骨硬化蛋白单克隆抗体治疗骨质疏松

Sclerostin monoclonal antibody in the treatment of osteoporosis

背景:骨硬化蛋白可负向调节骨代谢,其单克隆抗体可拮抗负向调节作用,在促进骨形成的同时抑制骨吸收。目的:旨在探讨骨硬化蛋白单克隆抗体在治疗骨质疏松中的作用机制及最新进展。方法:由第一作者应用计算机检索 PubMed、中国期刊全文数据库(CNKI)、维普数据库和万方数据库(2005年 5 月至 2013 年 5 月)相关文献。在标题、摘要、关键词中以"osteoporosis,antibody,sclerostin,Wnt,SOST"或"骨质疏松,单克隆抗体,骨硬化蛋白,Wnt 通路"为检索词进行检索。选择文章内容与骨硬化蛋白单克隆抗体有关者,同一领域文献则选择近期发表在权威杂志文章。结果与结论:初检得到 170 篇文献,根据纳入标准选择关于骨硬化蛋白单克隆抗体的 54 篇文献进行综述。骨硬化蛋白通过与 Wnt 经典信号通路共受体低密度脂蛋白受体相关蛋白 5/6 结合以阻断 Wnt 通路,从而抑制成骨细胞分化及矿化。其单克隆抗体通过与骨硬化蛋白特异性结合而间接促进骨形成、抑制骨吸收,在骨质疏松的治疗中有重大意义。同时,与其他治疗方法相比,骨硬化蛋白作用靶点的组织特异性及骨硬化蛋白单克隆抗体的结合特异性为其增加了应用优势。

BACKGROUND： Sclerostin can negatively regulate the bone metabolism, and the sclerostin monoclonal antibody can antagonize the negative regulation effect, inhibit bone resorption and promote bone formation. OBJECTIVE： To explore the mechanism and application progress of sclerestin monoclonal antibody in the treatment of osteoporosis. METHODS： An online search of PubMed database, CNKI database, VIP database and Wanfang database between May 2005 and May 2013 was performed by the first author to search the related articles with the key words of ＂osteoporesis, antibody, sclerostin, Wnt, SOST＂ in both English and Chinese. Articles related to sclerostin monoclonal antibody were included. For the articles in the same field, those published earlier or in the authorized journals were preferred. RESULTS AND CONCLUSION： A total of 170 articles were obtained after initial search, and finally 54 articles related to sclerostin monoclonal antibody were included for review according to the inclusion criteria. The sclerostin can block Wnt pathway through combining with low-density lipoprotein receptor-related protein 5/6, thus inhibiting the differentiation and mineralization of osteoblasts. By specifically binding to sclerostin, the sclerosin monoclonal antibody can indirectly promote bone formation and restrain bone absorption which has great significance in the treatment of osteoporosis. Meanwhile, compared with the other treatment method, the specific targeting of sclerostin and the binding specificity of sclerostin monoclonal antibody provide application advantaoes for the treatment of osteoDoresis.