Obesity and bone development in young girls

描述(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是有联系的。虽然超重本身可能会增加骨骼矿化，但动物研究和成人研究表明，肥胖伴随的新陈代谢障碍对骨骼有害。青春期肥胖是骨骼发育的关键时期，可能会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，结果喜忧参半。 研究报告称，肥胖会增加或削弱矿物质的积累。该项目旨在阐明450名正常体重、超重和肥胖的月经前女孩的肥胖、脂肪分布(内脏脂肪组织和肌肉脂肪含量)、胰岛素抵抗(HOMA-IR)和炎症(HsCRP)与骨量、密度、结构和强度的关系。与其他替代人体成分的研究不同，我们计划使用双能X射线吸收法(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还提供了全身骨矿含量的测量，但主要的骨参数，皮质骨和骨小梁密度(VBMD)，结构(如皮质厚度，骨膜和骨内周长)，特别是强度(强度-应变指数；骨强度指数)，将通过pQCT在承重和非承重部位测量。PQCT提供了不受骨骼大小变化影响的骨骼参数的三维估计，这与过去大多数在生长过程中依赖二维成像技术的研究相比是一个重大的混淆。将测量空腹胰岛素、血糖和C反应蛋白(CRP)水平，以评估胰岛素抵抗(HOMA-IR)和炎症(HsCRP)与骨骼的关系。所有变量的重复测量(从最初评估起两年)将在正常体重(n=50)、肥胖(n=50)和肥胖/高胰岛素抵抗(n=50)女孩的子样本(n=150)中进行，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。在月经前期女孩中提出的混合(横截面和纵向)设计提供了极好的力量来检查肥胖、代谢危险因素和骨骼之间的关系，以及评估它们对骨骼发育关键阶段的矿物质积累和结构和强度变化的影响。我们希望澄清目前有争议的关系，并提供开发有效干预措施以优化骨骼发育所需的关键信息。

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.