Étude des mécanismes du désordre minéral et osseux en insuffisance rénale chronique

 

Fabrice Mac-Way

Centre de recherche de l'Hôtel-Dieu de Québec

 

Domaine : appareil locomoteur et arthrite

Programme chercheurs-boursiers cliniciens - Junior 1

Concours 2015-2016

Kidney disease affects a large number of people in Canada. Once diagnosed, renal insufficiency (inability of kidneys to function properly) will progress to advanced chronic kidney disease (CKD) and to dialysis unless renal transplantation is performed. Bone disorders are the major complications of CKD and affect every CKD patients. Recently, it has been recognized that bone anomalies are directly associated with vascular deposition of calcium in CKD patients. Therefore, these patients suffer from increased bone fractures, increased cardiovascular events and mortality.

Recently, a specific cell in the bone called the osteocytes, seem to play a role in the development of bone anomalies in CKD. Osteocytes secrete a molecule called sclerostin which impairs bone formation. Another molecule, DKK1 which is also found in osteocytes, has been shown to impair bone formation. Decreased bone formation leads to decreased bone resistance and fractures. How osteocytes anomalies are involved in the development of bone disorders in CKD is currently unknown.

The aim of my research program is to understand the specific role of osteocytes and how molecules that impair bone formation lead to the development of bone and vascular disease in CKD. We will study animal models of CKD to specifically address how osteocytes dysfunction is associated with diminished bone strength. We will also study if specific treatments that inhibit sclerostin and DKK1 will improve bone strength and decrease vascular deposition of calcium in these animal models. Finally, we will correlate our animal results with a study in CKD patients looking directly at the association between sclerostin, DKK1 and bone fractures risk. With better understandings of the role of osteocytes in CKD, our hope is that new therapies will be available for better treatments of patients with bone disease to reduce fractures and cardiovascular mortality.