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Toothpaste in the control of

plaque/gingivitis and
periodontitis
ROBI N M. DAVI ES
Periodontal diseases are infections initiated by bac-
terial biolms that form on the surfaces of teeth in
close proximity to their supporting tissues. The
inammatory and immune responses to these bio-
lms are primarily responsible for the subsequent
destruction of the periodontal tissues. Gingivitis and
periodontitis are a continuum and although the
susceptibility of an individual to periodontitis is
inuenced by many factors, such as smoking, dia-
betes and genetics, the weight of evidence indicates
that the prevention of gingival inammation prevents
periodontitis (39).
Periodontal diseases are prevalent in populations
around the world (3). In the USA, 82% of adults
have gingivitis affecting one or more teeth (4) and,
in western Europe, 36% of those aged 3544 years
have moderate periodontitis and approximately
10% have severe periodontitis (62). The prevalence
and severity of periodontitis increases with age (48)
and as the increasing elderly population retain
more of their teeth into later life, periodontal dis-
ease will pose an increasing threat to their natural
dentition.
The focus of any attempt to prevent and control
periodontal disease is the maintenance of an
effective level of plaque control by the individual at
home. Toothbrushing is a societal norm (7, 33, 48).
In the UK, 74% of adults claimed to brush their
teeth twice a day and yet, despite this acceptable
frequency of toothbrushing, 72% were found to
have visible plaque on at least one tooth;
2534 year olds had a mean of 30% of teeth
affected and those aged 65 years had 44% of teeth
affected (48). The available evidence indicates that
most people nd it difcult to maintain a level of
plaque control commensurate with periodontal
health, and there is a need to improve the oral
cleanliness of the majority of the population if
periodontal health is to be improved.
The principle and benets of adding chemical
agents to dentifrices is exemplied by the inclusion
of uoride in dentifrices, which has been a major
factor in reducing the prevalence of dental caries
worldwide (12). Given the importance of plaque
bacteria in initiating periodontal disease, the incor-
poration of an agent into toothpaste that would
reduce the formation of plaque and or its patho-
genicity is a logical development.
The potential of an agent to enhance plaque
control and periodontal health is assessed in a
number of stages (1). Following encouraging results
from in vitro tests, clinical studies, of up to 1 month
in duration, are undertaken to assess the potential of
an agent to improve plaque control and gingival
health. If positive, then randomized controlled
clinical trials of at least 6 months duration are
undertaken to provide regulatory bodies with evi-
dence of effectiveness and safety. An agent with
antiplaque activity must have demonstrated a sig-
nicant benet on gingival health in randomized
controlled studies of at least 6 months duration if it
is to receive approval (6, 13). This requirement will
be adopted in this review and, given the increasing
importance of evidence-based dentistry, priority will
be given to systematic reviews rather than to tradi-
tional reviews.
Metal salts
The most widely used metals in oral health care
products are tin (Sn
2+
) and zinc (Zn
2+
). They have the
ability to limit bacterial growth and plaque formation
(26).
23
Periodontology 2000, Vol. 48, 2008, 2330
Printed in Singapore. All rights reserved
2008 The Author.
Journal compilation 2008 Blackwell Munksgaard
PERIODONTOLOGY 2000
Tin
Stannous uoride dentifrices were launched initially
in the 1950s to deliver the anticaries benet of uo-
ride and it was only found later that Sn
2+
had anti-
microbial effects (69). Seven randomized controlled
clinical trials (9, 10, 4446, 53, 74) of SnF
2
dentifrices
fullled the entry criteria for a systematic review (52).
Gingivitis
All seven studies reported a statistically signicant
reduction in gingivitis in favor of SnF
2
compared
with placebo or an NaF formulation. The reductions
ranged from 18 to 22% (Table 1).
The systematic review (52) concluded that stan-
nous uoride resulted in a signicant reduction in
gingivitis when compared with the control: weighted
mean difference were obtained of )0.15 (gingival
index) and )0.21 (gingivitis severity index).
Plaque
Only three studies reported a statistically signicant
plaque reduction (723%) compared with the control
(Table 1). A meta-analysis of the Turesky index pro-
vided a weighted mean difference of )0.31 (52).
