BIOMARKERS FOR TOTAL BODY BURDEN OF FLUORIDE

氟化物总体负荷的生物标志物

• 批准号: 6535658
• 负责人: THOMAS R SHEARER
• 金额: $ 31.41万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6535658
• 关键词: biomarker; bone metabolism; clinical research; diagnostic tests; drug adverse effect; epidemiology; fluoridation; fluoride ion; human subject; longitudinal human study; poisoning; toxicology

DESCRIPTION (provided by applicant): While the benefit of fluoridation in the prevention of dental caries has been overwhelmingly substantiated, the effect of fluoridation on other chronic health problems is less clear. For example, fluoridation has been linked with osteoporosis, bone cancer, uterine cancer, fertility rates, testosterone levels, gastro-duodenal manifestations, and otosclerosis. The majority of studies evaluating the impact of fluoridation on chronic health conditions, however, have been ecological. In ecological studies, the unit of analysis is an aggregate on individuals rather than the individual itself and, in most cases both exposure status and disease status are based on the aggregate. Aggregating exposure and disease status data can lead to inappropriate conclusions regarding relationships at the individual level (ecological fallacy). The purpose of this research is to identify a biomarker for long-term fluoride exposure that can be used in future epidemiologic research on the impact of fluoride exposure on human health. Developing a fluoride biomarker will improve the precision of fluoride exposure measures and provide better estimates of individual level fluoride exposure. This will reduce misclassification of fluoride exposure, thereby enhancing our ability to detect dose-response relationships between fluoride exposure and health outcome measures. The fluoride content of bone appears to reflect total body burden of fluoride and is an appropriate "gold standard" for a fluoride biomarker. For this reason, we will recruit 210 patients scheduled for primary total hip or total knee replacement surgery in Portland and Salem, OR. Excised bone tissue along with fasting blood, fasting ductal saliva, and demographic information will be obtained from each study participant and analyzed for fluoride content at the Medical College of Georgia. While controlling for confounding variables, we will correlate bone fluoride to tissue fluoride in order to determine which tissue, if any, is the "best" biomarker for long-term fluoride exposure. In addition, we will obtain additional tissue samples from a subset (n=30) to evaluate the precision of the biomarker. This research is a collaborative effort between Oregon Health Sciences University and the Medical College of Georgia.

描述（由申请人提供）：虽然氟化在预防龋齿方面的益处已被绝大多数证实，但氟化对其他慢性健康问题的影响尚不清楚。例如，氟化与骨质疏松症、骨癌、子宫癌、生育率、睾酮水平、胃十二指肠表现和耳硬化症有关。然而，大多数评估氟化对慢性健康状况影响的研究都是生态学的。 在生态研究中，分析单位是个体的总体，而不是个体本身，并且在大多数情况下，暴露状态和疾病状态都是基于总体。汇总暴露和疾病状态数据可能会导致关于个体层面关系的不适当结论（生态谬误）。本研究的目的是确定长期氟化物暴露的生物标志物，可用于未来关于氟化物暴露对人类健康影响的流行病学研究。开发氟化物生物标记物将提高氟化物暴露测量的精度，并更好地估计个体氟化物暴露水平。这将减少氟化物暴露的错误分类，从而增强我们检测氟化物暴露与健康结果指标之间剂量反应关系的能力。骨骼的氟化物含量似乎反映了氟化物的全身负荷，并且是氟化物生物标志物的适当“金标准”。因此，我们将招募 210 名计划在俄勒冈州波特兰和塞勒姆进行初次全髋关节或全膝关节置换手术的患者。乔治亚医学院将从每位研究参与者处获取切除的骨组织以及空腹血液、空腹导管唾液和人口统计信息，并分析氟化物含量。在控制混杂变量的同时，我们将骨氟化物与组织氟化物相关联，以确定哪种组织（如果有）是长期氟化物暴露的“最佳”生物标志物。此外，我们将从子集 (n=30) 中获取额外的组织样本，以评估生物标志物的精度。这项研究是俄勒冈健康科学大学和佐治亚医学院之间的合作成果。