Genetic regulation of hip geometry, structure and fracture

骨质疏松性髋部骨折在老年人中很常见，也是住院的主要原因。髋部骨折可能导致手术、慢性活动减少、功能丧失、住院或死亡。术语骨质疏松症包括幼年型、继发性(如皮质类固醇所致)和绝经后骨质疏松症。后来的这一广泛的分组表明有很强的家族联系。先前的研究表明，有骨折家族史的人患骨折的风险会增加四倍以上。此外，对双胞胎的研究一直表明，骨矿密度(BMD)、骨的宽带超声衰减和髋关节结构指数等表型具有很强的遗传性。这证实了某些人罹患这种疾病的基因基础。在过去的40年里，澳大利亚的社区健康总体上有了很大的改善，这导致了寿命的延长。相比之下，髋部骨折的发生率和由此造成的公共卫生资金枯竭继续快速增加。目前，澳大利亚每年因骨质疏松症而付出的代价是75亿美元。髋部骨折占了这些费用的大部分。制定有效的预防战略至关重要。该项目旨在通过提高对髋关节几何和结构遗传方面对髋部骨折易感性的影响方式的了解，为澳大利亚国家研究计划之一做出贡献。我们已经成功地完成了基因组筛选项目，研究了家系中的遗传连锁，以定位过去调节BMD的基因。然而，BMD只是许多相关表型中的一个。关于髋部骨折，几何和结构被认为是特别重要的。在这个项目中，我们将利用现有的资源推进遗传连锁和关联的研究，以检查与髋关节骨折相关的基本问题。

Osteoporotic hip fracture is common in the elderly and a major cause of hospitalization. Hip fracture may lead to surgery, chronic reduced mobility, loss of function, institutionalization or death. The term osteoporosis covers a heterogeneous syndrome including juvenile, secondary (e.g. corticosteroid induced) and postmenopausal osteoporosis. This later broad grouping shows evidence of a strong familial association. Previous work has shown that a family history of fracture increases the risk of fracture by more than four fold. Furthermore, studies in twins have persistently shown that phenotypes such as bone mineral density (BMD), broadband ultrasound attenuation of bone and hip structural indices are strongly inherited. This confirms a genetic basis for the disease in some individuals. Community health in general has improved substantially in Australia in the past four decades and this has resulted in increased longevity. In contrast, the incidence of hip fracture and the resulting drain on public health funding continues to increase rapidly. Presently the cost of osteoporosis in Australia is $7.5 billion per annum. Hip fracture accounts for the majority of these costs. Instituting effective prevention strategies is essential. This project aims to contribute to one of Australia's National Research Pritoities by improving understanding about the way in which inherited aspects of hip geometry and structure contribute to the hip fracture susceptibility. We have successfully completed genome screen projects studying genetic linkage in the families to localize genes regulating BMD in the past. However, BMD is only one of a number of relevant phenotypes. In relation to hip fracture, geometry and structure are thought to be particularly important. In this project we will make use of existing resources to advance studies of both genetic linkage and association to examine fundamental issues related to hip facture.