Bone marrrow adiposity and the bone frailty found in osteogenesis imperfecta mice

Details

Supervisors

André, Grégoire

Faculty

Faculté des sciences de la motricité

Degree label

Master [120] en sciences de la motricité, orientation générale, à finalité approfondie

Abstract

enOsteogenesis imperfecta is a genetic disease of connective tissues, mostly due to mutations in COL1A1 or COL1A2 genes. The mutations in the type 1 collagen cause bone fragility, musculo-skeletal deformations and lower bone mass density, but it can also cause extra-skeletal symptoms as collagen is the most abundant protein in skin, bone and tendons. These symptoms vary within the forms but can include hyperlaxity, dentinogenesis imperfecta, bluish sclerae or hearing impairments. Current treatments focus on symptom relief and improving quality of life through physiotherapy, surgery, and medication. Bisphosphonates are the gold standard, despite their side effects, and focus mainly on the quantitative improvements of the bone. As new strategies are currently being studied, bone marrow adiposity (BMA) grows interest, as in some metabolic disease like osteoporosis there is an inverse correlation between bone mass density (BMD) and BMA. This study aims to investigate the possible links between OI and BMA, and to see if the C-substance has an impact on it. To do so, oim mice were treated from week five to week seventeen, before being euthanized. Fractures were counted, and humeri were put through histological analysis to investigate the birefringence and the bone marrow adiposity in H&E stained sections. The treatment indeed allowed a reduction in the number of fractures in the OIT group as compared to the OIC one. The birefringence was significantly lower in the OIC group as compared to the WTC one, and the treatment allowed to reach similar values as the WTC mice, even though no significant difference were found between OIT and OIC, surely because the number of subjects was too low to assume such significance. The bone marrow adiposity was surprisingly lower in the OIC mice, and the treatment increased the adiposity area. No significance was found, again because the number of subjects was too low. In conclusion, the C-molecule allowed to decrease the fracture rate, improve the birefringence and increase the area occupied by adipocytes in the bone marrow.