Determining The Influences Of Cell Stress And Heat Shock Factor-1 Action In Osteoclast Formation And Pathological Bone Loss.
Funder
National Health and Medical Research Council
Funding Amount
$657,287.00
Summary
Cancer and rheumatoid arthritis cause painful bone destruction. This occurs due to increased numbers of bone destroying cells called osteoclasts. We found stress responses in bone cells can increase osteoclast numbers by activating proteins inside the bone cells that encourage osteoclasts to form. We will thus study whether cell stress blocking drugs might stop bone loss. As arthritis and cancer both cause stress responses, this work could identify a new way that such diseases affect bone.
Modulation Of Osteoclast Formation And Function To Prevent Joint Destruction In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$443,250.00
Summary
Rheumatoid arthritis is a disease that affects about 200,000 Australians. It is characterised by painful joint destruction leading to work disability, diminished quality of life and decreased life expectancy. The usual treatment of arthritis leads to less inflammation however it cannot be relied upon to control bone and joint destruction. Patients often have long term worsening of joint function despite short and medium term improvement in joint pain and swelling. One reason for this paradox may ....Rheumatoid arthritis is a disease that affects about 200,000 Australians. It is characterised by painful joint destruction leading to work disability, diminished quality of life and decreased life expectancy. The usual treatment of arthritis leads to less inflammation however it cannot be relied upon to control bone and joint destruction. Patients often have long term worsening of joint function despite short and medium term improvement in joint pain and swelling. One reason for this paradox may be that while research has mainly focused on inflammation, far less is known about the processes responsible for bone damage. Normally, specialised bone cells called osteoclasts carry out bone breakdown during growth and maintenance of the skeleton. In rheumatoid arthritis, these cells are responsible for the joint damage; this proposal, therefore, focuses on inhibiting the activity of these cells as a new therapy. So far, our work using a model of human rheumatoid arthritis has demonstrated that it is possible to separate joint inflammation from joint damage by selectively targeting osteoclasts with an inhibitor known as Osteoprotegerin. Besides Osteoprotegerin, we have identified two novel molecules named OCIL and sFRP-1 and shown that they are present in the joints of animals and humans with arthritis. Very recent experiments in our laboratory show that in the test tube, OCIL and sFRP-1 (like Osteoprotegerin) block osteoclast activity. The sFRP-1 molecule may also block a very important messenger molecule in arthritis called tumour necrosis factor. We therefore propose to study the effect of OCIL and sFRP-1 in the joints of mice with arthritis. We expect that these new inhibitors will have favorable effects on joint damage. If so, they could undergo further testing for use in humans. We believe that investigations along these lines may provide a rationale for an entirely new treatment approach to improve the long term outcome for patients with arthritis.Read moreRead less
Is Bisphosphonate Use For The Treatment Of Benign Bone Disease Associated With Impaired Dental Healing?
Funder
National Health and Medical Research Council
Funding Amount
$238,160.00
Summary
Osteoporosis (OSP) is a common condition where bones are thin and may break (fracture). Currently, approximately 2 million Australians suffer from OSP. This figure will rise over the next 20 years as people age. Recommended drug treatment of OSP involves medication called bisphosphonates. Recent research, including a warning from the National Adverse Drug Reaction Committee, has suggested a possible association between bisphosphonates and bone breakdown in the jaw (osteonecrosis) - a devastating ....Osteoporosis (OSP) is a common condition where bones are thin and may break (fracture). Currently, approximately 2 million Australians suffer from OSP. This figure will rise over the next 20 years as people age. Recommended drug treatment of OSP involves medication called bisphosphonates. Recent research, including a warning from the National Adverse Drug Reaction Committee, has suggested a possible association between bisphosphonates and bone breakdown in the jaw (osteonecrosis) - a devastating condition for which no effective treatment exists. This study seeks to determine if bisphosphonate use for the treatment of OSP or other non-cancerous (benign) bone disease (eg Paget's disease) slows dental healing and increases the risk of jaw osteonecrosis. This has major implications and significant potential benefits for the large numbers of people with OSP taking bisphosphonates. Currently, the chance of dental complications during bisphosphonate therapy and what factors predispose to such complications remains unclear. Given the large numbers of people at risk, these are important issues that require urgent careful investigation. We want to determine if long-term (more than 2 years' duration) bisphosphonate treatment of OSP or other benign bone disease slows dental healing and leads to jaw osteonecrosis. We will use a case-control study design given the expected low likelihood of slowed dental healing. This design involves identifying patients with slowed dental healing (cases), and patients with normal dental healing (controls). Cases and controls will then be compared for bisphosphonate use to see if it is more likely that cases have been taking bisphosphonates. Our results will help guide treatment recommendations for these drugs both nationally and internationally.Read moreRead less
Repair Of Tooth Enamel/dentine By Biomimetic Mineralisation
Funder
National Health and Medical Research Council
Funding Amount
$1,107,069.00
Summary
Dental caries (tooth decay) and erosion involve loss of tooth mineral and are major public health problems. The project will involve the proof-of-concept testing of a prototype dental professional product MI Enamel/Dentine RepairTM to repair early stages of mineral loss non-invasively. This will result in the development of a system which should revolutionize dental practice globally for the non-invasive repair of early tooth decay and erosion lesions with a surface seal of tooth-like mineral.
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.
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.