Obesity and osteoporosis are major public health concerns. Mounting evidence supports that they are linked. Whereas overweight per se may augment bone mineralization, animal studies and studies in adults suggest that the metabolic impairment that accompanies obesity is detrimental to bone. Obesity during adolescence, a critical time for bone development, likely has profound and lasting effects on bone strength and fracture risk. This notion has received little attention in adolescents and results are mixed, with studies reporting that mineral accrual is enhanced or impaired by obesity. The proposed project is designed to clarify the relationship of obesity, fat distribution (visceral adipose tissue and tigh muscle fat content), insulin resistance (HOMA-IR) and inflammation (hsCRP) with bone mass, density, structure and strength in 450 normal weight, overweight and obese premenarcheal girls. Unlike other studies with surrogates for body composition, we plan to measure soft tissue composition and adipose tissue (AT) distribution directly, using dual energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and peripheral quantitative computed tomography (pQCT). While DXA also provides a measure of whole body bone mineral mass, the primary bone parameters of interest, cortical and trabecular density (vBMD), structure (e.g., cortical thickness, periosteal and endosteal circumferences), and especially strength (strength-strain index; bone strength index), will be measured by pQCT at weight-bearing and non-weight-bearing sites. pQCT provides 3-dimensional estimates of bone parameters that are not confounded by changes in bone size, a significant confounder of most past studies which have relied on 2-dimensional imaging techniques during growth. Fasting levels of insulin, glucose, and C-reactive protein (CRP) will be measured to assess how insulin resistance (HOMA-IR) and inflammation (hsCRP) are related to bone. Repeat measures (2 years from initial assessment) of all variables will be obtained in a subsample (n=150) of normal weight (n=50), obese (n=50), and obese/high IR (n=50) girls to assess the effects of adiposity, insulin resistance and inflammation on changes in bone mass, density, structure and strength. The proposed mixed (cross-sectional and longitudinal) design in premenarcheal girls provides excellent power to examine associations between adiposity, metabolic risk factors and bone, as well as assess their effects on mineral accrual and changes in structure and strength during a critical phase of bone development. We expect to clarify the currently controversial relationships and provide critical information needed to develop efficacious interventions for optimal bone development.
Obesity during adolescence, a critical time for bone development, may impair mineral accrual and reduce bone strength, leading to greater fracture risk during adolescence and later in life. This study seeks to determine the effect of obesity and accompanying metabolic changes (insulin resistance and inflammation) on bone mineral accrual and related changes in structure and strength in young girls. The information is critical to developing effective prevention strategies to counter the linked risks of obesity and osteoporosis, both major public health concerns.
