Clinical Review

Osteoporosis: What About Men?

Clinician Reviews. 2015 September;25(9):542-545,549-552

References

1. Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22:465-475.

2. Bliuc D, Nguyen ND, Milch VE, et al. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009;301:513-521.

3. Gennari L, Bilezikian JP. Osteoporosis in men. Endocrinol Metab Clin North Am. 2007;36:399-419.

4. Ebeling PR. Clinical practice. Osteoporosis in men. N Engl J Med. 2008;358:1474-1482.

5. Watts NB, Adler RA, Bilezikian JP, et al; Endocrine Society. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:1802-1822.

6. Memon A, Pospula WM, Tantawy AY, et al. Incidence of hip fracture in Kuwait. Int J Epidemiol. 1998;27:860-865.

7. Maggi S, Kelsey JL, Litvak J, et al. Incidence of hip fractures in the elderly: a cross-national analysis. Osteoporos Int. 1991;1:232-241.

8. Rao SS, Budhwar N, Ashfaque A. Osteoporosis in men. Am Fam Physician. 2010;82:503-508.

9. Johnell O, Kanis J. Epidemiology of osteoporotic fractures. Osteoporos Int. 2005;16 (Suppl 2):S3-S7.

10. National Institutes of Health. NIH osteoporosis and related bone diseases national resource center. Osteoporosis in men. January 2012. National Institutes of Health Web site. Available at: http://www.niams.nih.gov/health_info/bone/osteoporosis/men.asp. Accessed April 22, 2015.

11. Bruder JM, Ma JZ, Basler JW, et al. Prevalence of osteopenia and osteoporosis by central and peripheral bone mineral density in men with prostate cancer during androgen-deprivation therapy. Urology. 2006;67:152-155.

12. Tracz MJ, Sideras K, Boloña ER, et al. Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. J Clin Endocrinol Metab. 2006;91:2011-2016.

13. World Health Organization. WHO scientific group on the assessment of osteoporosis at primary health care level. Summary meeting report. Geneva, Switzerland: World Health Organization. 2007. Available at: http://who.int/chp/topics/Osteoporosis.pdf. Accessed April 22, 2015.

14. The International Society for Clinical Densitometry. 2007 official positions & pediatric official positions of The International Society for Clinical Densitometry. The International Society for Clinical Densitometry Web site. Available at: http://www.iscd.org/wp-content/uploads/2012/10/ISCD2007OfficialPositions-Combined-AdultandPediatric.pdf. Accessed August 11, 2015.

15. U.S. Preventive Services Task Force. Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med. 2011;154:356-364.

16. Qaseem A, Snow V, Shekelle P, et al; 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 Intern Med. 2008;148:680-684.

17. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. National Osteoporosis Foundation Web site. Washington, DC: 2014. Available at: http://nof.org/files/nof/public/content/file/2791/upload/919.pdf. Accessed April 22, 2015.

18. Shepherd AJ, Cass AR, Carlson CA, et al. Development and internal validation of the male osteoporosis risk estimation score. Ann Fam Med. 2007;5:540-546.

19. Lynn HS, Woo J, Leung PC, et al; Osteoporotic Fractures in Men (MrOS) Study. An evaluation of osteoporosis screening tools for the osteoporotic fractures in men (MrOS) study. Osteoporos Int. 2008;19:1087-1092.

20. Adler RA, Tran MT, Petkov VI. Performance of the osteoporosis self-assessment screening tool for osteoporosis in American men. Mayo Clin Proc. 2003;78:723-727.

21. International Osteoporosis Foundation, The International Society for Clinical Densitometry. 2010 Official Positions on FRAX®. International Osteoporosis Foundation Web site. Available at: http://www.iofbonehealth.org/sites/default/files/PDFs/2010_Official_%20Positions_%20ISCD-IOF_%20FRAX.pdf. Accessed March 21, 2015.

22. Epocrates essentials. Epocrates Web site. Available at: www.epocrates.com. Accessed April 17, 2015.

23. American Pharmacist Association. Drug information handbook: a comprehensive resource for all clinicians and healthcare professionals. 21st ed. Alphen aan den Rijn, The Netherlands: Lexi-Comp, Inc. Wolters Kluwer; 2012-2013.

24. Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000;343:604-610.

25. Ringe JD, Dorst A, Faber H, et al. Alendronate treatment of established primary osteoporosis in men: 3-year results of a prospective, comparative, two-arm study. Rheumatol Int. 2004;24:110-113.

26. Ringe JD, Faber H, Farahmand P, et al. Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study. Rheumatol Int. 2006;26:427-431.

27. Boonen S, Orwoll ES, Wenderoth D, et al. Once-weekly risedronate in men with osteoporosis: results of a 2-year, placebocontrolled, double-blind, multicenter study. J Bone Miner Res. 2009;24:719-725.

28. Khosla S, Amin S, Orwoll E. Osteoporosis in men. Endocr Rev. 2008;29:441-464.

29. Boonen S, Reginster JY, Kaufman JM, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012;367:1714-1723.

30. Lyles KW, Colón-Emeric CS, Magaziner JS, et al; HORIZON Recurrent Fracture Trial. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799-1809.

31. Orwoll ES, Scheele WH, Paul S, et al. The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res. 2003;18:9-17.

32. Kaufman JM, Orwoll E, Goemaere S, et al. Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int. 2005;16:510-516.

33. Snyder PJ, Peachey H, Hannoush P, et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab. 1999;84:1966-1972.

34. Orwoll E, Teglbjærg CS, Langdahl BL, et al. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab. 2012;97:3161-3169.

35. Smith MR, Egerdie B, Hernández Toriz N, et al; Denosumab HALT Prostate Cancer Study Group. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361:745-755.

36. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Institute of Medicine Web site. Available at: http://www.iom.edu/reports/2010/dietary-reference-intakes-for-calcium-and-vitamin-d.aspx. Accessed April 10, 2015.

37. Avenell A, Mak JC, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev. 2014;4:CD000227.

Screening considerations. The Endocrine Society, ACP, and NOF recommend a DEXA scan of the spine and hip for men who are at increased risk for osteoporosis and have no contraindications to drug therapy.^5,16,17 In patients who have degenerative changes of the spine and hip that would likely obscure DEXA outcomes, a scan of the radius may provide a more accurate assessment of bone status. Men receiving androgen deprivation therapy for prostate cancer will have a greater decline of bone density in the radius than in the hip or spine and are therefore ideal candidates for DEXA of the forearm, as well.^5,11 Keep in mind, however, that no studies have looked at how well, or whether, men with osteoporosis measured only in the radius respond to treatment.⁵

A DEXA scan is not always widely available, nor is it a perfect predictor of fracture risk. In addition, it is not always cost effective. For some patients, the use of a validated clinical predictive tool is preferable as an initial option.

The Male Osteoporosis Risk Estimation Score (MORES) uses age, weight, and history of COPD to identify men 60 years or older who are at risk for osteoporosis (TABLE 2).¹⁸ The score can be easily calculated during a clinical encounter and is beneficial for identifying men who should be referred for DEXA scan. A score of ≥6 has been found to yield an overall sensitivity of 0.93 (95% confidence interval [CI], 0.85-0.97) and a specificity of 0.59 (95% CI, 0.56-0.62), with a number needed to screen to prevent one additional hip fracture of 279.¹⁸

The Osteoporosis Self-assessment Tool (OST) (http://depts.washington.edu/osteoed/tools.php?type=ost) is a calculated value that uses age and weight to determine an individual’s risk for osteoporosis (risk score=weight [in kg] – age [in years]/5).^16,19 Although there is not a defined value to determine a positive OST risk score, scores of -1 to 3 have been used in a variety of studies.¹⁶ In a study of 181 American men, the OST predicted osteoporosis with a sensitivity of 93% and a specificity of 66% when using a cutoff score of 3.²⁰

Treating men at risk

Pharmacologic therapy is recommended for men at an increased risk for fracture. This includes men who have had a hip or vertebral fracture without major trauma, as well as those who have not had such a fracture but have a BMD of the spine, femoral neck, and/or total hip of ≤-2.5.^5,17 This standard also applies to the radius when used as an alternative site.

Several organizations recommend screening men ages ≥70 years and those ages 50 to 69 who have risk factors for fractures or who sustained a fracture after age 50.

The International Society for Clinical Densitometry and International Osteoporosis Foundation endorse the use of the Fracture Risk Assessment Tool (FRAX). Available at http://shef.ac.uk/FRAX/tool.aspx?country=9, FRAX is a computer-based calculator that uses risk factors and BMD of the femoral neck to estimate an individual’s 10-year fracture probability.²¹ Men who are 50 years or older, have a T-score between -1.0 and -2.5 in the spine, femoral neck, or total hip, and a 10-year risk of ≥20% of developing any fracture or ≥3% of developing a hip fracture based on FRAX, should be offered pharmacotherapy.^5,17

Bisphosphonates are first-line therapy

Although oral bisphosphonates are first-line therapy for men who meet these criteria,⁴ pharmacotherapy should be individualized based on factors such as fracture history, severity of osteoporosis, comorbidities (eg, peptic ulcer disease, malignancy, renal disease, or malabsorption), and cost (TABLE 3).^22,23

Alendronate once weekly has been proven to increase BMD and to reduce the risk of fracture in men.^24,25 A randomized, placebo-controlled trial of 241 men with osteoporosis found that alendronate increased BMD by 7.1% (±0.3) at the lumbar spine, 2.5% (±0.4) at the femoral neck, and 2% (±0.2) for the total body. Those in the placebo group had a 1.8% (±0.5) increase in BMD of the lumbar spine, with no significant change in femoral neck or total-body BMD—and a higher incidence of vertebral fractures (7.1% vs. 0.8% for those on alendronate; P=.02).²⁴

Risedronate once daily has also been proven to increase BMD in the lumbar spine and hip, with a reduction in vertebral fractures.²⁶ Another investigation—a 2-year, multicenter double-blind placebo-controlled study of 284 men with osteoporosis—found that risedronate given once a week increased BMD in the spine and hip, but did not reduce the incidence of either vertebral or nonvertebral fractures.²⁷

Because a DEXA scan is not always available or cost effective, a validated clinical predictive tool is preferred as an intial screening option.