Lower fracture, higher cardiovascular risks seen with denosumab for patients on dialysis
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Key takeaways:
- Compared with oral bisphosphonate use, denosumab use was associated with a 45% lower risk for fractures among patients on dialysis.
- Cardiovascular risk was 36% higher with denosumab.
Among adults with osteoporosis on dialysis, use of denosumab significantly lowered fracture risk compared with bisphosphonate use, but cardiovascular risk was increased, according to study data.
“Some clinicians might be surprised by the potential association between denosumab use and an increased risk of major adverse cardiac events (MACE) in this population, especially given the focus on fracture prevention in dialysis patients. Additionally, the magnitude of the potential benefit of denosumab in reducing fractures — 45% relative risk reduction — is also surprising,” Soichiro Masuda, MD, PhD, physician in chief, in the department of orthopedic surgery at Kyoto City Hospital and visiting researcher in the department of pharmacoepidemiology at Kyoto University Graduate School of Medicine and Public Health, Japan, told Healio.
Masuda and colleagues sought to compare the effectiveness and safety of denosumab (Prolia, Amgen) with oral bisphosphonates for patients on dialysis. They used observational data from a Japanese commercial administrative claims database to emulate a target trial. Patients included in the study were aged 50 years or older (average age, 74.5 years), dependent on dialysis and were first prescribed denosumab (n = 658) or oral bisphosphonates (n = 374) to treat osteoporosis from April 2014 to October 2022. Safety outcomes were major adverse cardiac events (MACE; acute myocardial infarction, stroke, hospitalization for heart failure or CV death) as a composite and individually, and efficacy outcomes were a composite of all fractures and hip, vertebral and nonvertebral fractures individually. Patients were followed for 3 years.
During follow-up, 16.1% of denosumab users and 13.9% of oral bisphosphonate users switched to other osteoporosis drugs. Mean duration of use was 523 days for denosumab and 562 days for bisphosphonates; 158 denosumab users and 58 bisphosphonate users died, and no patients received a kidney transplant.
The 3-year risk for MACE was 34.6% (95% CI, 29.8%-40.1%) for denosumab users and 21% (95% CI, 15.9%-26.5%) for bisphosphonate users, for a 36% higher risk for MACE among denosumab vs. bisphosphonate users (weighted risk ratio = 1.36 [95% CI, 0.99-1.87]), although researchers noted the wide confidence interval.
The 3-year risk for fractures was 5.7% (95% CI, 3.7%-8%) for denosumab users and 11.7% (95% CI, 7.8%-16.5%) for bisphosphonate users, for a 45% lower fracture risk for denosumab vs. bisphosphonate users (weighted RR = 0.55 [95% CI, 0.28-0.93]).
“The potential trade-off between fracture prevention and cardiovascular risk highlighted in this study suggests that clinicians should carefully consider individual patient profiles when choosing between denosumab and oral bisphosphonates for osteoporosis management in dialysis patients. A patient-centered approach weighing the relative importance of fracture risk versus cardiovascular risk is crucial,” Masuda said.
“Although randomized controlled trials are needed to confirm these findings, conducting large trials in dialysis patients is almost impossible. Thus, future large-scale prospective studies with clinical data, such as glomerular filtration rate, are needed to confirm our findings,” he said.
For more information:
Soichiro Masuda, MD, PhD, can be reached at smasuda0306@gmail.com.
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