Abstract: Safety and Efficacy of Romosozumab vs Bisphosphonates in Women with Osteoporosis: A Systematic Review and Meta-Analysis

Objective To assess the comparative safety and effectiveness of romosozumab versus bisphosphonate therapy in postmenopausal women with osteoporosis.

Postmenopausal osteoporosis results from estrogen deficiency, causing increased bone resorption and decreased formation. Romosozumab promotes bone formation while reducing resorption, unlike bisphosphonates, which primarily inhibit osteoclast-mediated bone loss. Due to these mechanistic differences, the optimal first-line treatment for high-fracture-risk patients remains uncertain. This analysis assessed whether romosozumab provides advantages over bisphosphonates.

Methods A systematic search of Embase, Cochrane Library, PubMed, and Google Scholar identified relevant studies. From 2,450 screened records, nine met inclusion criteria. Data were analyzed in RevMan using a random-effects model, with outcomes as risk ratios (RR) and 95% confidence intervals (CI). Risk of bias was evaluated using RoB 2 for randomized studies and the Newcastle-Ottawa Scale for observational studies. Reporting adhered to PRISMA guidelines.

Results Primary outcomes included bone mineral density (BMD), lumbar spine (LS), trabecular bone score tissue thickness (TBSTT), and vertebral fracture incidence. Subgroup analyses by follow-up duration (12, 24, and 36 months) showed significantly greater LS BMD improvement with romosozumab(CI 1.42–2.26; ; RR = 1.79, 95% I² = 28%; P < 0.00001). Romosozumab also yielded superior TBSTT (CI 1.33–4.49; RR = 2.45; 95% I² = 0%; P = 0.004). Vertebral fracture incidence was significantly lower with romosozumab (RR = 0.46, 95% CI 0.25–0.83; I² = 0%; P = 0.01). Secondary outcomes adverse cardiovascular events, non-vertebral fractures, femoral neck BMD, and hip BMD showed no significant differences between treatments.

Conclusion Romosozumab demonstrates superior efficacy over bisphosphonates in postmenopausal osteoporosis, with greater reductions in vertebral fractures and improvements in LS BMD and TBSTT.