Advertisement

Current Treatment Options in Rheumatology

, Volume 4, Issue 4, pp 355–366 | Cite as

Management of Male Osteoporosis: an Update

  • Mohammed Almohaya
  • Ahmad Alobedollah
  • David L. KendlerEmail author
Osteoporosis (A Lau, Section Editor)
  • 17 Downloads
Part of the following topical collections:
  1. Topical Collection on Osteoporosis

Abstract

Purpose of review

Osteoporosis is a major health concern for men in our aging population. The incidence of osteoporotic fractures in men is expected to rise as life expectancy increases. When adjusted for age, one half of all hip fractures occur in men and of all osteoporotic fractures; hip fractures account for the highest morbidity and mortality. Several factors contribute to bone loss in men. Sex steroid deficiency plays an important role in male age-related bone loss. Careful evaluation for secondary causes of bone loss (including lifestyle factors, comorbidities, and risk medications) is warranted.

Recent findings

Osteoporosis guidelines recommend bone mineral density (BMD) testing in men over age 70, earlier in men with other risk factors. As in women, adequate calcium and vitamin D intake, regular weight-bearing exercise, smoking cessation, limiting excessive alcohol, and fall prevention strategies are recommended. Available clinical data support efficacy of bisphosphonates (alendronate, risedronate, zoledronic acid), denosumab, and anabolic therapy (teriparatide) in men with osteoporosis as well as in women. Abaloparatide, a parathyroid hormone-related peptide analog with demonstrated anti-fracture efficacy in women, awaits the conclusion of clinical trials in men. Romosozumab shows similar BMD and bone turnover marker effects in osteoporotic men compared to women; evaluation of safety concerns is ongoing.

Summary

Recent insights into osteoporosis pathophysiology and bone cell biology provide promising direction for effective therapeutic strategies for the management of male osteoporosis.

Keywords

Male osteoporosis Fracture Pathophysiology Testosterone Secondary osteoporosis Osteoporosis therapy 

Notes

Compliance with Ethical Standards

Conflict of interest

Dr. Kendler reports grants and personal fees from Amgen, grants and personal fees from Eli Lilly, grants from Astrazenica, personal fees from Pfizer, outside the submitted work.

Mohammed Almohaya declares that there is no conflict of interest.

