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.