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
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.
Relationships Between Human Osteoblasts And Haemopoietic Cells In Bone Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$436,450.00
Summary
Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collabora ....Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collaboration between osteoblasts and osteoclasts. Osteoblasts stimulate the formation of osteoclasts and also produce new bone at resporption sites. However, the way that the same type of cell can perform both these tasks, is not clear. Our studies are designed to increase our understanding of the development of human osteoblasts and of the factors that cause them to be sequentially pro-osteoclastic and then pro-osteogenic. We believe that an important factor in this process is vitamin D and we will test the hypothesis that this molecule is produced in bone and acts locally to regulate bone turnover.Read moreRead less
Sclerostin And Dickkopf-1 In Regulation Of Bone Mass
Funder
National Health and Medical Research Council
Funding Amount
$638,581.00
Summary
The WNT pathway is a powerful regulator of bone cell differentiation and bone formation. Two WNT modulators, sclerostin ad Dickkopf 1, are being developed for therapy in bone disease, but critical questions remain unanswered. In this study we use unique genetic mouse models created by the applicants to resolve specific deficiencies surrounding their actions and application as therapies.
Bone-specific Sclerostin And SIBLING Proteins In Osteoarthritis: Novel Contributions To Cartilage And Bone Pathology
Funder
National Health and Medical Research Council
Funding Amount
$441,058.00
Summary
Arthritis is a major clinical problem and involves the destruction of cartilage in joints. However, the mechanisms of how this cartilage destruction is initiated and progresses remain poorly understood. We recently discovered that that three proteins that play a role in bone are also produced in cartilage and are increased in cartilage during osteoarthritis. We will determine the role of each of these in the disease mechanism to provide new therapeutic and biomarker targets.
Rotator cuff (RC) tendon disease is a huge burden on the healthcare system in Australia and a major cause of morbidity in our aging population. Disorders of the RC are the most common cause of shoulder pain, which accounts for 1.2% of all visits to general practitioners. The prevalence of RC pathology increases with age to reach 30-50% by the seventh decade of life and a staggering 70-80% by the ninth. While most cases are treated conservatively, there are over 12,000 RC repair surgeries perform ....Rotator cuff (RC) tendon disease is a huge burden on the healthcare system in Australia and a major cause of morbidity in our aging population. Disorders of the RC are the most common cause of shoulder pain, which accounts for 1.2% of all visits to general practitioners. The prevalence of RC pathology increases with age to reach 30-50% by the seventh decade of life and a staggering 70-80% by the ninth. While most cases are treated conservatively, there are over 12,000 RC repair surgeries performed annually in Australia, with patients being committed to a prolonged convalescence. There are no drug therapies to specifically treat RC or other tendon injuries and many surgical repairs fail within 12 months. The limited treatment options for RC and other tendon disorders stems from a lack of knowledge of the molecular changes that precede and lead to rupture. It is recognised that the content of sulphated sugars or glycosaminoglycans (GAGs) on proteoglycans in tendon is the strongest predictor of the tisues strength. Accumulation of GAG is a well-recognised feature of torn tendons in man. The changes in proteoglycan synthesis and breakdown that precede and lead to tendon rupture have not been defined. We have developed a new model of shoulder tendon injury in sheep that induces regional degeneration mimicking that seen in human RC disorders. We have found changes in expression of specific proteoglycans and their degradative enzymes in early tendon disease. The current project will use this model in combination with a novel culture system and recently developed genetically modified mice to determine for the first time the changes that occur over time in proteoglycan metabolism that are responsible for tendon degeneration that leads to rupture. Successful completion of these studies will identify biomarkers to monitor disease progression and a platform for the development of new therapeutic strategies to treat this debilitating disorder.Read moreRead less
Inhibition Of Bone Resorption Increases Skeletal Mechanical Strength By Thickening Trabecular Structures
Funder
National Health and Medical Research Council
Funding Amount
$175,648.00
Summary
This project will identify the basis by which a number of therapies for osteoporosis decrease the risk of bone fractures. Currently at least four classes of these compounds in current use for the treatment of osteoporosis. Some of them have been found to have a very marked beneficial effect by halving the risk of fracture. This study will determine if each of these classes of compounds have the ability to increase the mechanical strength of bone to the same level and if each of these compounds h ....This project will identify the basis by which a number of therapies for osteoporosis decrease the risk of bone fractures. Currently at least four classes of these compounds in current use for the treatment of osteoporosis. Some of them have been found to have a very marked beneficial effect by halving the risk of fracture. This study will determine if each of these classes of compounds have the ability to increase the mechanical strength of bone to the same level and if each of these compounds has the same effects on bone structure. Further the effects of stimulating bone formation by subjecting the skeletal to mechanical stress, on the efficacy of each of the therapies will be established. Conversely the effect of aging, which imposes a limitation on bone formation, will be studied.Read moreRead less
Pathobiology Of The Small Leucine Rich Repeat Proteoglycans In Cartilage, Intervertebral Disc And Tendon Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$516,625.00
Summary
Back problems (M$700), OA (M$600), muscle and tendon disorders (M$500) accounted for 60% of musculoskeletal (MSK) health care expenditure in Australia in 1993-1994, were the second most common cause of presentations to a general practitioner, the third leading contributor to health system expenditure (>$3 billion) and accounted for ~300,000 hospital admissions, ~15 million medical services and over 13 million prescriptions. Significant disability due to MSK disease were noted in ~50% of peopl ....Back problems (M$700), OA (M$600), muscle and tendon disorders (M$500) accounted for 60% of musculoskeletal (MSK) health care expenditure in Australia in 1993-1994, were the second most common cause of presentations to a general practitioner, the third leading contributor to health system expenditure (>$3 billion) and accounted for ~300,000 hospital admissions, ~15 million medical services and over 13 million prescriptions. Significant disability due to MSK disease were noted in ~50% of people aged 65 years. Australian census data indicates that ageing trends will result in an increased incidence of MSK conditions as the longevity of the Australian population rises, exerting an ever increasing burden on the healthcare budget. Extreme levels of sporting or physical activity from traumatic loading of joints can lead to excessive loading of collagen fibres in MSK tissues leading to their failure and loss of tissue function. Common end stages of collagen fibre breakdown are preceded by matrix changes which may predispose MSK tissues to enzymatic and mechanical damage. One such change is an increased degradation of a family of small leucine-rich proteoglycans (SLRPs) which modulate the diameter, strength and assembly of collagen fibrils and bind and modify the effects of reparative growth factors and degradative cytokines within connective tissues. Altered synthesis of SLRPs and SLRP fragments have been identified in abnormal intervertebral disc, cartilage and tendon. Very little is known however about how these fragments are generated within these tissues and how they affect growth factor binding or collagen fibril formation. This deficiency will be addressed in our proposed study which will provide novel information on mechanisms of cartilage, intervertebral disc and tendon degeneration and potential therapeutic and diagnostic targets which may be exploited in future studies on the treatment of these musculoskeletal conditions.Read moreRead less