Staining
The use of a stannous uoride toothpaste is associ-
ated with an increase in tooth staining (9, 10, 46, 53).
Zinc
Zinc is retained within the oral cavity after tooth-
brushing (27), and clinical studies, of short duration,
suggested that dentifrices containing zinc citrate
inhibited plaque, particularly in heavy plaque form-
ers (30, 58, 59). Following 3 years of use of a uoride
toothpaste containing 0.5% zinc citrate, a signicant
reduction in plaque was maintained when compared
with a control toothpaste (35). One 6-month study in
adults compared two uoride toothpastes (one of
which contained 2% zinc citrate) for their effective-
ness in reducing plaque and improving gingival
health (75). After 6 months the toothpaste containing
zinc citrate had reduced plaque by 25%, heavy
plaque by 50%, gingivitis by 19% and gingival
bleeding by 67% when compared with the control
toothpaste.
Antibacterial agents
Chlorhexidine
Chlorhexidine digluconate is a powerful antiplaque
agent and numerous clinical trials have demon-
strated that mouthrinses containing this agent are
very effective in improving plaque control and
gingival health (2, 34). Attempts to formulate a
toothpaste have proved difcult because of the
inactivation of chlorhexidine by anionic ingredients.
However, the results of two randomized controlled
trials involving chlorhexidine toothpastes have been
published. One involved a toothpaste containing 1%
chlorhexidine (77) the other 0.4% chlorhexidine and
0.34% Zn
2+
(57). The studies demonstrated that, in
each case, the chlorhexidine toothpastes signicantly
reduced plaque and gingivitis but were accompanied
by an increase in calculus and tooth staining.
Triclosan
Triclosan is a nonionic molecule with a broad spec-
trum of antibacterial activity. It can be formulated in
Table 1. Studies of 6 months duration involving stannous uoride toothpastes
Study Active Control Plaque percentage
reduction vs. control
Gingivitis percentage
reduction vs. control
Beiswanger et al. (9) SnF NaF 3 19*
Beiswanger et al. (10) SnF NaF )2 18*
Mankodi et al. (44) SnF NaF 20* 21*
Mankodi et al. (45) SnF MFP 7* 22*
McClanahan et al. (46) SnF NaF 3 21*
Perlich et al. (53) SnF NaF 3 21*
Williams et al. (74) SnF NaF 23* 22*
NaF, sodium uoride; MFP, sodium monouorophosphate; SnF, stannous uoride.
*Statistically signicant.
24
Davies
conventional toothpastes but is not retained in the
mouth for more than a few hours and therefore does
not deliver a sustained level of antiplaque activity and
clinical benet. To overcome this problem, manu-
facturers have adopted different approaches.
Triclosan/copolymer
The addition of a copolymer (polyvinylmethyl ether
maleic acid) increases the uptake and retention of
triclosan (23) to oral surfaces (plaque, teeth and
mucosa). Subsequent studies have demonstrated that
Colgate Total, containing 0.3% triclosan, 2.0%
copolymer and uoride (1100 1450 p.p.m. F),
maintains concentrations of triclosan in plaque that
exceed the minimum inhibitory concentration values
of many plaque bacteria for up to 12 h (24).
The effectiveness of this dentifrice in reducing
plaque and improving gingival health has been as-
sessed in numerous randomized, controlled clinical
trials (5, 11, 14, 19, 20, 25, 32, 37, 42, 43, 51, 55, 70, 71)
and the results have been summarized in a number
of traditional reviews (21, 72). The range of percent-
age reductions (Table 2) for the triclosan copolymer
toothpaste vs. a uoride control were as follows:
plaque, 059%; and gingivitis, 032%.
Three systematic reviews (18, 29, 31) have been
published that compared the effectiveness of a den-
tifrice containing 0.3% triclosan, 2% copolymer and
sodium uoride (Colgate Total) with that of a con-
ventional uoride dentifrice. In a meta-analysis of
data from 16 studies (18), the weighted mean differ-
ence of )0.48 for the QuigleyHein Plaque Index
corresponds to a 23% reduction in plaque when
compared with a uoride dentifrice. The weighted
mean difference of )0.15 for heavy plaque deposits
corresponds to a 15%reduction of plaque. In relative
terms, there was a 49%reduction in the proportion of
sites that had heavy plaque. The weighted mean
difference of )0.26 for gingival inammation corre-
sponds to a 23% reduction. The weighted mean
difference of )0.34 for gingival bleeding corresponds
to a 12% reduction, which in relative terms corre-
sponds to a 49% reduction in the proportion of sites
with bleeding. The systematic reviews (18, 29, 31)
have conrmed Colgate Total to be signicantly more
effective than a standard uoride toothpaste in
improving plaque control and gingival health.
