Hypothalamic Signalling In Cortical And Trabecular Bone Anabolic Activity
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
Osteoporosis is a disease associated with an exponential rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in four men will be affected. They cause pain, disability that can be permanent disability and are associated with premature death. Current treatments are able to effectively increase bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent but the ....Osteoporosis is a disease associated with an exponential rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in four men will be affected. They cause pain, disability that can be permanent disability and are associated with premature death. Current treatments are able to effectively increase 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 reduces bone formation and by blocking this pathway we can achieve doubling of the amount of bone in key bone sites. 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. However, in order to be able to harness this pathway we must understand what molecules within the brain are responsible for the signals that reach the bone. Our proposal aims to identify the nerve signalling molecule(s) and the receptor for these signals within the brain that initiates the increase in bone formation. This project ultimately aims to identify a target for new therapies that could cause this beneficial effect by administration of a simple treatment, preferably by mouth in adult humans.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
Sex Steroids Modulate The Neuronal Control Of Bone Formation
Funder
National Health and Medical Research Council
Funding Amount
$620,647.00
Summary
It is well recognised that changes in sex hormones are pivotal to the development of osteoporosis in both men and women. Our group has been instrumental in identifying a novel and powerful system regualting bone mass and strength by neural activity. Recent findings indicate critical interactions between these two pathways in the control of bone formation. Greater understanding of these interactions could lead to therapies capable of controlling this extremely common disease.