Orthopaedic medicine utilises precise control of critical aspects of the bone healing response. This proposal looks at a novel, and powerful neural-based method for controlling these processes. This will be done by modulating the activity of the neuropeptide Y1 receptor, recently identified on osteoblastic cells and capable of powerful, inverse regulation of bone formation activity. Harnessing these effects will provide a critical tool for existing surgical practice.
Falls and broken bones are costly health problems among the elderly, even more so when there is a growing older population aged over 65 years. In Australia about 1 million older people have at least one fall each year and about 40-60% will sustain major injuries including broken bones. Therefore there is a need to identify effective ways to reduce falls and improve outcomes of those who break a bone, especially of the hip.
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
Gene Variants Related To Bone Density And Fracture.
Funder
National Health and Medical Research Council
Funding Amount
$330,375.00
Summary
Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. In addition, some people with bone fracture at the hip, or low bone density, have mutations in this gene. The gene is a master regulator of the cells that mak ....Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. In addition, some people with bone fracture at the hip, or low bone density, have mutations in this gene. The gene is a master regulator of the cells that make bone: this gives hope that it may be possible to alter bone formation through this master regulator.Read moreRead less
Bone Fragility: The Neglected Role Of Cortical Porosity
Funder
National Health and Medical Research Council
Funding Amount
$620,381.00
Summary
Cortical (outer shell) or compact bone constitutes 80% of the skeleton. It is not solid as implied by its name but made of inter-connected canals resembling a network of roads. We recently discovered that most of the bone loss with age occurs from these canals, not from t rabecular bone as currently believed. This suggests to know why and how bone breaks requires the study of the morphology of these canals and how they change with age. This is what we propose to do. It has never been done.
Development And Validation Of A Finite Element Model For Orthopaedic Screw Insertion Into Trabecular Bone
Funder
National Health and Medical Research Council
Funding Amount
$420,454.00
Summary
Osteoporosis is a disease of the bones that results in reduced bone strength and susceptibility to fragility fractures. Due to the spongy nature of osteoporotic bone, surgeons face major difficulties in obtaining secure fixation of bone screws. Our aim is to develop and validate a computer model of orthopaedic screw insertion into trabecular bone based on micro-computed tomography image data. This will allow an assessment of the most appropriate screw designs for stable fixation of implants.
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