Skip to main content

Advertisement

SpringerLink
Log in

Postmenopausal Osteoporosis Treatment Update

  • Osteoporosis (A Lau, Section Editor)
  • Published:
Current Treatment Options in Rheumatology Aims and scope Submit manuscript

Abstract

Purpose of review

To summarize existing evidence on the treatment of postmenopausal osteoporosis.

Recent findings

Despite increased interest in new targets for osteoporosis therapy, the mainstay of treatment remains to be bisphosphonates, denosumab, and teriparatide. Abaloparatide is a new parathyroid hormone-related peptide analog that has similar efficacy as teriparatide, but with monthly doses and a lower risk of hypercalcemia. This medication is approved in the USA for severe osteoporosis, but approval is pending in other countries. Romosozumab is a monoclonal antibody directed against sclerostin that has superior fracture protection compared with alendronate, but it may increase the risk of cardiovascular events based on the recent ARCH trial.

Summary

A combination of falls prevention, exercise, and adequate intake of calcium and vitamin D is recommended for prevention and treatment of osteoporosis. Pharmacologic therapy should be added to patients at high risk of fractures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

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

  1. Wade SW, Strader C, Fitzpatrick LA, Anthony MS, O’Malley CD. Estimating prevalence of osteoporosis: examples from industrialized countries. Arch Osteoporos. 2014;9:182. https://doi.org/10.1007/s11657-014-0182-3.

    Article  PubMed  CAS  Google Scholar 

  2. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster J-Y, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013;24:23–57. https://doi.org/10.1007/s00198-012-2074-y.

    Article  PubMed  CAS  Google Scholar 

  3. • Kanis JA, McCloskey EV, Harvey NC, Johansson H, Leslie WD. Intervention thresholds and the diagnosis of osteoporosis. J Bone Miner Res. 2015;30:1747–53. https://doi.org/10.1002/jbmr.2531. A concise discussion around the definition of osteoporosis, particularly the use of BMD vs. FRAX cutoffs when deciding on therapy.

    Article  PubMed  Google Scholar 

  4. Johnell O, Kanis JA, Oden A, Johansson H, De Laet C, Delmas P, et al. Predictive value of BMD for hip and other fractures. J Bone Miner Res. 2005;20:1185–94. https://doi.org/10.1359/JBMR.050304.

    Article  PubMed  Google Scholar 

  5. Trémollieres FA, Pouillès J-M, Drewniak N, Laparra J, Ribot CA, Dargent-Molina P. Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: sensitivity of the WHO FRAX tool. J Bone Miner Res. 2010;25:1002–9. https://doi.org/10.1002/jbmr.12.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J, et al. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int. 2007;18:1033–46. https://doi.org/10.1007/s00198-007-0343-y.

    Article  PubMed  CAS  Google Scholar 

  7. • Ioannidis G, Jantzi M, Bucek J, Adachi JD, Giangregorio L, Hirdes J, et al. Development and validation of the Fracture Risk Scale (FRS) that predicts fracture over a 1-year time period in institutionalised frail older people living in Canada: an electronic record-linked longitudinal cohort study. BMJ Open. 2017;7:e016477. https://doi.org/10.1136/bmjopen-2017-016477. Common fracture prediction tools such as FRAX are less useful. The authors developed a new prediction tool to evaluate the risk of fractures in frail older patients admitted to LTC.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hall SE, Criddle RA, Comito TL, Prince RL. A case-control study of quality of life and functional impairment in women with long-standing vertebral osteoporotic fracture. Osteoporos Int. 1999;9:508–15. https://doi.org/10.1007/s001980050178.

