Grant: Operating Grant

Paget's disease of bone (PDB) is the second most frequent bone disorder after osteoporosis, affecting approximately three percent of people over 55 years of age. Disabling complications of PDB, such as bone deformity, bone pain and fractures occur in about 30% of patients. PDB is caused by an excess activity of osteoclast cells, which are responsible for removing bone tissue. A genetic component of this disease is well-known and a mutation in a gene linked to PDB has been described in the French-Canadian population. Experiments have shown that this genetic mutation may predispose a person to PDB, although other factors are likely required to be present for the complete development of the disease. In this study, we aim 1) to investigate the role of other relatively-unstudied osteoclast-related genes in PDB, 2) to assess whether the already-known genetic mutation occurs in cells after conception and 3) to better characterize the consequences of a new genetic mutation on bone cell functions. By gaining more knowledge on the impact that specific genes may exert on osteoclast function in PDB, a better understanding is also gained regarding 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. By better understanding the factors that turn on and off bone diseases the development of new targeted treatments designed to regulate or suppress bone resorption becomes increasingly possible. Preventing and appropriately treating bone diseases would be of a major impact on public health by decreasing the direct and indirect costs associated with chronic bone diseases.