BIOMARKERS FOR TOTAL BODY BURDEN OF FLUORIDE

描述（由申请人提供）：虽然氟化在预防龋齿方面的好处已经得到了压倒性的证实，但氟化对其他慢性健康问题的影响却不太清楚。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方面的。在生态学研究中，分析单位是个体的总和，而不是个体本身，在大多数情况下，暴露状态和疾病状态都是基于总和。汇总暴露和疾病状况数据可能导致关于个人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，可用于未来氟化物暴露对人体健康影响的流行病学研究。开发氟化物生物标志物将提高氟化物暴露测量的准确性，并提供更好的个人水平氟化物暴露估计。这将减少对氟化物接触的错误分类，从而增强我们检测氟化物接触与健康结果措施之间剂量-反应关系的能力。骨骼中的氟化物含量似乎反映了氟化物的总体负担，是氟化物生物标志物的适当“金标准”。因此，我们将招募210名计划在波特兰和塞勒姆进行原发性全髋关节或全膝关节置换手术的患者。将从每个研究参与者那里获得切除的骨组织、空腹血液、空腹导管唾液和人口统计信息，并在乔治亚医学院分析氟化物含量。在控制混杂变量的同时，我们将把骨氟化物与组织氟化物联系起来，以确定哪个组织（如果有的话）是长期氟化物暴露的“最佳”生物标志物。此外，我们将从一个子集（n=30）中获得额外的组织样本来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乔治亚医学院的合作成果。

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.