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Bone and Mineral Metabolism

MON-826 - Comparative Safety and Efficacy of Romosozumab Combinations Versus Bisphosphonates in Women with Osteoporosis: A Systematic Review and Meta-Analysis

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Victoria Robinson, M.S.: No financial relationships to disclose
Objective
To evaluate the comparative efficacy and safety of romosozumab versus bisphosphonates in postmenopausal women with osteoporosis.

Introduction
Romosozumab is a monoclonal antibody that inhibits sclerostin, promoting osteoblast-driven bone formation, suppressing osteoclast activity, and leading to net gains in bone mass. Bisphosphonates are antiresorptive agents that bind to bone minerals and selectively inhibit osteoclast activity, reducing bone resorption and maintaining existing bone structures. These therapies reduce bone loss associated with postmenopausal estrogen deficiency, yet optimal initial treatment selection remains uncertain. We conducted a systematic review and meta-analysis to assess whether initiating therapy with an anabolic agent provides greater clinical benefit than antiresorptive therapy in postmenopausal women at high risk of fracture.

Methods
A comprehensive literature search across PubMed, the Cochrane Library, and Google Scholar identified 2,450 records; after duplicate removal and screening, 9 comparative studies were included. Search strategy incorporated MeSH terms including “romosozumab”, “bisphosphonates”, “postmenopausal osteoporosis”. Data synthesis was performed using Review Manager (RevMan) using a random-effects model, with results reported as risk ratios. Quality assessment was performed using the Cochrane Risk of Bias 2 tool for randomized trials and the Newcastle–Ottawa Scale for observational studies, and reporting was conducted in accordance with the PRISMA guidelines.

Results
The primary outcomes evaluated were Bone Mineral Density at the Lumbar Spine (LS), Trabecular Bone Score Tissue Thickness (TBSTT), and the incidence of vertebral fractures. Subgroup analyses evaluating the follow-up duration (12, 24, and 36 months) showed a significantly higher likelihood of lumbar spine BMD improvement with romosozumab compared with bisphosphonates (RR = 1.79, 95% CI 1.42–2.26; I² = 28%; P < 0.00001). The pooled analysis demonstrated a significantly improved TBSTT, a marker of bone microarchitecture, with romosozumab compared with bisphosphonates (RR = 2.45, 95% CI 1.33–4.49; I² = 0%; P = 0.004), and subgroup analyses evaluated the safety and efficacy of both drugs across a 12-, 24-, and 36-month follow-up period. There was a significantly reduced incidence of Vertebral Fractures in the Romosuzumab group compared to the bisphosphonates group (RR = 0.46, 95% CI 0.25–0.83; I² = 0%; P = 0.01). Secondary outcomes, including adverse cardiovascular events, non-vertebral fractures, and BMD at the femoral neck and hip, demonstrated no significant differences between the two pharmacotherapies.

Conclusion
Romosozumab demonstrated a significantly superior therapeutic response to bisphosphonates, with reduced vertebral fractures and improved LS BMD and TBSTT, in postmenopausal women with osteoporosis.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*