Zinc and Bone Metabolism in Thalassemia

描述(由申请人提供)： K23候选人(冯慧兰博士)是一名助理研究科学家，曾接受高级营养训练，并长期关注营养对患有慢性病儿童的影响。这份申请描述了一个全面的，跨学科的计划，它建立在候选人的优势之上，提供必要的技能和经验，使她发展成为一名独立的临床研究员。这位候选人的主要导师Elliott Vichinsky医学博士是一位国际公认的血液学专家，他曾指导过许多候选人成为独立的临床科学家。拟议的科学咨询委员会将由研究领域的高素质专家组成：锌和骨骼代谢以及生物统计学。这项研究的主要目的是确定补充锌是否能改善患有β-地中海贫血的年轻患者的骨健康。骨质疏松症是地中海贫血患者的重要并存疾病，导致生活质量下降。预防骨质疏松症最有效的方法是在早年建立强壮、致密的骨骼。疾病、内分泌和营养因素的综合作用可能是导致这一人群骨质疏松的原因。然而，即使输血良好、性腺功能正常的患者补充钙，也会出现骨量不足的情况。据推测，β地中海贫血患者的骨量较低，部分原因是缺锌。在地中海贫血患者中发现了次优的锌状态，补充锌已被证明改善了直线生长。为了验证基本假设，一项为期24个月的随机安慰剂对照试验将在60名患有β地中海贫血和低骨量(脊柱骨密度Z-Score&lt；-1.0)的年轻患者中进行，试验对象为锌补充剂(每天25毫克锌)加常规护理疗法(钙+维生素D)和单纯常规疗法。通过测量骨量(通过DXA和QCT)以及骨形成和骨吸收的标记物来评估骨健康状况将是主要的结果变量。第二个目标是通过使用锌代谢的隔室模型来评估在基线和补锌6个月后受试者的子样本中的锌稳态。这将是第一个研究补充锌对β-地中海贫血患者骨健康影响的研究。如果补充锌被发现具有重要的临床效果，这种简单、安全、非侵入性的治疗方法可能很快成为这些年轻患者的标准护理的一部分，并改善患有β-地中海贫血的儿童和成人患者的整体健康。

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.