    Article  PubMed  CAS  Google Scholar 

  9. Dyer SM, Crotty M, Fairhall N, Magaziner J, Beaupre LA, Cameron ID, et al. A critical review of the long-term disability outcomes following hip fracture. BMC Geriatr. 2016;16:158. https://doi.org/10.1186/s12877-016-0332-0.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hakestad KA, Nordsletten L, Torstveit MK, Risberg MA. Postmenopausal women with osteopenia and a healed wrist fracture have reduced physical function and quality of life compared to a matched, healthy control group with no fracture. BMC Womens Health. 2014;14:92. https://doi.org/10.1186/1472-6874-14-92.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Shuid AN, Khaithir TMN, Mokhtar SA, Mohamed IN. A systematic review of the outcomes of osteoporotic fracture patients after hospital discharge: morbidity, subsequent fractures, and mortality. Ther Clin Risk Manag. 2014;106:937. https://doi.org/10.2147/TCRM.S72456.

    Article  Google Scholar 

  12. 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;301:513–21. https://doi.org/10.1001/jama.2009.50.

    Article  PubMed  CAS  Google Scholar 

  13. Haentjens P, Magaziner J, Colón-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;152:380–90. https://doi.org/10.7326/0003-4819-152-6-201003160-00008.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kannegaard PN, van der Mark S, Eiken P, Abrahamsen B. Excess mortality in men compared with women following a hip fracture. National analysis of comedications, comorbidity and survival. Age Ageing. 2010;39:203–9. https://doi.org/10.1093/ageing/afp221.

    Article  PubMed  Google Scholar 

  15. Norton R, Campbell AJ, Lee-Joe T, Robinson E, Butler M. Circumstances of falls resulting in hip fractures among older people. J Am Geriatr Soc. 1997;45:1108–12.

    Article  PubMed  CAS  Google Scholar 

  16. Tricco AC, Thomas SM, Veroniki AA, Hamid JS, Cogo E, Strifler L, et al. Comparisons of interventions for preventing falls in older adults: a systematic review and meta-analysis. JAMA. 2017;318:1687–99. https://doi.org/10.1001/jama.2017.15006.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Huang AR, Mallet L, Rochefort CM, Eguale T, Buckeridge DL, Tamblyn R. Medication-related falls in the elderly: causative factors and preventive strategies. Drugs Aging. 2012;29:359–76. https://doi.org/10.2165/11599460-000000000-00000.

    Article  PubMed  CAS  Google Scholar 

  18. Watts NB. Adverse bone effects of medications used to treat non-skeletal disorders. Osteoporos Int. 2017;28:2741–6. https://doi.org/10.1007/s00198-017-4171-4.

    Article  PubMed  CAS  Google Scholar 

  19. Woolcott JC, Richardson KJ, Wiens MO, Patel B, Marin J, Khan KM, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169:1952–60. https://doi.org/10.1001/archinternmed.2009.357.

    Article  PubMed  Google Scholar 

  20. Cawthon PM. Gender differences in osteoporosis and fractures. Clin Orthop Relat Res. 2011;469:1900–5. https://doi.org/10.1007/s11999-011-1780-7.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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;97:1802–22. https://doi.org/10.1210/jc.2011-3045.

    Article  PubMed  CAS  Google Scholar 

  22. • Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, et al. American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2017;69:1095–110. https://doi.org/10.1002/acr.23279. The updated American guidelines on treatment and prevention of glucocorticoid-induced osteoporosis.

    Article  Google Scholar 

  23. •• Papaioannou A, Santesso N, Morin SN, Feldman S, Adachi JD, Crilly R, et al. Recommendations for preventing fracture in long-term care. CMAJ. 2015;187:1135–44, E450-61. https://doi.org/10.1503/cmaj.141331. Concise and comprehensive discussion of fracture prevention in LTC, including pharmacologic and non-pharmacologic treatment.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Giangregorio LM, Macintyre NJ, Thabane L, Skidmore CJ, Papaioannou A. Exercise for improving outcomes after osteoporotic vertebral fracture. Cochrane Database Syst Rev. 2013:CD008618. doi:https://doi.org/10.1002/14651858.CD008618.pub2.

  25. Kemmler W, Häberle L, von Stengel S. Effects of exercise on fracture reduction in older adults: a systematic review and meta-analysis. Osteoporos Int. 2013;24:1937–50. https://doi.org/10.1007/s00198-012-2248-7.

