The efficacy and safety of romosozumab sequential therapy in postmenopausal women: A systematic review and meta-analysis.

Abstract

Recent guidelines increasingly recognize the importance of sequential therapy in osteoporosis management. However, optimal protocols involving the anabolic agent romosozumab require further elucidation. While previous meta-analyses support the use of osteoanabolic sequential therapy, uncertainties remain regarding the specific application of romosozumab in such regimens. This meta-analysis aims to provide detailed evidence on the efficacy and safety of romosozumab sequential therapy, specifically focusing on fracture prevention and bone mineral density (BMD) improvement in postmenopausal women with osteoporosis. A systematic literature search of PubMed, Embase, and Web of Science was conducted from January 2014 to December 2024. Two authors independently extracted data and assessed bias, with disagreements resolved by a third. Effect sizes were pooled using fixed- and random-effects models. The primary outcome was fracture incidence; secondary outcomes included BMD changes and adverse event rates. Twelve randomized controlled trials were included. Sequential treatment with romosozumab followed by anti-resorptive agents (e.g., denosumab, alendronate) significantly reduced fracture incidence and increased BMD at the lumbar spine, total hip, and femoral neck compared to non-sequential therapy. Romosozumab sequential therapy may reduce fracture risk and improve BMD in postmenopausal women with osteoporosis, without a significant increase in short-term adverse events. However, evidence regarding new vertebral fractures and certain BMD outcomes remains limited in robustness, warranting further validation through high-quality, long-term studies.