Bone Metabolism in Adolescents Undergoing Bariatric Surgery

项目摘要/摘要 申请人Miriam Bredella MD是肌肉骨骼科的一名临床在职放射科工作人员。 马萨诸塞州总医院的影像和介入治疗和放射学副教授 哈佛医学院。在过去的11年里，Bredella博士的研究重点是高级功能 研究肥胖骨丢失机制的影像技术。她之前的指导经验， 出版和资金记录以及她目前和计划中的研究支持证明了她 致力于以患者为中心的研究，并为实现 K24大奖的目的和目的。K24奖的具体目的是：1) 使Bredella博士能够将50%的时间用于指导初级临床研究人员，这是基于她已经在NIH 为正在接受减肥手术的青少年的骨代谢资助R01；2)指导初级临床 来自内分泌和放射科以及其他对代谢感兴趣的专业的研究人员 研究，来自营养和新陈代谢T32项目的研究人员，以及居民和 内分泌学和放射学研究员，目标是将他们培养成能够 成功地争取与NIDDK使命相关的同行审查的赠款；3)使Dr。 Bredella将进一步建立以患者为中心的研究计划，将创新的翻译、 代谢成像的临床和结果研究，为未来的发展提供了理想的环境 临床研究领域的领先者。在教学方面，PI所在机构的培训环境非常出色 评估复杂代谢终点的资源和技术的可用性。重要的是，Bredella博士 从内分泌科和放射科的领导层那里得到了坚定的承诺，他们热情地 支持她迄今为止成功的指导努力和当前提案中的计划。具体研究 申请的目标是基于候选人成功资助的R01，调查病态肥胖 青春期男孩和女孩接受Roux-en-Y胃分流术(RYGB)或垂直袖状胃切除术(VSG) 1)通过有限元分析(FEA)估计的面积和体积骨密度和强度是否会减少， 皮质和骨小梁微结构将受损，而骨髓脂肪组织(MAT)将受到损害 增加和骨吸收标记物将超过骨形成标记物和2)研究新 RYGB和VSG术后骨骼改变的生理机制。报告提出的新方向 目前的应用将通过使用一种基于生物力学的新方法来评估RYGB和VSG术后骨折的风险 既包含骨骼强度(通过有限元分析)又包含骨骼负荷(通过肌肉骨骼建模)的方法， 从而解释了影响骨折风险的身体成分的极端变化。

Project Summary/Abstract The applicant, Miriam Bredella MD, is a clinically active staff radiologist in the Division of Musculoskeletal Imaging and Interventions at the Massachusetts General Hospital and an Associate Professor of Radiology at Harvard Medical School. Over the last 11 years Dr. Bredella’s research has focused on advanced functional imaging techniques investigating mechanisms of bone loss in obesity. Her prior mentoring experience, publication and funding record together with her current and planned research support demonstrate her commitment and passion for patient-oriented research and provide an excellent foundation to accomplish the goals and objectives of the K24 Award. The specific aims addressing the purpose of the K24 Award are: 1) To enable Dr. Bredella to dedicate 50% of her time to mentor junior clinical investigators based on her already NIH funded R01 grant on bone metabolism in adolescents undergoing bariatric surgery; 2) To mentor junior clinical investigators from the Endocrine and Radiology Departments and other specialties interested in metabolic research, investigators from the T32 program in Nutrition and Metabolism, and the pool of residents and fellows in Endocrinology and Radiology with the goal to develop them into clinical researchers who can successfully compete for peer-reviewed grants related to the mission of the NIDDK; and 3) To enable Dr. Bredella to further establish a patient-oriented research program that combines innovative translational, clinical, and outcomes research in metabolic imaging and that provides an ideal environment to develop future leaders in clinical research. The training environment at the PI's institution is outstanding in terms of didactic resources and availability of techniques to assess complex metabolic endpoints. Importantly, Dr. Bredella enjoys strong commitment from the leadership of both Endocrinology and Radiology who have enthusiastically endorsed her successful mentoring efforts to date and the plans in the current proposal. The specific research aims of the application are based on the candidate’s successfully funded R01, investigating in morbidly obese adolescent boys and girls undergoing Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG) 1) whether areal and volumetric BMD and strength estimates by finite element analysis (FEA) will decrease, and cortical and trabecular microarchitecture will be impaired whereas marrow adipose tissue (MAT) will increase and bone resorption markers will exceed those of bone formation markers and 2) investigating novel physiologic mechanisms mediating skeletal changes after RYGB and VSG. New directions proposed in the current application will estimate risk of fracture after RYGB and VSG by using a novel, biomechanically-based approach that encompasses both bone strength (by FEA) and skeletal loading (by musculoskeletal modeling), thereby accounting for extreme changes in body composition that influence fracture risk.