Caries Res 2001;35(suppl 1):6–9
Fluoride – Is It Capable of Fighting Old
and New Dental Diseases?
An Overview of Existing Fluoride Compounds and Their Clinical Applications
Eugenio Brambilla
Department of Pediatric Dentistry, University of Milan, Italy
Key Words
Caries prevention W Fluoride compounds W Topical
fluoride
Abstract
Since researchers first became aware of the anticaries
action of fluoride, they have been investigating the effect
of this preventive agent in inhibiting or arresting caries
development. Many forms of systemic or topical fluoride
have been studied and tested for clinical application.
Water, salt, milk fluoridation and the use of fluoride sup-
plements were introduced for systemic fluoridation
mainly using sodium fluoride. Solutions, gels, tooth-
pastes and rinses of sodium fluoride, stannous fluoride,
amine fluorides, acidulated phosphate fluoride and
monofluorophosphate were used for topical fluorida-
tion. More recently nonaqueous fluoride varnishes in an
alcoholic solution of natural resins and difluorosilane
agents in a polyurethane matrix were introduced. Al-
though all of these fluoridation methods have a caries-
preventive action, these benefits and the ease of applica-
tion is variable. As fluoride is a key component of oral
health promotion a coordinated approach on a commu-
nity and individual basis seems to be needed to maxi-
mize the cost-benefit ratio of prevention.
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Over the last 25 years, caries prevalence in the USA
and most European countries has dramatically declined
to an average as low as DMFT = 1.1 in 12-year-old-chil-
dren [Marthaler et al., 1996]. Although it is difficult to
give a straightforward reason for the present low caries
prevalence in these populations, consensus exists on the
important role of fluoride, particularly the widespread
home use of fluoride toothpaste and the increasing use of
professional topical fluoride applications [Haugejorden et
al., 1997; Newbrun, 1999]. This raises the question of
whether additional self-applied topical fluorides are still
effective in reducing caries in current low-caries-preva-
lence populations and whether the fluoride compounds
used until now have the necessary characteristics to
achieve significant results in terms of efficacy and effi-
ciency.
Fluoride Compounds Used in Caries Prevention
Neutral 2% sodium fluoride solution (NaF) applied
using the ‘paint-on’ technique was chronologically the
first effective topical solution tested [Newbrun, 1999].
This compound was largely used in water fluoridation and
topical fluoride applications but the introduction of topi-
cal fluoride agents with acidulated phosphate greatly
reduced its use except in toothpaste and mouth rinses.
Prof. E. Brambilla
Università degli Studi di Milano, Dipartimento di Medicina, Chirurgia e Odontoiatria
Clinica Odontostomatologica, Via Beldiletto 1–3
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I–20142 Milano (Italy)
Tel. +39 02 8138871, Fax +39 02 8130200, E-Mail Eugenio.Brambilla@unimi.it
University of Manitoba
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Over the last few years dental professionals have shown a
preference for gels, particularly APF, usually at a concen-
tration of 1.23% F – . Clinical trials on APF gel effective-
ness indicate an average reduction in caries of 23–26%
both in fluoride deficient and optimally fluoridated com-
munities [Bagramian, 1982; Johnston, 1994]. Stannous
fluoride is less frequently used, although 0.4% Sn2F gel
has been promoted as the agent of choice for caries pre-
vention.
Amine fluorides represent a group of fluoride com-
pounds extensively tested in Europe over the last 30 years.
They combine the anticaries effect of fluoride with the
protection afforded by long-chain aliphatic amines and
they show high fluoride incorporation into enamel. This
phenomenon is probably related to the activity of the
organic fraction of their molecule and a remarkable anti-
bacterial action against cariogenic microflora [Newbrun,
1999; Stephen, 1994].
Sodium monofluorophosphate (SMFP) has been used
as a fluoride source in toothpastes for several decades.
The efficacy of this compound has been extensively stud-
ied, particularly comparing NaF and SMFP toothpastes.
An approximate 5–10% greater reduction in caries devel-
opment for NaF than for SMFP toothpastes has been
demonstrated in 2- and 3-year clinical trials [Volpe et al.,
1995].
Current Strategies for Clinical Application
The clinical effects of fluorides are strictly dependent
on the methods that deliver the ion to the surface of the
tooth and into the plaque rather than the incorporation of
fluoride into enamel. From the variety of delivery meth-
ods cited in the literature those which are most frequently
clinically applied are listed below.
Water Fluoridation
The first studies linking the fluoride content of drink-
ing water with reduced caries prevalence appeared in the
1930s and more than a hundred studies have been
reported from many different countries over the past 40
years. As a community-based procedure, water fluorida-
tion at 1 ppm level has been consistently demonstrated to
be effective in reducing caries prevalence [WHO, 1994;
Olofsson and Bratthall, 2000]. When caries prevalence is
high and the caries development is monitored over a long-
term period a reduction of 40–49% in primary teeth and
50–59% in permanent teeth is found [Spencer, 1998;
Limeback, 1999].
Existing Fluoride Compounds and Their
Clinical Applications
Salt, Milk and Sugar Fluoridation
The main advantage of salt as a vehicle for fluoride is
that it does not require a community supply such as water
and gives individuals the freedom of choice. Until now
the use of this preventive method has been introduced
and well accepted in five countries: Switzerland (since
1955), France (since 1986), Costa Rica (since 1987),