The progression of gingivitis to periodontitis is an
unpredictable event but bleeding sites are more likely
to progress to periodontitis than nonbleeding sites
(41). Because Colgate Total signicantly reduced
gingival bleeding, further studies have assessed
whether the dentifrice could also have benecial ef-
fects on periodontitis.
A 3-year randomized clinical trial involving
adolescents who were at risk of developing early
periodontitis, demonstrated that Colgate Total was
indeed signicantly more effective than a uoride
toothpaste in preventing the onset of periodontitis
Table 2. Studies of 6 months duration involving triclosan copolymer (Tric copoly) toothpaste
Study Active Control Plaque percentage
reduction vs. control
Gingivitis percentage
reduction vs. control
Allen et al. (5) Tric copoly NaF 30* 23*
Bolden et al. (11) Tric copoly NaF 17* 29*
Cubells et al. (14) Tric copoly NaF 25* 20*
Deasy et al. (19) Tric copoly NaF 32* 26*
Denepitiya et al. (20) Tric copoly NaF 18* 32*
Garcia-Godoy et al. (25) Tric copoly NaF 59* 30*
Grossman et al. (28) Tric copoly NaF 14* 4
Kanchanakamol et al. (37) Tric copoly NaF 12* 1
Lindhe et al. (42) Tric copoly NaF 31* 27*
Mankodi et al. (43) Tric copoly NaF 12* 20*
McClanahan et al. (46) Tric copoly NaF 0 2*
Palomo et al. (51) Tric copoly NaF 11* 21*
Svatun et al. (68) Tric copoly NaF 19* 25*
Triratana et al. (70) Tric copoly NaF 35* 26*
Winston et al. (76) Tric copoly NaF 9 0
NaF, sodium uoride.
*Statistically signicant.
25
Toothpaste in the control of plaque/gingivitis and periodontitis
(22). After 3 years, Colgate Total reduced the amount
of attachment loss (early periodontitis) per subject by
50% and the number of affected sites by 41%. In
another study, patients who already had periodontitis
received oral hygiene instruction, but no subgingival
instrumentation, at 3-monthly intervals for 3 years.
Colgate Total was signicantly more effective than a
uoride dentifrice in reducing pocket depth and
further attachment loss (56).
Data from a 5-year clinical trial in Australia dem-
onstrated that Colgate Total could slow the progres-
sion of periodontitis in a normal adult population
(15). Finally, Colgate Total signicantly improved the
gingival health and periodontal status in smokers
whencompared witha standarduoride dentifrice (38).
No adverse events were reported in any of the
studies, and no shifts in the microora of supragin-
gival plaque favoring the growth of either opportu-
nistic or pathogenic bacterial species were observed
(16, 73, 78, 79).
Initially the benets of Colgate Total were attrib-
uted solely to the antibacterial activity of triclosan,
but a number of studies have demonstrated that tri-
closan may also exert an anti-inammatory effect.
Triclosan reduces skin and mucosal inammation (8,
40, 63) and there is clinical evidence that this may
also occur in the gingiva. The study was a crossover
design in which subjects stopped all mechanical
measures and rinsed for 2 weeks with 0.06%triclosan
plus Tween or 0.06% triclosan plus sodium lauryl
sulfate (54). As predicted, after 2 weeks the plaque
scores indicated that Tween had signicantly re-
duced the antibacterial antiplaque effect of triclo-
san. However, both mouthrinses had a comparable
effect on gingival inammation, which suggested that
triclosan had an anti-inammatory effect. Further
in vitro studies have demonstrated that triclosan
reduces the production of prostaglandinE
2
by cells
stimulated with either interleukin-1b or tumor
necrosis factor-a (47) and the production of inter-
leukin-1b from broblasts (49) stimulated by tumor
necrosis factor-a. More recently (50), it has been re-
ported that triclosan reduces the expression of
microsomal prostaglandin E synthase-1 in human
gingival broblasts.
