Comparative Effectiveness and Cardiovascular Safety of Romosozumab versus Teriparatide in Osteoporosis Patients with CKD: Target Trial Emulation Study.

BACKGROUND: Osteoporosis commonly coexists with chronic kidney disease (CKD), increasing skeletal fragility and cardiovascular risk. While romosozumab shows superior fracture prevention in general osteoporosis, evidence in chronic kidney disease stages 3-5 patients remains limited. METHODS: Using a target trial emulation design, we conducted a retrospective cohort study leveraging the TriNetX U.S. research network. Patients aged ≥40 years with osteoporosis and an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 were included. After 1:1 propensity score matching (PSM), outcomes were assessed using Cox proportional hazards models. The primary effectiveness outcomes were non-vertebral and vertebral fractures within 12 months. The secondary outcome was hip fractures. Safety outcomes included MACE, myocardial infarction (MI), stroke, and all-cause mortality. RESULTS: After PSM, 2,045 patients were included in each group. Romosozumab was associated with a significantly lower risk of vertebral fractures compared with teriparatide (HR, 0.64; 95% CI, 0.42-0.98), whereas no significant differences were observed for non-vertebral or hip fractures. In terms of cardiovascular safety, romosozumab was linked to a reduced risk of MACE (HR, 0.82; 95% CI, 0.70-0.97) and MI (HR, 0.77; 95% CI, 0.63-0.95). These findings were generally consistent across most subgroups and sensitivity analyses. CONCLUSION: In patients with osteoporosis and CKD, romosozumab was more effective than teriparatide in reducing vertebral fracture risk and was associated with a lower incidence of major cardiovascular events. These findings support the potential dual benefits of romosozumab in this high-risk population and highlight the need for further prospective studies, particularly in those with advanced CKD.