绝经后骨质疏松症患者胰岛素样生长因子1与相关骨代谢指标的关系

Correlation of insulin-like growth factor-1 and bone metabolism-related indexes in postmenopausal osteoporosis

背景:大量研究结果显示,胰岛素样生长因子1对骨代谢具有重要的调节作用,可增加骨形成,刺激成骨细胞的数量和活性,限制和减少骨吸收的破骨细胞的分化,目前胰岛素样生长因子1机制研究已进入火热阶段。目的:综述近年来关于绝经后骨质疏松症胰岛素样生长因子1与相关骨代谢指标的研究进展。方法:由第一作者检索2012年1月至2016年7月PubMed数据(http://www.ncbi.nlm.nih.gov/PubMed)及CNKI中国期刊全文数据库(http://www.cnki.net/),以"postmenopausal osteoporosis,insulin-like growth factor,bone metabolism,biochemical markers"为英文检索词;"绝经后骨质疏松症,胰岛素样生长因子1,骨代谢,骨转换指标"为中文检索词,检索摘要内同时包含上述检索词的文献。排除重复性研究,最终纳入36篇文献进行综述。结果与结论:(1)女性绝经后通过各种细胞因子作用调控而使得骨吸收增加,其中胰岛素样生长因子1在血液中结合胰岛素样生长因子结合蛋白3,使得生长激素发挥其生物作用;另外,血液中生长激素对脂肪组织、肌肉组织以及骨组织产生直接作用;(2)在骨组织中,生长激素对骨组织有直接的影响,同时通过胰岛素样生长因子1介导间接效应,使成骨细胞成熟与分化,加强骨胶原及非胶原蛋白的表达,从而促进骨质形成;(3)骨代谢的过程往往能反映成骨细胞和破骨细胞的活动及骨基质和骨矿化的变化,关于骨代谢标志物与胰岛素样生长因子体外实验中,胰岛素样生长因子1不仅可呈剂量依赖性刺激成骨细胞前体的增殖并向成骨细胞进行分化,促进碱性磷酸酶、Ⅰ型胶原以及骨钙素等成骨标志物的表达,并且还可刺激破骨细胞的活性和数目的增加;(4)但目前开展的相关临床研究较少,观测指标较少,缺少对于骨质疏松检测与治疗的参考范围等,这些都需要进一步研究探索。

BACKGROUND:Increasing evidence has shown that insulin-like growth factor-1(IGF-1)plays a regulatory role in bone metabolism and increases bone formation,stimulates osteoblast number and activity,as well as reduces osteoclast differentiation and bone resorption.The mechanism of IGF-1is an issue of concern.OBJECTIVE:To review the research advance in IGF-1and the bone metabolism-related indexes in postmenopausal osteoporosis.METHODS:The first author searched the PubMed and CNKI databases between January2012and July2016using the keywords of“postmenopausal osteoporosis,insulin-like growth factor,bone metabolism,biochemical markers”in English and Chinese,respectively.The repetitive articles were excluded,and36eligible articles were enrolled for overview.RESULTS AND CONCLUSION:Bone resorption is increased in postmenopausal woman through the regulation of a variety of cytokines,in which IGF-1in the blood is combined with IGF binding protein3,making growth hormone play its biological role.In addition,the growth hormone in the blood directly acts on the adipose tissue,and muscle and bones.Growth hormone exerts a direct effect on bone tissue,promotes osteoblast maturation and differentiation,and enhances the expression of collagen and non-collagen through IGF-1-mediated indirect effect,thus promoting bone formation.The process of bone metabolism is able to reflect the activities of osteoblasts and osteoclasts and the changes of bone matrix and bone mineralization.In vitro experiments show that IGF-1stimulates the proliferation of osteoblast precursors and differentiate into osteoblasts in a dose-dependent manner,promotes the expression of osteogenic markers such as alkaline phosphatase,type I collagen,and osteocalcin,and also stimulates the activity and number of osteoclasts.However,there are few clinical reports and few observation indicators,resulting in a lack of reference range for the detection and treatment of osteoporosis,which needs further exploration.