Hau Liu, MD, MBA, MPH; Neil M. Paige, MD, MSHS; Caroline L. Goldzweig, MD, MSHS; Elaine Wong, MD; Annie Zhou, MS; Marika J. Suttorp, MS; Brett Munjas, BA; Eric Orwoll, MD; Paul Shekelle, MD, PhD
Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs.
Acknowledgment: The authors gratefully acknowledge Smita Nayak, MD, for her expertise in osteoporosis screening tests and her assistance with our analysis.
Grant Support: This work was funded in part by the U.S. Department of Veterans Affairs Health Services Research and Development Evidence Synthesis Activity Pilot Program, Project ESP 05-226. Dr. Liu was supported by an Agency for Healthcare Research and Quality National Research Service Award (grant no. HS000028-19). Drs. Paige, Goldzweig, Wong, and Shekelle and Ms. Munjas were supported by the Veterans Affairs Administration. Ms. Zhou and Ms. Suttorp are employees of RAND Corporation. Dr. Orwoll is supported by National Institutes of Health funding (AR45647, AG027810, and RR024140).
Potential Financial Conflicts of Interest:Consultancies: E. Orwoll (Merck & Co., Eli Lilly, Servier). Honoraria: E. Orwoll (Merck & Co.). Grants received: E. Orwoll (Amgen, Pfizer, Eli Lilly, Novartis, Zelos Therapeutics, Imaging Therapeutics, Solvay Pharmaceuticals). Grants pending: H. Liu (Procter & Gamble).
Requests for Single Reprints: Hau Liu, MD, MBA, MPH, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, CA 95128; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Liu: Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, CA 95128.
Drs. Paige, Goldzweig, Wong, and Shekelle and Ms. Munjas: Veterans Affairs Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, West Los Angeles, CA 90073.
Ms. Zhou and Ms. Suttorp: RAND Corporation, 1776 Main Street, Santa Monica, CA 90401.
Dr. Orwoll: Endocrinology, 3181 SW Sam Jackson Park Road, Portland, OR 97239.
Screening for low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is the primary way to identify asymptomatic men who might benefit from osteoporosis treatment. Identifying men at risk for low BMD and fracture can help clinicians determine which men should be tested.
To identify which asymptomatic men should receive DXA BMD testing, this systematic review evaluates 1) risk factors for osteoporotic fracture in men that may be mediated through low BMD and 2) the performance of non-DXA tests in identifying men with low BMD.
Studies identified through the MEDLINE database (1990 to July 2007).
Articles that assessed risk factors for osteoporotic fracture in men or evaluated a non-DXA screening test against a gold standard of DXA.
Researchers performed independent dual abstractions for each article, determined performance characteristics of screening tests, and assessed the quality of included articles.
A published meta-analysis of 167 studies evaluating risk factors for low BMD–related fracture in men and women found high-risk factors to be increased age (>70 years), low body weight (body mass index <20 to 25 kg/m2), weight loss (>10%), physical inactivity, prolonged corticosteroid use, and previous osteoporotic fracture. An additional 102 studies assessing 15 other proposed risk factors were reviewed; most had insufficient evidence in men to draw conclusions. Twenty diagnostic study articles were reviewed. At a T-score threshold of −1.0, calcaneal ultrasonography had a sensitivity of 75% and specificity of 66% for identifying DXA-determined osteoporosis (DXA T-score, −2.5). At a risk score threshold of −1, the Osteoporosis Self-Assessment Screening Tool had a sensitivity of 81% and specificity of 68% to identify DXA-determined osteoporosis.
Data on other screening tests, including radiography, and bone geometry variables, were sparse.
Key risk factors for low BMD–mediated fracture include increased age, low body weight, weight loss, physical inactivity, prolonged corticosteroid use, previous osteoporotic fracture, and androgen deprivation therapy. Non-DXA tests either are too insensitive or have insufficient data to reach conclusions.
Table 1. Search Strategy
Table 2. GRADE Categories of Quality of Evidence
Study flow diagram.
Some articles assessed multiple risk factors. A total of 614 titles were identified for review; 20 articles evaluated male osteoporosis screening tools and were included in the analysis. BMD = bone mineral density; PSA = prostate-specific antigen.
