A medical dictionary bibilography

Summary: This journal article provides health professionals with information on the mechanisms of glucocorticoid induced osteoporosis in systemic lupus erythematosus SLE and outlines str

O STEOPOROSIS

J AMES N P ARKER , M.D

AND P HILIP M P ARKER , P H D., E DITORS

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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

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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., 1961-

Parker, Philip M., 1960-

Osteoporosis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James

N Parker and Philip M Parker, editors

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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

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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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

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

F ORWARD

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

C HAPTER 1 S TUDIES ON O STEOPOROSIS

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

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)

• 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

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)

• 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

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)

• 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

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

• 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

• 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)

• 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

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

• 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)

• The Epidemiology of Osteoporosis

Source: Journal of Rheumatology 23(45):2-5 1996

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

• 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)

• 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: fp@aafp.org Website: www.aafp.org

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: fp@aafp.org 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)

• 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

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 osteoclast-mediated 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

• 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

• OA: Protection from Osteoporosis?

Source: Arthritis Today p 8-10 November-December 1996

Osteoporosis

12

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 weight-bearing 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

• 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

• 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

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)

• 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, non-FDA 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 slow-release sodium fluoride; and examines the nutritional and lifestyle considerations for combating the condition, including taking vitamin D and calcium supplementation

• 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

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

• 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

• 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

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

• 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 corticosteroid-treated 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)

• 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

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

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)

• Review Article: Osteoporosis, Corticosteroids and Inflammatory Bowel Disease

Source: Alimentary Pharmacology and Therapeutics 9(3): 237-250 June 1995

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)

• 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

• 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

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

• 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

• 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

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

• 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

• 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

• 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)

• 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

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

• 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: info@oda.on.ca

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

• 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: agdjournal@agd.org 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

• 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

• 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

• 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)

224-7283

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)

• 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)

• 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

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

• 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

• 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

• 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 post-menopausal 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

• 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)

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 1-month 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

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

• 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

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

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 osteoblast-specific 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 behaviorally-based 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 self-efficacy, 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

• 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 27-week, 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

• 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

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

Timing: Fiscal Year 2001

Summary: There is no text on file for this abstract

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

Osteoporosis

32

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