Biomechanical Stimulation & Skeletal Health in Adolescents with Anorexia Nervosa

描述(申请人提供)：神经性厌食症是一种慢性疾病，会导致严重的发病率和死亡率，包括青春期骨量增加的损害。有效的预防和治疗战略仍不清楚。这项拟议的研究侧重于一种新的、非药物干预对骨标记物的短期和长期影响，以及预防患有AN的青少年骨密度和强度的有害变化。候选人的长期职业目标是找到一种安全、有效的干预措施，以防止这种慢性病对未来骨骼健康的长期负面影响。与这一目标相结合的是希望增加对预防高危儿童和青少年患者骨丢失的策略的了解，并阐明导致这些人群骨骼缺陷的途径。拟议的职业发展计划包括对候选人作为独立调查员的发展至关重要的4个领域的额外培训和指导：(1)骨生理学和生物力学；(2)流行病学方面的高级培训和分析这些纵向数据所需的统计方法；(3)使用新技术评估骨骼健康；以及(4)进一步发展领导和指导技能。研究计划包括3个目标：(1)确定低强度机械刺激(LMMS)对因AN住院的青少年骨转换的短期影响；(2)确定LMMS对活动期AN青少年骨几何和骨强度的长期影响；(3)确定LMMS对活动期AN青少年骨重建生化指标的长期影响。拟议的职业发展计划将提供必要的培训和数据，以支持奖励期间后期的R01申请。这些研究的结果将具有广泛的临床重要性，因为循证治疗方案可能来自这些数据，从而改善对患有这种常见慢性病的青少年和年轻女性的护理。鉴于目前在老年人中流行的骨质疏松症带来的保健负担，制定有效措施防止儿童和青春期骨丢失是至关重要的。

DESCRIPTION (provided by applicant): Anorexia nervosa is a chronic illness resulting in significant morbidity and mortality, including the compromised accrual of bone mass during adolescence. Effective prevention and treatment strategies remain unclear. The proposed study focuses on the short-term and long term effects of a novel, nonpharmacologic intervention on bone markers, and the prevention of deleterious changes in bone density and strength in adolescents with AN. The Candidate's long-range career goal is to find a safe, efficacious intervention to prevent the longterm negative effects of this chronic illness on future bone health. Coupled with this goal is a desire to increase understanding of the strategies to prevent bone loss in at-risk pediatric and adolescent patients, and to elucidate the pathways that lead to skeletal deficits in these populations. The proposed career development plan includes additional training and mentorship in 4 areas critical to the Candidate's development as an independent investigator: (1) bone physiology and biomechanics; (2) advanced training in epidemiology and the statistical methods needed to analyze these longitudinal data; (3) use of novel techniques for assessment of skeletal health; and (4) further development of leadership and mentoring skills. The research plan includes 3 aims: (1) To determine the short-term effects of low magnitude mechanical stimulation (LMMS) on bone turnover in adolescents who are hospitalized for AN; (2) To determine the longterm effects of LMMS on bone geometry and bone strength in ambulatory adolescents with a ; and (3) To determine the longterm effects of LMMS on biochemical indices of bone remodeling in ambulatory adolescents with AN. The proposed career development plan will provide the training and data necessary to support an R01 application during the later years of the award period. The results of these studies will have broad-reaching clinical importance, as evidence-based treatment protocols will likely stem from these data that result in improved care achieved for adolescents and young women with this common chronic disease. Given the health care burden associated with the current epidemic of osteoporosis in the elderly, establishing effective measures to prevent bone loss during childhood and adolescence is paramount.