    Article  PubMed  CAS  Google Scholar 

  26. Silva RB, Eslick GD, Duque G. Exercise for falls and fracture prevention in long term care facilities: a systematic review and meta-analysis. J Am Med Dir Assoc. 2013;14:685–9.e2. https://doi.org/10.1016/j.jamda.2013.05.015.

    Article  PubMed  Google Scholar 

  27. Cameron ID, Gillespie LD, Robertson MC, Murray GR, Hill KD, Cumming RG, et al. Interventions for preventing falls in older people in care facilities and hospitals. Cochrane Database Syst Rev. 2012;12:CD005465. https://doi.org/10.1002/14651858.CD005465.pub3.

    Article  PubMed  Google Scholar 

  28. Gillespie LD, Robertson MC, Gillespie WJ, Sherrington C, Gates S, Clemson LM, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2012:CD007146. doi:https://doi.org/10.1002/14651858.CD007146.pub3.

  29. Giangregorio LM, Papaioannou A, Macintyre NJ, Ashe MC, Heinonen A, Shipp K, et al. Too Fit To Fracture: exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture. Osteoporos Int. 2014;25:821–35. https://doi.org/10.1007/s00198-013-2523-2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Warensjö E, Byberg L, Melhus H, Gedeborg R, Mallmin H, Wolk A, et al. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study. BMJ. 2011;342:d1473.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cauley JA, Lacroix AZ. Wu L, Horwitz M, Danielson ME, Bauer DC, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med. 2008;149:242–50.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Zhao J-G, Zeng X-T, Wang J, Liu L. Association between calcium or vitamin D supplementation and fracture incidence in community-dwelling older adults: a systematic review and meta-analysis. JAMA. 2017;318:2466–82. https://doi.org/10.1001/jama.2017.19344.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Bischoff-Ferrari HA, Willett WC, Orav EJ, Oray EJ, Lips P, Meunier PJ, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367:40–9. https://doi.org/10.1056/NEJMoa1109617.

    Article  PubMed  CAS  Google Scholar 

  34. Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155:827–38. https://doi.org/10.7326/0003-4819-155-12-201112200-00005.

    Article  PubMed  Google Scholar 

  35. Avenell A, Mak JCS, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev. 2014:CD000227. doi:https://doi.org/10.1002/14651858.CD000227.pub4.

  36. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992;327:1637–42. https://doi.org/10.1056/NEJM199212033272305.

    Article  PubMed  CAS  Google Scholar 

  37. Khaw K-T, Stewart AW, Waayer D, Lawes CMM, Toop L, Camargo CA, et al. Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post-hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial. Lancet Diabetes Endocrinol. 2017;5:438–47. https://doi.org/10.1016/S2213-8587(17)30103-1.

    Article  PubMed  CAS  Google Scholar 

  38. Smith H, Anderson F, Raphael H, Maslin P, Crozier S, Cooper C. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women—a population-based, randomized, double-blind, placebo-controlled trial. Rheumatology (Oxford). 2007;46:1852–7. https://doi.org/10.1093/rheumatology/kem240.

    Article  CAS  Google Scholar 

  39. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303:1815–22. https://doi.org/10.1001/jama.2010.594.

    Article  PubMed  CAS  Google Scholar 

  40. Law M, Withers H, Morris J, Anderson F. Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Age Ageing. 2006;35:482–6. https://doi.org/10.1093/ageing/afj080.

    Article  PubMed  Google Scholar 

  41. Dawson-Hughes B, Harris SS. High-dose vitamin D supplementation: too much of a good thing? JAMA. 2010;303:1861–2. https://doi.org/10.1001/jama.2010.598.

    Article  PubMed  CAS  Google Scholar 

  42. Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ. 2010;182:1864–73. https://doi.org/10.1503/cmaj.100771.

