GENETICS OF BONE LOSS AND BONE STRENGTH IN MEN AND WOMEN

骨质疏松性骨折是由于年龄相关的骨强度下降。骨强度包括骨密度、结构、质量和转换，所有这些都是高度遗传的。最严重的髋部骨折发生在髋部。髋骨强度的降低是由于低峰值骨量和年龄相关的骨丢失的组合。髋部骨量的遗传率很高，但髋部骨丢失的遗传率尚未研究。女性的骨强度较低，髋部骨折的发生率高于男性。在男性中，骨强度的遗传性还没有被牢固地确立。在760对姐妹篇中测量了骨强度的遗传性，并且10 cM基因组筛选已经确定了影响骨强度的几个染色体位点。现在将测试两个假设：1。女性髋部的骨质流失率是由遗传决定的。在我们目前的研究中，这将通过重新测量500对姐妹篇的髋骨质量进行测试，如果是遗传的，则使用已经产生的基因型进行连锁分析。2.基因对男性骨骼强度的影响与女性相似，但某些基因位点具有性别特异性。这将通过测量700对兄弟的骨强度进行测试，将遗传力与我们的760对姐妹篇进行比较，并进行基因组筛选以确定影响男性骨强度的基因座。在理解骨强度的遗传基础方面，将实现三个主要目标：1）确定女性髋部骨丢失率是否具有遗传成分，如果是，则定位导致丢失的基因; 2）确定男性骨强度的遗传性，并将其与女性的遗传性进行比较; 3）丰富我们的数据库，以精细定位骨强度基因，并确定某些位点是否具有性别特异性。这一信息将导致更好地了解骨质疏松性髋部骨折的原因和男女之间的发病率差异，并最终导致新的治疗和预防性治疗。

Osteoporotic fracture is due to age-related reduction in bone strength. Bone strength comprises bone mineral density, structure, quality and turnover, all of which are highly heritable. The most serious osteoporotic fracture occurs at the hip. Reduction in hip bone strength is due to a combination of low peak bone mass and age-related bone loss. Heritability of bone mass at the hip is high, but heritability of bone loss at the hip has not been studied. Women have lower bone strength and higher incidence of hip fracture than men. In men, heritability of bone strength has not been firmly established. Heritability of bone strength has been measured in 760 pairs of sisters, and a 10 cM genome screen has identified several chromosomal loci influencing bone strength. Two hypotheses will now be tested: 1. The rate of bone loss at the hip in women is genetically determined. This will be tested by remeasuring hip bone mass in 500 pairs of sisters in our current study and, if heritable, perform linkage analysis using genotypic already generated. 2. The genetic effect on bone strength in men is similar to that in women, but certain loci are sex specific. This will be tested by measuring bone strength in 700 pairs of brothers, comparing heritabilities to those in our 760 of sisters, and performing a genome screen to identify loci influencing bone strength in men. Three major goals in understanding the genetic basis of bone strength will be achieved: 1) establish if the rate of bone loss at the hip in women has a genetic component, and if so, localize the genes that underlie the loss; 2) establish heritabilities of bone strength in men and compare these with those established in women; 3) enrich our database for fine mapping bone-strength genes and establish if certain loci are sex specific. This information will lead to a much better understanding of the causes of osteoporotic hip fracture and of the difference in incidence between men and women and, ultimately, to new therapeutic and preventative treatments.