S Since the primary effect of fluoride (F) on caries control is post-eruptive, any method of fluoride use, to be effective, should be able to maintain a constant fluoride concentration in the oral environment. Fluoridated water and F dentifrice are still regarded, respectively, as systemic and topical methods of F use, and they are considered to be the most effective F regimens for interfering with the caries process. However, our understanding of how these apparently different methods of F use maintain F in the oral environment has not been fully elucidated. Thus, the aim of this article is to consider evidence that fluoridated water and F dentifrice differ only in the manner that F is kept in the oral environment during the intervals that water is not being drunk or the teeth are not being brushed. Introduction The history of the importance of fluoride (F) in caries control can be divided into two phases: before its use for water fluoridation in the 1950s, and before the widespread use of F dentifrices in the 1980s. Also, on the basis of our understanding of fluoride’s effect on the caries process, it is apparent that, in the past, it was considered to be essentially systemic in action, but now is considered to be primarily a topical agent (Featherstone, 1999). Water fluoridation and F dentifrice are recognized as the most effective methods to control caries (Ellwood and Fejerskov, 2003). Fluoridated water had a relevant role in caries control until the 1980s-90s, when, in some countries, it was the only source of fluoride at the community level, and it is still considered important for many countries (see other articles in this issue). Since the 1990s, however, the widespread use of F dentifrice has had a tremendous effect on caries decline at the population level (Rölla et al., 1991). The epidemiological changes in caries promoted by F from drinking water or dentifrices have been observed both in developed (Brunelle and Carlos, 1990; Rölla et al., 1991) and developing countries. Brazil is an example of a developing country in which the anti- caries benefits of these two sources of F delivery are clearly evident (Cury et al., 2004). Thus, caries decline has occurred in Brazil in two phases (steps)—one from 1970 to 1980 and another after 1990—which may be attributed to the program of water fluoridation and the widespread use of F dentifrice, respectively. Currently, 45% of the Brazilian population has access to water fluoridation, mostly in south and southeast regions, but all dentifrices are fluoridated (90% containing MFP, i.e., sodium monofluorophosphate). However, fluoridated water and F dentifrice are still considered, respectively, systemic and topical methods of F use, which clouds the explanation of how these apparently different sources of F work efficiently on caries control by the same mechanism. Rationally, this may be facilitated by our understanding of the disease and how F may interfere with it. Dental Caries There is evidence to support dental caries as a dietary carbohydrate-modified bacterial infectious disease (van Houte, 1994). Its key feature is a dietary carbohydrate-induced enrichment of the plaque microbiota with organisms such as mutans streptococci and lactobacilli, which causes an increase of plaque’s pH-lowering and cariogenic potential. Among the dietary carbohydrates, sucrose is considered the most cariogenic, due to the changes provoked in plaque (biofilm) matrix composition (Rölla, 1989), which depend on the concentration and frequency of sucrose use (Cury et al., 1997; Aires et al., 2006; Ccahuana-Vásquez et al., 2006). Changes in the mineral structure of the enamel depend on the equilibrium between demineralization and remineralization processes occurring in dental biofilm fluid. Thus, every time sugar penetrates a cariogenic biofilm and is converted to acids by bacterial metabolism, the biofilm fluid becomes undersaturated with respect to enamel solubility properties, and demineralization occurs (Dawes, 2003). A critical low pH for tooth dissolution is maintained for a certain time, but it returns to physiological values when exposure to sugar ceases. Therefore, when the pH is raised and supersaturating conditions are again reached, a certain amount of mineral loss can be recovered by enamel, and this process has been named ‘remineralization’, a well-known salivary phenomenon. Ideally, any disease control should focus on the etiological factors involved, and for caries this would be the removal (or regular disorganization) of dental biofilm, and dietary counseling. However, the success of these strategies has been shown to be limited (Duggal and van Loveren, 2001; Nyvad, 2003), reinforcing the use of F as the most relevant method for controlling caries. In contrast, the mechanism explaining how F works to control this disease is not that hypothesized when the anti-caries benefits of F added to the water supply were demonstrated (Fejerskov et al., 1981). How Fluoride Controls Caries Today, there is consensus that the predominant effect of F is not systemic, pre-eruptively changing enamel structure, but mainly local, interfering with the caries process. Hence, F must be present in the right place (biofilm fluid, saliva) and at the right time (sugar exposure) to interfere with de- and remineralization events. For this effect, even sub-ppm values of available F are effective. Thus, as described previously, enamel is dissolved by the low pH reached in dental plaque due to acid production every time sugar is ingested (Fig. 1). However, if F is present in the biofilm fluid, and the pH is not lower than 4.5, at the same How to Maintain a Cariostatic Fluoride Concentration in the Oral Environment J.A. Cury*, L.M.A. Tenuta Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil; *corresponding author,
