Role of Cardiometabolic Risk Factors in Childhood Bone Development

The overall goal of this study is to clarify the relationship of adiposity with bone development during adolescence, and to explicate the mechanisms that regulate the effect of excess adiposity on bone. In this effort, we will conduct a 2-year longitudinal study in 400 children and adolescents aged 9-15 years. Using the peak adolescent growth period as a model for probing determinants of bone health may allow for a clearer picture of the processes that regulate bone development, as these processes are highly active at this growth stage. Unlike other studies with surrogates for adiposity, we plan to measure total and central adiposity directly, using dual energy X-ray absorptiometry (DXA) and magnetic resonance imaging. Both bone quantity and bone quality, the two principal determinants of bone strength, will be assessed by peripheral quantitative computed tomography (pQCT) at weight-bearing (tibia) and non-weight-bearing (radius) skeletal sites. Peripheral QCT provides 3-dimensional bone measurements that are not confounded by changes in bone size, a significant confounder of most past studies, which have relied on 2-dimensional bone imaging techniques. To identify mechanistic factors, which may explain the effect of adiposity on bone development, we will measure arterial stiffness, endothelial function, and fasting levels of glucose, insulin, lipids, and C-reactive protein (CRP) to assess how vascular dysfunction, insulin resistance, abnormal lipids, and inflammation are related to bone modeling activity, as measured by serum markers of bone formation and resorption. All measurements will be assessed at baseline and after 1 and 2 years of follow-up.