S S

ince 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 fluorides 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 (Rlla 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; Rlla 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 1990which 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 plaques 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 (Rlla, 1989), which depend on the
concentration and frequency of sucrose use (Cury et al., 1997;
Aires et al., 2006; Ccahuana-Vsquez 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, jcury@fop.unicamp.br
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
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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.
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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 (Sepp 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 (Rlla 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).
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