Costa Aline G, Bilezikian John P, Lewiecki E Michael
Columbia University, College of Physicians and Surgeons, Division of Endocrinology, Department of Medicine, Metabolic Bone Diseases Unit , 630 West 168th Street, NY 10032 , USA.
Expert Opin Biol Ther. 2014 May;14(5):697-707. doi: 10.1517/14712598.2014.895808. Epub 2014 Mar 25.
Disorders with inactivating mutations of the SOST gene result in reduced or absent expression of sclerostin and are associated with high bone mass. Sclerostin is an important regulator of bone formation due to its inhibitory actions in the osteoanabolic Wnt signaling pathway. Advances in understanding the mechanisms of action of this signaling molecule have led to the development of a pharmacological inhibitor of sclerostin with potential clinical applications as an osteoanabolic drug for the treatment of osteoporosis.
Romosozumab is the first humanized monoclonal sclerostin antibody to be tested in clinical trials. Similar to preclinical animal studies with sclerostin antibodies, initial clinical studies show that romosozumab increases bone formation and bone mineral density.
Blocking sclerostin action with romosozumab is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis; efficacy and safety data on large controlled studies are awaited.
伴有SOST基因失活突变的疾病会导致硬化素表达减少或缺失,并与高骨量相关。硬化素是骨形成的重要调节因子,因为它在骨合成代谢的Wnt信号通路中具有抑制作用。对这种信号分子作用机制认识的进展已促成了一种硬化素药理抑制剂的开发,该抑制剂作为一种用于治疗骨质疏松症的骨合成代谢药物具有潜在临床应用价值。
罗莫单抗是首个在临床试验中进行测试的人源化抗硬化素单克隆抗体。与抗硬化素抗体的临床前动物研究相似,初步临床研究表明罗莫单抗可增加骨形成和骨矿物质密度。
用罗莫单抗阻断硬化素作用是骨质疏松症骨合成代谢治疗中一种有前景的新治疗方法;有待大规模对照研究的疗效和安全性数据。