Professor Philip Sambrook Young Investigator Travel Award 2016
Dr Jinwen Tu (centre)
ANZAC Research Institute, Concord Repatriation General Hospital, Sydney
'Tamoxifen-Induced Deletion of the Glucocorticoid Receptor in Chondrocytes Enhances K/BxN Serum–Induced Arthritis in Mice'
Glucocorticoids (steroids) have been used successfully for many years to treat rheumatoid arthritis (RA). We have a clear understanding of how these drugs work, but we know much less about how the steroids that are produced by our own body (endogenous glucocorticoids) also affect the development and severity of diseases such as RA and osteoporosis. Dr Tu will present research at the 2016 Annual Scientific Meeting of the American Society for Bone and Mineral Research (ASBMR), in Atlanta, Georgia, that demonstrates the importance of the interactions between endogenous glucocorticoid molecules and cartilage cells in the development of RA. In a series of laboratory experiments, Dr Tu has shown that blocking the ‘signals’ that cartilage cells receive from endogenous glucocorticoids results in loss of control of cartilage cell behavior. As a result, cartilage cells release molecules that stimulate inflammation, leading to the destruction of cartilage and bone that are characteristic of RA. Understanding these complex processes is important in order to develop new, specifically targeted drugs that may help to control the devastating effects of RA on joints and bones.
AMGEN OA-ANZBMS Clinical Grant Program 2016
Clinical Associate Professor Amanda Vincent (left)
Monash Centre for Health Research and Implementation (MCHRI), Monash University, Victoria
'Improving awareness and management of bone health and fracture prevention in women with premature menopause.'
Up to 10% of women experience premature menopause (before the age of 40), which puts them at increased risk of developing osteoporosis. Both medical professionals and patients lack awareness of this increased risk, and action that could reduce osteoporosis and fracture risk is often not taken. Professor Vincent’s project will focus on identifying knowledge gaps via a consultation process with women, health professionals and support groups. This will inform the development of evidence based information for both women and health professionals, which will be made freely available on the Osteoporosis Australia website. Another arm of the project will investigate the ability of a new bone strength measurement technique, trabecular bone score, to improve the identification of women with premature menopause who are at risk of fracture. Lastly, the project will compare different methods of bone density testing in women with premature menopause due to Turner syndrome, a group in whom the usual method of bone density testing can be inaccurate.
AMGEN-GSK OA-ANZBMS Clinical Grant Program 2015
Professor Julie Pasco, Deakin University
‘Clinical utility of reference point indentation’
Measurement of bone mineral density is routinely used to assess fracture risk, but is not an accurate method of predicting who is more likely to have a fracture. Professor Pasco’s project will test an alternative way of measuring bone quality to assess fracture risk. The OsteoProbe will be used to measure the ability of bone to resist the growth of cracks in a group of men participating in the Geelong Osteoporosis Study. The new measures will be compared with other ways of measuring bone quality and strength, and the relationships with health behaviours, psychosocial factors and health conditions will be explored. This new research has the potential to change the way that bone health is assessed. The long-term goal is to improve the diagnosis and treatment of people at risk of fracture.
Dr Phillip Wong, MIMR-PHI Institute
‘Treatment of Osteoporosis in Patients with Inherited Red Blood Cell Disorders’
Osteoporosis and fracture is a common problem in adults with inherited red blood cell disorders that require regular blood transfusion. Over 50% of patients with these disorders have severe osteoporosis, even in early adult life. This bone disease progressively worsens, leading to fracture and pain. Working at Monash Health with one of the world’s largest groups of patients with inherited blood disorders, Dr Wong’s research has shown that patients lose excessive amounts of calcium in their urine, putting them at risk of kidney stones and weakened bones. This project examines the use of a diuretic (fluid tablet) to prevent the loss of calcium in the urine and reduce bone loss. This study will be the first of its kind worldwide to target calcium loss in urine to prevent bone loss and decrease kidney stones in people with inherited blood disorders needing transfusion.
Osteoporosis Australia bioDensity Equipment Award
The equipment proudly donated to OA by Performance Health Systems
Professor Belinda Beck, School of Allied Health Sciences, Griffith University, QLD
'Man vs Machine: What is the best type of weight training for osteoporosis?'
We know that exercise is good for bones, but we still have questions about the safest, most effective way to exercise if you have osteoporosis or low bone strength. Testing different exercise methods against each other is a useful way to answer these questions. Professor Beck’s project will test how well a new exercise machine, the bioDensity system, can stimulate stronger bones in people who have low bone density. The results will be compared to another group of people who perform conventional weight training, which is already known to improve bone strength. The trial will also compare how well the two methods reduce the risk of falling, which is a major cause of fractures in people with osteoporosis. This project will go a long way to providing health professionals with the evidence they need to prescribe safe and effective exercise to reduce the risk of fractures in people with osteoporosis.
RACP/Osteoporosis Australia Research Entry Award 2015
Dr Anne Trinh - ‘The optimisation of bone health in chronic neurological conditions’
As life expectancy in people with neurological conditions such as spina bifida and cerebral palsy improves, poor bone health and fractures are emerging as health issues for these patients. We have limited understanding of how often fractures occur in these patients. There is a clear need to investigate the extent and causes of osteoporosis in people with neurological conditions, and to establish the evidence needed to recommend the most appropriate treatments. Working closely with Dr Fran Milat at the Monash Institute of Medical Research, Dr Trinh aims to determine the prevalence of poor bone health and fractures in young adults with spina bifida and cerebral palsy, examining the complex relationships between the density and structure of bones, the composition of the body as a whole, and the risk of fractures. The team’s findings will inform the planning of clinical trials to determine how best to treat osteoporosis in adults with chronic neurological conditions.
AMGEN-GSK OA-ANZBMS Clinical Grant Program 2014
1. Dr Fran Milat - Monash Institute of Medical Research - 'The Optimisation of Bone Health in Chronic Neurological Conditions'
Cerebral palsy and spina bifida are common causes of physical disability in Australian children. Poor bone health is more likely to develop in these conditions, resulting in an increased risk of fractures in adulthood. These can have a devastating impact on already limited mobility. Dr Milat’s research will fulfil an unmet need to understand the causes of osteoporosis as well as the optimal treatment and prevention of fractures in adults with these conditions. Her findings will help in the planning of clinical trials to determine the optimal treatment of osteoporosis in adults with chronic neurological conditions, and contribute to the development of new treatment guidelines.
2. Dr Weiwen Chen - Garvan Institute of Medical Research, Sydney - 'Clinical applications of trabecular bone score (TBS) in populations at higher fracture risk'
The ‘gold standard’ for the assessment of bone strength is the measurement of its density – the quantity of bone related to its area. However, researchers have known for some time that measuring the quality of bone may be just as important as determining its density. Dr Chen’s research aims to understand how assessing the quality of the underlying ‘scaffold’ structure of bone might predict fracture risk more accurately than measuring its density alone. This will help improve the management of bone health in people with chronic diseases, who can be at higher risk of fracture despite often having normal bone density.
2014 Sambrook Award Recipient
Dr Kirtan Ganda
Dr Ganda is an endocrinologist at Sydney’s Concord General Repatriation Hospital. He has a strong commitment to improving bone health in the community through a combination of patient care, teaching and research. Dr Ganda’s research focusses on how best to prevent more fractures occurring in people who have already suffered a minimal trauma fracture due to osteoporosis, and an in-depth analysis of the effectiveness of the Minimal Trauma Fracture Service at Concord Hospital is the focus of his recently completed PhD. This research has been extended to include an analysis of secondary fracture prevention programs throughout Australia and overseas. Dr Ganda will use his award to present his latest findings at the Australian and New Zealand Bone and Mineral Society Annual scientific meeting in Queenstown, New Zealand, and the American Society for Bone and Mineral Research annual meeting in Houston, both taking place in September 2014.
RACGP/ Osteoporosis Australia Bone Health Research Grant Award 2014
Dr Simon Vanlint - 'Improving the bone health of cancer survivors - a pilot study of patient activation and resource provision to imrpove bone health management after breast and prostate cancer'
Dr Vanlint’s project aims to improve the bone health of cancer survivors. People with breast and prostate cancer make up the majority of cancer survivors in Australia today, and are 2-4 times more likely to develop osteoporosis than the general population. Osteoporosis is a serious and life-changing disease, but doctors and patients are often unaware of the effects that cancer and its treatment can have on the bones. By developing new patient information resources and more effective ways of communicating the importance of bone health, this project aims to empower patients with the knowledge and confidence they need to look after their own bone health. Information resources for both patients and doctors will also be used to help Dr Vanlint develop better ways for doctors to manage the bone health of people at risk of osteoporosis after breast or prostate cancer.
