BONE SIZE AND BONE TURNOVER: RELATIONSHIP TO FRACTURE RISK OVER TEN YEARS
Funder
National Health and Medical Research Council
Funding Amount
$428,225.00
Summary
The occurrence of fracture in the ageing population is a major public health problem because these fractures are responsible for considerable morbidity and mortality. Of women reaching 90 years of age, one third will fracture their hip and overall, one in every six women will sustain an osteoporotic fracture in her lifetime. The direct cost to the community is unknown but estimated, conservatively, at 175 million dollars annually. Most of this is likely to be the result of hip fractures which oc ....The occurrence of fracture in the ageing population is a major public health problem because these fractures are responsible for considerable morbidity and mortality. Of women reaching 90 years of age, one third will fracture their hip and overall, one in every six women will sustain an osteoporotic fracture in her lifetime. The direct cost to the community is unknown but estimated, conservatively, at 175 million dollars annually. Most of this is likely to be the result of hip fractures which occupy an estimated 400,000 bed-days annually. This bed occupancy is fourth next to mental illness, cardiac disease and cancer. The Geelong Osteoporosis Study is a large population-based epidemiological study currently under way to evaluate the major risk factors for fracture in women . This present study which will be an extension of the study to date, will provide in total, 8-10 years of data concerning the processes that result in increased bone fragility and fracture.Read moreRead less
Fractures, in particular femoral neck (FN) fractures, are a huge public health problem resulting in disabilities, mortality and financial cost to the community. The prevention of these fractures is based on estimation of bone strength. The decision whether someone needs treatment, or the effectiveness of a treatment can only be judged by estimating bone strength. The bottom line is that currently we cannot correctly estimate bone strength. Present methods such as bone mineral density (BMD) perfo ....Fractures, in particular femoral neck (FN) fractures, are a huge public health problem resulting in disabilities, mortality and financial cost to the community. The prevention of these fractures is based on estimation of bone strength. The decision whether someone needs treatment, or the effectiveness of a treatment can only be judged by estimating bone strength. The bottom line is that currently we cannot correctly estimate bone strength. Present methods such as bone mineral density (BMD) perform poorly. Most people who fracture are not detected by BMD because their BMD is either normal or high, and many people with low BMD never fracture. The main aim of this grant application is to develop new tools to allow doctors and scientists worldwide to better estimate FN strength. To develop new methods to replace BMD, scientists need to make use of the 3D aspects of the bone such as size, shape and internal architecture. Presently, these 3D aspects (structure) have not been adequately studied and scientists incorrectly approximate them. As a result new methods are not any better. A good quantification of structure is needed. Another reason for the failure to accurately estimate the strength of bones is that estimates are based on a single parameter whereas the bone, like any architectural structure (e.g. building), comprises many components acting together to maintain its strength. To determine the strength based on density alone is incorrect; the size, the shape and things inside the structure need to be considered as a whole. After quantifying correctly the structure and components of bone strength, we will determine how they can be used individually and together to better estimate the strength of the FN in men and women. Tools generated will be used to better determine people likely to fracture and needing treatment; to better tailor and monitor treatments. A better understanding of the causes and epidemiology of fractures will ensue.Read moreRead less
Osteoporosis is a disease associated with a progressive rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in 4 men will be affected. They cause pain, disability that can be permanent and are associated with loss of independence even premature death. Current treatments are able to partially restore bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent ....Osteoporosis is a disease associated with a progressive rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in 4 men will be affected. They cause pain, disability that can be permanent and are associated with loss of independence even premature death. Current treatments are able to partially restore bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent but these are limited by expense and safety concerns. We have discovered a pathway in the brain that when blocked, results in a doubling of the amount of bone in key bone sites and dramatic increases in bone strength. This occurs due to a marked increase in the amount of new bone formed. In fact, genetic manipulation of this pathway was able to double the speed at which bone is made by the skeleton. Excitingly, these increases in bone were possible in adult mice, suggesting such changes could be potential therapy for human patients. We went on to test the effectiveness of this pathway in animal models of human skeletal weakness and have shown that it is capable of remarkable benefits. However, in order to be able to harness this pathway we must understand what molecules within the bone that are responding to the signals from the brain. Our proposal aims to identify the nerve signalling molecule(s) and pathways for these signals within the bone that initiate the increase in bone formation. This project ultimately aims to identify a target for new therapies that could achieve this beneficial effect by administration in osteoporotic women and menRead moreRead less
Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, litt ....Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, little is known of the response properties, structure and organization of receptors and neurones responding to, and relaying information about painful stimuli, from bone to the brain. The objectives of this project are to reveal the fundamental neural mechanisms that account for the perception of bone pain. The project will test a series of specific hypotheses in order to explain why bone pain is often poorly controlled by standard pharmacological or surgical approaches. It is expected that this study will reveal the neural mechanisms responsible for relaying sensory information, in particular, that regarding painful stimuli, from bone to the brain. It will lead to a better understanding of the mechanisms of bone pain and form the template for future studies of its treatment.Read moreRead less
