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下降的倾向增加和骨强度降低。虽然骨骼结构有助于骨折风险，骨矿物质密度（BMD）是骨强度和骨折风险的关键决定因素。成人峰值骨密度的60%至80%的变异是遗传的。老年骨质疏松症是青年期达到的峰值骨量和丢失率的函数。在本奖项的任期内，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峰值骨强度的基因。该项目将集中在三个染色体区域，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BMD的基因。本研究的目的是在一个良好表征的细胞中，使用组合的位置克隆/候选方法来鉴定这些基因。 男性和女性的人口。这些基因的鉴定可能：1）导致预测骨质疏松症风险的分子测试，并允许早期预防措施的机构; 2）提供对基本骨细胞生物学和影响峰值BMD和易患骨质疏松症的其他因素的洞察力;和3）提供影响BMD的治疗剂的分子靶点。

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.