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Periodontology 2000, Vol. 48, 2008, 23–30  2008 The Author.

Printed in Singapore. All rights reserved Journal compilation  2008 Blackwell Munksgaard
PERIODONTOLOGY 2000

Toothpaste in the control of


plaque/gingivitis and
periodontitis
R O B I N M. D A V I E S

Periodontal diseases are infections initiated by bac- cleanliness of the majority of the population if
terial biofilms that form on the surfaces of teeth in periodontal health is to be improved.
close proximity to their supporting tissues. The The principle and benefits of adding chemical
inflammatory and immune responses to these bio- agents to dentifrices is exemplified by the inclusion
films are primarily responsible for the subsequent of fluoride in dentifrices, which has been a major
destruction of the periodontal tissues. Gingivitis and factor in reducing the prevalence of dental caries
periodontitis are a continuum and although the worldwide (12). Given the importance of plaque
susceptibility of an individual to periodontitis is bacteria in initiating periodontal disease, the incor-
influenced by many factors, such as smoking, dia- poration of an agent into toothpaste that would
betes and genetics, the weight of evidence indicates reduce the formation of plaque and ⁄ or its patho-
that the prevention of gingival inflammation prevents genicity is a logical development.
periodontitis (39). The potential of an agent to enhance plaque
Periodontal diseases are prevalent in populations control and periodontal health is assessed in a
around the world (3). In the USA, 82% of adults number of stages (1). Following encouraging results
have gingivitis affecting one or more teeth (4) and, from in vitro tests, clinical studies, of up to 1 month
in western Europe, 36% of those aged 35–44 years in duration, are undertaken to assess the potential of
have moderate periodontitis and approximately an agent to improve plaque control and gingival
10% have severe periodontitis (62). The prevalence health. If positive, then randomized controlled
and severity of periodontitis increases with age (48) clinical trials of at least 6 monthsÕ duration are
and as the increasing elderly population retain undertaken to provide regulatory bodies with evi-
more of their teeth into later life, periodontal dis- dence of effectiveness and safety. An agent with
ease will pose an increasing threat to their natural antiplaque activity must have demonstrated a sig-
dentition. nificant benefit on gingival health in randomized
The focus of any attempt to prevent and control controlled studies of at least 6 monthsÕ duration if it
periodontal disease is the maintenance of an is to receive approval (6, 13). This requirement will
effective level of plaque control by the individual at be adopted in this review and, given the increasing
home. Toothbrushing is a societal norm (7, 33, 48). importance of evidence-based dentistry, priority will
In the UK, 74% of adults claimed to brush their be given to systematic reviews rather than to tradi-
teeth twice a day and yet, despite this acceptable tional reviews.
frequency of toothbrushing, 72% were found to
have visible plaque on at least one tooth;
25–34 year olds had a mean of 30% of teeth Metal salts
affected and those aged 65 years had 44% of teeth
affected (48). The available evidence indicates that The most widely used metals in oral health care
most people find it difficult to maintain a level of products are tin (Sn2+) and zinc (Zn2+). They have the
plaque control commensurate with periodontal ability to limit bacterial growth and plaque formation
health, and there is a need to improve the oral (26).

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Davies

Tin ers (30, 58, 59). Following 3 years of use of a fluoride


toothpaste containing 0.5% zinc citrate, a significant
Stannous fluoride dentifrices were launched initially reduction in plaque was maintained when compared
in the 1950s to deliver the anticaries benefit of fluo- with a control toothpaste (35). One 6-month study in
ride and it was only found later that Sn2+ had anti- adults compared two fluoride toothpastes (one of
microbial effects (69). Seven randomized controlled which contained 2% zinc citrate) for their effective-
clinical trials (9, 10, 44–46, 53, 74) of SnF2 dentifrices ness in reducing plaque and improving gingival
fulfilled the entry criteria for a systematic review (52). health (75). After 6 months the toothpaste containing
zinc citrate had reduced plaque by 25%, heavy
Gingivitis plaque by 50%, gingivitis by 19% and gingival
bleeding by 67% when compared with the control
All seven studies reported a statistically significant
toothpaste.
reduction in gingivitis in favor of SnF2 compared
with placebo or an NaF formulation. The reductions
ranged from 18 to 22% (Table 1).
The systematic review (52) concluded that stan- Antibacterial agents
nous fluoride resulted in a significant reduction in
gingivitis when compared with the control: weighted Chlorhexidine
mean difference were obtained of )0.15 (gingival Chlorhexidine digluconate is a powerful antiplaque
index) and )0.21 (gingivitis severity index). agent and numerous clinical trials have demon-
strated that mouthrinses containing this agent are
Plaque very effective in improving plaque control and
gingival health (2, 34). Attempts to formulate a
Only three studies reported a statistically significant toothpaste have proved difficult because of the
plaque reduction (7–23%) compared with the control inactivation of chlorhexidine by anionic ingredients.
(Table 1). A meta-analysis of the Turesky index pro- However, the results of two randomized controlled
vided a weighted mean difference of )0.31 (52). trials involving chlorhexidine toothpastes have been
published. One involved a toothpaste containing 1%
chlorhexidine (77) the other 0.4% chlorhexidine and
Staining
0.34% Zn2+ (57). The studies demonstrated that, in
The use of a stannous fluoride toothpaste is associ- each case, the chlorhexidine toothpastes significantly
ated with an increase in tooth staining (9, 10, 46, 53). reduced plaque and gingivitis but were accompanied
by an increase in calculus and tooth staining.