Table 3. Characteristics of Non–Dual-Energy X-Ray Absorptiometry Osteoporosis Screening Tests
Table 4. Summary of Quality of Evidence
Table 5. Quality Assessment of Non–Dual-Energy X-Ray Absorptiometry Osteoporosis Screening Tests
Receiver-operating characteristic curves for calcaneal ultrasonography (left) and the Osteoporosis Self-Assessment Screening Tool (OST) (right) in identifying dual-energy x-ray absorptiometry (DXA)–determined osteoporosis.
The plotted curves were derived from abstracted data of included studies for calcaneal ultrasonography and OST against DXA as the reference standard. QUI = quantitative ultrasound index. *Threshold for positive test result: central DXA T-score = −1.5. †Threshold for positive test result: central DXA T-score = −2.0. ‡Threshold for positive test result: central DXA T-score = −2.5. §Threshold for positive test result: calcaneal ultrasonography T-score = −1.0. ∥Threshold for positive test result: bone mineral density T-score = −2.0. ¶Threshold for positive test result: bone mineral density T-score = −2.5. **Threshold for positive test result: OST score = −1.0.
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May 30, 2008
The Effects of Race, Ethnicity, and Underlying Medical Diseases on Osteoporosis
The Effects of Race, Ethnicity, and Underlying Medical Diseases on Osteoporosis: Still Unguided Territory for Internists
TO THE EDITOR: We were pleased to read the recently published American College of Physicians clinical guidelines and systematic review on screening for osteoporosis in men. This issue represents closure of a significant gap in previous guidelines issued to general internists and we commend the authors and the ACP for undertaking this project. Currently, Medicare coverage for bone mass measurements is limited to at-risk women with estrogen-deficiency, individuals with vertebral radiography suggestive of underlying osteoporosis, individuals on prolonged glucocorticoid therapy, patients with primary hyperparathyroidism, and those already on osteoporosis medication. Hopefully, the new ACP guidelines will help extend Medicare coverage to include at-risk male patients, as out-of-pocket expenses for DEXA screening are approximately $180 at our institution.
As much as the new ACP guidelines fulfill an unmet need, several questions remain unanswered. For example, the guidelines article quoted a prevalence of osteoporosis estimated at 7% in white men, 5% in black men, and 3% of Hispanic men, with little data available on Asian-American men and other ethnic groups[1,4]. However, the article fails to mention issues of race and ethnicity again. Given the fact that prevalence of osteoporosis in women clearly has been associated with racial and ethnic background (see the excellent review by Lane), further evaluation of such cultural and genetic factors in men should be considered.
Secondary osteoporosis, a topic which may have even less attention in the literature than osteoporosis in men, has thus far not been included in the screening guidelines for this population. Among men, 30-60% of osteoporosis cases are associated with secondary causes (most commonly hypogonadism, glucocorticoid use, and alcoholism). Secondary causes also affect perimenopausal women, with more than 50% of this population affected. The Annals systematic review is one of the first to evaluate the often confusing and contradictory literature addressing which secondary causes are most likely to affect bone health and eventually fracture risk. For example, studies suggest that hyperthyroidism, whether treated or untreated, is a secondary risk factor for osteoporosis. Yet, one specific study published in Clinical Endocrinology in 2004 found that the risk of osteoporosis in women with hyperthyroidism was only increased in the 3 years after induction of therapy, with treated women having a Z- score no different from age-matched controls after 3 years of therapy. No official recommendations have been made based on this data.
Long term oral glucocorticoid therapy also accounts for 1 out of 6 cases of male osteoporosis . The extent of bone damage is related to duration of therapy and dosage of the steroid, leading to a recommendation from the American College of Rheumatology to treat patients taking 5 mg or more of steroids per day for longer than 6 months. Yet, there is no statement from other societies endorsing this recommendation or forming screening guidelines of their own. Is it reasonable to classify "steroid exposure years" in the same way as we classify tobacco "pack years"?
Given the effects of race, ethnicity, and underlying medical disease on bone mineral density, we wonder if gender-based guidelines for osteoporosis are the most appropriate tact to take. Additionally, patients below the "usual" screening ages for osteoporosis may be at significant risk for fractures based on their underlying medical condition or treatments for the same. Perhaps an expanded fracture risk algorithm, similar to but more comprehensive than the WHO risk calculator, can be developed that includes more risk criteria. The undertaking for such an endeavor may be arduous, but groups such as the ACP and the American Association of Clinical Endocrinologists (AACE) can perhaps work together to ensure better and more cost-effective screening guidelines for a disease with such significant morbidity, mortality, and financial burden.
