Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment an ....Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment and assessment of a cohort of 1500 postmenopausal women with either low or high bone mineral density from pre-existing population cohorts in Australia. A genomewide association study will then be performed on these cases. Associated genes in different datasets will then be investigated further in our cohort, and high-density SNP mapping performed to identify true associated variants. These studies should identify most genetic variants associated with BMD variation and low trauma fracture in the general community, allowing development of diagnostic-disease predictive genetic tests, and informing development of novel therapeutic agents for osteoporosis.Read moreRead less
My research activities can be broadly classified into three strands: epidemiology of fracture, genetics of osteoporosis, and application of Bayesian approach in medical research. The major epidemiological work has included the development of models for in
The Role Of TWIST Family Basic Helix-Loop-Helix Transcription Factors In Bone Cell Commitment, Function And Repair
Funder
National Health and Medical Research Council
Funding Amount
$485,928.00
Summary
In developed countries, projected estimates predict an alarming trend of a two to three fold increase in the number of fractures that require surgical intervention and rehabilitation therapy in the coming decades as a consequence of an aging population. Fracture healing is a complex physiological process that involves the coordinated participation of different bone marrow cells, immune cells and skeletal progenitor cells. Multiple factors regulate interactions between these cell types that influ ....In developed countries, projected estimates predict an alarming trend of a two to three fold increase in the number of fractures that require surgical intervention and rehabilitation therapy in the coming decades as a consequence of an aging population. Fracture healing is a complex physiological process that involves the coordinated participation of different bone marrow cells, immune cells and skeletal progenitor cells. Multiple factors regulate interactions between these cell types that influence the capacity of bone cell progenitors to develop into functional bone forming cells known as osteoblasts. An understanding of the fracture healing is critical for the future advancement of fracture treatment, and for identifying the mechanisms of skeletal growth and repair as well as the causes of aging and disease. This proposal seeks to identify critical regulatory molecules that act to mediate bone cell progenitor recruitment and development during bone fracture repair.Read moreRead less
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
Gene Variants Related To Bone Density And Fracture.
Funder
National Health and Medical Research Council
Funding Amount
$330,375.00
Summary
Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. In addition, some people with bone fracture at the hip, or low bone density, have mutations in this gene. The gene is a master regulator of the cells that mak ....Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. In addition, some people with bone fracture at the hip, or low bone density, have mutations in this gene. The gene is a master regulator of the cells that make bone: this gives hope that it may be possible to alter bone formation through this master regulator.Read moreRead less
Osteoporosis is the commonest metabolic bone disease worldwide, and costs Australia >1% of GDP. It is a strongly inherited disease. We recently completed a genome-wide association study in 2000 postmenopausal women with either very high or very low bone density, and identified many genes contributing to BMD. The current study aims to use next-generation sequencing to study these women in greater genetic depth, aiming to identify more clearly the exact genetic determinants of bone mass.
Falls and broken bones are costly health problems among the elderly, even more so when there is a growing older population aged over 65 years. In Australia about 1 million older people have at least one fall each year and about 40-60% will sustain major injuries including broken bones. Therefore there is a need to identify effective ways to reduce falls and improve outcomes of those who break a bone, especially of the hip.
Geelong Osteoporosis Study: Fracture Risk Prediction Based On Twenty Years Of Prospective Data.
Funder
National Health and Medical Research Council
Funding Amount
$1,107,758.00
Summary
In this population-based study we will generate evidence, both environmental and genetic, for defining fracture risk in Australian men and women. This will help identify individuals likely to sustain fragility fractures so that suitable therapies can be recommended. The data will be useful for developing prognostic models in both a clinical setting and for genetic screening programmes.
The Impact Of Individualised Care Plans For Elderly Patients Discharged Home From Hospital After Neck Of Femur Fracture: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$475,920.00
Summary
Improved delivery of care to older Australians who sustain a broken hip is a major health need. Transitions from hospital remain a high-risk process. Written discharge plans are recommended nationally, but are not routinely implemented. This randomised controlled trial will test whether a discharge intervention can improve hip fracture patients capacity to live well in the community. The intervention harnesses existing services and infrastructure, and can be rapidly scaled up if effective.
Orthopaedic medicine utilises precise control of critical aspects of the bone healing response. This proposal looks at a novel, and powerful neural-based method for controlling these processes. This will be done by modulating the activity of the neuropeptide Y1 receptor, recently identified on osteoblastic cells and capable of powerful, inverse regulation of bone formation activity. Harnessing these effects will provide a critical tool for existing surgical practice.