Zinc
Zinc is retained within the oral cavity after tooth- Triclosan
brushing (27), and clinical studies, of short duration,
suggested that dentifrices containing zinc citrate Triclosan is a nonionic molecule with a broad spec-
inhibited plaque, particularly in heavy plaque form- trum of antibacterial activity. It can be formulated in

Table 1. Studies of 6 monthsÕ duration involving stannous fluoride toothpastes


Study Active Control Plaque percentage Gingivitis percentage
reduction vs. control 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 fluoride; MFP, sodium monofluorophosphate; SnF, stannous fluoride.
*Statistically significant.

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Toothpaste in the control of plaque/gingivitis and periodontitis

conventional toothpastes but is not retained in the ventional fluoride dentifrice. In a meta-analysis of
mouth for more than a few hours and therefore does data from 16 studies (18), the weighted mean differ-
not deliver a sustained level of antiplaque activity and ence of )0.48 for the Quigley–Hein Plaque Index
clinical benefit. To overcome this problem, manu- corresponds to a 23% reduction in plaque when
facturers have adopted different approaches. compared with a fluoride dentifrice. The weighted
mean difference of )0.15 for heavy plaque deposits
corresponds to a 15% reduction of plaque. In relative
Triclosan/copolymer
terms, there was a 49% reduction in the proportion of
The addition of a copolymer (polyvinylmethyl ether sites that had heavy plaque. The weighted mean
maleic acid) increases the uptake and retention of difference of )0.26 for gingival inflammation corre-
triclosan (23) to oral surfaces (plaque, teeth and sponds to a 23% reduction. The weighted mean
mucosa). Subsequent studies have demonstrated that difference of )0.34 for gingival bleeding corresponds
Colgate Total, containing 0.3% triclosan, 2.0% to a 12% reduction, which in relative terms corre-
copolymer and fluoride (1100 ⁄ 1450 p.p.m. F), sponds to a 49% reduction in the proportion of sites
maintains concentrations of triclosan in plaque that with bleeding. The systematic reviews (18, 29, 31)
exceed the minimum inhibitory concentration values have confirmed Colgate Total to be significantly more
of many plaque bacteria for up to 12 h (24). effective than a standard fluoride toothpaste in
The effectiveness of this dentifrice in reducing improving plaque control and gingival health.
plaque and improving gingival health has been as- The progression of gingivitis to periodontitis is an
sessed in numerous randomized, controlled clinical unpredictable event but bleeding sites are more likely
trials (5, 11, 14, 19, 20, 25, 32, 37, 42, 43, 51, 55, 70, 71) to progress to periodontitis than nonbleeding sites
and the results have been summarized in a number (41). Because Colgate Total significantly reduced
of traditional reviews (21, 72). The range of percent- gingival bleeding, further studies have assessed
age reductions (Table 2) for the triclosan ⁄ copolymer whether the dentifrice could also have beneficial ef-
toothpaste vs. a fluoride control were as follows: fects on periodontitis.
plaque, 0–59%; and gingivitis, 0–32%. A 3-year randomized clinical trial involving
Three systematic reviews (18, 29, 31) have been adolescents who were at risk of developing early
published that compared the effectiveness of a den- periodontitis, demonstrated that Colgate Total was
tifrice containing 0.3% triclosan, 2% copolymer and indeed significantly more effective than a fluoride
sodium fluoride (Colgate Total) with that of a con- toothpaste in preventing the onset of periodontitis

Table 2. Studies of 6 monthsÕ duration involving triclosan ⁄ copolymer (Tric ⁄ copoly) toothpaste
Study Active Control Plaque percentage Gingivitis percentage
reduction vs. control 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 fluoride.
*Statistically significant.

