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#282 Osteoporosis treatment for post-menopausal women

How effective are bisphosphonates and denosumab in preventing fractures in post-menopausal women?

Bisphosphonates and denosumab are similarly effective at reducing risk of fracture in post-menopausal women. Over 1-4 years, bisphosphonates or denosumab provide an absolute reduction of ~0.5-1.0% for hip fractures, ~1.5-3% for non-vertebral fractures and ~3-6% for vertebral fractures compared to placebo.  

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Differences statistically significant unless noted.
  • Bisphosphonates:
    • 11 systematic reviews1-11 compared alendronate, risedronate, or zoledronate to placebo:
      • Systematic reviews with best quality/reporting: over 1-4 years, bisphosphonates reduce:
        • Hip fracture [4-7 randomized controlled trials (RCTs), 9,863-11,859 patients]:1,2,3
          • 0.5-2.0% versus 1-3% placebo, number needed to treat (NNT)=100-200.
        • Non-vertebral fracture (4-6 RCTs, 9,625-12,397 patients):1,2,4
          • ~9% versus ~11% placebo, NNT=35-65.
        • Vertebral fracture (2-6 RCTs, 3139-7802 patients):1,2,3
          • 3-8% versus 7-13% placebo, NNT=16-33.
    • Consistent with other systematic reviews.3,5,7,8,10
    • Systematic reviews rarely distinguish true primary and secondary prevention.1-2 Best available data12 suggests similar relative benefits in primary and secondary prevention. Example alendronate:
      • Non-vertebral fracture: Relative risk 0.74 versus 0.81.
      • Vertebral fracture: Relative risk 0.60 versus 0.53.
  • Denosumab:
    • Five systematic reviews5,6,10,13,14 compared denosumab versus placebo: Absolute event rates by fracture type not reported.
    • Largest RCT15 (7868 post-menopausal women, T-score ≤-2.5) compared denosumab and placebo over 3 years:
      • Hip fracture: 0.7% versus 1.1% placebo, NNT=230.
      • Non-vertebral fracture: 6.1% versus 7.5% placebo, NNT=72.
      • Vertebral fracture: 2.3% versus 7.1% placebo, NNT=21.
  • Bisphosphonates versus denosumab:
    • 6 systematic reviews6,10,16-19 compared bisphosphonates and denosumab:
      • One systematic review10 reported no difference in hip, non-vertebral and vertebral fractures.
      • Four systematic reviews16-19 (4-11 RCTs, 1942-5446 patients) reported no difference in clinical fracture risk.
  • Overall limitations: Event rates infrequently reported, variable outcome definitions, industry funding of RCTs.
  • Previous articles provide guidance for screening osteoporosis20 and treatment duration.21
    • Atypical fracture risk with bisphosphonates increases with duration of therapy, particularly beyond 5 years.22
      • Fractures prevented outnumber atypical fractures at ~14-100:1 with 5 years of treatment.
  • Decision aids23 assess fracture risk and describe potential benefit to patients.
  • Drug cost only (per year):24
    • Risedronate and alendronate: ~$480.
    • Zoledronate IV infusion: ~$350.
    • Denosumab SC injection: ~$800.

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  • Samantha Moe PharmD
  • G. Michael Allan MD CCFP

1. Wells GA, Cranney A, Peterson J, et al. Cochrane Database Syst Rev. 2008; 1: CD001155.

2. Wells Ga, Cranney A, Peterson J, et al. Cochrane Database Syst Rev. 2008; 1: CD004523.

3. Serrano AJ, Beona L, Anitua E, et al. Gynecol Endocrinol. 2013; 29(12):1005-14.

4. Wang C. Am J Therap. 2017; 24:e544-552.

5. Freemantle N, Cooper C, Diez-Perez A, et al. Osteoporos Int. 2013; 24(1):209-17.

6. Jin YZ, Lee JH, Xu B, et al. BMC Musculoskeletal Disorders. 2019; 20:399

7. Liu GF, Wang ZQ, Liu L, et al. J Cel Biochem. 2018; 119:4469-81.

8. Saito T, Sterbenz JM, Malay S, et al. Osteoporos Int. 2017; 28:3289-3300.

9. Yang XC, Deng ZH, Wen T, et al. Cell Physiol Biochem. 2016; 40:781-95.

10. Barrionuevo, P, Kapoor E, Asi N, et al. J Clin Endrocrinol Metab. 104:1623-30.

11. Zhang J, Wang R, Zhao YL, et al. Asian Pacific Journal of Tropical Medicine. 2012: 743-48.

12. Stevenson M, Lloyd Jones M, De Nigris E, et al. Health Technol Assess. 2005; 9(22).

13. Anastasilakis AD, Toulis KA, Goulis DG, et al. Horm Metab Res. 209;41:721-9.

14. Von Keyserlingk C, Hoopkins R, Anastasilakis A, et al. Semin Arthritis Rheum. 2011; 41:178-86.

15. Cummings, SR, San Martin J, McClung MR, et al. New Engl J Med. 2009; 361;756-65.

16. Beaudoin C, Jean S, Bessette L, et al. Osteoporos Int. 2016; 27:2835-44.

17. Lin T, Wang C, Cai XZ, et al. Int J Clin Prac. 2012; 66(4):399-408.

18. Lyu H, Jundi B, Xu C. J Clin Endocrinol Metab. 2019; 104:1753-65.

19. Wu J, Zhang Q, Yan G, et al. J Orthop Surg Res. 2018; 13(1):194

20. Korownyk C, McCormack J, Allan GM. CFP. 2015; 61(7):612.

21. Turgeon RD, Kolber MR, Korownyk C, et al. Bisphosphonate: Forever of Five Years and Stop? Tools for Practice online publication #33. Available at: Accessed: Nov 19, 2020.

22. Black DM, Geiger EJ, et al. N Engl J Med. 2020; 383(8):743-53.

23. Mayo Clinic. Bone health Choice: Decision Aid. Available at: Accessed: Nov 20, 2020.

24. Hanley DA. Osteoporosis. RxTx, Online Edition. Canadian Pharmacists Association. Accessed Oct 16, 2020.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.