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，也是住院治疗的主要原因。髋部骨折可能导致手术、慢性活动能力降低、功能丧失、住院或死亡。骨质疏松症这一术语涵盖了一种异质性综合征，包括幼年性、继发性（如皮质类固醇诱导）和绝经后骨质疏松症。后来的广泛分组显示出强烈的家族联系。先前的研究表明，有骨折家族史的人发生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，诸如骨矿物质密度（BMD）、骨的宽带超声衰减和髋部结构指标等表型具有很强的遗传性。这证实了这种疾病在某些个体中的遗传基础。在过去四十年中，澳大利亚的社区卫生总体上有了很大的改善，从而延长了寿命。相比之下，髋部骨折的发生率及其对公共卫生资金的消耗继续迅速增加。目前，在澳大利亚，骨质疏松症的费用每年为75亿美元。髋部骨折占这些费用的大部分。制定有效的预防战略至关重要。该项目旨在通过提高对髋部几何和结构遗传方面对髋部骨折易感性的理解，为澳大利亚国家研究重点之一做出贡献。我们过去已经成功地完成了研究家族遗传连锁的基因组筛选项目，以定位调节骨密度的基因。然而，骨密度失调只是众多相关表型中的一种。对于髋部骨折，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来推进遗传连锁和关联的研究，以检查与髋部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.