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Fluoride and human health: Assessing novel biomarkers in detecting bone disorder

氟化物与人类健康：评估检测骨疾病的新型生物标志物

基本信息

批准号：
9057043
负责人：
Tewodros R Godebo
金额：
$ 8.79万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-20 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9057043
关键词：
15 year old Acquired Dental Fluorosis Adult Affect Africa African Area Award Biological Markers Biology Biometry Bone Diseases Bone Resorption Calcium Calcium Isotopes Child Chronic Clinical Clinical Research Cognitive Communities Complex Country Data Dental Dental Enamel Detection Development Diagnostic Diet Discipline Disease Early Diagnosis Environment Epidemiologic Studies Epidemiology Ethiopian Exposure to Fluorides Foundations Future Goals Grant Guidelines Health Homeostasis Human Individual Institution Knowledge Laboratories Lead Ligaments Light Link Magnesium Measurement Measures Mentors Mentorship Metabolic Bone Diseases Metabolism Methodology Methods Monitor Musculoskeletal Nail plate Neurotoxins Osteogenesis Osteomalacia Osteoporosis Osteosclerosis Outcome Pathogenesis Phase Population Positioning Attribute Preventive Qualifying Research Research Personnel Risk Roentgen Rays Role Route Scientist Severities Source Specific qualifier value Structure of nail of finger Symptoms System Techniques Testing Time Tooth structure Toxic effect Toxicology Training Training Activity Urine Variant Water fluoridation Work World Health Organization Writing analytical method base bioaccumulation bone calcification career drinking drinking water fluorosis improved innovation insight novel novel marker nutrition peer public health intervention public health relevance skeletal skills urinary water treatment

项目摘要

Fluorosis is endemic in at least 25 countries globally; more than 200 million people are exposed to high concentrations of naturally occurring fluoride (F─). Risk areas are mostly located in arid and semi-arid tropical and volcanic regions such as in the Main Ethiopian Rift Valley (MER), where a large fraction of groundwater sources have elevated concentrations of F─, affecting the health of nearly 8.5 million people. Drinking groundwater has traditionally been considered the major route for F─ exposure in this population; however, our preliminary measures of urinary F─ and other recent studies suggest that dietary sources may contribute to exposure. We expect that total F─ exposure from these sources can be more reliably estimated through nail F─ analysis, which will also enhance prediction of health outcomes. In addition, while many epidemiological and clinical studies have shown a strong correlation between F─ exposure and dental fluorosis (DF), skeletal fluorosis (SF) is more complex and variable, and remains poorly understood. Fluoride exposure in the presence of sufficient calcium (Ca) leads to an osteosclerotic form of SF, whereas in nutrition-deficient individuals, SF manifests as bone resorption, particularly among children. This novel and highly innovative project will employ clinical/radiographic fluorosis examinations and, for the first time, apply Ca isotope techniques developed in the field of geochemistry to detect F─-induced metabolic bone disorder. During the mentored phase, under the combined mentorship of highly qualified experts in environmental geochemistry and health (primary mentors), skeletal fluorosis, F─ metabolism and toxicity (co-mentors), and bone biology, toxicology, biostatistics, epidemiology and nutrition (collaborators), Dr. Tewodros R. Godebo, the candidate, will accomplish two key goals. First, he will improve understanding of all sources of F─ exposure through measurement of F─ in individuals’ fingernails and link this to DF outcomes (Aim 1). Second, he will obtain training in clinical diagnostic skills on SF and laboratory analytical methods, and additional didactic courses in biostatistics, epidemiology and nutrition, which will lay the foundation for research to be undertaken in the independent phase of this award (Aims 2-3). In this second phase, the candidate will build on his postdoctoral work to explore the effect of F─ exposure on SF using clinical and radiographic methods (Aim 2). He will also explore the effect of over-exposure to F─ on natural (biologically-induced) Ca isotope variations in urine (Aim 3). At the completion of the K99/R00 project, the project will have: 1) offered new insights on the effect of F─ exposure in the pathogenesis of SF (and DF); 2) for the first time, revealed the role of a novel Ca isotope biomarker application in urine for monitoring the pathogenesis of SF; 3) helped the candidate to achieve his long-term career goal of becoming an established scientist working independently in an academic institution; and 4) positioned the candidate to write and submit future R01 grants and collaborate with peers from various disciplines, building on the didactic and methodological knowledge gained in this research.

氟中毒在全球至少 25 个国家流行；超过2亿人接触到高浓度的天然氟化物 (F─)。风险区大多位于干旱地区半干旱热带和火山地区，例如埃塞俄比亚主裂谷 (MER)，那里大部分地下水源的 F─ 浓度升高，影响人们的健康近850万人。传统上饮用地下水被认为是主要途径对于 F─ 该人群中的暴露；然而，我们对尿 F─ 和其他最近的研究表明饮食来源可能会导致暴露。我们预计总F─ 通过指甲 F 分析可以更可靠地估计这些来源的暴露量，这将还增强了对健康结果的预测。此外，虽然许多流行病学和临床研究表明，F─暴露与氟斑牙（DF）、骨骼健康之间存在很强的相关性。氟中毒 (SF) 更为复杂和多变，目前人们对它的了解仍知之甚少。氟化物暴露于足够的钙 (Ca) 的存在会导致 SF 的骨硬化形式，而在对于营养缺乏的个体，SF表现为骨吸收，特别是在儿童中。这新颖且高度创新的项目将采用临床/放射线氟中毒检查，并且，首次应用地球化学领域发展的Ca同位素技术进行检测 F──引起的代谢性骨病。在导师阶段，在导师的共同指导下环境地球化学和健康领域的高素质专家（主要导师）、骨骼氟中毒、F─代谢与毒性（共同导师）、骨生物学、毒理学、生物统计学、流行病学和营养学（合作者），候选人 Tewodros R. Godebo 博士将完成两个关键目标。首先，他将通过以下方式增进对 F─ 暴露的所有来源的了解：测量个人指甲中的 F─ 并将其与 DF 结果联系起来（目标 1）。第二，他会获得 SF 和实验室分析方法的临床诊断技能培训，以及生物统计学、流行病学和营养学方面的额外教学课程，这将为为该奖项的独立阶段进行的研究奠定基础（目标 2-3）。在这个第二阶段，候选人将在博士后工作的基础上探索F的效果─ 使用临床和放射学方法对 SF 进行暴露（目标 2）。他还将探讨其效果过度接触 F─ 会影响尿液中天然（生物诱导的）Ca 同位素变化（目标 3）。在 K99/R00项目完成后，该项目将具有：1）提供了关于效果的新见解 F─ SF（和 DF）发病机制中的暴露； 2）首次公开角色新型 Ca 同位素生物标志物在尿液中的应用，用于监测 SF 的发病机制； 3）帮助实现成为一名知名科学家的长期职业目标的候选人在学术机构中独立工作； 4) 安排候选人撰写并提交未来的 R01 资助并与来自不同学科的同行合作，建立在教学和在本研究中获得的方法论知识。