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

• 批准号: 9891065
• 负责人: Tewodros R Godebo
• 金额: $ 24.35万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891065
• 关键词: 15 year old; Acquired Dental Fluorosis; Adult; Affect; Africa; African; Area; Award; Biological; Biological Markers; Biology; Biometry; Bone Diseases; Bone Resorption; Calcium; Calcium Isotopes; Child; Chronic; Clinical; Clinical Research; Cognitive; Communities; Complex; Consumption; Country; Data; Dental; Dental Enamel; Detection; Development; Diagnostic radiologic examination; Diet; Discipline; Disease; Early Diagnosis; Environment; Epidemiology; Ethiopian; Exposure to; Fluorides; Foundations; Functional disorder; 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; 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; bioaccumulation; bone; calcification; career; clinical diagnostics; drinking; drinking water; epidemiology study; fluorosis; ground water; improved; innovation; insight; novel; novel marker; nutrition; peer; public health intervention; public health relevance; skeletal; skills; urinary; water treatment

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2亿人暴露于 高浓度的天然氟化物（F─）。风险地区大多位于干旱和 半干旱热带和火山地区，如埃塞俄比亚大裂谷（MER）， 很大一部分地下水源的F-浓度升高， 近850万人。传统上，饮用地下水被认为是 然而，我们对尿氟和其他氟暴露的初步测量结果表明， 最近的研究表明，饮食来源可能会导致接触。我们期望总的F─ 通过指甲F分析可以更可靠地估计这些来源的暴露， 还能加强对健康结果的预测。此外，虽然许多流行病学和临床 研究表明，氟暴露与氟斑牙（DF）、骨骼肌损伤、 氟中毒（SF）更为复杂和多变，仍然知之甚少。氟暴露 足够钙（Ca）的存在导致SF的骨形成，而在 在营养缺乏的个体中，SF表现为骨吸收，特别是在儿童中。这 一个新颖和高度创新的项目将采用临床/放射学氟中毒检查， 首次应用地球化学领域发展起来的Ca同位素技术， 氟引起的代谢性骨紊乱。在辅导阶段，在以下人员的联合辅导下， 环境地球化学和健康方面的高素质专家（初级导师），骨骼 氟中毒，氟代谢和毒性（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），Tewodros R.候选人戈德博将完成 两个关键目标。首先，他将通过以下方法提高对所有氟暴露源的认识： 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，他将 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， 在本奖项的独立阶段进行研究的基础（目标2-3）。在这 第二阶段，候选人将在博士后工作的基础上探索F─ 使用临床和放射学方法对SF进行暴露（目标2）。他还将探讨 过量暴露于F─对尿中天然（生物诱导）Ca同位素变化的影响（目的3）。在 K99/R 00项目的完成，该项目将：1）提供关于效果的新见解 F暴露在SF（和DF）发病机制中的作用; 2）首次揭示了F暴露在SF（和DF）发病机制中的作用。 新的钙同位素生物标志物在尿液中的应用，以监测SF的发病机制; 3）有助于 候选人要实现他的长期职业目标，成为一个既定的科学家， 独立在学术机构;和4）定位候选人写和提交 未来的R 01赠款，并与来自不同学科的同行合作，建立在教学和 在这项研究中获得的方法学知识。