Zinc and Bone Metabolism in Thalassemia

地中海贫血中的锌和骨代谢

• 批准号: 7536045
• 负责人: ELLEN B FUNG
• 金额: $ 13.2万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-28 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7536045
• 关键词: Adolescent; Adult; Advisory Committees; Alkaline Phosphatase; Biometry; Bone Density; Bone Resorption; Calcium; Child; Childhood; Chronic Disease; Clinical; Clinical Investigator; Clinical Research; Collagen Type I; Development; Doctor of Philosophy; Dual-Energy X-Ray Absorptiometry; Endocrine; Endocrine System Diseases; Environment; Enzymes; Erythrocytes; Etiology; Excretory function; Foundations; Growth; Growth Disorders; Health; Hematology; Homeostasis; Hypogonadism; Intestines; Iron Overload; Leukocytes; Measurement; Mentors; Metabolism; Modeling; Morbidity - disease rate; N-terminal; Nutritional; Osteocalcin; Osteogenesis; Osteoporosis; Patients; Pediatric Hospitals; Physiologic calcification; Plasma; Population; Postmenopause; Prevention; Property; Public Health; Qualifying; Quality of life; Research; Research Institute; Research Support; Risk; Sampling; Scientist; Secondary to; Supplementation; Techniques; Testing; Thalassemia; Trace Elements; Training; Transfusion; Treatment Protocols; United States National Institutes of Health; Vertebral column; Vitamin D; Woman; Zinc; Zinc Sulfate; Zinc deficiency; absorption; base; beta Thalassemia; bone; bone health; bone mass; bone metabolism; chelation; crosslink; deoxypyridinoline; depressed; experience; field study; gonad function; immune function; improved; interest; novel; nutrition; prevent; primary outcome; programs; randomized placebo controlled trial; response; skills; standard care; success; treatment as usual; urinary

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.

描述（由申请人提供）： K23 候选人（Ellen Fung，博士 RD）是一名助理研究科学家，接受过高级营养培训，并且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，为她发展成为一名独立的临床研究者提供必要的技能和经验。该候选人的主要导师 Elliott Vichinsky 医学博士是一位国际公认的血液学专家，他指导了众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研究领域的高素质专家组成。本研究的主要目的是确定补充锌是否可以改善年轻β-地中海贫血患者的骨骼健康。骨质疏松症是地中海贫血患者的一种重要并发症，会导致生活质量下降。预防骨质疏松症最有效的方法是在早年建立坚固、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，即使是性腺功能正常、输血良好且补充钙的患者，骨量也较低。据推测，β-地中海贫血患者骨量低，部分原因是缺锌。地中海贫血患者的锌状态不佳，补充锌可改善线性生长。为了检验主要假设，将对 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）进行一项为期 24 个月的随机安慰剂对照试验，比较锌补充剂（25 毫克锌/天）加常规护理疗法（钙 + 维生素 D）与单独常规疗法的比较。根据骨量测量（通过 DXA 和 QCT）以及骨形成和吸收标志物估计的骨健康将是主要结果变量。第二个目标是通过使用锌代谢的区室模型来评估受试者子样本在基线和补锌 6 个月后的锌稳态。这将是第一项研究补充锌对β-地中海贫血患者骨骼健康影响的研究。如果发现补锌具有重要的临床效果，这种简单、安全、非侵入性的疗法可能会很快成为这些年轻患者标准护理的一部分，并改善患有β-地中海贫血的儿童和成人患者的整体健康状况。

项目成果

Dual-energy X-ray absorptiometry with serum ferritin predicts liver iron concentration and changes in concentration better than ferritin alone.

血清铁蛋白的双能量X射线吸收法可以预测肝铁浓度和浓度的变化比单独的铁蛋白更好。

• DOI: 10.1016/j.jocd.2010.05.003
• 发表时间: 2010-10
• 期刊: Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry
• 作者: Shepherd JA;Fan B;Lu Y;Marquez L;Salama K;Hwang J;Fung EB
• 通讯作者: Fung EB