Efficacy and Safety of Denosumab vs Zoledronic Acid in OI Adults: A Prospective, Open-Label, Randomized Study

Abstract

Objective To evaluate the efficacy and safety of denosumab and zoledronic acid in adult patients with OI. Design and methods This was a prospective, open-label study. Patients were randomized to receive denosumab 60 mg every 6 months or zoledronic acid 5 mg once for 12 months. Pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing. Percentage changes in the areal bone mineral density (aBMD), trabecular bone score (TBS) and bone turnover biomarkers (BTMs) from baseline to 6 and 12 months of treatment, as well as safety, were evaluated. Results A total of 51 OI adults (denosumab: 25, zoledronic acid: 26) were included, of whom 49 patients had identified pathogenic mutations. At 12 months, aBMD at the lumbar spine and total hip significantly increased by 4.34% (P = 0.005) and 1.45% (P = 0.023) in denosumab group and by 4.92% (P = 0.006) and 2.02% (P = 0.016) in zoledronic acid group, respectively. TBS showed an increasing trend by 1.39% and 2.70% in denosumab and zoledronic acid groups, respectively. Serum levels of β-CTX and ALP markedly decreased after denosumab treatment. Percentage changes in aBMD, TBS and BTMs during the treatment were similar between the two groups. OI patients with milder phenotypes showed a significantly higher increase in the TBS after 12 months of denosumab treatment than those with more severe phenotypes (P = 0.030). During the study period, denosumab group had fewer adverse events than the zoledronic acid group. Conclusion Denosumab effectively increases aBMD in OI adults, with similar efficacy to zoledronic acid. Long-term and large-sample studies are needed to confirm the anti-fracture efficacy and safety of denosumab in adult OI patients.