Denosumab linked to fewer repeat fractures than bisphosphonates

Clinical takeaway: Weigh refracture risk and the likelihood of treatment persistence when choosing an antiresorptive after a low-trauma fracture. If selecting denosumab, ensure dosing every 6 months and arrange a transition to bisphosphonate therapy before discontinuation to reduce rebound fracture risk.

Patients face particularly high risks of another fracture and death soon after a low-trauma fracture, making timely osteoporosis treatment a priority. Bisphosphonates and denosumab both reduce fracture risk compared with placebo, but randomized trials have not directly compared their effects on refracture or mortality in a postfracture population.

Among women, the estimated 3-year refracture risk was 14.4% with nitrogen-containing bisphosphonates versus 12.7% with denosumab, an absolute difference of 1.7 percentage points. Among men, the corresponding risks were 19.0% versus 16.0%, a difference of 3.0 percentage points.

The association was strongest among patients whose initial fracture occurred outside the hip or spine; no clear treatment difference emerged after an initial hip or vertebral fracture. All-cause mortality did not clearly differ between treatments in either sex.

Differences in treatment persistence may partly explain the findings, the authors suggest, and denosumab’s faster, more potent suppression of bone turnover could also contribute. The observational design cannot establish causation, and unmeasured factors, including bone mineral density, may have influenced the results.

Researchers used linked Australian health records to emulate monthly treatment trials among treatment-naive adults aged 50 or older who started alendronate, risedronate, zoledronic acid, or denosumab within 12 months of a low-trauma fracture. The primary outcomes were all-cause mortality and refracture within 3 years, analyzed in 15,099 and 14,343 patients, respectively.

The authors call for adequately powered head-to-head studies to confirm the findings by initial fracture site. Because bisphosphonates were analyzed together, the results do not establish how individual drugs compare with denosumab.

“Thus, the lower refracture risk seen with denosumab must be weighed against the need for careful long-term treatment planning,” the authors write.

Source: Lin M, et al. (2026 Nov 11) JAMA Netw Open. Bisphosphonates vs Denosumab After Low-Trauma Fractures