Gingival Health Changes Associated with BriteSmile Tooth

Transcription

The Clinical Research
Collaborative
Forsyth Institute
Gingival Health Changes
Associated with BriteSmile Tooth
Whitening
Final Report
August 2003
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Table of Contents
Executive Summary
Introduction 4
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EARLY STUDIES
POTENTIAL SIGNIFICANCE
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Material and Methods
EXPERIMENTAL DESIGN
Subject Selection
Experimental groups
Experimental design
Clinical measurements
Laboratory measurements
SUBJECT INCLUSION CRITERIA
SUBJECT EXCLUSION CRITERIA
TEST PROTOCOL
CALIBRATION OF THE BRITESMILE GAS-PLASMA LIGHT.
GINGIVAL AND PLAQUE EVALUATION
COLORIMETRIC ANALYSIS
RISK MITIGATION
STATISTICAL ANALYSIS
Results
SUBJECT POPULATION
SUBJECT WITHDRAWALS
TOOTH SHADE
Initial Tooth Shade
Tooth Shade at each visit
Change in Tooth Shade
TOOTH COLOR L*
Initial Tooth Color L*
Tooth Color L* at each visit
Change in Tooth Color L*
Factorial Analysis of change in L* by Peroxide and Light
TOOTH COLOR A*
Initial Tooth Color a*
Tooth Color a* at each visit
Change in Tooth Color a*
TOOTH COLOR B*
Initial Tooth Color b*
Tooth Color b* at each visit
Change in Tooth Color b*
TOOTH COLOR CHANGE (∆E)
GINGIVAL INDEX
Initial Gingival Index
Gingival Index at each visit
Gingival Index Change
Factorial analysis of Gingival Index Data
PLAQUE INDEX
Initial Plaque Index
Plaque Index at each visit
Plaque Index Change
BLEEDING ON PROBING
Initial Bleeding on Probing
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Bleeding .on Probing at each visit
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Bleeding on Probing Change
EDBI
Initial EDBI
EDBI at each visit
EDBI Change
POCKET DEPTH
Initial Pocket Depth
Pocket Depth at each visit
Pocket Depth Change
GINGIVAL CREVICE FLUID
Initial GCF flow
Initial Resting Volume
GCF flow at each visit
GCF Resting volume at each visit
GINGIVAL COLOR L*
Gingival Color L* at each visit
GINGIVAL COLOR A*
Initial Gingival Color a*
Gingival Color a* at each visit
Change in Gingival Color a*
GINGIVAL COLOR B*
Initial Gingival Color b*
Gingival Color b* at each visit
Change in Gingival Color b*
CHANGE IN GINGIVAL COLOR (∆E)
HYDROGEN SULFIDE MEASUREMENT
INTERLEUKIN 1 β MEASUREMENT
Initial IL1β values
IL1β values for all visits
MICROBIOLOGY DATA
Changes in P. gingivalis proportions
Changes in P. gingivalis proportions by factorial analysis
QUESTIONNAIRE DATA
Post-Treatment Evaluation
One-Week follow up Survey
Subject Recall Questionnaire
Discussion 114
Conclusions 116
References 116
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Section
1
Gingival Health Changes Associated with
BriteSmile Tooth Whitening
Final Report
August 2003
Executive Summary
The purpose of this study was to evaluate the effects of each component of the BriteSmile
treatment on measures of the gingival of participating research subjects.
Experimental Design: The effectiveness of each component of the BriteSmile 2000 tooth
whitening system on gingival health was evaluated in a randomized and blinded 6-month
clinical trial. 108 subjects were selected for having anterior gingivitis and were randomly
assigned to one of four treatment groups. 98 subjects completed the study. Anterior teeth
of the test group (peroxide + light) were treated for one hour by the combined application of
a gel containing 15% peroxide and irradiation with a high intensity light (the standard
BriteSmile treatment). Placebo controls included a placebo gel which had the same
composition as the peroxide gel but without peroxide and a placebo light treatment which
was accomplished by turning on the BriteSmile light fan and a timer after the orange total
light block goggles were in place. The peroxide control group received topical application of
15% peroxide gel and placebo light. The light control group received application of a
placebo gel and regular intensity light irradiation. The true placebo group received a
placebo gel and placebo light. This experimental design permitted evaluation of the
combined peroxide + light treatment with peroxide alone, light alone, and nothing to
determine the relative effectiveness of the combination therapy relative to the individual
components of the treatment.
Reproduction of Original Studies. The original finding that BriteSmile treatment reduced
Gingival Index through 6 months was reproduced. The concomitant tooth whitening effect
was an initial reduction of approximately 5 Vita shade steps in a group accepted with C2 or
darker tooth shade. Factorial analysis of tooth color change revealed that light and peroxide
work independently (rather than synergistically) in changing tooth color.
Power of the Placebo. The placebo light and gel group was an excellent control. It was so
good that 55% of placebo- treated subjects felt there some tooth whitening and 41% were
willing to recommend it to their friends (q.v. Q1,Q6, Post-Treatment questionnaire) even
though no change in tooth shade was seen (q.v. Tooth Shade section). The response of the
placebo group tells us that much of the gingival health benefit of the BriteSmile treatment
was realized through improved home care. More than 50% of the reduction in Gingival
Index seen in BriteSmile treatment was also seen in Placebo treatment. Plaque index , a
measure of home care, was reduced by approximately one-half from baseline in all groups
to the same degree and maintained at a low level throughout the study. The Eastman
Dental Bleeding Index (EDBI), Gingival Crevice Fluid Flow (GCF flow) and GCF resting
volume were reduced to the same extent by both BriteSmile and Placebo treatments. From
these observations we may conclude that the BriteSmile treatment process, even without
the tooth whitening is a powerful stimulus to improve home care and gingival health.
The central question remaining is:
Is there an added benefit of light and/or peroxide to improve gingival health beyond
the placebo effect?
Using the factorial design of this clinical study, one may factor out the effects of light and
peroxide on reduction in gingival index. This reveals that the effect of light alone is much
greater than peroxide, peaks 1 week after treatment and thereafter declines.
Considering the microbiological response, a treatment-related major change in the
proportion of P. gingivalis was found. P. gingivalis is a recognized periodontal pathogen and
a black-pigmented organism that one would expect to absorb light strongly. Through
detailed analysis of the percentage P. gingivalis in plaque within each treatment group, it
was found that a remarkable proliferation occurred at 6-months in the placebo treated group
that was not seen in any of the other groups.
8
5
P. gingivalis
Proportion
(%)
2
0
Light + Light
Peroxide
Peroxide Placebo
2
This proliferation from an average of 2% in other treatment groups to 6% in the placebo
treated group may be the genesis of a new periodontal disease lesion. At periodontally
diseased sites, levels of up to 20% are seen.
The effect of light and peroxide on the proportion of P. gingivalis in periodontal plaque is
clearly inhibitory as seen in the following figure.
This figure indicates that the proportion of P. gingivalis was less at all visits with light
application (Light(1)) compared with no light (Light(0)). Peroxide, though less effective may
also have had some effect. Analysis of interaction indicated that light and peroxide work
independently and that generally peroxide did not improve the ability of light to suppress P.
gingivalis.
Conclusions: Intensified homecare appears to explain much of the improved gingival health
associated with BriteSmiles tooth whitening. In addition, evidence for gingival health
improvement associated particularly with the light component of BriteSmiles therapy was
obtained through factorial analysis. Data suggests that this benefit could be through
suppression of black pigmented species such as P. gingivalis.
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Section
2
Introduction
Early Studies
Early studies in the periodontal effects of a combined application of 15% peroxide gel
and high-intensity light exposure for 1 hour (the BriteSmile treatment) revealed that
significant changes in gingival index were associated with the treatment. The gingival index
was measured by the method of Loe and Silness (1963) and is described as follows:
0 = Normal gingiva.
1 = Mild; slight color change; slight edema.
2 = Moderate; Redness and Glazing.
3 = Severe; Marked redness and edema; ulceration; spontaneous bleeding.
The observed changes are illustrated in the following figure.
1.0
Peroxide + Light
Peroxide
Light
0.8
Gingival
Index
0.6
0.4
*
0.2
0.0
Pre3-Month
treatment
6-Month
Figure 1 Gingival Index values of subjects treated by Peroxide + Light, Peroxide alone and Light alone.
This figure indicates that pre-treatment, subjects had little gingivitis as indicated
by gingival index values of approximately 0.6. Following the treatment, redness was
reduced to a greater level than before treatment in all groups. By the 6-month
observation period, the peroxide + light treatment remained at lowered levels which
were significantly lower than that of the light control treated group.
4
At the same time, plaque index (Silness and Loe 1964) was evaluated. The
plaque index of is defined as:
0 = No plaque.
1 = Film at gingival margin: remove plaque with probe.
2 = Moderate; seen with naked eye.
3 = Abundance of material.
If one considers the plaque index as a reasonable estimate of oral cleanliness the following
figure indicates that none of the changes seen in gingival index status were seen in visible
plaque accumulation.
1.0
0.8
Plaque
Index
0.6
Peroxide + Light
Peroxide
Light
0.4
0.2
0.0
Pre3-Month
treatment
6-Month
Figure 2 Plaque Index values of subjects treated by Peroxide + Light, Peroxide alone and Light alone.
In this case, patients came in with low levels of visible plaque (the average plaque index
being approximately 0.1) and low levels were maintained throughout the study and were not
affected by therapy.
Taken together, these data suggest that treatment with light + peroxide significantly
reduced gingival inflammation without materially affecting the amount of visible plaque. This
observation immediately suggests the possibility that the therapy may have altered the
bacterial composition of the periodontal environment to one more favorable to periodontal
health.
Potential Significance
There are few if any single gingival periodontal treatments that produce beneficial
effects that can so easily be measured 6 months later. If this observation can be
reproduced, it could substantially change the common professional conception from a belief
that tooth whitening is a deleterious treatment that can be tolerated to obtain an end to a
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view that periodontal health is an added benefit of tooth whitening. On a more profound
note, it could completely change our approach to maintaining healthy gums.
A survey of the literature indicates that therapeutic effects of peroxide are primarily
associated with peroxide-containing dentifrice preparations and mouth rinses (Marshall et al.
1995). In this connection, a modest decrease in signs of inflammation is usually reported.
Effects of periodontal health associated with tooth whitening procedures are much less
common. This is to be expected since trays used for take-home procedures are generally
contoured so that they do not touch the gingiva. Similarly, the BriteSmile system strives to
minimize gingival exposure through the use of Opaldam, a brush-on isolation material.
Despite these measures, however, it is almost certain that small amount of peroxide find
their way to the gingiva and could have measureable beneficial effects.
Following a literature survey, only one study has reported a statistically significant
improvement in measures of gingival health following a tooth whitening procedure. In this
study (Scherer et al. 1992), the gingival effects of Rembrandt Lighten Bleaching Gel
compared to a placebo control was reported following 4 weeks use of the take-home
peroxide preparation. These data were reported as % of sites inflamed (GI>1). Comparison
of their results with the Britesmile study using the same analytic method are illustrated in the
following figure.
