families by Nancy E., MD Lane (2001); ISBN: 0195142381; http://www.amazon.com/exec/obidos/ASIN/0195142381/icongroupinterna

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The Osteoporosis Cure : Reverse the Crippling Effects With New Treatments by Harris McIlwain (Author), Debra Fulghum Bruce (Author); ISBN: 0380793369; http://www.amazon.com/exec/obidos/ASIN/0380793369/icongroupinterna

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The Osteoporosis Cure Clip Strip Display: Reverse the Crippling Effects with New Treatments by Harris H. McIlwain, Debra Fulghum Bruce; ISBN: 0380802384; http://www.amazon.com/exec/obidos/ASIN/0380802384/icongroupinterna

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The Osteoporosis Exercise Book : Building Better Bones [LARGE PRINT] by David Gelbart, Sherri R. Betz; ISBN: 0967515203; http://www.amazon.com/exec/obidos/ASIN/0967515203/icongroupinterna

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The Osteoporosis Handbook: Every Woman's Guide to Prevention and Treatment by Sydney Lou Bonnick (2000); ISBN: 0878332596; http://www.amazon.com/exec/obidos/ASIN/0878332596/icongroupinterna

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The Osteoporosis Prevention Guide: The Natural Strategy for Strengthening Your Bones by Sarah Brewer; ISBN: 0285634313; http://www.amazon.com/exec/obidos/ASIN/0285634313/icongroupinterna

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The Osteoporosis Primer by Janet E. Henderson (Editor), David Goltzman (Editor) (2000); ISBN: 0521644461; http://www.amazon.com/exec/obidos/ASIN/0521644461/icongroupinterna

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The Osteoporosis Remedy: Designing a Personal Prevention Program by Stephen Schettini; ISBN: 1583330860; http://www.amazon.com/exec/obidos/ASIN/1583330860/icongroupinterna

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The Osteoporosis Solution by Carl Germano, et al (2000); ISBN: 1575664968; http://www.amazon.com/exec/obidos/ASIN/1575664968/icongroupinterna

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The Osteoporosis: Well Women and the Marketing of Fear by Gill Sanson; ISBN: 0141006315; http://www.amazon.com/exec/obidos/ASIN/0141006315/icongroupinterna

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The Parathyroid Hormone: An Unexpected Bone Builder for Treating Osteoporosis by James F. Whitfield, et al; ISBN: 1570595569; http://www.amazon.com/exec/obidos/ASIN/1570595569/icongroupinterna

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The Silent Thief: Osteoporosis, Exercises and Strategies Prevention and Treatment (Your Personal Health) by Karine Bohme, Frances, MD Budden (2001); ISBN: 1552975398; http://www.amazon.com/exec/obidos/ASIN/1552975398/icongroupinterna

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The Strong Bones Diet: The High Calcium, Low Calorie Way to Prevent Osteoporosis by Lois Goulder, Leo Lutwak (1988); ISBN: 0937404209; http://www.amazon.com/exec/obidos/ASIN/0937404209/icongroupinterna

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Tiene Usted Osteoporosis? by Carlos Mautalen (2000); ISBN: 950524665X; http://www.amazon.com/exec/obidos/ASIN/950524665X/icongroupinterna

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Todas Las Respuestas Sobre LA Osteoporosis by Carmen T. Moran (2002); ISBN: 9875201685; http://www.amazon.com/exec/obidos/ASIN/9875201685/icongroupinterna

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Todas Las Respuestas Sobre Osteoporosis by Carmen T. Moran (2003); ISBN: 9507684298; http://www.amazon.com/exec/obidos/ASIN/9507684298/icongroupinterna

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Trends & Perspectives in the Diagnosis & Management of Osteoporosis by William A. Peck (Editor) (1989); ISBN: 1850702039; http://www.amazon.com/exec/obidos/ASIN/1850702039/icongroupinterna

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Tumor Bone Diseases and Osteoporosis in Cancer Patients: Pathophysiology, Diagnosis, and Therapy by Jean-Jacques Body (Editor); ISBN: 0824763998; http://www.amazon.com/exec/obidos/ASIN/0824763998/icongroupinterna

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U.S. Osteoporosis Diagnostic and Therapeutic Markets: Strategic Alliances Offer New Dimensions by Market Intelligence (1994); ISBN: 0788901222; http://www.amazon.com/exec/obidos/ASIN/0788901222/icongroupinterna

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Understanding and Managing Osteoporosis by John L. Decker (Editor); ISBN: 0380754290; http://www.amazon.com/exec/obidos/ASIN/0380754290/icongroupinterna

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Understanding Calcium and Osteoporosis by American Allergy Association, Irene T. McPherrin (Editor) (1987); ISBN: 0961670843; http://www.amazon.com/exec/obidos/ASIN/0961670843/icongroupinterna

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Understanding Osteoporosis (Family Doctor Series) by Juliet E. Compston; ISBN: 1898205248; http://www.amazon.com/exec/obidos/ASIN/1898205248/icongroupinterna

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Understanding Osteoporosis and Its Treatment: A Guide for Physicians and their Patients by G. F. B. Birdwood; ISBN: 1850704090; http://www.amazon.com/exec/obidos/ASIN/1850704090/icongroupinterna

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Understanding Osteoporosis Chart by Anatomical Chart (2003); ISBN: 1587797593; http://www.amazon.com/exec/obidos/ASIN/1587797593/icongroupinterna

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Understanding, Preventing and Overcoming Osteoporosis by Jane Plant, Gill Tidey (2004); ISBN: 1852270772; http://www.amazon.com/exec/obidos/ASIN/1852270772/icongroupinterna

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Walk Tall! An Exercise Program for the Prevention and Treatment of Osteoporosis by Sara Meeks; ISBN: 0937404624; http://www.amazon.com/exec/obidos/ASIN/0937404624/icongroupinterna

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What You Can Do About Osteoporosis (The Dell Medical Library) by Judith Sachs, Lawrence G. Raisz; ISBN: 0440213606; http://www.amazon.com/exec/obidos/ASIN/0440213606/icongroupinterna

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What Your Doctor May Not Tell You About Osteoporosis: Help Prevent--and Even Reverse--the Disease that Burdens Millions of Women by Felicia, Md. Cosman (2003); ISBN: 0446679038; http://www.amazon.com/exec/obidos/ASIN/0446679038/icongroupinterna

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Wild Yam: Nature's Progesterone: The Safe and Little Known Answer to Hormonal Imbalance, Pms, Menopause and Osteoporosis (Woodland Health Ser) by Rita Elkins, Woodland Publishing (1999); ISBN: 1885670257; http://www.amazon.com/exec/obidos/ASIN/1885670257/icongroupinterna

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Winning the Osteoporosis Therapy Race [DOWNLOAD: PDF] by BioSeeker Group AB (Author); ISBN: B00008R5UZ; http://www.amazon.com/exec/obidos/ASIN/B00008R5UZ/icongroupinterna

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Winning With Osteoporosis by Harris H. McIlwain (Editor), et al; ISBN: 0471304891; http://www.amazon.com/exec/obidos/ASIN/0471304891/icongroupinterna

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Women's Health Guide: A Natural Approach to Breast Cancer, Hearst Disease, Fibroids, Pms, Bulemia, Childbirth, Menopause, and Osteoporosis by Gale Jack (Editor), Wendy Esko (Editor); ISBN: 1882984250; http://www.amazon.com/exec/obidos/ASIN/1882984250/icongroupinterna

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Yoga Builds Bones: Easy, Gentle Stretches That Prevent Osteoporosis by Jan Maddern, et al (2002); ISBN: 1931412057; http://www.amazon.com/exec/obidos/ASIN/1931412057/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “osteoporosis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed

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Bone loss: causes, detection, and therapy Author: Albanese, Anthony A. (Anthony August),; Year: 1962; New York: Liss, c1977; ISBN: 0845116002 http://www.amazon.com/exec/obidos/ASIN/0845116002/icongroupinterna

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Estrogen cytosol receptors in postmenopausal osteoporosis Author: Davidson, Bert Johan,; Year: 1973; [Minneapolis?: s.n.], 1978

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Estrogens and androgens in postmenopausal women with osteoporosis or endometrial carcinoma: an investigation into the role of endogenous ovarian and adrenal sex steroids and their bioavailability in the pathogenesis of postmenopausal osteoporosis and endometrial carcinoma Author: Davidson, Bert Johan,; Year: 1979; [S.l.: s.n.], 1983

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Hormones in immobilization osteoporosis. Author: Burkhart, James MacDonald,; Year: 1967; [Minneapolis] 1967

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Localised disuse osteoporosis: experimental studies in the adult rat Author: Sevastikoglou, J. A. (John A.); Year: 2004; Uppsala: Almqvist; Wiksell, 1976

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Osteoporosis: your head start on the prevention and treatment of brittle bones Author: Fardon, David F.; Year: 1983; New York: Macmillan Pub. Co., c1985; ISBN: 0025371207 http://www.amazon.com/exec/obidos/ASIN/0025371207/icongroupinterna

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Osteoporosis. B. E. C. Nordin, guest editor. Author: Nordin, B. E. C. (Börje Edgar Christopher); Year: 2001; London, Philadelphia, Saunders, 1973

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Osteoporosis. Edited by Uriel S. Barzel. Author: Barzel, Uriel S.; Year: 1970; New York, Grune; Stratton [c1970]

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Sex steroids in the clinical management of osteoporosis Author: Gordan, Gilbert S. (Gilbert Saul),; Year: 1976; Chicago: Year Book Medical Publishers, c1982; ISBN: 0815199252 http://www.amazon.com/exec/obidos/ASIN/0815199252/icongroupinterna

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The bone dynamics in osteoporosis and osteomalacia. Author: Frost, Harold M.,; Year: 1966; Springfield, Ill., Thomas [c1966]

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The reversibility of disuse osteoporosis: experimental studies in the adult rat Author: Mattsson, Sten.; Year: 1964; Copenhagen: Munksgaard, 1972; ISBN: 8716010442

Chapters on Osteoporosis In order to find chapters that specifically relate to osteoporosis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and osteoporosis using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “osteoporosis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on osteoporosis: in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Chapter 27: Reflex Sympathetic Dystrophy and Transient Regional Osteoporosis Source: in Klippel, J.H., et al., eds. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation. 2001. p. 451-454. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. Website: www.arthritis.org. PRICE: $69.95 plus shipping and handling. ISBN: 0912423293. Summary: This chapter provides health professionals with information on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of reflex sympathetic dystrophy (RSD) and the clinical features, diagnosis, and treatment of transient regional osteoporosis. RSD is a symptom complex characterized by severe pain, swelling, and autonomic dysfunction in an extremity. RSD has been observed in every race and geographic location. Although RSD occurs most commonly in people 40 to 60 years old, it can occur in children and the elderly. Current hypotheses on the mechanisms that lead to the development of RSD are based on two different processes: altered sympathetic outflow and regional inflammation. The most prominent and disabling feature of RSD is an intense, deep, chronic burning sensation exacerbated by movement, dependent posture, and emotional stress. Hand or foot involvement is most common. Local edema and vasomotor changes often accompany the pain. The clinical stages of RSD have been identified. Stage 1 lasts 3 to 6 months and is characterized by pain, hypersensitivity, swelling, and vasomotor changes that lower or raise the temperature in the extremity. Stage 2 is characterized by persistent pain, disability, and atrophic skin changes. Stage 3 features atrophy of subcutaneous tissues and, often, contractures. Diagnosis is based on recognition of the clinical features. Although there are no defining laboratory abnormalities, plain radiographs, bone scans, thermography, and autonomic function studies can help support the diagnosis. Various modalities have been used to treat RSD. Pain control is achieved through the use of narcotic analgesics. Antidepressant medications also provide pain relief and improve depressive symptoms. Oral corticosteroids have proved very effective in the management of RSD. Physiotherapy is used to mobilize the affected extremity and lessen local edema. Sympathetic nerve blockade is a popular treatment for RSD, but no controlled studies demonstrating long term efficacy have been conducted. The syndrome of transient regional osteoporosis, seen mainly in young and middle aged persons, manifests as monarticular or oligoarticular pain accompanied by osteopenia of the affected joint. The syndrome is more common in men than in women. Diagnosis is based on the presence of joint pain, diminished joint mobility, and localized osteopenia on plain radiographs. Treatment consists of avoiding weight bearing and taking analgesics. Corticosteroids are not beneficial. Although most patients recover completely in several weeks, recurrence is common. 2 figures, 2 tables, and 25 references.

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Osteoporosis and Osteomalacia Source: in Maddison, P.J. et al., Eds. Oxford Textbook of Rheumatology. Volume 2. New York, NY: Oxford University Press, Inc. 1993. p. 1005-1024. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals presents an overview of osteoporosis and osteomalacia. Epidemiological data on osteoporosis are provided. Types of osteoporosis are described, including postmenopausal, age-related, idiopathic, juvenile, and endocrine- and drug-induced osteoporosis. The clinical features of osteoporosis are highlighted. Its pathogenesis is explained. The use of risk factor assessment, bone mass measurement, bone biopsy, and biochemical markers in the diagnosis of osteoporosis is

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discussed. The role of calcium and calcitonin supplementation, exercise, and hormone replacement therapy (HRT) in the prevention of osteoporosis is examined. Approaches to treating established osteoporosis are considered, including the use of HRT, calcitonin, bisphosphonates, testosterone and anabolic steroids, vitamin D and metabolites, sodium fluoride, and parathyroid hormone. In addition, the clinical and laboratory features and causes of osteomalacia and rickets are presented. 114 references, 12 figures, and 6 tables. •

Osteopenia and Osteoporosis: Prevention and Treatment Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 289-292. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Osteoporosis (abnormal loss of bone density) is a major cause of hospitalization and disability in the elderly. This chapter on the prevention and treatment of osteopenia (subnormally mineralized bone) and osteoporosis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and UC, together known as inflammatory bowel disease (IBD). Although less well recognized, in patients with IBD, a decreased bone mass may be present. Osteoporosis is present in 23 to 59 percent of patients with IBD, and bone loss occurs in both trabecular bone (less dense bone found in vertebrae, ribs, the pelvis, and the ends of long bones) and cortical bone (bone that is 70 to 90 percent mineralized). Patients with IBD have not only the general risk factors for osteoporosis but also additional factors including low weight and body mass index; poor calcium intake, owing to lactase (the enzyme to digest milk sugars or lactose) deficiency; malnutrition; ileal resection; sex hormone deficiency; reduced physical activity; smoking, in women; the presence of bone resorptive cytokines (interleukin 6, interleukin 1, tumor necrosis factor or TNF); and corticosteroid therapy. The most important wayts to prevent osteoporosis are to achieve the highest bone mass during young adulthood and to decrease the rate of subsequent bone loss. Preventive strategies include exercising, consuming an adequate amount of dietary calcium and vitamin D, avoiding excess alcohol and smoking, and replacing sex steroids when they are deficient. 2 tables. 17 references.

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Management of Primary Biliary Cirrhosis: Osteoporosis Source: in Lindor, K.D. Heathcote, E.J. Poupon, R., eds. Primary Biliary Cirrhosis: From Pathogenesis to Clinical Treatment. Boston, MA: Kluwer Academic Publishers. 1998. p. 92-101. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. Summary: Primary biliary cirrhosis (PBC) is a chronic cholestasic (lack of bile flow) liver disease of unknown etiology (cause), although the association with a large number of autoimmune disorders suggests that the disease may be of autoimmune origin. The disease usually affects middle aged women and progresses from asymptomatic disease with only laboratory abnormalities to a severe cholestatic disease with deep jaundice, xanthomas (fatty tumors in the skin), portal hypertension (high blood pressure), and eventually liver failure. This chapter on osteoporosis (bone thinning) is from a

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monograph that reprints papers from a conference held in November 1997 in Chicago, Illinois, on the clinical features (symptoms), pathogenesis, and treatment of PBC. Bone disease complicates the natural history in patients with PBC. The author discusses the incidence of bone disease in PBC, bone turnover in PBC, and the management of osteoporosis in PBC. Although bone turnover may change during the disease, it is generally accepted that osteoporosis in PBC results from impaired osteoblast function probably as the consequence of cholestasis, and is particularly related to the duration of the disease, postmenopausal condition, and intestinal calcium malabsorption. The management of osteoporosis is addressed to prevent the development of bone loss. Calcium and vitamin D supplements are mandatory, particularly in patients with severe cholestasis and in countries with a low rate of sunlight irradiation. Calcitonin has minor effects, if any, for preventing bone loss, whereas both sodium fluoride and cyclical etidronate are effective for treating trabecular osteopenia (subnormally mineralized bone). 4 figures. 1 table. 42 references. •

Debilitating Diseases: Osteoporosis, Alcoholism, Arthritis, and Renal Disease Source: in Frank-Spohrer, G.C. Community Nutrition: Applying Epidemiology to Contemporary Practice. Gaithersburg, MD: Aspen Publishers, Inc. 1996. p. 535-557. Contact: Available from Aspen Publishers, Inc. 7201 McKinney Circle, Frederick, MD 21701. (800) 638-8437. PRICE: $48.00. ISBN: 0834207842. Summary: This chapter on debilitating diseases, including osteoporosis, alcoholism, arthritis, and renal disease, is from a nursing text on community nutrition. The author describes the occurrence and etiology of these four diseases, identifies secondary and tertiary prevention approaches for each one, and lists and enumerates the role of dietary components in the secondary prevention of these diseases. One chart summarizes the general dietary recommendations for renal patients. The author also relates suggestions to the Healthy People 2000 objectives. 4 figures. 7 tables. 59 references.

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Effects of Postmenopausal Osteoporosis on the Mandible Source: in Zarb, G., et al., eds. Aging, Osteoporosis, and Dental Implants. Chicago, IL: Quintessence Publishing Co, Inc. 2002. p. 207-215. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $78.06 plus shipping and handling. ISBN: 0867154071. Summary: This chapter on the effects of postmenopausal osteoporosis on the mandible (lower jaw) is from a book that contains the proceedings of a symposium on Aging, Osteoporosis and Dental Implants, held at the University of Toronto (Canada) in November 2000. The proceedings attempt to reconcile the current clinical understanding of aging, with or without osteoporosis (abnormal loss of bone density), with overall dental patient management strategies, placing particular emphasis on the induction and maintenance of the osseointegrated (an induced healing process where alloplastic materials are maintained in bone) response (necessary for dental implants). This chapter reviews the evidence available in the literature addressing the question of whether postmenopausal osteoporosis affects the mandible. The authors present results of experiments studying the effects of ovariectomy (removal of the ovaries) on bone changes in the edentulous (without teeth) and dentate (with teeth) mandibles of aged female rats, a model for postmenopausal osteoporosis. The literature review reveals that the lack of reliability of radiological techniques in assessing bone changes in the

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mandible, the lack of control for confounding factors, and the cross sectional design of most of the studies make it very difficult to draw conclusions on the effect of postmenopausal osteoporosis on the mandible. 4 figures. 1 table. 64 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to osteoporosis have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 •

California women's health directory Source: Los Angeles, CA: KCET; San Francisco, CA: KQED. 1994. 34 pp. Contact: Available from Cayleen Nakamura, Associate Director, KCET Community Television of Southern California, KCET Community Outreach, 4401 Sunset Boulevard, Los Angeles, CA 90027. Telephone: (213) 953-5245 / fax: (213) 953-5331. Summary: This directory of women's health resources is designed to help women in California locate resources and information in their community, allowing them to become active and educated consumers in the health care arena. It first looks briefly at six issues of concern all women face: osteoporosis, breast cancer, cardiovascular disease, violence, depression, and smoking: then the body of the directory lists the various health centers arranged alphabetically by topic. The directory also provides a list of women's organizations, libraries and publications, and other resources.

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Who? What? Where?: Resources for women's health and aging Source: Bethesda, MD: National Institute on Aging, U.S. Department of Health and Human Services. 1992. 82 pp. Contact: Available from National Institute on Aging Information Center, P.O. Box 8057, Gaithersburg, MD 20898-8057. Telephone: (301) 587-2528 or (800) 222-2225 or (800) 2224225 TDD / fax: (301) 589-3014 / e-mail: [email protected] / Web site: http://www.nih.gov/nia. Available at no charge. Summary: This directory lists resources available to women which can help them cope with the processes of aging. The first section provides resources for health promotion and prevention. Topics included here are skin care, nutrition and exercise, and menopause. The second section concentrates on common disorders associated with age such as osteoporosis, urinary incontinence, cancer, and heart disease. The third section focuses on other aspects of women's lives such as widowhood, finances, and caregiving.

12

You will need to limit your search to “Directory” and “osteoporosis” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “osteoporosis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

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The final sections provided information on women's health research and other organizations and readings.

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CHAPTER 8. MULTIMEDIA ON OSTEOPOROSIS Overview In this chapter, we show you how to keep current on multimedia sources of information on osteoporosis. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on osteoporosis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “osteoporosis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “osteoporosis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on osteoporosis: •

Women and Nutrition Source: Los Angeles, CA: National Health Video, Inc. 1993. (videocassette). Contact: Available from National Health Video, Inc. 12021 Wilshire Boulevard, Suite 550, Los Angeles, CA 90025. (800) 543-6803. Fax (310) 477-8198. E-mail: [email protected]. PRICE: $89.00 plus shipping and handling. Summary: Women are often seen as the nutrition caregiver gender but too often they are not aware of their own nutritional needs. This health education videotape program focuses on the differences between men and women in the area of nutrition. The program addresses nutrition and weight management, iron levels, contraception (birth control), osteoporosis (a bone disease characterized by loss of bone density), menopause, PMS (premenstrual syndrome), cancer, and heart disease. The program notes that weight management efforts are often guided only partly by health concerns. Social goals, such as conforming to unrealistic fashion standards, are often more powerful. Women have special needs for nutrients such as iron and calcium that exceed

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those for men. Heart disease is the number one cause of female mortality. The program stresses that nutrition is important for all women, no matter what their ages. Viewers are reminded to eat a variety of foods, especially grains, fruits, vegetables, lean meat and low fat dairy foods, and reducing fats, sodium (salt), and sweets. The accompanying teacher's guide includes a transcript of the video narration, a list of learning activities and teaching objectives, and a quiz for pre and posttesting. The video features many different people of different ethnic groups and ages; a variety of interactions with health care providers are also depicted. Simple graphics are used to explore some of the scientific concepts covered. •

Vitamin D: Not Just for Bones Source: Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, 1992, 60 minutes. Contact: WIN, 1 WIN WAY, Bethesda, MD 20892-3665. Summary: In this lecture, Dr. DeLuca discusses the major functions of Vitamin D in the body; studies demonstrating potential therapeutic uses for synthetic Vitamin D compounds; and his own laboratory's progress on developing several such compounds. According to Dr. DeLuca, Vitamin D is, in fact, not a vitamin but a prohormone that remains inactive until metabolized in the liver and the kidney. The principal active metabolite of Vitamin D, calcitrol, acts with parathyroid hormone (PTH) to regulate the blood calcium level. It also plays a role in building up bone and is an important regulator of intestinal calcium absorption. Disturbance of this regulatory mechanism can result in osteoporosis (brittle bones), as well as in several disorders characterized by a deficiency or an oversupply of calcium or PTH in the blood (hypo- and hypercalcemia; hypo-and hyperparathyroidism). Vitamin D deficiency results in rickets (soft, weak bones) and osteomalacia in adults. Dr. DeLuca discusses several clinical studies demonstrating an age-related decline in formation of the active Vitamin D metabolite in response to PTH. He describes research he is conducting to develop synthetic Vitamin D compounds that would stimulate bone formation in osteoporotic patients without producing hypercalcemia. He predicts that within a decade these compounds will be important contributors to the treatment of postmenopausal and age-related osteoporosis. Dr. DeLuca goes on to discuss evidence strongly suggesting that Vitamin D influences other biologic processes, including cellular differentiation and regulation of the immune system. Work is ongoing in his laboratory to develop Vitamin D "differentiation compounds" that may have a future role in cancer therapy. The lecture concludes with a discussion of other potential therapeutic uses for Vitamin D, including the treatment of psoriasis, renal osteodystropy (bone disease found with kidney failure), and infertility.

