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Research ArticleTools for Practice

Osteoporosis in postmenopausal women

Samantha Moe, Allison Paige and G. Michael Allan
Canadian Family Physician May 2021, 67 (5) 346; DOI: https://doi.org/10.46747/cfp.6705346
Samantha Moe
Clinical Evidence Expert at the College of Family Physicians of Canada (CFPC).
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Allison Paige
Medical Lead of Kildonan Medical Centre at Seven Oaks General Hospital in Winnipeg and Lecturer at the University of Manitoba.
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G. Michael Allan
Director of Programs and Practice Support at the CFPC.
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Clinical question

How effective are bisphosphonates and denosumab for preventing fractures in postmenopausal women?

Bottom line

Bisphosphonates and denosumab are similarly effective. Over 1 to 4 years, bisphosphonates or denosumab provide an absolute reduction of about 0.5% to 1.0% for hip fractures, 1.5% to 3% for nonvertebral fractures, and 3% to 6% for vertebral fractures, compared with placebo.

Evidence

Differences are statistically significant unless noted.

Bisphosphonates

  • Eleven systematic reviews1 compared alendronate, risedronate, or zoledronate with placebo.

  • The systematic reviews with the best quality and reporting found that over 1 to 4 years, bisphosphonates reduced the following.

    • - Hip fracture (4-7 RCTs, 9863-11 859 patients)2-4: 0.5% to 2.0% vs 1% to 3% with placebo (NNT = 100-200).

    • - Nonvertebral fracture (4-6 RCTs, 9625-12 397 patients)2,3,5: about 9% vs about 11% with placebo (NNT = 35-65).

    • - Vertebral fracture (2-6 RCTs, 3139-7802 patients)2-4: 3% to 8% vs 7% to 13% with placebo (NNT = 16-33).

  • Results are consistent with other systematic reviews.1

  • Systematic reviews rarely distinguish true primary and secondary prevention.2,3 The best data6 suggest similar relative benefit in primary and secondary prevention (eg, alendronate: relative risk is 0.74 vs 0.81 for nonvertebral fracture and 0.60 vs 0.53 for vertebral fracture).

Denosumab

  • Five systematic reviews1 compared denosumab with placebo; absolute event rates by fracture type not reported.

  • The largest RCT7 (7868 postmenopausal women, T-score ≤ -2.5) compared denosumab with placebo over 3 years.

    • - Hip fracture: 0.7% vs 1.1% placebo (NNT = 230).

    • - Nonvertebral fracture: 6.1% vs 7.5% placebo (NNT = 72).

    • - Vertebral fracture: 2.3% vs 7.1% placebo (NNT = 21).

Bisphosphonates versus denosumab

  • One systematic review1 reported no difference in hip, nonvertebral, and vertebral fractures.

  • Four systematic reviews1 (4-11 RCTs, 1942-5446 patients) reported no difference in clinical fracture risk.

Context

  • Overall limitations: event rates infrequently reported, variable outcome definitions, industry funding of RCTs.

  • Atypical fracture risk with bisphosphonates increases with duration of therapy, particularly beyond 5 years.8.

    - Fractures prevented outnumber atypical fractures at about 14-100:1 with 5 years of treatment.

  • Approximate drug cost (per year)9: $480 for risedronate and alendronate, $350 for zoledronate intravenous infusion, $800 for denosumab subcutaneous injection.

Implementation

The osteoporosis screening tool is a simplified tool that reliably predicts osteoporosis and identifies those who would benefit from bone mineral density testing.10 Before starting a bisphosphonate or denosumab, discuss fracture risk and potential risks and benefits with the patient. The Mayo Clinic’s Bone Health Choice Decision Aid provides information to support that discussion.11 When prescribing, consider duration of therapy. Evidence suggests that after 5 years of treatment, discontinuation of bisphosphonates carries little to no increased future fracture risk,12 and atypical fracture risk increases with duration of therapy beyond 5 years.8

Notes

Tools for Practice articles in Canadian Family Physician are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice{at}cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.

Footnotes

  • Competing interests

    None declared

  • The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

  • Copyright© the College of Family Physicians of Canada

References

  1. 1.↵
    1. Moe S,
    2. Allan GM.
    Osteoporosis treatment for post-menopausal women. Tools for Practice #282. Edmonton, AB: Alberta College of Family Physicians; 2020.
  2. 2.↵
    1. Wells GA,
    2. Cranney A,
    3. Peterson J,
    4. Boucher M,
    5. Shea B,
    6. Robinson V, et al.
    Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008;(1):CD001155.
  3. 3.↵
    1. Wells GA,
    2. Cranney A,
    3. Peterson J,
    4. Boucher M,
    5. Shea B,
    6. Robinson V, et al.
    Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008;(1):CD004523.
  4. 4.↵
    1. Serrano AJ,
    2. Begoña L,
    3. Anitua E,
    4. Cobos R,
    5. Orive G.
    Systematic review and meta-analysis of the efficacy and safety of alendronate and zoledronate for the treatment of postmenopausal osteoporosis. Gynecol Endocrinol 2013;29(12):1005-14. Epub 2013 Sep 25.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Wang C.
    Efficacy and safety of zoledronic acid for treatment of postmenopausal osteoporosis: a meta-analysis of randomized controlled trials. Am J Ther 2017;24(5):e544-52.
    OpenUrlCrossRef
  6. 6.↵
    1. Stevenson M,
    2. Jones ML,
    3. De Nigris E,
    4. Brewer N,
    5. Davis S,
    6. Oakley J.
    A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis. Health Technol Assess 2005;9(22):1-160.
    OpenUrlPubMed
  7. 7.↵
    1. Cummings SR,
    2. San Martin J,
    3. McClung MR,
    4. Siris ES,
    5. Eastell R,
    6. Reid IR, et al.
    Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361(8):756-65.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Black DM,
    2. Geiger EJ,
    3. Eastell R,
    4. Vittinghoff E,
    5. Li BH,
    6. Ryan DS, et al.
    Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates. N Engl J Med 2020;383(8):743-53.
    OpenUrlPubMed
  9. 9.↵
    1. Hanley DA.
    Osteoporosis. In: Canadian Pharmacists Association, editors. RxTx. Online ed. Ottawa, ON: Canadian Pharmacists Association; 2020.
  10. 10.↵
    1. Korownyk CS,
    2. McCormack J,
    3. Allan GM.
    Who should receive bone mineral density testing? Can Fam Physician 2015;61:612.
    OpenUrlFREE Full Text
  11. 11.↵
    1. Mayo Clinic
    . Bone health choice decision aid. Rochester, MN: Mayo Clinic; 1998. Available from: https://osteoporosisdecisionaid.mayoclinic.org/index.php/osteo/index. Accessed 2020 Nov 20.
  12. 12.↵
    1. Kolber MR,
    2. Sadowski CA,
    3. Korownyk CS.
    Bisphosphonates: forever or 5 years and stop? Can Fam Physician 2015;61:443.
    OpenUrlFREE Full Text
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Canadian Family Physician: 67 (5)
Canadian Family Physician
Vol. 67, Issue 5
1 May 2021
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Osteoporosis in postmenopausal women
Samantha Moe, Allison Paige, G. Michael Allan
Canadian Family Physician May 2021, 67 (5) 346; DOI: 10.46747/cfp.6705346

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Samantha Moe, Allison Paige, G. Michael Allan
Canadian Family Physician May 2021, 67 (5) 346; DOI: 10.46747/cfp.6705346
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