Background: The comparison of the efficacy of zoledronate and denosumab for treating osteoporosis is controversial, and few randomized controlled trials have compared these two drugs in practical patients with acute osteoporotic vertebral compression fractures (OVCFs). We conducted a randomized controlled study to compare the efficacy of zoledronate and denosumab in patients with acute OVCF, with a focus on the occurrence of new OVCF. Methods: We enrolled 206 subjects who had their first acute OVCF, without any previous history of osteoporosis medication. The patients were randomly assigned to receive either intravenous zoledronate once a year or subcutaneous denosumab twice a year. We investigated the OVCF recurrence, clinical outcome, bone mineral density (BMD), and bone turnover markers over 12 months. Results: The final cohort comprised 89 participants (mean age of 75.82 ± 9.34 years, including 74 women [83.15%]) in the zoledronate group and 86 patients (mean age of 75.53 ± 10.23 years, including 71 women [82.56%]) in the denosumab group. New OVCFs occurred in 8 patients (8.89%) in the zoledronate group and 11 patients (12.79%) in the denosumab group (odds ratio, 1.485 [95% confidence interval, 0.567-3.891], p = 0.419). No significant difference was observed in the survival analysis between the two groups (p = 0.407). The clinical outcome, including the visual analog scale score for pain and simple radiographic findings, did not differ between the two groups. The changes in BMD and bone turnover markers were also not significantly different between the two groups. Additionally, drug-related adverse events did not differ between the groups in terms of safety. Conclusions: The efficacy of zoledronate was comparable to that of denosumab in terms of the occurrence of new OVCFs, as well as of the overall clinical course in patients with their first acute OVCF. Notably, this study represents the first comparison of these two drugs in patients with acute OVCF. However, further research with large-scale and long-term follow-up is necessary.
Keywords: compression fracture; denosumab; osteoporosis; treatment outcome; zoledronate.