Ahmad Alobedollah declares that there is no conflict of interest.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Gennari L, Bilezikian JP. Osteoporosis in men. Endocrinol Metab Clin N Am. 2007;36(2):399–419.  https://doi.org/10.1016/j.ecl.2007.03.008.CrossRefGoogle Scholar
  2. 2.
    Kanis JA, Oden A, McCloskey EV, Johansson H, Wahl DA, Cooper C. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int. 2012;23(9):2239–56.  https://doi.org/10.1007/s00198-012-1964-3.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet (London, England). 1999;353(9156):878–82.  https://doi.org/10.1016/s0140-6736(98)09075-8.CrossRefGoogle Scholar
  4. 4.
    Haentjens P, Magaziner J, Colon-Emeric CS, Vanderschueren D, Milisen K, Velkeniers B, et al. Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med. 2010;152(6):380–90.  https://doi.org/10.7326/0003-4819-152-6-201003160-00008.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009;301(5):513–21.  https://doi.org/10.1001/jama.2009.50.CrossRefPubMedGoogle Scholar
  6. 6.
    Jiang HX, Majumdar SR, Dick DA, Moreau M, Raso J, Otto DD, et al. Development and initial validation of a risk score for predicting in-hospital and 1-year mortality in patients with hip fractures. J Bone Miner Res. 2005;20(3):494–500.  https://doi.org/10.1359/jbmr.041133.CrossRefPubMedGoogle Scholar
  7. 7.
    Gullberg B, Johnell O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int. 1997;7(5):407–13.CrossRefGoogle Scholar
  8. 8.
    Ebeling PR. Osteoporosis in men. N Engl J Med. 2008;358(14):1474–82.  https://doi.org/10.1056/NEJMcp0707217.CrossRefPubMedGoogle Scholar
  9. 9.
    Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22(3):465–75.  https://doi.org/10.1359/jbmr.061113.CrossRefPubMedGoogle Scholar
  10. 10.
    Kanis JA, Bianchi G, Bilezikian JP, Kaufman JM, Khosla S, Orwoll E, et al. Towards a diagnostic and therapeutic consensus in male osteoporosis. Osteoporos Int. 2011;22(11):2789–98.  https://doi.org/10.1007/s00198-011-1632-z.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hans D, Downs RW, Jr., Duboeuf F, Greenspan S, Jankowski LG, Kiebzak GM et al. Skeletal sites for osteoporosis diagnosis: the 2005 ISCD official positions. J Clin Densitom : the official journal of the International Society for Clinical Densitometry. 2006;9(1):15–21. doi: https://doi.org/10.1016/j.jocd.2006.05.003.
  12. 12.
    Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam study. Bone. 2004;34(1):195–202.CrossRefGoogle Scholar
  13. 13.
    Duan Y, Beck TJ, Wang XF, Seeman E. Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. J Bone Miner Res. 2003;18(10):1766–74.  https://doi.org/10.1359/jbmr.2003.18.10.1766.CrossRefPubMedGoogle Scholar
  14. 14.
    Wang XF, Duan Y, Beck TJ, Seeman E. Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone. 2005;36(6):978–86.  https://doi.org/10.1016/j.bone.2004.11.015.CrossRefPubMedGoogle Scholar
  15. 15.
    Khosla S, Melton LJ, 3rd, Atkinson EJ, O'Fallon WM. Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinol Metab 2001;86(8):3555–3561. doi: https://doi.org/10.1210/jcem.86.8.7736.
  16. 16.
    Gennari L, Merlotti D, Martini G, Gonnelli S, Franci B, Campagna S, et al. Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J Clin Endocrinol Metab. 2003;88(11):5327–33.  https://doi.org/10.1210/jc.2003-030736.
  17. 17.
    Szulc P, Joly-Pharaboz MO, Marchand F, Delmas PD. Insulin-like growth factor I is a determinant of hip bone mineral density in men less than 60 years of age: MINOS study. Calcif Tissue Int. 2004;74(4):322–9.  https://doi.org/10.1007/s00223-003-0090-9.CrossRefPubMedGoogle Scholar
  18. 18.
    Khosla S, Amin S, Orwoll E. Osteoporosis in men. Endocr Rev. 2008;29(4):441–64.  https://doi.org/10.1210/er.2008-0002.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Seeman E. Osteoporosis in men: epidemiology, pathophysiology, and treatment possibilities. Am J Med. 1993;95(5a):22s–8s.CrossRefGoogle Scholar
  20. 20.
    Drake MT, Murad MH, Mauck KF, Lane MA, Undavalli C, Elraiyah T, et al. Clinical review. Risk factors for low bone mass-related fractures in men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2012;97(6):1861–70.  https://doi.org/10.1210/jc.2011-3058.
  21. 21.
    Seeman E, Hopper JL, Young NR, Formica C, Goss P, Tsalamandris C. Do genetic factors explain associations between muscle strength, lean mass, and bone density? A twin study. Am J Phys. 1996;270(2 Pt 1):E320–7.  https://doi.org/10.1152/ajpendo.1996.270.2.E320.CrossRefGoogle Scholar
  22. 22.
    Cummings SR, Cawthon PM, Ensrud KE, Cauley JA, Fink HA, Orwoll ES. BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women. J Bone Miner Res. 2006;21(10):1550–6.  https://doi.org/10.1359/jbmr.060708.CrossRefPubMedGoogle Scholar
