The effectiveness of bisphosphonates vs denosumab in people with dementia or frailty post hip fracture: a multi-database cohort study

Summary: Brief rationale: The effectiveness of bisphosphonates versus denosumab after hip fracture, especially in people with dementia or frailty, remains unclear. Main result: Bisphosphonates were associated with a higher rate of subsequent fracture and a lower mortality rate in men. There are no differences by dementia or frailty status. Significance of the paper: Sex may influence antiresorptive treatment choice. Purpose: The relative effectiveness of first-line antiresorptive medications post-hip fracture in people with dementia or frailty is not understood. We investigated the risk of a subsequent fracture and death in people prescribed bisphosphonates or denosumab following hip fracture, including in people with dementia and frailty. Methods: Parallel population-based cohort studies were conducted in Australia, Hong Kong, Taiwan, and the United Kingdom. People aged ≥ 50 prescribed or dispensed a bisphosphonate or denosumab within 60 days of discharge following their first hip fracture were included. Subgroup analyses were conducted for people with dementia, frailty, women, and men. Outcomes were second hip fracture, any subsequent fracture, and death. Inverse probability of treatment weighted Cox and competing risk models were used to estimate hazard ratios (HR) and subdistribution hazard ratios (sHRs) with 95% confidence intervals (CIs) for outcomes. Results across jurisdictions were combined using meta-analyses. Results: There were 18,292 bisphosphonate users and 8560 denosumab users. Bisphosphonates versus denosumab were associated with similar rates of second hip fracture (sHR 1.13; 95% CI 0.76–1.69) and mortality (HR 0.99; 95% CI 0.94–1.04), but higher rates of any subsequent fracture (sHR 1.16; 95% CI 1.11–1.21), including in men (sHR1.27; 95% CI 1.15–1.42) but not in women (sHR 1.23; 95% CI 1.00–1.52), or in people with dementia or frailty. Men who used bisphosphonates had lower rates of mortality (HR 0.90; 95% CI 0.81–0.99) than men who used denosumab. Conclusion: Bisphosphonate users had higher rates of subsequent fracture than denosumab users. Mortality rates in men were lower with bisphosphonates than denosumab. There were no significant differences by dementia and frailty status.