Grant: Project Grant

Osteogenesis Imperfecta (OI) is an inherited disorder in which the gene for a key structural molecule in bone (type I collagen) is mutated, resulting in brittle bones that fracture easily. Our clinical studies have shown that children with OI, even with the mildest forms, have slow growth and low muscle mass, which to date remain largely unexplained and untreated. It has been recently discovered that bone cells produce a hormone osteocalcin that can affect energy balance in the whole body. We hypothesize that since OI patients have abnormal activity of bone cells, their osteocalcin levels may be affected. In fact, in experimental OI in mice with mutation in collagen type I, we observed a 2-fold increase in osteocalcin. Since such change in hormonal status can affect the function of the whole body, we propose to examine how OI mice produce and utilize energy and how these differences may affect bone and muscle function as well as overall growth. We will also examine if children with severe OI have differences in their metabolism and body temperature compared to control population. A better understanding of the systemic consequences of collagen type I mutations obtained in this study will help to address compromised growth and low muscle mass in OI patients and to improve the care of children with OI.