Bibliography: Multimedia on Osteoporosis The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in osteoporosis (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The

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following multimedia has been indexed on osteoporosis (for more information, follow the hyperlink indicated): •

An Aging process, osteoporosis [videorecording] Source: produced and distributed by Fairview General Audio-Visuals; Year: 1985; Format: Videorecording; Cleveland, Ohio: Fairview, c1985

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Bone loss and osteoporosis [videorecording]: women at risk Source: Pierre J. Bouis, Jr; Year: 1988; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1988

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Controversies in thyroid cancer therapy, adrenal imaging and osteoporosis evaluation [slide] Source: the Society of Nuclear Medicine; Year: 1992; Format: Slide; [New York, NY]: The Society, [1992]

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Estrogens & osteoporosis [videorecording]: recent advances Source: [presented by] Audio-Video Digest Foundation; Year: 1983; Format: Videorecording; Glendale, Calif.: The Foundation, c1983

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NIH consensus, osteoporosis [videorecording] Source: HSN, Hospital Satellite Network program of continuing education; Year: 1984; Format: Videorecording; [Los Angeles, Calif.]: The Network, c1984

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Nutrition for osteoporosis [videorecording] Source: [presented by] Bruce Miller Enterprises; Year: 1991; Format: Videorecording; Dallas, TX: Bruce Miller Enterprises, c1991

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Osteoporosis [slide]. Year: 1984; Format: Slide; [Columbus, Ohio]: Center for Continuing Medical Education, the Ohio State University College of Medicine, [1984]

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Osteoporosis [videorecording] Source: Dept. of Medicine, Emory University, School of Medicine; Year: 1979; Format: Videorecording; Atlanta: Emory Medical Television Network: [for loan and sale by A. W. Calhoun Medical Library], 1979

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Osteoporosis [videorecording] Source: [presented by] Marshfield Medical Foundation, in cooperation with Marshfield Clinic and St. Joseph's Hospital; Year: 1986; Format: Videorecording; Marshfield, WI: Marshfield Video Network, [1986]

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Osteoporosis [videorecording] Source: a Whiteford-Cohen production for the University of Maryland at Baltimore; Year: 1990; Format: Videorecording; Baltimore, Md.: Video Press, University of Maryland at Baltimore, c1990

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Osteoporosis [videorecording] Source: [presented by] Marshfield Video Network, in cooperation with Marshfield Clinic, St. Joseph's Hospital, and Marshfield Medical Research Foundation; Year: 1988; Format: Videorecording; Marshfield, WI: The Network, c1988

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Osteoporosis [videorecording]: current concepts Source: a presentation of the Health Communications Network, Medical University of South Carolina; Year: 1987; Format: Videorecording; [Charleston, S.C.]: The Network, 1987

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Osteoporosis [videorecording]: prevention and treatment Source: [presented by] Accredited Professional Educational Seminars; Year: 1987; Format: Videorecording; Oakland, Calif.: The Seminars, c1987

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Osteoporosis of aging [motion picture]: a film report Source: Richmond W. Smith, Jr., in collaboration with Harold M. Frost; produced by Communication Films a unit of Walter Landor and Associates, Industrial Design; Year: 1967; Format: Motion picture; East Hanover, N. J.: Sandoz Pharmaceuticals: [for loan by Sandoz Pharmaceuticasl, Medical Film Library, 1967?]

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Osteoporosis of the spine [videorecording]: radiologic assessment Source: the Radiological Society of North America; Year: 1987; Format: Videorecording; Oak Brook, Ill.: The Society, c1987

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Osteoporosis, a silent epidemic [videorecording] Source: presented by Ayerst Laboratories; produced by MED; Year: 1983; Format: Videorecording; [New York, N.Y.]: Ayerst, c1983

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Osteoporosis, can we prevent it? [videorecording] Source: by Elizabeth B. Connell, Frederic C. McDuffie, B. Lawrence Riggs; Year: 1984; Format: Videorecording; Atlanta, Ga.: Emory University and the Arthritis Foundation, c1984

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Osteoporosis, how can we treat it? [videorecording] Source: by Lamar L. Fleming, Frederic C. McDuffie, B. Lawrence Riggs; Year: 1985; Format: Videorecording; Atlanta, Ga.: Emory University and the Arthritis Foundation, c1985

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Osteoporosis, normal aging or metabolic disorder [videorecording] Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital [and] Marshfield Medical Research Foundation; Year: 1989; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, [1989]

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Osteoporosis, prevention and treatment [videorecording] Source: [presented by] Marshfield Video Network, in cooperation with Marshfield Clinic, St. Joseph's Hospital, and Marshfield Medical Research Foundation; Year: 1988; Format: Videorecording; Marshfield, WI: The Network, [1988]

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Skeletal aging [slide]: prevention and management of osteoporosis Source: Robert Marcus; Year: 1986; Format: Slide; Garden Grove, Calif.: Medcom, c1986

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The Role of exercise in the prevention of osteoporosis [videorecording] Source: [presented by] Marshfield Video Network, in cooperation with Marshfield Clinic, St. Joseph's Hospital, and Marshfield Medical Research Foundation; Year: 1988; Format: Videorecording; Marshfield, WI: The Network, [1988]

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CHAPTER 9. PERIODICALS AND NEWS ON OSTEOPOROSIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover osteoporosis.

News Services and Press Releases One of the simplest ways of tracking press releases on osteoporosis is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “osteoporosis” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to osteoporosis. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “osteoporosis” (or synonyms). The following was recently listed in this archive for osteoporosis: •

IV ibandronate may prevent bone loss in postmenopausal women Source: Reuters Industry Breifing Date: October 08, 2003 http://www.reutershealth.com/archive/2003/10/08/business/links/20031008drgd001 .html

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Four shots a year may curb menopausal bone loss Source: Reuters Health eLine Date: October 08, 2003

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Merck, Lilly present results of osteoporosis trials Source: Reuters Industry Breifing Date: September 23, 2003

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PTH therapy for osteoporosis works best when not given with alendronate Source: Reuters Industry Breifing Date: September 22, 2003

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Osteoporosis drugs no better in combination Source: Reuters Health eLine Date: September 22, 2003

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Lilly drug for severe osteoporosis wins respect Source: Reuters Industry Breifing Date: September 19, 2003

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Osteoporosis drugs seen gaining from HRT woes Source: Reuters Industry Breifing Date: September 12, 2003

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Teva says it will appeal Merck osteoporosis drug ruling Source: Reuters Industry Breifing Date: August 29, 2003

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Risperidone may increase osteoporosis risk in premenopausal schizophrenics Source: Reuters Industry Breifing Date: August 20, 2003

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Bone loss occurs early in diabetic women Source: Reuters Health eLine Date: August 11, 2003

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Loss of oestrogen receptors linked to osteoporosis Source: Reuters Industry Breifing Date: July 23, 2003

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Loss of estrogen receptors linked to osteoporosis Source: Reuters Health eLine Date: July 23, 2003

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Lilly wins EU approval for osteoporosis drug Forsteo Source: Reuters Industry Breifing Date: June 17, 2003

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Roche osteoporosis drug gets U.S. approval Source: Reuters Health eLine Date: May 19, 2003

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Unigene's nasally delivered osteoporosis drug accepted for review by FDA Source: Reuters Industry Breifing Date: May 05, 2003

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German osteoporosis rates up 30 percent Source: Reuters Health eLine Date: April 28, 2003

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Alendronate prevents bone loss after discontinuation of HRT Source: Reuters Industry Breifing Date: April 21, 2003

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Consumer group warns against osteoporosis drug Source: Reuters Health eLine Date: April 02, 2003

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Consumer group cautions patients against use of Eli Lilly osteoporosis therapy Source: Reuters Industry Breifing Date: April 01, 2003

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Zelos raises funds for phase I osteoporosis drug trial Source: Reuters Industry Breifing Date: March 24, 2003

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Vitamin D receptor polymorphism influences alendronate's effect on osteoporosis Source: Reuters Industry Breifing Date: March 21, 2003

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NPS reports positive top-line results for osteoporosis drug Source: Reuters Industry Breifing Date: February 26, 2003

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EntreMed cancer drug shows preclinical promise for osteoporosis Source: Reuters Industry Breifing Date: February 24, 2003

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Osteoporosis a risk for fragile X gene carriers Source: Reuters Health eLine Date: February 13, 2003

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Merck pits Fosamax osteoporosis drug head-to-head with rival Actonel Source: Reuters Industry Breifing Date: February 05, 2003

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Osteoporosis more prevalent in women with COPD than those with asthma Source: Reuters Industry Breifing Date: January 21, 2003

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deCODE claims identification of genetic variations linked to osteoporosis Source: Reuters Industry Breifing Date: January 09, 2003

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Growth hormone increases bone density in men with osteoporosis Source: Reuters Industry Breifing Date: December 31, 2002

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Teva gets tentative FDA ok for osteoporosis drug Source: Reuters Industry Breifing Date: December 30, 2002

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Genome Therapeutics, Wyeth extend osteoporosis alliance Source: Reuters Industry Breifing Date: December 30, 2002

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Aventis osteoporosis drug approved for once-weekly use Source: Reuters Industry Breifing Date: December 19, 2002

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Upsher-Smith, Unigene in osteoporosis-drug licensing deal Source: Reuters Industry Breifing Date: December 02, 2002

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Accelerated bone loss not seen after withdrawal of alendronate Source: Reuters Industry Breifing Date: December 02, 2002

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FDA clears osteoporosis, attention-deficit drugs Source: Reuters Health eLine Date: November 27, 2002

Periodicals and News 501

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FDA approves Lilly's Forteo for osteoporosis Source: Reuters Medical News Date: November 26, 2002

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FDA approves Lilly osteoporosis drug Source: Reuters Industry Breifing Date: November 26, 2002

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Lab tests can pick up undiagnosed bone disorders in older women with osteoporosis Source: Reuters Medical News Date: November 22, 2002

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Recombinant parathyroid hormone outperforms bisphosphonate in osteoporosis Source: Reuters Industry Breifing Date: November 07, 2002

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Increased osteoporosis screening could save millions for Medicare Source: Reuters Industry Breifing Date: November 01, 2002

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Beta-blockers eyed as possible osteoporosis therapy Source: Reuters Health eLine Date: November 01, 2002

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Ferring in osteoporosis-drug pact with Beth Israel Deaconess Medical Center Source: Reuters Industry Breifing Date: October 31, 2002

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Older men not usually treated for osteoporosis Source: Reuters Health eLine Date: October 28, 2002

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Osteoprotegerin polymorphisms associated with postmenopausal osteoporosis risk Source: Reuters Medical News Date: October 25, 2002

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Synthetic steroid receptor ligand prevents osteoporosis without genotropic effects Source: Reuters Medical News Date: October 24, 2002 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date

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at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “osteoporosis” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “osteoporosis” (or synonyms). If you know the name of a company that is relevant to osteoporosis, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “osteoporosis” (or synonyms).

Newsletters on Osteoporosis Find newsletters on osteoporosis using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “osteoporosis.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “osteoporosis” (or synonyms) into the “For these words:” box. The following list was generated using the options described above:

Periodicals and News 503

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Health Span. [Newsletter] Source: Novato, CA: Buck Center for Research in Aging. 1990 -. [8 p. average]. Contact: Available from Buck Center for Research in Aging. 505A San Marin Drive, Suite 300, Novato, CA 94945. (415) 899-1800. PRICE: Free. Summary: This newsletter, published by the Buck Center for Research in Aging in Marin County, California, includes articles on all aspects of health concerns affecting the aged. The issue examined (Fall 1991) contains articles about Alzheimer's disease research, heart disease, skin cancers, and osteoporosis. The articles range from short reports of recent research activities, to health hints, to reports on national needs in the field of aging. The newsletter also deals specifically with the needs of the aging in Marin County and with the goals of Buck Center For Research in Aging, which is seeking county permission to build a scientific research facility.

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Greene County Senior Citizens Round Table News [Newsletter] Source: Catskill, NY: Greene County Department for the Aging. [4 p. average]. Contact: Available from Greene County Department for the Aging. 19 South Jefferson Avenue, Catskill, NY 12414. (518) 943-5332. Summary: A typical issue of this newsletter, which is directed to senior citizens and their families, covers health matters and happenings in the chapter's area. There are articles on such topics as summer fruit selection, osteoporosis, and Alzheimer's support groups. The newsletter also includes reader poems and senior citizens club meeting dates.

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “osteoporosis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on osteoporosis: •

Glucocorticoid-Induced Osteoporosis in SLE Source: Lupus News. 23(1): 24-25. Spring 2003. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article discusses glucocorticoid-induced osteoporosis (GIOP), a less recognized but serious side effect of glucocorticoids, in patients with systemic lupus erythematosus (SLE). Glucocorticoids (steroids) have long been used in the treatment of patients with SLE. Steroids lower bone mass by slowing the function of osteoblasts which leads to a reduction of bone formation, increasing bone resorption, disrupting the metabolism of calcium, and affecting the hormones which lead to bone loss. To prevent GIOP, patients should take the lowest dosage of steroids that is effective

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or stop taking steroids altogether, consume 1500 mg of calcium per day, supplement vitamin D consumption to 800 IU per day, take biphosphonates such as alendronate, risedronate, and pamidronate to prevent bone resorption, use hormone replacement therapy if female, start an exercise program, stop smoking, and use alcohol and caffeine in moderation or not at all. •

Glucocorticoid-Induced Osteoporosis: Prevention and Treatment Source: Bulletin on the Rheumatic Diseases. 49(4): 1-4. 2000. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (404) 872-7100. Fax (404) 872-9559. Summary: This newsletter article provides health professionals with information on the pathogenesis and clinical course of glucocorticoid induced osteoporosis (GIOP) and the management options for both primary prevention and treatment. Bone loss from glucocorticoids is related to dose and duration of treatment, hormonal status, genetics, and baseline bone mineral density (BMD). Glucocorticoids are associated with a decrease in gonadal hormones that can accelerate bone resorption and decrease bone formation, and they interfere with osteoblast maturation and accelerate apoptosis. In addition, they decrease calcium absorption from the gastrointestinal tract and increase renal excretion of calcium. Baseline BMD should be determined, and bone preserving therapy should begin at the initiation of glucocorticoid treatment. Patients receiving glucocorticoids should take calcium and vitamin D supplements. Other preventive measures that should be considered include treatment with bisphosphonates, calcitonin, and estrogen and testosterone replacements. The article also presents an approach to management of GIOP in patients who have normal BMD, patients who have osteopenia, and patients who have osteoporosis. 33 references.

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Preventing Osteoporosis : Why Milk Matters Now for Female Teens Source: NIH News and Features. 65-66. Summary: This newsletter article for the general public discusses the importance of a nutritionally balanced diet during childhood and adolescence in preventing the onset of damaging adult illness such as osteoporosis. Nutritional imbalances during adolescence results in this bone-crippling disease because the occurrence of osteoporosis is influenced by bone mass attained during the first three decades of life and the bone lost after a menopause. The article presents the recommended daily allowance of calcium for adolescent females, and it reports on nutrition research on factors affecting acquisition of peak bone mass in female adolescents and on a study of calcium requirements during adolescent pregnancies. In addition, the article discusses the impact of osteopenia, amenorrhea, and disordered eating on the adolescent female athlete, and it considers the public health implications of the declining calcium intake in female adolescents.

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Serial Bone Mineral Density Studies in the Evaluation and Management of Osteoporosis Source: Bulletin on the Rheumatic Diseases. 46(5):3-7; August 1997. Contact: Arthritis Foundation, 1330 West Peachtree Street, Atlanta, GA 30309. (404) 8727100. (404) 872-9559 (fax). Summary: This newsletter article for health professionals discusses the use of serial bone mineral density (BMD) studies in the evaluation and management of osteoporosis. Types of information that can be derived from performing BMD studies are presented,

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including the density of bone in an individual compared with an age- and sex-matched population, the risk of the individual with respect to a predetermined threshold for fractures, the prognosis for an individual, and the impact of therapy on decay curves over time. Guidelines are provided for determining which patients are candidates for BMD baseline and follow-up studies. Factors that should be considered when selecting a bone densitometry technique are identified, and guidelines for determining intervals for follow-up BMD studies are offered. 12 references and 5 tables. •

Osteoporosis Revolution Source: Lupus News. 17(3):4-5; Autumn 1997. Contact: Lupus Foundation of America, Inc., 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (301) 670-9292. (301) 670-9486 (fax). Summary: This newsletter article for individuals with lupus reports on the revolution in the approach to the prevention and treatment of osteoporosis in postmenopausal women. The most important aspects of this revolution include the development of bone densitometry to measure the mineral content of the bones of the lower lumbar spine and of the upper end of the femur to help determine the risk of fracture and the use of bone markers to predict bone loss and assess the response to therapy. Another aspect of this revolution is the development of new agent drugs to inhibit bone breakdown, including bisphosphonates such as alendronate, estrogen analogs, and nasal calcitonin. Studies are also being conducted on the effectiveness of parathyroid hormone and fluoride in increasing bone formation.

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Minimizing Bone Loss Due to Steroid Therapy Source: Skin and Allergy News. 28(3):25; March 1997. Summary: This newsletter article for health professionals explains how the use of a daily regimen of calcium carbonate and vitamin D3 can counter the osteoporosis caused by long-term steroid therapy. This regimen is an over-the-counter treatment, and it is simpler, safer, and less costly than treatment with calcitriol. A 2-year, double-blind, placebo-controlled trial shows that patients on prednisone plus placebo lost bone mineral density in the spine at a rate of 2 percent per year and in the trochanter at 0.9 percent per year, whereas patients on prednisone plus the regimen gained bone mineral density at 0.72 percent per year in the spine and 0.85 percent in the trochanter.

Academic Periodicals covering Osteoporosis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to osteoporosis. In addition to these sources, you can search for articles covering osteoporosis that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical

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periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for osteoporosis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with osteoporosis. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to osteoporosis: Alendronate •

Systemic - U.S. Brands: Fosamax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202794.html

Androgens •

Systemic - U.S. Brands: Andro L.A. 200; Androderm; AndroGel 1%; Android; Android-F; Andronate 100; Andronate 200; Andropository 200; Andryl 200; Delatest; Delatestryl; Depotest; Depo-Testosterone; Everone 200; Halotestin; ORETON Methyl; T-Cypionate; Testamone 100; Testaqua; Te http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202036.html

Androgens and Estrogens •

Systemic - U.S. Brands: Andrest 90-4; Andro-Estro 90-4; Androgyn L.A. DeComberol; Deladumone; Delatestadiol; depAndrogyn; Depo-Testadiol; Depotestogen; Duo-Cyp; Duo-Gen L.A. Dura-Dumone 90/4; Duratestin; Estratest; Estratest H.S. Halodrin; Menoject-L.A. OB; Premarin with http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202037.html

Caffeine •

Systemic - U.S. Brands: Cafcit; Caffedrine Caplets; Dexitac Stay Alert Stimulant; Enerjets; Keep Alert; Maximum Strength SnapBack Stimulant Powders; NoDoz Maximum Strength Caplets; Pep-Back; Quick Pep; Ultra Pep-Back; Vivarin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202105.html

Calcitonin •

Nasal-Systemic - U.S. Brands: Miacalcin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203482.html

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Systemic - U.S. Brands: Calcimar; Cibacalcin; Miacalcin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202106.html

Calcium Supplements •

Systemic - U.S. Brands: Alka-Mints; Amitone; Calcarb 600; Calci-Chew; Calciday 667; Calcilac; Calci-Mix; Calcionate; Calcium 600; Calglycine; Calphosan; CalPlus; Caltrate 600; Caltrate Jr; Chooz; Citracal; Citracal Liquitabs; Dicarbosil; Gencalc 600; Liquid Cal-600; Liquid-Ca http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202108.html

Conjugated Estrogens and Medroxyprogesterone for Ovarian Hormone Therapy (Oht) •

Systemic - U.S. Brands: Note: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/209441.html

Copper Supplements •

Systemic - U.S. Brands: Note: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202164.html

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Corticosteroids •

Dental - U.S. Brands: Kenalog in Orabase; Orabase-HCA; Oracort; Oralone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202010.html

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Inhalation - U.S. Brands: AeroBid; AeroBid-M; Azmacort; Beclovent; Decadron Respihaler; Pulmicort Respules; Pulmicort Turbuhaler; Vanceril; Vanceril 84 mcg Double Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202011.html

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Nasal - U.S. Brands: Beconase; Beconase AQ; Dexacort Turbinaire; Flonase; Nasacort; Nasacort AQ; Nasalide; Nasarel; Nasonex; Rhinocort; Vancenase; Vancenase AQ 84 mcg; Vancenase pockethaler http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202012.html

•

Ophthalmic - U.S. Brands: AK-Dex; AK-Pred; AK-Tate; Baldex; Decadron; Dexair; Dexotic; Econopred; Econopred Plus; Eflone; Flarex; Fluor-Op; FML Forte; FML Liquifilm; FML S.O.P. HMS Liquifilm; Inflamase Forte; Inflamase Mild; I-Pred; Lite Pred; Maxidex; Ocu-Dex; Ocu-Pred; Ocu-Pr http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202013.html

•

Otic - U.S. Brands: Decadron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202014.html

•

Rectal - U.S. Brands: Anucort-HC; Anu-Med HC; Anuprep HC; Anusol-HC; Anutone-HC; Anuzone-HC; Cort-Dome; Cortenema; Cortifoam; Hemorrhoidal HC; Hemril-HC Uniserts; Proctocort; Proctosol-HC; Rectosol-HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203366.html

Ergotamine, Belladonna Alkaloids, and Phenobarbital •

Systemic - U.S. Brands: Bellergal-S http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202217.html

Estrogens •

Systemic - U.S. Brands: Alora; Aquest; Climara; Clinagen LA 40; Delestrogen; depGynogen; Depo-Estradiol; Depogen; Dioval 40; Dioval XX; Dura-Estrin; Duragen-20; E-Cypionate; Estinyl; Estrace; Estraderm; Estragyn 5; Estragyn LA 5; Estra-L 40; Estratab; Estro-A; Estro-Cyp; Estro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202226.html

•

Vaginal - U.S. Brands: Estrace; Estring; Ogen; Ortho Dienestrol; Premarin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202227.html

Estrogens and Progestins (Ovarian Hormone Therapy) •

Systemic - U.S. Brands: Activella; Note: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500070.html

Etidronate •

Systemic - U.S. Brands: Didronel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202233.html

Pamidronate •

Systemic - U.S. Brands: Aredia http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202662.html

510 Osteoporosis

Raloxifene •

Systemic - U.S. Brands: Evista http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203396.html

Risedronate •

Systemic - U.S. Brands: Actonel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203554.html

Sodium Fluoride •

Systemic - U.S. Brands: Fluoritab; Fluorodex; Flura; Flura-Drops; Flura-Loz; Karidium; Luride; Pediaflor; Pharmaflur; Phos-Flur http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202527.html

Tamoxifen •

Systemic - U.S. Brands: Nolvadex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202545.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Medications 511

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to osteoporosis by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “osteoporosis” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for osteoporosis: •

Teriparatide (trade name: Parathar) http://www.rarediseases.org/nord/search/nodd_full?code=1001

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

515

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

13

These publications are typically written by one or more of the various NIH Institutes.

516 Osteoporosis

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources 517

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “osteoporosis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “osteoporosis” (or synonyms) into the “For these words:” box. The following is a sample result: •

Physical Activity and Health. A Report of the Surgeon General Source: Atlanta, GA: Department of Health and Human Services. 1996. 298 p. Contact: Superintendent of Documents, P.O. Box 371954, Pittsburgh, PA 15250-7954. Summary: This report provides information about the relationship between physical activity and health. Chapter one offers introductory information and summarizes conclusions. Chapter two examines the historical development of physical activity promotion as a means of improving health. Chapter three explores physiologic responses and long-term adaptations to exercise. Chapter four focuses on the effects of physical activity and cardiorespiratory fitness with regard to various health problems, including osteoarthritis and osteoporosis. Studies on physical activity in persons with arthritis and on the biologic effects of physical activity on the health and function of joints are highlighted. Results indicate that regular moderate exercise programs appear to relieve symptoms and improve function among people with both osteoarthritis (OA) and rheumatoid arthritis. Although no evidence demonstrates that physical activity causes OA, certain sports-related injuries have been shown to increase the risk of developing OA. Studies on physical activity and osteoporosis are identified. Results show that weight-bearing physical activity appears to build greater bone mass in childhood and early adolescence and maintain bone mass in adulthood. Research on physical activity and the prevention of fractures and falls is also highlighted. Findings indicate that physical activity appears to protect against falling, thus reducing the occurrence of fractures. Remaining chapters present data on patterns and trends in physical activity and review efforts to increase physical activity. Numerous references, 11 figures, and 38 tables.

•

The oral health and chronic disease connection Source: Washington, DC: Association of State and Territorial Health Officials. 2002. 7 pp. Contact: Available from Association of State and Territorial Health Officials, 1275 K Street, N.W., Suite 800, Washington, DC 20005. Telephone: (202) 371-9090 / fax: (202) 371-9797 / e-mail: [email protected] / Web site: http://www.astho.org. Available from the Web site at no charge.

