GENETICS OF BONE LOSS AND BONE STRENGTH IN WOMEN & MEN

我们已经表明，骨矿物质密度（BMD）和结构的QTL似乎是性别特异性的。这些潜在的重要发现将通过将目前的兄弟样本量从700对扩大到1000对，并将这些数据与我们在1225对姐妹中收集的数据进行比较来证实。骨大小是决定骨强度和骨折风险的重要因素。我们已经证明，股骨颈骨扩张率的显著增加是可遗传的，并且连锁分析已经确定了许多QTL。没有收集到男性的可比数据。我们将对兄弟进行为期5年的纵向研究，以确定是否存在性别特异性基因导致骨大小的扩大。股骨近端定量计算机断层扫描（CT）提供了皮质骨和小梁骨的体积骨密度、结构表型和与体内骨强度相关的机械表型。我们发现白人和黑人男性在皮质骨密度上存在显著差异。在女性中，我们发现QTL与股骨颈皮质和小梁体积骨密度有关。为了证实这些关键发现，我们建议增加300对兄弟和300对姐妹的CT表型样本量。这些特定目标的实现将提供关于性别特异性基因存在的基本信息，这些基因是骨密度、骨结构和体内生物力学表型正常变化的基础，这些都是骨强度和骨折风险的关键组成部分。此外，它将提供有关的资料

We have shown that QTL for both bone mineral density (BMD) and structure appear to be sex-specific. These potentially important findings will be corroborated by enlarging the current sample size of brothers from 700 to 1,000 pairs and comparing these with data we have collected in 1,225 sister pairs. Bone size is an important factor in determining bone strength and hence fracture risk. We have shown that there is a significant increase in the rate of bone expansion at the femoral neck that it is heritable, and that linkage analysis has identified a number of QTL. No comparable data have been collected in men. We will perform a 5 year longitudinal study in brother pairs to establish if there are sex-specific genes for expansion of bone size. Quantitative computerized tomography (CT) at the proximal femur provides volumetric BMD of cortical and trabecular bone, structural phenotypes, and mechanical phenotypes related to in vivo bone strength. We have found significant differences between white and black men in cortical BMD. In women, we have found QTL for cortical and trabecular volumetric BMD at femoral neck. To corroborate these key findings we propose to increase our sample size by 300 pairs of brothers and 300 pairs of sisters for CT phenotypes. Achievement of these specific aims will provide fundamental information on the presence of sex-specific genes underlying the normal variation in bone density, bone structure, and in vivo biomechanical phenotypes, all key components of bone strength and risk of fracture. Further, it will provide information on the genes underlying differences in bone strength between American whites and blacks. It is expected that these proposed studies will greatly contribute to our understanding for the reasons for the higher risk of osteoporotic fracture in women than men and in American whites than blacks. Importantly the genes responsible for these differences are likely to provide targets for novel and more specific therapy aimed at prevention and treatment of osteoporotic fracture.