25.00%
80.00%
70.00%
60.00%
50.00%
40.00%
30.00%
20.00%
10.00%
0.00%
20.00%
Britesmile
Peroxide
Light
15.00%
Rembrant
10.00%
Control
5.00%
0.00%
Baseline
12w
Baseline
24w
4w
6w
Figure 3 Reduction in gingivitis by tooth whitening procedures ) from two studies measured as percent of
gingival sites inflamed (GI>1). (Data of Britesmile 2001 and Scherer et al. 1992.)
In the archives of gingival and periodontal therapy there appear to be no examples of
treatments applied intensively for one hour as is done in the Britesmiles treatment. We
simply don’t know the magnitude of effectiveness this type of therapy might have. Certainly,
the ability to produce a sustained effect for 6 months following a single treatment is a
response seldom seen in periodontal therapy.
In the design of a study to more fully investigate the effects of tooth whitening
treatments on periodontal health, we have critically evaluated the shortcomings of the last
study from the standpoint of how it can be improved for the purpose of evaluating
periodontal effects. First, subjects were not selected to have gingival disease so that effects
were small. A second deficiency was that it seems likely that the application of either
peroxide or light or peroxide and light may reduce gingivitis. Hence, one deficiency of the
study as conducted for evaluation of gingival effects is that there was no non-treatment
control group.
6
Section
3
Material and Methods
Experimental design
Subject Selection
Dark starting tooth shades were not a requirement for this study, however, in order
that tooth whitening be recommended, a minimum of C1(Vita) on the maxillary incisors was
be required.
Subjects were selected that had gingivitis or even mild periodontitis in the anterior
maxillary sextant. Seven sites were be tested for bleeding following the protocol defined by
the Eastman Interdental Bleeding Index (EIBI, Caton et al. 1988).
Right
Left
Lateral
Bicuspid
1
2
3
Lateral
Centrals
4
5
Bicuspid
6
Cuspid
7
Cuspid
Figure 4 sites to be evaluated for gingival bleeding by the Eastman Interdental Bleeding index.
Sites tested will be the interproximal papillae of all maxillary anterior teeth to the cuspid-first
bicuspid interproximal. By this method, a wooden interdental cleaner (Stim-U-Dent,
Johnson & Johnson, New Brunswick, NJ) will be inserted between the teeth from the facial
aspect, depressing the interdental tissues 1 to 2 mm. The path of insertion will be parallel to
the occlusal plane with care being taken not to direct the point of the cleaner apically. The
cleaner will be inserted and removed four times, and the presence or absence of bleeding
within 15 seconds will be recorded. Subjects will be selected based on their having at least
3 of the 7 sites tested that bleed.
Subjects who were enrolled into this study received $200 compensation for their
participation. Subjects in treatment groups other than Peroxide + Light were offered a
complimentary tooth whitening at the end of the study. Because of the extensive
measurements involved, most appointments required approximately 2 hours. The baseline
appointment took approximately 3 hours due to the 1-hour treatment time. Subjects
received toothbrushes and toothpaste (Crest) to standardize home care.
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Experimental groups
The study was a parallel design clinical trial of one hundred subjects randomly assigned to
one of four experimental groups (approximately25 subjects/experimental group). The
experimental groups were:
1. The test group (Peroxide + light, the full BriteSmile therapy; BriteSmile light plus the
15% hydrogen peroxide gel).
2. The peroxide control group. (BriteSmile 15% hydrogen peroxide gel with a placebo
light application)
3. The light control group (BriteSmile light alone with a placebo gel).
4. The control group (placebo light and placebo gel).
Experimental design
Peroxide
+
Light
+
P+L+ P+L-
-
P-L+ P-L-
Figure 5 Experimental design illustrating the fully factorial nature of the experiment.
This design provided for full factorial analysis to determine additive effects of light and
peroxide. By this design, subjects were evaluated for the BriteSmile treatment (P+L+), total
placebo treatment (P-L-) as well as the peroxide alone control (P+L-) and the light alone
control (P-L+). The placebo gel was provided by the manufacturer and had the same
composition as the peroxide gel but without peroxide. The placebo light treatment was
accomplished by turning on the BriteSmile light fan (but not the light) and setting an audible
timer after the orange total light block goggles were in place. A placebo light was included
since clear evidence of subject bias for treatment superiority in the P-L+ group was
observed in the first study. It was recognized that this effect could affect the diligence of
home care application. Factorial analysis proceeds by considering peroxide or light
independently in a General Linear Models analysis.
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C = clinical measurements
M = microbial samples
G = gingival crevice fluid samples
Treatment
M
C
G
M
M
C
G
Baseline
1-week
M
C
G
M
C
G
1-month
6-months
Clinical Measurements:
Tooth Shade
Gingival Index
Plaque Index
Tooth color
Gingival papilla color
(Plaque sample)
GCF volume
(GCF sample)
Pocket Depth
Attachment Level
Bleeding on probing
Pocket H 2S
Figure 6. Time points at which response evaluations occurred
Clinical measurements, gingival crevice fluid samples (GCF) and microbiological samples
were taken at four visits; at baseline, 1 week following treatment, 3-months following
treatment and 6-months following treatment. In addition, one set of microbiological samples
was taken immediately following treatment. Measurements and samples were taken in the
order listed.
The specific measurements used for this study apply to three desired outcome
measurements, reproduction of the original observation, evaluation of microbiological
changes and evaluation of tissue responses.
Reproduction of the original observation: Tooth shade, tooth color (colorimeter), gingival
index and plaque index reproduce the principal elements of the earlier study.
Microbiological changes: Many bacteria live in the oral cavity. Some investigators have
suggested that as many as 600 species may be identified. Measurement of the standard
battery of 40 periodontal bacteria provided a representative analysis of bacterial changes
that could occur. For an effect to last for 6 months following a single treatment, it is
assumed that a measurable change in the microbial composition will have occurred. The
panel of organisms used in this analysis include periodontal pathogens (P. gingivalis, T.
forsythensis (formarily B. forsythus), T. denticola, and A. actinomycetemcomitans), bacteria
thought to be pre-pathogenic (e.g. P. nigrescens, F. periodonticum and other
Fusobacterium, C. rectus, Eubacterium sp., P. micros, E. corrodens and Selenomonas
noxia), bacteria thought to be beneficial (e.g. A. naeslundii and other Actinomycetes, S.
sanguis and other Streptococci) and bacteria principally associated with gingivitis (e.g. V.
parvula). From an analysis of changes occurring in these representative species will provide
insight into any microbial changes that may occur.
Changes in tissue response: It is possible that changes associated with BriteSmile therapy
could be seen most clearly directly by measurement of tissue changes. Many changes in
tissue response can be evaluated by clinical diagnostics. These measures are those most
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commonly understood by clinicians. The most common clinically related diagnostic
measurement is periodontal probing (pocket depth, attachment level and bleeding on
probing). In this case, we used a special probe with a computer interface be used (The
Florida Probe). This instrument measured changes as small as 0.2 mm and at the same
time, controlled the force of probing. We do not expect probing changes to be large since
the subjects chosen for this study do not periodontitis, only some level of gingivitis.
Nevertheless, with sufficient resolution, changes could be detected should they occur.
Gingival papilla color was included since the Minolta colorimeter is available from previous
studies. A second level of responses focuses on the inflammatory fluid that appears in the
gingival sulcus, the gingival crevice fluid (GCF). The actual volume was measured nondestructively using a chair-side instrument (Periotron) and is a measure of the degree of
inflammation present in the tissues. More importantly, the fluid contains mediators of
periodontal descruction some of which were measured. One of the most important
mediators is interleukin-1-beta (IL1β). This cytokine is produced by the inflammatory cells of
the body and is one of the most powerful stimulators of bone resorption known. This
substance was measured by laboratory methods. Finally, there is the recently available
methodology to measure hydrogen sulfide (H2S) in the periodontal pocket or sulcus. H2S is
the most important odor component of halitosis. To associate reduction of halitosis with
BriteSmile therapy would be of obvious benefit.
Clinical measurements
Tooth Shade: As in previous studies, the tooth shade of the four maxillary incisors will be
recorded based on the Vita shade guide.
Gingival Index and Plaque Index: In order to test the reproducibility of the initial study,
the primary outcome variable of this study will be gingival index change measured at 6
months. Also, the size will be set to equal that of the initial study (25/group; 100 for the
entire study)
Indices will be recorded on all maxillary and mandibular teeth from the first molar
forward at each evaluation period. These indices will be recorded in the GI/PI
Evaluation Form (Appendix). The criteria for these indices is as follows:
Gingival Index of Loe and Silness (1963).
0 = Normal gingiva.
Plaque Index of Silness and Loe (1964).
0 = No plaque.
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Tooth and Gingival Papilla Color: Tooth color was measured at 9 points on each
maxillary incisor tooth surface (4 teeth) as in the current studies using the Minolta
Chromameter. Papilla color was recorded as one chromameter measurement on each
papilla from the buccal interproximal between the maxillary cuspid and first bicuspid on
the right to the same papilla on the left (7 maxillary buccal interproximal papillae).
Figure 7 Tooth color measurement sites (9 sites on 4 teeth, all maxillary):
Right
Lateral Central
Incisor
Incisor
8
9
6
3
7
5
2
9
8
Central
Incisor
7
7
8
Left
Lateral
Incisor
9
7
8
9
6
4 6
5
4
4
5
6
4
5
1
2
1 1
2
3 1
2
3
3
Figure 8 Papilla measurement sites(7 interperoximal papillae, all maxillary):
Right
Left
Lateral
Bicuspid
1
2
Lateral
Centrals
3
4
5
Cuspid
Bicuspid
6
7
Cuspid
Plaque Sample: All visible plaque will be harvested from the surfaces adjacent to the
buccal gingival margin of eight teeth; maxillary incisors, cuspids and first bicuspids.
Figure 9 Plaque sampling sites(8 tooth surfaces, all maxillary):
Samples from each tooth were taken using sterile Gracey curettes. Each plaque sample
was placed into a labeled individual 1.7 ml snap-top centrifuge tube (VWR Cat. 20170-33)
containing 0.15 ml. Tris EDTA buffer. Following the collection of all samples, 0.1 ml of 0.5N
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NaOH was added to each vial and mixed by vortex with the sample and buffer. This sample
is stable at room temperature for up to 3 months and is safe to transport.
GCF volume: The gingival fluid volume will be measured on mesio-buccal of each
papilla from the buccal interproximal between the maxillary cuspid and first bicuspid on
the right to the same papilla on the left (8 maxillary buccal interproximal surfaces).
Figure 10 Gingival fluid sampling sites(8 interproximal surfaces, all maxillary):
Right
Left
Lateral
Lateral
Centrals
Bicuspid
Bicuspid
Cuspid
Cuspid
1
4
3
2
7
6
8
5
Measurements were taken from the mesio-buccal of each test tooth. The sample was
obtained by placing a calibrated Periotron filter paper strip gently into the orifice of the
sulcus and allowing to remain for 30 seconds. The sample was removed and the
volume of aspirated fluid measured using a calibrated Peritron instrument. After
measuring and recording the volume, all the filter paper strips were placed into one
Eppindorf vial for cold storage until assayed for IL1-β.