Physician Resources 519

Summary: This access brief addresses oral health and the role of state public health. The brief provides an overview of the relationship between oral health and certain chronic diseases, focusing on diabetes, cardiovascular disease, osteoporosis, and obesity. The brief provides examples of innovative national and state programs addressing oral health and chronic diseases, such as the National Network for Oral Health Access and the Missouri Diabetes and Oral Health pilot program. •

In their own words: Adolescent girls discuss health and health care issues Source: New York, NY: Commonwealth Fund. 1997. 70 pp. Contact: Available from Commonwealth Fund, One East 75 Street, New York, NY 10021-2692. Telephone: (888) 777-2744 or (212) 606-3840 / Web site: http://www.cmwf.org. Available at no charge. Summary: This report presents the issues addressed and the findings from the qualitative phase of a two-phase program of research undertaken to better understand adolescent girls' health. The overall objective of this phase was to gain a better understanding of the informational and health care needs of adolescent girls. Among the issues explored are: access to health care services and information inside and outside the school system; sources of health care support; confidentiality and other factors that encourage or deter use of health care; ease or difficulty in communicating with health care professionals, mental health issues; adolescent girls' understanding of conditions such as heart disease, lung, breast, and cervical cancer, and osteoporosis; attitudes toward health behaviors; and knowledge, attitudes, and experiences related to reproductive health and sexuality. This report is intended to be read in conjunction with the findings of the survey, The health of adolescent girls.

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “osteoporosis” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category.

16 17

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 28624 644 1003 103 17 30391

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “osteoporosis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

18

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

19

The HSTAT URL is http://hstat.nlm.nih.gov/.

20

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 21 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 22

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 23 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Osteoporosis In the following section, we will discuss databases and references which relate to the Genome Project and osteoporosis. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “osteoporosis” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for osteoporosis: •

Acroosteolysis with Osteoporosis and Changes in Skull and Mandible Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?102500

•

Aminoaciduria with Mental Deficiency, Dwarfism, Muscular Dystrophy, Osteoporosis, and Acidosis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?204730

•

Macroepiphyseal Dysplasia with Osteoporosis, Wrinkled Skin, and Appearance Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?248010

•

Osteoporosis and Oculocutaneous Hypopigmentation Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601220

24

Aged

Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

522 Osteoporosis

•

Osteoporosis, Involutional Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?166710

•

Osteoporosis, Juvenile Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?259750

•

Osteoporosis-pseudoglioma Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?259770 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner

Physician Resources 523

syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html •

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “osteoporosis” (or synonyms) into the search box and click “Go.”

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Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “osteoporosis” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

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Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on osteoporosis can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to osteoporosis. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to osteoporosis. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “osteoporosis”:

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Guides on osteoporosis Osteoporosis http://www.nlm.nih.gov/medlineplus/tutorials/osteoporosisloader.html

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Other guides Bone Diseases http://www.nlm.nih.gov/medlineplus/bonediseases.html Hip Injuries and Disorders http://www.nlm.nih.gov/medlineplus/hipinjuriesanddisorders.html Osteogenesis Imperfecta http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html

Within the health topic page dedicated to osteoporosis, the following was listed: •

General/Overviews Tone Your Bones Source: University of Alabama at Birmingham http://www.toneyourbones.org

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Diagnosis/Symptoms Bone Densitometry http://www.nlm.nih.gov/medlineplus/tutorials/bonedensitomertryloader.html Bone Density Testing Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=WO00024 Bone Markers Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/bone_markers/glance.ht ml Diagnosing Osteoporosis Source: International Osteoporosis Foundation http://www.osteofound.org/osteoporosis/diagnosis.html Glossary of Orthopaedic Diagnostic Tests Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=372&topcategory=Abou t%2520Orthopaedics Osteoporosis Tests Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=176&topcategory=Osteo porosis

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Warning Signs of Osteoporosis Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=86&topcategory=Osteop orosis •

Treatment Medications & Osteoporosis Source: National Osteoporosis Foundation http://www.nof.org/patientinfo/medications.htm Osteoporosis and Raloxifene Source: American Academy of Family Physicians http://familydoctor.org/handouts/468.html Use of Bisphosphonates in Metabolic Bone Diseases Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=p128i&doctitle=Use%2Bof%2BBisphospho nates%2Bin%2BMetabolic%2BBone%2BDiseases&doctype=HTML%2BFact%2BShee t

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Nutrition Calcium & Vitamin D Source: National Osteoporosis Foundation http://www.nof.org/prevention/calcium.htm Calcium Supplements Source: National Osteoporosis Foundation http://www.nof.org/prevention/calcium_supplements.htm Calcium: A Guide to Common Sources Source: American Academy of Pediatrics http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZ817KZ84D& sub_cat=110 Vitamin A and Bone Health Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r617i&doctitle=Vitamin%2BA%2Band%2B Bone%2BHealth&doctype=HTML%2BFact%2BSheet

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Coping Strategies for Osteoporosis: Coping With Chronic Pain Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r202i&doctitle=Coping%2Bwith%2BChron ic%2BPain&doctype=HTML%2BFact%2BSheet

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Specific Conditions/Aspects Alcohol and Bone Health Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r706i&doctitle=Alcohol%2Band%2BBone %2BHealth&doctype=HTML%2BFact%2BSheet

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Asthma and Bone Health Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r610i&doctitle=Asthma%2Band%2BBone %2BHealth&doctype=HTML%2BFact%2BSheet Falls and Related Fractures Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r613i&doctitle=Falls%2Band%2BRelated% 2BFractures%253A%2BThe%2BRisk%2Bof%2BUndiagnosed%2BOsteoporosis&doct ype=HTML%2BFact%2BSheet First Fracture May Be Warning Sign Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=388&topcategory=Osteo porosis&all=all Fitness & Bone Health: The Skeletal Risk of Overtraining Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r614i&doctitle=Fitness%2Band%2BBone% 2BHealth%253A%2BThe%2BSkeletal%2BRisk%2Bof%2BOvertraining&doctype=HT ML%2BFact%2BSheet Oral Manifestations of Bone Loss Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r704i&doctitle=Oral%2BManifestations%2 Bof%2BBone%2BLoss&doctype=HTML%2BFact%2BSheet Osteoporosis and Arthritis: Two Common but Different Conditions Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r611i&doctitle=Osteoporosis%2Band%2B Arthritis%253A%2BTwo%2BCommon%2Bbut%2BDifferent%2BConditions&doctyp e=HTML%2BFact%2BSheet Transient Osteoporosis of the Hip Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=294&topcategory=Hip What Breast Cancer Survivors Need to Know About Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r805i&doctitle=What%2BBreast%2BCance r%2BSurvivors%2BNeed%2Bto%2BKnow%2BAbout%2BOsteoporosis&doctype=HT ML%2BFact%2BSheet What People with Anorexia Nervosa Need to Know about Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r803i&doctitle=What%2BPeople%2Bwith %2BAnorexia%2BNervosa%2BNeed%2Bto%2BKnow%2BAbout%2BOsteoporosis& doctype=HTML%2BFact%2BSheet What People with Lupus Need to Know About Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r801i&doctitle=What%2BPeople%2Bwith %2BLupus%2BNeed%2Bto%2BKnow%2BAbout%2BOsteoporosis&doctype=HTML %2BFact%2BSheet

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What People with Rheumatoid Arthritis Need to Know about Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r802i&doctitle=What%2BPeople%2Bwith %2BRheumatoid%2BArthritis%2BNeed%2Bto%2BKnow%2BAbout%2BOsteoporosi s&doctype=HTML%2BFact%2BSheet What Recovering Alcoholics Need to Know About Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r804i&doctitle=What%2BRecovering%2B Alcoholics%2BNeed%2Bto%2BKnow%2BAbout%2BOsteoporosis&doctype=HTML %2BFact%2BSheet •

Children Childhood and Adolescent Nutrition: Why Milk Matters Now for Children and Teens Source: National Institute of Child Health and Human Development http://www.nichd.nih.gov/milk/milk_facts.htm Juvenile Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r609i&doctitle=Juvenile%2BOsteoporosis &doctype=HTML%2BFact%2BSheet Kids and Their Bones: A Guide for Parents Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/osteoporosis/kidbones.htm Osteoporosis Prevention Starts Early Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=134&topcategory=Osteo porosis

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From the National Institutes of Health Osteoporosis Overview Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/osteo.html Questions and Answers on the Use of Hormones After Menopause for Osteoporosis and Recent Findings from the Women's Health Initiative Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/osteoporosis/hormones.htm What Breast Cancer Survivors Need to Know About Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r805i&doctitle=What%2BBreast%2BCance r%2BSurvivors%2BNeed%2Bto%2BKnow%2BAbout%2BOsteoporosis&doctype=HT ML%2BFact%2BSheet What Recovering Alcoholics Need to Know About Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r804i&doctitle=What%2BRecovering%2B Alcoholics%2BNeed%2Bto%2BKnow%2BAbout%2BOsteoporosis&doctype=HTML %2BFact%2BSheet

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Journals/Newsletters News Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/news.asp

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Latest News Dairy Consumption Helps Adolescent Girls Lose Weight Source: 09/23/2003, Canadian Press http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14072 .html Death Rates After Broken Hip Hold Steady in UK Source: 10/03/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14176 .html Four Shots a Year May Curb Menopausal Bone Loss Source: 10/08/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14223 .html More News on Osteoporosis http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/alphanews_o.html#O steoporosis PTH and Alendronate: Combining Treatments Shows No Bone Density Advantage Source: 10/03/2003, National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.nih.gov/news/pr/oct2003/niams-03.htm

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Men Osteoporosis and Men Source: Food and Drug Administration http://www.fda.gov/fdac/features/2002/502_men.html Osteoporosis in Men: Bone up on the Facts Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=MC00015

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Organizations International Osteoporosis Foundation http://www.osteofound.org/ National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ National Institutes of Health Osteoporosis and Related Bone Diseases~National Resource Center Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.osteo.org

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National Osteoporosis Foundation http://www.nof.org:80/ •

Prevention/Screening Height Loss: When To Be Concerned Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00826 How Can I Prevent Osteoporosis? Source: National Osteoporosis Foundation http://www.nof.org/prevention/index.htm How Physical Medicine & Rehabilitation Physicians Use Exercise to Prevent and Treat Osteoporosis Source: American Academy of Physical Medicine and Rehabilitation http://www.aapmr.org/condtreat/other/osteotreat.htm How to Keep Your Bones Healthy Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?thread_id=87&topcategory=osteopo rosis National Bone Health Campaign: Bone Health Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/nccdphp/dnpa/bonehealth/bonehealth.htm Phytoestrogens and Bone Health Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r618i&doctitle=Phytoestrogens%2Band%2 BBone%2BHealth&doctype=HTML%2BFact%2BSheet Task Force Urges Routine Osteoporosis Screening for Women 65 and Older to Identify Those at Risk for Fracture Source: Agency for Healthcare Research and Quality http://www.ahrq.gov/news/press/pr2002/ostscrpr.htm

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Research Bone Loss after Stopping Estrogen or Alendronate Therapy Source: American College of Physicians http://www.annals.org/cgi/content/full/137/11/I-31 Ending Hormone Therapy Leads to Rapid Bone Loss in Elderly Women Source: Endocrine Society http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZW7Z7LL9D& sub_cat=2 Promising New Treatment Preserves Bone Mass in Mice; May Help Women and Men with Osteoporosis Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute on Aging http://www.nih.gov/news/pr/oct2002/nia-24.htm

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PTH and Alendronate: Combining Treatments Shows No Bone Density Advantage Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.nih.gov/news/pr/oct2003/niams-03.htm Relationship between Use of Cholesterol-Lowering Drugs (Statins) and Osteoporosis in Women after Menopause Source: American College of Physicians http://www.annals.org/cgi/content/full/139/2/I-27 Statement on Hormone Therapy for the Prevention and Treatment of Postmenopausal Osteoporosis Source: American College of Obstetricians and Gynecologists http://medem.com/medlb/article_detaillb.cfm?article_ID=ZZZJLS9PJLD&sub_cat =2009 •

Statistics Fast Facts on Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=fast&doctitle=Fast%2BFacts%2Bon%2BOst eoporosis&doctype=HTML%2BFact%2BSheet

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Teenagers “Calcium Crisis” Affects American Youth Source: National Institute of Child Health and Human Development http://www.nih.gov/news/pr/dec2001/nichd-10.htm

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Women Bone Health and Osteoporosis: A Guide for Asian Women Aged 50 and Older Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r901i&doctitle=Bone%2BHealth%2Band% 2BOsteoporosis%253A%2BA%2BGuide%2Bfor%2BAsian%2BWomen%2BAged%2B 50%2Band%2BOlder&doctype=HTML%2BFact%2BSheet Caffeine and Bone Density in Older Women Source: American Dietetic Association http://webdietitians.org/Public/NutritionInformation/index_2648.cfm Osteoporosis and Asian American Women Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r601i&doctitle=Osteoporosis%2Band%2B Asian%2BAmerican%2BWomen&doctype=HTML%2BFact%2BSheet Peak Bone Mass in Women Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r701i&doctype=HTML%2BFact%2BSheet &doctitle=Peak%2BBone%2BMass%2Bin%2BWomen

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system

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(mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on osteoporosis. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Osteoporosis Source: Atlanta, GA: Arthritis Foundation. 1998. 16 p. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. http://www.arthritis.org. PRICE: Single copy free from local Arthritis Foundation chapter (call 800-283-7800 for closest local chapter); bulk orders may be purchased from address above. Summary: This brochure uses a question and answer format to provide people who have osteoporosis with information on this disease, which causes bones to lose mass and become brittle and leads to fractures, reduced height, and rounded shoulders. Some 80 percent of those affected by the disease are women, since they lose bone mass rapidly after menopause as a result of a drop in estrogen level. The brochure explains what happens in osteoporosis and outlines its many risk factors. It also explains how osteoporosis, can be prevented and how it is diagnosed from the medical history, a physical examination, and tests, particularly bone measurement tests. Treatment is based on behavior modification and medication. Several drugs for treating osteoporosis, including calcitriol, sodium fluoride, and estrogen receptor modulators, are being investigated. The brochure also provides information on the Arthritis Foundation. 1 figure.

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Osteoporosis: A Woman's Guide Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 12 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet provides women with information on reducing bone loss and preventing osteoporosis, a disease in which the skeleton becomes so weakened that the slightest injury can mean a broken bone. Osteoporosis has no early warning signs and few outward indications until a fracture occurs. Risk factors include age, gender, race, normal or early menopause, lifestyle, use of certain medications, and family history. Women can protect themselves against osteoporosis by taking estrogen, alendronate, or raloxifene; consuming enough calcium; and engaging in weight-bearing exercise. A bone mass measurement taken around the time of menopause may be helpful in deciding whether to initiate treatment. Women who already have osteoporosis may be

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able to slow its progress by consuming enough calcium, taking estrogen replacement drugs, and using calcitonin or alendronate. The pamphlet provides a safety checklist to help women eliminate common fracture hazards and presents information on the National Osteoporosis Foundation. •

Talking With Your Doctor About Osteoporosis Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 12 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet provides women with guidelines on talking to their doctor about osteoporosis. Suggestions on preparing for a visit to a doctor to discuss osteoporosis, communicating with the doctor during the visit, and following instructions given during the visit are presented. The pamphlet also includes a questionnaire to help women determine whether they are at risk for osteoporosis; identifies ways to prevent it; and provides sample questions that women should ask their doctor as young adults, during midlife, and as older adults.

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Osteoporosis: Can It Happen to You? Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 2 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet provides women with information on osteoporosis, a disease known as the 'silent thief' because it progresses without symptoms or pain until bones start to break. However, the disease is preventable if bone loss is detected early. A list of questions to help women determine whether they are at risk for developing osteoporosis is presented. In addition, the pamphlet offers suggestions for women who already have osteoporosis and highlights the activities of the National Osteoporosis Foundation.

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Stand Up to Osteoporosis: Your Guide To Staying Healthy and Independent Through Prevention and Treatment Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 26 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This booklet provides the general public with information on preventing and treating osteoporosis, a disease characterized by a loss of bone mass that leads to reduced bone strength and increased risk of fractures. The booklet presents facts about osteoporosis, explains how bone loss occurs, and lists risk factors. Risk can be reduced by consuming enough calcium and vitamin D; exercising; and taking various medications such as estrogen replacement therapy (ERT), alendronate, and raloxifene. The booklet also discusses the diagnosis and treatment of osteoporosis. Bone mass measurement is commonly used for diagnosis, while various medications, such as ERT, calcitonin, and alendronate, may be used for treatment. Several additional medications are under investigation: bisphosphonates, selective estrogen receptor modulators,

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sodium fluoride, parathyroid hormone, and vitamin D metabolites. The booklet offers suggestions on preventing falls and speaking to one's doctor about osteoporosis. In addition, the booklet presents several osteoporosis profiles. 9 figures, 1 table, and 1 reference. •

Style Wise: A Fashion Guide for Women With Osteoporosis Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 31 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This booklet provides women who have osteoporosis with guidelines on finding stylish, comfortable, and properly fitting clothing. There are five basic steps to dressing well: choosing silhouettes and colors that complement one's personal style, assessing current wardrobe for comfort and safety, accessorizing to highlight natural assets, finding the design elements that work best with one's body shape, and selecting clothes with these elements in mind. Silhouettes that balance the S-curve of the osteoporotic figure are the A line, the tent, the princess line, and the tunic. Accessories that help disguise osteoporosis are scarves, jewelry, narrow or chain belts slung low on the hips, and hats. The booklet provides guidelines on using these accessories, offers suggestions on finding properly fitting shoes and undergarments and using shoulder pads, and presents tips on using various clothing design elements to one's advantage.

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Men With Osteoporosis: In Their Own Words Source: Washington, DC: National Osteoporosis Foundation (NOF). 1998. 10 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet uses a question and answer format to provide men who have osteoporosis with information on this disease, which is characterized by a loss of bone mass and by poor bone quality. The pamphlet outlines the risk factors for osteoporosis, explains how it is diagnosed, and outlines steps people should take to preserve bone health. Preventive measures include changing an unhealthy lifestyle, consuming enough calcium and vitamin D, engaging in a regular regimen of weight-bearing exercise, recognizing and treating any underlying medical conditions that affect bone health, and discussing with a doctor the use of medications known to cause bone loss. The pamphlet also includes comments from several men on living with osteoporosis.

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What People With Arthritis Need to Know About Osteoporosis Source: Washington, DC: National Osteoporosis Foundation. 1997. 12 p. Contact: National Osteoporosis Foundation. 1232 22nd Street N.W., Washington, DC 20037-1292. (202) 223-2226. Website: www.nof.org. PRICE: Single copy $0.40; 500 or more copies $0.35. Summary: This booklet for individuals with arthritis explains what they need to know about osteoporosis. It clarifies the difference between osteoporosis and osteoarthritis and defines rheumatoid arthritis. The differences among these three conditions are outlined. The booklet also offers strategies that arthritis patients can use to prevent and treat osteoporosis, including being sure of their diagnosis, knowing the side effects of

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any medications being taken, using exercise to help relieve joint stiffness and pain, eating a healthy and balanced diet, getting adequate amounts of calcium, eliminating other risk factors for osteoporosis, and undergoing a bone density test to predict the chance of a future fracture. 1 chart. •

Facts About Osteoporosis, Arthritis, and Osteoarthritis Source: Washington, DC: National Osteoporosis Foundation (NOF). 1997. 6 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet provides people who have osteoporosis, arthritis, and osteoarthritis with information on these painful chronic diseases. Osteoporosis is characterized by a loss of bone mass and by poor bone quality, which lead to reduced bone strength and increased risk of fractures. The pamphlet lists the risk factors for osteoporosis and highlights prevention and treatment strategies. Osteoarthritis (OA), the most common form of arthritis, is a degenerative joint disease that leads to the thinning or destruction of the cartilage. The pamphlet presents the features of OA, identifies risk factors, and comments on diagnosis and treatment. Rheumatoid arthritis (RA) is an inflammatory disease of the lining of the joints that has no known cause. The pamphlet presents the warning signs of RA and provides information on diagnosis, treatment, and outcomes.

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Medications and Bone Loss: Are You at Risk for Osteoporosis? Source: Washington, DC: National Osteoporosis Foundation (NOF). 1997. 18 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This booklet provides the general public with information on the relationship between using certain medications and developing osteoporosis. This disease is characterized by inadequate bone formation, excessive bone removal, or both, leading to reduced bone strength and increased risk of fractures. The booklet briefly describes the bone remodeling process and identifies the risk factors for osteoporosis. One risk factor that is often overlooked is the use of certain medications that can damage bones and lead to osteoporosis. One class of drugs that has particularly damaging effects is glucocorticoids, which interfere with the bone remodeling process and calcium regulation in various ways. Bone loss increases with the dose and the duration of treatment. Other drugs that can cause osteoporosis are thyroid hormones, phenytoin and barbiturate anticonvulsants, aluminum-containing antacids, methotrexate, cyclosporine A, gonadotropic releasing hormone analogs, heparin, and cholestyramine. The booklet offers suggestions on minimizing the harmful effects of steroids and other medications. 2 figures, 2 tables, and 2 references.

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How Strong Are Your Bones? Find Out If You Are at Risk for Osteoporosis Source: Washington, DC: National Osteoporosis Foundation (NOF). 1997. 15 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost.

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Summary: This brochure uses a question and answer format to provide the general public with information on osteoporosis and bone density testing. Osteoporosis is a disease that causes bones to weaken and break easily. The brochure describes the normal bone remodeling process, explains how osteoporosis occurs, identifies its causes and risk factors, and discusses the medical tests available to measure bone density. The brochure presents the features of these tests, explains the information that the test provides the patient and the doctor, identifies candidates test, and explains what the results of the test mean. In addition, the brochure highlights treatments that can slow bone loss and prevent osteoporotic fractures, such as estrogen replacement therapy, alendronate, and calcitonin. 8 figures, 1 table, and 1 reference. •

Osteoporosis: The Silent Bone Thinner Source: Bethesda, MD: National Institute on Aging. 1996. 6 p. Contact: National Institute on Aging Information Center, P.O. Box 8057, Gaithersburg, MD 20898-8057. (800) 222-2225. (800) 224-4225 (tty). Summary: This pamphlet for individuals with osteoporosis presents an overview of this disease. It explains who is at risk for getting osteoporosis and discusses the diagnosis and treatment of osteoporosis. Treatment options include hormone replacement therapy. In addition, the pamphlet suggests ways of preventing osteoporosis, including getting enough dietary calcium and vitamin D and engaging in regular weight-bearing exercise, and it lists sources of additional information.

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Osteoporosis and Women: A Major Public Health Problem Source: Washington, DC: National Osteoporosis Foundation (NOF). 1995. 6 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet uses a question and answer format to provide women with information on osteoporosis, demonstrably the foremost health problem for women. Osteoporosis is characterized by a loss of bone mass, which leads to reduced bone strength, poor bone quality, and an increased risk of fractures. The pamphlet outlines the serious effects of osteoporosis and explains why women are at higher risk than men. Other topics include whether osteoporosis is a normal part of aging and how women know they have it.

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Menopause and Osteoporosis: Choices for a Healthy Future Source: Washington, DC: National Osteoporosis Foundation (NOF). 199x. 23 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This booklet provides women with information about the impact of menopause on osteoporosis, a disease characterized by a loss of bone mass and by poor bone quality, which lead to reduced bone strength and increased risk of fractures. Following menopause, production of estrogen, which has an important role in the bone renewal process, ceases. In many women, the loss of estrogen after menopause leads to rapid bone removal. The booklet lists the risk factors for osteoporosis, explains how a bone mineral density test can determine the strength of a woman's bones, and outlines

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steps women can take to prevent osteoporosis, among them the use of estrogen replacement therapy or hormone replacement therapy, which slows or stops bone loss in postmenopausal women. Additional medications that may be used to treat osteoporosis include calcitonin and alendronate. Other approaches include consuming enough calcium and vitamin D and exercising. The booklet also lists some questions women should ask their doctor about osteoporosis, offers suggestions for improving health and well-being, presents a list of resources, and concludes with information on the National Osteoporosis Foundation. 3 figures and 1 table. •

Living With Osteoporosis Source: Washington, DC: National Osteoporosis Foundation (NOF). 199x. 12 p. Contact: Available from National Osteoporosis Foundation. 1150 17th Street, NW, Suite 500, Washington, DC 20036-4603. (202) 223-2226. Fax (202) 223-2237. Website: www.nof.org. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet identifies some of the causes of falls and presents steps people who have osteoporosis can take to avoid them. Preventive measures include having regular vision and hearing examinations; knowing how medications may affect coordination or balance; limiting alcohol consumption; being careful to avoid getting up too quickly after eating, lying down, or resting; keeping the nighttime house temperature above 65 degrees; using walking aids; wearing proper footwear; and maintaining a regular program of exercise. In addition, the pamphlet presents tips on coping with a fall, offers suggestions to help people modify their daily activities to avoid bending forward at the waist or twisting, and presents ideas for making each room in the house fall-proof.

