Treatment of osteoporosis in men
- Joel S Finkelstein, MD
Joel S Finkelstein, MD
- Associate Professor of Medicine
- Harvard Medical School
- Elaine W Yu, MD
Elaine W Yu, MD
- Assistant Professor of Medicine
- Harvard Medical School
Osteoporosis is a leading cause of morbidity and mortality in older people. While less common in men than women, over 8 million men in the United States have low bone mass or osteoporosis [1,2]. The mortality rate associated with hip fractures [3,4], as well as vertebral and other major fractures , is higher in men than in women. In addition, men are even less likely than women to be evaluated or receive antiresorptive therapy after a hip fracture (4.5 versus 49.5 percent, respectively) [6-8].
The treatment of osteoporosis in men consists of lifestyle measures and drug or hormonal therapy. An overview of the approach to therapy of osteoporosis in men will be presented here. The diagnosis, evaluation, and epidemiology of osteoporosis in men are discussed separately. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men" and "Epidemiology and etiology of osteoporosis in men".)
In general, lifestyle modifications should be encouraged for all men with osteoporosis. A weight-bearing exercise regimen may be modestly beneficial, given the association of reduced physical activity with bone loss and fracture in older men and the positive effect of exercise in women with osteoporosis (see "Epidemiology and etiology of osteoporosis in men", section on 'Physical activity and strength' and "Overview of the management of osteoporosis in postmenopausal women", section on 'Exercise'). In addition, smoking and excessive alcohol intake should be avoided.
As a general rule, men with osteoporosis should receive adequate calcium (1000 mg/day in younger men, 1000 to 1200 mg daily in older men, total diet plus supplement) and vitamin D (600 to 800 international units/day) supplementation. Older persons confined indoors and other high-risk groups may have low serum 25-hydroxyvitamin D (25[OH]D) concentrations at this intake level and may require higher intakes of vitamin D. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Groups at high risk'.)
In some trials, calcium and vitamin D have been shown to reduce fracture risk in men and women when administered at a dose of at least 700 international units/day (see "Calcium and vitamin D supplementation in osteoporosis"). However, in most cases, the addition of pharmacologic or hormonal therapy is necessary for the treatment of osteoporosis in men .
- 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.
- Watts NB, Adler RA, Bilezikian JP, et al. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97:1802.
- Kanis JA, Oden A, Johnell O, et al. The components of excess mortality after hip fracture. Bone 2003; 32:468.
- Haentjens P, Magaziner J, Colón-Emeric CS, et al. Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med 2010; 152:380.
- Center JR, Nguyen TV, Schneider D, et al. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 1999; 353:878.
- Kiebzak GM, Beinart GA, Perser K, et al. Undertreatment of osteoporosis in men with hip fracture. Arch Intern Med 2002; 162:2217.
- Feldstein A, Elmer PJ, Orwoll E, et al. Bone mineral density measurement and treatment for osteoporosis in older individuals with fractures: a gap in evidence-based practice guideline implementation. Arch Intern Med 2003; 163:2165.
- Feldstein AC, Nichols G, Orwoll E, et al. The near absence of osteoporosis treatment in older men with fractures. Osteoporos Int 2005; 16:953.
- Ebeling PR, Wark JD, Yeung S, et al. Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study. J Clin Endocrinol Metab 2001; 86:4098.
- Katznelson L, Finkelstein JS, Schoenfeld DA, et al. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996; 81:4358.
- Behre HM, Kliesch S, Leifke E, et al. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab 1997; 82:2386.
- Greenspan SL, Oppenheim DS, Klibanski A. Importance of gonadal steroids to bone mass in men with hyperprolactinemic hypogonadism. Ann Intern Med 1989; 110:526.
- Finkelstein JS, Klibanski A, Neer RM, et al. Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1989; 69:776.
- Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, et al. Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone: A Controlled Clinical Trial. JAMA Intern Med 2017; 177:471.
- Amory JK, Watts NB, Easley KA, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004; 89:503.
- Basurto L, Zarate A, Gomez R, et al. Effect of testosterone therapy on lumbar spine and hip mineral density in elderly men. Aging Male 2008; 11:140.
- van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 2002; 13:777.
- Papaioannou A, Morin S, Cheung AM, et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 2010; 182:1864.
- Kanis JA, McCloskey EV, Johansson H, et al. Case finding for the management of osteoporosis with FRAX--assessment and intervention thresholds for the UK. Osteoporos Int 2008; 19:1395.
