Bone Metabolism and Body Composition in Young Athletes

年轻运动员的骨代谢和身体成分

• 批准号: 8443084
• 负责人: Madhusmita Misra
• 金额: $ 18.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443084
• 关键词: Adipose tissue; Adolescence; Adolescent; Adult; Affect; Amenorrhea; Award; Body Composition; Body fat; Bone Density; Clinical; Complex; Contraceptive Agents; Deterioration; Development; Distal; Dual-Energy X-Ray Absorptiometry; Educational process of instructing; Endocrinology; Ensure; Environment; Estradiol; Estrogens; Ethics; Fatty acid glycerol esters; Finite Element Analysis; Funding; Funding Opportunities; Goals; Gonadotropins; Grant; Habits; Hormones; Hypogonadism; Impairment; Institution; Insulin-Like Growth Factor I; Leptin; Longitudinal Studies; Marrow; Measures; Mentors; Metabolic; Midcareer Investigator Award in Patient-Oriented Research; Oral; Pattern; Physiological; Population; Protocols documentation; Radial; Randomized; Randomized Controlled Trials; Reporting; Research; Research Personnel; Research Support; Resources; Risk; Structure; Techniques; Testing; Thick; Time; Training; Training Programs; Visceral; Weight; Woman; Work; adipokines; adiponectin; base; bone; bone health; bone mass; bone metabolism; bone strength; career; design; ghrelin; innovation; interest; multidisciplinary; novel; patient oriented; patient oriented research; pill; programs; prospective; public health relevance; sedentary; subcutaneous; substantia spongiosa; success; therapeutic development; tibia; transdermal estrogen; treatment strategy; young adult

DESCRIPTION (provided by applicant): Mentoring is a critical component of the career of a patient-oriented-researcher, and essential for a successful career in patient-oriented research. The PI has a successful record of mentoring a number of fellows and trainees in the complex techniques of metabolic and bone health assessment in a large population of young athletes, particularly those with associated amenorrhea. The scientific aims of the application are based on the candidate's successfully funded R01, investigating: 1) whether low fat mass and altered levels of adipokines and fat regulated hormones determine alterations in LH pulsatility patterns in amenorrheic athletes (AA), that differentiate them from eumenorrheic athletes (EA) and non-athletes, and 2) treatment strategies to optimize bone accrual and structure in AA over a 12-month period. Several new directions are proposed in the current application, and it is hypothesized (1) that bone strength [assessed using finite element analysis (FEA)] is lower in AA compared with EA and non-athletes 14-21 y at baseline and decreases prospectively over a one- year duration in AA, whereas bone strength increases in EA over the same duration, (2) that greater visceral adipose tissue (VAT) and marrow fat are associated with lower bone density, impaired microarchitecture and lower bone strength, and (3) that in young AA, compared to oral estradiol or no treatment, transdermal estradiol replacement will increase bone strength to approximate that in controls, associated with decreases in marrow fat and no changes in regional body composition. Detailed assessment of regional body composition and bone strength will be performed. Adipocytokines will be measured and related to changes in bone density, structure and strength in longitudinal studies, controlling for traditional risk factrs. The mentoring goals of this proposal include the development of a comprehensive multidisciplinary mentoring and training program, in which trainees will be selected, based on their interest in patient oriented research, work habits and ethical standards. Projects will be selected that are unique and achievable, and significant time will spent by the PI guiding trainees in protocol design, regulatory requirements, didactic coursework, and funding opportunities. Trainees will be exposed to detailed techniques of body composition and bone strength assessment. This K-24 proposal is critical to support the PI's significant time spent in mentoring. 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, the PI enjoys significant support from her Unit and Division Chiefs, who have enthusiastically endorsed her successful mentoring efforts to date and the plans in the current proposal. Taken together, the proposed K-24 application offers a strong mentoring program in patient oriented research that is based on the teaching of important principles of endocrinology and metabolism. The studies are to be carried out in a population at significant risk for impaired bone accrual, with which the PI has significant expertise. The Midcareer Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support to reduce clinical and administrative responsibilities, and ensure the candidate's continued success as a mentor and clinical researcher.

描述（由申请人提供）：指导是以患者为导向的研究人员职业生涯的重要组成部分，对于以患者为导向的研究的成功职业生涯至关重要。PI在指导大量年轻运动员（特别是伴有闭经的运动员）的代谢和骨骼健康评估的复杂技术方面，成功地指导了许多研究员和学员。申请的科学目的是基于候选人成功资助的R 01，调查：1）低脂肪量和脂肪因子和脂肪调节激素水平的改变是否决定了闭经运动员（AA）LH脉动模式的改变，这将他们与闭经运动员（EA）和非运动员区分开来，和2）在12个月的时间内优化AA的骨积累和结构的治疗策略。在本申请中提出了几个新的方向，并且假设（1）与EA和非运动员14-21岁相比，AA中的骨强度[使用有限元分析（FEA）评估]在基线时较低，并且在AA中在一年的持续时间内前瞻性地降低，而在EA中骨强度在相同的持续时间内增加，（2）内脏脂肪组织（VAT）和骨髓脂肪增多与骨密度降低、微结构受损和骨强度降低相关，（3）在年轻AA中，与口服雌二醇或未治疗相比，经皮雌二醇替代将使骨强度增加至接近对照组，与骨髓脂肪减少有关，而局部身体成分没有变化。将对局部身体组成和骨强度进行详细评估。在纵向研究中，将测量脂肪细胞因子，并将其与骨密度、结构和强度的变化联系起来，控制传统的风险因素。该提案的指导目标包括制定一个全面的多学科指导和培训计划，根据学员对以患者为导向的研究的兴趣、工作习惯和道德标准来选择学员。将选择独特且可实现的项目，PI将花费大量时间指导受训者进行方案设计、法规要求、教学课程和资助机会。学员将接触到身体成分和骨骼强度评估的详细技术。这份K-24提案对于支持PI在指导上花费的大量时间至关重要。PI所在机构的培训环境在教学资源和评估复杂代谢终点的技术可用性方面非常出色。重要的是，首席执行官得到了其股长和司长的大力支持，他们热情地赞同她迄今为止成功的辅导工作和目前提案中的计划。总的来说，拟议的K-24应用程序提供了一个强大的指导计划，以患者为导向的研究，是基于内分泌学和代谢的重要原则的教学。这些研究将在具有骨累积受损显著风险的人群中进行，PI具有丰富的专业知识。以患者为导向的研究的中期职业研究者奖是一个理想的机制，以确保必要的支持，以减少临床和行政责任，并确保候选人作为导师和临床研究人员的持续成功。