GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Funder
National Health and Medical Research Council
Funding Amount
$363,000.00
Summary
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of indivi ....Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known that the liability to fracture is determined in part by genes. Previous studies, including from our group, have suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is proposed that common variations of certain genes are associated with fracture risk independent of BMD. That is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence, some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic) BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite relatively good (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information. This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc) to assess the risk of future fracture.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less