- http://www.shef.ac.uk/NOGG/index.html (Accessed on March 10, 2011).
- Cosman F, de Beur SJ, LeBoff MS, et al. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int 2014; 25:2359.
- Ensrud KE, Taylor BC, Peters KW, et al. Implications of expanding indications for drug treatment to prevent fracture in older men in United States: cross sectional and longitudinal analysis of prospective cohort study. BMJ 2014; 349:g4120.
- http://www.shef.ac.uk/NOGG/NOGG_Pocket_Guide_for_Healthcare_Professionals.pdf (Accessed on June 21, 2012).
- Qaseem A, Forciea MA, McLean RM, et al. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med 2017; 166:818.
- Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 2007; 357:1799.
- 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.
- Crandall CJ, Newberry SJ, Diamant A, et al. Comparative effectiveness of pharmacologic treatments to prevent fractures: an updated systematic review. Ann Intern Med 2014; 161:711.
- MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 2008; 148:197.
- Crandall CJ, Newberry SJ, Diamant A, et al. Treatment to prevent fractures in men and women with low bone density or osteoporosis: Update of a 2007 report, AHRQ March 2012. http://www.ncbi.nlm.nih.gov/books/NBK92566/pdf/TOC.pdf (Accessed on September 12, 2012).
- Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med 2000; 343:604.
- Ringe JD, Faber H, Dorst A. Alendronate treatment of established primary osteoporosis in men: results of a 2-year prospective study. J Clin Endocrinol Metab 2001; 86:5252.
- Ringe JD, Dorst A, Faber H, Ibach K. Alendronate treatment of established primary osteoporosis in men: 3-year results of a prospective, comparative, two-arm study. Rheumatol Int 2004; 24:110.
- Sawka AM, Papaioannou A, Adachi JD, et al. Does alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women. BMC Musculoskelet Disord 2005; 6:39.
- Borgström F, Johnell O, Jönsson B, et al. Cost effectiveness of alendronate for the treatment of male osteoporosis in Sweden. Bone 2004; 34:1064.
- Schousboe JT, Taylor BC, Fink HA, et al. Cost-effectiveness of bone densitometry followed by treatment of osteoporosis in older men. JAMA 2007; 298:629.
- Ito K, Elkin EB, Girotra M, Morris MJ. Cost-effectiveness of fracture prevention in men who receive androgen deprivation therapy for localized prostate cancer. Ann Intern Med 2010; 152:621.
- Ringe JD, Faber H, Farahmand P, Dorst A. Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study. Rheumatol Int 2006; 26:427.
- Boonen S, Orwoll ES, Wenderoth D, et al. Once-weekly risedronate in men with osteoporosis: results of a 2-year, placebo-controlled, double-blind, multicenter study. J Bone Miner Res 2009; 24:719.
- Sato Y, Iwamoto J, Kanoko T, Satoh K. Risedronate sodium therapy for prevention of hip fracture in men 65 years or older after stroke. Arch Intern Med 2005; 165:1743.
- 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.
- "The Pink Sheet". 2002; 64:3.
- Kurland ES, Heller SL, Diamond B, et al. The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1-34)]. Osteoporos Int 2004; 15:992.
- 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.
- http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Protelos_and_Osseor/human_referral_prac_000025.jsp&mid=WC0b01ac05805c516f. (Accessed on February 23, 2017).
- Bolland MJ, Grey A. Cessation of strontium ranelate supply. BMJ 2017; 357:j2580.
- Bolland MJ, Grey A. Ten years too long: strontium ranelate, cardiac events, and the European Medicines Agency. BMJ 2016; 354:i5109.
- http://www.servier.com/content/cessation-marketing-protelososseor-extract-letter-sent-european-medicine-agency-ema-and (Accessed on May 31, 2017).
- LIFESTYLE MEASURES
- TREATMENT OF SECONDARY CAUSES
- Testosterone therapy
- Glucocorticoid-induced osteoporosis
- Androgen deprivation therapy
- PHARMACOLOGIC THERAPY
- Candidates for therapy
- - Fracture risk assessment
- - Limitations
- Choice of therapy
- - Bisphosphonates
- Oral bisphosphonates
- IV bisphosphonates
- Adverse effects and precautions
- Duration of therapy
- - Parathyroid hormone
- - Combination therapy
- - Denosumab
- - Strontium ranelate
- - Other
- MONITORING THE RESPONSE TO THERAPY
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS