Bone Metabolism in Adolescents Undergoing Bariatric Surgery

接受减肥手术的青少年的骨代谢

• 批准号: 9897530
• 负责人: Miriam Antoinette Bredella
• 金额: $ 18.99万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897530
• 关键词: Accounting; Address; Adipose tissue; Adolescent; Adolescent obesity; Adrenal Glands; Adult; Androgens; Anorexia Nervosa; Award; Biomechanics; Body Composition; Bone Density; Bone Resorption; Charge; Childhood; Clinical; Clinical Investigator; Clinical Research; Clinical and Translational Science Awards; Complex; Development; Distal; Dual-Energy X-Ray Absorptiometry; Endocrine; Endocrinology; Environment; Estrogens; Faculty; Fatty acid glycerol esters; Female Adolescents; Finite Element Analysis; Foundations; Functional Imaging; Funding; Future; Gastrectomy; Gastric Bypass; General Hospitals; Goals; Grant; Growth Disorders; Hip Fractures; Hip region structure; Impairment; Institution; Insulin; Insulin-Like Growth Factor I; Intervention; Investigation; Investigative Techniques; Joints; Lead; Leadership; Magnetic Resonance Imaging; Male Adolescents; Marrow; Massachusetts; Mediating; Mentors; Metabolic; Metabolism; Mid-Career Clinical Scientist Award (K24); Mission; Modeling; Morbid Obesity; Musculoskeletal; National Institute of Diabetes and Digestive and Kidney Diseases; Non obese; Obesity; Osteogenesis; Outcomes Research; Patients; Peer Review; Peer Review Grants; Peripheral; Physiological; Positioning Attribute; Procedures; Publications; Radial; Radiology Specialty; Research; Research Peer Review; Research Personnel; Research Project Grants; Research Support; Resources; Risk; Risk Estimate; Site; Somatotropin; Spinal Fractures; Structure; Techniques; Thinness; Time; Training; Translational Research; United States National Institutes of Health; Vertebral column; Weight-Bearing state; Work; bariatric surgery; base; bone loss; bone metabolism; bone strength; bone turnover; cardiometabolic risk; career; catalyst; experience; falls; fracture risk; ghrelin; innovation; interest; medical schools; medical specialties; metabolic imaging; mid-career faculty; muscle form; musculoskeletal imaging; novel; novel imaging technique; nutrition; patient oriented research; programs; prospective; radiologist; skeletal; soft tissue; subcutaneous; synergism; tibia; training opportunity

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.

项目总结/摘要 申请人Miriam Bredella医学博士是肌肉骨骼科临床活跃的放射科医生 马萨诸塞州总医院的影像学和介入学， 哈佛医学院。在过去的11年里，Bredella博士的研究重点是先进的功能性 研究肥胖症骨丢失机制的成像技术。她之前的指导经验， 出版物和资金记录以及她目前和计划的研究支持表明，她 承诺和热情，以病人为导向的研究，并提供了一个很好的基础，以完成 K24奖项的目标和宗旨。K24奖的具体目标是：1） 使Bredella博士能够将50%的时间用于指导初级临床研究人员， 资助R01赠款对骨代谢的青少年接受减肥手术; 2）指导初级临床 来自内分泌和放射科以及其他对代谢相关领域感兴趣的专业的研究人员 研究，来自营养和代谢T32计划的调查人员，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临床研究人员， 成功竞争与NIDDK的使命相关的同行评审赠款;以及3） Bredella进一步建立一个以患者为导向的研究计划，结合创新的翻译， 代谢成像的临床和结果研究，并提供了一个理想的环境，发展未来 临床研究的领导者。PI机构的培训环境在教学方面非常出色 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 内分泌科和放射科的领导层都对我有很强的承诺， 委员会赞同她迄今为止成功的辅导工作和目前提案中的计划。具体研究 申请的目的是基于候选人成功资助的R01，调查病态肥胖 接受Roux-en-Y胃旁路术（RYGB）或垂直袖状胃切除术（VSG）的青少年男女 1)通过有限元分析（FEA）进行的面积和体积BMD和强度估计值是否会降低， 皮质和小梁微结构将受损，而骨髓脂肪组织（MAT）将 增加和骨吸收标志物将超过骨形成标志物，和2）研究新的 生理机制介导RYGB和VSG后的骨骼变化。建议的新方向 目前的应用将通过使用一种新的基于生物力学的方法来估计RYGB和VSG后的骨折风险， 包括骨强度（通过FEA）和骨骼负荷（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。