Grant: Operating Grant

Paget's disease of bone (PDB) is a common bone disorder, affecting approximately three percent of people over 55 years of age. This disease may lead to severe disabilities, including most frequently bone pain, fractures and bone deformity. A genetic component of this disease is already known and a mutation in a gene linked to PDB has been described in some French-Canadian families. However this genetic variation does not fully explain the development of the disease, in particular when some common virus envelopes are absent, and in more than half of families with PDB, the causal genes are still unknown. In this study, we aim at 1) studying how three other genes may be involved in the development of this disease, 2) determining the factors that give rise to early clinical symptoms and cellular changes in healthy relatives carrier of the already known mutation, and 3) explaining how about one third of patients may develop PDB even in the absence of common virus envelopes cited above. This research project will lead to a better understanding of the molecular mechanisms of this and other similar bone diseases which are increasingly prevalent in our aging Canadian population, such as osteoporosis and bone metastases. Enhancing our knowledge of the factors associated with the early stages of development of these common bone diseases will facilitate the discovery of new innovative treatments to better control bone cells activity. Preventing and appropriately treating bone diseases would have a major impact on public health by decreasing the direct and indirect costs associated with chronic bone diseases.