Probe measurements (Pocket Depth, Attachment Level and Bleeding on probing): The
depth of the periodontal sulcus or pocket will be measured at three sites across the
buccal surface on each of the 8 test teeth using the Florida periodontal probe.
Right
Left
Lateral
Bicuspid
Lateral
Centrals
Cuspid
Bicuspid
Cuspid
Controlled force of probing was set to light pressure(approximately 15 gram). Any site
bleeding as a result of this controlled-force probe measurement within 15 seconds of
probing was recorded as a bleeding site. Pocket depth, was measured using the
Florida disk probe and taken to an accuracy of 0.2 mm.
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Pocket H2S: Occurrence of hydrogen sulfide in the pocket was determined using the
Dimond Probe 2000 (Diamond General development Corp.) Measurements were taken
on the mesio-buccal of each tooth at the same sites GCF samples are taken (8
maxillary interproximal surfaces).
EDBI: The EDBI as described in the screening section will be repeated at the end of
each visit to determine if any changes in this bleeding index occurs.
Laboratory measurements
Mediator
The GCF levels of IL-1β were measured by specific ELISA determination of the eluate from
filter paper strips used to collect GCF.
Microbiological
The microbial composition was determined by DNA:DNA hybridization. These methods
require only that bacteria be scraped from the tooth surface, placed into a vial and taken to
the laboratory. From that sample, 40 representative bacteria were identified and quantified
by established methods. Changes in the levels or proportions of these bacteria can be clear
indicators of ecologic change.
This report documents observations that were made over the entire 6-month treatment
period.
Sample processing: Samples will be analyzed by DNA-DNA hybridization (Socransky et al.
1994). Prior to analysis, samples will be sonicated in a water bath sonicator for 1 min.
followed by boiling for 5 minutes. The samples will be neutralized using 0.8 ml 5 M
ammonium acetate. The released DNA will be placed into the extended slots of a Minislot
(Immunetics, Cambridge MA) and then concentrated onto a nylon membrane (Boehringer
Manheim) by vacuum and fixed to the membrane by exposure to ultraviolet light.
Up to 28 samples of denatured DNA and two standards of each probe species (105 and 106
bacterial equivalents/sample) are applied to each nylon membrane using a Minislot
apparatus. The membrane is then rotated 90° and placed into a Miniblotter 45 (Immunetics,
Cambridge MA). The following 40 digoxigen-labeled DNA probes are hybridized in
individual channels of the Miniblotter.
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Table 1. List of 40 bacteria evaluated in each sample.
Actinomyces naeslundii 1
Streptococcus constellatus
Streptococcus
anginosus
Streptococcus sanguis
Actinomyces
gerencseriae
Streptococcus oralis
Eubacterium nodatum
Porphyromonas gingivalis
Actinobacillus
actinomycetemcomitans
Capnocytophaga
(serotypes a & b)
ochracea
Fusobacterium nucleatum ss
vincentii
Actinomyces israelii
Streptococcus
Campylobacter rectus
intermedius
Treponema socranskii
Treponema denticola
Eubacterium saburreum
Prevotella nigrescens
Actinomyces
odontolyticus (serotype
Peptostreptococcus micros
I)
Fusobacterium
nucleatum ss
Veillonella parvula
polymorphum
Actinomyces naeslundii 2 (A.
viscosus)
Campylobacter showae
Fusobacterium
Campylobacter gracilis
periodonticum
Neisseria mucosa
Fusobacterium nucleatum
ss nucleatum
Capnocytophaga
gingivalis
Streptococcus gordonii
Tanerella forsynthesis
(formarily Bacteroides
forsythus)
Selenomonas noxia
Propionibacterium acnes
(serotypes I & II)
Prevotella melanogenica
Streptococcus mitis
Eikenella corrodens
Gemella morbillorum
Capnocytophaga
sputigena
Leptotrichia buccalis
After washing, the resulting hybrids were detected using digoxigenin conjugated to alkaline
phosphatase, Attophos substrate and a Storm Fluorimager. The signal intensity of each
unknown is compared with the standards on the same membrane to provide counts of
individual species to determine numbers of bacteria found in the extracted DNA of each
sample. DNA probes and reagents have been adjusted to obtain a detection limit of 104
bacteria and specificity is maintained with increases of > 103 bacteria.
Data Evaluation: Samples from teeth of subjects were compared for each of the 40
bacteria by considering bacterial counts and proportions. Bacterial counts were
determined directly from the samples and expressed as numbers of bacteria x 105.
Bacterial proportions were computed by summing over all bacteria in each sample to
provide a normalization denominator in expressing each bacterium as a percent.
Bacterial counts and proportions were compared between groups using Kruskal-Wallis
non-parametric tests with a p<0.001 accepted as being statistically significant to
compensate for multiple (n=40) comparisons (Socransky et al. 1991). To reduce the
effects of multiple testing, differences in complexes (Socransky et al 1998) were also be
tested.
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Subject Inclusion Criteria
1.
2.
3.
4.
5.
6.
7.
Signed informed consent form.
Good general health as evidenced by the medical history.
Ages 18 to 65 (male or female).
Availability for the 6-month duration of the study.
Have not undergone a professional whitening treatment within 12 months.
Average tooth shade of Vita C2 or darker on maxillary central incisors
At least three of the seven interproximal sites tested for the Eastman Interdental
Bleeding Index were positive
Subject Exclusion Criteria
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Need for prophylactic antibiotic therapy prior to invasive dental procedures
Presence of orthodontic appliances.
A soft or hard tissue tumor of the oral cavity.
Carious lesions requiring immediate treatment.
Restorations on any anterior teeth, which will interfere with color measurement
procedures.
Advanced periodontal disease (characterized by the presence of purulent exudate, tooth
mobility and/or extensive alveolar bone loss).
Is participating in another clinical study or panel test.
Extremely sensitive to sunlight or taking medication that creates sunlight sensitivity
Congenital tooth stains or dental defects or prominent tetracycline staining or fluorosis on
the 4 maxillary incisors
Mouth breathers
People on niphedipine, dilantin or calcium channel blockers.
Test protocol
Calibration of the BriteSmile Gas-Plasma Light.
The light intensity was calibrated using standard light meter (Model LM-10 power meter
head attached to Model FM meter, Coherent, Auburn, CA). The light intensity was set to a
level of 130-160 mV/cm2 and checked at least once daily.
Gingival and Plaque Evaluation
Gingival and plaque indices are recorded on all maxillary and mandibular teeth from the first
molar forward at each evaluation period: pre-treatment, post-treatment (gingival index only),
1-week recall, 1-month recall and 6 month recall. These indices are recorded in the GI/PI
Evaluation Form (Appendix V). The criteria for these indices is as follows:
15
Gingival Index of Loe and Silness.
0 = Normal gingiva.
Plaque Index of Silness and Loe.
0 = No plaque.
Colorimetric Analysis
An objective method for the evaluation of changes in tooth color has been through the use of
reflectance spectroscopy. Currently, manufacturers use reflectance spectrophotometers
(colorimeters) for quality control of color matching in ceramics, paint and plastics.
The Commission Internationale d’Eclairage (CIE) has developed the LAB color mode
as an international color standard to overcome device dependency of the RGB and CMYK
modes and to linearize the color space coordinates produced by the tristimulus coordinate
system. In a digital LAB color image, each color was uniquely specified by the three
coordinate values of L*, a* and b*. The Lightness coordinate (L) went from 0 (black) to 100
(white). The a* coordinate went from +80 (red) to -80 (green). The b* coordinate went from
+80 (yellow ) to –80 (blue) (Berger-Schunn 1994). This relationship was illustrated in the
following figure.
White
L*
Green
-
+ Yellow
b*
a*
-
L* = whiteness
a* = Red/Green
b* = Yellow/Blue
C* = Chromaticity
h = Hue
C*
h
+
Red
Blue
Black
Figure 11. CIELAB color space.
16
The Minolta Chromameter has been used in several studies to evaluate tooth color change
resulting from whitening procedures . In this study, it is used both in the evaluation of tooth
color change and gingival color change. In practice, the L* component (Lightness) and the
b* component, (yellow) has appeared to be most relevant to changes in tooth color. This
technique has provided an objective method to evaluate tooth color change. When coupled
with subjective shade guide changes, results have been described both in objective and
more clinically understood subjective form. To our knowledge, this equipment has never
been used to evaluate gingival color changes.
Risk mitigation
Past experience and institutional board review have agreed that risks to the subjects were
minimal in these procedures.
There have been reports of occasional transient
hypersensitivity after the use of tooth whitening products with hydrogen peroxide. The
sensitivity can occur in any of the teeth and typically lasts for a few days. All subjects were
questioned post-treatment about sensitivity during and after treatment, and at recall visits.
Extreme sensitivity experienced during the procedure was considered as basis for
termination of the whitening procedure for that subject. In no case had this occurred.
Palliative treatment in the form of fluoride gel application and desensitizing toothpaste were
available to treat prolonged tooth sensitivity. In no case was this required.
Statistical Analysis
Analytical method: Overall tests for main effects were done by F test followed by between
groups comparisons using least square means adjusted for the baseline covariate. By this
analysis, the dependant variables related to inflammation included the gingival index, the
EDBI, and the average gingival color ( L*, a*, b* ) of each subject in a treatment group at the
time point being evaluated. The covariate was the average pre-treatment value of each
subject. Post-hoc evaluation was by Fisher's Least-Significant-Difference Test. Differences
at pre-treatment in each parameter were evaluated by analysis of variance (ANOVA).
Significance differences from pre-treatment were tested by a one-sample t-test of
differences against an assumed mean value of 0. Analysis of questionnaire data was by
chi-square analysis.
17
For each individual, values from the four maxillary incisors were evaluated for shade.
Ordinal changes in shade guide values were calculated using the conversion defined in the
following table.
Shade Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Designation
B1
A1
B2
D2
A2
C1
C2
D4
A3
D3
B3
A3.5
B4
C3
A4
C4
Table 2. The numerical equivalent of the Vita shade guide evaluations uses the manufacturers
recommendations for ordering sequence. By this scale, B1 (lightest) = 1 and C4 (darkest)=16. Hence, larger
shade guide values are darker.
Gingiva and tooth color were measured using a Minolta CR 123 chromameter Measured L*,
a* and b* values from chromameter measurements were recorded electronically.
The color change (∆E) was computed from the recorded values as:
(∆L*)2 + (∆a*)2 + (∆b*)2 . These values were computed from changes in the chromameter
measurements (post-treatment value – pre-treatment value). Each of these parameters was
averaged across the four teeth in each subject and each subject average was used to
evaluate change by analysis of covariance (ANCOVA). Overall tests for main effects were
done by F test followed by between groups comparisons using least square means adjusted
for the baseline covariate. By this analysis, the dependant variable was the average shade,
L*, a*, b* or ∆E value of each subject in a treatment group at the time point being evaluated.
