Background: Dialysis patients have high rates of fracture morbidity, but evidence on optimal management strategies for osteoporosis is scarce. Objective: To determine the risk for cardiovascular events and fracture prevention effects with denosumab compared with oral bisphosphonates in dialysis-dependent patients. Design: An observational study that attempts to emulate a target trial. Setting: A Japanese administrative claims database (April 2014 to October 2022). Patients: Adults aged 50 years or older who have initiated denosumab or oral bisphosphonates for osteoporosis in dialysis-dependent patients. Measurements: The safety outcome was major adverse cardiac events (MACE). The effectiveness outcome was a composite of all fractures. Follow-up was 3 years. Results: A total of 1032 patients were identified (658 denosumab users and 374 oral bisphosphonate users). Overall average age was 74.5 years, and 62.9% were women. The weighted 3-year risk difference for MACE was 8.2% (95% CI, –0.2