Brittany Bohinc, MD
John E. Snyder, MS, MD
Wilmington, N.C. 28401
Potential Financial Conflicts of Interest: None disclosed.
1. Qaseem A, Snow V, Shekelle P, Hopkins, Jr. R, Forciea MA, Owens DK, AND for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Screening for Osteoporosis in Men: A Clinical Practice Guideline from the American College of Physicians. Ann Int Med 2008 148: 680-684.
2. Liu H, Paige NM, Goldzweig CL, Wong E, Zhou A, Suttorp MJ, Munjas B, Orwoll E, and Shekelle P. Screening for Osteoporosis in Men: A Systematic Review for an American College of Physicians Guideline. Ann Intern Med 2008; 148: 685-701.
3. CMS Manual System. Medicare Benefit Policy, Pub 100-02 on Bone Mass Measurements. Acquired from: http://www.cms.hhs.gov/transmittals/downloads/R70BP.pdf on May 29, 2008.
4. Looker AC, Orwoll ES, Johnston CC Jr, Lindsay RL, Wahner HW, Dunn WL, Calvo MS, Harris TB, and Heyse SP. Prevalance of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res. 1997;12:1761-8.
5. Lane, NE. Epidemiology, etiology, and diagnosis of osteoporosis. American Journal of Obstetrics and Gynecology (2006) 194, S3"“11.
6. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285:785-795.
7. Karga H, Papapetrou PD, Korkovouni A, Papandroulaki F, Polymeris A, Pampouras G. Bone mineral density in hyperthyroidism. Clinical Endocrinology. 61(4): 466-472.
8. Seeman E, Melton LJ, O'Fallon WM, Riggs BL. Risk factors for spinal osteoporosis in men. Am J Med 1983;75:977-83.
9. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. 2001 Update. Arthritis Rheum 2001; 44:1496-503.
Santa Clara Valley Medical Center and Stanford University
June 25, 2008
Response to Drs. Bohinc and Snyder -
We thank Drs. Bohinc and Snyder for their insightful comments regarding our recent systematic review and guideline on screening for osteoporosis in men for the American College of Physicians (1,2). We concur that a deeper evaluation of race and ethnicity in male osteoporosis, as has been performed in women, would be preferable and is much needed. However, our ability to make conclusive remarks regarding the effects of race and ethnicity on screening in men is limited by the lack of research in this area. We have attempted to better understand the effects of secondary causes of male osteoporosis. Our review evaluates the existing literature on key secondary causes of male osteoporosis, including, alcoholism, androgen deprivation therapy/hypogonadism, and rheumatologic disease. Once again, a limitation of data in men makes it difficult to draw strong conclusions regarding many of these risk factors.
Ultimately, our review and guideline serves not only to synthesize the current literature on screening in male osteoporosis, but also to highlight the major gaps in our understanding of this topic. As Drs. Bohinc and Snyder point out, these gaps in the existing literature are many. As such, our papers serve not only as a review and guideline to be used by clinicians, but as a call for increased research and awareness of this important, yet often under-diagnosed and under-treated, condition.
Hau Liu, MD, MBA, MPH Santa Clara Valley Medical Center San Jose, CA
Paul Shekelle, MD, PhD Veterans Affairs Greater Los Angeles Healthcare System Los Angeles, CA
Amir Qaseem, MD, PhD, MHA American College of Physicians Philadelphia, PA
Eric Orwoll, MD Oregon Health and Science University Portland, Oregon
Liu H, Paige NM, Goldzweig CL, Wong E, Zhou A, Suttorp MJ, et al. Screening for Osteoporosis in Men: A Systematic Review for an American College of Physicians Guideline. Ann Intern Med. 2008;148:685–701. doi: 10.7326/0003-4819-148-9-200805060-00009
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Published: Ann Intern Med. 2008;148(9):685-701.
Endocrine and Metabolism, Guidelines, Metabolic Bone Disorders, Prevention/Screening.
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