The covariate was the average pre-treatment value of each subject. Post-hoc evaluation
was by Fisher's Least-Significant-Difference Test. Differences at pre-treatment in each
parameter were evaluated by analysis of variance (ANOVA). Significance differences from
pre-treatment were tested by a one-sample t-test of differences against an assumed mean
value of 0. Analysis of questionnaire data was by chi-square and Fisher’s exact test.
18
Section
4
Results
Subject population
Ninety-eight subjects completed the study with 10 dropouts. The average age of the
population was 37 years (range 19-65 years). The population was 56% female (55) and
45% male (43). The ethnic composition of the group was predominately Caucasian (82%)
with 8% black 5% Hispanic and 4% Asian.. No significant differences between experimental
groups in any demographic variables were found.
Table 3. Age (years) of subjects participating in the study
Group
BriteSmile
Peroxide Control
Light Control
Placebo
Average
Mean
37
32
40
39
37
Standard Deviation
10.53
10.71
12.35
12.08
11.66
Table 4. Gender of subjects participating in the study
Group
Female
Male
Peroxide + light
16
9
Peroxide Control
15
10
Light Control
12
14
Placebo
12
10
Total
55
43
Table 5. Race of subjects participating in the study
Race
Frequency
Percent
Asian
4
4.08
Black
8
8.16
Hispanic
5
5.10
Unknown
1
1.02
White
80
81.63
19
Minimum
19
20
20
19
19
Maximum
57
60
65
58
65
Subject withdrawals
Ten subjects were enrolled and subsequently withdrew. The reasons given for withdrawal
from the study are listed in the following table.
Table 6. Reasons given for subject withdrawal.
Subject
Comments
Treatment
621 Subject withdrew after baseline; was unwilling to submit to repeated probings. Light + Peroxide
609 Subject could not be contacted for 6M visit
Light + Peroxide
681 Subject did not arrive for baseline visit and was withdrawn
Light
662 Subject withdrew at baseline
Peroxide
708 Subject withdrew prior to baseline
Peroxide
697 Subject did not arrive for baseline visit and was withdrawn
Placebo
678 Subject ineligible at baseline visit.
Placebo
665 Subject ineligible prior to baseline
Placebo
643 Subject withdrew at baseline
Placebo
616 Subject found Florida probe "excruciatingly painful" and withdrew after baseline.
Placebo
The last subject was seen on August 21, 2003.
Tooth Shade
Although the primary intent of this study is the investigation of gingival health associated with
tooth whitening, the whitening effect on teeth is included to demonstrate that a whitening
effect was achieved in the study and to provide a basis for comparing analytical power of
subsequent measures.
Initial Tooth Shade
Table 7 Initial Tooth shade
Treatment
Light + Peroxide
Light
Peroxide
Placebo
N
25
26
25
22
Mean
6.59
7.12
5.59
6.47
SEM
0.55
0.57
0.37
0.44
StDev
2.73
2.92
1.83
2.06
The average initial tooth shade of this subject group was 6.4. (between Vita C1 and C2).
The distribution of tooth shade values is illustrated in the following figure.
20
Table 8 Distribution of initial tooth shade values.
45.0%
40.0%
35.0%
30.0%
25.0%
20.0%
15.0%
10.0%
5.0%
0.0%
1
2
3
4
5
6
Table 9 ANOVA of initial shade values
Sum-ofSource
df
Squares
TREAT
30.50
3
Error
560.91
94
7
8
9
10 11 12 13 14 15 16
Mean-Square
F-ratio
P
10.17
5.97
1.70
0.17
Evaluation of initial tooth shade values by ANOVA indicates that baseline values of the four treatment
groups are not significantly different (P > 0.05).
Tooth Shade at each visit
Tooth shade was decreased by all treatments but not by the control treatment.
Table 10. Tooth shade values for each of the 5 evaluation times ( mean ± standard error of the mean).
Treatment
Light + Peroxide
Light
Peroxide
Placebo
N
25
25
22
26
Baseline Post-Treatment 1 Week
1 Month
6.59 ± 0.55
1.7 ± 0.22
2.39 ± 0.3 2.8 ± 0.38
7.12 ± 0.57
4.65 ± 0.45
5.31 ± 0.53 5.78 ± 0.52
5.59 ± 0.37
3.38 ± 0.43
3.88 ± 0.42 4.22 ± 0.42
6.47 ± 0.44
6.28 ± 0.42
6.7 ± 0.48 6.53 ± 0.47
21
6 Months
3.04 ± 0.34
6.82 ± 0.67
4.81 ± 0.41
7.01 ± 0.62
Figure 12 Tooth shade before and after treatment by Light + Peroxide, Light alone, Peroxide alone or placebo.
Whiskers indicate standard error of the mean. Shade reduction following treatment by light + peroxide was
significantly greater than any other group at all visits.
Evaluation of tooth shade by analysis of covariance (ANCOVA) using the baseline value as
the covariate revealed that the peroxide + light treatment produced a greater reduction in
shade than seen following any of the other treatments. Both light and peroxide reduced
tooth shade values greater than the placebo. In general, peroxide alone produced greater
reduction in shade than light alone. This difference, however, never achieved statistical
significance.
22
Table 11. Evaluation of tooth shade values by ANCOVA for each of the 5 evaluation times. Values listed are
the probability of the difference being observed by chance for each treatment pair at each visit.
Peroxide +
Light
Light
Peroxide
Baseline vs. Post-Treatment
Light
< 0.001
Peroxide < 0.001
0.27
Placebo < 0.001
< 0.001
Peroxide +
Light
Light
< 0.001
Peroxide
Baseline vs. 1 Week
Light
< 0.001
Peroxide < 0.001
0.29
Placebo < 0.001
< 0.001
Peroxide +
Light
Light
< 0.001
Peroxide
Baseline vs. 1 Month
Light
< 0.001
Peroxide < 0.001
0.20
Placebo < 0.001
0.02
Peroxide +
Light
Light
< 0.001
Peroxide
Light
< 0.001
Peroxide < 0.001
Placebo < 0.001
23
0.10
0.25
0.007
Change in Tooth Shade
The change in tooth shade from baseline clearly illustrates the comparative levels of
effectiveness of each of the four treatments.
Figure 13 Change in tooth shade from baseline following treatment by each of the four treatment groups.
24
Tooth Color L*
The colorimeter is a reflectance spectrophotometer which provides L*, a* and b* values
when applied to teeth. The tooth lightness value (L*) is one of the colorimeter parameters
that changes with tooth whitening effect of peroxide and/or light. This parameter is given a
value of 100 for pure white and 0 for black.
Initial Tooth Color L*
Table 12 Initial Tooth lightness (L*) values
Treatment
N
Light + Peroxide
Light
Peroxide
Placebo
25
26
25
22
L*
SEM
0.77
0.80
0.53
0.49
Mean
55.75
54.70
57.01
54.87
StDev
3.85
4.10
2.65
2.31
The average initial lightness of all teeth in the study was 55.6.
Table 13. ANOVA of initial Tooth lightness (L*) values.
Source
TREAT
Error
Sum-ofSquares
83.07
1055.80
df
3
94
MeanSquare
27.69
11.23
F-ratio
2.47
P
0.07
In this case, the initial L* values were close to being significantly different. The following
comparison of ANOVA values for each treatment comparison indicates that the initial
lightness of the teeth treated with peroxide alone is somewhat greater than other groups
(see red bar at baseline in the following figure). This difference, however, was not
statistically significant.
Table14. ANOVA of initial shade values
Light + Peroxide
Light
Peroxide
Placebo
0.27
0.19
0.37
Light
Peroxide
0.02
0.86
0.03
Tooth Color L* at each visit
Table 15. L* tooth color values for each of the 5 evaluation times ( mean ± standard error of the mean).
Treatment
N
Baseline Post Treatment
1 Week
1 Month
6 Months
56.78 ± 0.78 56.69 ± 0.75 55.61 ± 0.76
Light + Peroxide 25 55.75 ± 0.77 57.66 ± 0.73
25 54.70 ± 0.80 54.94 ± 0.75
55.35 ± 0.83 54.76 ± 0.79 53.73 ± 0.90
Light
22
57.01
±
0.53
58.08
±
0.45
57.83
± 0.46 57.51 ± 0.53 56.85 ± 0.52
Peroxide
26 54.87 ± 0.49 54.23 ± 0.50
55.32 ± 0.53 54.62 ± 0.58 53.85 ± 0.67
Placebo
25
Figure 14 L* tooth color before and after treatment by Light + Peroxide, Light alone, Peroxide alone or placebo.
Whiskers indicate standard error of the mean. Increasing lightness following treatment by light + peroxide was
significantly greater than placebo or light at all visits immediately post-treatment and at 1 Month. The effect of
peroxide treatment on increasing lightness was at no time significantly different from that of peroxide + light.
Evaluation of L* tooth color by analysis of covariance (ANCOVA) using the baseline value
as the covariate revealed that the peroxide + light treatment produced a greater increase in
lightness than either light or peroxide alone. Treatment by light alone was statistically
different from placebo only at the immediate post-treatment period. At all other evaluation
points, light was indistinguishable from placebo in its effect on increasing lightness.
Treatment by peroxide alone was never significantly different than treatment by peroxide +
light in its effect on increasing lightness. None of the statistically significant effects persisted
to 6 months.
26
Table 16. Evaluation of L* tooth color values by ANCOVA for each of the 5 evaluation times. Values listed are
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
<0.001
0.05
<0.001
Peroxide +
Light
0.25
0.82
0.13
Peroxide +
Light
0.03
0.54
0.009
Peroxide +
Light
0.08
0.93
0.08
Light
0.001
0.02
Light
0.37
0.66
Light
0.13
0.54
Light
0.07
0.94
Peroxide
<0.001
Peroxide
0.20
Peroxide
0.04
Peroxide
0.07
Change in Tooth Color L*
Figure 15 Change in tooth lightness (L*) from baseline following treatment by each of the four treatment groups.
27
Factorial Analysis of change in L* by Peroxide and Light
The observation that the effect of Peroxide on increased lightness persists through 6 months
while the effect of Light does not can be investigated using the factorial design of the study.
By this analysis, the effects of peroxide and light alone can be combined with the effects of
peroxide + light effectively doubling the number of subjects for each test and allowing us to
separate the effects of light and peroxide on tooth whitening. The following table represents
the adjusted least squares mean computed at each visit for those subjects treated with
peroxide (either peroxide alone or peroxide + light) and those subjects treated with light
(either light alone or peroxide + light). These values represent a least squares estimate of
the effect of each of these single therapies at each visit. It is assumed in this analysis that
light and peroxide work independently. This independence was investigated by introducing
the Light*Peroxide interaction into the analysis. This effect is not significant at any of the
visits suggesting that peroxide and light work independently in their ability to effect tooth
lightness.
Table 17. Evaluation of L* tooth color values by factorial analysis. Values listed are the least squares means of
the effect of no treatment (0) or treatment (1) on L* by the factors Light or Peroxide at each visit.
