Lim Sian Yik, Bolster Marcy B
Straub Bone & Joint Center, Straub Medical Center, Honolulu, HI.
Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Drug Des Devel Ther. 2017 Apr 13;11:1221-1231. doi: 10.2147/DDDT.S127568. eCollection 2017.
Increased understanding of bone biology has led to the discovery of several unique signaling pathways that regulate bone formation and resorption. The Wnt signaling pathway plays a significant role in skeletal development, adult skeletal homeostasis, and bone remodeling. Sclerostin is an inhibitor of the Wnt signaling pathway. Romosozumab, a humanized monoclonal antibody that binds to sclerostin, prevents sclerostin from exerting this inhibitory effect. Therefore, in the presence of romosozumab, the Wnt signaling pathway is activated leading to bone formation and bone mineral density gain. Clinical studies of romosozumab have shown that this agent is one of the most potent bone anabolic agents in development to date. Romosozumab does not act solely as an anabolic agent, but rather, it has effects on increasing bone formation as well as reducing bone resorption. In the clinical studies, patients tolerated romosozumab well with no major safety signals reported. In a Phase III study, romosozumab as compared to placebo has been shown to reduce vertebral fractures by 73% after 1 year of treatment. Sequential therapy with romosozumab for 1 year followed by denosumab in the second year reduced vertebral fractures by 75% as compared to the group that received placebo for 1 year and denosumab in the second year. Romosozumab holds significant potential, by a novel mechanism of action, to expand our ability to treat osteoporosis. More studies are needed to determine the ideal setting in which romosozumab may be used to optimize osteoporosis treatment.
对骨生物学认识的不断加深，促使人们发现了多种调节骨形成和骨吸收的独特信号通路。Wnt信号通路在骨骼发育、成人骨骼稳态及骨重塑过程中发挥着重要作用。硬化蛋白是Wnt信号通路的一种抑制剂。罗莫单抗是一种与人硬化蛋白结合的人源化单克隆抗体，可阻止硬化蛋白发挥这种抑制作用。因此，在罗莫单抗存在的情况下，Wnt信号通路被激活，从而导致骨形成和骨矿物质密度增加。罗莫单抗的临床研究表明，该药物是目前正在研发的最有效的骨合成代谢药物之一。罗莫单抗并非单纯作为一种合成代谢药物起作用，相反，它具有增加骨形成以及减少骨吸收的作用。在临床研究中，患者对罗莫单抗耐受性良好，未报告重大安全信号。在一项III期研究中，与安慰剂相比，罗莫单抗治疗1年后可使椎体骨折减少73%。与第一年接受安慰剂治疗、第二年接受地诺单抗治疗的组相比，第一年使用罗莫单抗连续治疗1年、第二年使用地诺单抗治疗可使椎体骨折减少75%。罗莫单抗通过一种新的作用机制，具有显著的潜力来扩展我们治疗骨质疏松症的能力。需要更多研究来确定使用罗莫单抗优化骨质疏松症治疗的理想环境。
