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.
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
Maintenance Of Bone Strength In Aged Rats: The Vitamin D Requirement
Funder
National Health and Medical Research Council
Funding Amount
$543,301.00
Summary
Hip fracture remains the most devastating of the osteoporotic fractures particularly in women in whom the incidence increases to about 3% per annum by the ninth decade. This incidence is bound to increase as the population ages with increasing longevity. Supplementation of diets of elderly female nursing home residents with vitamin D and calcium has been shown to reduce the risk of hip fracture by 30% in two years. However we do not know how much vitamin D is necessary to maintain optimal bone s ....Hip fracture remains the most devastating of the osteoporotic fractures particularly in women in whom the incidence increases to about 3% per annum by the ninth decade. This incidence is bound to increase as the population ages with increasing longevity. Supplementation of diets of elderly female nursing home residents with vitamin D and calcium has been shown to reduce the risk of hip fracture by 30% in two years. However we do not know how much vitamin D is necessary to maintain optimal bone strength. This project will determine the level of vitamin D required to maintain optimal bone strength in aged rats using a simple blood test which could then be used to screen the elderly and identify those at risk of hip fracture from low vitamin D levels. The project will also investigate the effects of vitamin D on the bone cells that maintain optimal skeletal architecture. This information is essential for comparison with the current knowledge of other biochemical bone markets in blood and vitamin D status in the elderly, in order to develop nutritional recommendations to reduce the incidence of hip fracture.Read moreRead less
Hip fracture remains the most devastating of the osteoporotic fractures particularly in women, in whom the incidence increases to about 3% per annum by the ninth decade. This incidence is bound to increase as the population ages with increasing longevity. Supplementation of diets of elderly female nursing home residents with vitamin D and calcium has been shown to reduce the risk of hip fracture by 30% in two years. However we do not know how much vitamin D is necessary to maintain optimal bone ....Hip fracture remains the most devastating of the osteoporotic fractures particularly in women, in whom the incidence increases to about 3% per annum by the ninth decade. This incidence is bound to increase as the population ages with increasing longevity. Supplementation of diets of elderly female nursing home residents with vitamin D and calcium has been shown to reduce the risk of hip fracture by 30% in two years. However we do not know how much vitamin D is necessary to maintain optimal bone strength. This project will determine the level of vitamin Drequired to maintain optimal bone strength in adult and senescent rats using a simple blood test which could then be used to screen the elderly and identify those at risk a hip fracture from low vitamin D levels. The project will also investigate the effects of vitamin D on bone cells which is necessary to maintain optimal skeletal architecture. This information is essential for comparison with the current knowledge of other biochemical bone markers in blood and vitamin D status in the elderly, in order to develop nutritional recommendations to reduce the incidence of hip fracture.Read moreRead less
Radiostereometric Analysis Of The Effect Of A Large Articulation On Prosthetic Wear And Migration After Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$192,186.00
Summary
At total hip replacement, there has been a recent trend to use prostheses with a larger ball and liner in the socket. This may decrease the risk of post-operative dislocation, but may also increase the amount of wear, leading to bone loss and loosening of prostheses, which may then require replacement. This project will use a special type of x-ray to determine whether wear and movement of these new prostheses is clinically acceptable, so that they can be used with confidence in patients.
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.