    Article  PubMed  PubMed Central  Google Scholar 

  43. •• Qaseem A, Forciea MA, McLean RM, Denberg TD. Clinical Guidelines Committee of the American College of Physicians. 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;166:818–39. https://doi.org/10.7326/M15-1361. Updated American guidelines on osteoporosis for both women and men. Summarizes recent evidence and makes recommendations for use. Some recommendations were controversial (see text for discussion).

    Article  PubMed  Google Scholar 

  44. •• Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, et al. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. 2017;12:43. https://doi.org/10.1007/s11657-017-0324-5. Comprehensive review of osteoporosis treatment and prevention in women and men, including special populations. Makes recommendations for UK setting.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Mithal A, Wahl DA, Bonjour J-P, Burckhardt P, Dawson-Hughes B, Eisman JA, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009;20:1807–20. https://doi.org/10.1007/s00198-009-0954-6.

    Article  PubMed  CAS  Google Scholar 

  46. Bischoff-Ferrari HA. How to select the doses of vitamin D in the management of osteoporosis. Osteoporos Int. 2007;18:401–7. https://doi.org/10.1007/s00198-006-0293-9.

    Article  PubMed  CAS  Google Scholar 

  47. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169:551–61. https://doi.org/10.1001/archinternmed.2008.600.

    Article  PubMed  CAS  Google Scholar 

  48. Gallagher JC, Sai A, Templin T, Smith L. Dose response to vitamin D supplementation in postmenopausal women: a randomized trial. Ann Intern Med. 2012;156:425–37. https://doi.org/10.7326/0003-4819-156-6-201203200-00005.

    Article  PubMed  Google Scholar 

  49. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53–8. https://doi.org/10.1210/jc.2010-2704.

    Article  PubMed  CAS  Google Scholar 

  50. Bauer DC. Clinical practice. Calcium supplements and fracture prevention. N Engl J Med. 2013;369:1537–43. https://doi.org/10.1056/NEJMcp1210380.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010;341:c3691.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Lewis JR, Radavelli-Bagatini S, Rejnmark L, Chen JS, Simpson JM, Lappe JM, et al. The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of randomized controlled trials. J Bone Miner Res. 2015;30:165–75. https://doi.org/10.1002/jbmr.2311.

    Article  PubMed  CAS  Google Scholar 

  53. Manson JE, Allison MA, Carr JJ, Langer RD, Cochrane BB, Hendrix SL, et al. Calcium/vitamin D supplementation and coronary artery calcification in the Women’s Health Initiative. Menopause. 2010;17:683–91. https://doi.org/10.1097/gme.0b013e3181d683b5.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354:669–83. https://doi.org/10.1056/NEJMoa055218.

    Article  PubMed  CAS  Google Scholar 

  55. Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, et al. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet (London, England). n.d.;365:1621–8. https://doi.org/10.1016/S0140-6736(05)63013-9.

  56. Castelo-Branco C, Cortés X, Ferrer M. Treatment persistence and compliance with a combination of calcium and vitamin D. Climacteric. 2010;13:578–84. https://doi.org/10.3109/13697130903452804.

    Article  PubMed  CAS  Google Scholar 

  57. Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet (London, England). 2011;377:1276–87. https://doi.org/10.1016/S0140-6736(10)62349-5.

    Article  CAS  Google Scholar 

  58. Hendrickx G, Boudin E, Van Hul W. A look behind the scenes: the risk and pathogenesis of primary osteoporosis. Nat Rev. Rheumatol. 2015;11:462–74. https://doi.org/10.1038/nrrheum.2015.48.

    Article  PubMed  Google Scholar 

  59. Dempster DW, Lambing CL, Kostenuik PJ, Grauer A. Role of RANK ligand and denosumab, a targeted RANK ligand inhibitor, in bone health and osteoporosis: a review of preclinical and clinical data. Clin Ther. 2012;34:521–36. https://doi.org/10.1016/j.clinthera.2012.02.002.

    Article  PubMed  CAS  Google Scholar 

  60. Khosla S. Pathogenesis of age-related bone loss in humans. J Gerontol A Biol Sci Med Sci. 2013;68:1226–35. https://doi.org/10.1093/gerona/gls163.

