Sclerostin: A Key Regulator Of Bone Mineralisation And Bone Catabolism
Funder
National Health and Medical Research Council
Funding Amount
$536,653.00
Summary
The regulation of bone mass is critical for many areas of human disease including osteoporosis, osteoarthritis, inflammatory bone loss conditions, e.g. rheumatoid arthritis, cancers of bone and problems relating to orthopaedic prosthesis failure. The osteocyte, the most abundant bone cell, plays a central role in normal bone biology and is likely key to these diseases. Sclerostin is one osteocyte product that may be a key to understanding how boneÍs mass and composition is controlled locally.
The Effects Of A Two Year Randomised Exercise Intervention On Markers Of Bone Turnover In Postmenopausal Women
Funder
National Health and Medical Research Council
Funding Amount
$43,573.00
Summary
Osteoporosis is a condition where the bones become more fragile and can break more easily. In Australia after age 60, three out of every five women and three out of every ten men will fracture a bone. When people fracture a hip they lose their independence and become much less mobile. Exercise is one lifestyle approach which may help in preventing osteoporosis by slowing bone loss and keeping the muscles strong. Previous research has not been able to clearly demonstrate the usefulness of exercis ....Osteoporosis is a condition where the bones become more fragile and can break more easily. In Australia after age 60, three out of every five women and three out of every ten men will fracture a bone. When people fracture a hip they lose their independence and become much less mobile. Exercise is one lifestyle approach which may help in preventing osteoporosis by slowing bone loss and keeping the muscles strong. Previous research has not been able to clearly demonstrate the usefulness of exercise due partly to the difficulty in getting people to exercise for a least one year, which is how long bone studies must be carried out for. We have conducted two large research studies in women past the menopause where they have done weight training exercises. In the previous study we showed the greatest increase in bone mass occurred in those women lifting the heaviest weights. In a recently completed two year study in 126 woman, which forms the basis of this proposal, we found a weight training program was effective at increasing the bone mass at the hip, a common fracture site. The fitness group did not show any increase. So although we have been able to show this type of exercise helps increase bone mass we don't know how the bone is able to respond to this. The question we wish to address with this proposal is does exercise slow the breakdown of bone or does it help form new bone? The best way to be able to answer this question is by measuring certain products in blood, known as bone markers. Bone is continually turning overthese markers are released from bone into the blood. By studying these bone markers in blood samples taken from the subjects over two years it will helps us determine how exercise is affecting bone. From our previous studies we know that weight training can help slow bone loss. By measuring the bone markers we will then be able to make recommendations to people on how exercise will help prevent bone loss.Read moreRead less
Does Teriparatide Reverse Osteonecrosis Of The Jaw In Patients With Cancer? A Randomised, Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$357,412.00
Summary
Osteonecrosis of the jaw (ONJ) is debilitating and associated with drugs that increase bone strength and reduce the bone remodeling rate (bisphosphonates or denosumab). Up to 15% of patients with bone marrow cancer and 1 out of 952 patients with osteoporosis treated with bisphosphonates may get ONJ. This 8-week trial of subcutaneous teriparatide (a hormone that forms new bone) or placebo injections aims to promote resolution of ONJ, measured clinically and by x-ray, and improve quality of life.