[email protected] Adv Dent Res 20:13-16, July, 2008 Key Words Fluoride, caries, dentifrice, drinking water. Presented at a symposium entitled “Fluoride and Caries Decline”, sponsored by the IADR Cariology Research, Behavioral, Epidemiologic & Health Services Research, and Pharmacology/Therapeutics/ Toxicology Groups, presented during the 35th Annual Meeting of the American Association for Dental Research and the 83rd Annual Session of the American Dental Education Association, March 9, 2006, Orlando, Florida, USA, and supported by the Colgate-Palmolive Co. 13 by on April 19, 2010 http://adr.sagepub.com Downloaded from 14 Cury & Tenuta Adv Dent Res 20:13-16, July, 2008 time that hydroxyapatite (HA) is dissolved, fluorapatite (FA) is formed (ten Cate et al., 2003). The net result is a decrease in enamel dissolution, since a certain amount of calcium (Ca) and inorganic phosphorus (Pi) that was lost as HA is recovered by enamel as fluorapatite. This indirect effect of F reducing enamel demineralization when the pH drops is complemented by its effect on remineralization when the pH rises (Fig. 2). It is well-known that saliva is able to remineralize enamel (Edgar and Higham, 1995), but this effect is enhanced in the presence of F (Dijkman et al., 1990). Consequently, small amounts of Ca and Pi lost by enamel during the pH drop can be more efficiently recovered if F is still present in the oral environment after the cariogenic challenge. This physicochemical effect of F, reducing demineralization and enhancing remineralization of dental enamel (or dentin), could be supplemented by some antibacterial effect if an appropriate concentration of F can be maintained in the oral environment (see other articles in these Proceedings) by the current methods of F use. Therefore, although F does not have a direct effect on the etiological factors responsible for the disease, by reducing tooth demineralization and enhancing remineralization, F is extremely effective in helping saliva to control the caries process, resulting in reduction of caries lesions. If the current methods of F use were able to interfere with biofilm formation or its metabolism when dietary sugars are consumed, the disease could be controlled more efficiently. Nevertheless, the aim is the maintenance of a constant low level of F in the oral environment, and this could be achieved by any method of F administration, either systemic or topic. Also, if this is acceptable, the classification of methods of F use should be re-evaluated, since it is conceptually misleading. Among these different methods of F delivery (Ellwood and Fejerskov, 2003), drinking water and dentifrices present unique properties to control the caries process, since the oral environment is daily exposed to low concentrations of F. Water Fluoridation In individuals drinking fluoridated water and eating a normal diet, the baseline F concentration in saliva is higher than that found in persons exposed to F-deficient water (Oliveby et al., 1990). Actually, blood is considered as the central ‘compartment’ responsible for F distribution to any part of the organism and, of course, to the oral cavity (Fig. 3). When either optimally fluoridated water or food prepared with it is ingested, a transient increase in salivary F levels is observed. Absorbed F will be taken up by bone, especially in children, in whom newly forming bone can retain up to 90% of the absorbed F, compared with 50% in adults. From the sub-compartment of bone that undergoes constant remodeling, F can return to the blood. Thus, an increased blood concentration is maintained by both daily F intake and exchange with F accumulated in remodeling bone. As a consequence, with regular intake, salivary F concentration is maintained at a higher level, reflecting F concentrati ons i n the bl ood. However, there is no homeostatic mechani sm t o mai nt ai n bl ood fluoride concentration (Waterhouse et al., 1980), and, consequently, the salivary F steady state is dependent on F intake. Thus, when the external supply Fig. 1 - Enamel demineralization in the presence of F in dental biofilm. Sugars (sucrose, glucose, fructose) are converted to acids in the biofilm. When the pH decreases to below 5.5, undersaturation with respect to hydroxyapatite (HA) is reached in the biofilm fluid, resulting in mineral dissolution. However, if the pH is higher than 4.5 and in the presence of F, the biofilm fluid is supersaturated with respect to fluorapatite (FA), and there is reprecipitation of minerals in enamel. As a consequence, net demineralization is reduced. Fig. 2 - Enamel remineralization in the presence of F in dental biofilm. After exposure to sugars has ceased, acids in the biofilm are cleared by saliva and converted to salts. As a result, the pH increases, and at pH 5.5 or above, the biofilm fluid is supersaturated with respect to HA and FA. Thus, Ca and Pi lost by enamel can be more efficiently recovered if F is still present in the biofilm. Fig. 3 - Schematic illustration of how fluoride levels from drinking water intake are kept constant in the oral environment. by on April 19, 2010 http://adr.sagepub.com Downloaded from Adv Dent Res 20:13-16, July, 2008 Maintaining a Cariostatic F Concentration in the Oral Environment 15 of F is interrupted, the concentration in the blood decreases, as well as that in the exchangeable bone sub-compartment (Rao et al., 1995). Since this decrease in F concentration in the bone sub-compartment can last several days (Likins et al., 1956; Zipkin et al., 1956), an apparent equilibrium may be suspected, but in fact does not exist. As a result, the higher F concentration in saliva can no longer be sustained. If this model is valid, an optimal level of F could not be maintained in dental biofilm (the right place!) if the supply of fluoridated water is interrupted. In fact, the concentration of F in dental biofilm of children