Regulation Of Key Pathways Causing Peri-implant Bone Loss.
Funder
National Health and Medical Research Council
Funding Amount
$403,639.00
Summary
The failure of bone prostheses is becoming a major health problem in our aging population. Despite the impressive success of joint replacement surgery, a significant number of arthroplasties fail. It is now apparent that most implants fail due to bone loss around them which leads to loosening. This project aims to obtain a better understanding of the causes of implant failure and find ways to extend the life of these implants .
Improving The Functional Outcomes Of Lower Limb Orthopaedic Surgery
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
While orthopaedic surgery usually achieves pain relief and improves function somewhat, it can often leave a patient unable to perform certain activities. And these abnormal movement patterns are likely to cause further problems. This project will objectively measure post-surgical function, in order to improve the surgery and rehabilitation of some of the most complex orthopaedic conditions. The goal is that patients receive the maximum benefit from surgery.
Femoroacetabular impingement (FAI) is a common cause of hip pain characterised by extra bone formation at the hip, called a cam-deformity. FAI is thought to create hip joint damage and osteoarthritis. Our 5 year longitudinal study of people with FAI in two (Melbourne and Brisbane) sites will investigate whether factors (such as cam-deformity size, hip contact force, muscle strength and joint range) can predict hip joint damage (measured with magnetic resonance imaging) over two years.
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
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.
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.
Regulation Of Osteoclast Differentiation And Function By The PKC Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$424,189.00
Summary
Developing strategies to control the formation of osteoclasts which underlines many disorders such as osteoporosis and osteoarthritis has been a major focus of bone research.The proposed research examines the fundamental role of Protein Kinase C (PKC) in bone resorption.This work will help elucidate the role of PKC in osteoclast formation;define the physiological role of PKC in bone structure and bone resorption in vivo and develop the treatment of bone disorders.
Interaction Of Rab3D And Tctex-1 Is Required For Bone Resorption Through The Regulation Of Post-TGN Vesicle Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$391,510.00
Summary
Osteoclasts are multinucleated cells responsible for the breakdown-resorption of bone tissue. Elevated osteoclast numbers and-or activities is a major hallmark of a number of debilitating Orthopaedic-related diseases including osteoporosis, arthritis, bone cancer and aseptic loosening. Among these, osteoporosis is endemic in Western society with an estimated 1 in 2 women and 1 in 3 men sustaining a fracture in their lifetime. It is well accepted that the transport of carrier vesicles containing ....Osteoclasts are multinucleated cells responsible for the breakdown-resorption of bone tissue. Elevated osteoclast numbers and-or activities is a major hallmark of a number of debilitating Orthopaedic-related diseases including osteoporosis, arthritis, bone cancer and aseptic loosening. Among these, osteoporosis is endemic in Western society with an estimated 1 in 2 women and 1 in 3 men sustaining a fracture in their lifetime. It is well accepted that the transport of carrier vesicles containing bone destructive enzymes is critical for bone resorption by osteoclasts. Although vesicle transport has been shown to be associated with microtubules (the cells skeleton), the molecular mechanisms responsible for vesicle and microtubule interaction are largely unknown. We have identified a novel interaction between Rab3D, a vesicle transport molecule, with Tctex-1, a microtubule-binding protein. We propose that the binding of Rab3D to Tctex-1 in osteoclasts is essential for the interaction of vesicles with microtubules and, hence, osteoclast function. The focus of this project is to further confirm our hypothesis by analysing the importance of this interaction in osteoclast-mediated bone resorption. The anticpated outcomes of the proposed project are: 1) Rab3D-mediated vesicle transport is directed via the microtubule network; 2) Interaction between Rab3D and Tctex-1 is cruical for the coupling of Rab3D-mediated vesicle transport to the microtubules; and 3)Disruption of the Rab3D-Tctex-1 interaction may impair bone resorption. Understanding the molecular mechanisms which regulate osteoclastic vesicle trafficking might therefore enable us to develop new strategies to specifically target and inhibit breakdown of bone tissue.Read moreRead less
A Randomised Controlled Trial Examining Stability Of New Types Of Highly Porous Surfaced Acetabular Components In Total Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$216,490.00
Summary
Numbers of total hip replacements are steadily increasing. The most common complication of hip replacement is late implant loosening, which can be predicted by early migration. We will examine early migration of a trabecular metal acetabular cup without screws, compared to a titanium fibre metal acetabular cup fixed with screws. Ideally, an acetabular cup would achieve a level of initial stability by press-fit alone without screws, as screws increase the risk of bone loss around the prosthesis.