Lim Sian Yik, Bolster Marcy B
Hawaii Pacific Health Medical Group, Honolulu, HI, USA.
Department of Family Medicine, John E Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
Int J Womens Health. 2022 Dec 15;14:1733-1747. doi: 10.2147/IJWH.S315184. eCollection 2022.
As one of the most potent osteoanabolic agents with a unique mechanism of action, romosozumab has high efficacy for osteoporosis treatment. It is a monoclonal antibody against sclerostin, a natural inhibitor of the Wnt signaling pathway, and by inhibiting sclerostin, activation of Wnt signaling occurs with a cascade of changes ultimately leading to bone mineral density (BMD) gains. Romosozumab stimulates bone modeling and has a dual effect of activating bone formation while inhibiting bone resorption. With this unique mechanism of action, treatment with romosozumab leads to a rapid and significant gain in BMD; these gains are higher than seen with bisphosphonates, denosumab, or parathyroid hormone (PTH) analogs. The FRAME and ARCH studies represent two pivotal trials demonstrating the efficacy of romosozumab in treating osteoporosis. Treatment with romosozumab should be followed by an antiresorptive agent, as this approach has demonstrated maintenance of or greater increases in BMD and reduced fracture risk even after finishing romosozumab treatment. As an osteoanabolic agent, romosozumab has shown superiority to alendronate in reducing fracture risk, increasing bone density, and potentially more rapid fracture risk reduction. Recent data have suggested that romosozumab prior to antiresorptive therapy may be the ideal treatment sequence, especially in high-risk patients and patients at imminent risk of fracture. Carrying a black box warning, romosozumab should be avoided in patients who have had myocardial infarction or stroke in the past year. Further studies are needed to clarify the increased cardiovascular risk attributed to this drug. Romosozumab has expanded our osteoporosis armamentarium and has enabled novel approaches, including "treat to target." Future studies are needed to evaluate the optimal use sequence and to assess its safety, especially in patients with cardiovascular risk factors.
作为作用机制独特的最强效骨合成代谢药物之一，罗莫单抗在骨质疏松症治疗方面具有高效性。它是一种针对硬化素的单克隆抗体，硬化素是Wnt信号通路的天然抑制剂，通过抑制硬化素，Wnt信号得以激活，并引发一系列变化，最终导致骨矿物质密度（BMD）增加。罗莫单抗刺激骨塑形，具有激活骨形成同时抑制骨吸收的双重作用。凭借这种独特的作用机制，罗莫单抗治疗可使BMD迅速显著增加；这些增加幅度高于双膦酸盐、地诺单抗或甲状旁腺激素（PTH）类似物。FRAME和ARCH研究是两项关键试验，证明了罗莫单抗治疗骨质疏松症的疗效。罗莫单抗治疗后应接着使用抗吸收药物，因为这种方法已证明即使在完成罗莫单抗治疗后，仍能维持或进一步增加BMD并降低骨折风险。作为一种骨合成代谢药物，罗莫单抗在降低骨折风险、增加骨密度以及可能更快速降低骨折风险方面已显示出优于阿仑膦酸钠的效果。近期数据表明，在抗吸收治疗之前使用罗莫单抗可能是理想的治疗顺序，尤其是在高危患者和即将发生骨折风险的患者中。罗莫单抗带有黑框警告，过去一年有心肌梗死或中风的患者应避免使用。需要进一步研究以阐明该药物导致心血管风险增加的原因。罗莫单抗扩展了我们治疗骨质疏松症的药物库，并开启了包括“靶向治疗”在内的新方法。需要未来的研究来评估最佳使用顺序并评估其安全性，尤其是在有心血管危险因素的患者中。
