Denosumab for osteoporosis reduced fracture risk by 45% but raised the risk of major adverse cardiovascular events by 36% in dialysis-dependent patients, prompting calls for further research.
Summary:
An observational study emulating a target trial found that denosumab reduces fracture risk by 45% but increases the risk of major adverse cardiovascular events (MACE) by 36% in dialysis-dependent patients with osteoporosis. Conducted using a Japanese claims database, the study compared denosumab and oral bisphosphonates in 1,032 patients aged 50 and older. While denosumab was effective at preventing fractures, its associated cardiovascular risks align with findings from prior research, underscoring the need for further studies to guide treatment decisions in this population.
Key Takeaways:
- Risk-Benefit Tradeoff with Denosumab: In dialysis-dependent patients, denosumab reduced fracture risk by 45% but increased the risk of MACE, including heart attacks and strokes, by 36%.
- Comparison with Bisphosphonates: The study highlights denosumab’s fracture prevention effectiveness compared to oral bisphosphonates but raises concerns about its cardiovascular safety profile.
- Implications for Clinical Practice: These findings align with prior research on denosumab’s cardiovascular risks and call for more targeted studies to optimize osteoporosis management in high-risk dialysis patients.
An observational 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.
Study Findings
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 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.
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