- Design
- Cochrane systematic review of randomised trials
- Population
- 17 trials, 4,132 men aged 50 and over
- Primary outcome
- Hip, vertebral and other fractures; adverse events
- Effect
- Bisphosphonate hip fracture RR 0.73 (0.06 to 8.51); vertebral RR 0.49 (0.14 to 1.74); very low certainty
Most osteoporosis trials enrol women. This Cochrane review looked only at men aged 50 or over: 17 trials, 4,132 participants, testing bisphosphonates, PTH analogues, denosumab and romosozumab.
For bisphosphonates against placebo over up to two years, fracture events were very rare: hip fracture 2 per 1,000 versus 3 per 1,000 (RR 0.73, 95% CI 0.06 to 8.51), symptomatic vertebral fracture 4 versus 8 per 1,000 (RR 0.49, 0.14 to 1.74). The certainty was very low because of imprecision, risk of bias and suspected publication bias. Bisphosphonates probably did not increase adverse events (RR 1.06) or serious adverse events (RR 0.95). Evidence for the other agents was similarly uncertain.
This is an absence of good evidence, not evidence of no effect: trials in men have been small and short, powered for bone density rather than fractures. Treatment in men will continue to lean on extrapolation from women and on bone density responses.
- Keep treating men at high fracture risk, recognising the evidence is extrapolated from women
- Explain to men that fracture benefit in male-only trials has not been reliably measured
- Look for and treat secondary causes — hypogonadism, glucocorticoids, alcohol — in every man with osteoporosis
- Bisphosphonates were not associated with more adverse events than placebo
Why it matters
It exposes how thin the male-specific evidence is for a common treatment decision.
Don't overread it
Very uncertain evidence does not show the drugs fail in men; the trials were too small and short to tell.
The statistics, in plain English
A risk ratio of 0.73 with an interval from 0.06 to 8.51 is compatible with a large benefit or a large harm — it tells us almost nothing, because there were only four hip fractures.
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