Research Fund Previous Awardees
2007 Fellowships
Mathis Grossmann
Department of Medicine, Austin Health, University of Melbourne
Role of androgens in bone microarchitecture in men
Deficiency of testosterone, the main male sex hormone, can lead to decreased bone density, or osteoporosis, which in turn increases fracture risk. The mechanisms of how testosterone deficiency leads to structural decay of the skeleton in men have not been established. The effects of testosterone replacement on bone architecture in men with abnormally low testosterone levels are also unknown. With the development of high resolution micro-computed tomography, it is now possible to quantify the effects of deficiency and replacement of testosterone on bone micro-architecture and so gain to insight into bone size, shape, thickness and other structural parameters. This enables to predict bone strength and fracture risk. The Austin Health is the only centre in Australia (only 11 machines world wide) to have this technology. We will use this technology to look at serial changes in bone parameters in men treated with testosterone to better understand the mechanisms by which testosterone affects the male skeleton, and how this changes bone architecture and fracture risk.
Significance of the proposal
Decreased bone density (osteoporosis) in men is neglected even though the life time risk for fracture is 25% for men. Moreover, 30% of all hip fractures in the community occur in men. A most important risk factor for osteoporosis is deficiency of the main male sex hormone (testosterone). Yet, no prospective studies have been done to examine the morphological changes produced by testosterone deficiency, or on the effects of testosterone replacement on bone architecture. Our study will lead to a better understanding into of the mechanisms of how testosterone deficiency leads to increased bone fragility. It will also elucidate the structural consequences of testosterone replacement on the male skeleton, and help to better predict, and ultimately to prevent, fractures in men.
2007 Scholarships
Charles Chen
Institute of Bone & Joint Research, Royal North Shore Hospital
Common pathways influencing osteoporosis and atherosclerosis risk
Osteoporosis is a common skeletal disorder, affecting aging populations worldwide. There is strong evidence for a major genetic contribution to variation in bone density and bone metabolism from twin studies. Twin and family studies also show genes have a major effect on body fat, blood pressure and blood vessel function. There is evidence of inverse relationship between certain cardiovascular and bone risk factors. The proposed study will use the powerful twin model to examine the relationship between cardiovascular and bone risk factors. Twins provide advantage in medical research by reducing sample size that need to be studied due to matching for age, sex and many environmental and lifestyle factors.
Twin studies of osteoporosis have been running at the Royal North Shore Hospital since 1996, in conjunction within the Australian Twin Registry, recruiting large numbers of same sexed identical and non identical twins. Bone density has been measured and blood collected. Continued contact has been maintained with most twins by newsletters and repeat visits in many twin pairs. Given the relatively long period since baseline measurements were made, these twin studies offer the opportunity to unravel the interaction between bone, fat, cardiovascular risk factors and osteoporotic risk factors with a very large sample size and long duration of follow up (9 years).
The proposed research will investigate the following hypotheses using the powerful twin model:
- Bone mineral density (BMD) and bone strength measures are lower at clinically relevant sites in subjects who are hyperlipidemic and in subjects with impaired arterial stiffness or aortic calcification
- Loss of BMD is greater in patients with atherogenic risk factors than in subjects without them
- Atherogenic risk factors are associated with within-pair differences in biochemical markers of bone turnover and in circulating levels of relevant hormones and cytokines, demonstrable by cross-trait, cross-twin analysis in discordant twin pairs
The project is likely to lead to a better understanding of these diseases including the clinical importance of basic science in this area, better identification of those at high or low risk of the respective diseases and have therapeutic implications based upon risk factor modification.
2006 Fellowships
Dr. Paul Anderson
Hanson Institute, IMVS
Vitamin D deficiency and femoral bone loss
The bone diseases, osteomalacia and osteoporosis are characterised by low bone mineral content and an increase in fracture risk. The consequence of vitamin D deficiency, due either to the lack of sunlight exposure, diminished capacity to produce vitamin D or to poor nutrition results in inadequate bone mineralisation.
Our studies will focus on defining these levels of serum 25D and investigating the mechanisms by which vitamin D deficiency leads to osteomalacia or osteoporosis using well characterised animal models for vitamin D-deficiency and post-menopausal osteoporosis.
The main questions we are investigating include:
- What is the minimum level of serum 25D necessary to prevent the development of osteoporosis?
- What is the effect of the interaction between vitamin D and dietary calcium intake on skeletal health?