Is Periosteal Bone Formation Responsible For Sexual Dimorphism In Bone Fragility
Funder
National Health and Medical Research Council
Funding Amount
$316,320.00
Summary
Men and women sustain fractures as they age because their bones become fragile. Women sustain fractures more often than men. Bone thinning occurs in both sexes but it is usually believed that this thinning or loss of bone is greater in women than men. We have evidence to suggest that this may not be correct. In fact, it is likely that men and women lose a similar amount of bone, about half what they started with, but during ageing, men lay down more bone on the outside surface of the bone than w ....Men and women sustain fractures as they age because their bones become fragile. Women sustain fractures more often than men. Bone thinning occurs in both sexes but it is usually believed that this thinning or loss of bone is greater in women than men. We have evidence to suggest that this may not be correct. In fact, it is likely that men and women lose a similar amount of bone, about half what they started with, but during ageing, men lay down more bone on the outside surface of the bone than women compensating for the similar amount lost on the inside of the bone. We also have evidence to suggest than men and women who get spine fractures do so because the process of laying down bone may fail to occur normally. We will study these processes of bone loss inside the bone and bone gain outside the bone to try to better understand why bones become weak. We will measure the bone size and its density in healthy men and women and patients with fractures to determine how the increasing size of the bone produced by laying down bone on its outside helps to keep it strong and to preserve the bone that would otherwise be lost if it didn't occur or if a disease developed that might reduce the compensatoryRead moreRead less
The Role Of TWIST Family Basic Helix-Loop-Helix Transcription Factors In Bone Cell Commitment, Function And Repair
Funder
National Health and Medical Research Council
Funding Amount
$485,928.00
Summary
In developed countries, projected estimates predict an alarming trend of a two to three fold increase in the number of fractures that require surgical intervention and rehabilitation therapy in the coming decades as a consequence of an aging population. Fracture healing is a complex physiological process that involves the coordinated participation of different bone marrow cells, immune cells and skeletal progenitor cells. Multiple factors regulate interactions between these cell types that influ ....In developed countries, projected estimates predict an alarming trend of a two to three fold increase in the number of fractures that require surgical intervention and rehabilitation therapy in the coming decades as a consequence of an aging population. Fracture healing is a complex physiological process that involves the coordinated participation of different bone marrow cells, immune cells and skeletal progenitor cells. Multiple factors regulate interactions between these cell types that influence the capacity of bone cell progenitors to develop into functional bone forming cells known as osteoblasts. An understanding of the fracture healing is critical for the future advancement of fracture treatment, and for identifying the mechanisms of skeletal growth and repair as well as the causes of aging and disease. This proposal seeks to identify critical regulatory molecules that act to mediate bone cell progenitor recruitment and development during bone fracture repair.Read moreRead less
Apportioning Deficits In Bone Size And Density In Women With Fractures To Growth Or Ageing By Studies In Their Daughters
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Women fracture their bones because the bones are small and break easily and because the bones are thin or low in denseness (very porous like a honey comb). This study is aimed at identifying why women with fractures have small bones and why the bones are so porous. They may have these problems because they lost a lot of bone as they get older or because growth was abnormal so the size of the bone didn't reach its potential size or because the denseness of the bones didn't develop properly. The s ....Women fracture their bones because the bones are small and break easily and because the bones are thin or low in denseness (very porous like a honey comb). This study is aimed at identifying why women with fractures have small bones and why the bones are so porous. They may have these problems because they lost a lot of bone as they get older or because growth was abnormal so the size of the bone didn't reach its potential size or because the denseness of the bones didn't develop properly. The study will be carried out in women with spine or hip fractures and their daughters. All participants will have bone densitometry, provide a 24 hour urine sample and a fasting blood sample of 20 ml whole blood. Informed consent will be obtained from all participants. The bone density scan is associated with radiation exposure of about 4 mSv, about one tenth of a chest x ray, temporary bruising may follow taking blood. If we can understand the different ways osteoporosis can occur we can then start to devise specific treatments tailored to the individual. Also if we can identify the causes of small bones and bone thinness during growth it may be possible to correct some of these causes before the reduced growth and reduced building of bone occurs. We might also prevent the thinning of bone by identifying and removing causes of bone thinning.Read moreRead less
Twist-1 Mediated Regulation Of Multipotential Mesenchymal Stem Cell Self-Renewal And Cell Fate Determination
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
In Australia, there is an increasing incidence of fractures and skeletal related problems that require surgical intervention and rehabilitation therapy. These are complex processes that involve the coordination of different bone and immune cells. We will investigate important regulatory molecules that mediate bone-cartilage stem cell recruitment and development during normal skeletal growth and remodelling. This study will help advance therapies for fracture repair and joint deterioration.
Cell Biology Of Stress Fractures: Activation Of Remodelling At Sites Of Non-union
Funder
National Health and Medical Research Council
Funding Amount
$493,817.00
Summary
Stress fractures are debilitating injuries. We characterised a model of stress fractures in rat ulnae, learning that they heal by activated remodelling, that key genes are expressed in a temporal pattern, and that part of the fracture remains un-healed, similar to many clinical cases. Now, we will examine cell localisation of important genes necessary for remodelling, and test the efficacy of different growth factors to activate a healing response in the non-healed section of the fracture.