骨重建失衡导致骨质疏松发生的作用机制及其药

背景：目前骨重建失衡被认为是造成骨质疏松的关键因素，如在骨质疏松发生过程中干预重建失衡，则可一定程度逆转骨质疏松状态并改善预后。破骨抑制和成骨诱导性药物则是针对此致病机制的靶点药物。因此综述性回顾骨质疏松的骨重建失衡机制对于骨质疏松药物治疗具有指导意义，破骨抑制和成骨诱导性药物的临床应用现状和治疗效果也急需进行系统性总结，以起到临床用药指导的作用。

目的：综述骨质疏松的骨重建失衡发生机制，并总结破骨抑制药物和成骨诱导药物针对骨重建失衡的调节作用机制，对比2 种药物的临床作用效果，为骨质疏松的药物治疗选择进行指导。

方法：检索PubMed、Web of Science、中国知网数据库建库至2020年2月发表的相关文献，英文检索词为“osteoporosis，bone remodeling，antiresorptive，anabolic，bisphosphonate，RANKL inhibitor，PTH analogue，anti-sclerostin antibody”，中文检索词为“骨质疏松，骨重建，破骨抑制，成骨诱导，双膦酸盐，RANKL 抑制剂，甲状旁腺素类似物，抗硬化素抗体”。共检索到相关文献144 篇，按照纳入与排除标准，最终纳入84 篇文献进行总结。

结果与结论：①骨质破坏发生后，可引起机体发生骨重塑，而骨重塑则会导致可逆性非可逆性两种类型的骨缺失发生；②可逆性骨缺失约历时3 个月，依次经历骨吸收、骨重填和新骨矿化过程，修复后的骨量和骨质均优；③而不可逆性骨缺失则存在破骨-成骨失衡，虽然也有一定的新骨形成，但新生的骨质较差，易再次发生骨结构破坏；④双膦酸盐、RANKL 抑制性抗体属于破骨抑制药物，其作用机制为减慢骨重建速率以减少逆转期骨吸收量，但新生骨量和质量也会相应减少；⑤而特里帕肽、甲状旁腺素类似物等成骨诱导类药物则利于缺损骨质修复，完善破坏的哈弗氏管系统结构，使得新生骨质获得优良的力学强度。

BACKGROUND:Currently,bone remodeling imbalance is considered as a core reason leading to effective early intervention is performed to regulate bone remodeling imbalance at initial stage that can reverse osteoporosis and improve prognosis to some and anabolic agents are two types of anti-osteoporosis drugs addressing bone remodeling ,investigating the mechanism of bone remodeling imbalance is essential to guide medical treatment in addition,clinical application and therapeutic effect between antiresorptive and anabolic agents urgently need to be systematically summarized and may serve as a guide for clinical medication.

OBJECTIVE:To review mechanism of bone remodeling imbalance in osteoporosis,summarize action mechanism of antiresorptive and anabolic agents in regulating bone remodeling imbalance,and compare their clinical effects so as to give clinical medical guidance.

METHODS:Related articles were searched in PubMed databases,Web of Science and CNKI from inception to February 2020.The key words were “osteoporosis,bone remodeling,antiresorptive,anabolic,bisphosphonate,RANKL inhibitor,PTH analogue,anti-sclerostin antibody” in English and ,144 articles were searched,and according to the inclusion and exclusion criteria,84 eligible articles were included in final analysis.

RESULTS AND CONCLUSION:(1) Bone remodeling is activated by bone and irreversible deficits are two bone reforming types followed by remodeling.(2) The reversible one goes through bone resorption,bone refilling and secondary mineralization process for 3 months and new forming bone exhibits high mechanical strength.(3) The irreversible deficit occurred after bone remodeling imbalance that bone forming rate is much lower than resorption there is certain amount of new forming bone generated in breaking area but the bone quality is unsatisfied,which tends to break again.(4) Bisphosphonates and RANKL inhibitors belong to antiresorptive agents,and are capable to reduce bone resorption,but bone forming mass is also decreased accordingly.(5) In addition,anabolic agents including PTH analogues and anti-sclerostin antibodies are benefit for reconstructing damaged bone structure,especially haversian canal,and significantly promote bone quality and mechanical property as well.

0 引言 Introduction

随着人群寿命的不断增加，骨质疏松的发病率、致死率和治疗花费也逐年提升[1]。年龄和性别为导致骨质疏松发生的最明确直观因素，年龄超过50岁或女性绝经期后，由于骨重塑异常，导致了骨量锐减、矿化异常及微观下骨结构的破坏，致使外界微小的受力损伤、甚至无外伤发生也可导致骨折[2-3]。

为从根源解决这一问题，需在骨折发生前即对骨质疏松开展防治工作，故理解骨质疏松的发生机制至关重要。骨重建失衡学说是目前被广泛接受的骨质疏松发病理论[4]，其认为骨质疏松时骨形成-吸收平衡被打破，骨吸收大于骨形成，而导致骨质吸收及强度下降。而破骨抑制类和成骨诱导类药物则是据此机制进行的正反两条药物干预途径[5-6]。

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