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106
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Int J Dent Hygiene. 2023;21:106–115.wileyonlinelibrary.com/journal/idh
Received: 16 September 2021
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Revised: 23 May 2022
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Accepted: 11 Septemb er 2022
DOI : 10.1111/i dh.12626
ORIGINAL ARTICLE
Antigingivitis efficacy of a sodium bicarbonate toothpaste:
Pooled analysis
Charles R. Parkinson | Andrew Butler | Martin R. Ling
This is an op en access arti cle under the ter ms of the Creative Commons Attribution L icense, which pe rmits use, dis tribu tion and reprod uction in any med ium,
provide d the original wor k is properly cited.
© 2022 Haleon Consumer Healthcare PLC. International Journal of Dental Hygiene published by John Wiley & Sons Ltd.
Clinic altrials.go v: NCT 03703245.
Haleon , Weybridge, UK
Correspondence
Charle s Parki nson, Haleon, St George's
Avenue, Weyb ridge, S urrey K T13 0DE,
UK.
Email: charlie.x.parkinson@haleon.com
Funding information
Haleon
Abstract
Objective: The objective of this study was to investigate the antigingivitis and anti-
plaque treatment effect of a toothpaste containing 67% w/w sodium bicarbonate,
at the individual tooth site, tooth region and whole mouth (overall) level, by way of a
pooled analysis of data from similarly designed clinical trials.
Methods: Six randomized controlled GSKCH clinical trials, 12– 24 weeks in duration,
were selected based on pre- specified criteria which included access to patient level
data, pre- treatment dental prophylaxis, >20 bleeding sites and mild– moderate gin-
givitis at screening and use of 67% sodium bicarbonate toothpaste and non- sodium
bicarbonate (regular) toothpaste (negative control) for ≥4 weeks. Efficacy outcomes
comprised plaque index (TPI), modified gingival index (MGI) and gingival bleeding
(bleeding index (BI), number of bleeding sites (BS)). Treatment comparisons were
made using ANCOVA for whole mouth (overall) scores and by tooth site region (fa-
cial overall, lingual overall; margin/body overall, facial margin/body, lingual margin/
body; papillae/interproximal overall, facial papillae/interproximal, lingual papillae/in-
terproximal). Pooled data for BI, MGI, and TPI at individual tooth sites was plotted as
a mouthmap to summarize treatment response (change from baseline) by tooth site,
at the 24- week timepoint.
Results: For all measures, whole mouth and for all tooth regions at all post- treatment
timepoints, significant (p < 0.001) differences in favour of the 67% sodium bicarbonate
toothpaste compared with control were observed. At the 24- week timepoint, facial
regions demonstrated greater improvements than lingual regions, with the greatest
between treatment improvement seen for the facial- papillae regions for bleeding (BS/
BI), facial- margin regions for MGI and facial- body regions for TPI. All individual tooth
sites demonstrated numerically greater reductions from baseline for the 67% sodium
bicarbonate toothpaste than the control toothpaste following 24 weeks use, with the
greatest improvements (change from baseline) seen for posterior and papillae tooth
sites for bleeding, margin tooth sites for MGI and body tooth sites for TPI.
Conclusion: This pooled analysis of patient level- data, limited to GSKCH long- term gin-
givitis clinical studies, demonstrates that twice daily use of a 67% sodium bicarbonate
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1 | INTRODUCTION
Gingivitis is an inflammatory response to the presence of dental
plaque,1 which typically presents as redness, swelling (oedema), and/
or bleeding of the gums at the gingival margin surrounding the tooth.
Gingivitis is a reversible condition but if left untreated it can progress
to the irreversible phase of periodontitis, where inflammation extends
to the underlying tissues, periodontal ligament, and alveolar bone.2
The resulting loss of these structures can eventually lead to tooth loss
through destruction of the periodontal tissues supporting the tooth.2
Dental plaque is a soft, sticky, colourless deposit of bacteria
which collects on the teeth and along the gingival margin. It is a
causative agent of gingivitis and periodontitis.3,4 Gingivitis can be
prevented and resolved through effec tive plaque control, primarily
via mechanical plaque removal, i.e., toothbrushing.4, 5
Sodium bicarbonate is an ingredient added to toothpastes to aid
plaque removal. It is hypothesized to physically displace plaque from
the tooth surface (mechanical disruption by particles of sodium bicar-
bonate), and/or interfere with the adhe sion characteristics of the bio-
film leading to a reduction of biofilm structural integrity.6 Numerous
clinical studies have been conducted evaluating the ef ficacy of 67%
sodium bicarbonate toothpastes to reduce plaque and provide im-
provements in gingival health.7 – 16 These studies generally report im-
provement s in the measures of plaque and/or gingival health in favour
of the 67% sodium bicarbonate toothpaste compared with a control
toothpaste (non- sodium bicarbonate toothpaste). In a meta- analysis
investigating the ef ficacy of sodium bicarbonate toothpastes in con-
trollin g plaque and gingivitis, Valkenbur g et al.17 repo rted that sodium
bicarbonate toothpastes showed ‘promising results with respect to
plaq ue in sin gl e use stu die s’, how ev er only a sma ll impr ov em ent in gi n-
gival health (as measured by bleeding scores) for sodium bicarbonate
toothpastes relative to a control product was reported. The analysis
highlighted significant variability and uncertainly in the composition
of the sodium bica rbonate tooth paste s, where the quantity of sodi um
bicarbonate in toothpaste can range from 35% to 67% w/w. Sodium
bicarbonate concentration in toothpaste has been suggested to have
positive relationship for plaque removal efficiency, but a statistically
significant relationships has not been observed.6
Single use clinical studies conducted specifically on 67% sodium
bicarbonate toothpastes have reported that the greatest plaque re-
moval advantage for sodium bicarbonate toothpastes, compared with
non- sodium bicarbonate toothpastes, is in the lingual interproximal
areas.14,18 It would therefore be valuable to explore the plaque con-
trol and gingival health treatment effect of 67% sodium bicarbonate
toothpastes, overall and at the tooth region/tooth site level to inter-
rogate the mode of action of 67% sodium bicarbonate toothpastes,
and to explore whether the results from single- use brushing stud-
ies translate to similar plaque control and improvements in gingival
health in longer- term (>4 week) gingival health clinical studies.
