Denosumab initiation for osteoporosis may decrease fracture risk but increase risk of CV events in dialysis patients: Study

Researchers have found in a observational study that dialysis patients on denosumab (Prolia, Xgeva) had a lower risk for fracture but higher risk for a certain heart event. The study emulated a target trial to determine the risk for major adverse cardiovascular events (MACE) and fracture prevention effects with denosumab versus bisphosphonates in dialysis-dependent patients. The researchers estimated that denosumab lowers fracture risk by 45% but increases MACE risk by 36%. The researchers note that more studies are needed to confirm these findings. The study is published in Annals of Internal Medicine.

Researchers from Kyoto University studied data from 1,032 dialysis-dependent patients aged 50 and older identified by a Japanese administrative claims database as initiating either denosumab or oral bisphosphonates for osteoporosis. Since fracture morbidity in dialysis patients is high, the researchers aimed to provide evidence on optimal management strategies for osteoporosis.

The researchers used observational data from the database to emulate a target trial comparing the risk for MACE and the effectiveness in fracture prevention among dialysis-dependent patients taking denosumab vs bisphosphonates. Eligible patients for the study had to be at least 50 years old, undergoing dialysis, diagnosed with osteoporosis and newly initiated either denosumab or an oral bisphosphonate for osteoporosis management between April 2015 and October 2021. Of the 1,032 eligible patients identified, 658 were denosumab users and 374 were oral bisphosphonate users.

The primary safety outcome evaluated was MACE, including acute myocardial infarction, stroke, hospitalization for heart failure, or cardiovascular death, and the effectiveness outcome were all types of composite fractures. The researchers estimated that that the risk for fractures was 45% lower and the risk for MACE was 36% higher for denosumab compared with oral bisphosphonates. At a three-year follow up, the risk for MACE increased by 8.2%.

The findings are consistent across patient subgroups and raise concerns about treating dialysis-dependent patients with denosumab. Although the researchers note that their estimates need to be confirmed in future studies, the findings are consistent with a recent meta-analysis that found a 46% increase in cardiovascular adverse events with denosumab compared with bisphosphonates in postmenopausal women. The researchers hope that these results will inform future studies on the comparative effectiveness and safety of these medications in dialysis-dependent patients.

Reference:

Soichiro Masuda, Toshiki Fukasawa, Shuichi Matsuda, et al. Cardiovascular Safety and Fracture Prevention Effectiveness of Denosumab Versus Oral Bisphosphonates in Patients Receiving Dialysis: A Target Trial Emulation. Ann Intern Med. [Epub 7 January 2025]. doi:10.7326/ANNALS-24-03237