Monitoring Bone Loss And Response To Therapy Through Bone Material And Structural Composition
Funder
National Health and Medical Research Council
Funding Amount
$696,111.00
Summary
Millions of scripts are filled for treatment of osteoporosis. However, there is no way of knowing if these drugs are right for these individuals, if it improves bone strength or are actually doing harm. Bone density measurement is of limited value. We have developed a new analysis method that measures changes in bone structure that tell us if the treatment is or is not working so alternative treatment can be used. The aim of this study is to test this new method.
GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Funder
National Health and Medical Research Council
Funding Amount
$363,000.00
Summary
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of indivi ....Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known that the liability to fracture is determined in part by genes. Previous studies, including from our group, have suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is proposed that common variations of certain genes are associated with fracture risk independent of BMD. That is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence, some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic) BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite relatively good (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information. This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc) to assess the risk of future fracture.Read moreRead less
Interaction Between PTH And Y2 Bone Anabolic Pathways
Funder
National Health and Medical Research Council
Funding Amount
$731,311.00
Summary
Osteoporosis is a costly condition that affects more than 150 million people worldwide and fills more hospital beds than any other disease*. People who have osteoporotic fractures experience a diminished quality of life and a reduced life expectancy. Although there are currently a number of therapies in use to reduce further loss of bone in osteoporotic patients, there is only one to replace lost bone, parathyroid hormone. For clinical and economic reasons, there is a need for additional bone-bu ....Osteoporosis is a costly condition that affects more than 150 million people worldwide and fills more hospital beds than any other disease*. People who have osteoporotic fractures experience a diminished quality of life and a reduced life expectancy. Although there are currently a number of therapies in use to reduce further loss of bone in osteoporotic patients, there is only one to replace lost bone, parathyroid hormone. For clinical and economic reasons, there is a need for additional bone-building therapies. Like all tissues, the nervous system affects skeletal function. We recently discovered a powerful control pathway by which the nervous system regulates bone formation. This project will test whether altering the function of this neural pathway can increase bone formation and whether it can work together with parathyroid hormone therapy to produce an enhanced bone formation response greater than either therapy alone. This research is important because of the need for new osteoporosis therapies to repair weakened bones. The knowledge gained from this study has the potential to provide a very important and useful contribution to skeletal health and thus aged health worldwide. *The Burden of Brittle Bones: Costing Osteoporosis in Australia. A report prepared by Access Economics Pty. Ltd. September 2001Read moreRead less
GLUCOCORTICOID EFFECTS ON BONE: THE ROLE OF THE OSTEOBLAST
Funder
National Health and Medical Research Council
Funding Amount
$464,520.00
Summary
Glucocorticoids (usually referred to as cortisone) are used as therapeutic agents in almost all fields of medicine, where they have been proven to be of great benefit to countless patients suffering from diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and malignancies. Glucocorticoids are also of live saving benefit to patients who have undergone organ transplantation. It is, however, well known that glucocorticoids may also exert deleterious effects on bone, muscle, ca ....Glucocorticoids (usually referred to as cortisone) are used as therapeutic agents in almost all fields of medicine, where they have been proven to be of great benefit to countless patients suffering from diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and malignancies. Glucocorticoids are also of live saving benefit to patients who have undergone organ transplantation. It is, however, well known that glucocorticoids may also exert deleterious effects on bone, muscle, cartilage and skin, causing osteoporosis, muscle wasting and skin damage. As a matter of fact, cortisone-induced muscle and bone disease is one of the most frequent and serious side effects associated with glucocorticoid treatment, and substantially affects quality of life and co-morbidity in many patients. In the present project, we aim to develop new strategies for the understanding and prevention of costisone-induced bone disease. The first step is to investigate the mechanisms of actions of glucocorticoids in bone. To this aim, we have generated a model in which a cortisone- inactivating enzyme is produced in excess in the bone forming cells (osteoblasts). Previous studies have shown that these cells are protected against the effects on cortisone, while other cells not producing this enzyme remained vulnerable. We now intend to use this model to study the mechanisms of glucocorticoid action on bone and muscle under normal and diseased conditions (e.g. in a model of glucocorticoid excess and in a model of rheumatoid arthritis). We also intend to study how internal glucocorticoids affect the development of bone forming cells. Our long-term aim is to uncover new ways to target drug action to the desired tissues and cells, while protecting other tissues and cells from deleterious side effects.Read moreRead less
Does Teriparatide Reverse Osteonecrosis Of The Jaw In Patients With Cancer? A Randomised, Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$137,700.00
Summary
Osteonecrosis of the jaw (ONJ) is a debilitating bone condition involving damage and suboptimal healing of bone involving the jaw. This has been associated with bisphosphonate therapy, which is commonly used for the treatment of both cancer and osteoporosis. My research aims to investigate the role of recombinant parathyroid hormone in the stimulation of bone formation and healing and, thus, its potential to reverse ONJ.
Regulation Of Bone Resorption And Formation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,596,183.00
Summary
Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. ....Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. Osteoporosis results from an excess of bone breakdown over formation, and our Program aims to identify the factors that regulate these processes, and develop new therapies that can modify them. We will also determine what it is about bone cell properties that make some cancers, especially those of breast and prostate, particularly prone to spread to bone.Read moreRead less
The Effect Of Androgen Replacement Therapy On Bone And Muscle Health In Men With Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
Low testosterone (T) levels are common in men with poor kidney function. Low T is known to cause reduced energy, decreased strength and low libido. Normal T is also needed for healthy bones and muscles. Men with kidney disease are already at risk of fractures, poor strength and quality of life. However, there are few studies that look at replacing T to men with kidney failure. We will investigate how low T affects bone and muscle and assess how giving T can benefit bone, muscle and function.
Menopause is one of the important risk factors for bone loss, structural decay and bone fragility. We aim to quantify the biochemical, microstructural and biomechanical basis of loss of bone strength during and after menopause. A cohort of 324 pairs of female-female twins aged 25 to 75 years old will be followed up for up to 9 years. Defining the structural basis of bone fragility provides a rational means to identifying women at risk for fracture.