We (GSK Consumer Healthcare/Haleo [GCKCH]) have conducted
and reported six long- term (>4 week) clinical studies investigating
improvements in plaque control and gingival health associated with
pre- existing gingivitis, for a 67% sodium bic arbonate toothpaste rel-
ative to a negative control toothpaste (regular toothpaste without
sodium bicarbonate).10,11,13,15,16 These studies were of very similar
design, following guidelines for the conduct of antigingivitis stud-
ies.19 They were conducted in three different countries (India, China
and USA) and employed different examiners. A pooled analysis of
these studies, with available patient- level dat a, can provide reliable
information (with reduced heterogeneity) on the treatment effect
for 67% w/w sodium bicarbonate toothpastes compared with a non-
sodium bicarbonate toothpaste for the whole mouth, by tooth site
region and at the individual tooth site level, and permit comment on
the purported mode of action of sodium bicarbonate.
The aim of this study was therefore to provide a comprehensive
overview of antigingivitis and plaque control treatment effect for
67% w/w sodium bicarbonate toothpastes compared with a negative
control toothpaste, for whole mouth (overall) and by tooth site re-
gion (fa cial overall , lingual over all; ma rgin/ bo dy over all, faci al margin/
body, lingual margin/body; papillae/interproximal overall, facial papil-
lae/interproximal, lingual papillae/interproximal) and individual tooth
site by way of a pooled anal ysis of similar ly conducted clinical studies
employing 67% w/w sodium bicarbonate toothpaste. The primary
outcome was to be considered successful if there was a minimum
statistically signif icant difference of 15% observed between the 67%
w/w so di um bic arb on ate toothp as te and the neg at ive co nt ro l [0 % so -
dium bicarbonate toothpastes or regular marketed toothpastes] for
the overall number of bleeding sites to infer on potential ef fective-
ness and permit comment on the relative efficacy by tooth region.
2 | MATERIALS AND METHODS
2.1 | Pooled analysis study design
Six randomized, blinded, parallel- group controlled clinical studies
investigating a 67% w/w sodium bicarbonate- containing toothpaste
on measures of gingivitis and plaque accumulation were identified
toothpaste effectively removes plaque from all tooth sites, and results in clinically
significant improvements in measures of gingival health, overall and for all the tooth
regions investigated, compared with a non- sodium bicarbonate (regular) toothpaste
following 24 weeks twice daily use.
KEYWORDS
gingivitis, plaque, pooled analysis, sodium bicarbonate, toothpaste
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fr o m our re cor d s (r e porte d prio r to 201 8) fo r incl usi o n in the po ole d-
analyses (13 studies were identified, and six met pre- defined inclu-
sion criteria). Inclusion of these studies in the pooled analysis was
det er mined based on those meeting the pre- spe ci fi ed cri teria and in
agreement with Preferred Reporting Items for Systematic Reviews
and Meta- Analyses (PRISMA) guidelines (Setting Inclusion Criteria
to Avoid Bias in Selecting Studies). The criteria for the selection of
studies were set a priori and based on criteria for establishing effi-
cacy of an ti gi ng iv itis of to ot hpastes (po pu la ti on, disease stage, clini-
cal assessment measure[s], length of study, treatment procedures)
and acce ss to pa ti ent- leve l data. Two reviewer s as se sse d th e stu di es
for inclusion. The following pre- specified criteria were employed:
clinical studies conducted by GSKCH/Haleo allowing full access
to study protocols, reports and patient level study data; inclusion
of a pre- treatment full- mouth prophylaxis; subject eligibility (>20
bleeding sites and mild– moderate gingivitis at Screening); compa-
rable indices of gingivitis or plaque accumulation, and a treatment
consisting of a 67% w/w sodium bicarbonate toothpaste for at least
4 weeks. Details of all the studies identified and reason(s) for ex-
clusion, along with the study location and study durations, salient
procedural aspects and summary details of the participation cri-
teria for subjects in the six studies are provided in supplementary
data Tables S1 and S2. The trial was registered at clini caltr ials.gov
(NCT03703245). Anonymized individual par ticipant data and study
documents can be requested for fur ther research from www.clini
c a l s t u d y d a t a r e q u e s t . c o m .
2.1.1 | Individual studies
All studies were single- center, examiner- blind, 2 or 3 treatments,
parallel group, stratified, randomized, with a dental prophylaxis
per f o r m e d at Ba seline (or at Sc r e e n i n g ) pr ior to st ar t of ra ndomize d
product use. The study design, selection of endpoints, and con-
trols in these studies were similar (supplementary data Tables S1
and S2). Eligible subjects were randomly assigned to one of either
a 67% w/w sodium bicarbonate toothpaste (or additionally 62%
w/w sodium bicarbonate toothpaste where also investigated), or
a negative control (non- sodium bicarbonate toothpaste). Subjects
used the allocated study treatment as part of twice- daily tooth-
brushing for 6 weeks,13 12 weeks10 ,11 and 24 weeks.15,16 For all
studies, the examiner, study statis tician and employees of GSKCH
who may have influenced study outcomes were blinded to treat-
ment allocations. The test product s were supplied in plain tubes
to help maintain blinding. The primary endpoints of the individual
studies were gingival bleeding (bleeding site, BI at four sites) and
inflammation (MGI at four sites) at the final time point measured.