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Boning up on osteoporosis: A guide to prevention and treatment Source: Washington, DC: National Osteoporosis Foundation. 1991. 60 pp. Contact: Available from Laurie Gibson Lindberg, Information Specialist, National Osteoporosis Foundation, 1150 17th Street, N.W., Suite 500, Washington, DC 20036-4603. Telephone: (202) 223-2226 / fax: (202) 223-2237 / Web site: http://www.nof.org. $2.00. Summary: This booklet provides a thorough overview of the prevention and treatment of osteoporosis. Prevention approaches are indicated for all stages of life including childhood, adolescence, young adulthood, midlife, and old age. Among the material presented are the following nutrition topics: the role of calcium; food sources of calcium and calcium supplements; the RDAs; lactose intolerance; calcium absorption and excretion; and vitamin D. Fourteen exercises for good posture and body mechanics are described and illustrated, as well as general guidelines for exercise programs. Information is included on estrogen replacement therapy, accident prevention, and additional suggested readings.

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There's Good News for Women!: You Can Take Charge of Your Health, Achieve a Healthy Weight, and Help Prevent Heart Disease, Breast Cancer, and Osteoporosis Source: Weight Watchers International, 8 p., N.D. Contact: Weight Watchers International, 360 Lexington Ave., 11th Floor, New York, NY 10017. (800) 651-6000. Summary: This brochure focuses on the small steps that women can take to improve their health, reduce their weight, and prevent certain diseases. According to the

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brochure, the key to good health is to reach and maintain a healthy weight. Excess weight increases the risk of heart disease, osteoporosis, and breast cancer. The brochure advises that women initiate a diet lower in fat and higher in carbohydrates, and to increase physical activity. The recommendations in this brochure are part of the principles of the Weight Watchers program, which include maintaining an active lifestyle; having a positive, healthy outlook; and belonging to a weight loss support group. •

Osteoporosis and Corticosteroid-Induced Osteoporosis Source: American College of Rheumatology. 2000. 3 p. Contact: American College of Rheumatology. 1800 Century Place, Suite 250, Atlanta, GA 30345. (404) 633-3777. Website: www.rheumatology.org. Email: [email protected]. Summary: This fact sheet provides information on osteoporosis, a skeletal disease characterized by abnormal decrease in bone mass and strength resulting in an increased susceptibility of bone fractures of the spine, hip, or wrist. Bone loss is normal as people age but certain factors or conditions, including menopause, cigarette smoking, lack of calcium, lack of exercise, and certain medications, can increase the risk of developing osteoporosis. Diagnosis is made using X-ray densitometry (DEXA), CT scans, and plain x-rays. Treatment for osteoporosis includes having a healthy diet emphasizing adequate calcium and vitamin D consumption, regular weight-bearing exercise, and for postmenopausal women estrogen, biphosphonates, calcitonin, and ralaxofene. Prolonged corticosteroid use can also cause osteoporosis by decreasing calcium absorption in the intestine and increasing the rate of breakdown of bone. Corticosteroidinduced osteoporosis (CIO) is diagnosed using DEXA and is treated the same way nonCIO induced osteoporosis is. If possible the dose of corticosteroids is decreased.

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OI Issues: Osteoporosis Source: Gaithersburg, MD: Osteogenesis Imperfecta Foundation (OIF). 1997. 2 p. Contact: Available from Osteogenesis Imperfecta Foundation. 804 West Diamond Avenue, Suite 210, Gaithersburg, MD 20878. (800) 981-2663 or (301) 947-0083. Fax (301) 947-0456. Website: www.oif.org. PRICE: Single copy free. Summary: This fact sheet provides health professionals and people who have osteogenesis imperfecta (OI) with information on osteoporosis in OI. It explains that OI is a genetic disorder in which defective collagen makes the bones fragile and identifies the features of Type I, II, III, and IV OI. The fact sheet discusses the relationship between OI and osteoporosis and explains that to minimize bone loss, people with OI should perform activities such as isometric exercise, weight lifting, standing, and walking; consume adequate amounts of calcium; and use various therapeutic agents to minimize bone loss. Other topics include the impact of menopause on OI and the factors that may interfere with a bone density measurement in people with OI. In addition, the fact sheet identifies a resource for information on osteoporosis.

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Osteoporosis and Your Bones Source: American Family Physician. 54(3): 995-996. September 1, 1996. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org.

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Summary: This fact sheet for the general public discusses what osteoporosis is, how it can be prevented, symptoms, diagnosis, and treatment options. The sheet explains that osteoporosis is a decrease in density or thickness of bone and that prevention entails a diet containing enough calcium and vitamin D. A family history of osteoporosis, shortening of height, a deformity of the spine, and pain in the back or neck are all symptoms associated with osteoporosis. Bone density measurements and blood and urine laboratory tests can confirm a suspicion of osteoporosis, and if confirmed, treatment can involve drug therapy to reduce calcium loss. •

Patient Information Guide: Osteoporosis and Diabetes Source: Practical Diabetology. 17(2): 15-16. June 1998. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: This fact sheet provides guidelines for self care among people with both diabetes and osteoporosis. It explains that certain complications of diabetes increase the risk of falling, and osteoporosis increases the risk of fracturing a bone during a fall. This fact sheet presents suggestions for preventing falls and fractures, including taking steps to fall-proof one's home, following general safety guidelines and prescribed treatment regimens, and being alert to the side effects of medications and other factors that may increase the risk of falling. The fact sheet is designed for physicians to photocopy and distribute to patients. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “osteoporosis” (or synonyms). The following was recently posted: •

ACR Appropriateness Criteria for osteoporosis and bone mineral density Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2001); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3263&nbr=2489&a mp;string=osteoporosis

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Diagnosis and treatment of osteoporosis Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 2002 August; 67 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3411&nbr=2637&a mp;string=osteoporosis

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Management of postmenopausal osteoporosis: position statement of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2002 March; 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3179&nbr=2405&a mp;string=osteoporosis

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Osteoporosis Source: American Health Care Association - Professional Association; 1998; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1810&nbr=1036&a mp;string=osteoporosis

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Osteoporosis Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2002 February; 63 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3435&nbr=2661&a mp;string=osteoporosis

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Osteoporosis prevention, diagnosis, and therapy Source: National Institutes of Health (NIH) Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy - Independent Expert Panel; 2000 March 27-29; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2535&nbr=1761&a mp;string=osteoporosis

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Osteoporosis. Guide to prevention, diagnosis, and treatment Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 1999 (revised 2001); 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3430&nbr=2656&a mp;string=osteoporosis

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Osteoporosis: prevention and treatment Source: University of Michigan Health System - Academic Institution; 2002 March; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3541&nbr=2767&a mp;string=osteoporosis

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Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update Source: American College of Rheumatology - Medical Specialty Society; 1996 September 3 (updated 2001); 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2934&nbr=2160&a mp;string=osteoporosis

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Screening for osteoporosis in postmenopausal women: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002 September 17); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3417&nbr=2643&a mp;string=osteoporosis Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

American Indian and Alaska Native Women's Health: Mature Women Summary: This page features links to information about osteoporosis and hormone replacement therapy. Source: Indian Health Service http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6882

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An Osteoporosis Overview Summary: Men as well as women suffer from this preventable disease, characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to Source: NIH Osteoporosis and Related Bone Diseases~National Resource Center http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2374

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Asian American Women and Osteoporosis Summary: This consumer health information fact sheet provides information about osteoporosis as it relates specifically to Asian American women. It discusses risk factors, prevention and treatment options. Source: NIH Osteoporosis and Related Bone Diseases~National Resource Center http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3528

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healthfinder® just for you: Women Summary: healthfinder®'s just for you: Women section features topics such as breast cancer, osteoporosis, and pregnancy. Source: U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7014

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Latino Women and Osteoporosis Summary: This consumer health information fact sheet provides information about osteoporosis as it relates specifically to Hispanic (Latino) women. It discusses risk factors, prevention and treatment options. Source: NIH Osteoporosis and Related Bone Diseases~National Resource Center http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3529

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News and Press Releases - Osteoporosis and Related Bone Diseases/National Resource Center Summary: This page provides the latest press releases, reports and announcements related to osteoporosis and other bone diseases. Source: NIH Osteoporosis and Related Bone Diseases~National Resource Center http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1530

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One-Minute Osteoporosis Risk Test Source: International Osteoporosis Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7669

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Osteoporosis Source: American Academy of Orthopaedic Surgeons http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7398

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Osteoporosis and African-American Women Summary: This consumer health information fact sheet provides information about osteoporosis as it relates specifically to African American women. It discusses risk factors, prevention and treatment options. Source: NIH Osteoporosis and Related Bone Diseases~National Resource Center http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3527

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Osteoporosis in Men Summary: This consumer health information fact sheet discusses the risk factors associated with osteoporosis in men and prevention methods you can take to reduce your chances of developing this bone disease. Source: NIH Osteoporosis and Related Bone Diseases~National Resource Center http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3934

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Osteoporosis Information for American Indian/Alaska Native Women Summary: This brief fact sheet describes how osteoporosis affects minority women. Source: National Women's Health Information Center, U.S. Public Health Service's Office on Women's Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6939

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Osteoporosis Prevention, Diagnosis, and Therapy: NIH Consensus Statement Summary: This NIH consensus statement covers risks, prevention, treatment, and research related to osteoporosis. Source: National Institutes of Health, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6357

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Osteoporosis What you should know Source: Federation of Chinese American and Chinese Canadian Medical Societies http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7277

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Osteoporosis: Progress and Promise Summary: Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6728

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Osteoporosis: The Bone Thief Summary: Online patient education fact sheet that provides information about prevention, diagnosis and treatment options for this bone disease that thins and weakens bones to the point where they break Source: National Institute on Aging, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2375

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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to osteoporosis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources

A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/specific.htm

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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

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Med Help International: http://www.medhelp.org/HealthTopics/A.html

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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

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WebMDHealth: http://my.webmd.com/health_topics

Associations and Osteoporosis The following is a list of associations that provide information on and resources relating to osteoporosis: •

Addison and Cushing International Federation Telephone: 31-153699339 Fax: 31-153699339 Email: [email protected] Web Site: www.nvacp.nl Background: The Addison and Cushing International Federation (ACIF), established in 1996, is a platform of organisations involved in the support of those affected with Addison's disease, Cushing's syndrome (or disease) and related adrenal or pituitaryrelated diseases (e.g., Acromegaly, CAH and other disorders). ACIF maintains a listing of organisations, support groups and individuals who want to start support groups in countries where none exist, that are involved in the field of adrenal and pituitary disorders. The ACIF web site remains a part of the web site of the Dutch Addison and Cushing Society (NVACP). Whenever possible, messages will be diverted to existing patient support groups already known to ACIF. Addison's disease is a rare disorder characterized by deficiency of certain hormones (i.e., hydrocortisone and aldosterone)

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produced by the outer region (cortex) of the adrenal glands. Acute episodes (Addisonian crises) may be characterized by excessive loss of sodium and water in the urine, dehydration, low blood pressure (hypotension), extreme muscle weakness, confusion, and coma. In most cases, however, the disease's onset is chronic and progressive where affected individuals may experience fatigue, weakness, weight loss, abdominal pain, and abnormal darkening of the skin in certain areas of the body. Cushing's syndrome is a hormonal disorder characterized by abnormally increased levels of certain hormones (i.e., corticosteroid hormones) produced by the adrenal glands. Associated symptoms and findings may include abnormal roundness and reddening of the face, weight gain, wasting of the limbs, excessive hair growth, loss of bone density and susceptibility to fractures (osteoporosis), increased blood pressure (hypertension), susceptibility to bruising, mental changes, and/or other abnormalities. •

Back Pain Association of America, Inc Telephone: (410) 255-3633 Fax: (410) 255-7338 Email: [email protected] Background: The Back Pain Association of America, Inc. (BPAA) is a national nonprofit organization dedicated to providing information and support to people who are affected by back and neck pain, their family members, friends, and health care professionals. Established in 1991 and consisting of nearly 4,000 members, BPAA offers programs and information to help affected individuals learn more about their spinal disorders and ways to cope with them. The organization also has a program to help individuals prevent back injuries. BPAA publishes a self-titled quarterly newsletter that helps readers stay informed of updated information and new forms of treatment. The organization s 'Friends Across America' networking program enables affected individuals to exchange information and support via telephone. BPAA also has a physician referral service as well as an information service for physicians who treat back and neck pain. In addition, the Association also promotes research and offers a variety of fact sheets including 'The Relationship Between Nerve Damage and Leg Pain,' 'Urinary Problems and Diseases of the Spine,' 'Arachnoiditis, Questions and Answers,' and 'A Guide to Abdominal and Stretching Exercises.'. Relevant area(s) of interest: Osteoporosis

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Hormone Foundation Telephone: Toll-free: (800) 467-6663 Fax: (310) 941-0259 Email: [email protected] Web Site: www.hormone.org Background: The Hormone Foundation is dedicated to serving as a resource for the public by promoting the prevention, treatment and cure of hormone-related diseases. It provides information on diseases including congenital adrenal hyperplasia, diabetes insipidus, hypoparathyroidism, hypothyroidism, polycystic ovary syndrome, and pseudohypoparathyroidism. Relevant area(s) of interest: Osteoporosis

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National Gaucher Foundation, Inc Telephone: (301) 816-1515 Toll-free: (800) 428-2437 Fax: (301) 816-1516 Email: [email protected] Web Site: http://www.gaucherdisease.org Background: The National Gaucher Foundation is a not-for-profit organization that supports medical research into causes of Gaucher disease. Gaucher disease is a rare metabolic disorder characterized by the accumulation of a fatty substance, a lipid called glucocerebrosidase. The most common symptoms of Gaucher disease are enlargement of the liver and spleen, anemia, reduced platelets (resulting in easy bruising and long clotting times), bone infarctions often leading to damage to the shoulder or hip joints, and a generalized demineralization of the bones (osteoporosis) that can lead to spontaneous fractures. Founded in 1984, the National Gaucher Foundation encourages scientific investigation into developing treatments for Gaucher disease. The organization hopes that this research will ultimately lead to a cure for the disease. In addition to funding vital research, the National Gaucher Foundation offers an extensive range of services to people with Gaucher disease and their families. These services include financial assistance and patient and physician education programs. The Foundation also publishes a quarterly newsletter.

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NIH Osteoporosis and Related Bone Diseases National Resource Center Telephone: (202) 223-0344 Toll-free: (800) 624-2663 Fax: (202) 293-2356 Email: [email protected] Web Site: http://www.osteo.org Background: NIH Osteoporosis and Related Bone Diseases National Resource Center (NIH ORBD-NRC) is dedicated to expanding awareness and enhancing knowledge and understanding of the prevention, early detection, and treatment of these diseases, as well as strategies for coping with them. Osteoporosis is a disease characterized by low bone mass and structural deterioration on bone tissue, leading to bone fragility and an increased susceptibility to fractures of the hip, spine, and wrist. Founded in 1994, NIH ORBD-NRC provides affected individuals, families, health-care professionals and families with an important link to resources and information on metabolic bone diseases. The Center collects information on materials, programs, and support services on metabolic bone diseases and disseminates this information widely through publications (e.g., 'Fast Facts on Primary Hyperparathyriodism,' 'Hypophosphatasia,' and 'Myeloma Bone Disease'), online services, professional and patient meetings and general media outreach. In addition, its extensive database provides individuals with answers to their questions or refers them to sources of additional information. The Resource Center is supported by the National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health. Relevant area(s) of interest: Osteoporosis

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Progeria Research Foundation Telephone: (978) 535-2594 Fax: (978) 535-5849

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Email: [email protected] Web Site: http://www.progeriaresearch.org Background: The Progeria Research Foundation is a non-profit organization whose mission is to fund medical research to discover the cause, effective treatment, and cure for Hutchinson-Gilford Progeria Syndrome ('Progeria'), and to raise awareness about Progeria by educating the families, the public and health professionals. Progeria is a terminal, 'premature aging' syndrome that afflicts children. After the first year of life, severe developmental failure begins and the child's hair falls out. Over the next few years, the children are susceptible to strokes, arthritis, and osteoporosis. Their final average height is 3 feet, their final average weight is 33 pounds, and the average life expectancy is 13 years. Amazingly, the brain is unaffected; these remarkable children are recognized for their intelligence and lovable personalities throughout their shortened lives. Children with Progeria are genetically predisposed to premature, progressive cardiovascular disease. Death occurs almost exclusively due to widespread atherosclerosis (heart disease). Thus, finding a cure for Progeria may help the millions of people that suffer from heart disease and other conditions related to aging. PRF is always looking for volunteers to translate for the families that are located all over the world and speak over a dozen different languages; to donate or hold fundraisers to raise money; and to participate in many other ways to further the quest for a cure. •

Severe Chronic Neutropenia International Registry Australia Telephone: 61-3-5333 4811 Fax: 61-3-5333 4813 Email: [email protected] Web Site: http://freyja.ballarat.edu.au:8080/~scnirau/ Background: The Severe Chronic Neutropenia International Registry Australia (SCNIRAU) is the Australian division of the Severe Chronic Neutropenia International Registry. The Australian division, which registered its first patient in 1994, currently has over 30 patients registered, while over 400 patients are registered internationally. Chronic Neutropenia is a blood disorder characterized by abnormally low levels of certain white blood cells known as neutrophils that are produced by the bone marrow and play an essential role in fighting infection. Individuals with Chronic Neutropenia may be abnormally susceptible to certain bacterial infections and may experience other associated symptoms and/or findings. The International Registry is committed to documenting the clinical course of Severe Chronic Neutropenia (SCN); monitoring and assessing long-term safety of primary treatments in individuals with SCN in the United States, Canada, Europe, and Australia; and studying the incidence and outcome of certain previously identified adverse events including osteoporosis, splenomegaly, cytogenetic abnormalities, myeloplastic syndrome, and leukemia.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to osteoporosis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with osteoporosis.

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The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about osteoporosis. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “osteoporosis” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “osteoporosis”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “osteoporosis” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “osteoporosis” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.27

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

27

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)28: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

28

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 553

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

554 Osteoporosis

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries 555

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

556 Osteoporosis

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

557

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on osteoporosis: •

Basic Guidelines for Osteoporosis Eating disorders Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000341.htm Hyperthyroidism Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000356.htm Osteoporosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000360.htm

•

Signs & Symptoms for Osteoporosis Bone pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003180.htm Bone pain or tenderness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003180.htm

558 Osteoporosis

Low back pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003108.htm Neck pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003025.htm •

Diagnostics and Tests for Osteoporosis spine or hip X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003806.htm Alkaline phosphatase Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003470.htm ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Calcitonin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003699.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Spine CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003787.htm TSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm Urine protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003580.htm Urine protein electrophoresis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003589.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

•

Nutrition for Osteoporosis Calcium in diet Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002412.htm

Online Glossaries 559

Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm Vitamin D Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002405.htm •

Background Topics for Osteoporosis Alcohol consumption Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001944.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Fracture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Fractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Insidious Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002382.htm Malignancy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002253.htm Peripheral Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002273.htm Smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

561

OSTEOPOROSIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acclimatization: Adaptation to a new environment or to a change in the old. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acitretin: An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of etretinate with the advantage of a much shorter half-life when compared with etretinate. [NIH]

Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different

562 Osteoporosis

from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Monophosphate: Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH]

Dictionary 563

Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airways: Tubes that carry air into and out of the lungs. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alendronate Sodium: A drug that affects bone metabolism. It is used in treating osteoporosis and Paget's disease, and is being studied in the treatment of hypercalcemia (abnormally high levels of calcium in the blood) and in treating and reducing the risk of bone pain caused by cancer. Alendronate sodium belongs to the family of drugs called bisphosphonates. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH]

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Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Bone Loss: The resorption of bone in the supporting structures of the maxilla or mandible as a result of periodontal disease. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration.

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Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Alcohols: Compounds possessing both a hydroxyl (-OH) and an amino group (NH2). [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgen suppression: Treatment to suppress or block the production of male hormones. Androgen suppression is achieved by surgical removal of the testicles, by taking female sex

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hormones, or by taking other drugs. Also called androgen ablation. [NIH] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH]

Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angulation: Deviation from the normal long axis, as in a fractured bone healed out of line. [NIH]

Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

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Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthropometry: The technique that deals with the measurement of the size, weight, and proportions of the human or other primate body. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and

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febrifuge. [EU] Antirheumatic Agents: Drugs that are used to treat rheumatoid arthritis. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Aromatic: Having a spicy odour. [EU] Arrestins: Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors. [NIH]

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Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthralgia: Pain in the joint. [NIH] Arthropathy: Any joint disease. [EU] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Articular: Of or pertaining to a joint. [EU] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH]

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Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Avian: A plasmodial infection in birds. [NIH] Axilla: The underarm or armpit. [NIH] Back Injuries: General or unspecified injuries to the posterior part of the trunk. It includes injuries to the muscles of the back. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical

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manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH]

Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH]

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Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blind spot: (1) A small area of the retina where the optic nerve enters the eye; occurs normally in all eyes.(2) Any gap in the visual field corresponding to an area of the retina where no visual cells are present; associated with eye disease. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH]

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Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bolus injection: The injection of a drug (or drugs) in a high quantity (called a bolus) at once, the opposite of gradual administration (as in intravenous infusion). [EU] Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [NIH]

Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins. [NIH] Bone Regeneration: Renewal or repair of lost bone tissue. It excludes bony callus formed after bone fracture but not yet replaced by hard bone. [NIH] Bone Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH]

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Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bone Transplantation: The grafting of bone from a donor site to a recipient site. [NIH] Bony Callus: The bony deposit formed between and around the broken ends of a fractured bone during normal healing. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Compounds: Inorganic or organic compounds that contain boron as an integral part of the molecule. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brace: Any form of splint or appliance used to support the limbs or trunk. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broadband: A wide frequency range. Sound whose energy is distributed over a broad range of frequency (generally, more than one octave). [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cadaver: A dead body, usually a human body. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases,

Dictionary 575

antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcaneus: The largest of the tarsal bones and is situated at the lower and back part of the foot forming the heel. [NIH] Calcifediol: The major circulating metabolite of vitamin D3 produced in the liver and the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [NIH] Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Citrate Malate: It transmits extracellular signals within cells. [NIH] Calcium Metabolism Disorders: Disorders in the processing of calcium in the body, including absorption, transport, storage, and utilization. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually

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composed of mineral salts. Also called stones. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogenicity: The ability to cause cancer. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for

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example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Castration: Surgical removal or artificial destruction of gonads. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Degranulation: The process of losing secretory granules (secretory vesicles). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by exocytosis. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU]

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Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Centchroman: A non-steroidal anti-fertility agent with anti-hormonal properties. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chaperonins: A class of sequence-related molecular chaperones found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are chaperonin 10 and chaperonin 60. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or

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immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholecalciferol: An antirachitic oil-soluble vitamin. [NIH] Cholelithiasis: Presence or formation of gallstones. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]

Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrogenesis: The formation of cartilage. This process is directed by chondrocytes which continually divide and lay down matrix during development. It is sometimes a precursor to osteogenesis. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]

Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chronotropic: Affecting the time or rate, as the rate of contraction of the heart. [EU] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH]

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Ciliary Arteries: Three groups of arteries found in the eye which supply the iris, pupil, sclera, conjunctiva, and the muscles of the iris. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clodronate: A drug used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). It may decrease pain, the risk of fractures, and the development of new bone metastases. [NIH] Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Codon: A set of three nucleotides in a protein coding sequence that specifies individual

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amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be

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used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine.

