Cardiovascular Outcomes Associated with Romosozumab Versus Denosumab in Chronic Kidney Disease

Background and Objective: Romosozumab carries a warning for potential severe cardiovascular events, while denosumab is widely used for osteoporosis but requires safety considerations in advanced chronic kidney disease (CKD). Given the limited direct real-world evidence comparing these treatments, in this study, we aimed to compare the cardiovascular and survival outcomes associated with romosozumab versus denosumab in adults with CKD. Materials and Methods: In this retrospective propensity score-matched cohort study, we utilized de-identified electronic health records from the TriNetX Global Collaborative Network, where eligible participants were adults aged 40 to 90 years with CKD who initiated either romosozumab or denosumab. Patients with bone/bone marrow malignancies or recent acute cardiovascular events were excluded. Following 1:1 propensity score matching based on demographics, diagnoses, medications, and laboratory characteristics, patients were followed for up to 1095 days. The primary outcome was a composite cardiovascular measure (all-cause mortality, acute myocardial infarction, or cerebrovascular event), while secondary outcomes included the individual components of the composite outcome and acute heart failure. Outcomes were evaluated using fixed-window cumulative risks, risk ratios (RRs), odds ratios, and hazard-ratio estimates. Results: After 1:1 propensity score matching, 1201 patients remained in each cohort; the mean age was 74.1 years in the romosozumab cohort and 74.2 years in the denosumab cohort, and 94.9% and 93.8%, respectively, were women. Romosozumab was associated with lower 1095-day cumulative risk of the composite cardiovascular outcome than denosumab (12.6% vs. 18.8%; RR, 0.668 [95% CI, 0.553-0.808]), as well as lower cumulative risk of cerebrovascular event (5.0% vs. 7.0%; RR, 0.714 [95% CI, 0.518-0.985]), all-cause mortality (6.6% vs. 9.5%; RR, 0.693 [95% CI, 0.526-0.913]), acute myocardial infarction (3.8% vs. 6.2%; RR, 0.613 [95% CI, 0.429-0.878]), and heart failure (2.7% vs. 6.1%; RR, 0.438 [95% CI, 0.292-0.659]). Conclusions: In this propensity score-matched EHR cohort of adults with CKD, cardiovascular and survival estimates associated with romosozumab versus denosumab varied by follow-up window and analytic approach. Although 1095-day fixed-window cumulative risks were lower in the romosozumab cohort, corresponding time-to-event estimates were neutral or directionally inconsistent. These findings should not be interpreted as evidence of cardioprotection or causal superiority but rather as showing no clear and consistent excess cardiovascular risk signal for romosozumab compared with denosumab.