drinking optimally fluoridated water decreased almost 20-fold when the ingestion ceased (Nobre dos Santos and Cury, 1988) (Table 1). This interruption was transient, lasting 6 months, and after intake from water fluoridation resumed, the F concentration in dental biofilm returned to the same level found previously (Cury, 1989). Analysis of these data gives support to the absence of a homeostatic mechanism to control F in the oral environment, as opposed to Ca, which did not decrease significantly during this period (unpublished observations). Also, the findings support past epidemiological data showing a caries increase when children living in areas with high F concentration in the water moved to low-F areas (Fejerskov et al., 1981). It should be emphasized, however, that the example in Table 1 illustrates the need for constant exposure to fluoridated water in a region where, 20 years ago, the only source of community F was drinking water. It is important to notice that F levels in the dental biofilm were shown to be maintained, even after interruption of water fluoridation, in a low-caries population using F dentifrice on a regular basis (Seppä et al., 1996). This means that an additive effect on F concentration in the biofilm would not be expected to occur when these methods of F delivery are simultaneously available. Furthermore, it should be cautioned that this approach to explaining how F from drinking water fits the current concepts on the mechanism of action of F may not be used to recommend any other method of F ingestion (i.e., supplements), since water fluoridation is unique as a public health strategy for F delivery. Fluoride Dentifrice Similarly to fluoridated water ingestion, the concentration of F in saliva increases every time teeth are brushed with F-containing dentifrice. After 3 min, the F concentration in saliva is more than 100 times higher than the baseline value, but after 2 hrs, it returns almost to baseline values (Bruun et al., 1984; Duckworth and Morgan, 1991). However, during toothbrushing, F is spread throughout the oral cavity and is stored in some compartments (Ekstrand and Oliveby, 1999), such as the enamel surface and any remaining dental biofilm. In this way, after toothbrushing, salivary clearance dilutes the residual F in saliva, but the enamel surface and remaining biofilm are able to take up fluoride, as calcium-fluoride (CaF 2 )-like deposits, maintaining certain F levels in the right place to control caries. These reservoirs would release F to the fluid of the biofilm during pH-cycling due to sugar exposure (Rölla et al., 1993; ten Cate, 1997), reducing enamel demineralization and enhancing its remineralization. If this is true, F should be found in dental biofilm either soon after toothbrushing or preferably for longer periods. In an in situ study, 10 hrs after toothbrushing, the F concentration in dental biofilm of the group using F dentifrice was 30 times higher than that found in the control group (Paes Leme et al., 2004) (Table 2). Also, even 14 days after APF fluoride application, which forms a high quantity of CaF 2 -like deposits, a high concentration of F was found in the biofilm (Table 2). Thus, the effect on reduction of enamel demineralization observed could be attributed to this residual F maintained in the biofilm by these modes of F use. Conclusion Since F must be available in the biofilm to interfere with the caries process, systemic and topical F act in caries control essentially by the same mechanism, differing only in the manner in which F is maintained in the oral environment between the intervals of intake/use. Exchangeable bone deposits of F may function as a fluorapatite reservoir and release F to the blood, from where it will be subsequently released to saliva. Also, CaF 2 -like deposits on the tooth surface and biofilm increase F availability in the biofilm fluid at times after the use of F products. Therefore, the effect of an anti-caries regimen may be limited by F storage in these different reservoirs. Once fluoridated water or F-dentifrice is no longer used, its protective effect cannot be maintained, since the reservoirs will be exhausted within several days, and F would not be available in the oral environment to interfere with de- and remineralization processes. This would explain why slow-fluoride-release devices are effective in caries control (Toumba, 2001). References Aires CP, Tabchoury CP, Del Bel Cury AA, Koo H, Cury JA (2006). Effect of sucrose concentration on dental biofilm formed in situ and on enamel demineralization. Caries Res 40:28-32. Brunelle JA, Carlos JP (1990). Recent trends in dental caries in US children and the effect of water fluoridation. J Dent Res 69:723-727. Bruun C, Givskov H, Thylstrup A (1984). 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Means ± SD of Fluoride Concentration in Dental Plaque from Schoolchildren According to the Conditions of Water Fluoridation (Piracicaba, SP, Brazil, 1986-1987) Water Fluoridation Status mg F/g Biofilm Wet Weight Fluoridated (0.8 ppm F) 3.2 ± 1.8 (n = 91) Interrupted (0.06 ppm F) 0.2 ± 0.09 (n = 41) Re-fluoridated (0.7 ppm F) 2.6 ± 1.9 (n = 55) TABLE 2. Means ±SD (n=15) of Fluoride Concentration in Dental Biofilm and Enamel Demineralization (DZ), According to the Treatments Treatments mg F/g Biofilm Wet Weight DZ a Non-F dentifrice (control) 1.5 ± 0.5 1253.6 ± 697.2 APF b + non-F dentifrice 7.1 ± 12.0 971.4 ± 671.5 F dentifrice 46.6 ± 46.6 405.4 ± 216.4 a Area of mineral loss as measured by cross-sectional microhardness determination (Paes Leme et al., 2004). b APF = acidulated phosphate fluoride (one application at the beginning of the study). by on April 19, 2010 http://adr.sagepub.com Downloaded from 16 Cury & Tenuta Adv Dent Res 20:13-16, July, 2008 Caries Res 31:356-360. 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