Skeletal health in obesity and after bariatric surgery

描述(申请人提供)：病态肥胖是一个重要的公共卫生问题，但肥胖症与骨骼之间的复杂关系尚不清楚。这项建议旨在研究肥胖和肥胖治疗对骨骼健康的影响，并促进我成为一名独立临床研究员的长期目标。最近的流行病学数据表明，病态肥胖成年人的骨折发生率比人们普遍认为的要高，在某些骨骼部位可能与正常体重的成年人持平或超过。此外，Roux-en-Y胃旁路手术作为治疗病态肥胖的一种方法正变得越来越受欢迎，但越来越多的人担心这种手术会导致加速的骨丢失和增加骨折的风险。我们在这一领域的知识因双能X射线吸收法在肥胖和减肥过程中的已知局限性而变得复杂。这项建议寻求使用先进的成像技术对肥胖和胃旁路手术后的骨密度、微结构和强度进行更全面和准确的评估。使用定量计算机断层扫描和高分辨率非侵入性成像对病态肥胖成人的前瞻性纵向队列在胃旁路手术前和术后2年内进行研究。正常体重和非手术肥胖对照组将被招募进行横断面和纵向比较。我们还将研究连接脂肪组织和骨骼的复杂生理学，并评估胃旁路术后加速骨丢失的潜在机制。职业发展计划包括一个五年的指导计划，其中将包括教学和研究培训，并将由知名科学家指导，这些科学家是根据他们在肥胖症和代谢性骨骼疾病方面的专业知识挑选出来的。总而言之，拟议的研究将检验关于肥胖和胃旁路手术对骨骼影响的创新假设，同时为候选人提供一个培训平台和研究利基，以建立作为临床研究员的独立性。肥胖对骨骼的影响的特征可能会为如何优化肥胖患者的骨骼健康提供见解，揭示如何将接受胃旁路手术的患者的骨折风险降至最低，并揭示脂肪组织和骨骼之间的复杂相互作用。

DESCRIPTION (provided by applicant): Morbid obesity is an important public health problem, but the complex relationship between obesity and the skeleton is poorly understood. This proposal has been designed to examine the impact of obesity and obesity treatments on skeletal health, and to facilitate my long-term goal of becoming an independent clinical investigator. Recent epidemiologic data suggest that fracture rates in morbidly obese adults are higher than is commonly believed, and may equal or surpass rates in normal-weight adults at certain skeletal sites. Furthermore, Roux-en-Y gastric bypass surgery is becoming increasingly popular as a treatment for morbid obesity, but there is growing concern that the surgery results in accelerated bone loss and increased risk of fractures. Our knowledge in this field has been complicated by known limitations in dual-energy x-ray absorptiometry in obesity and during weight loss. This proposal seeks to provide a more complete and accurate evaluation of bone density, microarchitecture, and strength in both obesity and after gastric bypass surgery using advanced imaging techniques. A prospective, longitudinal cohort of morbidly obese adults will be studied before and for 2 years after gastric bypass surgery using quantitative computed tomography and high- resolution non-invasive imaging. Normal-weight and non-surgical obese controls will be recruited for cross-sectional and longitudinal comparisons. We will also examine the complex physiology connecting adipose tissue and the skeleton, and evaluate potential mechanisms of accelerated bone loss after gastric bypass. The career development plan consists of a five year mentored program that will incorporate didactic and research training and will be guided by well-established scientists who have been selected based upon their expertise in obesity and metabolic bone disease. In summary, the proposed research will test innovative hypotheses about the skeletal consequences of obesity and gastric bypass surgery, while providing a training platform and investigational niche for the candidate to establish independence as a clinical investigator. Characterization of obesity's effects on bone may yield insights on how to optimize skeletal health in obese patients, uncover ways to minimize fracture risk for patients undergoing gastric bypass surgery, and shed light on the complex interactions between adipose tissue and bone.