Newby et al.11 included use of the Gingival Index (GI) (at six sites),
rather than MGI (four sites), as the index to measure visual signs
of gingival inflammation. Discussed later (exclusion of data), it was
no t pos sib le to in clu de stu dy New by et al .11 for th e poo led an aly sis
for measures of gingival bleeding and inflammation, however, this
study included plaque/TPI data on comparable tooth surfaces and
the refore plaqu e/ TPI dat a from Newby et al.11 was included in the
pooled analyses.
A single population was defined for each study for all Safety,
Baseline, and Demographic summaries, as well as for the analysis
of efficacy measures. The Intent- to- Treat (ITT) Population consisted
of all subjects who were randomized to treatment , who were dis-
pensed study medication, and had at least one post- baseline effi-
cacy measure.
2.1.2 | Study products
All the clinical studies employed substantially equivalent 67% w/w
sodium bicarbonate toothpastes; the Test sodium bicarbonate for-
mulations only dif fered with respect to flavour and fluoride level
(932 ppm to 1450 ppm fluoride, as sodium fluoride, according to local
regulation under which the studies were conducted). The control
formulations were either marketed regular fluoride toothpastes in
the county where the study was conducted (Crest Cavity Protection
for Jose et al.16 and Akwagyirama et al.,
15 MacLeans FreshMint
for Newby et al.11 or non- marketed regular fluoride toothpastes
manufactured by GSK Consumer Healthcare/Haleon Kakar et al.10;
Lomax et al.13). These ‘non- marketed’ formulations were versions of
Aquafesh Fresh and Minty, without the coloured stripes.
2.2 | Participants
The subject populations included male and non- pregnant, non-
lactating female subjects at least 18 years of age with pre- existing
ging iviti s (m il d to mo der at e) as deter min ed by an ap propr iatel y qua li-
fied clinical examiner.
2.3 | Statistical analysis
Data for the studies included in this pooled analysis were an-
onymized prior to analyses. Individual subject data were used from
the individual studies.
All efficacy variables were summarized by descriptive statistics
(n, adjusted mean, standard error [SE]). Statistical ana lyses tested the
null hypothesis of no difference between treatments versus the al-
ternative that there is a difference between treatments. Two- sided
statistical significance testing (alpha level [α] = 0.05) comparing 67%
sodium bicarbonate toothpaste to negative control toothpaste was
performed for the primar y and secondar y endpoints using the anal-
ysis of covariance (ANCOVA) method of analysis with factors for
treatment and study including the baseline value as a covariate and
smoking status (yes/no) as a stratification factor. The statistical anal-
ysis software used was SAS Studio version 9.4. Analyses were based
on the ITT Population.
Missing data were not imputed. Overall, there were very little
missing data (all included studies had <10% missing data).
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2.3.1 | Analysis periods
For the pooled data, analyses were performed at Week 6, Week 12,
and Week 24 as determined by the time points included in the indi-
vidual clinical studies.
2.3.2 | Exclusion of data from analysis
All data recorded were included where possible. If it was not possible
to convert data from one clinical index to another then the most com-
mon index was used. Newby et al.11 was not included in the pooled
analysis for measures of gingival inflammation as the GI index (meas-
ured at six tooth sites), is neither direc tly nor accurately comparable
to the MGI nor the number of bleeding sites/BI (measured at four
tooth sites). However, plaque/TPI data was included in the pooled
analysis as it was on comparable tooth surfaces to the other studies.
2.3.3 | Demographic and baseline characteristics
Demographic and baseline characteristics summaries were pro-
duced on the ITT Population for individual studies and pooled data.
No formal analysis of the demographic data was conducted; the
characteristics were summarized by treatment groups. The sum-
mary of demographic characteristics included age, sex, race, and
ethnicit y (where available). The summar y of baseline characteristics
included stratification factor, baseline number of bleeding sites (low
and high), and smoking status (smoker and non- smoker).
2.3.4 | Efficacy analysis
Efficacy variables for each of the indices under investigation were
‘overall (whole mouth/region)’, ‘margin’, ‘papillae’ for number of
bleeding sites, BI and MGI; ‘overall’, ‘body’, and ‘interproximal’ (distal
and mesial) for TPI. Papillae and margin (number of bleeding sites,
BI, and MGI) are considered analogous to interproximal (distal and
mesial) and body sites (TPI), respectively. The specific teeth regions
of interest included overall (whole mouth), lingual (all teeth lingual
sites), and facial (all teeth facial sites).
2.3.5 | Primary efficacy endpoint
The primar y efficacy analysis for this pooled analysis focused on the
number of bleeding sites over 24 weeks as this is the longest time
point in the individual studies included in the pooled analysis, and
is considered to be a scientifically and clinically valid endpoint on
which to infer on potential effectiveness of 67% sodium bicarbo-
nate in improving gingival health. The outcome was to be considered
successful if there was a minimum statistically significant differ-
ence of 15% observed between the 67% w/w sodium bicarbonate
toothpaste and the negative control toothpaste for the number of
bleeding sites to infer on potential effectiveness.19
The efficacy variable of number of bleeding sites/index, MGI and
plaque (overall, margin/body, and papillae/interproximal) was summa-
rized and analysed for each of the three overall tooth sites (overall,
lingual, and facial). Each time point data were summarized (n, missing,
mean, median, SD, SE, minimum, and maximum) for the above effi-
ca cy variab le s by tre atm en t gr ou ps. This data set inclu de d the adjus te d
mean and SE of each treatment group, adjusted means (SE) of the
treatment difference between 67% sodium bicarbonate and 0% so-
dium bicarbonate (negative control), 95% CI, % difference, and p- value.
