Denosumab vs oral bisphosphonates: Which is safer in patients receiving dialysis?

Among patients on dialysis, the use of denosumab reduced the risk for fractures by as much as 45 percent but increased the risk for major adverse cardiovascular events (MACE) by 36 percent when compared with oral bisphosphonates, a study has shown.

“The estimates, however, are imprecise and need to be confirmed in future studies,” the authors said.

This observational study attempted to emulate a target trial using data from a Japanese administrative claims database from April 2014 to October 2022. The authors identified 1,032 dialysis-dependent patients aged 50 years and above who initiated denosumab or oral bisphosphonates for osteoporosis. They assessed MACE as a safety outcome and a composite of all fractures as an effectiveness outcome.

Of the patients, 658 were denosumab users and 374 were oral bisphosphonate users (mean age 74.5 years, 62.9 percent women).

At 3 years, the weighted risk difference for MACE was 8.2 percent (95 percent confidence interval [CI], –0.2 to 16.7), with a weighted 3-year risk ratio of 1.36 (95 percent CI, 0.99–1.87). For composite fractures, the weighted 3-year risk difference was –5.3 percent (95 percent CI, –11.3 to –0.6), with a weighted risk ratio of 0.55 (95 percent CI, 0.28–0.93).

This study was limited by the lack of clinical data on kidney or osteoporosis disease severity and cardiovascular or other metabolic risk with residual confounding. In addition, kidney endpoints were not included in the safety outcomes.