Denosumab versus zoledronic acid for osteoporosis treatment in patients with primary biliary cholangitis (the DELTA Study): A multicenter, non-inferiority randomized trial.

BACKGROUND: Osteoporosis is a common complication in patients with primary biliary cholangitis (PBC). This study aimed to compare the efficacy and safety of denosumab and zoledronic acid (ZOL) in treating osteoporosis in PBC patients. METHODS: This multicenter, randomized, open-label trial enrolled Japanese patients with PBC and osteoporosis. Patients were randomized to receive either subcutaneous denosumab 60 mg every 6 months (denosumab group) or i.v. zoledronic acid 5 mg yearly (ZOL group). The primary endpoint was the mean percent change in bone mineral density (BMD) at the lumbar spine and total hip from baseline to 12 months. RESULTS: Of 47 enrolled patients, 41 (87.2%) completed the study (denosumab: n=21; ZOL: n=20). At 12 months, lumbar spine BMD increased by 7.5% in the denosumab group and 6.4% in the ZOL group, demonstrating the non-inferiority of denosumab (95% CI: -1.6% to 3.8%). Although the total hip BMD increased more in the denosumab group than in the ZOL group (5.0% vs. 2.6%, p<0.01), the difference did not meet the predefined non-inferiority margin (95% CI: -1.3% to 6.2%). Serum ALP to upper limit of normal ratio and bone turnover markers significantly decreased in both groups; however, the rates of change were not significantly different between them. The incidence of adverse events was significantly lower in the denosumab group compared with the ZOL group (14.3% vs. 50.0%, p=0.013). CONCLUSIONS: Denosumab is a safe and effective treatment option for osteoporosis in patients with PBC.