Jamaica (since 1987) and Germany (since 1991) [WHO,
1994; Olofsson and Bratthall, 2000].
Encouraging results have also been reported with milk
fluoridation, another possible community-based vehicle
for prevention, which gives consumers the choice. A 5-
year trial with fluoridated milk performed in Scotland on
4.5- and 5.5-year-old children receiving daily 200 ml of
fluoridated milk (containing 1.5 mg F – ) at school showed
results, in terms of caries reduction, similar to those of
fluoridated water [Stephen et al., 1984; Marino, 1995].
Similar studies were conducted or are in progress in Chile,
China and Bulgaria [Künzel, 1993; Pakhomov, 1996;
Olofsson and Bratthall, 2000].
Fluoride Supplements
Among the alternative dietary measures for the daily
delivery of fluoride to children, the use of fluoride tablets
has been the most widely accepted. The results of pub-
lished trials show that the use of fluoride tablets is effec-
tive in preventing dental caries in both deciduous and
permanent dentitions. The effectiveness would seem to be
greater the earlier the child begins to take the fluoride sup-
plement – from 40 to 80% reduction being expected in
both deciduous and permanent dentitions if supplemen-
tation starts before 2 years of age [Riordan, 1999; Ste-
phen, 1999; Olofsson and Bratthall, 2000].
Fluoride Rinses
In an attempt to find simple, time-saving and effective
methods for fluoride application mouth rinses were devel-
oped in the 1950s. The efficacy and efficiency of topical
fluorides solutions have been studied in a large number of
clinical trials: unbuffered and acidified NaF, APF, SnF2,
amine fluorides and ammonium fluoride have been
tested. Among the different formulations used [e.g., acid
phosphate fluoride (100–3,000 ppm F), sodium fluoride
(45–3,000 ppm F), stannous fluoride (100–250 ppm F),
ammonium fluoride (1,000 ppm F) and amine fluorides
(250 ppm F)], sodium fluoride would seem to be the pre-
ferred agent [Adair, 1998; Hind, 1999; Olofsson and
Bratthall, 2000].
Caries Res 2001;35(suppl 1):6–9 7
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 Fluoridated Toothpastes
Investigations into the effectiveness of adding fluoride
to toothpaste have been carried out since 1945 and cover
a wide range of active ingredients in various abrasive for-
mulations. Fluoride compounds and their combinations
that have been tested for caries-inhibitory properties
when incorporated into a toothpaste include sodium fluo-
ride, acidulated phosphate fluoride, stannous fluoride,
SMFP and amine fluorides. The results of more than 100
trials of some of these agents show that brushing with a
fluoridated toothpaste will significantly reduce the inci-
dence of dental caries [Holt and Murray, 1997; van Rij-
kom et al., 1998; ten Cate and van Loveren, 1999]. In
countries where fluoridated toothpaste use is widespread,
it is probably the most important means for the topical
application of fluoride. There is strongly supported evi-
dence that the decline in the prevalence of dental caries
recorded in most industrialized countries can be attribut-
ed mainly to the widespread use of fluoridated tooth-
pastes [Haugejorden et al., 1997; ten Cate and van Love-
ren, 1999; Olofsson and Bratthall, 2000].
Topical Solutions and Gels
Since the1940s the most common fluoride solution
was initially 2% sodium fluoride which was applied for
3–4 min after oral prophylaxis. Subsequently a number of
other compounds were used such as stannous fluoride,
acidulated phosphate fluoride and amine fluorides [van
Rijkom et al., 1998]. Topical fluoride solutions have
largely been substituted by gels, which have the advantage
of being used in mouth trays, so that the entire mouth can
be treated in a single application.
ride for up to 180 days and fluoride glass devices, which
release it for up to 1 year [Beltran-Aguilar et al., 2000].
These devices could be an interesting possibility for high
caries risk or handicapped subjects, although they are not
easily found on the market.
Conclusions – Implications for Future Research
Fluoride is a key component of oral health promotion
and probably the most important factor in caries pre-
vention. Biochemical studies of fluoride-enamel interac-
tions are providing new acquisitions into the action mech-
anisms of systemic and topical fluorides, disclosing new
approaches for enhancing their benefits. A synthesis of
the new possibilities and the well-known fluoridation
techniques today seems to be the most important tool
needed to deal with a clinical situation which is more
complex than in the past. Some particular aspects of car-
ies decline, for example, the increased retention of teeth
by adults, will make the long-term effects of fluoride com-
pounds used a crucial factor. Finally, the increasing prev-
alence of exposed roots and the long-term exposure of res-
torations to secondary caries focuses our attention on a
new class of natural-artificial surfaces which must be con-
sidered in planning the preventive strategies based on top-
ical fluoride use in the future.

Fluoride Varnishes
The aim of this fluoride treatment is to prolong the
contact time between fluoride and the tooth surface,
thereby improving fluoride incorporation into the surface
layers of the enamel [Seppa, 1999; Beltran-Aguilar et al.,
2000]. Experimental studies have shown that varnishes
supply fluoride more efficiently than other topical agents.
Fluoride varnish treatment effectively inhibits demineral-
ization, resulting in highly significant caries reductions,
ranging from about 50 to 70% in fissures and an even
higher percentage in the proximal surfaces [Seppa, 1999;
Beltran-Aguilar et al., 2000].

Slow Release Devices

A number of devices which slowly release fluoride into
the oral cavity have been proposed in the literature. These
include copolymer membrane devices, which release fluo-

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