Prediction Of Adverse Outcomes Following A Fragility Fracture
Funder
National Health and Medical Research Council
Funding Amount
$148,426.00
Summary
Individuals with an existing fracture are at increased risk of adverse outcomes such as re-fracture and premature mortality, but it is not clear why. We propose to evaluate risk factors, and prognostic models, for predicting the risk of adverse outcomes. We also propose to develop a quantitative risk-benefit framework for evaluating the clinical utility of such prognostic models and help ensure that therapies appropriately address real-life experience of osteoporotic patients.
The Effect Of Antiepileptic Medication On Indices Of Bone Health And Risk Factors For Falls And Fractures
Funder
National Health and Medical Research Council
Funding Amount
$469,605.00
Summary
Epilepsy is a common brain disorder and most patients with epilepsy take anti-epileptic drugs (AEDs) for many years. These patients have high rates of bone fractures, but the reasons are uncertain. Earlier studies identifying an association between AED use and bone disease were performed on institutionalised patients, and more recent studies on outpatient populations have been conflicting. A better understanding of this problem is critical for designing potential preventive measures and treatmen ....Epilepsy is a common brain disorder and most patients with epilepsy take anti-epileptic drugs (AEDs) for many years. These patients have high rates of bone fractures, but the reasons are uncertain. Earlier studies identifying an association between AED use and bone disease were performed on institutionalised patients, and more recent studies on outpatient populations have been conflicting. A better understanding of this problem is critical for designing potential preventive measures and treatments. One important additional mechanism by which AEDs may increase fracture risk is impairment of gait and balance, leading to a high risk of falls. We have novel data demonstrating the power of a Twin and Matched Sibling approach to study this important problem. This study showed that chronic AED use was associated with significant deficits in bone mineral density (BMD), a key predictor of the risk of fractures. The proposed project will ask the following questions: 1. Is BMD and estimated bone strength lower in the bones most at risk for fracture in women and men chronically taking AEDs? 2. Is the loss of bone in measurements over time greater in patients continuing to take AEDs? 3. Is the risk of bone loss greater for certain types of AEDs, and is the risk influenced by length of exposure, age and menopausal status? 4. How does AED treatment lead to reductions in BMD and bone strength? 5. Are measures of muscle strength, gait and balance impaired in patients taking AEDs compared with matched people not taking AEDs? The proposed study will utilise twins and pairs of siblings to investigate the effects of the long-term use of AEDs for epilepsy on measures of bone mass and strength, indices of bone turnover, vitamin D status, calcium regulating hormones, mineral levels, sex hormone levels, and measures of muscle strength, gait and balance function. In addition, a group of patients newly commencing AED treatment for epilepsy will be studied over 2 years.Read moreRead less
Sex Hormones And Heart Disease In Older Women Study (The SHOW Study)
Funder
National Health and Medical Research Council
Funding Amount
$594,672.00
Summary
Cardiovascular disease (CVD, heart disease and stroke) is the leading cause of death in women aged 65 and over. Counter-intuitively, androgens may be as, or even more important, than estrogens in determining CVD risk and all-cause mortality in women, but this is yet to be verified. We will document blood levels of androgens in women aged 70+ and determine whether androgens are associated with CVD and death in this large cohort of elderly well women.
Type 2 Diabetic Renal Complications And Microvascular Injury: Novel Predictors Of Onset And Progression, Mechanisms Of Association With Cardiovascular Disease And The Benefits Of Fenofibrate.
Funder
National Health and Medical Research Council
Funding Amount
$84,448.00
Summary
We will investigate the mechanisms of diabetic complications related to kidney and blood vessel disease, focusing on identifying people at greater risk and ways to improve or prevent these complications. In addition, we will look at how diabetic kidney disease affects non-kidney related problems like heart disease and examine the benefit of fenofibrate on both. This greater understanding will aid further drug development in kidney and cardiovascular diseases.
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
Clinically Severe Obesity: A Better Understanding Of A Complex Condition, Improving Health Outcomes Through Effective Therapies, And Delivering A Comprehensive Clinical Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$701,539.00
Summary
Clinically severe obesity impacts on the health of 7-8% or 1.5 million Australians, yet poor access to integrated effective care. This challenging area of healthcare is distorted by perceptions and beliefs that are frequently contrary to clinical and physiological research findings. Professor Dixon’s plan is to: 1) To learn more about clinically severe obesity, 2) improve the assessment and delivery of effective care, and 3) improve clinical capacity to better care for these Australians.
The Relationship Between Non-Alcoholic Fatty Liver Disease And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Non alcoholic Fatty Liver Disease (NAFLD) threatens to become a major public health problem. Its increasing prevalence is associated with parallel increases in obesity and diabetes. This study aims to understand the mechanisms involved in progression to liver failure and liver cancer in the setting of diabetes and the impact of NAFLD on blood sugar levels and diabetes complications (esp. cardiovascular). Using a recently developed animal model of type 2 diabetes and fatty liver, it will better d ....Non alcoholic Fatty Liver Disease (NAFLD) threatens to become a major public health problem. Its increasing prevalence is associated with parallel increases in obesity and diabetes. This study aims to understand the mechanisms involved in progression to liver failure and liver cancer in the setting of diabetes and the impact of NAFLD on blood sugar levels and diabetes complications (esp. cardiovascular). Using a recently developed animal model of type 2 diabetes and fatty liver, it will better define a novel therapeutic agent.Read moreRead less
The overall aim is to improve treatments and outcomes for people with osteoporosis. This will be achieved by better predicting those who are likely to fracture and subsequently those who do well post fracture from those who do poorly. Following an osteoporotic fracture there is an increased risk of re- fracture and of premature death. This research will define those risk factors for fracture, re-fracture and early death in a large group of men and women followed for over 20 years.