Romosozumab increases bone mineral density in postmenopausal Chinese women with osteoporosis: A randomised phase three study.

Background: Osteoporosis, most commonly affecting postmenopausal women, imposes a high medical and financial burden in China, highlighting the need for more effective treatments. This phase three, multicentre, randomised, double-blind, placebo-controlled study, conducted across 31 centres in mainland China, aimed to assess the efficacy, safety, and pharmacokinetic and pharmacodynamic profiles of romosozumab in Chinese women with postmenopausal osteoporosis at high risk of fracture (NCT05067335). Methods: Three hundred and twenty-seven patients were randomised 2:1 to romosozumab 210 mg (n = 218) or matched placebo (n = 109) for 6 months, followed by open-label romosozumab for 6 months in all patients. The Primary endpoint was the percentage change from baseline in bone mineral density (BMD) of the lumbar spine after 6 months of romosozumab treatment. Results: Baseline patient characteristics were well balanced. By month 6, the least-square mean (LSM [95% CI]) percentage change from baseline in BMD of the lumbar spine was significantly higher with romosozumab (9.81% [9.18%, 10.45%]) versus placebo (0.44% [-0.42%, 1.31%]), with a between-group difference of 9.37% (8.34%, 10.39%; p < 0.001). Significant improvements were also observed at the total hip (2.93% [2.53%, 3.33%] vs 0.07% [-0.49%, 0.63%]; difference: 2.86% [2.18%, 3.54%; p < 0.001]) and femoral neck (3.33% [2.65%, 4.01%] vs -0.15% [-0.94%, 0.65%]; difference: 3.48% [2.58%, 4.38%; p < 0.001]). In patients initially randomised to romosozumab, BMD continued to increase at all sites through month 12. With romosozumab, an initial large increase from baseline in the bone-forming marker procollagen type 1 N-telopeptide (P1NP) was observed, whilst the bone resorption marker serum type I collagen C-telopeptide (sCTX) decreased, demonstrating dual effects on bone formation and resorption. Romosozumab was well tolerated, with low incidence of serious and severe treatment-emergent adverse events (TEAEs), and few TEAEs leading to treatment or study discontinuation. Conclusion: These findings demonstrate the efficacy and safety of romosozumab for the treatment of osteoporosis in Chinese women with postmenopausal osteoporosis. The Translational Potential of this Article: In this phase three, multicentre, randomised, double-blind, placebo-controlled study, romosozumab treatment was effective and well tolerated in Chinese women with postmenopausal osteoporosis, being broadly consistent with findings observed outside of China. These results provide robust evidence to support the use of romosozumab in Chinese women with postmenopausal osteoporosis.