    Article  PubMed  CAS  Google Scholar 

  61. Silva BC, Bilezikian JP. Parathyroid hormone: anabolic and catabolic actions on the skeleton. Curr Opin Pharmacol. 2015;22:41–50. https://doi.org/10.1016/j.coph.2015.03.005.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996;348:1535–41.

    Article  PubMed  CAS  Google Scholar 

  63. Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention. Trial. 1998;280 https://doi.org/10.1001/jama.280.24.2077.

  64. McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001;344:333–40. https://doi.org/10.1056/NEJM200102013440503.

    Article  PubMed  CAS  Google Scholar 

  65. Masud T, McClung M, Geusens P. Reducing hip fracture risk with risedronate in elderly women with established osteoporosis. Clin Interv Aging. 2009;4:445–9. https://doi.org/10.2147/CIA.S8200.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. vol. 282. 1999. doi:https://doi.org/10.1001/jama.282.14.1344.

  67. Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. vol. 11. 2000.

  68. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809–22. https://doi.org/10.1056/NEJMoa067312.

    Article  PubMed  CAS  Google Scholar 

  69. Lyles KW, Colón-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;357:1799–809. https://doi.org/10.1056/NEJMoa074941.

    Article  PubMed  CAS  Google Scholar 

  70. Crandall CJ, Newberry SJ, Diamant A, Lim Y-W, Gellad WF, Booth MJ, et al. Comparative effectiveness of pharmacologic treatments to prevent fractures: an updated systematic review. Ann Intern Med. 2014;161:711–23. https://doi.org/10.7326/M14-0317.

    Article  PubMed  Google Scholar 

  71. Brown JP, Kendler DL, McClung MR, Emkey RD, Adachi JD, Bolognese MA, et al. The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis. Calcif Tissue Int. 2002;71:103–11. https://doi.org/10.1007/s00223-002-2011-8.

    Article  PubMed  CAS  Google Scholar 

  72. Schnitzer T, Bone HG, Crepaldi G, Adami S, McClung M, Kiel D, et al. Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Alendronate Once-Weekly Study Group. vol. 12. 2000.

  73. McClung MR, Zanchetta JR, Racewicz A, Roux C, Benhamou C-L, Man Z, et al. Efficacy and safety of risedronate 150-mg once a month in the treatment of postmenopausal osteoporosis: 2-year data. Osteoporos Int. 2013;24:293–9. https://doi.org/10.1007/s00198-012-2056-0.

    Article  PubMed  CAS  Google Scholar 

  74. Frediani B, Baraldi E, Cremonesi G. Effect of clodronate treatment on risk of fracture: a systematic review and meta-analysis. Calcif Tissue Int. 2014;95:295–307. https://doi.org/10.1007/s00223-014-9903-2.

    Article  PubMed  CAS  Google Scholar 

  75. • Maraka S, Kennel KA. Bisphosphonates for the prevention and treatment of osteoporosis. BMJ. 2015;351:h3783. High yield review of bisphosphonate drug mechanism, evidence and recommendations.

    Article  PubMed  CAS  Google Scholar 

  76. Lin JH. Bisphosphonates: a review of their pharmacokinetic properties. Bone. 1996;18:75–85.

    Article  PubMed  CAS  Google Scholar 

  77. FDA. Update of Safety Review Follow-up to the October 1, 2007 Early Communication about the Ongoing Safety Review of Bisphosphonates. Drug Saf Inf Heathcare Prof 2008. https://wayback.archive-it.org/7993/20170112032108/http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm136201.htm (accessed January 20, 2018).

  78. Khan AA, Rios LP, Sándor GKB, Khan N, Peters E, Rahman MO, et al. Bisphosphonate-associated osteonecrosis of the jaw in Ontario: a survey of oral and maxillofacial surgeons. J Rheumatol. 2011;38:1396–402. https://doi.org/10.3899/jrheum.100221.

    Article  PubMed  CAS  Google Scholar 

  79. Brown JP, Morin S, Leslie W, Papaioannou A, Cheung AM, Davison KS, et al. Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays. Can Fam Physician. 2014;60:324–33.