Adjusted LS
Treatment
mean
Post-treatment
LIGHT
0 55.86125
LIGHT
1 56.62262
PEROXIDE
0 55.29583
PEROXIDE
1 57.18804
1-Week
LIGHT
0 56.26359
LIGHT
1 56.40099
PEROXIDE
0 56.07549
PEROXIDE
1 56.58909
1-Month
LIGHT
0 55.76519
LIGHT
1 56.05258
PEROXIDE
0 55.40683
PEROXIDE
1 56.41094
6-Months
LIGHT
0 55.02678
LIGHT
1 55.02316
PEROXIDE
0 54.55798
PEROXIDE
1 55.49196
SE
N
0.17406
0.16699
0.17424
0.17052
47
51
48
50
0.21029
0.20176
0.21051
0.20602
47
51
48
50
0.23844
0.22877
0.23869
0.23359
47
51
48
50
0.25947
0.24894
0.25974
0.2542
47
51
48
50
28
Computing differences between presence and absence of peroxide or light given by the
adjusted LS means in the table above, the following figure was derived.
Figure 16. Difference in adjusted least squares means in effect of light and peroxide on the increase in L*.
Recorded L* data was evaluated by a General Linear Models fitting of factorial data. The
model used in this case included the initial value of b* as a covariate with Peroxide and Light
as factors. Since the interaction factor Peroxide*Light was not significant in data from any of
the visits, it was omitted in the following tabulation. The r-square values indicating goodness
of fit of this model were:
Visit
Pre Treatment
1 Week
1 Month
6 Months
R-squared
0.88875
0.83590
0.79543
0.78914
29
Table 18. Evaluation of L* tooth color values by factorial analysis. Values listed are the General Linear Models
parameters describing the effect of no treatment or treatment on L* by the factors Light or Peroxide at each visit.
P-values represent the probability of the factor effect being observed by chance at each visit.
Meandf
F-ratio
P
Square
Post-Treatment
LIGHT
13.98374
1
13.98374
9.89735
0.002
PEROXIDE
82.82886
1
82.82886
58.62423
<0.001
LV0
800.0589
1
800.0589
566.26198
<0.001
Error
132.8105
94
1.41288
1 Week
LIGHT
0.45546
1
0.45546
0.22083
0.64
PEROXIDE
6.10248
1
6.10248
2.95882
0.08
LV0
885.46743
1
885.46743 429.32379
<0.001
Error
193.87218
94
2.06247
1 month
LIGHT
1.99228
1
1.99228
0.75138
0.39
PEROXIDE
23.32424
1
23.32424
8.79661
0.004
LV0
824.69918
1
824.69918 311.03067
<0.001
Error
249.24142
94
2.6515
6 months
LIGHT
0.00031
1
0.00031
0.0001
0.99
PEROXIDE
20.17977
1
20.17977
6.42685
0.01
LV0
946.2987
1
946.2987
301.37718
<0.001
Error
295.152
94
3.13991
This analysis indicates that significant increase in tooth lightness by peroxide treatment was
seen through 6 months. In contrast, the effect of light treatment on the increase in tooth
lightness was seen only at the post-therapy visit. The initial lightness level (LV0) was a
significant effect in the lightness increase at all visits.
Source
Sum-ofSquares
Tooth Color a*
Initial Tooth Color a*
Table 19. Initial Tooth a* values
N
Light + Peroxide
Light
Peroxide
Placebo
25
26
25
22
Mean
-1.15
-1.10
-1.34
-1.17
a*
SEM
0.08
0.10
0.07
0.18
30
StDev
0.41
0.53
0.35
0.85
Table 20. ANOVA of initial Tooth a* values.
Source
TREAT
Error
Sum-ofSquares
0.82
29.02
df
3
94
MeanSquare
0.27
0.31
F-ratio
0.88
P
0.45
There was no significant difference in baseline values between treatment groups
Tooth Color a* at each visit
Treatment
Light +
Peroxide
Light
Peroxide
Placebo
N
25
26
25
22
Baseline
Post
Treatment
1 Week
1 Month
6 Months
-1.15 ± 0.08
-0.83 ± 0.18
-1.17 ± 0.11
-1.13 ± 0.11
-1.11 ± 0.09
-1.17 ± 0.18
-1.1 ± 0.1
-1.34 ± 0.07
-0.93 ± 0.12
-0.81 ± 0.13
-1.4 ± 0.08
-1.09 ± 0.07
-1.22 ± 0.16
-1.38 ± 0.09
-1.01 ± 0.11
-1.05 ± 0.12
-1.4 ± 0.08
-1.02 ± 0.1
-1 ± 0.07
-1.27 ± 0.06
Figure 17. a* tooth color before and after treatment by Light + Peroxide, Light alone, Peroxide alone or placebo.
Whiskers indicate standard error of the mean. The effect of peroxide treatment on decreasing a* values (more
negative = less red) was at times significantly different than placebo but at no time significantly different from that
of peroxide + light
31
Table 21. Evaluation of a* tooth color values by ANCOVA for each of the 5 evaluation times. Values listed are
Light
Peroxide
Placebo
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
Peroxide
Light
0.94
0.006
0.007
0.59
0.63
0.03
Peroxide +
Light
Peroxide
Light
0.59
0.45
0.82
0.58
0.28
0.20
Peroxide +
Light
Peroxide
Light
0.66
0.19
0.08
0.27
0.48
0.02
Peroxide +
Light
Peroxide
Light
0.36
0.33
0.06
0.32
0.91
0.05
Change in Tooth Color a*
Figure 18. Change in a*. Changes less than 0.1 (the approximate standard error) are relatively meaningless.
As seen in other studies, changes in a* appear small and of little significance.
32
Tooth Color b*
Initial Tooth Color b*
Table 22. Initial Tooth b* values.
Treatment
N
Light + Peroxide
Light
Peroxide
Placebo
25
26
25
22
Mean
1.87
1.35
1.18
1.82
b*
SEM
0.46
0.33
0.44
0.27
StDev
2.30
1.70
2.22
1.27
Table 23. ANOVA of initial Tooth b* values.
Source
TREAT
Error
Sum-ofSquares
8.49
351.64
df
3
94
MeanSquare
2.83
3.74
F-ratio
P
0.76
0.52
There was no significant difference in baseline values between treatment groups.
Tooth Color b* at each visit
Table 24. b* tooth color values for each of the 5 evaluation times ( mean ± standard error of the mean).
Post
Treatment
Baseline
1 Week
1 Month
6 Months
Treatment
-1.14 ± 0.3
-0.87 ± 0.36
-0.55 ± 0.35
0.03 ± 0.36
Light + Peroxide 1.87 ± 0.46
1.82
±
0.27
2.53
±
0.3
1.42
±
0.31
1.63
±
0.34
1.94
± 0.32
Light
1.35 ± 0.33
1.15 ± 0.33
0.44 ± 0.3
0.51 ± 0.26
1.29 ± 0.32
Peroxide
1.18 ± 0.44
0.59 ± 0.46
-0.07 ± 0.45
0.23 ± 0.45
0.53 ± 0.44
Placebo
33
Figure 19. b* tooth color value before and after treatment by Light + Peroxide, Light alone, Peroxide alone or
placebo. Whiskers indicate standard error of the mean. Decreasing values of b* are interpreted as decreasing
yellowness. Decreasing b* following treatment by light + peroxide was significantly greater than any other
treatment at any visit. Both the effect of peroxide and light alone treatments significantly decreased yelloowness
relative to placebo.
Decreasing values of b* are considered measures of decreasing yellowness. Evaluation of
b* tooth color by analysis of covariance (ANCOVA) using the baseline value as the covariate
revealed that the peroxide + light treatment produced a greater decrease in yellowness than
either light or peroxide alone. Treatment by light alone significantly decreased yellowness at
all visits except 6 months relative to placebo. Neither treatment by peroxide alone nor
treatment by light alone were significantly different than treatment by peroxide + light in its
effect on decreasing yellowness. Statistically significant reduction in yellowness persisted to
6 months following treatment by peroxide alone and peroxide + light.
34
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
Light
<0.001
<0.001
0.08
<0.001
<0.001
Peroxide +
Light
Light
<0.001
<0.001
0.12
<0.001
0.02
Peroxide +
Light
Light
<0.001
<0.001
0.57546
<0.001
0.00326
Peroxide +
Light
Light
<0.001
<0.001
0.03
<0.001
0.33
Change in Tooth Color b*
Figure 20. Changes in tooth yellowness (b*) following treatment.
35
Peroxide
<0.001
Peroxide
<0.001
Peroxide
<0.001
Peroxide
0.002
Factorial Analysis of change in b* by Peroxide and Light
The observation that the effects of both Peroxide and Light alone treatments decreased
yellowness through 1-6 months suggests investigation using the factorial design of the study
to elicit possible synergism. As previously noted, the effects of peroxide and light alone can
be combined with the effects of peroxide + light effectively doubling the number of subjects
for each test and allowing us to evaluate synergism by looking at the cross product term.
The following table represents the adjusted least squares mean computed at each visit for
those subjects treated with peroxide (either peroxide alone or peroxide + light) and those
subjects treated with light (either light alone or peroxide + light). These values represent a
least squares estimate of the effect of each of these single therapies at each visit. In this
case, it is not assumed that light and peroxide work independently so that the Light*Peroxide
interaction can be evaluated. This effect was significant only at visits up to one week. After
one week, statistically significant synergistic effects could not be seen suggesting that
peroxide and light work independently in their ability to reduce tooth yellowness.
LIGHT
LIGHT
PEROXIDE
PEROXIDE
LIGHT
LIGHT
PEROXIDE
PEROXIDE
LIGHT
LIGHT
PEROXIDE
PEROXIDE
LIGHT
LIGHT
PEROXIDE
PEROXIDE
Adjusted
LS-Mean SE
N
Post-treatment
0
1.59662
0.121
47
1
-0.05257
0.116
51
0
1.80392
0.12
48
1
-0.25988
0.117
50
1-Week
0
0.71239
0.125
47
1
-0.26784
0.12
51
0
0.89997
0.124
48
1
-0.45542
0.121
50
1-month
0
0.96816
0.125
47
1
-0.07503
0.12
51
0
1.03545
0.124
48
1
-0.14232
0.121
50
6-months
0
1.26951
0.146
47
1
0.60978
0.14
51
0
1.58642
0.145
48
1
0.29287
0.141
50
36
1.64919
2.0638
0.98023
1.35539
1.04319
1.17777
0.65973
1.29355
Figure 21. Difference in adjusted least squares means in effect of light and peroxide on the decrease in b*.
Recorded b* data was evaluated by a General Linear Models fitting of factorial data. The
model used in this case included the initial value of b* as a covariate, Peroxide*Light as an
interaction factor with Peroxide and Light as factors. The r-square values indicating
goodness of fit of the model with the data from each visit were:
Visit
Pre Treatment
1 Week
1 Month
6 Months
R-squared
0.86099
0.81601
0.80695
0.74011
37
Table 25. Evaluation of b* tooth color values by factorial analysis. Values listed are the General Linear Models
parameters describing the effect of no treatment or treatment on b* by the factors Light or Peroxide at each visit.
