Bisphosphonates vs Denosumab After Low-Trauma Fractures
Authors' conclusion
In this cohort study emulating a target trial, initiation of N-BP and denosumab therapy was associated with similar mortality, whereas initiation of N-BP was associated with higher refracture risk, particularly after NHNV fractures.
Study context
- Population
- Treatment-naive adults 50 years or older through the 12 months after incident low-trauma fracture, New South Wales, Australiacohort · women 12,529 · men 2,570
- Participants
- 15,099 adults
- Exposure
- N-BP vs denosumab
- Outcome
- All-cause mortality and refracture
- Follow-up
- Three-year
Methodological detailsnew-user, active-comparator design, inverse probability weighting, Linked administrative health data
- New-user, active-comparator design
- Inverse probability weighting
- Linked administrative health data
Main finding
As reported in the abstract
N-BP vs DenosumabEstimate (95% CI)
No clear association
ITT HR for all-cause mortality, women 0.98(0.87–1.10)
No clear association
ITT HR for all-cause mortality, men 1.09(0.93–1.25)
Higher refracture risk with N-BP
ITT HR for refracture, women 1.14(1.05–1.26)
Higher refracture risk with N-BP
ITT HR for refracture, men 1.21(1.03–1.42)
Per 1000 person-years
- All-cause mortality rate, women, N-BP
- 48.1
- All-cause mortality rate, women, denosumab
- 48.9
- All-cause mortality rate, men, N-BP
- 123.0
- All-cause mortality rate, men, denosumab
- 116.4
- Refracture rate, women, N-BP
- 52.7
- Refracture rate, women, denosumab
- 46.5
- Refracture rate, men, N-BP
- 70.5
- Refracture rate, men, denosumab
- 58.8
Observational data: associations, not effects.
Further findings
| Outcome | Estimate | |
|---|---|---|
| Refracture, per-protocol analysisN-BPvs DenosumabPer-protocol | HR for refracture, women 1.30 (95% CI 1.09–1.55) | |
| Refracture, per-protocol analysisN-BPvs DenosumabPer-protocol | HR for refracture, men 1.48 (95% CI 1.10–1.98) | |
| Refracture following nonhip-nonvertebral (NHNV) fracturesN-BPvs Denosumab | HR for refracture, women 1.21 (95% CI 1.06–1.38) | |
| Refracture following nonhip-nonvertebral (NHNV) fracturesN-BPvs Denosumab | HR for refracture, men 1.54 (95% CI 1.10–2.15) | |
| 0.512Ratio (log scale) |
Refracture, competing-risk analysis
- Competing-risk estimates were similar
- Fine-Gray competing-risk analysis
Original publication
Bisphosphonates vs Denosumab After Low-Trauma Fractures. JAMA Netw Open. Published 2 November 2026. doi:10.
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