Triclosan/zinc citrate
The second approach to overcoming the lack of
substantivity and efcacy of triclosan has been to
combine triclosan with zinc citrate (17), the latter
having been shown to be substantive and inhibit
plaque (30, 59) and gingivitis (75). A number of
clinical studies of at least 6 months duration (6468)
have generally shown that dentifrices containing
varying concentrations of zinc citrate and triclosan
are signicantly more effective than a uoride den-
tifrice in controlling plaque and gingivitis (Table 3).
No evidence of a shift in the normal oral ora or
development of bacterial resistance to triclosan was
observed after 7 months of daily use (35, 36).
Triclosan/pyrophosphate
A third approach has been the addition of pyro-
phosphate, a clinically proven anticalculus agent.
Five randomized controlled clinical trials have com-
pared this formulation with a uoride dentifrice (28,
51, 55, 68, 76). In comparison to the control denti-
frice, only one study (28) reported a signicant
reduction (13.9%) in plaque, and two studies (28, 68)
reported a signicant reduction in gingival bleeding
(Table 4).
Amine uoride/stannous uoride
Most clinical trials have assessed a combination of
amine uoride stannous uoride toothpaste and
Table 3. Studies of 6 months duration involving triclosan zinc citrate toothpastes
Study Active (%) Control Plaque % reduction
vs. control
Gingivitis % reduction
vs. control
ZCT Tric
Palomo et al. (51) 0.5 0.2 NaF )6 )4
Saxton (58) 0.5 0.2 MFP 33 52*
Stephen et al. (64) 0.5 0.2 MFP 25 50*
Svatun et al. (65) 1.0 0.2 MFP 37* 34*
Svatun et al. (66) 0.5 0.2 NaF 26* 42*
Svatun et al. (67) 0.75 0.3 MFP 28* 50*
MFP, sodium monouorophosphate; NaF, sodium uoride; Tric, triclosan; ZCT, zinc citrate.
*Statistically signicant.
26
Davies
rinse on plaque and gingivitis. Two randomized
controlled clinical trials of the amine uoride stan-
nous uoride toothpaste have been published. The
rst involved adolescents with a sodium uoride
toothpaste serving as a control group (60). After
6 months there was no difference in plaque scores,
but the amine uoride stannous uoride toothpaste
had reduced gingivitis by 7.6% and gingival bleeding
by 15.8% when compared with the control. Another
study involving adults (61) reported no signicant
differences after 6 months between the amine uo-
ride stannous uoride and control toothpaste with
respect to the plaque and gingival indices, but did
observe a signicant reduction in the percentage of
bleeding sites.
Concluding remarks
In the UK the volume sales of toothpaste have
changed little over the past 10 years; in 1995, total
toothpaste sales were 15.7 million litres compared
with 17.9 million litres in 2004. What has changed,
however, is that the percentage sale of regular uo-
ride toothpastes has declined from 45.1% of volume
in 2000 to 38.4% in 2004 whilst, at the same time,
volume sales of all in one toothpastes have increased
from 24 to 27.8%. This reects the development and
marketing by the oral care industry of toothpastes,
many of which deliver oral health benets in addition
to caries prevention.
The toothpastes considered in this review vary in
their effectiveness in improving plaque control and,
more importantly, gingival health, when compared
with a conventional uoride dentifrice. Toothpastes
containing triclosan copolymer and triclosan zinc
citrate improve plaque control and gingival health,
both safely and effectively, in studies of 6 months
duration. A recent systematic review questioned the
public health signicance of such relatively short-
term improvements (80). However, the unsupervised
use of a triclosan copolymer toothpaste has been
shown to prevent the onset and progression of peri-
odontitis in studies of at least 3 years duration (15,
22, 55).
However, the data supporting the effectiveness of
triclosan pyrophosphate are weak.
Stannous uoride toothpastes have been incon-
sistent in their effect on dental plaque but have
consistently improved gingival health. Their use,
however, is accompanied by staining of the teeth.
The data on toothpastes containing zinc citrate and
amine uoride stannous uoride are insufcient to
make rm recommendations regarding their efcacy.
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27
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