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Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective tissue: The supporting or framework tissue of the animal body, formed of fibrous and ground substance with more or less numerous cells of various kinds. [NIH] Connective tissue: The supporting or framework tissue of the animal body, formed of fibrous and ground substance with more or less numerous cells of various kinds. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Diseases: Diseases of the cornea. [NIH]

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Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a

Dictionary 585

representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cyproterone Acetate: An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, ... New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU]

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Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demography: Statistical interpretation and description of a population with reference to distribution, composition, or structure. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dental Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Dental implant: A small metal pin placed inside the jawbone to mimic the root of a tooth. Dental implants can be used to help anchor a false tooth or teeth, or a crown or bridge. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU]

Dictionary 587

Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] DEXA: A method (dual energy X-ray absortiometry) used to estimate total body fat and percent of body fat. Potential disadvantages include whole body radiation and the long time required for scanning while the subject lies on a hard table. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphoresis: Perspiration, especially profuse perspiration. Called also sudoresis. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digital rectal examination: DRE. An examination in which a doctor inserts a lubricated, gloved finger into the rectum to feel for abnormalities. [NIH] Dihydrotachysterol: Vitamin D. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphosphonates: Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU]

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Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of singlestranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH]

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Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] Ductus Arteriosus: A fetal blood vessel connecting the pulmonary artery with the descending aorta. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric Conductivity: The ability of a substrate to allow the passage of electrons. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromagnetic Fields: Fields representing the joint interplay of electric and magnetic forces. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current.

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[NIH]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium:

A layer of epithelium that lines the heart, blood vessels (endothelium,

Dictionary 591

vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] Environment Design: The structuring of the environment to permit or promote specific patterns of behavior. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi

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and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epiphyseal: Pertaining to or of the nature of an epiphysis. [EU] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Equilenin: 3-Hydroxyestra-1,3,5(10),6,8-pentaen-17-one. A naturally occurring steroid with estrogenic activity obtained from the urine of pregnant mares. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen Receptor Modulators: Substances that possess antiestrogenic actions but can also produce estrogenic effects as well. They act as complete or partial agonist or as antagonist. They can be either steroidal or nonsteroidal in structure. [NIH] Estrogen receptor positive: ER+. Breast cancer cells that have a protein (receptor molecule) to which estrogen will attach. Breast cancer cells that are ER+ need the hormone estrogen to grow and will usually respond to hormone (antiestrogen) therapy that blocks these receptor sites. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations

Dictionary 593

as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etidronate: A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] Etretinate: An oral retinoid used in the treatment of keratotic genodermatosis, lichen planus, and psoriasis. Beneficial effects have also been claimed in the prophylaxis of epithelial neoplasia. The compound may be teratogenic. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excrete: To get rid of waste from the body. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU]

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Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Fractures: Fractures of the femur. [NIH] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its

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length, it is the most slender of the long bones. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Finite Element Analysis: A computer based method of simulating or analyzing the behavior of structures or components. [NIH] Flexor: Muscles which flex a joint. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluoridation: The addition of fluorine usually as a fluoride to something, as the adding of a fluoride to drinking water or public water supplies for prevention of tooth decay in children. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Flush: Transient, episodic redness of the face and neck caused by certain diseases, ingestion of certain drugs or other substances, heat, emotional factors, or physical exertion. [EU] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Foetoplacental: Pertaining to the fetus and placenta. [EU] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Forearm: The part between the elbow and the wrist. [NIH] Fosamax: A Merck's osteoporosis drug. [NIH] Fracture Fixation: The use of metallic devices inserted into or through bone to hold a fracture in a set position and alignment while it heals. [NIH] Fracture Healing: The physiological restoration of bone tissue and function after a fracture. It includes bony callus formation and normal replacement of bone tissue. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is

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used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrectomy: An operation to remove all or part of the stomach. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and

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order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH]

Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid:

A compound that belongs to the family of compounds called

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corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH] Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a

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nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadal Dysgenesis: Any of several developmental anomalies involving the total or partial failure of the indifferent embryonic gonad to differentiate into ovary or testis. This concept includes gonadal agenesis. [NIH] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH]

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Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Resources: Available manpower, facilities, revenue, equipment, and supplies to produce requisite health care and services. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another.

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[NIH]

Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. [NIH] Heat-Shock Proteins 90: A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

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Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Heparin-binding: Protein that stimulates the proliferation of endothelial cells. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also

Dictionary 603

called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU]

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Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercalciuria: Abnormally large amounts of calcium in the urine. [NIH] Hyperkeratosis: 1. Hypertrophy of the corneous layer of the skin. 2a. Any of various conditions marked by hyperkeratosis. 2b. A disease of cattle marked by thickening and wringling of the hide and formation of papillary outgrowths on the buccal mucous membranes, often accompanied by watery discharge from eyes and nose, diarrhoea, loss of condition, and abortion of pregnant animals, and now believed to result from ingestion of the chlorinated naphthalene of various lubricating oils. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild

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symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypovitaminosis: A condition due to a deficiency of one or more essential vitamins. [EU] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterectomy: Excision of the uterus. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: (antigens). [NIH]

The activity of the immune system against foreign substances

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH]

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Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incisor: Anything adapted for cutting; any one of the four front teeth in each jaw. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU]

Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Inertia: Inactivity, inability to move spontaneously. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH]

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Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH]

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Interferometry: Measurement of distances or movements by means of the phenomena caused by the interference of two rays of light (optical interferometry) or of sound (acoustic interferometry). [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH]

Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH]

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Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

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Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Ketotifen: A cycloheptathiophene that interferes with the release of inflammatory mediators and blocks histamine H1 receptors. It has been proposed as an anti-asthmatic and for the treatment of rhinitis, skin allergies, and anaphylaxis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Lactose Intolerance: The disease state resulting from the absence of lactase enzyme in the musocal cells of the gastrointestinal tract, and therefore an inability to break down the disaccharide lactose in milk for absorption from the gastrointestinal tract. It is manifested by indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH]

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Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: circulation. [NIH]

Services offered to the library user. They include reference and

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH]

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Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [NIH] Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH]

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Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumbago: Pain in the lumbar region. [EU] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH]

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Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malformation: A morphologic defect resulting from an intrinsically abnormal developmental process. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mass Screening: Organized periodic procedures performed on large groups of people for the purpose of detecting disease. [NIH] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [NIH] Materials Testing: The testing of materials and devices, especially those used for implants, prostheses, sutures, adhesives, etc., for hardness, strength, durability, safety, and efficacy. [NIH]

Matrix metalloproteinase: A member of a group of enzymes that can break down proteins,

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such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical castration: Refers to the use of drugs to suppress the function of the ovaries or testicles. [NIH] Medical Records: illnesses. [NIH]

Recording of pertinent information concerning patient's illness or

Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some

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primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] Metrorrhagia: Uterine bleeding, usually irregular or acyclic, between periods. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH]

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Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (10-6 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently labeled with radioisotopes or various reagents acting as tags or markers. [NIH] Microvilli: Minute projections of cell membranes which greatly increase the surface area of the cell. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH]

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Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the chaperonins, the heat-shock proteins 70, and the heat-shock proteins 90. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

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Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal Diseases: Diseases of the muscles and their associated ligaments and other connective tissue and of the bones and cartilage viewed collectively. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU]

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Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nadir: The lowest point; point of greatest adversity or despair. [EU] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Neck Pain: Discomfort or more intense forms of pain that are localized to the cervical region. This term generally refers to pain in the posterior or lateral regions of the neck. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrolithiasis: Kidney stones. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH]

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Nervousness: Excessive excitability and irritability, with mental and physical unrest. [EU] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]

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Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oestradiol: Growth hormone. [NIH] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligoelement: A chemical substance, minute amounts of which can be found in living organisms. [EU] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH]

Dictionary 623

Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oophorectomy: Surgery to remove one or both ovaries. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]

Orchiectomy: The surgical removal of one or both testicles. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU]

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Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteocytes: Mature osteoblasts that have become embedded in the bone matrix. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi. [NIH] Osteodystrophy: Defective bone formation. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium. [NIH]

Osteolytic: Causing the breakdown of bone. [NIH] Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]

Osteonectin: Non-collagenous, calcium-binding glycoprotein of developing bone. It links collagen to mineral in the bone matrix. In the synonym SPARC glycoprotein, the acronym stands for secreted protein, acidic and rich in cysteine. [NIH] Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH]

Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Osteosclerosis: An abnormal hardening or increased density of bone tissue. [NIH] Osteotomy: The surgical cutting of a bone. [EU]

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Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxazolidinones: Derivatives of oxazolidin-2-one. They represent an important class of synthetic antibiotic agents. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by

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disorganization of personality function. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parathyroidectomy: Excision of one or both of the parathyroid glands. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Patella: The flat, triangular bone situated at the anterior part of the knee. [NIH] Patent ductus arteriosus: Abnormal persistence of the opening in the arterial duct that connects the pulmonary artery to the descending aorta; this opening normally closes within 24 hours of birth. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic fracture: A broken bone caused by disease, often by the spread of cancer to the bone. [NIH] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of

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tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: regimen. [NIH]

Voluntary cooperation of the patient in following a prescribed

Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perennial: Lasting through the year of for several years. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: simplex. [NIH]

Inflammation of the periodontal membrane; also called periodontitis

Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH]

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Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Perspiration: Sweating; the functional secretion of sweat. [EU] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphonic Acids: Inorganic or organic derivatives of phosphonic acid with the general formula ROP(OH)2. This includes phosphonates and phosphonic acid esters. The tautomeric

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form of this compound (P(OH)3) = phosphorous acids. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylating: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Phylogeny: The relationships of groups of organisms as reflected by their evolutionary history. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

Physicochemical: Pertaining to physics and chemistry. [EU] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pityriasis: A name originally applied to a group of skin diseases characterized by the formation of fine, branny scales, but now used only with a modifier. [EU] Pityriasis Rubra Pilaris: A chronic skin disease characterized by small follicular papules, disseminated reddish-brown scaly patches, and often, palmoplantar hyperkeratosis. The papules are about the size of a pin and topped by a horny plug. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plant Oils: Oils derived from plants or plant products. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized

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regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Poliomyelitis: An acute viral disease, occurring sporadically and in epidemics, and characterized clinically by fever, sore throat, headache, and vomiting, often with stiffness of the neck and back. In the minor illness these may be the only symptoms. The major illness, which may or may not be preceded by the minor illness, is characterized by involvement of the central nervous system, stiff neck, pleocytosis in the spinal fluid, and perhaps paralysis. There may be subsequent atrophy of groups of muscles, ending in contraction and permanent deformity. The major illness is called acute anterior p., infantile paralysis and Heine-Medin disease. The disease is now largely controlled by vaccines. [EU] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled

Dictionary 631

cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polymyalgia Rheumatica: A syndrome in the elderly characterized by proximal joint and muscle pain, high erythrocyte sedimentation rate, and a self-limiting course. Pain is usually accompanied by evidence of an inflammatory reaction. Women are affected twice as commonly as men and Caucasians more frequently than other groups. The condition is frequently associated with temporal arteritis and some theories pose the possibility that the two diseases arise from a single etiology or even that they are the same entity. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Population Characteristics: Qualities and characterization of various types of populations within a social or geographic group, with emphasis on demography, health status, and socioeconomic factors. [NIH] Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postmenopause: The physiological period following the menopause, the permanent cessation of the menstrual life. Since in the United States the age of the menopause ranges between 48 and 55 years, generally conceived as middle age, the postmenopause often refers to women considerably older. [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in

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the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Private Sector: That distinct portion of the institutional, industrial, or economic structure of a country that is controlled or owned by non-governmental, private interests. [NIH]

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Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Progeny: The offspring produced in any generation. [NIH] Progeria: An abnormal congenital condition characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying, hair loss, hearing loss, cataracts, arthritis,osteoporosis, diabetes mellitus, atrophy of subcutaneous fat, skeletal hypoplasia, and accelerated atherosclerosis. Many affected individuals develop malignant tumors, especially sarcomas. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progestogen: A term applied to any substance possessing progestational activity. [EU] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids

634 Osteoporosis

having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Prosthesis Implantation: Surgical insertion of a prosthesis. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate

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donors. EC 2.7.10. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH]

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Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [NIH]

Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an

Dictionary 637

antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radius: The lateral bone of the forearm. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Ramus: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Rebound effect: The characteristic of a drug to produce reverse effects when either the effect of the drug has passed, or when the patient no longer responds to the drug. [EU] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH]

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Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal cell carcinoma: A type of kidney cancer. [NIH] Renal Osteodystrophy: Decalcification of bone due to hyperparathyroidism secondary to chronic kidney disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Reproductive History: An important aggregate factor in epidemiological studies of women's health. The concept usually includes the number and timing of pregnancies and their outcomes, the incidence of breast feeding, and may include age of menarche and menopause, regularity of menstruation, fertility, gynecological or obstetric problems, or contraceptive usage. [NIH]

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Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH]

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Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid

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or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Saturate: Means fatty acids without double bond. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scoliosis: A lateral curvature of the spine. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the

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elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serologic Tests: Diagnostic procedures involving immunoglobulin reactions. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The

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primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: female or male. [NIH]

The biological characteristics which distinguish human beings as

Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Problems: Situations affecting a significant number of people, that are believed to be

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sources of difficulty or threaten the stability of the community, and that require programs of amelioration. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Socioeconomic Factors: Social and economic factors that characterize the individual or group within the social structure. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soy Proteins: Proteins which are present in or isolated from soybeans. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of

Dictionary 645

a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Splint: A rigid appliance used for the immobilization of a part or for the correction of deformity. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Spontaneous Fractures: Fracture in the course of a normal movement of a bone weakened by disease. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Squamous: Scaly, or platelike. [EU] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to

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induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomachic: Medicine that acts like a tonic on the stomach. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH]

Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Strontium: An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU]

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Subtrochanteric: Below a trochanter. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synchrotron: An accelerator in which the particles are guided by an increasing magnetic field while they are accelerated several times in an approximately circular path by electric fields produced by a high-frequency generator. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachyphylaxis: 1. Rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. 2. Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. [EU] Talc: A native magnesium silicate. [NIH] Talin: A 235-kDa cytoplasmic protein that is also found in platelets. It has been localized to regions of cell-substrate adhesion. It binds to integrins, vinculin, and actins and appears to participate in generating a transmembrane connection between the extracellular matrix and the cytoskeleton. [NIH] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the tarsus. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH]

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Tarsal Bones: The seven bones which form the tarsus - namely, calcaneus, talus, cuboid, navicular, and first, second and third cuneiforms. The tarsus is a skeletal part of the foot. [NIH]

Tarsus: The region of the articulation between the foot and the leg. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratogenicity: The power to cause abnormal development. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermography: Measurement of the regional temperature of the body or an organ by infrared sensing devices, based on self-emanating infrared radiation. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH]

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Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotoxicosis: The clinical syndrome that reflects the response of the peripheral tissues to an excess of thyroid hormone. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tibia: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the fibula laterally, the talus distally, and the femur proximally. [NIH] Tibiae: The long bone on the medial and pre-axial border of the leg. [NIH]

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Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH]

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Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triad: Trivalent. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH]

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Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ulna: The long and medial bone of the forearm. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder.

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[NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urolithiasis: Stones in the urinary system. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetarianism: Dietary practice of consuming only vegetables, grains, and nuts. [NIH]

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Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinculin: A cytoskeletal protein associated with cell-cell and cell-matrix interactions. The amino acid sequence of human vinculin has been determined. The protein consists of 1066 amino acid residues and its gene has been assigned to chromosome 10. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Weight Lifting: A sport in which weights are lifted competitively or as an exercise. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH]

Dictionary 655

White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoledronate: A drug that belongs to the family of drugs called bisphosphonates. It is used to prevent bone fractures and reduce bone pain in people who have cancer that has spread to the bone. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

657

INDEX 3 3-dimensional, 63, 561, 634 A Abdomen, 561, 572, 574, 608, 612, 625, 627, 639, 645, 646, 649 Abdominal, 11, 409, 546, 561, 562, 610, 614, 625, 632, 639, 652 Abdominal Pain, 11, 546, 561, 614, 652 Ablation, 336, 561, 566 Abortion, 561, 604, 622 Acantholysis, 561, 627 Acceptor, 561, 612, 625 Acclimatization, 26, 561 Acetylcholine, 561, 621 Acidity, 561, 628 Acitretin, 166, 561 Acne, 561, 585 Acoustic, 120, 316, 361, 369, 383, 411, 561, 608 Actin, 129, 452, 561, 596, 619, 620 Actinin, 452, 561 Acute renal, 444, 561, 601 Adaptability, 561, 577, 578 Adaptation, 41, 43, 58, 214, 246, 334, 473, 561, 562 Adenine, 562, 636 Adenoma, 277, 562 Adenosine, 445, 562, 569, 575, 629 Adenosine Monophosphate, 445, 562 Adenovirus, 29, 46, 562 Adenylate Cyclase, 415, 445, 562 Adhesives, 562, 573, 614 Adipocytes, 562, 611 Adipose Tissue, 62, 399, 562, 612 Adjustment, 562 Adjuvant, 44, 110, 342, 343, 358, 562 Adjuvant Therapy, 343, 562 Adolescence, 11, 15, 29, 35, 45, 60, 68, 75, 142, 143, 245, 287, 504, 518, 538, 562, 627 Adrenal Cortex, 562, 563, 566, 584, 592, 603, 622, 633 Adrenal Glands, 546, 562 Adrenergic, 562, 568, 591 Adverse Effect, 7, 14, 61, 65, 88, 95, 124, 434, 436, 562, 628, 643 Aerobic, 79, 562, 563, 625 Aerobic Exercise, 79, 563 Afferent, 563, 611

Affinity, 107, 415, 461, 563, 612, 644 Agar, 563, 630 Age Groups, 27, 33, 200, 563 Age of Onset, 563, 652 Aged, 80 and Over, 563 Ageing, 191, 225, 298, 359, 361, 411, 462, 468, 563 Agenesis, 563, 599 Agonist, 59, 64, 116, 126, 300, 414, 415, 419, 448, 563, 580, 592, 637, 647 Airways, 278, 563 Aldosterone, 545, 563 Alendronate Sodium, 8, 11, 351, 563 Alertness, 563, 574 Algorithms, 80, 109, 113, 564, 572 Alimentary, 16, 237, 281, 564, 591, 626 Alkaline, 8, 11, 13, 32, 43, 50, 61, 75, 86, 98, 266, 301, 558, 564, 565, 575, 646, 648 Alkaline Phosphatase, 8, 11, 13, 32, 43, 50, 61, 75, 86, 266, 301, 564 Alkaloid, 564, 618, 626 Alleles, 78, 564, 602, 611 Allergen, 564, 586 Allogeneic, 564, 601 Allylamine, 564 Alpha Particles, 564, 636 Alternative medicine, 502, 564 Aluminum, 20, 304, 536, 564 Alveolar Bone Loss, 21, 22, 23, 24, 93, 352, 374, 375, 447, 448, 564 Alveolar Process, 564, 639 Ambulatory Care, 243, 564 Amenorrhea, 14, 158, 184, 324, 360, 392, 418, 419, 446, 482, 504, 564, 566, 631 Amine, 564, 602 Amino Acid Sequence, 414, 415, 445, 456, 565, 567, 596, 633, 654 Amino Alcohols, 372, 565 Amino-terminal, 415, 565, 633 Ammonia, 564, 565, 598, 652 Amplification, 386, 565 Ampulla, 565, 579 Anabolic Steroids, 9, 205, 488, 565 Anaesthesia, 565, 606 Anal, 74, 565, 591, 613, 619 Analgesic, 14, 164, 565, 605, 610, 618, 623 Analog, 28, 55, 381, 392, 418, 428, 429, 430, 440, 457, 565

658 Osteoporosis

Analogous, 105, 565, 630, 651 Analysis of Variance, 120, 565 Analytes, 526, 565 Anaphylatoxins, 565, 582 Anaphylaxis, 565, 610 Anatomical, 112, 301, 485, 565, 579, 606, 641 Androgen suppression, 256, 268, 318, 344, 565 Androgenic, 402, 459, 566 Androgens, 33, 55, 148, 222, 281, 376, 396, 437, 440, 449, 458, 486, 508, 562, 566, 568, 584 Androstenedione, 326, 396, 566 Anemia, 523, 547, 566, 571, 595, 601, 619, 624, 628, 648 Anesthesia, 143, 566, 590 Anesthetics, 566, 570, 592 Angina, 566, 621 Angiogenesis, 99, 138, 371, 566, 615 Angioplasty, 566 Angulation, 80, 566 Animal model, 8, 26, 32, 33, 52, 84, 88, 112, 114, 131, 137, 143, 145, 164, 426, 566 Anions, 395, 566, 609 Anisotropy, 268, 566 Anode, 566 Anomalies, 566, 599, 648 Anorexia, 81, 132, 148, 233, 236, 299, 324, 360, 392, 418, 419, 446, 528, 566, 624 Anorexia Nervosa, 81, 132, 148, 233, 236, 299, 324, 360, 392, 418, 446, 528, 566 Anovulation, 58, 567, 631 Antagonism, 567, 575 Anthropometry, 67, 567 Antibacterial, 365, 366, 438, 439, 567, 644 Antibiotic, 365, 366, 439, 567, 617, 625, 644, 648 Antibodies, 95, 135, 174, 407, 458, 567, 570, 600, 603, 605, 614, 630 Anticoagulant, 132, 135, 567, 634 Anticonvulsant, 4, 567, 628 Antidepressant, 97, 487, 567 Antigen, 130, 142, 427, 563, 565, 567, 582, 597, 602, 604, 606, 607, 615 Antigen-Antibody Complex, 567, 582 Anti-infective, 567, 609 Anti-Inflammatory Agents, 567, 584 Antimetabolite, 567, 616, 640 Antimicrobial, 93, 365, 366, 567, 588 Antineoplastic, 567, 584, 597, 616 Antioxidant, 61, 567, 569, 625

Antipruritic, 567, 579 Antipyretic, 567, 610 Antirheumatic Agents, 4, 568 Antiviral, 568, 608, 640 Anuria, 568, 610 Anus, 565, 568, 569, 574, 581, 637 Anxiety, 247, 568, 625 Aorta, 92, 568, 589, 626, 654 Aphakia, 568, 639 Apolipoproteins, 568, 612 Apoptosis, 79, 101, 114, 115, 116, 130, 140, 407, 504, 568 Approximate, 451, 568 Aqueous, 568, 571, 585, 611 Arachidonate 15-Lipoxygenase, 568, 612 Arachidonate Lipoxygenases, 568, 612 Arachidonic Acid, 27, 445, 454, 568, 611, 612, 633 Arginine, 434, 565, 568, 621 Aromatase, 55, 144, 397, 568 Aromatic, 372, 568, 628 Arrestins, 116, 568 Arterial, 90, 96, 141, 422, 423, 434, 564, 569, 579, 604, 621, 626, 634, 647 Arteries, 89, 91, 568, 569, 572, 576, 580, 584, 613, 616, 619, 636, 649 Arterioles, 569, 572, 576 Arteriolosclerosis, 569 Arteriosclerosis, 371, 569 Arteriosus, 445, 569, 635 Arteritis, 15, 569, 631 Artery, 48, 85, 90, 252, 566, 569, 576, 584, 587, 590, 626, 636 Arthralgia, 359, 569 Arthropathy, 167, 569 Arthroplasty, 43, 569 Articular, 569, 624 Artifacts, 28, 569 Ascorbic Acid, 569, 604 Aseptic, 569, 623, 646 Assay, 54, 66, 146, 201, 374, 402, 569 Asymptomatic, 4, 13, 342, 392, 488, 569, 571 Ataxia, 522, 569, 648 ATP, 121, 562, 569, 588, 597, 629, 634, 635 Atresia, 114, 569 Atrophy, 81, 247, 393, 396, 404, 405, 436, 450, 451, 487, 522, 561, 570, 630, 633 Attenuation, 40, 80, 111, 113, 120, 381, 383, 411, 441, 570 Atypical, 167, 270, 570 Autacoids, 570, 606

Index 659

Autoantibodies, 91, 570 Autoantigens, 570 Autoimmune disease, 33, 279, 369, 371, 570, 619 Autoimmunity, 134, 570 Autologous, 62, 91, 570, 601 Autologous bone marrow transplantation, 570, 601 Autonomic, 487, 561, 570, 627 Avian, 452, 570 Axilla, 570, 574 B Back Injuries, 546, 570 Back Pain, 19, 276, 282, 324, 378, 427, 444, 546, 558, 570 Bacteria, 372, 375, 386, 439, 453, 567, 570, 571, 578, 586, 590, 591, 594, 601, 603, 608, 616, 617, 644, 645, 651, 653 Bacterial Infections, 548, 570, 578 Bacterial Physiology, 562, 570 Bactericidal, 570, 592 Bacteriophage, 570, 630, 651 Barbiturate, 536, 570 Basal Ganglia, 569, 570, 604 Basal Ganglia Diseases, 569, 570, 604 Base, 56, 57, 80, 97, 102, 137, 147, 297, 394, 562, 571, 586, 596, 610, 648 Basement Membrane, 571, 593 Basophils, 571, 577, 599, 611 Bed Rest, 360, 392, 418, 446, 571 Benign, 168, 562, 569, 571, 600, 620, 636 Benzene, 571, 609 Beta-Thalassemia, 317, 571 Bilateral, 168, 231, 282, 571, 626, 631 Bile, 326, 418, 488, 571, 579, 596, 603, 609, 612, 632, 646 Bile Acids, 571, 646 Bile Acids and Salts, 571 Bile duct, 571, 596, 632 Bile Pigments, 571, 609 Biliary, 488, 571, 575, 579 Binding Sites, 95, 571 Bioavailability, 52, 107, 338, 376, 486, 571 Bioavailable, 142, 168, 571 Bioengineering, 96, 466, 516, 572 Biological response modifier, 572, 608 Biological therapy, 572, 599 Biomarkers, 44, 77, 124, 138, 311, 454, 572 Biophysics, 144, 572 Biopsy, 14, 17, 50, 63, 105, 147, 172, 197, 381, 487, 558, 572, 627 Biopsy specimen, 381, 572