    PubMed  PubMed Central  Google Scholar 

  80. Bronson WH, Kaye ID, Egol KA. Atypical femur fractures: a review. Curr Osteoporos Rep. 2014;12:446–53. https://doi.org/10.1007/s11914-014-0239-7.

    Article  PubMed  Google Scholar 

  81. Dell RM, Adams AL, Greene DF, Funahashi TT, Silverman SL, Eisemon EO, et al. Incidence of atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res. 2012;27:2544–50. https://doi.org/10.1002/jbmr.1719.

    Article  PubMed  Google Scholar 

  82. Lo JC, Hui RL, Grimsrud CD, Chandra M, Neugebauer RS, Gonzalez JR, et al. The association of race/ethnicity and risk of atypical femur fracture among older women receiving oral bisphosphonate therapy. Bone. 2016;85:142–7. https://doi.org/10.1016/j.bone.2016.01.002.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65. https://doi.org/10.1056/NEJMoa0809493.

    Article  PubMed  CAS  Google Scholar 

  84. Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017;5:513–23. https://doi.org/10.1016/S2213-8587(17)30138-9.

    Article  PubMed  CAS  Google Scholar 

  85. Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guañabens N, et al. Discontinuation of denosumab therapy for osteoporosis: a systematic review and position statement by ECTS. Bone. 2017;105:11–7. https://doi.org/10.1016/j.bone.2017.08.003.

    Article  PubMed  Google Scholar 

  86. Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen J-EB, McClung M, et al. Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM Trial and its extension. J Bone Miner Res 2017. doi:https://doi.org/10.1002/jbmr.3337.

  87. Block GA, Bone HG, Fang L, Lee E, Padhi D. A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res. 2012;27:1471–9. https://doi.org/10.1002/jbmr.1613.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434–41. https://doi.org/10.1056/NEJM200105103441904.

    Article  PubMed  CAS  Google Scholar 

  89. Hodsman AB, Bauer DC, Dempster DW, Dian L, Hanley DA, Harris ST, et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev. 2005;26:688–703. https://doi.org/10.1210/er.2004-0006.

    Article  PubMed  CAS  Google Scholar 

  90. Hodsman A. Scientific Advisory Council of Osteoporosis Canada, Papaioannou A, Clinical Guidelines Committee, Ann Cranney, Writing Group on the Systematic Review of Parathyroid Hormone for the Treatment of Osteoporosis. Clinical practice guidelines for the use of parathyroid hormone in the treatment of osteoporosis. CMAJ. 2006;175:48. https://doi.org/10.1503/cmaj.060624.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Campbell EJ, Campbell GM, Hanley DA. The effect of parathyroid hormone and teriparatide on fracture healing. Expert Opin Biol Ther. 2015;15:119–29. https://doi.org/10.1517/14712598.2015.977249.

    Article  PubMed  CAS  Google Scholar 

  92. Sikon A, Batur P. Profile of teriparatide in the management of postmenopausal osteoporosis. Int J Womens Health. 2010;2:37–44. https://doi.org/10.2147/IJWH.S4919.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Andrews EB, Gilsenan AW, Midkiff K, Sherrill B, Wu Y, Mann BH, et al. The US postmarketing surveillance study of adult osteosarcoma and teriparatide: study design and findings from the first 7 years. J Bone Miner Res. 2012;27:2429–37. https://doi.org/10.1002/jbmr.1768.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Nevitt MC, Chen P, Dore RK, Reginster JY, Kiel DP, Zanchetta JR, et al. Reduced risk of back pain following teriparatide treatment: A meta-analysis. Osteoporos Int. 2006;17:273–80. https://doi.org/10.1007/s00198-005-2013-2.

    Article  PubMed  Google Scholar 

  95. Hadji P, Zanchetta JR, Russo L, Recknor CP, Saag KG, McKiernan FE, et al. The effect of teriparatide compared with risedronate on reduction of back pain in postmenopausal women with osteoporotic vertebral fractures. Osteoporos Int. 2012;23:2141–50. https://doi.org/10.1007/s00198-011-1856-y.

