骨重建失衡导致骨质疏松发生的作用机制及其药物治疗策略

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、WebofScience、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。

Action mechanism of bone remodeling imbalance in osteoporosis and relevant medical treatment strategy

BACKGROUND: Currently, bone remodeling imbalance is considered as a core reason leading to osteoporosis. An effective early intervention is performed to regulate bone remodeling imbalance at initial stage that can reverse osteoporosis and improve prognosis to some extent. Antiresorptive and anabolic agents are two types of anti-osteoporosis drugs addressing bone remodeling imbalance. Therefore, investigating the mechanism of bone remodeling imbalance is essential to guide medical treatment in osteoporosis. 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.