骨质疏松与血管钙化  

Osteoporosis and vascular calcification

作　　者：李蕊[1] 刘有军[1] 乔爱科[1] 杨海胜 LI Rui;LIU Youjun;QIAO Aike;YANG Haisheng(Department of Biomedical Engineering,Institute of Environment and Life,Beijing University of Technology,Beijing 100124,China)

机构地区：[1]北京工业大学环境与生命学部生物医学工程系,北京100124

出　　处：《中国骨质疏松杂志》2021年第11期1646-1650,共5页Chinese Journal of Osteoporosis

基　　金：国家自然科学基金(11702008);北京市自然科学基金(7202003);北京市教委科研计划(KM202010005035)。

摘　　要：骨质疏松症与血管钙化是严重威胁中老年人健康的两类重要疾病,通常认为它们与增龄相关且相互独立,但越来越多的临床和基础研究表明,二者密切联系,且可能拥有共同的危险因素,并受同样的通路、蛋白质和激素等的调控,包括RANKL-RANK-OPG通路、Wnt通路及甲状旁腺激素等。典型Wnt通路的抑制剂硬骨素不仅在骨重建中发挥着关键作用,在血管钙化中也扮演着重要角色。研究发现,血管钙化发生时,血管平滑肌细胞发生骨样细胞转分化并分泌硬骨素,但硬骨素在血管钙化中起到保护或损害作用仍存在争议。近期临床研究表明,靶向Wnt通路、用于治疗骨质疏松症的硬骨素抗体(罗莫单抗)具有促进骨形成和抑制骨吸收的双重作用,其治疗效果优于其他抗骨质疏松药物;但第三期临床试验发现,其会增加心血管疾病的患病风险,而其机制尚不清楚,有待深入研究。总之,研究骨质疏松和血管钙化之间关系及其共性机制,对避免某种特异性药物的不良反应、以及同时防治两种疾病有重要意义。Osteoporosis and vascular calcification are two important diseases threatening the health of middle-aged and elderly people.They have been generally considered to be independently related to aging.However,emerging clinical and basic studies have indicated that they are closely related and may share common risk factors.Also,they may be regulated by the same pathways,proteins,and hormones,including RANKL-RANK-OPG pathway,Wnt signaling pathway,and parathyroid hormone,etc.Sclerostin,a Wnt signaling pathway inhibitor,plays a key role not only in bone remodeling,but also in vascular calcification.Studies have found that,when vascular calcification occurs,vascular smooth muscle cells undergo osteoid cell trans-differentiation and secrete sclerostin.However,whether sclerostin is protective or detrimental in the calcification of blood vessels remains controversial.Recent clinical studies have shown that,a sclerostin antibody(romosozumab),which targets the Wnt pathway and is used to treat osteoporosis,has dual effects on promoting bone formation and inhibiting bone resorption.Its therapeutic effect is better than other anti-osteoporosis drugs.However,phase III clinical trials have shown that it can increase the risk of cardiovascular diseases.The underlying mechanism remains unclear and requires further research.In summary,investigating the relationship between osteoporosis and vascular calcification and their common mechanism is of great significance to avoid the side effects of a specific drug and to prevent and treat both diseases at the same time.

关 键 词：骨质疏松 血管钙化 WNT通路 硬骨素 罗莫单抗 

分 类 号：R681[医药卫生—骨科学] R543[医药卫生—外科学]