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
Does Childhood Physical Activity, Fitness And Fatness Impact On Knee Structural Change 20 Years Later?
Funder
National Health and Medical Research Council
Funding Amount
$301,977.00
Summary
Interventions to increase participation of physical activity (PA) and to reduce obesity in childhood are advocated to reduce the risks of cardiovascular and other diseases in adulthood, but the associations of childhood PA and obesity with knee osteoarthritic changes in adulthood are unknown. This study, with follow-up of a large cohort of Australian children over 20 years, will be the first to determine these associations using the powerful technique of magnetic resonance imaging.
Chemokines are small molecules that are released by a number of cell types, particularly monocytes, when inflammation occurs. Chronic inflammatory disease is associated with severe bone erosion and loss of bone quality. Surprisingly, chemokines control osteoclast development as well as macrophage activation; even if the osteoclast has formed, blocking chemokine signalling prevents bone resorption. Chemokines are a new and exciting target to control osteoclast formation.
Common Pathways Influencing Osteoporosis And Atherosclerosis Clinical Risk
Funder
National Health and Medical Research Council
Funding Amount
$443,090.00
Summary
It is recognised there are strong inherited effects on bone density and bone turnover as well as cardiovascular markers like serum cholesterol and arterial function. The study will examine the relationship between osteoporosis and atherosclerosis risk using the powerful twin model and two established large twin cohorts in Sydney and Melbourne. The work may lead to better prediction of common risk factors for these two important conditions.
A Longitudinal Study Of Knee Osteoarthritis Using X-ray And Magnetic Resonance Imaging
Funder
National Health and Medical Research Council
Funding Amount
$861,925.00
Summary
Osteoarthritis is the most common form of arthritis and commonly affects the hand hip and knee in older Australians with an annual cost of around 4 billion dollars. This study will lead to a greater understanding of the role of factors influencing the development and progression of osteoarthritis of the knee by utilising a novel magnetic resonance imaging technique. In particular, it will focus on the role of physical activity and bone underlying the cartilage. If associations are discovered, ac ....Osteoarthritis is the most common form of arthritis and commonly affects the hand hip and knee in older Australians with an annual cost of around 4 billion dollars. This study will lead to a greater understanding of the role of factors influencing the development and progression of osteoarthritis of the knee by utilising a novel magnetic resonance imaging technique. In particular, it will focus on the role of physical activity and bone underlying the cartilage. If associations are discovered, accurate public health messages regarding prevention can then be developed.Read moreRead less
An Evaluation Of Bone Density Screening In Premenopausal Women
Funder
National Health and Medical Research Council
Funding Amount
$175,046.00
Summary
Fractures due to osteoporosis are a major public health problem. Bone density is one of the major predictors of these osteoporotic fractures and is the result of the amount of bone gained in early life (i.e peak bone mass) and subsequent bone loss. Cigarette smoking, physical inactivity and inadequate calcium intake are widely regarded as risk factors for osteoporosis (as well as for other common diseases). Despite this information being widely available and actively promoted, the prevalence of ....Fractures due to osteoporosis are a major public health problem. Bone density is one of the major predictors of these osteoporotic fractures and is the result of the amount of bone gained in early life (i.e peak bone mass) and subsequent bone loss. Cigarette smoking, physical inactivity and inadequate calcium intake are widely regarded as risk factors for osteoporosis (as well as for other common diseases). Despite this information being widely available and actively promoted, the prevalence of these risk factors in the population remains unacceptably high suggesting that education alone at the public health level is not sufficient to modify these behaviours. In women (mean age 33) taking part in a study of the determinants of bone mass in children, we recently reported substantial change in these behaviours at 12 months follow-up when women received an information leaflet and individualised bone density information. These women were highly selected and it is unclear if this response is representative of all women. The aims of this study are, therefore, to test hypotheses in a random electoral roll sample of 400 women aged 25-44 from metropolitan Hobart relating to the effect of different types of educational programs and low initial bone mass on both lifestyle changes and changes in bone density over two years. This study will lead to accurate information about how best to target osteoporosis prevention programs in the younger age groups. Furthermore, as risk factors for cardiovascular and other diseases are often similar to those for osteoporosis, it is likely to provide insights into the prevention of these diseases and, as a result, have much greater potential for decreasing disease in the community.Read moreRead less
Gene Variants Related To Bone Density And Fracture.
Funder
National Health and Medical Research Council
Funding Amount
$330,375.00
Summary
Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. In addition, some people with bone fracture at the hip, or low bone density, have mutations in this gene. The gene is a master regulator of the cells that mak ....Bone density and osteoporosis have a genetic component. Identifying genes that are involved in determining bone density may permit advances in controlling osteoporosis. We have identified a variant that is related to bone density high enough to protect individuals four fold against Colle's fracture, the common wrist fracture seen in women. In addition, some people with bone fracture at the hip, or low bone density, have mutations in this gene. The gene is a master regulator of the cells that make bone: this gives hope that it may be possible to alter bone formation through this master regulator.Read moreRead less