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

Abstract Background: Patients undergoing hemodialysis are at an elevated risk of fractures; however, substantial evidence on osteoporosis treatment in this population is lacking. We explored the efficacy of denosumab, an anti-IgG2 antibody, 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 mortality. Kaplan–Meier curves and log-rank tests were used to assess survival and fracture/mortality risks, respectively. A Cox proportional hazards model was used to analyze fractures and all-cause mortality. Results: Among 263 patients undergoing hemodialysis, 52 (19.8%) received denosumab. The median age was 71.7±12.1 years, with 93 (35.4%) females, and the median dialysis duration was 48 months (interquartile range, 4–114). During the study, 52 (22.8%) non-denosumab-treated patients had fractures compared to eight (3.0%) in the denosumab group. No significant differences were observed in the unadjusted model (HR, 0.51; 95% CI, 0.24–1.08). Adjusting for competing mortality and clinical factors, the HR remained at 0.51 (95% CI, 0.22–1.20). Regarding all-cause mortality, no significant differences were observed in the unadjusted model (HR, 0.68 [95% CI, 0.43–1.07]); however, a significant reduction in mortality was observed in the adjusted model (HR, 0.46 [95% CI, 0.26–0.81]). Notably, the denosumab group showed a significant decrease in mortality, particularly in cardiovascular disease-related cases (HR, 0.32 [95% CI, 0.14–0.75]). Conclusions: Denosumab may significantly 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.