P-values represent the probability of the factor effect being observed by chance at each visit.
Source
BV0
LIGHT
PEROXIDE
PEROXIDE*LIGHT
Error
BV0
LIGHT
PEROXIDE
PEROXIDE*LIGHT
Error
BV0
LIGHT
PEROXIDE
PEROXIDE*LIGHT
Error
BV0
LIGHT
PEROXIDE
PEROXIDE*LIGHT
Error
Sum-of-Squares df Mean-Square
Post-Therapy
230.54822
1
230.54822
66.31483
1
66.31483
103.91201
1
103.91201
9.87238
1
9.87238
63.67509
93
0.68468
1-Week
235.78627
1
235.78627
23.42742
1
23.42742
44.81829
1
44.81829
3.42163
1
3.42163
67.80734
93
0.72911
1-Month
227.04856
1
227.04856
26.53378
1
26.53378
33.84222
1
33.84222
2.04575
1
2.04575
67.89835
93
0.73009
6-Months
213.89124
1
213.89124
10.61221
1
10.61221
40.82242
1
40.82242
3.38529
1
3.38529
92.77871
93
0.99762
F-ratio
P
336.7249
96.85545
151.7676
14.419
< 0.001
< 0.001
< 0.001
< 0.001
323.3886 < 0.001
32.13148 < 0.001
61.46975 < 0.001
4.69287
0.03
310.9872 < 0.001
36.34318 < 0.001
46.3535 < 0.001
2.80206
0.1
214.4014 < 0.001
10.63752 0.002
40.91979 < 0.001
3.39336
0.07
This analysis indicates that significant decrease in tooth yellowness (b*) by all treatments
was seen through 6 months. The interaction effect measured by the Peroxide*Light factor
ceased to be significant after 1-week. The initial yellowness level (BV0) was a significant
effect in the yellowness reduction at all visits.
38
Tooth Color change (∆E)
Total color change is often considered a measure of overall effect. The analysis by this
method reveals that the Light + Peroxide treatment produced, by far, the greatest overall
color change. One of the advantages of this measure is that it is not necessary to interpret a
physical significance on the color change. It says only that the greatest color change
occurred, in this case, following Light + Peroxide treatment.
Table 26. Computed total color change for each treatment at each visit.
Post
Treatment
Treatment
1 Week
1 Month
6 Months
Light + Peroxide
Placebo
Light
Peroxide
3.71 ± 0.33
1.63 ± 0.20
1.47 ± 0.20
1.41 ± 0.22
3.36 ± 0.27
1.39 ± 0.22
1.79 ± 0.20
1.95 ± 0.21
2.93 ± 0.29
1.71 ± 0.29
1.99 ± 0.16
1.54 ± 0.16
2.68 ± 0.22
1.75 ± 0.30
1.92 ± 0.24
1.88 ± 0.23
Figure 22. Tooth color change was computed for each of the treatments. The combined treatment of Light +
peroxide produced a significantly greater color change than any of the other treatments.
The overall color change measured by ∆E is an indication of how much of a change has
occurred by the treatment being tested. By this analysis, neither Light alone or Peroxide
alone produced a significant overall color change. Only the combination of light + peroxide
produced a statically significant change relative to placebo.
39
Table 27 Evaluation of E in tooth color by ANCOVA for each of the 5 evaluation times. Values listed are the
probability of the difference being observed by chance for each treatment pair at each visit.
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
< 0.001
< 0.001
< 0.001
Peroxide +
Light
< 0.001
< 0.001
< 0.001
Peroxide +
Light
0.008
< 0.001
< 0.001
Peroxide +
Light
0.03
0.02
0.01
40
Light
Peroxide
0.86
0.64
0.54
Light
Peroxide
0.61
0.22
0.09
Light
Peroxide
0.19
0.42
0.64
Light
Peroxide
0.90
0.63
0.73
Gingival Index
Since Gingival Index change was the variable first noted to be effected by the BriteSmile
tooth whitening treatment (q.v. Introduction), it is of considerable interest in this study.
Initial Gingival Index
The average initial gingival index of each group is listed in the following table.
Table 28. Initial Gingival Index of subjects participating in the study
N
Mean
Light + Peroxide
25
0.55
Light
26
0.68
Peroxide
25
0.69
Placebo
22
0.86
SEM
0.08
0.11
0.08
0.11
StDev
0.42
0.54
0.42
0.53
Analysis of variance of these data indicates that there are no significant differences between
groups at baseline.
Table 29. ANOVA of baseline Gingival Index values.
Sum-ofSource
df
Squares
Treatment
1.08
3
Error
21.59
94
Mean-Square
F-ratio
P
0.36
0.23
1.56
0.20
Gingival Index at each visit
Analysis of mean values for each group are summarized in the following table.
Table 30. Mean Gingival Index (±SEM) of subjects participating in the study for all visits.
PostTreatment
N
Baseline Treatment
1 Week
1 Month
Light + Peroxide
25
0.55 ± 0.08 0.95 ± 0.08 0.29 ± 0.06 0.4 ± 0.06
Light
25
0.68 ± 0.11 1.02 ± 0.1 0.44 ± 0.05 0.49 ± 0.07
Peroxide
22
0.69 ± 0.08 0.99 ± 0.11 0.53 ± 0.08 0.54 ± 0.1
Placebo
26
0.86 ± 0.11 1.04 ± 0.14 0.57 ± 0.09 0.67 ± 0.12
41
6 Months
0.46 ± 0.06
0.75 ± 0.08
0.73 ± 0.09
0.64 ± 0.11
Figure 23. Gingival index of each group at each visit (mean + SEM). Elevated values immediately post
treatment suggest slight irritation as a result of placement of materials over the gingival during treatment. The
gingival index of all groups decreased following therapy. Of all treatment groups, the Light + Peroxide group
was most effective in reducing Gingival Index.
These data indicate that the combination of Light + Peroxide produced the lowest gingival
index of all other groups at every visit. Statistically significant differences were seen 1 week
following treatment where Light + Peroxide produced less than placebo or peroxide alone.
42
Table 31. ANCOVA p-values at each treatment for each group.
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
0.88
0.578
0.24
Peroxide +
Light
0.18
0.03
0.04
Peroxide +
Light
0.75
0.49
0.27
Peroxide +
Light
0.03
0.06
0.72
43
Light
0.68
0.29
Light
0.35
0.40
Light
0.70
0.41
Light
0.80
0.08
Peroxide
0.51
Peroxide
0.96
Peroxide
0.64
Peroxide
0.13
Gingival Index Change
Figure 24. Average change in Gingival Index from baseline. Positive change represents change in the direction
of increased inflammation. Negative values represent decreases relative to baseline.
These data indicate that Gingival Index increased in all groups immediately post-treatment.
These changes are likely indicative of increased redness resulting from the treatment.
Although differences were not significantly different from each other, Light + Peroxide > Light
> Peroxide > Placebo. One week and one month later all groups had gingival index levels
less than baseline. At 6-months, only Light + Peroxide and Placebo groups were less than
baseline. In this measure the Placebo group had a surprising level of gingival index
reduction which suggests that at least a portion of this change may be the result of improved
oral hygiene.
44
Factorial analysis of Gingival Index Data
The observation that the effect Peroxide + Light and to a lesser extent Light alone
decreased gingival index at 1 week suggests that investigation using the factorial design of
the study could reveal the time dependency characteristic. By this analysis, the effects of
peroxide and light alone can be combined with the effects of peroxide + light effectively
doubling the number of subjects for each test and allowing us to separate the effects of light
and peroxide on tooth whitening. The following table represents the adjusted least squares
mean computed at each visit for those subjects treated with peroxide (either peroxide alone
or peroxide + light) and those subjects treated with light (either light alone or peroxide +
light). These values represent a least squares estimate of the effect of each of these single
therapies at each visit
Adjusted
Least-Squares
Mean
SE
Post-Therapy
Treatment
LIGHT
LIGHT
PEROXIDE
PEROXIDE
0
1
0
1
LIGHT
LIGHT
PEROXIDE
PEROXIDE
0
1
0
1
LIGHT
LIGHT
PEROXIDE
PEROXIDE
0
1
0
1
LIGHT
LIGHT
PEROXIDE
PEROXIDE
0
1
0
1
0.95006
1.04165
0.97256
1.01915
1-Week
0.52346
0.38632
0.48294
0.42685
1-Month
0.56419
0.48254
0.54444
0.50229
6-Months
0.64622
0.64003
0.65983
0.62641
N Difference
0.057
0.0545
0.0564
0.055
47
51 -0.09159
48
50 -0.04659
0.0452
0.0433
0.0448
0.0437
47
51 0.13714
48
50 0.05609
0.0547
0.0523
0.0541
0.0528
47
51 0.08165
48
50 0.04215
0.055
0.0526
0.0544
0.0531
47
51 0.00619
48
50 0.03342
Computing differences between presence and absence of peroxide or light given by the
adjusted LS means in the table above, the following figure was derived.
45
Figure 25. Gingival Index reduction of Light and Peroxide estimated from the least squares adjusted means
derived by factorial analysis.
This analysis suggests that Light is more effective in reducing gingival index than peroxide
but the effect fades such that 6 months later there is little residual effect.
Recorded Gingival Index data was evaluated by a General Linear Models fitting of factorial
data. The model used in this case included the initial value of GI as a covariate,
Peroxide*Light as an interaction with Peroxide and Light as factors. The r-square values
indicating goodness of fit of this model were:
Visit
Pre Treatment
1 Week
1 Month
6 Months
R-squared
0.47679
0.25803
0.31646
0.32049
46
Table 32. Evaluation of Gingival Index by factorial analysis. Values listed are the General Linear Models
parameters describing the effect of no treatment or treatment on Gingival Index by the factors Light or Peroxide
at each visit. P-values represent the probability of the factor effect being observed by chance at each visit.
Source
GIV0
LIGHT
PEROXIDE
PEROXIDE*LIGHT
Error
GIV0
LIGHT
PEROXIDE
PEROXIDE*LIGHT
Error
GIV0
LIGHT
PEROXIDE
PEROXIDE*LIGHT
Error
GIV0
LIGHT
PEROXIDE
PEROXIDE*LIGHT
Error
Sum-of-Squares df Mean-Square
Post-Treatment
12.55995
1
12.55995
0.19915
1
0.19915
0.05173
1
0.05173
0.0212
1
0.0212
13.91802
93
0.14966
1-Week
1.92234
1
1.92234
0.44647
1
0.44647
0.07498
1
0.07498
0.0905
1
0.0905
8.76948
93
0.0943
1-Month
5.04591
1
5.04591
0.15829
1
0.15829
0.04234
1
0.04234
0.00174
1
0.00174
12.80525
93
0.13769
6-months
4.78306
1
4.78306
0.00091
1
0.00091
0.02662
1
0.02662
0.97004
1
0.97004
12.94927
93
0.13924
F-ratio
P
83.92535
1.33071
0.34566
0.14162
< 0.001
0.25164
0.55801
0.70753
20.38636
4.73478
0.79516
0.95977
< 0.001
0.03
0.37484
0.32979
36.64665
1.1496
0.30749
0.01262
< 0.001
0.28641
0.58055
0.91079
34.35135
0.00654
0.19116
6.96669
< 0.001
0.93572
0.66297
0.01
By this analysis, it is clear that the initial gingival index value (GI0) was a significant
determinant at all visits. The major treatment effects was with light. This was statistically
significant only at 1-Week. The interaction between light and peroxide in gingival index
change was never significant until 6-months. One must be skeptical about this interaction
after so much time has passed.
