Written by Babatunde Carew
Spoon Feed
In dialysis-dependent patients with osteoporosis, denosumab reduced fracture risk but showed a statistically insignificant increase in major adverse cardiac events compared to oral bisphosphonates.
Denosumab in dialysis – fracture fighter or heartbreaker?
Osteoporosis is common with a worldwide prevalence estimated at 19.7%, and chronic kidney disease (CKD) is a significant risk factor. In advanced CKD and dialysis patients, osteoporosis management is challenging due to altered bone turnover and poor renal clearance of typical first line agents, the bisphosphonates. This observational study evaluated cardiovascular safety and fracture prevention of denosumab versus oral bisphosphonates in dialysis-dependent osteoporosis patients. Using a Japanese claims database (2014–2022), 1,032 patients were analyzed. Denosumab increased major adverse cardiac events (MACE) risk (risk ratio 1.36, 95%CI 0.99–1.87) driven mostly by acute myocardial infarction (RR 3.50, 95%CI 1.44 to 21.4) while reducing composite fracture risk (RR 0.55, 95%CI 0.28–0.93). Limitations of the study include potential unmeasured confounding from factors like family history of MACE and missing data (serum calcium, eGFR, bone mineral density). Further, if denosumab was preferably prescribed to patients with more severe renal and mineral-bone disease, its cardiovascular risk may have been overestimated, while its fracture prevention effect may have been underestimated.
How does this change my practice?
This study does not change my current practice. Bisphosphonates are not recommended for dialysis patients in the U.S. and are not typically considered for this population. The increased MACE demonstrated with denosumab was not statistically significant, but the significant increase in acute myocardial infarction makes me pause. Prior studies have suggested it may even provide a cardioprotective effect in dialysis patients. More data outside of Japan is needed before changing treatment patterns regarding denosumab or bisphosphonates in this population.
Source
Cardiovascular Safety and Fracture Prevention Effectiveness of Denosumab Versus Oral Bisphosphonates in Patients Receiving Dialysis : A Target Trial Emulation. Ann Intern Med. 2025 Feb;178(2):167-176. doi: 10.7326/ANNALS-24-03237. Epub 2025 Jan 7. PMID: 39761590
