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
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 .
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.
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
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.