The variables were summarized into a single dataset and a sum-
mary table by study and pooled for investigation of treatment ef-
fects in all areas. Mouth map plot of overall score for all tooth sites
and for various time points were produced for variables BI, MGI, and
TPI for pooled data.
Exploration of Country Effect: The overall efficacy variables
were explored via tabulation by country and treatment groups only.
This summary allowed exploration of potential cultural differences
in measures/responses associated with measures of gingivitis and
plaque accumulation in groups of subjec ts associated with the stud-
ies selected in this pooled analysis. No formal statistical analyses
were performed for this. The descriptive summary (n, missing, mean,
SD, SE, median, minimum, and maximum) was presented by countr y
and treatment group for overall number of bleeding sites, BI, MGI,
and TPI and for overall tooth sites.
3 | RESULTS
3.1 | Participants
A total of 2846 subjec ts were screened across all six studies (in
three counties, India (three studies), USA (two studies) and China
(one study)) [all subjects]. Of these, 1601 subjects were randomized
- 640 subjects in 67% sodium bicarbonate group and 641 subjects
in Negative Control group (320 subjec ts were in a third treatment
group - 62% sodium bicarbonate). A total of 1474 (92.1%) subject s
completed the studies. In the 67% sodium bicarbonate group, 57
subjects did not complete the study (four did not meet study crite-
ria; one withdrew due to an adverse event; 31 were lost to follow-
up; five had protocol violations; 15 withdrew consent; one listed as
‘other’). In the Negative control group, 50 subjects did not complete
the study (one withdrew due to an adverse event; 35 were lost to
follow- up; two had protocol violations; 10 withdrew consent; two
listed as ‘other’).
3.1.1 | Demographic characteristics
A total of 908 subjects (59.2%) were female and 626 subjects (40.8%)
were male across all 6 pooled studies [ITT population]. The major-
ity of subjects (70.7%) were of Asian heritage, 22.2% of subject s
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PARKINSON et al .
were of White heritage. The majority of subjects (54.4%) were not
of Hispanic or Latino ethnicity (Ethnicity was only captured in t wo
studies). The mean (SD) age of subjects was 34.2 years (11.07 years)
with a range of 18 to 79 years across all six studies.
3.1.2 | Baseline characteristics
Overall, 100 0 (65.2%) subject s had a high number of bleeding sites
(≥45) at baseline and the majority of subjects (91.2%) were non-
smokers across all 6 studies. A total of 929 (60.6%) subjects were
non- smokers with baseline number of bleeding sites ≥45; 71 (4.6%)
were smokers with ≥45 bleeding sites; 470 (30.6%) were non-
smokers with <45 bleeding sites; 64 (4.2%) were smokers with <45
bleeding sites.
3.2 | Efficacy
The primar y endpoint (number of bleeding sites) and secondary ef-
ficacy endpoints (BI, MGI and TPI) for overall (whole mouth/region)
and tooth site region are summarized in Tables 1 and 2, respec-
tively. The between- treatment differences (67% sodium bicarbo-
nate vs negative control) in the adjusted mean for all measures for
whole mouth (overall), at all timepoints were st atistically significant
(p < 0.00 01) in favour of 67% sodium bicarbonate toothpaste, and
demonstrated progressive improvements at each time point.
Analysis by tooth region revealed that for all regions, statisti-
cally significant (p < 0.00 01) differences in favour of 67% sodium
bicarbonate toothpaste compared with the control were observed,
also with progressive improvements at each time point. Comparison
between regions showed that facial regions provided numerically
greater between treatment improvements (% difference in favour
of 67% sodium bicarbonate) than lingual regions for all measures
at all post- treatment time points. Margin/body regions (overall, lin-
gual and facial) provided numerically greater between treatment
improvements than papillae/interproximal regions for MGI and TPI,
respectively, at all timepoints. However, for BS/BI, papillae (overall,
lingual and facial) regions showed slightly greater between treatment
improvements than margin areas. The greatest between treatment
improvements (% difference in favour of 67% sodium bicarbonate)
were seen for the papillae facial areas for BS (−54.16%)/BI (−53.72%)
and margin/body facial for MGI and TPI (−25.95 and −23.08, respec-
tively) at 24 weeks.
Figures 1– 3 present ‘mouth maps’ depicting reductions from
baseline for measures of gingival health and plaque for 67% sodium
bicarbonate and control toothpastes by tooth site, at week 24 (BI
(Figure 1), MGI (Figure 2) and TPI (Figure 3)). For all measures at all
tooth sites, numerically greater reductions from baseline were ob-
served for the 67% sodium bicarbonate toothpaste compared with
the control. For BI, highest baseline scores were seen in the poste-
rior teeth and for papillae sites (notably in the facial regions). For
all regions and treatment s, generally the largest reductions from
baseline following treatment were observed in papillae sites, with
the exception the upper palatal region where margin sites showed
greater reduction from baseline than papillae sites. For MGI, the
baseline scores were generally consistent across all regions although
slightly higher baseline scores were observed for the posterior teeth
(tooth numbers 6 and 7) in the upper facial region. For MGI, the high-
est baseline scores were seen in the papilla sites (compared with the
equivalent margin tooth site) in all regions, however in contrast to BI,
the greatest reductions from baseline were generally observed for
the margin sites. For TPI, elevated baseline scores were observed
for the posterior teeth (tooth numbers 6 and 7), most notably for the
facial region. Body sites generally demonstrated the lowest baseline
scores, and the greatest change from baseline was obser ved in the
body sites.
It was obser ved that the improvement in all gingivitis variables
(number of bleeding sites, BI, and MGI) at all relevant time points for
relevant treatment groups was consistent across countries (USA and
India). Similarly, the improvement in plaque variable ( TPI) at all rele-
vant time points for relevant treatment groups was also consistent
across countries (China, India, and USA).
