Skeletal health in obesity and after bariatric surgery

描述（由申请人提供）：病态肥胖是一个重要的公共卫生问题，但肥胖与骨骼之间的复杂关系知之甚少。这项提案的目的是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者的长期目标。最近的流行病学数据表明，病态肥胖成人的骨折率比通常认为的要高，并且在某些骨骼部位可能等于或超过正常体重成人的骨折率。此外，Roux-en-Y胃旁路手术作为一种治疗病态肥胖的方法越来越受欢迎，但越来越多的人担心手术会加速骨质流失和增加骨折的风险。我们在这一领域的知识因已知的双能x射线吸收测定法在肥胖和减肥期间的局限性而变得复杂。本研究旨在利用先进的成像技术对肥胖患者和胃旁路手术后的骨密度、微结构和强度进行更完整和准确的评估。一项前瞻性、纵向队列的病态肥胖成人将在胃分流手术前后2年内使用定量计算机断层扫描和高分辨率无创成像进行研究。将招募正常体重和非手术肥胖对照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质流失的潜在机制。职业发展计划包括一个为期五年的指导计划，该计划将结合教学和研究培训，并将由根据肥胖和代谢性骨病方面的专业知识选出的知名科学家指导。总之，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，使其成为一名独立的临床研究者。表征肥胖对骨骼的影响可能有助于了解如何优化肥胖患者的骨骼健康，发现减少胃分流手术患者骨折风险的方法，并阐明脂肪组织与骨骼之间复杂的相互作用。

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. PUBLIC HEALTH RELEVANCE: Severe obesity may be associated with defects in skeletal health, and weight-loss surgery may further lead to accelerated bone loss and increased risk of fractures. The proposed project will provide an in- depth analysis of the effects of obesity and weight-loss surgery on bone health. The knowledge gained from these studies will improve the clinical care of obese patients and those who are considering weight-loss surgery as well as shed light on the complex interplay between bone and adipose tissue.