RACP/Osteoporosis Australia Research Entry Award 2014
Dr Weiwen Chen - 'Effects of osteoporotic fractures and treatment on mortality risk'
Osteoporosis Australia has partnered with the Royal Australian College of Physicians (RACP) to support talented trainees as they enter the early stages of a research career into the prevention and treatment of osteoporosis. The 2014 RACP - Osteoporosis Australia Research Entry Award was granted to Dr Weiwen Chen, at Sydney’s Garvan Institute of Medical Research, to investigate the causes of early death following fractures due to osteoporosis.
Dr Chen’s previous research has found that people who have suffered certain types of fracture due to osteoporosis are more likely to die early than those who haven’t. The causes are not always clear, and may be very complex. Research has also shown that osteoporosis treatments not only make further fractures less likely to occur, but also reduce the risk of early death. A better understanding of the problem of early death after fracture would help to improve both doctor’s and patient’s awareness of how important it is to diagnose osteoporosis and start treatment early in order to prevent further fractures.
This project will examine the records of all patients admitted to hospital emergency departments in NSW over several years, collecting information on fractures, whether the patient was diagnosed with osteoporosis and started on treatment, any subsequent hospital admissions and the age at which the patient died. Detailed information about hospital admissions will help build an understanding of the trail of events leading from the fracture to the death of the patient. Well organised services that set out to ‘capture’ patients who arrive at hospital with a fracture have been shown to reduce rates of re-fracture – this project will also investigate for the first time whether Fracture Liaison Services have an impact on the rate of early death in hospitals in which they are established.
This will be the first Australian study of this size to show the relationship between osteoporotic fracture and the risk of early death. Dr Chen and her team hope that the findings will make osteoporosis a higher priority for both hospitals and general practitioners.
AMGEN-GSK OA-ANZBMS Clinical Grant Program 2013
1. Associate Professor Craig Munns - The Children’s Hospital at Westmead, Sydney - 'A fracture prevention service to optimise bone health and prevent osteoporosis in the paediatric population'
A/Professor Munns will conduct research into osteoporosis in children who have had fractures. Identifying children who may have osteoporosis will help doctors to intervene early so that fractures in later life are prevented.
2. Professor Susan Davis – Monash University - 'Achieving targeted assessment of bone health in women at midlife'
Professor Davis has been awarded a grant for research into the prevalence of osteoporosis in women having bone density testing at midlife.
This research project will help doctors understand when it is most useful to test middle-aged women for osteoporosis so that action can be taken to reduce the risk of future fractures.
AMGEN-GSK OA-ANZBMS Clinical Grant Program 2012
1. Dr Jackie Center - Garvan Institute of Medical Research - Fracture associated mortality: An international study combining multiple datasets
Dr Center’s research aims to understand why elderly people who have osteoporotic fractures are at increased risk of dying early. Failure to understand the serious consequences of fracture is a potential cause of the poor treatment rates of osteoporotic fracture worldwide. During this project, Dr Center found that fractures of the arm or leg bones, usually considered less serious than hip or spinal fractures, increase the risk of early death in elderly people. Although the risk of dying is not as high as after a hip fracture, arm and leg fractures are very common, so the overall impact of these fractures in the community is significant. These findings highlight the importance of detecting and treating osteoporosis in the elderly, particularly to prevent second fractures. The team will now go on to investigate whether osteoporosis treatment improves survival after fracture – early results suggest that it does. Ultimately, Dr Center’s research aims to understand the reasons why some people are more likely to die after a fracture. This will help doctors to predict which patients will do badly after a fracture, so that they can take action to prevent early death. Dr Center has recently been awarded a grant from the National Health and Medical Research Council to continue this research. The findings have been published in several prestigious scientific journals, presented at conferences in Australia, the US and the UK, and have also been covered by the media.
2. Professor Marlena Kruger - Massey University, Palmerston North, NZ - Health, vegetables, herbs and fruit study (The Scarborough Fair Study)
Professor Kruger’s project set out to determine whether eating more fruits and vegetables slows down the rate of bone loss that commonly occurs at menopause. Special ‘marker’ molecules that are released from bone that has broken down are often detected at higher levels in women after they have been through the menopause. Dr Kruger’s team found that women eating a diet that is rich in fruits, vegetables and herbs showed lower levels of bone markers in their urine than women eating their normal diet. The research also showed that certain fruits, vegetables and herbs are more effective than others in reducing levels of bone markers. These encouraging results may lead to a larger trial to determine whether increasing fruit and vegetables in the diet leads to improved bone health and fewer fractures in this group of women in the longer term. Dr Kruger’s work has been presented at conferences and published in scientific journals.