47
Plaque Index
Plaque index is considered a measure of home care. Many studies indicate that gingivitis is
directly related to plaque index.
Initial Plaque Index
Table 33. Initial Plaque Index of subjects participating in the study
N
Mean
SEM
StDev
Light + Peroxide
25
0.39
0.07
0.36
Light
26
0.43
0.08
0.41
Peroxide
25
0.47
0.08
0.41
Placebo
22
0.47
0.10
0.46
Analysis of variance of these data indicate that there are no significant differences between
groups at baseline.
Table 34 ANOVA of baseline Plaque Index values.
Sum-ofSource
df
Squares
TREAT
0.10
3
Error
15.65
94
Mean-Square
F-ratio
P
0.03
0.17
0.21
0.89
Plaque Index at each visit
Table 35. Mean Plaque Index (±SEM) of subjects participating in the study for all visits.
Treatment
N Baseline
1 Week
1 Month
6 Months
Britesmile (Light + Peroxide gel)
25 0.39 ± 0.07 0.18 ± 0.06 0.22 ± 0.05 0.28 ± 0.06
Control (placebo light, placebo gel)
26 0.47 ± 0.1 0.29 ± 0.1 0.28 ± 0.08 0.29 ± 0.12
Light (+ placebo gel)
25 0.43 ± 0.08 0.25 ± 0.06 0.25 ± 0.06 0.47 ± 0.1
Peroxide (Peroxide Gel+ placebo light)
22 0.47 ± 0.08 0.27 ± 0.05 0.34 ± 0.06 0.25 ± 0.06
48
Figure 26. Plaque index of each group at each visit (mean + SEM). The plaque index of all groups was
significantly reduced at 1 Week compared to Baseline (statistics not shown).
Differences between groups thereafter were slight and generally not statistically significant.
The one significant difference, that of Light treatment at 6-months could be important but
seems likely aberrant. Clearly, all groups greatly improved their homecare following
treatment and this improvement was maintained through 6 months. These observations in
conjunction with those in the Gingival Index section essentially reproduce the original
observation that Gingival Index was decreased by BriteSmiles tooth whitening whereas
plaque index was not affected.
49
Baseline vs. 1 Week
Peroxide +
Light
Light
Light
0.49
Peroxide
0.44
0.93
Placebo
0.37
0.81
Peroxide +
Light
Light
Light
0.827
Peroxide
0.237
0.33
Placebo
0.69
0.85
Peroxide +
Light
Light
Light
0.09
Peroxide
0.54
0.02
Placebo
0.76
0.05
Peroxide
0.88
Peroxide
0.45
Peroxide
0.77
Plaque Index Change
Figure 27.. Average change in Plaque Index from baseline. Negative change represents change in the direction
of decreased visible presence of plaque. Positive values represent increases relative to baseline.
50
Bleeding on Probing
Bleeding on probing (BOP) is and old clinical outcome measure. Considerable research
has been conducted to understand why and how it occurs but there remains considerable
controversy. One interpretation is that it is a measure of capillary fragility. As gingivitis
advances, proteolytic enzymes are released by degranulation of white blood cells. These
enzymes weaken blood vessel walls and make them susceptible to mechanical breakage.
The clinical technique, in this case is to measure with a constant (15 g) probe pressure and
record the incidence of visible bleeding.
Initial Bleeding on Probing
Table 37.. Initial fraction of sites bleeding on probing of subjects participating in the study
N
Mean
SEM
StDev
Light + Peroxide
25
0.21
0.03
0.17
Light
26
0.33
0.04
0.18
Peroxide
25
0.28
0.04
0.18
Placebo
22
0.24
0.04
0.20
groups at baseline.
Table 38. ANOVA of baseline BOP values.
Sum-ofSource
Squares
TREAT
0.18
Error
3.20
df
Mean-Square
F-ratio
P
3
94
0.06
0.03
1.80
0.15
Bleeding on Probing at each visit
Table 39. Mean fraction of sites bleeding (±SEM) for all visits.
Treatment
N
Baseline
1 Week
Light + Peroxide
25
0.21 ± 0.03
0.13 ± 0.02
Light
26
0.24 ± 0.04
0.18 ± 0.04
Peroxide
25
0.33 ± 0.04
0.2 ± 0.03
Placebo
22
0.28 ± 0.04
0.21 ± 0.04
51
1 Month
0.14 ± 0.03
0.22 ± 0.05
0.22 ± 0.04
0.21 ± 0.04
6 Months
0.16 ± 0.03
0.23 ± 0.04
0.25 ± 0.03
0.26 ± 0.04
Figure 28. Average proportion of sites bleeding in each group at each visit (mean + SEM). Although BOP is
reduced in all groups after treatment, there were no significant differences between treatment groups.
Bleeding probing was lowest in subjects treated by Light + peroxide at all visits. When
corrected for baseline levels by ANCOVA (see following table), none of the differences were
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
0.890
0.21
0.26
Peroxide +
Light
0.71
0.44
0.14
Peroxide +
Light
0.48
0.14
0.16
52
Light
0.26
0.32
Light
0.69
0.26
Light
0.44
0.47
Peroxide
0.92
Peroxide
0.46
Peroxide
0.99
Bleeding on Probing Change
Figure 29. Average change in BOP from baseline. Negative change represents a decrease in bleeding relative
to the baseline visit.
This figure suggests that the greatest change in BOP occurred in the light treated sites. The
differences, however, are not statistically significant.
53
EDBI
The Eastman Dental Bleeding Index (EDBI) was developed to provide a rapid measure of
bleeding tendency following a mechanical perturbation of the gingival papilla. It is generally
recognized that the more severe the gingivitis, the higher the EDBI.
Initial EDBI
Table 41.. Initial EDBI of subjects participating in the study
N
Mean
SEM
StDev
Light + Peroxide
25
0.48
0.06
0.32
Light
26
0.57
0.06
0.31
Peroxide
25
0.59
0.06
0.30
Placebo
22
0.51
0.07
0.31
groups at baseline.
Table 42. ANOVA of baseline EDBI values.
Source
Sum-of-Squares
df
TREAT
Error
0.19
8.99
3
94
MeanSquare
0.06
0.10
F-ratio
P
0.68
0.57
EDBI at each visit
Table 43. Mean EDBI (±SEM) of subjects participating in the study for all visits.
Treatment
N
Post-Treatment
1 Week
1 Month
Light + Peroxide
25
0.48 ± 0.06
0.2 ± 0.05
0.27 ± 0.05
Light
26
0.51 ± 0.07
0.31 ± 0.06
0.32 ± 0.06
Peroxide
25
0.57 ± 0.06
0.28 ± 0.05
0.25 ± 0.05
Placebo
22
0.59 ± 0.06
0.35 ± 0.06
0.32 ± 0.05
54
6 Months
0.33 ± 0.06
0.35 ± 0.07
0.36 ± 0.05
0.38 ± 0.05
Figure 30. Average proportion of sites bleeding following EBDI stimulation in each group at each visit (mean +
SEM). Although EBDI is reduced in all groups after treatment, there were no significant differences between
treatment groups.
EDBI was lowest in subjects treated by Light + peroxide at all visits. When corrected for
baseline levels by ANCOVA (see following table), none of the differences were statistically
significant.
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
Light
0.58
0.11
0.28
0.12
0.30
Peroxide +
Light
Light
0.27
0.95
0.29
0.51
0.08
Peroxide +
Light
Light
0.94
0.99
0.95
0.93
0.88
55
Peroxide
0.99
Peroxide
0.47
Peroxide
0.93
EDBI Change
Figure 31. Average change in EDBI from baseline. Negative change represents a decrease in bleeding relative
to the baseline visit.
56
Pocket Depth
Pocket depth is the distance from the base of the sulcus that surrounds the teeth to the tip of
the gingival. In this case, pocket depth was measured with the Florida Probe to an precision
of 0.02 mm. In this subject population, it was not expected that pocket depth changes would
be large since there is essentially no periodontal disease.
Initial Pocket Depth
Table 45. Initial Pocket Depth of subjects participating in the study
N
Mean
SEM
StDev
Light + Peroxide
25
2.03
0.05
0.26
Light
26
2.17
0.08
0.38
Peroxide
25
2.01
0.06
0.28
Placebo
22
2.05
0.07
0.31
groups at baseline.
Table 46. ANOVA of baseline Pocket Depth values.
Sum-ofSource
df
Squares
TREAT
0.39
3
Error
9.11
94
Mean-Square
F-ratio
P
0.13
0.10
1.35
0.26
Pocket Depth at each visit
Table 47. Mean Pocket Depth (millimeters, ±SEM) of subjects participating in the study for all visits.
Treatment
Light + Peroxide
Light
Peroxide
Placebo
N
25
26
25
22
Baseline
2.03 ± 0.05
2.05 ± 0.07
2.17 ± 0.08
2.01 ± 0.06
1 Week
1.97 ± 0.04
2.04 ± 0.06
2.06 ± 0.08
1.95 ± 0.06
57
1 Month
2.04 ± 0.05
2.02 ± 0.07
2.06 ± 0.07
1.95 ± 0.06
6 Months
2.14 ± 0.05
2.16 ± 0.06
2.14 ± 0.05
2.12 ± 0.04
Figure 32. Pocket depth of each group at each visit (mean + SEM). All treatments exhibit a transient reduction
and return to baseline levels. None of these changes are statistically different between treatment groups..
Table 48 ANCOVA p-values at each treatment for each group.
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
Light
0.84
0.99
0.84
0.29
0.225
Peroxide +
Light
Light
0.22
0.27
0.91
0.60
0.51
Peroxide +
Light
Light
0.20
0.88
0.26
0.92
0.19
58
Peroxide
0.30
Peroxide
0.58
Peroxide
0.81
Pocket Depth Change
Figure 33. Average change in Pocket Depth from baseline. Negative change represents pocket depth
reduction. Positive values represent increases in Pocket Depth relative to baseline.
These data suggest that the largest pocket depth reduction occurred with Light treatment
which was greatest at 1 week and 1 month and then returned to baseline. The p-values
associated with these pocket depth reductions relative to placebo were 0.2 (1-Week), 0.5 (1Month) and 0.2 (6-Months). This trend, though suggestive was not statistically significant. It
appears that all treatments except placebo may have benefited by pocket depth reduction at
1-week.