3.3 | Safety
This pooled analysis of individual patient level dat a focused on
the efficacy of t wice- daily use of a 67% w/w sodium bicarbonate
toothpaste, with no study specific objective to pool the safety data
across the studies. All the products were generally well tolerated in
the clinical studies. Further det ails of the adverse events reported
within the individual studies are provided in the supplementary data
Table S3.
4 | DISCUSSION
To the authors’ knowledge, this is the first pooled analysis of in-
dividual patient level data from similarly designed clinical studies
investigating the gingival health benefits of a 67% sodium bicar-
bonate toothpaste. Pooled analysis of these six studies, conducted
across three countries involving 1474 subjects demonstrates large
and statistically significant improvements in measures of gingivitis
(number of bleeding sites, BI, and MGI); a greater than 15% dif fer-
ence between the 67% w/w sodium bicarbonate toothpaste and the
negative control was obser ved for the measures of gingival health.
Notably, over the 24- week treatment period, the number of bleeding
sites per subject reduced from a mean of 56 to a mean of 16 bleeding
sites in the 67% sodium bicarbonate toothpaste treatment group.
Expressed in terms of proportion (%) with respect to the number
sites assessed (128/subject), this represents a reduction from 44%
bleeding sites at baseline to approximately 12% after 24 weeks twice
daily use; which could be describ ed as a shif t from “generalized” gin-
givitis (≥30% sites of the teeth affected by gingival inflammation) or
“localized” gingivitis (<30% sites) gingivitis” to “incipient gingivitis”
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TAB LE 1 Bleeding sites mean values and treatment differences overall and by tooth site region and visit (IT T population)
Tooth Site Region Visit (week)
67% Sodium
bicarbonate Negative control
Comparison of 67% sodium bicarbonate with
negative control in number of bleeding sites
n
Adjusted
Meana (SE) nAdj meana (SE)
Adj mean diff
(SE) 95% CI % Diff
Overall Baseline 498 56.4 (1.03) 505 56.0 (1.01)
6497 25.55 (0.4 03) 505 36.32 (0.400) −10.77 (0.562)*(−11.87, −9.66) −29. 6 4
12 410 18.19 (0.409) 422 3 0.52 (0.404) −12.34 (0.569)*(−1 3.4 5 , −1 1. 22) −40.42
24 222 15.93 (0.596) 228 3 0.77 (0. 588) −14.84 (0.837)*(−16 .48 , −13 .19) −48.22
Overall lingual Baseline 498 31.0 (0.54) 505 30.9 (0.51)
6497 14.94 (0.259) 505 20.48 (0.257) −5.54 (0.361)*(−6.25, −4.83) −27.0 7
12 410 10.85 (0. 262) 422 17.20 (0.259) −6.35 (0.364)*(−7.06, −5.63) −36.93
24 222 10.07 (0.365) 228 17.98 (0.360) −7.91 (0.513)*(−8.92, −6.9 0) −43.99
Overall facial Baseline 498 25.4 (0.55) 505 25.1 (0.55)
6497 10.63 (0.220) 505 15.83 (0.218) −5.20 (0.307)*(−5.81, −4.60) −32.87
12 410 7.34 (0.219) 422 13.32 (0.217) −5.98 (0.305)*(−6.58, −5.38) −44.88
24 222 5.87 (0.3 43) 228 12.78 (0.339) −6.90 (0.482)*(−7. 85, −5.96) −54.03
Margin overall Baseline 498 28.1 (0.60) 505 27.8 (0.60)
6497 13.64 (0.230) 505 18.48 (0.228) −4.85 (0.321)*(−5.47, −4.22) −26. 2 2
12 410 9.46 (0.227) 422 14.98 (0.224) −5.53 (0.316)*(−6.15, −4.91) −36. 89
24 222 7.38 (0.349) 228 13.90 (0.344) −6.52 (0.490)*(−7.48, −5.56) −46.9 2
Margin lingual Baseline 498 16.2 (0.35) 505 16.2 (0.34)
6497 8.49 (0.159) 505 10.95 (0.157) −2.46 (0. 221)*(−2 .89, −2.0 2) −22. 4 4
12 410 5.97 (0.156) 422 8.87 (0.154) −2.89 (0.217)*(−3.32, −2.47) −32.6 4
24 222 4.64 (0.215) 228 7.99 (0.212) −3.36 (0.302)*(−3.95, −2.76) −41 .99
Margin facial Baseline 498 11.9 (0.31) 505 11.7 (0.30)
6497 5.15 (0.126) 505 7.51 (0.125) −2.36 (0.176) (−2 .70, −2.0 1) −31.40
12 410 3.48 (0.124) 422 6 .11 (0.122) −2.62 (0.172) (−2 .9 6, −2 . 29 ) −42.97
24 222 2.75 (0.206) 228 5.89 (0. 203) −3.14 (0.290) (−3.71, −2.57) −53. 28
Papillae overall Baseline 498 28. 3 (0.48) 505 28.2 (0.46)
6497 11.93 (0.240) 505 17.82 (0.238) −5.89 (0.335)*(−6.55, −5.23) −33.05
12 410 8.73 (0. 251) 422 15.53 (0. 248) −6.80 (0.349)*(−7.48, −6.11) −43.77
24 222 8.56 (0.378) 228 16.86 (0.373) −8.30 (0.531)*(−9.34, −7. 26) −49.23
Papillae lingual Baseline 498 14.8 (0.24) 505 14.7 (0.23)
6497 6.46 (0.156) 505 9.53 (0.155) −3.07 (0.218)*(−3.50, −2.64) −32. 21
12 410 4.88 (0.159) 422 8 .33 (0.157) −3.45 (0.221)*(−3.89, −3.0 2) −41.42
24 222 5.41 (0.239) 228 10.01 (0.236) −4.59 (0.336)*(−5.25, −3.93) −45.90
Papillae facial Baseline 498 13.5 (0.29) 505 13.4 (0.29)
6497 5.48 (0.143) 505 8.29 (0.142) −2.81 (0. 200)*(−3.20, −2.42) −33.92
12 410 3.86 (0.142) 422 7.20 (0.141) −3.34 (0.198)*(−3.73, −2.95) −46.43
24 222 3.14 ( 0. 214) 228 6.86 (0. 211) −3.71 (0. 301)*(−4.31, −3.12) −54.16
Note: % Dif fer = 10 0* (Adjusted mean in 67% sodium bicarbonate – adjusted mean in negative)/(Adjuste d mean in negative control).
