Risk of all-cause mortality in elderly patients with hip fractures treated with denosumab

Background Hip fractures markedly increase the risk of all-cause mortality and subsequent fractures. Although prior meta-analyses and clinical trials such as Health Outcomes and Reduced Incidence with zoledronic acid Once Yearly (HORIZON ) Recurrent Fracture Trial have suggested that zoledronic acid may reduce mortality, large-scale database studies are often limited by residual confounding. AIM Using detailed clinical data from a geriatric fracture center, this study evaluated whether denosumab treatment reduces mortality in real-world elderly hip fracture patients. Methods This cohort study included 738 patients aged ≥ 65 years with fragility hip fracture. The treatment group (n = 368) received at least one dose of denosumab postoperatively plus calcium/vitamin D, while the control group (n = 370) received calcium/vitamin D only. Primary outcomes were all-cause mortality. Multivariate Cox models were used to adjust for age, sex, Charlson Comorbidity Index (CCI), and other potential confounders. Results During follow-up, 62 deaths (8.4%) occurred. Male (HR = 2.61, 95% CI: 1.38–4.92, p = 0.003), age ≥ 85 years (HR = 10.40, 95% CI: 3.82–28.33, p < 0.001), and CCI > 3 (HR = 7.40, 95% CI: 2.91–18.82, p < 0.001) were significant risk factors for mortality. Denosumab use was not associated with reduced mortality(p = 0.730), even after multiple doses (p = 0.890). Notably, advanced age was strongly associated with non-adherence (OR = 6.90, 95% CI: 2.31–20.83, p = 0.001). Conclusion In this real-world cohort of high-risk elderly patients with hip fracture, denosumab did not significantly reduce all-cause mortality. Advanced age was not only a predictor of mortality but also a critical barrier to treatment adherence. These findings highlight a “treatment paradox” in this vulnerable population and underscore the need for pragmatic trials and integrated multidisciplinary strategies to improve both treatment implementation and outcomes.