Efficacy and safety of romozumab in the treatment of osteoporosis in adults: a meta-analysis

Abstract

OBJECTIVE: Romosozumab is a novel biologic agent currently being used to treat osteoporosis in postmenopausal women at high risk of fracture. This meta-analysis aims to systematically evaluate the efficacy and safety of romosozumab compared with placebo, alendronate sodium, teriparatide, and denosumab in the treatment of osteoporosis in adults. METHODS: The medical keywords “anti-sclerostin antibody,” “romosozumab,” “AMG 78500,” and “osteoporosis” were used to search PubMed, CNKI, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials comparing the safety and efficacy of romosozumab with alendronate, teriparatide, denosumab, or placebo in adult patients with osteoporosis. Two researchers independently screened studies, assessed risk of bias, and extracted data. The Cochrane Collaboration's risk of bias tool was used for quality assessment, and meta-analysis was performed using RevMan 5.4. The primary outcome was the percentage change from baseline in bone mineral density (BMD) at 6 and 12 months; secondary outcomes were the incidence of adverse events and cardiovascular complications during treatment. RESULTS: A total of 10 randomized controlled trials involving 12,570 patients were included. Compared with placebo, alendronate, and teriparatide, romosozumab significantly increased BMD at the lumbar spine, total hip, and femoral neck at 6 and 12 months. Compared with denosumab, romosozumab significantly increased lumbar spine BMD at 6 and 12 months (MD=3.68, 95%CI: 0.34-7.01, P=0.03; MD=5.20, 95%CI: 3.19-7.21, P<0.00001), while no significant differences were found in total hip and femoral neck BMD. In terms of safety, romosozumab had a lower incidence of adverse events compared with alendronate (RR=0.96, 95%CI: 0.93-0.99, P=0.02) but a higher incidence compared with teriparatide (RR=1.13, 95%CI: 1.01-1.25, P=0.03). No significant differences were found versus placebo or denosumab (RR=0.98, 95%CI: 0.96-1.00, P=0.11; RR=2.64, 95%CI: 0.74-9.36, P=0.13). Importantly, romosozumab did not significantly increase the risk of cardiovascular complications compared with other treatments (RR=1.25, 95%CI: 0.94-1.67, P=0.12). CONCLUSION: Romosozumab rapidly improves lumbar spine BMD with an overall manageable safety profile, particularly suitable for adult osteoporosis patients at high fracture risk who require rapid bone mass increase and have no cardiovascular contraindications. This meta-analysis is based on limited data and has certain limitations; more high-quality, longer-duration follow-up studies are needed to confirm the results.

1. Introduction

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to increased bone fragility and fracture risk. It commonly occurs in the elderly, especially postmenopausal women [1-2]. Treatment strategies primarily aim to either reduce bone resorption or increase bone formation. Most available drugs are antiresorptive, such as bisphosphonates, calcitonin, estrogen and its analogs, and denosumab, while teriparatide, a parathyroid hormone analog, is the main anabolic agent [3]. Unfortunately, no drug has a dual effect on bone, and all have limitations and adverse events.

The core pathology of osteoporosis lies in the uncoupling of bone resorption and formation, with relative insufficiency of bone formation [4]. Sclerostin, secreted by osteocytes, antagonizes Wnt signaling by competitively binding to LRP5/6, thereby reducing osteoblastic activity and contributing to bone loss [5]. Therefore, sclerostin monoclonal antibodies have been developed to neutralize sclerostin, restore Wnt signaling, and promote bone formation [6]. Among these, romosozumab, a humanized anti-sclerostin antibody, has emerged as a promising therapeutic agent due to its dual mechanism of action—stimulating bone formation and inhibiting bone resorption—and has been approved for the treatment of postmenopausal osteoporosis since 2019 [7].