3. Dr Egon Perilli – Austin Health, University of Melbourne - The material and structural basis of bone fragility in postmenopausal women with osteopenia or osteoporosis
The current gold standard for diagnosing osteoporosis is the measurement of bone density - the amount of mineral and other matter that it contains. Although bone density can give the doctor a good idea of a patient’s bone health, it is not always a reliable way of predicting whether or not the patient is likely to suffer a fracture. Fracture risk is also thought to be dependent on the overall structure of the bone – its porosity. In this project, Dr Perilli used a specialized technique to measure bone porosity in women known to have low bone density, comparing the results to a group of women with normal bone density. Bone porosity was found to be a better predictor of fracture than a low bone density measurement on its own. Most importantly, this was found to be the case in women with bone density not quite low enough to be diagnosed as osteoporosis – it is this group that is actually most at risk of fracture. These findings have important implications for the care of patients with poor bone health. They suggest that doctors should measure bone porosity in patients who, according to their bone density measurement, may not officially have osteoporosis, but may nevertheless have a higher risk of fracture than is usually thought. Patients with high bone porosity may benefit from treatment with osteoporosis drugs to prevent future fracture. This research has been published in several scientific journals and has been presented at conferences in Australia and overseas. It also contributed to the awarding of the Flinders University Vice Chancellor Early Career Researcher award to Dr Perilli.
RACP/Osteoporosis Australia Research Entry Award 2012
Dr Philip Wong - Thalassaemia bone disease and the role of iron overload on bone biology
Osteoporosis Australia has partnered with the Royal Australian College of Physicians (RACP) to support talented trainees as they enter the early stages of a research career into the prevention and treatment of osteoporosis. The 2012 RACP - Osteoporosis Australia Research Entry Award was granted to Dr Phillip Wong, at Melbourne’s Prince Henry’s Institute, to investigate the blood disease thalassaemia and its effects on bone. Thalassaemia is an incurable genetic disorder that affects the production of haemoglobin, the protein in red blood cells that transports oxygen around the body. One of the less understood complications of severe thalassaemia is osteoporosis. Dr Wong’s RACP - Osteoporosis Australia fellowship project aimed to understand the link between thalassaemia and osteoporosis, and in particular, how iron overload and iron chelators may be key to this association. Dr Wong’s research has discovered a previously unknown link between kidney stones, reduced bone density and thalassaemia. This research may contribute to the development of improved drugs to deal with the consequences of iron overload in people with thalassaemia.
RACGP/Osteoporosis Australia Bone Health Research Grant
Dr Oliver Frank, University of Adelaide - Increasing prevention, detection and treatment of osteoporosis through automated opportunistic reminders to patients, general practitioners and practice nurses
The aim of Dr Frank’s study is test the effectiveness of reminders issued to patients, GPs, and practice nurses in increasing screening, prevention and treatment of osteoporosis. The study requires developing specific software modules for existing clinical records systems that will recognise certain patient scenarios and deliver reminders on-screen to GPs.
If this strategy is found to be effective, widespread implementation as part of GPs’ electronic clinical record systems is expected. This is envisaged to reduce the prevalence of preventable fractures due to osteoporosis, and ensure more Australians enjoy a healthy and independent life in their later years. It will also improve population health and reduce costs of health care.
A/ Professor Tania Winzenberg (with Dr Dawn Dore and Professor Graeme Jones) - Vitamin D for correcting deficiency in adolescents: a general practice-based RCT
Improving children’s bone density (a measure of their bone strength) may reduce both the risk of childhood fracture and the risk of fractures due to osteoporosis in older adult life. Vitamin D is important for children’s bone health but it is unknown whether correcting mild to moderate vitamin D deficiency in children will result in clinically important improvements in bone density. Adolescents are at particular risk of vitamin D deficiency and are also a group who may not take medications regularly. The optimal dosage approach for adolescents, to help them take vitamin D regularly enough to correct deficiency, is not known.
