Effect of denosumab on the incidence of fractures and mortality in patients undergoing hemodialysis: A retrospective cohort study

Background: Patients undergoing hemodialysis are at an elevated risk of fractures; however, substantial evidence for osteoporosis treatment in this population is lacking. We explored the efficacy of denosumab, an anti-IgG2 antibody that targets the receptor activator of nuclear factor-kappa B ligand, in reducing fracture incidence and all-cause mortality in patients undergoing hemodialysis. Methods: This retrospective cohort study—conducted from December 2013 to December 2022—evaluated the effects of denosumab on fracture incidence and all-cause mortality. Patients who initiated denosumab treatment during the study period were defined as the denosumab group, while those without a history of denosumab administration were defined as the non-denosumab group. Kaplan–Meier curves and log-rank tests were used to assess survival and fracture/mortality risks, respectively. Cox proportional hazards models were used to analyze both fractures and all-cause mortality. Results: Among 214 patients undergoing hemodialysis, 52 (24.3%) received denosumab. The median age was 73.0 ± 11.5 years, with 92 (43.0%) females, and the median dialysis duration was 59 months (interquartile range, 6–126). During the study, thirty-seven non-denosumab-treated patients had fractures compared to eight in the denosumab group. No significant differences were observed in the unadjusted model (HR, 0.53; 95% confidence interval (CI), 0.24–1.14). Adjusting for competing mortality and clinical factors, the HR remained at 0.64 (95% CI, 0.27–1.51). Regarding all-cause mortality, we found a statistically significant difference in the unadjusted model (HR, 0.61 [95% CI, 0.38–0.98]). A significant reduction in mortality was observed in the adjusted model (HR, 0.46 [95% CI, 0.26–0.80]). Notably, the denosumab group showed a significant decrease in mortality, particularly in cardiovascular disease-related cases (HR, 0.33 [95% CI, 0.14–0.78]). Conclusions: Denosumab may reduce all-cause mortality in patients undergoing hemodialysis, particularly in those with cardiovascular complications. This finding offers a promising direction for osteoporosis treatment in patients undergoing hemodialysis.