Biotechnology, 152, 155, 485, 502, 517, 521, 522, 523, 572 Bladder, 572, 582, 606, 619, 634, 638, 652, 653 Blind spot, 185, 572 Blister, 572, 627 Bloating, 572, 606, 614 Blood Cell Count, 572, 601, 628 Blood Coagulation, 446, 572, 575, 649 Blood Coagulation Factors, 572 Blood Glucose, 572, 601, 607 Blood pressure, 75, 349, 414, 422, 423, 488, 546, 572, 576, 604, 618, 631, 636, 644 Body Composition, 30, 34, 35, 67, 74, 76, 134, 142, 349, 399, 573 Body Fluids, 572, 573, 589, 644, 652 Body Mass Index, 18, 45, 106, 123, 235, 299, 488, 573, 625 Bolus, 281, 429, 430, 431, 573 Bolus infusion, 573 Bolus injection, 281, 429, 430, 431, 573 Bone Cements, 573, 631 Bone Development, 37, 101, 102, 143, 245, 573 Bone Marrow Cells, 64, 86, 145, 573, 615 Bone metastases, 259, 377, 443, 573, 580, 593 Bone Morphogenetic Proteins, 463, 573 Bone Regeneration, 466, 573 Bone scan, 13, 14, 19, 21, 174, 487, 574, 587, 641 Bone Transplantation, 21, 574 Bony Callus, 573, 574, 595 Boron, 304, 305, 394, 574 Boron Compounds, 394, 574 Boron Neutron Capture Therapy, 574 Bowel, 16, 17, 295, 488, 565, 574, 587, 607, 608, 646, 652 Bowel Movement, 574, 587, 646 Brace, 409, 574 Brachial, 192, 574 Brachial Plexus, 192, 574 Brachytherapy, 574, 608, 609, 636, 655 Bradykinin, 574, 621 Branch, 299, 372, 555, 574, 596, 613, 626, 635, 644, 648, 650 Broadband, 40, 111, 574 Buccal, 97, 374, 375, 574, 604, 613 C Cadaver, 80, 574 Caffeine, 152, 327, 350, 504, 508, 532, 574, 636

660 Osteoporosis

Calcaneus, 29, 40, 149, 161, 182, 187, 201, 281, 575, 648 Calcifediol, 575 Calcification, 48, 62, 77, 85, 89, 90, 92, 96, 132, 141, 149, 252, 288, 333, 569, 575, 587 Calcineurin, 46, 575 Calcitriol, 9, 123, 147, 175, 197, 346, 446, 505, 533, 575 Calcium Carbonate, 13, 44, 145, 389, 437, 505, 573, 575 Calcium Channels, 575, 626 Calcium Citrate Malate, 436, 575 Calcium Metabolism Disorders, 398, 575 Calculi, 575, 599 Calmodulin, 46, 59, 100, 575, 576 Caloric intake, 58, 576 Capillary, 138, 574, 576, 612, 640, 654 Carbohydrate, 576, 584, 598, 631 Carbon Dioxide, 576, 629, 639 Carcinogen, 576, 592 Carcinogenic, 571, 576, 607, 633, 646 Carcinogenicity, 440, 576 Carcinoma, 189, 267, 301, 312, 394, 395, 402, 427, 456, 486, 576, 585 Cardiac, 122, 252, 327, 346, 371, 414, 564, 574, 576, 589, 592, 593, 619, 646 Cardiopulmonary, 75, 576 Cardiorespiratory, 518, 563, 576 Cardiovascular System, 434, 576 Carnitine, 366, 399, 576 Carotene, 417, 576, 639 Carotenoids, 89, 576 Carotid Arteries, 77, 576 Case report, 167, 216, 235, 282, 576, 577, 580 Case series, 577, 580 Case-Control Studies, 67, 96, 577, 591 Castration, 393, 450, 577 Cataract, 259, 269, 568, 577, 639 Catecholamine, 577, 628 Catheterization, 566, 577 Cations, 577, 609 Caudal, 577, 587, 604, 631 Causal, 57, 89, 116, 119, 177, 577, 591 Cause of Death, 77, 106, 369, 371, 384, 577 Celiac Disease, 16, 47, 174, 246, 263, 279, 324, 577 Cell Adhesion, 452, 577, 607 Cell Death, 79, 100, 407, 568, 577, 597 Cell Degranulation, 445, 577 Cell Differentiation, 61, 62, 144, 577, 643

Cell Division, 522, 570, 577, 578, 599, 617, 630 Cell membrane, 46, 575, 577, 586, 593, 609, 617, 628 Cell proliferation, 61, 101, 130, 451, 569, 578, 608, 643 Cell Respiration, 578, 625, 639 Cell Survival, 578, 599, 601 Cell Transplantation, 578, 601 Cellulose, 578, 630 Centchroman, 388, 402, 403, 578 Central Nervous System, 561, 571, 574, 575, 578, 598, 600, 611, 618, 619, 623, 630, 642 Centrifugation, 578, 601 Cerebellar, 247, 569, 578, 638, 651 Cerebellum, 578, 638 Cerebral, 118, 204, 569, 570, 578, 583, 592, 593, 601, 626, 649 Cerebral Cortex, 569, 578, 593 Cerebral Palsy, 118, 578 Cerebrovascular, 571, 576, 578, 648 Cerebrum, 578, 652 Cervical, 519, 574, 578, 601, 620 Cervix, 561, 578 Chaperonins, 578, 618 Character, 92, 578, 585, 598 Chemotactic Factors, 578, 582 Chemotaxis, 32, 579 Chemotherapy, 44, 110, 123, 339, 340, 342, 360, 392, 418, 419, 446, 462, 562, 579 Chin, 249, 283, 301, 313, 322, 579, 616 Cholecalciferol, 304, 327, 417, 579 Cholelithiasis, 459, 579 Cholestasis, 489, 579 Cholesterol Esters, 579, 612 Cholestyramine, 536, 579 Chondrocytes, 579, 594 Chondrogenesis, 88, 579 Chondroitin sulfate, 305, 579 Chromaffin System, 579, 590 Chromatin, 95, 568, 579, 591, 621 Chromosomal, 74, 76, 77, 86, 565, 579 Chromosome, 54, 90, 108, 458, 579, 600, 611, 654 Chronic Disease, 87, 132, 141, 441, 518, 519, 531, 536, 579, 581 Chronic renal, 20, 132, 579, 631 Chronotropic, 414, 579 Chylomicrons, 579, 612 Ciliary, 569, 579, 580, 653 Ciliary Arteries, 569, 580

Index 661

Ciliary Body, 569, 580, 653 Circulatory system, 580, 590 Cirrhosis, 104, 323, 324, 334, 488, 580, 631, 632 CIS, 51, 66, 134, 456, 580, 639 Clear cell carcinoma, 580, 586 Climacteric, 203, 219, 321, 438, 462, 580 Clinical Medicine, 122, 126, 214, 251, 298, 382, 580, 632 Clinical study, 148, 580, 583 Clinical trial, 6, 9, 26, 33, 51, 80, 88, 93, 104, 118, 121, 125, 133, 134, 135, 139, 156, 165, 211, 260, 320, 335, 340, 344, 354, 359, 517, 580, 583, 585, 588, 618, 635, 637 Clodronate, 197, 376, 580 Clomiphene, 360, 580 Clone, 62, 580 Cloning, 74, 95, 390, 572, 580 Coagulation, 49, 572, 580, 601, 649 Codon, 258, 580, 597 Coenzyme, 213, 569, 581 Cofactor, 581, 634, 649 Cognition, 72, 126, 141, 581 Cohort Studies, 119, 131, 132, 581, 591 Colitis, 17, 232, 581 Collagen disease, 581, 603 Collagenases, 93, 581 Collapse, 186, 389, 426, 444, 565, 574, 581 Colloidal, 581, 589 Colon, 35, 49, 52, 148, 263, 522, 581, 607, 610, 652 Colorectal, 49, 148, 581 Colorectal Cancer, 49, 148, 581 Combination Therapy, 52, 104, 109, 267, 364, 581, 592 Combinatorial, 107, 581 Comorbidity, 119, 581 Complement, 34, 60, 86, 140, 149, 535, 565, 582, 597, 607, 614 Complementary and alternative medicine, 309, 310, 332, 582 Complementary medicine, 310, 582 Compliance, 69, 81, 124, 582 Computational Biology, 517, 521, 582 Computer Simulation, 108, 582 Computerized tomography, 582 Conception, 561, 583, 594, 646 Concomitant, 24, 282, 302, 372, 381, 382, 583 Cone, 568, 583, 629 Confounding, 134, 490, 583

Congestion, 583, 592 Conjunctiva, 580, 583, 607 Connective Tissue Diseases, 198, 583 Consciousness, 438, 565, 583, 586, 588, 635 Constriction, 235, 583, 609 Consumption, 4, 29, 34, 79, 129, 131, 295, 504, 530, 538, 539, 559, 583, 622, 625 Continuum, 453, 583 Contraception, 396, 493, 583 Contraindications, ii, 10, 583 Control group, 15, 30, 34, 45, 47, 68, 119, 583, 637 Controlled clinical trial, 49, 60, 118, 124, 125, 148, 185, 276, 583 Controlled study, 143, 274, 281, 583 Convulsions, 567, 570, 583 Coordination, 139, 538, 578, 583, 619 Cornea, 583, 584, 598, 641, 653 Corneal Diseases, 299, 583 Corneal Ulcer, 439, 584 Corneum, 584, 591 Coronary, 35, 49, 77, 85, 91, 148, 252, 265, 309, 371, 576, 584, 616, 619, 621 Coronary heart disease, 35, 49, 148, 265, 309, 371, 576, 584 Coronary Thrombosis, 584, 616, 619 Corpus, 584, 633, 649, 654 Corpus Luteum, 584, 633 Cortex, 5, 546, 584, 638 Cortisol, 272, 584 Cortisone, 336, 584, 587, 632 Cowpox, 584, 653 Cowpox Virus, 584, 653 Cranial, 420, 578, 584, 600, 623, 627 Creatinine, 418, 584, 610 Criterion, 105, 143, 187, 584 Cross-Sectional Studies, 35, 584, 591 Cultured cells, 427, 585 Curative, 585, 640, 648 Cutaneous, 272, 585, 613, 653 Cyclic, 126, 217, 284, 336, 372, 413, 420, 445, 562, 574, 576, 585, 599, 621, 628, 634 Cyclosporine, 363, 536, 585 Cyproterone, 223, 393, 450, 585 Cyproterone Acetate, 393, 450, 585 Cytochrome, 568, 585 Cytokine, 66, 82, 115, 128, 130, 132, 133, 145, 374, 585 Cytoplasm, 85, 568, 571, 577, 585, 591, 599, 621, 640 Cytoskeleton, 585, 607, 647 Cytotoxic, 585, 605, 636, 643

662 Osteoporosis

D Dairy Products, 57, 299, 312, 585 Data Collection, 118, 125, 585, 595 Decision Making, 9, 68, 249, 585 Degenerative, 48, 213, 215, 372, 374, 391, 416, 462, 536, 585, 602, 624, 639, 640 Dehydration, 546, 586 Dehydroepiandrosterone, 283, 327, 328, 396, 586 Deletion, 51, 568, 586 Delivery of Health Care, 586, 600 Dementia, 132, 246, 278, 420, 481, 586 Demography, 586, 631 Dendrites, 586, 621 Dendritic, 59, 586, 615 Dental Caries, 586, 595, 644 Dental Hygienists, 22, 23, 586 Dental implant, 466, 489, 586, 624 Dentists, 21, 53, 586 Depolarization, 586, 643 Deprivation, 94, 109, 171, 190, 237, 255, 256, 267, 299, 301, 340, 341, 457, 586 Dermis, 586, 651 DES, 237, 299, 565, 586 Desensitization, 116, 586 Deuterium, 587, 603 DEXA, 19, 26, 40, 44, 71, 78, 93, 97, 105, 112, 123, 135, 139, 148, 242, 286, 391, 441, 539, 587 Dexamethasone, 210, 272, 352, 587 Diabetes Insipidus, 546, 587 Diabetes Mellitus, 35, 132, 587, 598, 601, 633 Diagnostic procedure, 357, 502, 587, 642 Diaphoresis, 361, 587 Diarrhea, 47, 579, 587, 610, 614 Diastole, 587 Diastolic, 414, 422, 423, 587, 604 Diastolic blood pressure, 414, 587 Diencephalon, 587, 604, 649 Digestion, 564, 571, 574, 587, 606, 608, 612, 646, 653 Digestive system, 355, 587, 618 Digestive tract, 412, 587, 643 Digital rectal examination, 142, 587 Dihydrotachysterol, 399, 587 Dihydrotestosterone, 585, 587, 638 Dihydroxy, 397, 398, 408, 563, 587, 640 Dilatation, 561, 566, 587, 633, 653 Dilator, 587, 621 Dimethyl, 388, 403, 418, 587 Diphosphonates, 136, 372, 421, 587

Diploid, 587, 630 Discrete, 67, 71, 392, 415, 573, 588, 613 Disinfectant, 588, 592 Disposition, 244, 370, 588 Dissection, 110, 588 Dissociation, 234, 563, 588, 609 Dissociative Disorders, 588 Distal, 3, 40, 58, 63, 142, 173, 191, 219, 239, 249, 265, 285, 417, 446, 455, 588, 589, 635 Diuresis, 462, 574, 588 Dizziness, 361, 436, 461, 588 DNA Topoisomerase, 588, 597 Dominance, 213, 481, 588 Dorsal, 588, 631 Dose-dependent, 36, 79, 82, 271, 588 Double-blind, 11, 93, 123, 125, 142, 148, 267, 281, 310, 505, 588 Double-blinded, 148, 588 Doxycycline, 83, 93, 439, 588 Drive, ii, vi, 20, 23, 74, 121, 293, 445, 449, 466, 489, 503, 505, 588, 611 Drug Interactions, 10, 510, 589 Duct, 565, 577, 589, 626, 640, 645 Ductus Arteriosus, 444, 445, 589 Duodenum, 571, 589, 646 Dyes, 571, 589, 621 Dyspareunia, 589, 592 Dysphoric, 165, 589 Dysplasia, 247, 319, 521, 523, 589 Dyspnea, 390, 589 Dystrophy, 118, 299, 487, 521, 522, 589 E Eating Disorders, 8, 19, 148, 236, 324, 482, 589 Ectopic, 85, 96, 102, 587, 589 Edema, 487, 589, 620 Effector, 561, 582, 589, 628 Elastic, 361, 383, 410, 411, 447, 589, 598, 644 Elasticity, 387, 388, 392, 411, 569, 589 Elastin, 581, 583, 589, 593 Elective, 265, 589 Electric Conductivity, 566, 589 Electrocoagulation, 580, 589 Electrode, 412, 566, 589 Electrolysis, 566, 577, 589 Electrolyte, 422, 423, 563, 584, 589, 610, 617, 631, 644 Electromagnetic Fields, 412, 413, 589 Electrophoresis, 558, 589 Elementary Particles, 590, 621, 635 Embolus, 590, 606

Index 663

Embryo, 561, 573, 577, 590, 597, 606, 622, 624, 630 Emollient, 590, 598, 622 Empirical, 103, 590 Endarterectomy, 566, 590 Endemic, 147, 590, 645 Endocrine Glands, 590, 626 Endocrine System, 151, 263, 590 Endocytosis, 52, 116, 590 Endogenous, 55, 59, 129, 137, 486, 570, 572, 590, 634, 651 Endometrial, 7, 95, 126, 246, 395, 402, 434, 486, 590 Endometriosis, 132, 300, 402, 419, 590 Endometrium, 402, 438, 590, 615 Endonucleases, 87, 590 Endopeptidases, 590, 634 Endothelial cell, 89, 139, 590, 594, 602, 649 Endothelium, 590, 591, 621, 630 Endothelium-derived, 591, 621 Endotoxic, 591, 612 Endotoxin, 591, 652 End-stage renal, 20, 579, 591, 631 Energy balance, 591, 611 Enhancer, 52, 418, 591 Enteral Nutrition, 65, 591 Environment Design, 144, 591 Environmental Exposure, 591, 623 Environmental Health, 76, 337, 516, 518, 591 Enzymatic, 565, 575, 576, 582, 586, 591, 602, 615, 639 Eosinophilic, 232, 591 Eosinophils, 577, 591, 599, 611 Epidemic, 80, 241, 469, 477, 479, 496, 591, 645 Epidemiologic Studies, 69, 142, 591 Epidemiological, 39, 70, 72, 96, 138, 173, 417, 466, 487, 591, 638 Epidermis, 427, 561, 572, 584, 586, 591, 603, 627 Epinephrine, 562, 591, 621, 652 Epiphyseal, 144, 592 Epithelial, 51, 456, 562, 580, 584, 592, 593 Epithelial Cells, 456, 592 Epithelium, 114, 427, 571, 590, 592, 609, 639 Equilenin, 377, 592 Erythema, 272, 592 Erythrocytes, 566, 572, 573, 592 Esophagus, 569, 587, 592, 628, 646 Essential Tremor, 522, 592

Estradiol, 55, 59, 60, 95, 120, 132, 143, 168, 198, 222, 297, 302, 328, 341, 374, 438, 509, 592 Estriol, 438, 592 Estrogen Receptor Modulators, 533, 592 Estrogen receptor positive, 123, 592 Estrone, 64, 438, 592 Ethanol, 65, 66, 120, 592, 594 Ether, 396, 593 Ethnic Groups, 67, 494, 593 Etidronate, 10, 14, 156, 170, 176, 181, 194, 195, 201, 296, 376, 409, 470, 489, 509, 593 Etretinate, 408, 561, 593 Eukaryotic Cells, 390, 593, 606, 623 Evoke, 593, 646 Excipient, 385, 428, 593 Excitability, 436, 461, 593, 620, 621 Excrete, 568, 593, 610 Exocytosis, 577, 593 Exogenous, 135, 590, 593, 634, 652 Expiration, 593, 639 Extensor, 30, 593, 635 External-beam radiation, 593, 609, 636, 655 Extracellular, 32, 41, 433, 446, 460, 575, 590, 593, 594, 607, 615, 617, 624, 644, 647, 648 Extracellular Matrix, 41, 433, 460, 593, 594, 607, 615, 624, 647 Extracellular Matrix Proteins, 593, 615 Extracellular Space, 593 Extraction, 375, 568, 593, 639 Extremity, 441, 487, 574, 594, 626, 641 Eye Infections, 562, 594 F Facial, 232, 259, 433, 460, 594, 626 Family Planning, 517, 594 Fat, 26, 49, 61, 74, 111, 148, 211, 349, 373, 494, 539, 562, 568, 571, 573, 576, 584, 587, 590, 594, 611, 612, 619, 625, 631, 633, 640, 644 Fatigue, 41, 44, 546, 594 Fatty acids, 314, 594, 598, 612, 633, 641 Femoral Fractures, 233, 379, 432, 594 Femoral Neck Fractures, 360, 392, 418, 594, 602 Fentanyl, 282, 594 Fermentation, 372, 450, 451, 594 Fetal Blood, 589, 594 Fetus, 561, 573, 594, 595, 629, 632, 653 Fibrin, 572, 594, 630, 649 Fibrinogen, 135, 594, 630, 649

664 Osteoporosis

Fibroblast Growth Factor, 463, 594 Fibroblasts, 147, 426, 594, 608 Fibrosis, 104, 118, 139, 154, 169, 251, 338, 394, 523, 564, 594, 641 Fibula, 594, 649 Filtration, 372, 444, 595, 610 Finite Element Analysis, 42, 595 Flexor, 593, 595 Fluorescence, 83, 595 Fluoridation, 289, 595 Fluorine, 595 Flush, 361, 595 Focus Groups, 12, 595 Foetoplacental, 595, 622 Folate, 89, 304, 306, 595 Fold, 13, 128, 363, 410, 433, 457, 460, 595 Folic Acid, 303, 304, 595 Follicles, 114, 595 Follow-Up Studies, 505, 595 Fosamax, 22, 174, 184, 294, 295, 338, 346, 353, 500, 508, 595 Fracture Fixation, 203, 217, 595 Fracture Healing, 42, 86, 88, 595 Free Radicals, 66, 567, 588, 595 Fructose, 595, 599 Fungi, 365, 366, 453, 594, 596, 608, 616, 617, 655 G Gait, 30, 50, 127, 596 Gallbladder, 561, 571, 587, 596 Gallstones, 571, 579, 596 Gas, 565, 576, 595, 596, 603, 606, 614, 621, 647, 653 Gastrectomy, 132, 596 Gastric, 129, 576, 596, 602 Gastrin, 596, 603 Gastrointestinal, 104, 161, 235, 316, 423, 424, 440, 504, 574, 591, 592, 596, 610, 611, 642, 646, 652 Gastrointestinal tract, 504, 592, 596, 610, 611, 642, 652 Gastrostomy, 591, 596 Gelsolin, 452, 596 Gene Expression, 43, 51, 61, 77, 85, 86, 101, 102, 130, 146, 523, 596 Gene Therapy, 28, 49, 91, 115, 160, 206, 242, 455, 456, 562, 596 General practitioner, 209, 596 Generator, 395, 426, 596, 647 Genetic Code, 596, 622 Genetic Engineering, 429, 430, 431, 572, 580, 597

Genetic Markers, 45, 103, 597 Genetic transcription, 597, 633, 651 Genistein, 59, 319, 366, 367, 597 Genital, 438, 580, 597, 609, 653 Genitourinary, 597, 653 Genotype, 45, 72, 78, 85, 87, 102, 108, 169, 210, 370, 597, 628 Germ Cells, 597, 625, 644, 648 Germ Layers, 573, 597 Gestation, 65, 597, 629 Gestational, 18, 597 Giant Cells, 597, 641 Gingivitis, 375, 597 Ginseng, 297, 314, 597 Glomerular, 444, 445, 597, 610 Glomeruli, 597 Glomerulonephritis, 444, 597 Glomerulus, 597 Glucose, 19, 121, 522, 569, 572, 578, 587, 598, 599, 601, 607, 641 Glucose Intolerance, 121, 587, 598 Glucose tolerance, 598 Glucose Tolerance Test, 598 Glucuronic Acid, 598, 602 Glutamic Acid, 595, 598, 621, 633 Glutamine, 415, 598 Gluten, 47, 577, 598 Glycerol, 598, 628 Glycerophospholipids, 598, 628 Glycine, 319, 564, 571, 598, 621, 642 Glycoprotein, 445, 594, 597, 598, 624, 649, 652 Glycosaminoglycan, 579, 598 Glycoside, 440, 598, 640 Glycosidic, 599, 622 Goats, 585, 599 Gonad, 599 Gonadal, 5, 15, 55, 64, 82, 120, 367, 377, 391, 400, 401, 402, 406, 418, 419, 443, 504, 599, 646 Gonadal Dysgenesis, 367, 391, 400, 401, 402, 406, 599 Gonadotropic, 536, 599 Gout, 394, 599 Governing Board, 599, 632 Grade, 34, 599 Grading, 200, 599 Graft, 289, 599, 603, 605 Grafting, 574, 599, 606 Graft-versus-host disease, 289, 599 Granulocytes, 599, 643, 655 Gravidity, 599, 626

