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.
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
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.
Fragility Fractures: The Neglected Role Of Cortical Porosity
Funder
National Health and Medical Research Council
Funding Amount
$865,474.00
Summary
We just discovered that bone lost with age occurs mostly from pores within the cortex (outer shell) of the bone; These pores become larger (porosity) making bones fragile. This process is poorly detected by bone density (currently used tool) so that most people with weak bones are missed. To address this issue, we have for the first time, develop a technology to accurately quantify porosity in living peoples. With teams around the world, we aim here to fill this gap in the diagnosis.
The Micro-structural Basis Of Bone Loss And Fragility After Menopause: A Longitudinal Co-twin Control Study
Funder
National Health and Medical Research Council
Funding Amount
$873,950.00
Summary
Every woman becomes postmenopausal. Not all lose bone or sustain fractures after menopause. We will identify women who lose bone and those who don't and so identify women at risk for fracture so that they can be targeted for treatment and identify those who do not need to be treated. This will be done by measuring bone structure and how strong the bone is using a new, safe, quick technology that can be used in clinical practice
Premature Mortality Post Fracture:A NSW Linked Data Study
Funder
National Health and Medical Research Council
Funding Amount
$391,012.00
Summary
Osteoporotic fractures are associated with increased morbidity and mortality. Anti-osteoporosis medications reduce re-fracture and possibly morality, yet osteoporosis is poorly treated. This study will link information from >260,000 people (45&Up study) with hospital admissions, medications and deaths to create the largest, detailed dataset of its kind. We will be able to determine cause of any fracture-associated mortality and the effect of medication to improve osteoporosis management.
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
Improving Outcomes In Osteoporosis And Bone Health
Funder
National Health and Medical Research Council
Funding Amount
$348,494.00
Summary
Osteoporotic fractures are a common and increasing problem as the population ages. They are associated with increased risk of re-fracture and early death yet most patients remain untreated. This proposal will identify which fracture patients are at highest risk of re-fracture and premature death (b) identify whether osteoporosis treatment decreases this risk and (c) increase osteoporosis awareness and treatment uptake by general practitioners with an integrated fracture risk prediction tool.
The Relationship Between Osteoporosis And Diabetes: Exploring The Bone-metabolism Interface
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Osteoporosis and diabetes are two common conditions that affect many Australians. Diabetes patients have an increased risk of fractures, however the underlying mechanisms for this increased fracture risk is unknown. We hypothesise that there are changes in the bone remodelling as a result of increased insulin levels (as seen in type 2 diabetes) and will explore the factors that contribute to the increased fracture risk and examine how treatments can reduce fracture rates.
Osteoporosis is a common problem with increased premature mortality associated with hip and even more minor fractures. The cause of increased mortality is debated although osteoporosis treatment may decrease this risk. This study will be the first to examine survival of all subjects in NSW admitted for a fracture including cause for subsequent hospitalisation and treatment taken. This study will help define the cause of the mortality and the role of anti osteoporosis treatment on outcome.