Abbreviations: CI, confidence interval, % Diff, percentage difference, ITT, intent- to- treat, n, number of subject s, SE, standard error.
aUnadjus ted mean for baseline values.
*p < 0.0001.
112
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PARKINSON et al .
TAB LE 2 Treatment (% dif ference) by tooth site region, index and timepoint (ITT population)
Comparison of 67% sodium bicarbonate with negative control toothpaste
Bleeding Index (BI) Gingival Inflammation (MGI) Plaque Index (TPI)
Tooth Site Region Visit (week) Mean Diff (SE) 95% CI % Diff Mean Dif f (SE) 95% CI % Diff Mean Dif f (SE) 95% CI % Diff
Overall (whole mouth) 6−0.12* (0.006) −0 .13, − 0.11 −3 0.8 8 −0.30* (0.020) −0.34, −0.26 −1 5.4 3 − 0.27* (0.020) −0.31, −0.23 −8.86
12 −0.14* (0.007) −0.15, − 0.12 −41.2 8 −0.28* (0.027) −0.34, − 0.23 −13.06 −0.30* (0.021) −0.34, − 0.26 −1 0.32
24 −0.16* (0.010) −0.18, −0.14 −4 7. 8 0 −0 .42* (0.026) −0.47, −0.37 −1 9. 42 − 0.45* (0.028) −0.50, −0.40 −15 . 3 3
Overall lingual 6−0.13 * (0.009) −0.15, − 0.11 −28 .74 − 0.27* (0.022) −0.31, −0.22 −1 3 .7 1 −0.25* (0.020) −0.29, −0.21 −7.72
12 −0.14* (0.009) −0.16, − 0.13 −38.3 0 −0.24* (0.029) −0.30, −0.19 −11. 0 1 −0.30* (0.021) −0.34, −0.26 −9. 62
24 −0.18 * (0.012) −0.20, −0.15 −44.05 − 0. 41* (0.029) −0.46, − 0.35 −18.07 −0.38* (0.027) −0.43, −0.33 −12 . 71
Overall facial 6−0.11* (0.007) −0.13 , −0 .10 −33. 69 −0.32* (0.021) −0.37, −0.28 −1 7. 28 −0.29* (0.027) −0. 34, −0.23 −10.10
12 −0.13 * (0.007) −0.14, −0 .11 −45.26 −0.32* (0.028) −0.38, −0.27 −15 . 2 7 −0.30* (0.028) −0.36, −0. 25 −11 . 0 6
24 −0.15* (0.011) −0.17, −0.13 −53 .67 −0.4 4* (0.027) −0.50, − 0.39 −20.91 −0.52* (0.038) −0.60, −0.45 −1 8 . 09
Margin/body over all 6−0.11* (0.007) −0.12, −0.09 −27.45 −0.33* (0.023) − 0.38 , −0.29 −18 . 0 8 −0.28* (0.024) −0.33, −0.24 −9.9 0
12 −0.12* (0.007) −0 .13, − 0.11 −38.22 −0.32* (0.030) −0.38, −0.26 −1 5 .7 1 −0.32* (0.026) −0.37, −0.27 −1 1 .4 6
24 −0.14* (0.011) −0.16, − 0.12 −47.05 −0.48* (0.030) − 0.54, −0.42 −2 3.0 0 −0.50* (0.037) −0.58, −0.43 −18.9 0
Margin/body lingual 6−0.12* (0.010) −0 .14, −0.10 −24.36 −0.30* (0.025) −0.35, −0.25 −15.85 −0.26* (0.023) −0.30, −0.21 −8.27
12 −0.13 * (0.010) −0.15, − 0.11 −34.93 −0.27* (0.032) −0. 33, −0.20 −12. 5 6 −0.33* (0.025) −0.38, −0.28 −10. 7 7
24 −0.15* (0.014) −0.18, − 0.12 −42.80 −0.44* (0.032) −0.50, −0.37 −2 0.3 4 −0.43* (0.035) −0.50, −0.36 −15.25
Margin/body facial 6−0.10 * (0.007) −0.11, −0.08 −32.20 −0.36* (0.026) −0.41, −0.31 −20. 51 −0.31* (0.034) −0.37, −0.24 −1 1 .9 0
12 −0.11* (0.007) −0.12, −0.09 −43.50 −0.38* (0.033) −0.45, −0. 31 −19.1 0 −0.30* (0.036) −0.37, −0.23 −1 2 . 3 2
24 −0.13 * (0.012) −0.16, − 0.11 −53.10 −0. 52* (0.033) −0.58, −0.46 −25.95 −0.58* (0.052) −0.68, −0.48 −2 3.0 8
Papillae/interproximal
overall
6−0.14* (0.008) −0.15, − 0.12 −3 4.53 −0.26 (0.019) −0.30, − 0.22 −1 2 .9 1 −0.26* (0.019) −0.30, −0.22 −8.38
12 −0.15* (0.008) −0.17, −0.14 −44.33 −0.24 (0.026) −0.29, −0.19 −1 0 . 58 −0.30* (0.020) −0.33, −0.26 −9. 8 0
24 −0.19* (0.012) −0.21, −0.17 −48.62 −0.37 (0.025) −0.41, −0. 32 −15 .94 −0.42* (0.025) −0.47, −0.37 −13 .77
Papillae/interproximal
lingual