Index 665

Gravis, 229, 599 Growth factors, 5, 6, 37, 61, 62, 95, 139, 388, 403, 406, 433, 463, 599 Guanylate Cyclase, 599, 621 H Habitual, 578, 600 Hair follicles, 586, 600, 654 Half-Life, 66, 561, 600 Haploid, 600, 630 Haplotypes, 78, 600 Haptens, 563, 600 Headache, 574, 600, 607, 630, 632 Health Behavior, 34, 56, 235, 318, 519, 600 Health Care Costs, 45, 104, 388, 600 Health Education, 38, 334, 348, 493, 600 Health Expenditures, 600 Health Policy, 68, 204, 291, 471, 600 Health Promotion, 50, 105, 119, 217, 476, 490, 531, 600 Health Resources, iv, 9, 26, 490, 600 Health Services, 146, 586, 600 Health Status, 39, 68, 600, 631 Heart attack, 576, 600 Heart Transplantation, 218, 600 Heat-Shock Proteins, 601, 618 Heat-Shock Proteins 90, 601, 618 Hematocrit, 129, 572, 601 Hematopoiesis, 462, 601 Hematopoietic Stem Cell Transplantation, 222, 601 Hemiparesis, 601 Hemiplegia, 252, 601 Hemodialysis, 575, 601, 610 Hemoglobin, 129, 566, 571, 572, 592, 601, 611, 648 Hemoglobinopathies, 596, 601 Hemoglobinuria, 522, 601 Hemolytic, 601, 648 Hemorrhage, 589, 600, 601, 646 Hemostasis, 49, 210, 462, 601, 607, 642 Heparin, 4, 210, 223, 248, 329, 463, 536, 602 Heparin-binding, 463, 602 Hepatic, 161, 162, 433, 460, 598, 602 Hepatitis, 104, 433, 460, 468, 602 Hepatocyte, 210, 579, 602 Hereditary, 48, 102, 150, 583, 599, 602, 639, 648 Heredity, 8, 379, 596, 597, 602 Heterodimer, 573, 602 Heterogeneity, 39, 99, 102, 134, 563, 602 Heterotrophic, 596, 602 Heterozygotes, 588, 602

Hirsutism, 585, 602 Histamine, 329, 565, 602, 610 Histidine, 415, 602 Histology, 60, 94, 99, 112, 115, 602 Homeostasis, 6, 20, 32, 76, 94, 124, 128, 137, 145, 398, 409, 458, 573, 602 Homodimer, 602, 651 Homogeneous, 77, 86, 441, 569, 583, 602 Homologous, 564, 596, 602, 647 Hormonal therapy, 390, 402, 602 Hormone therapy, 219, 341, 562, 603 Horny layer, 591, 603 Host, 91, 93, 97, 104, 136, 140, 378, 466, 570, 603, 605, 611, 653, 654 Human growth hormone, 195, 284, 603 Humoral, 117, 453, 603 Humour, 603 Hybrid, 84, 85, 128, 580, 603 Hybridization, 43, 603 Hybridomas, 603, 608 Hydrocortisone, 545, 603 Hydrogel, 52, 603 Hydrogen, 441, 462, 561, 564, 571, 576, 587, 593, 603, 612, 618, 621, 622, 625, 628, 635 Hydrolysis, 121, 445, 590, 603, 612, 628, 635 Hydrophilic, 360, 603 Hydrophobic, 129, 598, 603, 612 Hydroxylation, 575, 603 Hydroxylysine, 581, 604 Hydroxyproline, 50, 394, 565, 581, 604 Hyperbilirubinemia, 604, 609 Hypercalciuria, 5, 7, 9, 147, 392, 604 Hyperkeratosis, 604, 629 Hyperlipidemia, 48, 90, 96, 362, 468, 604 Hyperplasia, 402, 434, 546, 604 Hypersensitivity, 487, 564, 565, 586, 604, 611, 640 Hypertension, 35, 75, 171, 208, 267, 422, 423, 482, 483, 546, 569, 576, 600, 604, 631 Hyperthyroidism, 4, 217, 359, 557, 604 Hypertrophy, 394, 604 Hyperuricemia, 599, 604 Hypnotic, 570, 604 Hypogonadism, 3, 4, 16, 17, 20, 55, 65, 116, 132, 213, 337, 359, 396, 604 Hypokinesia, 604, 626 Hypoplasia, 604, 633 Hypotension, 546, 583, 604 Hypothalamic, 5, 213, 604

666 Osteoporosis

Hypothalamus, 429, 430, 431, 587, 604, 629, 649 Hypothyroidism, 4, 546, 604 Hypovitaminosis, 205, 605 Hypoxemia, 394, 605 Hypoxia, 605, 648 Hysterectomy, 367, 377, 391, 400, 401, 402, 406, 605 I Ibuprofen, 605, 610 Id, 116, 303, 323, 432, 435, 526, 530, 531, 540, 541, 542, 545, 554, 556, 605 Ileal, 488, 605 Ileum, 605 Immune function, 605, 651 Immune response, 562, 567, 570, 584, 600, 605, 614, 646, 653, 654 Immune system, 459, 494, 570, 572, 605, 611, 614, 619, 653, 655 Immunization, 605, 632, 647 Immunodeficiency, 162, 522, 605 Immunogenic, 605, 612 Immunoglobulin, 567, 605, 618, 642 Immunohistochemistry, 40, 51, 605 Immunology, 48, 174, 266, 562, 563, 605 Immunophilin, 575, 605 Immunosuppressant, 605, 616 Immunosuppressive, 349, 363, 575, 598, 605 Immunosuppressive Agents, 349, 363, 605 Immunosuppressive therapy, 363, 605 Immunotherapy, 572, 586, 605 Impairment, 4, 54, 269, 433, 569, 579, 594, 606, 616 Implant radiation, 606, 608, 609, 636, 655 Implantation, 583, 606, 622 Impotence, 393, 450, 606, 626 In situ, 27, 43, 51, 123, 606 In Situ Hybridization, 27, 43, 51, 606 Incision, 606, 609 Incisor, 51, 606 Incontinence, 396, 490, 606 Indicative, 144, 373, 379, 381, 467, 606, 626, 653 Indigestion, 606, 610 Indomethacin, 366, 606 Induction, 85, 116, 129, 466, 489, 566, 606 Inertia, 143, 606 Infancy, 606, 640 Infant, Newborn, 563, 606 Infarction, 371, 606 Infertility, 132, 279, 494, 606

Infiltration, 597, 607 Inflammatory bowel disease, 16, 17, 132, 176, 202, 237, 238, 244, 263, 363, 394, 444, 488, 607 Influenza, 89, 607 Infusion, 55, 65, 82, 133, 137, 252, 573, 607, 651 Ingestion, 10, 300, 314, 595, 598, 604, 607, 630, 648 Initiation, 34, 69, 216, 415, 504, 607, 633, 651 Initiator, 32, 607 Innervation, 574, 607, 628, 641, 650 Inorganic, 389, 394, 574, 607, 618, 628, 644 Inotropic, 414, 607 Inpatients, 251, 607 Insight, 72, 74, 150, 232, 241, 607 Insomnia, 141, 607, 632 Insulator, 607, 619 Insulin, 5, 19, 61, 71, 81, 95, 115, 266, 271, 310, 364, 384, 399, 433, 463, 598, 607, 652 Insulin-dependent diabetes mellitus, 607 Insulin-like, 61, 81, 95, 115, 271, 310, 364, 384, 399, 433, 463, 607 Integrins, 607, 647 Interferometry, 381, 608 Interferon, 104, 608 Interferon-alpha, 608 Interleukin-1, 217, 608 Interleukin-2, 608 Interleukin-6, 66, 132, 164, 218, 266, 374, 608 Interleukins, 605, 608 Intermittent, 32, 137, 194, 195, 197, 213, 217, 409, 420, 421, 608, 613 Internal radiation, 608, 609, 636, 655 Interstitial, 574, 593, 608, 609, 655 Intervertebral, 608, 613 Intervertebral Disk Displacement, 608, 613 Intestinal, 365, 366, 395, 396, 399, 437, 445, 489, 494, 575, 576, 577, 598, 608, 614 Intestinal Flora, 365, 366, 608 Intestinal Mucosa, 577, 608 Intestine, 414, 445, 539, 571, 574, 581, 608, 610 Intoxication, 608, 655 Intracellular, 28, 46, 102, 451, 456, 575, 606, 607, 608, 615, 621, 631, 634, 643 Intramuscular, 609, 626 Intravenous, 157, 218, 252, 267, 284, 344, 573, 607, 609, 626

Index 667

Intrinsic, 563, 571, 609 Invasive, 28, 41, 149, 373, 389, 426, 609, 614 Involuntary, 106, 570, 592, 609, 619, 638 Involution, 26, 334, 609 Iodine, 107, 609 Ionization, 609 Ionizing, 28, 388, 441, 564, 591, 609, 636 Ions, 36, 446, 561, 571, 575, 576, 579, 588, 589, 596, 603, 609 Iris, 394, 569, 580, 583, 609, 653 Irradiation, 382, 419, 489, 574, 609, 655 Ischemia, 570, 609 Isoflavones, 59, 330, 331, 609 Isotonic, 462, 609 J Jaundice, 488, 604, 609 Jejunostomy, 591, 610 K Kb, 76, 516, 610 Ketoprofen, 374, 375, 610 Ketotifen, 232, 610 Kidney Disease, 309, 337, 349, 352, 355, 494, 516, 523, 610, 638 Kidney Failure, 494, 591, 610 Kidney Failure, Acute, 610 Kidney Failure, Chronic, 610 Kidney stone, 108, 290, 412, 610, 620, 653 Kinetic, 45, 609, 610 L Labile, 582, 610 Lactation, 65, 217, 610, 622 Lactose Intolerance, 19, 538, 610 Large Intestine, 581, 587, 608, 610, 637, 643 Latent, 44, 610, 632 Least-Squares Analysis, 611, 638 Lens, 269, 568, 577, 611, 654 Leptin, 45, 258, 611 Lethargy, 604, 611 Leucine, 299, 611 Leukemia, 222, 342, 522, 548, 596, 611 Leukocytes, 571, 572, 573, 579, 591, 599, 606, 608, 611, 621, 652 Leukotrienes, 320, 454, 568, 611, 612 Libido, 396, 566, 611 Library Services, 554, 611 Life cycle, 596, 611 Life Expectancy, 32, 139, 361, 377, 449, 548, 611 Ligament, 611, 634, 645 Ligands, 107, 407, 607, 611 Likelihood Functions, 611, 638

Linear Models, 611, 638 Linkage, 73, 75, 76, 77, 78, 107, 132, 159, 222, 377, 379, 597, 611 Linkage Disequilibrium, 76, 379, 611 Lip, 427, 612 Lipid A, 59, 75, 90, 612 Lipid Peroxidation, 612, 625 Lipolysis, 445, 612 Lipophilic, 360, 612 Lipopolysaccharides, 612 Lipoprotein, 61, 76, 135, 612, 613 Lipoprotein Lipase, 61, 612 Lipoprotein(a), 135, 612 Lipoxygenase, 27, 90, 454, 568, 611, 612 Lipoxygenase Inhibitors, 454, 612 Litter, 79, 612 Liver scan, 612, 641 Liver Transplantation, 211, 245, 334, 337, 612 Lobe, 603, 612 Localization, 46, 78, 96, 441, 459, 605, 612 Localized, 33, 54, 78, 415, 452, 487, 586, 601, 602, 606, 613, 620, 629, 630, 641, 647, 652 Locomotion, 613, 630 Locomotor, 419, 613 Logistic Models, 613, 638 Longitudinal Studies, 21, 105, 118, 585, 613 Longitudinal study, 35, 38, 40, 58, 97, 141, 163, 184, 613 Long-Term Care, 16, 144, 205, 310, 613 Low Back Pain, 193, 307, 324, 483, 613 Low-density lipoprotein, 612, 613 Lumbago, 359, 391, 450, 462, 613 Lung Transplantation, 235, 299, 613 Lupus, 5, 12, 134, 210, 223, 503, 505, 528, 613, 647 Lymph, 110, 578, 580, 590, 591, 603, 613, 641 Lymph node, 110, 578, 613, 641 Lymphatic, 591, 606, 613, 616, 630, 644, 645, 649 Lymphatic system, 613, 644, 645, 649 Lymphocyte, 459, 567, 614, 615 Lymphoid, 567, 614 Lymphoma, 4, 223, 522, 614 Lysine, 294, 330, 604, 614, 633 Lytic, 614, 642 M Macrophage, 89, 100, 130, 403, 404, 452, 455, 608, 614

668 Osteoporosis

Magnetic Resonance Imaging, 172, 369, 441, 447, 614, 641 Major Histocompatibility Complex, 600, 614 Malabsorption, 9, 16, 47, 94, 400, 489, 522, 577, 614 Malabsorption syndrome, 94, 400, 614 Malformation, 269, 614 Malignancy, 10, 117, 377, 443, 559, 614 Malignant, 522, 567, 569, 614, 619, 620, 624, 633, 636 Malignant tumor, 614, 619, 624, 633 Malnutrition, 16, 17, 299, 488, 570, 614, 619 Mammary, 394, 438, 456, 612, 614, 637, 647 Mammogram, 575, 614, 617 Mandible, 24, 53, 314, 466, 489, 521, 564, 579, 614, 639 Manifest, 601, 614 Mass Screening, 120, 614 Mastocytosis, 234, 266, 614 Materials Testing, 99, 614 Matrix metalloproteinase, 93, 614 Meat, 373, 494, 615 Medial, 96, 569, 615, 623, 649, 650, 652 Mediate, 27, 32, 64, 85, 140, 150, 390, 445, 615, 618 Mediator, 41, 66, 82, 120, 133, 149, 210, 608, 615, 642 Medical castration, 65, 615 Medical Records, 615, 639 Medical Staff, 588, 615 Medicament, 366, 438, 615 MEDLINE, 517, 521, 523, 615 Medullary, 439, 615 Megakaryocytes, 573, 615 Melanin, 609, 615, 628, 652 Melanocytes, 615 Melanoma, 522, 574, 615 Membrane Lipids, 615, 628 Memory, 483, 566, 586, 615 Menarche, 143, 615, 638 Menstrual Cycle, 64, 126, 615, 622, 632, 633 Menstruation, 564, 615, 616, 622, 632, 638 Mental, iv, 26, 127, 165, 247, 335, 355, 516, 519, 520, 521, 524, 546, 578, 579, 581, 586, 588, 594, 604, 615, 616, 621, 632, 635, 641, 642, 652 Mental Disorders, 355, 604, 616, 632, 635 Mental Health, iv, 26, 165, 335, 355, 516, 519, 520, 616, 632, 635 Mental Processes, 588, 616, 635

Mental Retardation, 247, 524, 616 Mentors, 40, 50, 135, 616 Mesenchymal, 61, 62, 101, 102, 466, 616 Meta-Analysis, 156, 275, 301, 616 Metabolic disorder, 189, 405, 496, 547, 587, 599, 616 Metabolite, 27, 117, 123, 456, 457, 494, 561, 575, 587, 592, 616 Metaplasia, 96, 616 Metastasis, 271, 301, 340, 615, 616 Metastatic, 128, 616, 641 Methionine, 587, 616 Methotrexate, 536, 616 Methylprednisolone, 363, 616 Metrorrhagia, 394, 616 MI, 18, 41, 66, 91, 99, 106, 123, 138, 166, 283, 289, 300, 426, 454, 463, 559, 616 Microbe, 616, 650 Microbiology, 48, 562, 570, 617 Microcalcifications, 575, 617 Microgram, 9, 617 Microorganism, 581, 617, 654 Microscopy, 83, 571, 617 Microspheres, 302, 617 Microvilli, 395, 617 Migration, 282, 617 Milligram, 295, 617 Milliliter, 573, 617 Mineralization, 8, 48, 65, 77, 90, 96, 99, 111, 118, 138, 143, 197, 277, 458, 617, 624 Mineralocorticoids, 562, 584, 617 Minocycline, 439, 617 Mitogen-Activated Protein Kinase Kinases, 617 Mitogen-Activated Protein Kinases, 115, 617 Mitosis, 568, 617 Mobility, 276, 363, 367, 375, 400, 401, 406, 434, 487, 618 Mobilization, 106, 396, 618 Modeling, 108, 136, 185, 452, 455, 618 Modification, 15, 89, 396, 533, 565, 597, 618, 636 Modulator, 314, 343, 364, 618 Molecular Chaperones, 453, 578, 601, 618 Monitor, 16, 17, 50, 122, 137, 257, 287, 288, 373, 584, 618, 621 Monoclonal, 603, 609, 618, 636, 655 Monocyte, 89, 618 Mononuclear, 618, 652 Morphine, 618, 620, 623 Morphological, 137, 454, 563, 590, 615, 618

Index 669

Morphology, 43, 93, 139, 577, 618 Motility, 596, 606, 618, 642 Motion Sickness, 618, 620 Mucosa, 613, 618, 646 Mucositis, 618, 649 Mucus, 618, 652 Multicenter study, 11, 618 Multiple Myeloma, 4, 128, 132, 401, 406, 619 Multiple sclerosis, 167, 619 Multivariate Analysis, 164, 619 Muscle Contraction, 446, 619 Muscle Fibers, 619, 620 Muscle relaxant, 619, 628 Muscle Spindles, 619, 628 Muscular Atrophy, 522, 619 Muscular Dystrophies, 589, 619 Musculoskeletal Diseases, 98, 619 Musculoskeletal System, 619, 623 Myalgia, 472, 607, 619 Myelin, 619 Myeloma, 400, 547, 619 Myocardial infarction, 91, 394, 584, 616, 619 Myocardium, 616, 619 Myopathy, 81, 619 Myopia, 619, 638, 639 Myosin, 575, 619, 620 Myotonic Dystrophy, 522, 620 N Nadir, 11, 620 Narcosis, 620 Narcotic, 487, 594, 618, 620 Nasal Mucosa, 607, 620 Nasogastric, 591, 620 Nausea, 361, 606, 620, 632, 652 NCI, 1, 336, 339, 340, 341, 342, 344, 354, 515, 580, 620 Neck Pain, 546, 620 Neonatal, 394, 620 Neoplasia, 246, 522, 593, 620 Neoplasm, 620, 652 Neoplastic, 603, 614, 620 Nephrolithiasis, 108, 229, 230, 412, 620 Nephropathy, 610, 620 Nephrosis, 620 Nephrotic, 363, 620 Nephrotic Syndrome, 363, 620 Nerve Fibers, 574, 620, 650 Nervousness, 436, 461, 621 Neural, 563, 603, 621, 639 Neuromuscular, 109, 114, 561, 621

Neuronal, 59, 575, 620, 621 Neurons, 59, 586, 619, 620, 621, 647 Neurosecretory Systems, 590, 621 Neurotransmitter, 561, 562, 565, 574, 598, 602, 621, 643, 646 Neutralization, 130, 621 Neutrons, 564, 574, 609, 621, 636 Neutrophils, 548, 568, 577, 599, 611, 621 Nitric Oxide, 59, 124, 338, 434, 621 Nitrogen, 33, 564, 566, 593, 598, 610, 621, 652 Nitroglycerin, 124, 338, 621 Nuclear, 42, 66, 89, 95, 134, 174, 296, 301, 381, 441, 495, 570, 593, 621 Nuclei, 42, 441, 564, 596, 597, 614, 617, 621, 623, 635 Nucleic acid, 101, 377, 390, 448, 596, 603, 606, 621, 622, 636, 640 Nucleic Acid Hybridization, 603, 622 Nucleus, 85, 568, 570, 571, 579, 585, 587, 590, 591, 593, 608, 618, 621, 622, 635, 648 Nutritional Status, 140, 622 O Observational study, 49, 148, 622 Occult, 231, 264, 622 Ocular, 269, 622 Odds Ratio, 622, 638 Odour, 568, 622 Oestradiol, 211, 622 Oestrogen, 314, 320, 498, 622 Ointments, 396, 622 Oligoelement, 622 Oligomenorrhea, 622, 631 Oligosaccharides, 45, 380, 622 Oliguria, 610, 623 Oncogene, 522, 623 Oophorectomy, 132, 360, 392, 416, 418, 446, 623 Opacity, 577, 586, 623 Operon, 623, 633 Ophthalmic, 241, 509, 623 Opium, 618, 623, 626 Opsin, 623, 639, 640 Optic Chiasm, 604, 623 Optic Nerve, 572, 623, 639, 641 Oral Health, 22, 23, 518, 519, 623 Oral Hygiene, 375, 623 Oral Manifestations, 22, 23, 528, 623 Orchiectomy, 132, 313, 340, 623 Organ Culture, 27, 623 Organ Transplantation, 122, 363, 623 Organelles, 578, 585, 615, 623

670 Osteoporosis

Osseointegration, 466, 573, 624 Ossification, 102, 624, 640 Osteocytes, 99, 100, 101, 138, 407, 624 Osteodystrophy, 20, 102, 294, 624 Osteogenesis, 104, 128, 131, 153, 200, 275, 359, 387, 526, 539, 573, 579, 624 Osteogenic sarcoma, 624 Osteolysis, 128, 159, 236, 624 Osteolytic, 90, 129, 624 Osteomalacia, 13, 20, 140, 336, 377, 401, 406, 443, 453, 471, 473, 486, 487, 494, 575, 624 Osteonectin, 394, 624 Osteopetrosis, 43, 51, 128, 624 Osteosarcoma, 445, 446, 624 Osteosclerosis, 433, 460, 624 Osteotomy, 447, 448, 624 Outpatient, 50, 248, 625 Ovariectomy, 36, 58, 64, 79, 83, 124, 130, 133, 145, 154, 160, 206, 393, 459, 489, 625 Ovaries, 434, 489, 568, 615, 623, 625, 631, 643 Ovary, 58, 64, 114, 566, 584, 592, 599, 622, 625, 630, 646 Overdose, 143, 625 Overexpress, 37, 101, 625 Overweight, 75, 106, 221, 298, 302, 625 Ovulation, 567, 580, 625 Ovum, 584, 597, 611, 625, 633, 655 Oxazolidinones, 463, 625 Oxidation, 61, 86, 97, 454, 561, 567, 568, 585, 612, 625 Oxidative metabolism, 611, 625 Oxidative Stress, 59, 625 Oxygen Consumption, 625, 639 Oxygenation, 445, 454, 605, 625 P Palliative, 585, 622, 625, 648 Palsy, 118, 192, 625 Pamidronate, 104, 129, 157, 185, 218, 252, 284, 352, 376, 504, 509, 625 Pancreas, 561, 572, 587, 607, 625, 652 Pancreatic, 428, 429, 430, 522, 576, 625 Pancreatic cancer, 522, 625 Panic, 436, 461, 625 Papaverine, 385, 386, 623, 626 Paralysis, 334, 601, 626, 630 Parathyroid Glands, 446, 626, 640 Parathyroidectomy, 50, 137, 626 Parenteral, 52, 364, 626 Paresis, 601, 626 Parity, 65, 626

Parkinsonism, 132, 626 Parotid, 626, 641 Paroxysmal, 522, 626 Patch, 626, 651 Patella, 382, 626 Patent ductus arteriosus, 444, 445, 626 Pathologic, 26, 81, 409, 568, 572, 584, 604, 626, 635, 639, 645, 653 Pathologic fracture, 409, 626 Pathologic Processes, 568, 626 Pathologies, 115, 362, 627 Patient Compliance, 10, 52, 69, 106, 368, 627 Patient Education, 16, 188, 309, 533, 544, 552, 554, 559, 627 Pediatrics, 45, 97, 104, 117, 198, 238, 284, 527, 627 Pelvic, 590, 627, 634 Pelvis, 98, 384, 427, 488, 561, 613, 625, 627, 653 Pemphigus, 175, 561, 627 Perception, 34, 583, 627, 641 Percutaneous, 125, 231, 396, 627 Perennial, 627, 651 Perfusion, 605, 627, 650 Pericardium, 627, 647 Perimenopausal, 4, 126, 191, 295, 627 Periodontitis, 21, 23, 25, 93, 375, 447, 448, 597, 627 Peripheral blood, 135, 601, 608, 627 Peripheral Nervous System, 601, 621, 625, 627, 646 Peripheral Nervous System Diseases, 601, 627 Peripheral stem cells, 599, 627 Pernicious, 132, 628 Pernicious anemia, 132, 628 Peroneal Nerve, 628, 641 Perspiration, 587, 628 PH, 40, 185, 381, 388, 460, 573, 628 Pharmacists, 185, 199, 240, 628 Pharmacokinetic, 107, 157, 628 Pharmacologic, 6, 7, 8, 14, 28, 69, 127, 139, 146, 232, 244, 426, 566, 570, 600, 628, 650 Pharynx, 607, 628 Phenotype, 32, 37, 49, 50, 54, 61, 69, 73, 77, 78, 79, 101, 102, 130, 135, 144, 145, 628 Phenyl, 388, 403, 442, 628 Phenylalanine, 628, 652 Phenytoin, 536, 628 Phosphates, 98, 628 Phosphodiesterase, 46, 628