    Article  PubMed  CAS  Google Scholar 

  96. Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. Vol. 349. 2003. doi:https://doi.org/10.1097/01.OGX.0000115856.54444.D6.

  97. Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. Vol. 349. 2003. doi:https://doi.org/10.1056/NEJMoa035725.

  98. Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: The DATA study randomised trial. Lancet. 2013;382:50–6. https://doi.org/10.1016/S0140-6736(13)60856-9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Boonen S, Marin F, Obermayer-Pietsch B, Simões ME, Barker C, Glass EV, et al. Effects of previous anti-resorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2008;93:852–60. https://doi.org/10.1210/jc.2007-0711.

    Article  PubMed  CAS  Google Scholar 

  100. Cosman F, Wermers RA, Recknor C, Mauck KF, Xie L, Glass EV, et al. Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the anti-resorptive agent. J Clin Endocrinol Metab. 2009;94:3772–80. https://doi.org/10.1210/jc.2008-2719.

    Article  PubMed  CAS  Google Scholar 

  101. Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. Vol. 353. 2005. doi:https://doi.org/10.1097/01.ogx.0000193859.78235.fe.

  102. Cranney A, Papaioannou A, Zytaruk N, Hanley D, Adachi J, Goltzman D, et al. Parathyroid hormone for the treatment of osteoporosis: a systematic review. CMAJ. 2006;175:52–9. https://doi.org/10.1503/cmaj.050929.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Tella SH, Kommalapati A, Correa R. Profile of abaloparatide and its potential in the treatment of postmenopausal osteoporosis. Cureus. 2017;9:e1300. https://doi.org/10.7759/cureus.1300.

    Article  PubMed  PubMed Central  Google Scholar 

  104. • Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316:722–33. https://doi.org/10.1001/jama.2016.11136. ACTIVE trial of abaloparatide, a PTHrP analog, vs. teriparatide or placeo in severe postmenopausal osteoporosis. Abaloparatide has similar efficacy as teriparatide but with fewer episodes of hypercalcemia.

    Article  PubMed  CAS  Google Scholar 

  105. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA. 2003;290:1729–38. https://doi.org/10.1001/jama.290.13.1729.

    Article  PubMed  CAS  Google Scholar 

  106. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–33. https://doi.org/10.1001/jama.288.3.321.

    Article  PubMed  CAS  Google Scholar 

  107. Cranney A, Tugwell P, Zytaruk N, Robinson V, Weaver B, Adachi J, et al. Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis. Endocr Rev. 2002;23:524–8. https://doi.org/10.1210/er.2001-4002.

    Article  PubMed  CAS  Google Scholar 

  108. Peng L, Luo Q, Lu H. Efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: A systematic review and meta-analysis. Medicine (Baltimore). 2017;96:e8659. https://doi.org/10.1097/MD.0000000000008659.

    Article  CAS  Google Scholar 

  109. Cummings SR, Ensrud K, Delmas PD, LaCroix AZ, Vukicevic S, Reid DM, et al. Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med. 2010;362:686–96. https://doi.org/10.1056/NEJMoa0808692.

    Article  PubMed  CAS  Google Scholar 

  110. Ellis AJ, Hendrick VM, Williams R, Komm BS. Selective estrogen receptor modulators in clinical practice: a safety overview. Expert Opin Drug Saf. 2015;14:921–34. https://doi.org/10.1517/14740338.2015.1014799.

    Article  PubMed  CAS  Google Scholar 

  111. Berry SD, Samelson EJ, Pencina MJ, McLean RR, Cupples LA, Broe KE, et al. Repeat bone mineral density screening and prediction of hip and major osteoporotic fracture. JAMA. 2013;310:1256–62. https://doi.org/10.1001/jama.2013.277817.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, et al. Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with anti-resorptive drugs. Am J Med. 2002;112:281–9.

