Molecular And Histopathological Investigation Of Stress Fracture Healing And Effects Of Anti-inflammatory Drugs.
Funder
National Health and Medical Research Council
Funding Amount
$412,652.00
Summary
Stress fractures are debilitating injuries affecting children, adolescents and adults in sport, and army recruits. They also occur in horse and greyhound racing, often resulting in euthanasia of the animals involved. They incur considerable costs in medical expenses, time lost from sport and interruption to military training. But, there is almost no information on the mechanism of healing of these fractures. Non-steroidal anti-inflammatory drugs (NSAIDs) are still the most widely used medication ....Stress fractures are debilitating injuries affecting children, adolescents and adults in sport, and army recruits. They also occur in horse and greyhound racing, often resulting in euthanasia of the animals involved. They incur considerable costs in medical expenses, time lost from sport and interruption to military training. But, there is almost no information on the mechanism of healing of these fractures. Non-steroidal anti-inflammatory drugs (NSAIDs) are still the most widely used medication in management of musculoskeletal injuries, yet their effect on healing of stress fractures is unknown. NSAIDs delay fracture healing, but until recently there has been no standardised way of studying stress fractures. We have created, for the first time, a well-characterised, non-invasive model of stress fractures in the forearm of rats that closely resembles the clinical situation. This provides a novel and unique opportunity to determine the histological and molecular mechanism of stress fracture healing, and to investigate effects of antiinflammatory-analgesic medications on this process. Rats will have an experimental stress fracture produced in one forelimb, and its healing will be examined up to ten weeks using microscopic investigation and analysis of the genes that are turned off or on to initiate the process. Groups of rats will also be treated with antiinflammatory drugs such as ibuprofen, specific COX-2 inhibitors and a new class of drugs that target early immune responses called C5a receptor antagonists. The analgesic Paracetamol will also be investigated as an alternative to the NSAIDs described above. There is widespread use of anti-inflammatory agents in managing stress fractures, so it is vital that their effects on stress fracture healing be examined. This project has enormous significance for optimising approaches for clinical management of stress fractures and for understanding the interaction of anti-inflammatory or analgesic agents in that process.Read moreRead less
Randomised Trial Of Ibuprofen For The Prevention Of Ectopic Bone-related Pain And Disability After Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$364,217.00
Summary
Joint replacement is a well-established treatment for severe osteoarthritis of the hip. While most patients benefit substantially from the procedure, many still experience some pain and disability after surgery. New evidence suggests that one important cause of this pain and disability may be abnormal bone deposits that form in the muscles around the hip (ectopic bone formation) during the first few months after surgery. Ectopic bone formation is seen in about 40% of all patients with hip replac ....Joint replacement is a well-established treatment for severe osteoarthritis of the hip. While most patients benefit substantially from the procedure, many still experience some pain and disability after surgery. New evidence suggests that one important cause of this pain and disability may be abnormal bone deposits that form in the muscles around the hip (ectopic bone formation) during the first few months after surgery. Ectopic bone formation is seen in about 40% of all patients with hip replacements. If the formation is extensive, all movement of the hip is lost and revision surgery is necessary. However, even when the formation is less severe, movement at the hip can be restricted resulting in pain and disability. There is growing evidence that treatment with a non-steroidal anti-inflammatory drug at the time of surgery may halve the risk of ectopic bone formation. While this would be expected to decrease the risk and severity of post-operative pain and disability, there is little evidence available about the long-term effects of these drugs after hip replacement. For this reason, together with concerns about possible side-effect of these drugs, orthopaedic surgeons have generally been reluctant to prescribe these drugs routinely for the prevention of ectopic bone formation. Ibuprofen appears to be the non-steroidal anti-inflammatory drug with the lowest risk of side effects. If it was shown to be effective in reducing the incidence of pain and disability associated with ectopic bone formation after hip replacement, it may well be considered worthwhile by doctors and patients alike. If such benefits were realised, this preventive strategy is likely to be a highly cost-effective way to improve long-term outcome among the rapidly growing numbers of patients that receive hip replacements. This study will provide reliable evidence about the short and long-term effects of ibuprofen among 1,000 patients receiving hip replacements in Australia.Read moreRead less