6−0.15* (0.010) −0.17, −0.13 −33.95 −0.24 (0.023) −0.28, −0.19 −1 1 .68 −0. 24* (0.019) −0.28, −0. 20 −7.4 3
12 −0.15* (0.010) −0.17, −0.14 −41.97 −0.22 (0.029) −0.28, −0.17 − 9. 59 0.29* (0.020) −0.33, −0.25 −9.03
24 −0.21* (0.016) −0.24, −0.18 −45.40 −0.38 (0.028) −0.43, −0.32 −1 5 .9 4 −0.35* (0.024) −0.40, −0.31 −11. 4 8
Papillae/interproximal facial 6−0.13* (0.009) −0.15, −0.11 −35.06 −0.28 (0.020) −0.32, −0.24 −14 . 2 6 −0.28* (0.025) −0.32, −0.23 −9.3 1
12 −0.15* (0.009) −0.17, −0.13 −46.91 −0.26 (0.027) −0.32, −0.21 −1 1 .67 −0.30* (0.026) −0.35, −0.25 −10. 5 3
24 −0.17* (0.014) −0 .19, −0.14 −53 .72 −0.36 (0.026) −0.41, −0.31 −16 . 0 0 −0.49* (0.035) −0.56, −0.42 −16 . 0 3
Note: % Dif fe = 100* ( Adjusted mean in 67% sodium bicarbonate – adjus ted mean in negative)/(Adjusted mean in negative control).
Abbreviations: CI, confidence interval, % Diff, percentage difference, SE, standard error.
*p < 0.0001.
|
113
PARKINSON et al.
(only a few sites affected by mild inflammation).20 These results re-
inforce the clinically relevant long- term effect of twice daily use of
67% sodium bicarbonate toothpaste in reducing plaque build- up and
gingivitis, following a professional dental prophylaxis and continued
twice daily use.
The tooth site analysis demonstrated that at all timepoints the
plaque scores for the body sites demonstrated greater improve-
ments (% difference bet ween treatments) than interproximal sites
for the 67% sodium bicarbonate toothpaste. This observation con-
trasts with that reported for single- use plaque removal studies14
FIGURE 1 Bleeding index score at baseline and 24 weeks by tooth site for the 67% sodium bicarbonate toothpaste and control
toothpaste.
1.40
1.20
1.00
0.80
0.60
0.40
0.20
0.00
1.40
1.20
1.00
0.80
0.60
0.40
0.20
0.00
1.40
1.20
1.00
0.80
0.60
0.40
0.20
0.00
M
P
P
P
P
P
M
P
UR7 UR6 UR5 UR4 UR3 UR2 UR1 UL1 UL2 UL3 UL4 UL5 UL6 UL7
1.40
1.20
1.00
0.80
0.60
0.40
0.20
0.00
UPPER FACIAL
LR7 LR6 LR5 LR4 LR3 LR2 LR1 LL1 LL2 LL3 LL4 LL5 LL6 LL7
LOWER FACIAL
UR7 UR6 UR5 UR4 UR3 UR2 UR1 UL1 UL2 UL3 UL4 UL5 UL6 UL7
UPPER PALATAL
LR7 LR6 LR5 LR4 LR3 LR2 LR1 LL1 LL2 LL3 LL4 LL5 LL6 LL7
LOWER LINGUAL
MPM
P
M
PM
P
M
PM
P
Reductions in bleeding index scores from baseline (wk 0–24)
Margin (M), Papilla (P)
Control wk 0
wk 24
Sodium
bicarbonate
wk 0
wk 24
FIGURE 2 Modified gingival index score at baseline and 24 weeks by tooth site for the 67% sodium bicarbonate toothpaste and control
toothpaste.
2.50
2.00
1.50
1.00
0.50
0.00
2.50
2.00
1.50
1.00
0.50
0.00
2.50
2.00
1.50
1.00
0.50
0.00
UR7 UR6 UR5 UR4 UR3 UR2 UR1 UL1 UL2 UL3 UL4 UL5 UL6 UL7
2.50
2.00
1.50
1.00
0.50
0.00
UPPER FACIAL
LR7 LR6 LR5 LR4 LR3 LR2 LR1 LL1 LL2 LL3 LL4 LL5 LL6 LL7
UR7 UR6 UR5 UR4 UR3 UR2 UR1 UL1 UL2 UL3 UL4 UL5 UL6 UL7
UPPER PALATAL
LR7 LR6 LR5 LR4 LR3 LR2 LR1 LL1 LL2 LL3 LL4 LL5 LL6 LL7
LOWER LINGUALLOWER FACIAL
MPM
P
P
P
P
M
P
M
P
MPM
P
MP
M
P
P
Reduction in MGI scores from baseline (wk 0–24)
Margin (M), Papilla (P)
Control wk 0
wk 24
Sodium
bicarbonate
wk 0
wk 24
114
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PARKINSON et al .
where a 67% sodium bicarbonate toothpaste demonstrated the
greatest removal of plaque in the interproximal tooth site areas.
