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: 8821991
• 负责人: Tewodros R Godebo
• 金额: $ 9万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-20 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8821991
• 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; 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; Relative (related person); 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; nutrition; peer; public health intervention; public health relevance; skeletal; skills; urinary; water treatment

DESCRIPTION (provided by applicant): 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. F�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.

描述(申请人提供)：氟中毒在全球至少25个国家流行；超过2亿人暴露在高浓度的自然产生的氟(F�)中。风险地区大多位于干旱和半干旱的热带和火山地区，如埃塞俄比亚主要裂谷(MER)，那里的很大一部分地下水来源F-�浓度升高，影响了近850万人的健康。饮用地下水传统上被认为是这一人群接触F-�的主要途径；然而，我们对尿液F-�的初步测量和其他最近的研究表明，饮食来源可能是导致暴露的原因之一。我们预计，通过指甲F�分析可以更可靠地估计来自这些来源的总F�暴露，这也将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F-�暴露与氟斑牙(DF)有很强的相关性，但氟骨症(SF)更为复杂和多变，对其了解仍然很少。在存在足够钙(Ca)的情况下，F�暴露会导致骨硬化型SF，而在营养不足的人中，SF表现为骨吸收，特别是在儿童中。这个新颖且极具创新性的项目将使用临床/放射学氟中毒检查，并首次应用在地球化学领域开发的钙同位素技术来检测F-�引起的代谢性骨病。在指导阶段，候选人特沃德罗斯·R·戈德博博士将在环境地球化学和健康(主要导师)、氟骨症、F-�代谢和毒性(共同导师)以及骨生物学、毒理学、生物统计学、流行病学和营养学(合作者)等领域的高素质专家的共同指导下，实现两个关键目标。首先，他将通过测量个人指甲中的F�，提高对F�暴露的所有来源的理解，并将其与DF结果联系起来(目标1)。其次，他将接受关于SF和实验室分析方法的临床诊断技能的培训，以及生物统计学、流行病学和营养学的额外教学课程，这将为以下研究奠定基础 在本奖项的独立阶段进行(目标2-3)。在第二阶段，候选人将在他博士后工作的基础上，使用临床和放射学方法探索F-�暴露对SF的影响(目标2)。他还将探索过量接触F-�对尿液中自然(生物诱导的)钙同位素变化的影响(目标3)。在K99/R00项目完成后，该项目将有：1)对F-�暴露在 第一次揭示了尿中钙同位素生物标记物在监测SF发病机制中的作用；3)帮助候选人实现了他的长期职业目标，即成为在学术机构独立工作的知名科学家；以及4)在本次研究中获得的教学和方法知识的基础上，使候选人能够撰写和提交未来的R01资助，并与来自不同学科的同行合作。