Identification Of Novel PTH Anabolic Targets In Osteoblasts
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
Osteoporosis is a major disease affecting Australians. Whilst there are a number of drugs available that will reduce bone loss, there are few drugs available that build new bone, and little is known of the action of these drugs. New targets have been identified that modulate bone formation, and this project aims to validate these in appropriate models and determine their mechanism of action.
Sclerostin: A Key Regulator Of Bone Mineralisation And Bone Catabolism
Funder
National Health and Medical Research Council
Funding Amount
$536,653.00
Summary
The regulation of bone mass is critical for many areas of human disease including osteoporosis, osteoarthritis, inflammatory bone loss conditions, e.g. rheumatoid arthritis, cancers of bone and problems relating to orthopaedic prosthesis failure. The osteocyte, the most abundant bone cell, plays a central role in normal bone biology and is likely key to these diseases. Sclerostin is one osteocyte product that may be a key to understanding how boneÍs mass and composition is controlled locally.
The Effects Of A Two Year Randomised Exercise Intervention On Markers Of Bone Turnover In Postmenopausal Women
Funder
National Health and Medical Research Council
Funding Amount
$43,573.00
Summary
Osteoporosis is a condition where the bones become more fragile and can break more easily. In Australia after age 60, three out of every five women and three out of every ten men will fracture a bone. When people fracture a hip they lose their independence and become much less mobile. Exercise is one lifestyle approach which may help in preventing osteoporosis by slowing bone loss and keeping the muscles strong. Previous research has not been able to clearly demonstrate the usefulness of exercis ....Osteoporosis is a condition where the bones become more fragile and can break more easily. In Australia after age 60, three out of every five women and three out of every ten men will fracture a bone. When people fracture a hip they lose their independence and become much less mobile. Exercise is one lifestyle approach which may help in preventing osteoporosis by slowing bone loss and keeping the muscles strong. Previous research has not been able to clearly demonstrate the usefulness of exercise due partly to the difficulty in getting people to exercise for a least one year, which is how long bone studies must be carried out for. We have conducted two large research studies in women past the menopause where they have done weight training exercises. In the previous study we showed the greatest increase in bone mass occurred in those women lifting the heaviest weights. In a recently completed two year study in 126 woman, which forms the basis of this proposal, we found a weight training program was effective at increasing the bone mass at the hip, a common fracture site. The fitness group did not show any increase. So although we have been able to show this type of exercise helps increase bone mass we don't know how the bone is able to respond to this. The question we wish to address with this proposal is does exercise slow the breakdown of bone or does it help form new bone? The best way to be able to answer this question is by measuring certain products in blood, known as bone markers. Bone is continually turning overthese markers are released from bone into the blood. By studying these bone markers in blood samples taken from the subjects over two years it will helps us determine how exercise is affecting bone. From our previous studies we know that weight training can help slow bone loss. By measuring the bone markers we will then be able to make recommendations to people on how exercise will help prevent bone loss.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.
Micro-architectural Bone Structure Determined By Magnetic Resonance Imaging (MRI)
Funder
National Health and Medical Research Council
Funding Amount
$52,288.00
Summary
Osteoarthritis is the main form of arthritis. Bone metabolism is involved in osteoarthritis, however it is unknown how this relates to knee structures prior to disease onset. Magnetic Resonance Imaging techniques enable measurement of a healthy knee joint to a diseased one. By using the Geelong Osteoporosis Study, we will demonstrate how bone metabolism affects change in knee structure, and the risk of osteoarthritis.
How Does Osteocalcin Reverse Glucocorticoid-Induced Dysmetabolism?
Funder
National Health and Medical Research Council
Funding Amount
$635,038.00
Summary
The benefits of glucocorticoids (GCs) are often compromised by adverse effects such as bone loss, diabetes & obesity. There is now evidence that osteocalcin regulates fuel metabolism. Osteocalcin may therefore be a potential target to prevent the adverse metabolic effects of GC therapy. We aim to determine how osteocalcin regulates energy metabolism in adipose tissue and the liver under conditions of GC excess, and whether and how osteocalcin acts through a G-protein coupled receptor.
Functional Effects Of Polymorphic Variation Of The Aromatase (CYP19) Gene On Enzyme Activity:relationship To Disease
Funder
National Health and Medical Research Council
Funding Amount
$237,708.00
Summary
After menopause, oestrogen synthesis changes from an ovarian to an adipose source by concersion of androgens to estrogens, a process catalyzed by aromatase, the product of the CYP19 gene. We will generate mutants of the CYP19 gene that we have previously found in humans by site-directed mutagenesis and observe the effects of these mutants on aromatase function. This research will help with diagnosis and treatment of breast and other cancers and osteoporosis in humans .
The Regulation Of Vitamin D-Dependent Bone Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$612,535.00
Summary
This project aims to establish the cellular basis for the importance of vitamin D in bone. This information is necessary to develop public health nutritional recommendations for improving in skeletal health and reducing the incidence of hip factures in the elderly. Furthermore our data have the potential to reveal novel activities of vitamin D that could eventuate as pharmacological targets.
Effect Of Bisphosphonates On Bone Architecture And Glucose Metabolism In Men With Prostate Cancer Receiving Androgen Deprivation Therapy: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$566,215.00
Summary
Androgen deprivation therapy (ADT) is a type of hormonal treatment which is effective for prostate cancer treatment. However, ADT may cause bone fragility, weight gain, diabetes and heart disease. We will examine the effects of a bone strengthening treatment on bone structure and glucose metabolism in men receiving ADT. This trial should help in better define the risk benefit ratio of ADT, and therefore provide treating doctors with better guidance as to when and how to use this therapy.