25
Davies

(22). After 3 years, Colgate Total reduced the amount necrosis factor-a (47) and the production of inter-
of attachment loss (early periodontitis) per subject by leukin-1b from fibroblasts (49) stimulated by tumor
50% and the number of affected sites by 41%. In necrosis factor-a. More recently (50), it has been re-
another study, patients who already had periodontitis ported that triclosan reduces the expression of
received oral hygiene instruction, but no subgingival microsomal prostaglandin E synthase-1 in human
instrumentation, at 3-monthly intervals for 3 years. gingival fibroblasts.
Colgate Total was significantly more effective than a
fluoride dentifrice in reducing pocket depth and
Triclosan/zinc citrate
further attachment loss (56).
Data from a 5-year clinical trial in Australia dem- The second approach to overcoming the lack of
onstrated that Colgate Total could slow the progres- substantivity and efficacy of triclosan has been to
sion of periodontitis in a normal adult population combine triclosan with zinc citrate (17), the latter
(15). Finally, Colgate Total significantly improved the having been shown to be substantive and inhibit
gingival health and periodontal status in smokers plaque (30, 59) and gingivitis (75). A number of
when compared with a standard fluoride dentifrice (38). clinical studies of at least 6 monthsÕ duration (64–68)
No adverse events were reported in any of the have generally shown that dentifrices containing
studies, and no shifts in the microflora of supragin- varying concentrations of zinc citrate and triclosan
gival plaque favoring the growth of either opportu- are significantly more effective than a fluoride den-
nistic or pathogenic bacterial species were observed tifrice in controlling plaque and gingivitis (Table 3).
(16, 73, 78, 79). No evidence of a shift in the normal oral flora or
Initially the benefits of Colgate Total were attrib- development of bacterial resistance to triclosan was
uted solely to the antibacterial activity of triclosan, observed after 7 months of daily use (35, 36).
but a number of studies have demonstrated that tri-
closan may also exert an anti-inflammatory effect.
Triclosan/pyrophosphate
Triclosan reduces skin and mucosal inflammation (8,
40, 63) and there is clinical evidence that this may A third approach has been the addition of pyro-
also occur in the gingiva. The study was a crossover phosphate, a clinically proven anticalculus agent.
design in which subjects stopped all mechanical Five randomized controlled clinical trials have com-
measures and rinsed for 2 weeks with 0.06% triclosan pared this formulation with a fluoride dentifrice (28,
plus Tween or 0.06% triclosan plus sodium lauryl 51, 55, 68, 76). In comparison to the control denti-
sulfate (54). As predicted, after 2 weeks the plaque frice, only one study (28) reported a significant
scores indicated that Tween had significantly re- reduction (13.9%) in plaque, and two studies (28, 68)
duced the antibacterial ⁄ antiplaque effect of triclo- reported a significant reduction in gingival bleeding
san. However, both mouthrinses had a comparable (Table 4).
effect on gingival inflammation, which suggested that
triclosan had an anti-inflammatory effect. Further
Amine fluoride/stannous fluoride
in vitro studies have demonstrated that triclosan
reduces the production of prostaglandinE2 by cells Most clinical trials have assessed a combination of
stimulated with either interleukin-1b or tumor amine fluoride ⁄ stannous fluoride toothpaste and

Table 3. Studies of 6 monthsÕ duration involving triclosan ⁄ zinc citrate toothpastes


Study Active (%) Control Plaque % reduction Gingivitis % reduction
vs. control 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 monofluorophosphate; NaF, sodium fluoride; Tric, triclosan; ZCT, zinc citrate.
*Statistically significant.

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Toothpaste in the control of plaque/gingivitis and periodontitis

Table 4. Studies of 6 monthsÕ duration involving triclosan ⁄ pyrophosphate toothpaste


Study Active (%) Control Plaque % reduction Gingivitis % reduction
vs. control vs. control
Tric Pyro
Grossman et al. (28) 0.28 5.0 NaF 14* )4
Palomo et al. (51) 0.3 5.0 NaF )2.5 0
Renvert & Birkhed (55) 0.3 5.0 MFP 0 20
Svatun et al. (68) 0.3 5.0 MFP 9.5 24*
Winston et al. (76) 0.28 5.0 NaF 12 6
MFP, sodium monofluorophosphate; NaF, sodium fluoride; Tric, triclosan; Pyro, pyrophosphate.
*Statistically significant.

rinse on plaque and gingivitis. Two randomized term improvements (80). However, the unsupervised
controlled clinical trials of the amine fluoride ⁄ stan- use of a triclosan ⁄ copolymer toothpaste has been
nous fluoride toothpaste have been published. The shown to prevent the onset and progression of peri-
first involved adolescents with a sodium fluoride odontitis in studies of at least 3 yearsÕ duration (15,
toothpaste serving as a control group (60). After 22, 55).
6 months there was no difference in plaque scores, However, the data supporting the effectiveness of
but the amine fluoride ⁄ stannous fluoride toothpaste triclosan ⁄ pyrophosphate are weak.
had reduced gingivitis by 7.6% and gingival bleeding Stannous fluoride toothpastes have been incon-
by 15.8% when compared with the control. Another sistent in their effect on dental plaque but have
study involving adults (61) reported no significant consistently improved gingival health. Their use,
differences after 6 months between the amine fluo- however, is accompanied by staining of the teeth.
ride ⁄ stannous fluoride and control toothpaste with The data on toothpastes containing zinc citrate and
respect to the plaque and gingival indices, but did amine fluoride ⁄ stannous fluoride are insufficient to
observe a significant reduction in the percentage of make firm recommendations regarding their efficacy.
bleeding sites.

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