Chronic fluoride toxicity: dental fluorosis

Abstract

Dental fluorosis occurs as a result of excess fluoride ingestion during tooth formation. Enamel fluorosis and primary dentin fluorosis can only occur when teeth are forming, and therefore fluoride exposure (as it relates to dental fluorosis) occurs during childhood. In the permanent dentition, this would begin with the lower incisors, which complete mineralization at approximately 2-3 years of age, and end after mineralization of the third molars. The white opaque appearance of fluorosed enamel is caused by a hypomineralized enamel subsurface. With more severe dental fluorosis, pitting and a loss of the enamel surface occurs, leading to secondary staining (appearing as a brown color). Many of the changes caused by fluoride are related to cell/matrix interactions as the teeth are forming. At the early maturation stage, the relative quantity of amelogenin protein is increased in fluorosed enamel in a dose-related manner. This appears to result from a delay in the removal of amelogenins as the enamel matures. In vitro, when fluoride is incorporated into the mineral, more protein binds to the forming mineral, and protein removal by proteinases is delayed. This suggests that altered protein/mineral interactions are in part responsible for retention of amelogenins and the resultant hypomineralization that occurs in fluorosed enamel. Fluoride also appears to enhance mineral precipitation in forming teeth, resulting in hypermineralized bands of enamel, which are then followed by hypomineralized bands. Enhanced mineral precipitation with local increases in matrix acidity may affect maturation stage ameloblast modulation, potentially explaining the dose-related decrease in cycles of ameloblast modulation from ruffle-ended to smooth-ended cells that occur with fluoride exposure in rodents. Specific cellular effects of fluoride have been implicated, but more research is needed to determine which of these changes are relevant to the formation of fluorosed teeth. As further studies are done, we will better understand the mechanisms responsible for dental fluorosis.

Fig. 1

Dental fluorosis. a Mild with slight accentuation of the perikymata. b Moderate, showing a white opaque appearance. c Moderate, white opaque enamel with some discoloration and pitting. d Severe.

Fig. 2

Concentrations of fluoride in drinking water are related to caries incidence in children and severity of dental fluorosis. Adapted from a report of the Department of Health and Human Services of US (1991) [24].

Fig. 3

Change in dental fluorosis prevalence among children aged 12–15 years participating in 2 national surveys in the USA (1986–1987 and 1999–2004). Dental fluorosis (based on Dean’s fluorosis index) is defined as: very mild, mild, moderate or severe. Percentages do not sum to 100 due to rounding. Error bars = 95% CI. Sources: National Health and Nutrition Examination Survey (1999–2004) [27] and National Survey of Oral Health in U.S. School Children (1986–1987) [27].

Fig. 4

Microradiograph of fluorosed enamel from Colorado Springs. Note the radiolucent outer third of the enamel with a well-calcified surface layer. From Newbrun [97], reprinted with permission.

Fig. 5

SDS PAGE separation of proteins in secretory and maturation stages of enamel matrix of fluoride-treated and untreated rat tooth. A = Standard; B = 0 ppm; C = 10 ppm; D = 25 ppm; E = 50 ppm; F = 100 ppm. From DenBesten [51], reprinted with permission.

Fig. 6

Degradation of amelogenin adsorbed on apatite crystals by MMP-20. Amelogenins were pre-bound to carbonated hydroxyapatite crystals containing different amounts of fluoride (X-axis) and then degraded by MMP-20. Y-axis indicates the percentages of amelogenins degraded by MMP-20 from apatite crystals as compared to the amount of amelogenin initially bound. Note the decreased degradation of amelogenin from the apatite crystal surface as the concentration of fluoride in the apatite increases.