Obesity and bone development in young girls

描述（由申请人提供）：肥胖和骨质疏松症是主要的公共卫生问题。越来越多的证据支持它们之间存在联系。虽然超重本身可能会增加骨矿化，但动物研究和成人研究表明，伴随肥胖的代谢障碍对骨骼有害。青春期肥胖是骨骼发育的关键时期，可能对骨骼强度和骨折风险产生深远而持久的影响。这一概念在青少年中很少受到关注，结果好坏参半， 研究报告称，肥胖会增强或削弱矿物质积累。本研究拟对450名正常体重、超重和肥胖的月经前期女孩的肥胖、脂肪分布（内脏脂肪组织和紧肌脂肪含量）、胰岛素抵抗（HOMA-IR）和炎症（hsCRP）与骨量、密度、结构和力量的关系进行研究。与其他身体成分替代品的研究不同，我们计划使用双能X线吸收法（DXA）、磁共振成像（MRI）和外周定量计算机断层扫描（pQCT）直接测量软组织成分和脂肪组织（AT）分布。虽然DXA还提供全身骨矿物质质量的测量，但是感兴趣的主要骨参数、皮质和骨小梁密度（vBMD）、结构（例如，皮质厚度、骨膜和骨内膜周长），特别是强度（强度-应变指数;骨强度指数），将通过pQCT在负重和非负重部位测量。pQCT提供了骨参数的三维估计值，不受骨大小变化的混淆，骨大小变化是过去大多数生长期间依赖二维成像技术的研究的重要混淆因素。将测量胰岛素、葡萄糖和C反应蛋白（CRP）的空腹水平，以评估胰岛素抵抗（HOMA-IR）和炎症（hsCRP）与骨的相关性。将在正常体重（n=50）、肥胖（n = 50）和肥胖/高IR（n=50）女孩的子样本（n=150）中获得所有变量的重复测量值（自初始评估后2年），以评估肥胖、胰岛素抵抗和炎症对骨量、密度、结构和强度变化的影响。建议的混合（横截面和纵向）设计在月经前期的女孩提供了很好的权力，检查肥胖，代谢危险因素和骨之间的关联，以及评估其对矿物质积累和骨发育的关键阶段的结构和强度的变化的影响。我们希望澄清目前有争议的关系，并提供必要的关键信息，以制定有效的干预措施，以实现最佳的骨发育。

DESCRIPTION (provided by applicant): 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.