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
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
Osteoporosis is a disease associated with a progressive rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in 4 men will be affected. They cause pain, disability that can be permanent and are associated with loss of independence even premature death. Current treatments are able to partially restore bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent ....Osteoporosis is a disease associated with a progressive rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in 4 men will be affected. They cause pain, disability that can be permanent and are associated with loss of independence even premature death. Current treatments are able to partially restore bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent but these are limited by expense and safety concerns. We have discovered a pathway in the brain that when blocked, results in a doubling of the amount of bone in key bone sites and dramatic increases in bone strength. This occurs due to a marked increase in the amount of new bone formed. In fact, genetic manipulation of this pathway was able to double the speed at which bone is made by the skeleton. Excitingly, these increases in bone were possible in adult mice, suggesting such changes could be potential therapy for human patients. We went on to test the effectiveness of this pathway in animal models of human skeletal weakness and have shown that it is capable of remarkable benefits. However, in order to be able to harness this pathway we must understand what molecules within the bone that are responding to the signals from the brain. Our proposal aims to identify the nerve signalling molecule(s) and pathways for these signals within the bone that initiate the increase in bone formation. This project ultimately aims to identify a target for new therapies that could achieve this beneficial effect by administration in osteoporotic women and menRead moreRead less
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