#282 Osteoporosis treatment for post-menopausal women
CLINICAL QUESTION
How effective are bisphosphonates and denosumab in preventing fractures in post-menopausal women?
BOTTOM LINE
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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EVIDENCE
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.
- Hip fracture [4-7 randomized controlled trials (RCTs), 9,863-11,859 patients]:1,2,3
- Systematic reviews with best quality/reporting: over 1-4 years, bisphosphonates reduce:
- 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.
- 11 systematic reviews1-11 compared alendronate, risedronate, or zoledronate to placebo:
- 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.
- 6 systematic reviews6,10,16-19 compared bisphosphonates and denosumab:
- 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.
- Atypical fracture risk with bisphosphonates increases with duration of therapy, particularly beyond 5 years.22
- 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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