The main aim of this trial is to test two different vitamin D dosages to see if they both correct vitamin D deficiency in adolescents. The study will also show whether vitamin D deficient adolescents can be successfully identified through general practice and provide preliminary data on whether correcting vitamin D deficiency results in significant improvements in bone density.
OA/ANZBMS Research Fellowship 2011 supported by Amgen
Dr Michelle McDonald PhD research Officer,Bone growth Foundation Fellow, Orthopaedic Research and Biotechnology Department the Kids Research Institute, The Children's Hospital Westmead
Osteoporosis is a highly common and deleterious disease. As a result, significant research effort has gone into developing treatment strategies. Until recently the most common treatment has been agents that prevent further bone resorption, anti-resorptives. Emerging new therapeutics aim to enhance bone formation and hence help rebuild the skeleton, these are known as anabolics. A new class of anabolic agents known to modulate a specific biological pathway in bone cells, known as the Wnt/β catenin pathway, are currently being trialled in patients with extremely promising outcomes. As an orthopaedic research lab we have an invested interest in how these novel agents may act in a bone repair scenario. This is of particular interest considering most presenting osteoporotic patients have sustained a fracture. Little is known about the mechanism of this particular pathway during bone repair. We have obtained and developed numerous biological tools that will allow us to modify the Wnt/β catenin pathway whilst accurately assessing the numerous stages of bone repair. Such investigations will expand greatly the knowledge base of fracture repair biology. Furthermore, orthopaedic surgeons are commonly challenged with high trauma fractures that have impaired healing responses or fracture repair in patients with complicating underlying disease. In such cases intervention with therapeutics that enhance bone formation would be advantageous. Our work aims to support the theory that emerging anabolic therapies for osteoporosis will also enhance bone repair, thereby potentiating their successful application during the management of orthopaedic trauma.
OA/ANZBMS Research Fellowship 2010 supported by Amgen
Tania Winzenberg, Senior Research Fellow, Menzies Research Institute
Finding out how likely someone is to have a fracture from osteoporosis i.e. assessing their fracture risk, can be useful in deciding how to treat a patient who has osteoporosis. If someone is told that they may be at high risk of having a fracture, they may also decide to make changes in their lifestyle to improve the strength of their bones. We will examine these 2 different uses of fracture risk assessments in 2 studies. In one study, we will interview general practitioners to find about how they might use tools to assess fracture risk in their patients. This will include finding ways to make it easier for GPs to perform calculations and finding out whether GPs would use fracture risk information to change their patient’s treatment or to motivate patients to change their behaviour to reduce their risk. In the second study we will measure bone density and lifestyle behaviours in women who were made aware of their fracture risk in a study over 10 years ago.
Dr Emily Gianatti, Austin Health, University of Melbourne. Testosterone treatment in men with Type 2 Diabetes Mellitus
Men with type 2 diabetes mellitus frequently have low testosterone levels (main male sex hormone). Lowered testosterone levels have been associated with worse diabetic control, greater insulin resistance and increased weight. Low testosterone levels are also associated with osteoporosis in men without diabetes. This large, double blind, placebo controlled, randomized trial will investigate the effect of intramuscular testosterone injections on a range of factors in men with type 2 diabetes, including bone mineral density.
ANZ Wicking Trust
Dr Robyn Daly, University of Melbourne, Western Hospital. 'Osteo-cise' - Better Bones for Life
A community, evidence-based, exercise, falls prevention and education program titled 'Osteo-cise: Better Bones for Life'. A collaborative project involving 3 centres (University of Melbourne, Western Hospital / Deakin University / Geelong Hospital) and Osteoporosis Victoria.
Myer Foundation, National Scholarship
Dr Belal Khan, University of Melbourne, Western Hospital
This project addresses the balance between the benefits of dietary calcium on bone and any potential adverse cardiovascular outcomes. It also investigates the influence of vitamin D deficiency on these outcomes
Macquarie Group Foundation Fellowship
Charles Chen, Institute of Bone & Joint Research, Royal North Shore Hospital. Common pathways influencing osteoporosis and atherosclerosis risk.
The study used 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).
OA/NHMRC Scholarship 2008-2009
Estabelle Ang, Center for Orthopaedic Research/University of Western Australia. Control of osteoclastic activity and its potential therapeutic treatment for bone diseases.