  23. 23.
    Watts NB, Adler RA, Bilezikian JP, Drake MT, Eastell R, Orwoll ES, et al. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(6):1802–22.  https://doi.org/10.1210/jc.2011-3045.
  24. 24.
    Schousboe JT, Vokes T, Broy SB, Ferrar L, McKiernan F, Roux C, et al. Vertebral fracture assessment: the 2007 ISCD official positions. J Clin Densitom. 2008;11(1):92–108.  https://doi.org/10.1016/j.jocd.2007.12.008.CrossRefPubMedGoogle Scholar
  25. 25.
    Szulc P. Biochemical bone turnover markers and osteoporosis in older men: where are we? J Osteoporos. 2011;2011:704015.  https://doi.org/10.4061/2011/704015.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Bauer DC, Garnero P, Harrison SL, Cauley JA, Eastell R, Ensrud KE, et al. Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study. J Bone Miner Res. 2009;24(12):2032–8.  https://doi.org/10.1359/jbmr.090526.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Tosteson AN, Melton LJ 3rd, Dawson-Hughes B, Baim S, Favus MJ, Khosla S, et al. Cost-effective osteoporosis treatment thresholds: the United States perspective. Osteoporos Int. 2008;19(4):437–47.  https://doi.org/10.1007/s00198-007-0550-6.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    • Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD open. 2015;1(1):e000014.  https://doi.org/10.1136/rmdopen-2014-000014 The authors provide a review of pathophysiology and fracture risk assessment and suggested treatment thresholds in glucocorticoid-induced osteoporosis which differ from postmenopausal and age-related osteoporosis.
  29. 29.
    Rizzoli R, Body JJ, Brandi ML, Cannata-Andia J, Chappard D, El Maghraoui A, et al. Cancer-associated bone disease. Osteoporos Int. 2013;24(12):2929–53.  https://doi.org/10.1007/s00198-013-2530-3.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kaufman JM, Reginster JY, Boonen S, Brandi ML, Cooper C, Dere W, et al. Treatment of osteoporosis in men. Bone. 2013;53(1):134–44.  https://doi.org/10.1016/j.bone.2012.11.018.
  31. 31.
    Orimo H, Nakamura T, Hosoi T, Iki M, Uenishi K, Endo N, et al. Japanese 2011 guidelines for prevention and treatment of osteoporosis--executive summary. Arch Osteoporos. 2012;7:3–20.  https://doi.org/10.1007/s11657-012-0109-9.
  32. 32.
    Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000;343(9):604–10.  https://doi.org/10.1056/nejm200008313430902.
  33. 33.
    Ringe JD, Farahmand P, Faber H, Dorst A. Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study. Rheumatol Int. 2009;29(3):311–5.  https://doi.org/10.1007/s00296-008-0689-2.CrossRefPubMedGoogle Scholar
  34. 34.
    Boonen S, Orwoll ES, Wenderoth D, Stoner KJ, Eusebio R, Delmas PD. Once-weekly risedronate in men with osteoporosis: results of a 2-year, placebo-controlled, double-blind, multicenter study. J Bone Miner Res. 2009;24(4):719–25.  https://doi.org/10.1359/jbmr.081214.CrossRefPubMedGoogle Scholar
  35. 35.
    Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J, Langdahl B, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012;367(18):1714–23.  https://doi.org/10.1056/NEJMoa1204061.
  36. 36.
    Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357(18):1799–809.  https://doi.org/10.1056/NEJMoa074941.CrossRefPubMedGoogle Scholar
  37. 37.
    Orwoll E, Teglbjaerg CS, Langdahl BL, Chapurlat R, Czerwinski E, Kendler DL, 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(9):3161–9.  https://doi.org/10.1210/jc.2012-1569.CrossRefPubMedGoogle Scholar
  38. 38.
    Smith MR, Egerdie B, Hernandez Toriz N, Feldman R, Tammela TL, Saad F, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361(8):745–55.  https://doi.org/10.1056/NEJMoa0809003.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Orwoll ES, Scheele WH, Paul S, Adami S, Syversen U, Diez-Perez A, 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(1):9–17.  https://doi.org/10.1359/jbmr.2003.18.1.9.CrossRefPubMedGoogle Scholar
  40. 40.
    Kaufman JM, Orwoll E, Goemaere S, San Martin J, Hossain A, Dalsky GP, et al. Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int. 2005;16(5):510–6.  https://doi.org/10.1007/s00198-004-1713-3.CrossRefPubMedGoogle Scholar
  41. 41.
    Amory JK, Watts NB, Easley KA, Sutton PR, Anawalt BD, Matsumoto AM, 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(2):503–10.  https://doi.org/10.1210/jc.2003-031110.
  42. 42.
    Tracz MJ, Sideras K, Bolona ER, Haddad RM, Kennedy CC, Uraga MV, 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(6):2011–6.  https://doi.org/10.1210/jc.2006-0036.CrossRefPubMedGoogle Scholar
  43. 43.
    Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med. 2004;350(5):459–68.  https://doi.org/10.1056/NEJMoa022436.
  44. 44.
    Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study. J Clin Endocrinol Metab. 2005;90(5):2816–22.  https://doi.org/10.1210/jc.2004-1774.CrossRefPubMedGoogle Scholar
  45. 45.
    Gonnelli S, Cepollaro C, Montagnani A, Bruni D, Caffarelli C, Breschi M, et al. Alendronate treatment in men with primary osteoporosis: a three-year longitudinal study. Calcif Tissue Int. 2003;73(2):133–9.  https://doi.org/10.1007/s00223-002-1085-7.
  46. 46.
    Miller PD, Schnitzer T, Emkey R, Orwoll E, Rosen C, Ettinger M, et al. Weekly oral alendronic acid in male osteoporosis. Clin Drug Investig. 2004;24(6):333–41.Google Scholar
  47. 47.
    Boonen S, Lorenc RS, Wenderoth D, Stoner KJ, Eusebio R, Orwoll ES. Evidence for safety and efficacy of risedronate in men with osteoporosis over 4 years of treatment: results from the 2-year, open-label, extension study of a 2-year, randomized, double-blind, placebo-controlled study. Bone. 2012;51(3):383–8.  https://doi.org/10.1016/j.bone.2012.06.016.CrossRefPubMedGoogle Scholar
  48. 48.
    Sawka AM, Papaioannou A, Adachi JD, Gafni A, Hanley DA, Thabane L. 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.  https://doi.org/10.1186/1471-2474-6-39.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Boonen S, Orwoll E, Magaziner J, Colon-Emeric CS, Adachi JD, Bucci-Rechtweg C, et al. Once-yearly zoledronic acid in older men compared with women with recent hip fracture. J Am Geriatr Soc. 2011;59(11):2084–90.  https://doi.org/10.1111/j.1532-5415.2011.03666.x.CrossRefPubMedGoogle Scholar
  50. 50.
    Saag KG, Shane E, Boonen S, Marin F, Donley DW, Taylor KA, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357(20):2028–39.  https://doi.org/10.1056/NEJMoa071408.CrossRefPubMedGoogle Scholar
  51. 51.
    Saag KG, Zanchetta JR, Devogelaer JP, Adler RA, Eastell R, See K, et al. Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum. 2009;60(11):3346–55.  https://doi.org/10.1002/art.24879.
  52. 52.
    Anderson FH, Francis RM, Peaston RT, Wastell HJ. Androgen supplementation in eugonadal men with osteoporosis: effects of six months’ treatment on markers of bone formation and resorption. J Bone Miner Res. 1997;12(3):472–8.  https://doi.org/10.1359/jbmr.1997.12.3.472.CrossRefPubMedGoogle Scholar
  53. 53.
    Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109–22.  https://doi.org/10.1056/NEJMoa1000485.
  54. 54.
    Szulc P, Bauer DC, Eastell R. Biochemical markers of bone turnover in osteoporosis. In: Primer on the metabolic bone diseases and disorders of mineral metabolism: John Wiley & Sons, Inc.; 2013. p. 297–306.Google Scholar
  55. 55.
    Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011;26(1):19–26.  https://doi.org/10.1002/jbmr.173.CrossRefPubMedGoogle Scholar
  56. 56.
    •• Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532–43.  https://doi.org/10.1056/NEJMoa1607948 This is placebo- controlled study in postmenopausal women demonstrated anti-fracture efficacy and safety of the sclerostin monoclonal antibody, romosozumab. The safety profile of romosozumab was comparable to placebo and cardiovascular risk was not increased in this study.CrossRefPubMedGoogle Scholar
  57. 57.
    Lewiecki EM, Blicharski SH,T, Goemaere S, Lippuner K, Meisner P, Miller PD, et al. ACR/ARHP annual meeting. ABSTRACT NUMBER. 2016;3212016.Google Scholar
  58. 58.
    •• Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417–27.  https://doi.org/10.1056/NEJMoa1708322 This study of romosozumab vs. alendronate showed fracture risk reduction with romosozumab in high risk postmenopausal women but with an increase in cardiovascular risk.CrossRefPubMedGoogle Scholar
  59. 59.
    •• Chapurlat RD. Odanacatib: a review of its potential in the management of osteoporosis in postmenopausal women. Therapeutic advances in musculoskeletal disease. 2015;7(3):103–9.  https://doi.org/10.1177/1759720x15580903. This review summarizes anti-fracture efficacy of odanacatib, a cathepsin K inhibitor with positive phase 2 and phase 3 clinical trial efficacy results.
  60. 60.
    • Drake MT, Clarke BL, Oursler MJ, Khosla S. Cathepsin K Inhibitors for Osteoporosis: Biology, Potential Clinical Utility, and Lessons Learned. Endocrine Rev. 2017;38(4):325–50.  https://doi.org/10.1210/er.2015-1114 The authors review the potential role of cathepsin k inhibitors in in clinical disorders of bone metabolism.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Mohammed Almohaya
    • 1
  • Ahmad Alobedollah
    • 1
  • David L. Kendler
    • 2
    Email author
  1. 1.Obesity, Endocrine & Metabolism CenterKing Fahad Medical CityRiyadhSaudi Arabia
  2. 2.Department of MedicineUniversity of British ColumbiVancouverCanada

Personalised recommendations