GENETIC DETERMINANTS OF PEAK BMD IN MEN & WOMEN

与年龄相关的骨质疏松性骨折主要是由于随着年龄的增长而增加的跌倒倾向和骨骼强度的降低。尽管骨骼结构与骨折风险有关，但骨密度（BMD）是骨强度和骨折风险的关键决定因素。成年人骨密度峰值的差异有60%到80%是遗传的。晚年骨质疏松症是青年时期骨量峰值和骨质流失率的函数。在本届奖项的任期内，我们已经确定了几个非常有前途的染色体区域，这些区域包含影响男性和女性骨骼强度峰值的基因。该项目将重点关注三个染色体区域，其中人类和动物模型的连锁数据表明，这些区域含有影响峰值骨密度的基因。本研究的目的是利用位置克隆/候选方法鉴定这些基因

Age related osteoporotic fractures are largely due to an increased propensity to fall with aging and a reduction in bone strength. Although skeletal architecture contributes to fracture risk, bone mineral density (BMD) is a critical determinant of bone strength and fracture risk. Between 60 and 80% of the variance in peak bone mineral density of adults is genetic. Osteoporosis in later life is a function of peak bone mass attained during young adulthood and rate of loss. During the tenure of the current award we have identified several highly promising chromosomal regions that contain genes that influence peak bone strength in men and women. This project will focus on three chromosomal regions where linkage data in both humans and animal models indicate that these regions harbor genes that affect peak BMD. The goals of this study are to identify these genes using a combined positional cloning/candidate approach in a well-characterized population of men and women. Identification of these genes may: 1) lead to molecular tests that predict osteoporosis risk and allow institution of early preventive measures; 2) provide insight into basic bone cell biology and other factors that affect peak BMD and predispose to osteoporosis; and 3) provide molecular targets for therapeutic agents to influence BMD.