Denosumab and Cardiovascular Risk in Dialysis Patients With Osteoporosis: A Retrospective Cohort Study

Background: Osteoporosis is common in dialysis patients, yet treatment options are limited due to safety concerns in advanced kidney disease. Denosumab, with non-renal clearance, has been increasingly used, but its cardiovascular safety remains uncertain. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, encompassing data from 139 health care organizations. Adults older than or equal to 50 years with osteoporosis and end-stage renal disease on dialysis treated with either denosumab or oral bisphosphonates were included. Propensity score matching (1:1) balanced demographics, comorbidities, medications, and laboratory variables. The primary outcome was major adverse cardiovascular events (MACE: myocardial infarction, stroke, and heart failure). Secondary outcomes included hypocalcemia, fractures, and all-cause mortality. Cox proportional hazards models estimated hazard ratios (HRs). Results: After matching, 2112 patients (1056 per group) were analyzed (mean age: 73.9 y, 63.1% female). Denosumab was associated with increased risk of MACE (32.3% vs. 24.1%; HR: 1.690, 95% CI: 1.301-2.194; p <0.001), acute myocardial infarction, heart failure, and hypocalcemia (HR: 2.247, 95% CI: 1.650-3.061; p <0.001). Fracture incidence and all-cause mortality were not significantly different between groups. Sensitivity analyses and subgroup evaluations confirmed the robustness of these findings. Conclusions: In dialysis-dependent patients with osteoporosis, denosumab may be associated with increased cardiovascular and electrolyte-related risks compared with bisphosphonates, without clear evidence of superior fracture protection. These findings highlight the need for careful risk-benefit assessment when prescribing denosumab and underscore the importance of future prospective studies to clarify its safety and efficacy in this high-risk population.