Index 671

Phospholipases, 628, 643 Phospholipids, 89, 92, 594, 612, 615, 628, 634 Phosphonic Acids, 587, 628 Phosphorous, 394, 398, 629 Phosphorus, 44, 58, 117, 176, 331, 380, 421, 437, 575, 626, 629 Phosphorylated, 95, 568, 581, 617, 629 Phosphorylating, 95, 629 Phosphorylation, 46, 95, 121, 617, 629, 634, 635 Photocoagulation, 580, 629 Photoreceptor, 629, 640 Phylogeny, 62, 629 Physical Examination, 13, 152, 533, 629 Physical Fitness, 111, 629 Physical Therapy, 11, 203, 629 Physicochemical, 136, 629 Physiologic, 9, 55, 70, 149, 458, 518, 563, 580, 600, 604, 609, 615, 616, 629, 633, 637, 639, 651 Physiology, 17, 82, 114, 115, 117, 119, 265, 301, 414, 428, 429, 430, 456, 590, 629 Pigments, 571, 576, 629, 639 Pilot study, 75, 117, 148, 208, 629 Pituitary Gland, 399, 428, 429, 430, 584, 594, 629 Pityriasis, 167, 629 Pityriasis Rubra Pilaris, 167, 629 Placenta, 568, 592, 594, 595, 629, 633 Plant Oils, 622, 629 Plants, 408, 454, 564, 576, 597, 598, 618, 629, 630, 631, 640, 650, 651 Plaque, 25, 92, 96, 566, 630 Plasma cells, 567, 619, 630 Plasmin, 630 Plasminogen, 135, 630 Plasminogen Activators, 630 Platelet Activation, 630, 643 Platelet Aggregation, 445, 565, 621, 630, 649 Platelets, 547, 577, 615, 621, 630, 642, 647, 649 Plexus, 574, 630, 641 Pneumonia, 583, 630 Poisoning, 608, 620, 630 Poliomyelitis, 132, 630 Pollen, 630, 636 Polycystic, 523, 546, 630, 631 Polycystic Ovary Syndrome, 546, 631 Polymerase, 631, 633 Polymorphic, 78, 85, 458, 579, 631

Polymorphism, 54, 76, 164, 167, 217, 219, 230, 257, 258, 272, 370, 379, 387, 499, 631 Polymyalgia Rheumatica, 15, 631 Polyposis, 581, 631 Polysaccharide, 372, 567, 578, 598, 631, 635 Polyunsaturated fat, 314, 320, 454, 631, 649 Population Characteristics, 46, 631 Porosity, 24, 63, 426, 631 Portal Hypertension, 488, 631 Portal Vein, 631 Posterior, 58, 565, 569, 570, 578, 588, 609, 620, 625, 631, 641 Postmenopause, 252, 459, 631 Postnatal, 37, 101, 247, 631, 645 Postsynaptic, 631, 643 Potassium, 306, 372, 422, 423, 431, 435, 563, 617, 631 Potentiates, 608, 632 Potentiation, 632, 643 Practicability, 632, 651 Practice Guidelines, 69, 152, 246, 310, 520, 540, 632 Precipitation, 412, 437, 632 Preclinical, 8, 91, 471, 499, 632 Predisposition, 74, 97, 368, 369, 370, 377, 379, 388, 418, 426, 449, 454, 632 Prednisolone, 616, 632 Prednisone, 336, 349, 352, 505, 632 Premenopausal, 4, 14, 110, 127, 154, 178, 335, 339, 340, 342, 390, 407, 498, 632 Premenstrual, 165, 300, 493, 632 Premenstrual Syndrome, 300, 493, 632 Prenatal, 101, 248, 590, 632 Prevalence, 17, 20, 22, 25, 39, 47, 60, 82, 108, 118, 133, 139, 161, 205, 211, 228, 229, 248, 249, 337, 369, 371, 375, 419, 622, 632 Primary Biliary Cirrhosis, 239, 400, 488, 632 Primary Prevention, 504, 632 Private Sector, 125, 146, 632 Probe, 95, 120, 137, 441, 633 Procollagen, 153, 427, 633 Progeny, 73, 633 Progeria, 547, 548, 633 Progesterone, 135, 148, 330, 331, 342, 402, 434, 456, 472, 485, 633, 646 Progestogen, 253, 300, 633 Progression, 12, 21, 25, 92, 96, 98, 109, 114, 139, 141, 234, 252, 368, 393, 450, 566, 633 Projection, 381, 623, 633, 638

672 Osteoporosis

Proline, 581, 604, 633 Promoter, 29, 37, 51, 66, 79, 85, 89, 95, 101, 130, 146, 150, 266, 390, 633 Promotor, 257, 633 Prone, 165, 312, 383, 411, 412, 633 Prophylaxis, 17, 44, 229, 240, 360, 371, 421, 586, 593, 633, 653 Proportional, 109, 114, 131, 370, 411, 633 Prospective study, 39, 109, 114, 131, 157, 198, 218, 220, 613, 633 Prostaglandin, 154, 218, 272, 274, 363, 410, 442, 444, 445, 447, 448, 456, 457, 633, 649 Prostaglandins A, 606, 633, 634 Prosthesis, 401, 406, 466, 634 Prosthesis Implantation, 401, 406, 634 Protease, 42, 62, 581, 634 Protease Inhibitors, 42, 634 Protein Binding, 634, 650 Protein C, 42, 57, 125, 374, 378, 444, 565, 568, 570, 580, 612, 624, 634, 652, 654 Protein Conformation, 565, 634 Protein Kinase C, 617, 634 Protein S, 57, 438, 439, 485, 523, 572, 596, 603, 624, 634, 640, 648 Protein-Serine-Threonine Kinases, 617, 634 Protein-Tyrosine Kinase, 597, 635 Proteinuria, 619, 620, 635 Proteoglycans, 299, 394, 571, 593, 635 Proteolytic, 573, 582, 594, 630, 635 Protocol, 27, 55, 98, 116, 125, 340, 342, 635 Protons, 441, 452, 564, 603, 609, 635, 636 Protozoa, 453, 617, 635 Proximal, 38, 50, 76, 80, 98, 120, 122, 142, 149, 157, 261, 314, 368, 378, 588, 631, 635 Psoriasis, 363, 394, 396, 494, 561, 593, 635 Psychiatric, 81, 616, 635 Psychiatry, 436, 461, 635, 646 Psychic, 580, 611, 616, 635, 642 Psychoactive, 635, 655 Psychology, 35, 118, 126, 268, 588, 635 Puberty, 45, 143, 273, 349, 376, 419, 449, 635 Public Policy, 471, 517, 635 Pulmonary, 120, 239, 253, 299, 394, 572, 583, 589, 591, 610, 611, 626, 635, 636, 654 Pulmonary Artery, 572, 589, 626, 635, 654 Pulmonary Edema, 610, 635 Pulmonary hypertension, 394, 636 Pulse, 65, 121, 383, 387, 618, 636 Purines, 636, 642 Pyrimidines, 636, 642

Q Quality of Life, 7, 33, 39, 44, 49, 72, 78, 110, 119, 148, 188, 220, 225, 235, 278, 386, 443, 636 Quercetin, 459, 636 R Race, 35, 39, 73, 92, 103, 376, 449, 485, 487, 533, 617, 636 Radiation therapy, 561, 562, 593, 608, 609, 636, 655 Radioactive, 574, 600, 603, 606, 608, 609, 612, 621, 636, 641, 655 Radiography, 453, 636 Radioisotope, 636, 650 Radiolabeled, 609, 636, 655 Radiological, 23, 40, 200, 212, 489, 496, 627, 636 Radiologist, 144, 636 Radiopharmaceutical, 596, 636 Radiotherapy, 574, 609, 636, 655 Radius, 40, 50, 58, 63, 99, 123, 142, 149, 368, 446, 455, 637 Ramus, 24, 637 Random Allocation, 637 Randomization, 29, 111, 124, 340, 637 Randomized clinical trial, 89, 150, 151, 199, 358, 637 Reagent, 386, 637 Rebound effect, 445, 446, 637 Receptivity, 118, 637 Recombinant, 4, 28, 62, 91, 106, 159, 180, 195, 256, 284, 360, 390, 501, 637, 653 Recombinant Proteins, 91, 637 Recombination, 596, 597, 637 Reconstitution, 130, 440, 637 Rectal, 509, 637 Rectum, 568, 574, 581, 587, 596, 606, 607, 610, 634, 637 Recurrence, 359, 361, 487, 638 Red Nucleus, 569, 638 Reductase, 199, 213, 247, 278, 397, 568, 616, 638 Refer, 1, 23, 290, 385, 574, 582, 588, 596, 612, 613, 621, 631, 638 Reflex, 487, 619, 638 Refraction, 566, 619, 638, 644 Regeneration, 473, 594, 637, 638 Regimen, 14, 32, 148, 183, 336, 338, 342, 378, 405, 409, 420, 421, 505, 535, 589, 627, 628, 638 Regression Analysis, 67, 638 Relative risk, 368, 638

Index 673

Relaxant, 626, 628, 638 Reliability, 258, 278, 489, 638 Remission, 638 Renal cell carcinoma, 259, 638 Renal Osteodystrophy, 20, 396, 473, 638 Renal pelvis, 610, 638 Reproductive History, 78, 87, 638 Research Design, 26, 33, 67, 639 Resection, 488, 639 Resorption, 6, 8, 9, 10, 11, 13, 15, 25, 27, 28, 31, 36, 41, 44, 46, 52, 57, 59, 61, 64, 66, 75, 78, 81, 82, 85, 86, 88, 90, 93, 94, 100, 104, 115, 116, 117, 121, 122, 133, 136, 140, 145, 147, 148, 160, 177, 257, 266, 353, 359, 362, 364, 365, 367, 375, 376, 377, 378, 384, 387, 388, 392, 393, 395, 400, 401, 403, 404, 406, 407, 414, 416, 420, 421, 426, 428, 432, 433, 440, 443, 444, 450, 451, 452, 454, 455, 458, 461, 463, 503, 504, 564, 573, 575, 587, 624, 639 Respiration, 409, 576, 618, 625, 639 Respiratory distress syndrome, 394, 639 Restoration, 595, 629, 637, 639, 655 Retina, 572, 580, 611, 619, 623, 639, 640, 653, 654 Retinal, 168, 259, 269, 583, 623, 639, 640 Retinal Detachment, 168, 269, 639 Retinoblastoma, 522, 639 Retinoid, 408, 561, 593, 639 Retinol, 294, 639, 640 Retrograde, 609, 639 Retroperitoneal, 562, 639 Retrospective, 69, 119, 132, 196, 265, 639 Retrospective study, 196, 639 Retroviral vector, 596, 640 Rheumatism, 6, 178, 211, 219, 223, 228, 468, 605, 640 Rheumatoid arthritis, 4, 12, 33, 128, 132, 152, 179, 184, 185, 218, 223, 254, 299, 363, 365, 366, 369, 371, 377, 394, 439, 443, 444, 518, 535, 536, 568, 581, 610, 640 Rhinitis, 610, 640 Rhodopsin, 445, 623, 639, 640 Ribavirin, 104, 640 Ribonuclease, 27, 640 Ribose, 562, 640 Ribosome, 640, 651 Rickets, 149, 396, 437, 488, 494, 575, 640 Rigidity, 389, 626, 630, 640 Risk patient, 127, 640 Rod, 409, 568, 629, 640 Rutin, 636, 640

S Salivary, 587, 625, 640 Salivary glands, 587, 640 Saponins, 640, 646 Sarcoidosis, 315, 444, 641 Saturate, 76, 641 Scans, 45, 80, 125, 135, 539, 641 Schizoid, 641, 655 Schizophrenia, 641, 655 Schizotypal Personality Disorder, 641, 655 Sciatic Nerve, 235, 628, 641, 650 Sclera, 580, 583, 641, 653 Scleroderma, 139, 569, 641 Sclerosis, 424, 522, 569, 581, 619, 641 Scoliosis, 8, 641 Sebaceous, 586, 641, 654 Secondary tumor, 616, 641 Secretory, 116, 314, 364, 577, 642 Secretory Vesicles, 577, 642 Sedative, 570, 642 Sedentary, 11, 79, 111, 120, 642 Sedimentation, 578, 631, 642 Seizures, 626, 628, 642 Selective estrogen receptor modulator, 59, 71, 126, 160, 376, 449, 459, 534, 637, 642, 647 Self Care, 474, 540, 642 Sella, 629, 642 Semen, 634, 642 Semisynthetic, 617, 642 Senescence, 56, 633, 642 Sensor, 369, 642 Sequela, 81, 642 Sequencing, 54, 95, 642 Serine, 415, 590, 617, 634, 642 Serologic, 47, 279, 642 Serologic Tests, 47, 642 Serotonin, 621, 628, 642, 652 Sex Characteristics, 562, 566, 622, 635, 642, 648 Sex Determination, 522, 643 Shock, 359, 384, 411, 453, 565, 578, 603, 643, 651 Signal Transduction, 61, 116, 121, 374, 575, 601, 643 Silicon, 131, 331, 643 Silicon Dioxide, 643 Skull, 521, 643, 648 Small intestine, 52, 579, 589, 603, 605, 608, 620, 643 Smallpox, 643, 653 Smoking Cessation, 56, 643

674 Osteoporosis

Smooth muscle, 414, 564, 565, 570, 574, 602, 618, 621, 626, 643, 646 Social Environment, 636, 643 Social Problems, 420, 643 Social Support, 35, 119, 644 Socioeconomic Factors, 631, 644 Sodium Fluoride, 7, 8, 10, 13, 15, 36, 272, 281, 306, 368, 421, 423, 424, 425, 488, 489, 510, 533, 535, 644 Soft tissue, 25, 40, 386, 573, 643, 644 Solid tumor, 566, 644 Solvent, 571, 592, 598, 644 Soma, 644 Somatic, 102, 115, 562, 580, 603, 617, 627, 644 Sound wave, 636, 644, 652 Soy Proteins, 59, 309, 644 Soybean Oil, 631, 644 Spatial disorientation, 588, 644 Specialist, 538, 549, 644 Specificity, 24, 70, 100, 121, 427, 563, 568, 575, 590, 644, 650 Spectroscopic, 112, 442, 644 Spectrum, 439, 644 Sperm, 566, 579, 630, 645, 648 Spinal cord, 199, 257, 416, 574, 578, 579, 601, 620, 627, 638, 641, 645 Spinal Cord Diseases, 601, 645 Spinous, 591, 645 Spleen, 399, 547, 613, 641, 645 Splenomegaly, 548, 624, 645 Splint, 574, 645 Spondylitis, 33, 132, 167, 212, 645 Spontaneous Fractures, 547, 645 Sporadic, 639, 645 Sprains and Strains, 613, 645 Squamous, 427, 645 Stabilization, 410, 628, 645 Staging, 641, 645 Staphylococcus, 617, 645 Stasis, 462, 645 Statistically significant, 15, 143, 645 Stem Cells, 61, 62, 86, 88, 231, 394, 466, 601, 627, 645 Stenosis, 96, 645, 646 Sterile, 569, 626, 645 Sterility, 258, 606, 645 Steroid, 5, 16, 19, 94, 119, 126, 207, 222, 230, 249, 253, 270, 277, 289, 352, 353, 369, 371, 377, 396, 397, 398, 402, 407, 434, 438, 443, 456, 459, 501, 505, 566, 568, 571, 584, 592, 601, 622, 640, 646

Steroid therapy, 353, 369, 371, 505, 646 Stimulant, 508, 574, 602, 646 Stimulus, 41, 588, 589, 607, 638, 646, 649 Stomach, 129, 294, 423, 424, 561, 587, 592, 596, 598, 603, 620, 628, 643, 645, 646 Stomachic, 462, 646 Stool, 581, 606, 610, 646 Stricture, 645, 646 Stroke, 49, 91, 141, 148, 204, 312, 355, 369, 371, 468, 472, 483, 516, 576, 646 Stromal, 48, 51, 55, 66, 90, 91, 115, 223, 573, 590, 646 Stromal Cells, 48, 51, 66, 90, 91, 115, 573, 646 Strontium, 187, 232, 270, 271, 301, 331, 646 Stupor, 611, 620, 646 Subacute, 606, 646 Subclinical, 77, 160, 606, 642, 646 Subcutaneous, 117, 271, 353, 487, 562, 589, 626, 633, 646 Subspecies, 644, 646, 653 Substance P, 616, 633, 637, 642, 646 Substrate, 95, 434, 589, 612, 646, 647 Subtrochanteric, 602, 647 Suction, 595, 647 Support group, 503, 539, 545, 647 Suppression, 65, 343, 344, 380, 421, 457, 565, 584, 647 Symphysis, 24, 409, 579, 634, 647 Symptomatic, 13, 267, 284, 301, 360, 382, 392, 416, 418, 428, 446, 647 Symptomatic treatment, 416, 428, 647 Synapse, 562, 647, 651 Synaptic, 621, 643, 647 Synchrotron, 83, 647 Synergistic, 361, 647 Systemic disease, 20, 23, 166, 451, 647 Systemic lupus erythematosus, 4, 5, 15, 91, 503, 581, 647 Systolic, 414, 422, 423, 604, 647 T Tachyphylaxis, 124, 647 Talc, 423, 647 Talin, 452, 647 Talus, 282, 647, 648, 649 Tamoxifen, 10, 59, 64, 123, 340, 510, 642, 647 Tarsal Bones, 575, 647, 648 Tarsus, 647, 648 Telangiectasia, 522, 648 Temporal, 15, 42, 51, 101, 387, 631, 648 Teratogenic, 593, 648

Index 675

Teratogenicity, 10, 648 Terminator, 581, 648 Testicles, 565, 615, 623, 648 Testicular, 5, 419, 568, 648 Testis, 566, 592, 599, 622, 648 Testosterone, 4, 5, 11, 33, 55, 58, 65, 71, 116, 120, 142, 338, 488, 504, 508, 565, 566, 638, 648 Tetany, 626, 648 Tetracycline, 83, 95, 200, 365, 366, 438, 439, 588, 617, 648 Thalamic, 569, 648 Thalamic Diseases, 569, 648 Thalassemia, 104, 170, 202, 296, 350, 400, 571, 648 Thermal, 566, 574, 588, 601, 621, 648 Thermography, 487, 648 Thigh, 594, 648 Third Ventricle, 604, 649 Thoracic, 71, 404, 405, 409, 410, 570, 574, 649, 655 Thorax, 561, 613, 649 Threonine, 617, 634, 642, 649 Threshold, 24, 81, 189, 505, 593, 604, 649 Thrombin, 594, 630, 634, 649 Thrombocytes, 630, 649 Thrombolytic, 630, 649 Thrombomodulin, 634, 649 Thrombosis, 134, 210, 248, 371, 459, 607, 634, 646, 649 Thromboxanes, 568, 649 Thrombus, 584, 606, 630, 649, 654 Thymidine, 51, 649 Thymus, 445, 605, 613, 649 Thyroid, 19, 50, 134, 416, 428, 429, 430, 456, 495, 536, 575, 604, 609, 626, 649, 652 Thyroid Gland, 604, 626, 649 Thyroid Hormones, 456, 536, 649, 652 Thyrotoxicosis, 400, 649 Thyrotropin, 605, 649 Tibia, 26, 63, 87, 143, 282, 314, 387, 594, 649 Tibiae, 27, 143, 649 Tibial Nerve, 641, 650 Ticks, 270, 650 Tin, 436, 461, 650 Tissue Distribution, 150, 650 Tomography, 4, 6, 63, 92, 97, 98, 113, 122, 131, 132, 182, 202, 368, 369, 381, 388, 447, 573, 582, 583, 641, 650 Tone, 434, 526, 623, 650 Tonic, 462, 646, 650

Tonicity, 609, 650 Tonus, 650 Tooth Loss, 23, 25, 93, 375, 386, 466, 650 Tooth Preparation, 562, 650 Topical, 98, 329, 592, 650 Torsion, 606, 650 Toxic, iv, 110, 423, 424, 445, 446, 571, 591, 647, 650 Toxicity, 65, 88, 129, 148, 408, 589, 650 Toxicology, 222, 321, 518, 650 Toxins, 567, 575, 598, 606, 650 Trace element, 294, 574, 595, 643, 650 Tracer, 45, 650 Trachea, 628, 649, 650 Transcription Factors, 85, 95, 102, 140, 651 Transdermal, 33, 281, 282, 396, 438, 651 Transduction, 116, 121, 643, 651 Transfection, 79, 101, 572, 596, 651 Transforming Growth Factor beta, 132, 463, 651 Transfusion, 319, 651 Transgenes, 146, 651 Translation, 130, 564, 651 Translational, 55, 135, 651 Transmitter, 373, 561, 615, 651 Trauma, 10, 142, 149, 163, 219, 231, 342, 361, 423, 424, 454, 571, 600, 648, 651 Treatment Outcome, 21, 466, 651 Trees, 138, 651 Tremor, 626, 651 Triad, 158, 230, 651 Tropism, 30, 651 Tryptophan, 581, 642, 652 Tuberous Sclerosis, 522, 652 Tumor marker, 572, 652 Tumor Necrosis Factor, 84, 91, 95, 128, 488, 652 Tumor suppressor gene, 50, 652 Tumour, 292, 652 Type 2 diabetes, 17, 18, 19, 77, 267, 652 Tyrosine, 51, 121, 455, 635, 652 U Ulcer, 652 Ulceration, 129, 652 Ulcerative colitis, 444, 607, 652 Ulna, 99, 652 Ultrasonography, 4, 652 Ultrasound test, 351, 652 Unconscious, 566, 605, 652 Urea, 610, 652 Uremia, 96, 610, 652 Ureters, 610, 652

676 Osteoporosis

Urethra, 634, 652, 653 Uric, 599, 604, 636, 653 Urogenital, 434, 597, 653 Urolithiasis, 132, 653 Uterus, 59, 60, 145, 438, 445, 561, 578, 584, 590, 605, 616, 625, 633, 653 Uvea, 653 Uveitis, 183, 653 V Vaccination, 653 Vaccine, 562, 635, 653 Vaccinia, 393, 653 Vaccinia Virus, 393, 653 Vacuoles, 590, 623, 653 Vagina, 436, 461, 578, 586, 616, 653 Vaginal, 396, 509, 653 Valves, 96, 653 Variola, 653 Vasculitis, 15, 653 Vasodilation, 626, 653 Vasodilator, 385, 386, 574, 602, 626, 653 Vasomotor, 44, 361, 487, 592, 653 VE, 165, 175, 295, 316, 350, 653 Vector, 28, 91, 651, 653 Vegetarianism, 295, 653 Vein, 143, 352, 609, 621, 626, 631, 654 Venous, 390, 572, 621, 634, 654 Venous Thrombosis, 390, 654 Ventricle, 635, 636, 647, 649, 654 Venules, 572, 576, 654 Veterinary Medicine, 517, 654 Villous, 577, 654 Vinculin, 452, 647, 654 Viral, 100, 584, 597, 607, 630, 651, 654

Virulence, 650, 654 Virus, 91, 162, 393, 417, 433, 460, 570, 584, 591, 597, 608, 630, 640, 643, 651, 653, 654 Visual field, 572, 623, 654 Vitamin A, 303, 398, 527, 639, 654 Vitreous, 611, 639, 654 Vitreous Humor, 639, 654 Vitro, 29, 32, 33, 36, 46, 48, 49, 51, 52, 54, 59, 61, 62, 79, 80, 81, 82, 88, 90, 91, 100, 101, 107, 124, 131, 133, 134, 141, 145, 210, 394, 396, 402, 415, 596, 602, 606, 654 Volition, 609, 654 Vulgaris, 175, 561, 654 W Weight Gain, 7, 211, 546, 654 Weight Lifting, 539, 654 Weight-Bearing, 6, 7, 10, 11, 12, 29, 68, 111, 268, 351, 362, 518, 533, 535, 537, 539, 654 White blood cell, 67, 548, 567, 611, 613, 614, 618, 619, 630, 655 Windpipe, 628, 649, 655 Withdrawal, 27, 65, 82, 137, 141, 144, 383, 411, 434, 500, 655 Womb, 653, 655 Wound Healing, 594, 607, 615, 655 X Xenograft, 566, 655 X-ray therapy, 609, 655 Y Yeasts, 372, 596, 608, 628, 655 Z Zoledronate, 36, 292, 341, 342, 655 Zymogen, 634, 655

Index 677

678 Osteoporosis

Index 679

680 Osteoporosis