Bone Metabolism and Body Composition in Young Athletes

描述（由申请人提供）：指导是面向患者的研究人员职业生涯的重要组成部分，对于面向患者的研究事业的成功至关重要。PI在指导大量年轻运动员，特别是有相关闭经的年轻运动员进行代谢和骨骼健康评估的复杂技术方面取得了成功的记录。该申请的科学目的是基于候选人成功资助的R01，研究：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闭经运动员（AA）的LH脉搏模式的改变，从而区分闭经运动员（EA）和非运动员；2)在12个月的时间内优化AA的骨积累和结构的治疗策略。在目前的应用中提出了几个新的方向，并假设：(1)与EA和14-21岁的非运动员相比，AA的骨强度[使用有限元分析（FEA）评估]在基线时较低，并且在AA的一年内预期会降低，而EA的骨强度在相同的持续时间内会增加，(2)更大的内脏脂肪组织（VAT）和骨髓脂肪与较低的骨密度相关。(3)在年轻AA患者中，与口服雌二醇或未治疗相比，经皮雌二醇替代会使骨强度增加到与对照组相近的水平，与骨髓脂肪减少有关，且局部身体成分没有变化。将进行区域身体组成和骨骼强度的详细评估。在纵向研究中，脂肪细胞因子将被测量并与骨密度、结构和强度的变化相关，控制传统的风险因素。该提案的指导目标包括制定一个综合的多学科指导和培训计划，在该计划中，学员将根据他们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。将选择独特且可实现的项目，PI将花费大量时间在协议设计、监管要求、教学课程和资助机会方面指导受训者。学员将接触到身体成分和骨骼强度评估的详细技术。这个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是杰出的。重要的是，PI得到了她的单位和部门主管的大力支持，他们热情地支持她迄今为止成功的指导工作和当前提案中的计划。综上所述，拟议的K-24应用程序在以患者为导向的研究中提供了一个强大的指导计划，该计划基于内分泌学和代谢学的重要原则的教学。这些研究将在骨质累积受损风险较大的人群中进行，PI在这方面具有重要的专业知识。面向患者研究的职业中期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者的持续成功。

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.