BIOMARKERS FOR TOTAL BODY BURDEN OF FLUORIDE

说明(申请人提供)：虽然氟化对预防龋齿的益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还不太清楚。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症有关。然而，评估氟化对慢性健康状况的影响的大多数研究都是生态的。在生态学研究中，分析单位是关于个体而不是个体本身的集合，在大多数情况下，接触状况和疾病状况都是基于集合的。汇总暴露和疾病状况数据可能会导致关于个人层面上的关系的不适当结论(生态谬误)。本研究的目的是寻找一种长期接触氟的生物标志物，可用于未来氟暴露对人体健康影响的流行病学研究。开发氟生物标志物将提高氟暴露测量的精确度，并提供对个人水平氟暴露的更好估计。这将减少对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。骨骼中的氟化物含量似乎反映了全身氟化物的总负荷量，是一种合适的氟化物生物标志物的“金标准”。出于这个原因，我们将招募210名计划在波特兰和俄勒冈州塞勒姆接受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个研究参与者那里获得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，并对其进行氟化物含量分析。在控制混杂变量的同时，我们将把骨氟与组织氟联系起来，以确定哪个组织(如果有的话)是长期接触氟的“最佳”生物标志物。此外，我们将从一个子集(n=30)中获取额外的组织样本，以评估生物标记物的精确度。这项研究是俄勒冈健康科学大学和佐治亚州医学院的合作成果。

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.