However, this observation can be explained by considering the dif-
ferences in the nature of plaque between single- use plaque removal
studies and long- term gingival health studies (in subjects with pre-
existing gingivitis). Single- use plaque removal studies generally in-
clude ‘high plaque formers’ (typical TPI >2.5 inclusion criteria) with
no/low underlying gingivitis1 4 – 2 1 and explore the removal of imma-
ture plaque (plaque from subjects who have been asked to obtain
from oral hygiene procedures for 24 h), to provide understanding on
the mode of action of formulations.14 The nature of plaque in single
use studies is typically thin, of low complexity and less resistant to
removal than mature plaque that has been allowed to accumulate in
the ‘sheltered’ areas. In contrast, long- term oral hygiene and gingival
health studies generally explore removal of plaque with a range of
maturity. Nevertheless, in this pooled analysis of long- term plaque
and gingivitis studies, while the plaque reduction in the interprox-
imal sites was not the largest out of all the areas explored, it did
result in the greatest improvements (% difference compared with
control) in gingival bleeding, demonstrating that the nature/maturity
of pla que remove d is an imp orta nt fa c to r for peop le pr on e to gi ngi vi -
tis, and that even small reductions in mature plaque (in the interprox-
imal areas) can provide significant improvements in gingival health.
This pooled analysis also demonstrated that improvements in all
clinical measures of gingival health and oral hygiene were consis-
tent across the three countries in which the individual studies were
conducted.
An advantage of this pooled analysis is that it employed studies of
very similar design, which provided reliable information with reduced
heterogeneity, to explore plaque control and gingival health benefits of
a 67% sodium bica rb onate to ot hp aste at th e in di vidual tooth sit e le ve l.
However, equally this could be seen as a limitation, and the results
sho ul d only be viewed in the context of patients wit h gingi vi tis (no his-
tory of periodontitis) and who undergo/have access to an appropriate
standard of dental care (regular professional cleaning), and maintain
long- term compliance with maintain oral hygiene. This pooled analy-
sis also only included studies in which the Investigators had access to
patient- level data (studies conducted by GSKCH/Haleon) in order to
conduct a tooth site analysis. This study could be improved by con-
ducting a broader analysis using patient- level data from studies con-
ducted by other institutions. Anonymized individual participant data
and study documents from this study can be requested for further
research from w w w . c l i n i c a l s t u d y d a t a r e q u e s t . c o m .
5 | CONCLUSION
This pooled analysis of patient- level data from six similarly designed
studies demonstrates gingival health and plaque control in partici-
pants with mild to moderate gingivitis were significantly improved
following a professional dental clean and twice- daily brushing with a
67% sodium bicarbonate toothpaste compared with a regular (non-
sodium bicarbonate) toothpaste. Improvements in the measure of
gingival health and oral hygiene were consistent across all tooth sites
sug ge st ing that the mech an ic al act io n of sodium bic ar bo nate (toot h-
pastes) extends to all tooth sites.
6 | CLINICAL RELEVANCE
As a supplement to professional dental cleaning, the long- term
use of a sodium bicarbonate (67%) toothpaste twice daily is more
FIGURE 3 TPI score at baseline and 24 weeks by tooth site for the 67% sodium bicarbonate toothpaste and control toothpaste.
4.50
4.00
3.50
3.00
2.50
2.00
1.50
1.00
0.50
0.00
4.50
4.00
3.50
3.00
2.50
2.00
1.50
1.00
0.50
0.00
LR7 LR6 LR5 LR4 LR3 LR2 LR1 LL1 LL2 LL3 LL4 LL5 LL6 LL7
LOWER FACIAL
UR7 UR6 UR5 UR4 UR3 UR2 UR1 UL1 UL2 UL3 UL4 UL5 UL6 UL7
UPPER PALATAL
LR7 LR6 LR5 LR4 LR3 LR2 LR1 LL1 LL2 LL3 LL4 LL5 LL6 LL7
LOWER LINGUAL
UR7 UR6 UR5 UR4 UR3 UR2 UR1 UL1 UL2 UL3 UL4 UL5 UL6 UL7
4.50
4.00
3.50
3.00
2.50
2.00
1.50
1.00
0.50
0.00
UPPER FACIAL
DBMMBD
DBMMBD
D
BMMBD
DBM M BD
4.50
4.00
3.50
3.00
2.50
2.00
1.50
1.00
0.50
0.00
Reduction in plaque (TPI) scores from baseline (wk 0–24)
Distal (D), Body (B), Mesial (M)
MM
MM
MM
MM
Control wk 0
wk 24
Sodium
bicarbonate
wk 0
wk 24
|
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PARKINSON et al.
effective at removing plaque biofilms and improving gingival health
(at all tooth sites in the mouth) compared with a non- sodium bicar-
bonate toothpaste.
AUTHOR CONTRIBUTIONS
CP contributed to conception, design and interpretation of the study
and results and drafted the manuscript. AB and ML contributed to
conception, design and interpretation of the study and results and
critically reviewed the manuscript .
ACKNOWLEDGEMENT
Olgilvy Healthworld (David Davenpor t- Firth, Romina Ciccioli and Elli
Harper) and Jo Franklin (GSKCH) are thanked for design assistance
in producing the ‘mouthmap’ figures.
FUNDING INFORMATION
This study was funded by Haleon (previously GSK Consumer
Healthcare).
CONFLICT OF INTEREST
CP, AB and ML are employees of Haleon, who provided funding for
this study.
DATA AVAILAB ILITY STATE MEN T
The dat a that support the findings of this study are available on re-
quest from w w w . c l i n i c a l s t u d y d a t a r e q u e s t . c o m .
ORCID
Charles R. Parkinson https://orcid.org/0000-0001-5087-4468
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SUPPORTING INFORMATION
Additional supporting information can be found online in the
Suppor ting Information section at the end of this article.
How to cite this article: Parkinson CR, Butler A, Ling MR.
Antigingivitis efficacy of a sodium bicarbonate toothpaste:
Pooled analysis. Int J Dent Hygiene. 2023;21:106-115. doi:
10.1111/id h.1 2626
