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.
