硬骨抑素单克隆抗体治疗骨代谢相关疾病研究进展  

Advances in the treatment of bone metabolism-related diseases with monoclonal antibodies to sclerostin

作　　者：哈达 马涛 何海溶 梁枭 胡海洋 王金鹏 吴锦秋[2] HA Da;MA Tao;HE Hairong;LIANG Xiao;HU Haiyang;WANG Jinpeng;WU Jinqiu(Clinical School of Traditional Chinese Medicine,Gansu University of Traditional Chinese Medicine,Lanzhou 730030,China;Gansu Hospital of Traditional Chinese Medicine,Lanzhou 730050,China)

机构地区：[1]甘肃中医药大学中医临床学院,甘肃兰州730030 [2]甘肃省中医院,甘肃兰州730050

出　　处：《中国骨质疏松杂志》2025年第2期267-271,共5页Chinese Journal of Osteoporosis

基　　金：兰州市科技计划项目(2022-3-32)。

摘　　要：骨代谢紊乱可能引发骨代谢相关疾病,导致局部或全身骨病变,如骨质疏松症、囊性纤维化病和肌少症等。硬骨抑素作为一种抑制剂,可抑制Wntβ-catenin信号通路中的骨分化、骨生长效果。当Wnt蛋白失活后,硬骨抑素会与低密度脂蛋白LPR5/6蛋白相结合,并产生一系列反应,导致成骨细胞减少、破骨细胞增加,成为引发骨代谢疾病的诱因之一,在调节骨转换过程中起到负向作用。研究发现,硬骨抑素单克隆抗体在美国已被视为一种新型药物,在防治骨代谢疾病中取得一定进展。通过促进骨形成、抑制骨吸收,以及拮抗硬骨抑素对骨代谢的负向调节作用,取得较好的疗效。然而,硬骨抑素单克隆抗体在我国仍处于临床Ⅲ期试验阶段,心脑血管疾病患者应用此药物存在部分风险,故尚未广泛应用于临床治疗。笔者主要通过作用机制和信号通路研究,探讨硬骨抑素单抗如何发挥作用,并阐述其在临床上的适用范围和注意事项,旨在为临床防治骨代谢相关疾病提供新思路。Disorders of bone metabolism may lead to bone metabolism-related diseases,leading to local or systemic bone diseases,such as osteoporosis,cystic fibrosis,and sarcopenia.Osteostatin,as an inhibitor,inhibits bone differentiation and bone growth through Wntβ-catenin signaling pathway.When Wnt protein is inactivated,osteostatin may combine with low density lipoprotein LPR5/6 protein,and produce a series of reactions,resulting in the reduction of osteoblasts and the increase of osteoclasts,becoming one of the inducement of bone metabolic diseases,and playing a negative role in regulating the process of bone turnover.Studies have found that sclerostatin monoclonal antibody has been regarded as a new drug in the United States.It has made certain progress in the prevention and treatment of bone metabolic diseases.By promoting bone formation,inhibiting bone resorption,and antagonizing the negative regulating effect of sclerotic statin on bone metabolism,good curative effect is obtained.However,sclerostatin monoclonal antibody is still in the phase III clinical trial stage in China,and the application of this drug in cardiovascular and cerebrovascular patients has some risks.Therefore,it has not been widely used in clinical treatment.In this paper,through studying the mechanism of action and signaling pathway,we discuss how sclerostin plays its role,and expound its clinical application scope and precautions,aiming to provide new ideas for clinical prevention and treatment of bone metabolism related diseases.

关 键 词：硬骨抑素 骨代谢 骨形成 骨吸收 洛莫索珠单抗 

分 类 号：R589.5[医药卫生—内分泌]