Fractures And Bisphosphonates: Reviving Osteoporosis Treatment Uptake By Identifying The Genetic, Material, And Microstructural Risk Factors Of Atypical Femur Fractures.
Funder
National Health and Medical Research Council
Funding Amount
$1,053,094.00
Summary
Atypical femoral fractures (AFF) are uncommon, but catastrophic, complications of antiresorptive osteoporosis treatments including bisphosphonates. We will identify patients at risk of AFF by determining changes in their bone structure and quality, and identifying genes that increase the risk of these fractures. In this way, cheap and effective antiresorptive treatments can be targeted to patients at the lowest risk of AFF and alternative treatments to those at highest risk.
Vitamin D, Bone Loss, Fracture And Mortality Outcome
Funder
National Health and Medical Research Council
Funding Amount
$408,736.00
Summary
Vitamin D most commonly from sunlight exposure is considered an important determinant of health, including the liability to falls and fractures; not only in the elderly but in adulthood in general. This study aims to distinguish if low vitamin D levels cause adverse health outcomes or relate to ill health, limited sunlight exposure and nutritional change. Only if low vitamin D level is causative of ill health does replacement make good public health sense.
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.
Role Of The Osteoclast In Endochondral Fracture Repair
Funder
National Health and Medical Research Council
Funding Amount
$310,136.00
Summary
Failure of bone healing leads to significant pain and disability, such that augmentation of fracture repair is a dynamic and important field of study. A full understanding of bone repair is necessary before we can hope to introduce successful therapies. We theorise that by stimulating bone forming cells and inhibiting bone resorbing cells we may be able to provide optimal results. Bone resorbing cells, or osteoclasts, have long been considered essential to the initial stages of bone repair (endo ....Failure of bone healing leads to significant pain and disability, such that augmentation of fracture repair is a dynamic and important field of study. A full understanding of bone repair is necessary before we can hope to introduce successful therapies. We theorise that by stimulating bone forming cells and inhibiting bone resorbing cells we may be able to provide optimal results. Bone resorbing cells, or osteoclasts, have long been considered essential to the initial stages of bone repair (endochondral ossification) during which the early soft cartilaginous callus is replaced by hard mineralised callus. Our preliminary studies lead us to believe that endochondral ossification can indeed proceed without osteoclast activity. If we can safely eliminate osteoclast function early in the early stages of fracture repair, a number of therapeutic options open up for the augmentation of bone healing. The return of osteoclast function is necessary in the long term, so our strategy will also need to take this into account. This study will establish which systems are pivotal in endochondral ossification and therefore which interventions we should explore.Read moreRead less
Vertebral Body Strength: Contribution Of Bone Mass, Bone Structure And Material Properties
Funder
National Health and Medical Research Council
Funding Amount
$434,498.00
Summary
This study will determine the contributions to vertebral body strength made by its structural and material properties. Using state-of-the-art computed-tomography scanners, digitised representations of vertebral bodies in three-dimensions will be produced, which enable measurement of bone structure. After strength testing of the vertebral bodies, the structural and material properties, which combine to predict vertebral body strength, will be identified in an aged population.
An Abnormal Inflammatory Response Following Wrist Fracture Causes The Development Of Complex Regional Pain Syndrome (CRPS).
Funder
National Health and Medical Research Council
Funding Amount
$99,073.00
Summary
This project will contribute essential knowledge about what causes some people to develop Complex Regional Pain Syndrome (CRPS). CRPS affects approximately 5% of people following a fracture but can also occur with minimal injury. Sufferers experience gradually worsening levels of pain, skin discolouration, poor quality of life, and often severe depression. We will investigate the most likely cause of CRPS, which is thought to be an abnormal inflammatory reaction following injury.
Prostaglandin G/H Synthase-2 (PGHS-2) Is A Key Regulator Of Skeletal Adaptation And Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$301,018.00
Summary
Knowledge of the biology underlying bone formation is important for developing novel approaches to stimulate new bone formation in skeletal diseases associated with ageing or disability, or for maintenance of new bone around orthopaedic or dental implants. The discovery that a prostaglandin enzyme (PGHS-2) is a key factor in activity-related bone formation and normal bone turnover, as well as a pharmacological target for reducing inflammation, has considerable clinical significance. Specific inh ....Knowledge of the biology underlying bone formation is important for developing novel approaches to stimulate new bone formation in skeletal diseases associated with ageing or disability, or for maintenance of new bone around orthopaedic or dental implants. The discovery that a prostaglandin enzyme (PGHS-2) is a key factor in activity-related bone formation and normal bone turnover, as well as a pharmacological target for reducing inflammation, has considerable clinical significance. Specific inhibition of PGHS-2 by recent anti-inflammatory drugs avoids formation of gastric ulcers, but their influence on normal bone remodelling and fracture repair is not known and must be investigated. Many such inhibitors are in advanced clinical trials, but their effect on bone metabolism has not been published. This project is important because it employs novel experimental models to advance our knowledge of prostaglandin biology in skeletal adaptation, and elucidates important clinical consequences for specific inhibition of PGHS-2 in the skeleton. This project will investigate the regulation of prostaglandin production by PGHS enzymes following mechanical loading in vivo. It will use cell, molecular and histochemical techniques to determine if the genes that regulate the enzymes are influenced by mechanical stimuli, and if they are dependent on other molecules, associated with structural proteins (stress fibres) within the cell. It will investigate if inhibition of PGHS-2 by antiinflammatory drugs or stress-fibre inhibitors, depresses normal bone turnover and healing responses. The outcome of these experiments could indicate new approaches to stimulate bone formation, preserve bone mass, or minimise adverse skeletal effects of anti-inflammatory treatments related to orthopaedic or dental procedures.Read moreRead less
Cell Biology Of Stress Fractures: Activation Of Remodelling At Sites Of Non-union
Funder
National Health and Medical Research Council
Funding Amount
$493,817.00
Summary
Stress fractures are debilitating injuries. We characterised a model of stress fractures in rat ulnae, learning that they heal by activated remodelling, that key genes are expressed in a temporal pattern, and that part of the fracture remains un-healed, similar to many clinical cases. Now, we will examine cell localisation of important genes necessary for remodelling, and test the efficacy of different growth factors to activate a healing response in the non-healed section of the fracture.