Zinc and Bone Metabolism in Thalassemia

描述（由申请人提供）： K23候选人（Ellen Fung，PhD RD）是一名助理研究科学家，接受过营养方面的高级培训，长期关注营养对慢性病儿童的影响。该申请描述了一个全面的跨学科计划，该计划建立在候选人的优势之上，为她发展成为独立的临床研究者提供必要的技能和经验。候选人的主要导师Elliott Vichinsky博士是国际公认的血液学专家，他指导了许多候选人作为独立临床科学家取得成功。拟议的科学咨询委员会将由锌和骨代谢以及生物统计学等研究领域的高素质专家组成。本研究的主要目的是确定补锌是否能改善β地中海贫血年轻患者的骨骼健康。骨质疏松症是地中海贫血患者的一种重要并发症，导致生活质量下降。预防骨质疏松症最有效的方法是在早期建立强壮，致密的骨骼。疾病、内分泌和营养因素的结合可能导致该人群骨质疏松症的病因。然而，即使是具有正常性腺功能的输血良好的患者补充钙也具有低骨量。据推测，β地中海贫血患者骨量低，部分原因是锌缺乏。在地中海贫血患者中已经确定了次优的锌状态，并且锌补充剂已被证明可以改善线性生长。为了检验主要假设，将在60名患有β-地中海贫血和低骨量（脊柱BMD Z评分<-1.0）的年轻患者（9-25岁）中进行一项为期24个月的锌补充剂（25 mg Zn/天）加常规护理治疗（钙+维生素D）对比常规治疗的随机安慰剂对照试验。通过测量骨量（DXA和QCT）和骨形成和骨吸收标志物估计的骨健康将是主要结局变量。次要目的是通过使用锌代谢的房室模型评价基线时和补锌6个月后受试者子样本中的锌稳态。这将是第一个研究锌补充剂对β地中海贫血患者骨骼健康的影响。如果发现锌补充剂具有临床重要作用，这种简单，安全，非侵入性的疗法可以迅速成为这些年轻患者的标准护理的一部分，并改善β地中海贫血儿童和成人患者的整体健康状况。

DESCRIPTION (provided by applicant): The K23 candidate (Ellen Fung, PhD RD) is an Assistant Research Scientist with advanced training in nutrition and a long- standing interest in the impact of nutrition on children with chronic disease. This application describes a comprehensive, interdisciplinary program that builds upon the candidate's strengths to provide the skills and experience necessary for her development into an independent clinical investigator. The candidate's primary mentor, Elliott Vichinsky, MD is an internationally recognized expert in hematology who has mentored numerous candidates towards their success as independent clinical scientists. The proposed scientific advisory committee will consist of a team of highly qualified experts in the fields of study: zinc and bone metabolism and biostatistics. The primary aim of this study is to determine if zinc supplementation improves bone health in young patients with beta-Thalassemia. Osteoporosis is a significant co-morbidity in patients with thalassemia which leads to decreased quality of life. The most effective way to prevent osteoporosis is to build strong, dense bones in the early years. A combination of disease, endocrine and nutritional factors likely contribute to the etiology of osteoporosis in this population. However, even well transfused patients with normal gonadal function who are supplemented with calcium have low bone mass. It is hypothesized that patients with beta-Thalassemia have low bone mass, in part, due to zinc deficiency. Sub-optimal zinc status has been identified in patients with thalassemia and zinc supplementation has been shown to improve linear growth. To test the primary hypothesis, a 24 month randomized placebo-controlled trial of zinc supplementation (25 mg Zn/day) plus usual care therapy (calcium + vitamin D) vs. usual therapy alone will be conducted in 60 young patients (9-25 yrs) with beta-Thalassemia and low bone mass (spine BMD Z-score <-1.0). Bone health, as estimated from measurements of bone mass (by DXA and QCT) and markers of bone formation and resorption will be the primary outcome variables. The secondary aim will evaluate zinc homeostasis in a sub-sample of subjects at baseline and following 6 months of zinc supplementation through the use of compartmental models of zinc metabolism. This will be the first study to examine the effects of zinc supplementation on bone health in patients with beta-Thalassemia. If zinc supplementation is found to have a clinically important effect, this simple, safe, non-invasive therapy could quickly become a part of the standard care of these young patients and improve overall health in children and adult patients with beta-Thalassemia.