Bone, a rigid yet dynamic organ, plays a crucial part in supporting the structure and mechanical functions of the body. Bone consists of two major cell types: osteoblasts (bone-forming cells) and osteoclasts (bone-eating cells). The imbalance in these two cell types results in bone diseases. For instance, an increase in the number of osteoblasts results in osteopetrosis. On the other hand, an increase in the number of osteoclasts results in osteoporosis (including postmenopausal osteoporosis), which is associated with brittle bones, leading to higher risks of fractures.
Currently, treatments for bone diseases, such as the Bisphosphonates and Estrogen Replacement Therapy relies heavily on chemical compounds and has been shown to lack specificity and cause adverse side effects. If, however, natural substances can be successfully identified for use in bone disease treatment, the side effects caused by chemical compounds can be markedly reduced.
The study investigated the following hypothesis using in vitro and in viva model.
- Natural compounds inhibits RANKL-induced osteoclasts differentiation and activation as well as osteoclastic bone resorption
- Natural compounds modulate RANKL-induced signalling pathways
- Collagen-induced arthritis mouse model treated with natural compounds could protect cartilage destruction and bone erosion in inflammatory conditions
The results obtained from this study will provide greater understanding into the molecular mechanisms of bone diseases resulting from increased osteoclastic activity. The newly identified natural compounds will provide a wider range of treatment options that are safe and effective for patients suffering from bone diseases.
OA/NHMRC Scholarship, 2008-2009
Dr Cherie Chiang, Department of Medicine Austin Health/University of Melbourne. The role of male hormones in bone growth and development.
This research project investigated the mechanisms of bone formation and the central role androgens play in regulating bone formation in males. Male osteoporosis is a significant and costly health problem. In my retrospective study supported by the National Arthritis and Musculoskeletal Conditions Improvement Grants, over 20% of patients admitted with a hip fracture were male, while 20% of General Practitioners who responded to the survey consider osteoporosis to be a female problem only. The impact of male osteoporosis to the community has only been recently recognised.
Androgens (male hormones) play an important role in the growth and maintenance of bone in males. Understanding the mechanisms of bone formation and the central role androgens play in regulating bone formation in males will allow determination of the less profound effects in females, which will provide avenues for the prevention and reversal of bone fragility in both men and women.
Dr Emma Hamilton, Department of Medicine and Endrocrinology, Austin Health, University of Melbourne. The relationship between testosterone and the architecture of bone
Testosterone is an important hormone for the maintenance of healthy bone in men. Men with testosterone deficiency and men with prostate cancer on treatment that lowers testosterone levels are at increased risk of fractures, osteoporosis and reduced bone mineral density. The structural basis of this decrease in bone density is not well understood. The aim of this project is to examine the relationship between testosterone and bone structure - as assessed by both the new technique high resolution peripheral quantitative CT and conventional dual energy x-ray absorptiometry in men with testosterone deficiency and men with prostate cancer.
Dr Kathy Wu, ANZAC Institute, Concord Hospital. Role of androgens in bone microarchitecture in men.
Dr Rosie Meng
Curtin University Perth
St Vincent's Institute, University of Melbourne
Calcitonin inhibition of parathyroid hormone anabolic action
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.
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.
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.
Dr. Paul Anderson
Hanson Institute, IMVS
Vitamin D deficiency and femoral bone loss
The Childrens Hospital, Westmead
The role of the osteoclast in endochondral ossification during fracture repair
St Vincents Institute
Osteoclast mediated regulation of bone formation
Dr. Robin Daly
School of Exercise and Nutrition Sciences, Deakin University
The role and exercise and diet in the prevention of osteoporosis in older men
Department of Physiology, The University of Sydney
Citracal Osteoporosis Research Scholarship
Calcium Sensing in Bone Cells
School of Health Science, Griffith University
The effects of selected colony stimulating factors and interleukins on osteoclast development and function
Dr Yunbo Duan
Dept of Medicine and Endocrinology, University of Melbourne
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
Dept of Rheumatology, Royal North Shore Hospital,
The Institute of Bone and Joint Research, University of Sydney
Epidemiology of osteoporotic fractures in the frail elderly
Natalie El Haber
Dept of Medicine, Royal Melbourne Hospital, The University of Melbourne
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
Prevention of osteoporotic fractures in transplant patients
Dept of Physiology, University of Sydney
$2,000 (top up)
The role of the sympathetic nervous system in bone cell function