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
The Role Of Perlecan In Tensional Connective Tissues
Funder
National Health and Medical Research Council
Funding Amount
$605,037.00
Summary
Musculoskeletal diseases affect tension and weight bearing connective tissues which have notoriously poor repair capabilities. These conditions are difficult to treat clinically and surgical repair in many cases does not provide a return to optimal joint function impinging on the quality of life of afflicted individuals and their carers. Our project aims to better understand the structure and function of these tissues in health and disease with a view to improving repair strategies.
Furin: Carving-up Vital Substrates For Bone Remodelling And Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$815,972.00
Summary
Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures. It is caused by an imbalance between the cells that are constantly reabsorbing and reforming bone. The proposed project will address furin as a novel regulator of bone remodelling.
Short-term Use Of Intermittent PTH To Accelerate Healing Of Stress Fractures And During Bisphosphonate Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$633,331.00
Summary
Osteoporosis treatments prevent fractures by hindering cells that erode the skeleton. Normally, those cells also repair injuries like stress fractures. Some patients, treated for long periods, can suffer fractures because the treatment slows bone healing. We have an innovative model to test alternative treatments to accelerate stress fracture healing, while osteoporosis treatment continues. This could prevent unusual stress fractures, in patients who still need the bone-sparing effectiveness of ....Osteoporosis treatments prevent fractures by hindering cells that erode the skeleton. Normally, those cells also repair injuries like stress fractures. Some patients, treated for long periods, can suffer fractures because the treatment slows bone healing. We have an innovative model to test alternative treatments to accelerate stress fracture healing, while osteoporosis treatment continues. This could prevent unusual stress fractures, in patients who still need the bone-sparing effectiveness of osteoporosis treatment.Read moreRead less
Influence Of Osteocytes On Anabolic Bone Therapies
Funder
National Health and Medical Research Council
Funding Amount
$586,965.00
Summary
This project seeks to define the influence of changes in gene expression in cells called osteocytes, that exist within the substance of bone. These cells form a communication network within the bones of the skeleton, and appear to influence bone formation; changes in gene expression by these cells could influence the efficacy of current and emerging osteoporosis therapies.
Manipulating The Anabolic And Catabolic Responses For Bone Tissue Engineering
Funder
National Health and Medical Research Council
Funding Amount
$58,202.00
Summary
The repair of large bone defects represents a significant clinical problem. Evolving tissue engineering technologies may lead to significant improvements in orthopaedic treatments for these problems. We plan to compare novel biological approaches designed to maximise new bone formation while preventing bone resorption with existing synthetic graft materials. Our research data will be readily translated from the laboratory to a clinical setting.
Osteal Macrophages As Therapeutic Targets For Fracture Repair
Funder
National Health and Medical Research Council
Funding Amount
$618,015.00
Summary
Fragility fracture associated with osteoporosis is a substantial health problem costing $1.62 billion to treat in 2012 in Australia. There is no approved therapy to improve and accelerate fracture healing to help reduce this increasing health burden. This research will advance understanding of fracture repair in healthy and osteoporotic bone and progress development of a fracture therapy to improve bone repair by promoting specialised immune cells.
Relationships Between Human Osteoblasts And Haemopoietic Cells In Bone Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$436,450.00
Summary
Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collabora ....Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collaboration between osteoblasts and osteoclasts. Osteoblasts stimulate the formation of osteoclasts and also produce new bone at resporption sites. However, the way that the same type of cell can perform both these tasks, is not clear. Our studies are designed to increase our understanding of the development of human osteoblasts and of the factors that cause them to be sequentially pro-osteoclastic and then pro-osteogenic. We believe that an important factor in this process is vitamin D and we will test the hypothesis that this molecule is produced in bone and acts locally to regulate bone turnover.Read moreRead less