- What is the effect of age and oestrogen status on vitamin D requirement to prevent osteoporosis?
2006 Scholarships
Michelle McDonald
The Childrens Hospital, Westmead
$24,000
The role of the osteoclast in endochondral ossification during fracture repair
Osteoporosis causes skeletal weakening resulting in a dramatic increase in fractures in the elderly. One in three women and one in five men are affected, costing Australia $7 billion annually. Fortunately, treatments exist that reduce fractures in osteoporotic patients by up to 50%. Bisphosphonates, a common and effective treatment for osteoporosis, potently reduce the activity of osteoclasts, the cells that resorb bone. While osteoclasts may increase osteoporotic fractures, they are also involved in fracture healing. Thus bisphosphonate treatment may compromise the ability to heal fractures in this at risk population.
This work aims to reveal the importance of osteoclasts in fracture healing and to directly test the effect of bisphosphonate treatment on this process using a rodent fracture model developed by orthopaedic surgeons in our laboratory.
Jonathan Gooi
St Vincents Institute
$24,000
Osteoclast mediated regulation of bone formation
The maintenance of healthy bone structure depends on the activities of two cell types within the bone: osteoblasts (bone forming cells) and osteoclasts (bone destroying cells). Bone structure is constantly changing so that it can better resist dietary or physical stresses. These changes result from the co-ordinated or 'coupled' action of osteoblasts and osteoclasts. In osteoporosis, and in other diseases where bone is lost and weakened (including rheumatoid arthritis and cancer invasion), these activities become uncoupled, that is, osteoclasts destroy too much bone and the osteoblasts fail to compensate by making more bone. The way in which osteoclasts communicate this coupling signal to osteoblasts, and so stimulate bone formation is unknown.
Currently there is only one building therapy for osteoporosis on the market (Teriparatide), which is expensive and requires daily injection. It is not yet understood how this therapy works, but we do know that it depends on communication between osteoblasts and osteoclasts.
Thus, the aim of this project is to identify coupling signals that stimulate osteoblasts to build new, stronger bone, and so design more effective therapies for osteoporosis.
Update January 2008
As I enter the final year of my PhD, I have shown that communication between the osteoclast and osteoblast is necessary for the full effect of Teriparatide. When Teriparatide is co-administered with an osteoclast inhibitor there is a blunting of the full effect of Teriparatide, suggesting an osteoclast derived coupling signal that contributes to the osteoblasts ability to build new bone in the young growing rat.
Subsequently, whole genome microarray analysis has identified novel differentially expressed genes which may be potential 'coupling factor' candidates. The final year of my PhD will focus on examining candidate genes and their ability to stimulate osteoblasts to build new, stronger bones.
I would like to acknowledge the kind support of Sanofi-Aventis in funding the research scholarship. Without their support this work would not have been possible.
2005 Fellowships
Dr. Robin Daly
School of Exercise and Nutrition Sciences, Deakin University
$50,000
The role and exercise and diet in the prevention of osteoporosis in older men
2005 Scholarships
Shaimaa Atwa
Department of Physiology, The University of Sydney
$20,000
Citracal Osteoporosis Research Scholarship
Calcium Sensing in Bone Cells
Rouha Granfar
School of Health Science, Griffith University
$20,000
The effects of selected colony stimulating factors and interleukins on osteoclast development and function
2004 Fellowships
Dr Yunbo Duan
Dept of Medicine and Endocrinology, University of Melbourne
$40,000
Skeletal growth in Chinese and caucasion boys and girls
Dr Gerald Atkins
Dept Orthopaedic Surgery and Trauma, University of Adelaide
$10,000 (top up)
Bone remodeling in osteoporosis
2004 Scholarships
Charles Chen
Dept of Rheumatology, Royal North Shore Hospital,
The Institute of Bone and Joint Research, University of Sydney
$20,000
Epidemiology of osteoporotic fractures in the frail elderly
Natalie El Haber
Dept of Medicine, Royal Melbourne Hospital,
The University of Melbourne
$20,000
Does the heritability of gait and balance function help explain the familial aggregation of hip fracture: A twin study
Dr Dana Bliuc
Bone and Mineral Research Program, Garvan Institute of Medical Research
$20,000
Prevention of osteoporotic fractures in transplant patients
Tara Brennan
Dept of Physiology, University of Sydney
$2,000 (top up)
The role of the sympathetic nervous system in bone cell function
