Genetic regulation of hip geometry, structure and fracture

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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.