The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.
We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately exp ....We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately explore the relationship between prothesis wear and PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science experiments will seek to understand the underlying causes of PO and the findings will be important in interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological response to wear particles. The significance of these studies is that they will lead to improved outcomes for joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings an attendant morbidity and mortality.Read moreRead less
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
Chronic inflammation underlies common and debilitating diseases and causes pain by unknown mechanisms. There is an urgent need to gain a deeper understanding of the mechanisms of chronic pain, which will allow the development of improved therapies with fewer side-effects. Our research program investigates the mechanisms of pain that are associated with inflammatory bowel disease and irritable bowel syndrome, with the goal of developing more effective and selective therapies.
Creating perceptual experts in Australia's policing and security agencies. This project aims to create the next generation of experts in Australia’s policing and national security agencies, by improving crime scene evidence interpretation. Agencies are under pressure to develop more rigorous training practices that go beyond mere intuition and tradition. This project will use a novel approach that directs learning toward the most diagnostic perceptual cues. Expected outcomes include a solid empi ....Creating perceptual experts in Australia's policing and security agencies. This project aims to create the next generation of experts in Australia’s policing and national security agencies, by improving crime scene evidence interpretation. Agencies are under pressure to develop more rigorous training practices that go beyond mere intuition and tradition. This project will use a novel approach that directs learning toward the most diagnostic perceptual cues. Expected outcomes include a solid empirical basis for national training programs designed to create experts that are accurate, reliable, and continuously improving. Improving the training of experts will ensure the integrity of forensics as evidentiary tools available to police, lead to more reliable courtroom convictions and help safeguard Australia from terrorism and crime.Read moreRead less
Central pathways regulating visceral pain. This project aims to investigate the neural pathways within the spinal cord and brain processing colorectal pain perception. The project aims to identify the spinal cord neurons relaying colorectal signalling into the brain and the influence of descending modulation from the brainstem upon these pathways. The outcomes will greatly benefit fundamental understanding of the central pathways processing visceral pain.
Left of centre: Attentional distortions in the mental representation of space in healthy and clinical populations. Stroke patients cost the Australian economy $1.3bn pa in addition to their social burden, but effective diagnosis and rehabilitation is impeded by a lack of fundamental research into the cognitive and neural mechanisms that underlie attentional disorders. Our research will provide significant new insights into how the brain deploys attention in external and imagined space and will l ....Left of centre: Attentional distortions in the mental representation of space in healthy and clinical populations. Stroke patients cost the Australian economy $1.3bn pa in addition to their social burden, but effective diagnosis and rehabilitation is impeded by a lack of fundamental research into the cognitive and neural mechanisms that underlie attentional disorders. Our research will provide significant new insights into how the brain deploys attention in external and imagined space and will lead to more effective management and treatment of stroke victims. Our new test of attentional disorders is independent of a patient's inability to see or move and will enable more effective diagnosis. Our research provides the fundamental knowledge base for our discipline and is vital for developing the next generation of Australia's cognitive neuroscientists. Read moreRead less
The Risks And Benefits Of Contemporary Total Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$493,530.00
Summary
The number of hip replacements undertaken in Australia is steadily increasing. The most common complications of hip replacements are dislocation and loosening due to bone loss around the implant, requiring complex and expensive revision surgery. This study will investigate the incidence of dislocation and, using a new diagnostic imaging technique, the incidence and amount of bone loss around a relatively new prosthetic material, the outcomes of which are not known despite its increasing use.
Left to right is front to back: attentional distortions in near and far space for healthy and clinical populations. We are investigating a perceptual bias that makes people think objects right in front of them are actually slightly to the right but objects far away are slightly to the left. This project will help understand why this happens, to help reduce traffic collisions and help people with brain damage that causes similar perceptual biases.
Bio-inspired camouflage to prevent shark attacks on surfers. Bio-inspired camouflage to prevent shark attacks on surfers. This project aims to develop a new shark deterrent technology to protect surfers and paddlers. Shark attacks are physically and emotionally devastating for the victims, and make the community disproportionately afraid. Surfers are at most risk of attack, but current surfboard-mounted deterrents are ineffective and not widely used. This project will build on the recent discove ....Bio-inspired camouflage to prevent shark attacks on surfers. Bio-inspired camouflage to prevent shark attacks on surfers. This project aims to develop a new shark deterrent technology to protect surfers and paddlers. Shark attacks are physically and emotionally devastating for the victims, and make the community disproportionately afraid. Surfers are at most risk of attack, but current surfboard-mounted deterrents are ineffective and not widely used. This project will build on the recent discovery that white sharks do not attack counter-illuminated (light emitting) seal-shaped decoys, and use new information about shark vision to understand why this ‘camouflage’ is so successful. This will also help to protect threatened shark species by reducing reliance on culling programs to keep people safe in the water.Read moreRead less