Cardiovascular Safety and Fracture Prevention Effectiveness of Denosumab Versus Oral Bisphosphonates in Patients Receiving Dialysis : A Target Trial Emulation.

Abstract

Dialysis patients have high rates of fracture morbidity, but evidence on optimal management strategies for osteoporosis is scarce. To determine the risk for cardiovascular events and fracture prevention effects with denosumab compared with oral bisphosphonates in dialysis-dependent patients. An observational study that attempts to emulate a target trial. A Japanese administrative claims database (April 2014 to October 2022). Adults aged 50 years or older who have initiated denosumab or oral bisphosphonates for osteoporosis in dialysis-dependent patients. The safety outcome was major adverse cardiac events (MACE). The effectiveness outcome was a composite of all fractures. Follow-up was 3 years. 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% to 16.7%), with a weighted 3-year risk ratio of 1.36 (CI, 0.99 to 1.87). The weighted 3-year risk difference for composite fractures was -5.3% (CI, -11.3% to -0.6%), and the weighted 3-year risk ratio was 0.55 (CI, 0.28 to 0.93). Lack of clinical data on kidney or osteoporosis disease severity and cardiovascular or other metabolic risk with residual confounding. Safety outcomes did not include kidney end points. It was estimated that, compared with oral bisphosphonates, denosumab lowered the risk for fractures by 45% and increased the risk for MACE by 36%. The estimates, however, are imprecise and need to be confirmed in future studies. None.