Relationships Between Human Osteoblasts And Haemopoietic Cells In Bone Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$436,450.00
Summary
Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collabora ....Bone diseases, such as osteoporosis and osteoarthritis, currently afflict more than 4 million Australians. These diseases are characterised by abnormal bone remodelling, which can result in a net loss of bone (for example, in osteoporosis) or abnormal bone structure (for example, in osteoarthritis). We are seeking to better understand the factors that regulate bone remodelling, and particularly the cells involved in this process. Physiological bone remodelling results from the intimate collaboration between osteoblasts and osteoclasts. Osteoblasts stimulate the formation of osteoclasts and also produce new bone at resporption sites. However, the way that the same type of cell can perform both these tasks, is not clear. Our studies are designed to increase our understanding of the development of human osteoblasts and of the factors that cause them to be sequentially pro-osteoclastic and then pro-osteogenic. We believe that an important factor in this process is vitamin D and we will test the hypothesis that this molecule is produced in bone and acts locally to regulate bone turnover.Read moreRead less
Molecular Determinants Of Bone Remodelling In The Bone Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$317,640.00
Summary
There is little information regarding the expression of specific molecules in human bone tissue or their role in skeletal disease. The process of bone remodelling is fundamental for the maintenance of skeletal integrity. Our understanding of the molecular signalling involved in activating bone remodelling is principally derived from tissue culture and animal experiments. We will study human cancellous bone samples donated by patients undergoing surgery, and with the consent of the next-of-kin, t ....There is little information regarding the expression of specific molecules in human bone tissue or their role in skeletal disease. The process of bone remodelling is fundamental for the maintenance of skeletal integrity. Our understanding of the molecular signalling involved in activating bone remodelling is principally derived from tissue culture and animal experiments. We will study human cancellous bone samples donated by patients undergoing surgery, and with the consent of the next-of-kin, taken at autopsy. These molecular and histomorphometric studies will determine whether the understanding derived from tissue culture and animal experiments is consistent with associations demonstrable in the human cancellous bone microenvironment. The elucidation of the molecular signalling in the human bone microenvironment is essential for the effective diagnosis and treatment of bone disease. Recently reported studies have shown very persuasively that fatigue microdamage accumulates in the skeleton and is targeted for repair by remodelling. Our preliminary data shows that microcrack length is positively correlated with IL-11 mRNA gene expression. We will further investigate mRNA gene expression of a number of cytokines involved in bone cell signalling and their association with the level of microdamage in the bone. Using a animal model of controlled bone microdamage induction we will seek to determine the bone remodelling causal relationship between microdamage and cytokine signalling. Furthermore, the cellular and molecular mechanisms that lead to trabecular structures are not well understood. These studies will provide new insight into the processes that determine trabecular structures. This project will investigate these mechanisms and increase our understanding of bone cell function, essential for diagnosis and design of rational treatment for bone diseases.Read moreRead less
Intrinsic Bone Qualities In Fragility Fracture Patients: Mass, Microarchitecture, Mineralization And Damage Accumulation
Funder
National Health and Medical Research Council
Funding Amount
$447,027.00
Summary
Osteoporosis drug therapies have been associated with a significant reduction in fragility fracture. Patients receiving osteoporosis drugs, which have different effects on BMD, may have similar reductions in fractures. Furthermore, patients with fragility fractures may have abnormalities in bone structural and material properties. Changes to the process of bone renewal, due to drug therapy, may explain why fracture risk decreases where no detectable change to the structure of bone has been detec ....Osteoporosis drug therapies have been associated with a significant reduction in fragility fracture. Patients receiving osteoporosis drugs, which have different effects on BMD, may have similar reductions in fractures. Furthermore, patients with fragility fractures may have abnormalities in bone structural and material properties. Changes to the process of bone renewal, due to drug therapy, may explain why fracture risk decreases where no detectable change to the structure of bone has been detected. It has also been shown that when bone renewal is suppressed microdamage accumulates in bone tissue, leading to reduced bone toughness. The toughness of bone is of primary importance in relation to fragility fractures, and it has been shown that the fatigue strength and fracture toughness (work to fracture) reduce considerably with age. This proposed study would seek to elucidate the role of bone tissue-level properties in determining bone quality for human subjects: patients with fragility hip fractures on no osteoporosis drugs therapy, hip fracture patients on osteoporosis drugs therapies, and normal age- and sex-matched individuals. Our laboratory has extensive experience in the analysis of the structure of human bone tissue. Recently, we have developed novel and unique techniques to assess bone quality, using micro-CT, backscatter SEM imaging, confocal microscopy and immunohistochemistry. This multifaceted study will identify at the bone tissue-level the structural mechanisms (micro-architecture, mineralisation, and microscopic cracking) that are indicative of the efficacy of fragility fracture drugs. Better understanding of the mechanisms by which bones are less likely to fracture will enable better targeting of osteoporosis drug therapy to individuals at risk of fragility fracture.Read moreRead less
Vitamin D Activity To Regulate Bone Remodelling And Promote Bone Strength
Funder
National Health and Medical Research Council
Funding Amount
$497,001.00
Summary
While vitamin D and calcium supplementation is well known to protect against osteoporosis and hip fracture, the mechanisms by which this occur are not fully understood. Thus, this project aims to establish the cellular basis for the importance of direct action of vitamin D and calcium within the bone. This information is necessary to develop public health nutritional recommendations for improving skeletal health and reducing the incidence of hip factures in the elderly.