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
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.
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