    Article  PubMed  CAS  Google Scholar 

  113. Chapurlat RD, Palermo L, Ramsay P, Cummings SR. Risk of fracture among women who lose bone density during treatment with alendronate. The Fracture Intervention Trial. Osteoporos Int. 2005;16:842–8. https://doi.org/10.1007/s00198-004-1770-7.

    Article  PubMed  CAS  Google Scholar 

  114. Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2012;27:243–54. https://doi.org/10.1002/jbmr.1494.

    Article  PubMed  CAS  Google Scholar 

  115. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006;296:2927–38. https://doi.org/10.1001/jama.296.24.2927.

    Article  PubMed  CAS  Google Scholar 

  116. Schwartz AV, Bauer DC, Cummings SR, Cauley JA, Ensrud KE, Palermo L, et al. Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial. J Bone Miner Res. 2010;25:976–82. https://doi.org/10.1002/jbmr.11.

    Article  PubMed  CAS  Google Scholar 

  117. McClung MR. Sclerostin antibodies in osteoporosis: latest evidence and therapeutic potential. Ther Adv Musculoskelet Dis. 2017;9:263–70. https://doi.org/10.1177/1759720X17726744.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Drake MT, Clarke BL, Oursler MJ, Khosla S. Cathepsin K Inhibitors for Osteoporosis: Biology, Potential Clinical Utility, and Lessons Learned. Endocr Rev. 2017;38:325–50. https://doi.org/10.1210/er.2015-1114.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Mullard A. Merck &Co. drops osteoporosis drug odanacatib. Nat Rev. Drug Discov. 2016;15:669. https://doi.org/10.1038/nrd.2016.207.

    Article  PubMed  CAS  Google Scholar 

  120. • Saag KG, Petersen J, Grauer A. Romosozumab versus alendronate and fracture risk in women with osteoporosis. N Engl J Med. 2018;378:195–6. https://doi.org/10.1056/NEJMc1714810. ARCH trial of romosozumab vs. alendronate demonstrating a lower fracture incidence but a higher risk of cardiovascular events (see text for discussion).

    Article  PubMed  Google Scholar 

  121. • 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;375:1532–43. https://doi.org/10.1056/NEJMoa1607948. FRAME trial of romosozumab vs. placebo showing similar cardiovascular event incidence between groups (see text for discussion).

    Article  PubMed  CAS  Google Scholar 

  122. Kranenburg G, Bartstra JW, Weijmans M, de Jong PA, Mali WP, Verhaar HJ, et al. Bisphosphonates for cardiovascular risk reduction: a systematic review and meta-analysis. Atherosclerosis. 2016;252:106–15. https://doi.org/10.1016/j.atherosclerosis.2016.06.039.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Geriatric Medicine Residency Program, Faculty of Medicine, University of Toronto, Toronto, Canada

    Eric Kai-Chung Wong MD, FRCPC

  2. GERAS Centre, St. Peter’s Hospital, Hamilton Health Sciences, 88 Maplewood Ave, Hamilton, ON, L8M 1W9, Canada

    Eric Kai-Chung Wong MD, FRCPC & Alexandra Papaioannou BScN, MD, MSc, FRCPC, FACP

  3. Geriatric Medicine, McMaster University, Hamilton, Canada

    Alexandra Papaioannou BScN, MD, MSc, FRCPC, FACP

Authors
  1. Eric Kai-Chung Wong MD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandra Papaioannou BScN, MD, MSc, FRCPC, FACP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexandra Papaioannou BScN, MD, MSc, FRCPC, FACP.

Ethics declarations

Conflict of Interest

Eric Kai-Chung Wong declares that he has no conflict of interest. Alexandra Papaioannou declares that she has 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.

Additional information

This article is part of the Topical Collection on Osteoporosis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wong, E.KC., Papaioannou, A. Postmenopausal Osteoporosis Treatment Update. Curr Treat Options in Rheum 4, 142–157 (2018). https://doi.org/10.1007/s40674-018-0098-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40674-018-0098-y

Keywords

Search

Navigation