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
Identification Of The Mechanisms Of Lipotoxicity Within The Bone Marrow Milieu
Funder
National Health and Medical Research Council
Funding Amount
$416,007.00
Summary
Obesity and osteoporosis two major epidemics of our time. Bone and fat communicate with each other in two different ways. A hormonal communication links bone and fat in a positive manner. In contrast, at the local level, increasing levels of marrow fat with aging affect bone quality through the local release of toxic factors. We will identify these factors and will assess the potential reversibility of lipotoxicity in bone, as a new therapeutic approach to osteoporosis in the elderly.
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