59
Gingival Crevice Fluid
Gingival crevice fluid (GCF) is an exudates collected from around the necks of teeth in the
periodontal sulcus or pocket. It has the approximate composition of a plasma ultrafiltrate.
There are two aspects of GCF, the resting volume and the flow rate. Both were measured
in this study.
GCF resting volume is an indirect measure of pocket depth. It is the volume of fluid always
present about the tooth. It is measured in microliters and is typically less than 1 microliter.
GCF flow is a measure of underlying inflammation. As inflammation proceeds, the
permeability of capillaries is reduced by the action of inflammatory mediators. Hence, flow
increases with increasing gingivitis. It is measured in microliters/hour and is typically 20 to
50 µl/h for shallow pockets.
Initial GCF flow
Table 49. GCF flow of subjects participating in the study
N
Britesmile (Light + Peroxide gel)
Light (+ placebo gel)
Peroxide (Peroxide Gel+ placebo light)
Control (placebo light, placebo gel)
25
26
25
22
Mean
33.76
38.80
36.29
42.50
f
SEM
4.73
2.99
4.18
5.68
StDev
23.63
15.22
20.91
26.63
groups at baseline.
Table 50 ANOVA of GCF flow values.
Sum-ofSource
Squares
TREAT
974.48
Error
44583.53
df
Mean-Square
F-ratio
P
3
94
324.83
474.29
0.68
0.56
Mean-Square
F-ratio
P
0.01
0.02
0.40
0.75
Initial Resting Volume
Table 51. Initial GCF resting volume of subjects participating in the study
Vr
N
Mean
SEM
Light + Peroxide
25
0.25
0.02
Light
26
0.27
0.02
Peroxide
25
0.29
0.03
Placebo
22
0.29
0.03
Table 52. ANOVA of GCF resting volume values.
Sum-ofSource
df
Squares
TREAT
0.02
3
Error
1.50
94
60
StDev
0.10
0.11
0.15
0.14
GCF flow at each visit
Flow (µl/hour)
Table 53. Mean GCF flow (±SEM) for all visits.
Treatment
N
Baseline
Light + Peroxide
25
33.76 ± 4.73
Light
26
42.5 ± 5.68
Peroxide
25
38.8 ± 2.99
Placebo
22
36.29 ± 4.18
1 Week
27.7 ± 3.31
29.16 ± 2.34
32.82 ± 4.12
26.97 ± 2.5
1 Month
29.85 ± 3.55
34.7 ± 3.95
33.65 ± 2.44
30.03 ± 3.09
6 Months
26.01 ± 3.58
26.21 ± 3.21
30.66 ± 3.43
26.87 ± 2.79
Figure 34 GCF Flow of each group at each visit (mean + SEM). Although GCF Flow is reduced in all groups
after treatment, there were no significant differences between treatment groups.
61
Baseline vs. 1 Week
Peroxide +
Light
Light
Light
0.41
Peroxide
0.66
0.20
Placebo
0.64
0.21
Peroxide +
Light
Light
Light
0.69
Peroxide
0.77
0.49
Placebo
0.85
0.84
Peroxide +
Light
Light
Light
0.46
Peroxide
0.98
0.47
Placebo
0.59
0.21
Peroxide
0.97
Peroxide
0.64
Peroxide
0.57
GCF Resting volume at each visit
Table 55. Mean GCF resting volume (±SEM) for all visits.
Treatment
N
Baseline
1 Week
Light + Peroxide
25
0.25 ± 0.02
0.26 ± 0.02
Light
26
0.29 ± 0.03
0.24 ± 0.01
Peroxide
25
0.27 ± 0.02
0.26 ± 0.02
Placebo
22
0.29 ± 0.03
0.31 ± 0.03
62
1 Month
0.27 ± 0.02
0.29 ± 0.03
0.26 ± 0.02
0.22 ± 0.02
6 Months
0.20 ± 0.02
0.23 ± 0.02
0.24 ± 0.02
0.23 ± 0.02
Figure 35. GCF Resting Volume of each group at each visit (mean + SEM). GCF Resting differences relative to
placebo between treatment groups occurred at 1 week and one 1 month. In the first case, Peroxide was
greater than Placebo and at 1 month, the reverse was true.
Since these data clearly do not suggest a trend, it appears that GCF resting volume did not
appreciably change throughout the study.
63
Baseline vs. 1 Week
Baseline vs. 6 Months
Peroxide +
Light
Light
Light
0.98
Peroxide
0.12
0.12
Placebo
0.47
0.44
Peroxide +
Light
Light
Light
0.66
Peroxide
0.03
0.08
Placebo
0.89
0.57
Peroxide +
Light
Light
Light
0.27
Peroxide
0.33
0.90
Placebo
0.42
0.80
64
Peroxide
0.03
Peroxide
0.03
Peroxide
0.89
Gingival Color L*
Use of the Minolta colorimeter to evaluate gingival soft tissue was a speculative venture. In
theory, if the color change was sufficient, the reflectance spectrophotometry approach
should provide a measure of the change observed. In some cases, such as the
measurement of the lightness parameter L*, interpretation of the observed results is not as
clear as it was in the measure of tooth whitening.
Gingival Color L* at each visit
Figure 36 L* gingival before and after treatment by Light + Peroxide, Light alone, Peroxide alone or placebo.
Whiskers indicate standard error of the mean. No statistically significant differences were observed.
65
Table 57. Evaluation of L* gingival color values by ANCOVA for each of the 5 evaluation times. Values listed
are the probability of the difference being observed by chance for each treatment pair at each visit.
Baseline vs. Post Treatment
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
0.98
0.30
0.77
Peroxide +
Light
0.84
0.50
0.90
Peroxide +
Light
0.29
0.49
0.70
Peroxide +
Light
0.46
0.63
0.71
Light
0.29091
0.78029
Light
0.62488
0.75384
Light
0.07983
0.51554
Light
0.80414
0.73314
Peroxide
0.20
Peroxide
0.44
Peroxide
0.30
Peroxide
0.92
As indicated in the preceding table and figure, no statistically significant changes in L* could
be detected.
66
Gingival Color a*
The positive colorimeter a* parameter is red. If any meaningful interpretation of gingival
reflectance spectrometry can be made, it should be from a change in redness.
Initial Gingival Color a*
Table 58. Initial gingival a* values
N
Light + Peroxide
Light
Peroxide
Placebo
Mean
6.95
7.45
8.00
7.69
25
26
25
22
Table 59. ANOVA of initial gingival a* values.
Sum-ofSource
df
Squares
TREAT
14.66
Error
621.08
a*
SEM
0.41
0.53
0.56
0.56
Mean-Square
3
94
4.89
6.61
StDev
2.05
2.72
2.82
2.62
F-ratio
P
0.74
There was no significant difference in baseline values between treatment groups.
67
0.53
Gingival Color a* at each visit
Figure 37 a* gingival color before and after treatment by Light + Peroxide, Light alone, Peroxide alone or
placebo. Whiskers indicate standard error of the mean. The effect of peroxide treatment on decreasing a*
values (more negative = less red) was at times significantly different than placebo but at no time significantly
different from that of peroxide + light
The redness value a* appears to generally increase at the Post-Treatment evaluation time
and return to the baseline level at all other visits. This roughly corresponds to what was
seen in the Gingival Index measurement except there were no statistically significant
differences between treatment groups.
68
Table 60. Evaluation of a* gingival color values by ANCOVA for each of the 5 evaluation times. Values listed
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide
+ Light
0.31
0.41
0.89
Peroxide
+ Light
0.22
0.20
0.27
Peroxide
+ Light
0.99
0.21
0.72
Peroxide
+ Light
0.62
0.69
0.56
Light
0.06
0.26
Light
0.92
0.96
Light
0.20
0.72
Light
0.92
0.92
Peroxide
0.50
Peroxide
0.88
Peroxide
0.11
Peroxide
0.84
As previously noted, no statistically significant differences between treatment group
response in the gingival redness parameter a* were recorded.
69
Change in Gingival Color a*
Figure 38. Change in a*. Substantial positive changes in all Post-Treatment groups are apparent. There
appears to be a decrease in redness in Peroxide-treated groups in the 1 Week, 1 Month and 6 month
measurements. None of these changes were statistically significant.
70
Gingival Color b*
The positive b* parameter measures yellowness. Reduction in the b* is in the direction of
blue. The interpretation of an increase in b* for gingival analysis would be that the gingival is
less blue. In the same sense, a decrease in b* would be an increase in blueness. Gingiva
with a blue tint is generally seen when vasodilitation associated with gingivis is reduced.
Initial Gingival Color b*
Table 61. Initial gingival b* values.
b*
N
Light + Peroxide
Light
Peroxide
Placebo
Mean
25
26
25
22
Table 62. ANOVA of initial gingival b* values.
Sum-ofSource
Squares
TREAT
1.38
Error
253.04
SEM
6.12
6.19
6.43
6.32
StDev
0.29
0.28
0.36
0.39
1.46
1.43
1.82
1.85
df
Mean-Square
F-ratio
P
3
94
0.46
2.69
0.17
0.92
Gingival Color b* at each visit
Figure 39 b* gingival color value before and after treatment by Light + Peroxide, Light alone, Peroxide alone or
placebo. Whiskers indicate standard error of the mean. Decreasing values of b* are interpreted as increasing
blueness. The only statistically significant differences with respect to placebo treatment observed were in the
treatments peroxide + light and light alone at the immediate post-treatment time.
71
Table 63. Evaluation of b* gingival color values by ANCOVA for each of the 5 evaluation times. Values listed
Light
Peroxide
Placebo
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
Peroxide
Light
0.16
< 0.001
0.005
< 0.001
0.001
0.60
Peroxide +
Light
Peroxide
Light
0.57
0.12
0.31
0.30
0.62
0.62
Peroxide +
Light
Peroxide
Light
0.30
0.02
0.20
0.53
0.71
0.11
Peroxide +
Light
Peroxide
Light
0.82
0.09
0.14
0.51
0.37
0.02
72
Change in Gingival Color b*
Figure 40. Change in gingival lightness (L*) from baseline following treatment by each of the four treatment
groups.
Trends toward increased bluness (decreased yellowness) are seen throughout the study. Only the
Light+Peroxide and Light alone at the post-treatment period were statistically significant.
73
Change in Gingival Color (∆E)
As with tooth color change, the total color change of gingival may also considered a measure of overall effect.
The analysis by this method suggests that the Light + Peroxide treatment may have produced the greatest
overall color change. In this case, however, the difference was not statistically significant.
Table 64. Computed total color change for each treatment at each visit.
Post
Treatment
Treatment
1 Week
1 Month
Light + Peroxide
3.28 ± 0.37
3.47 ± 0.60
4.11 ± 0.59
Placebo
2.94 ± 0.43
2.57 ± 0.32
3.26 ± 0.33
Light
2.83 ± 0.39
2.76 ± 0.30
3.26 ± 0.46
Peroxide
3.46 ± 0.45
3.78 ± 0.53
3.03 ± 0.35
6 Months
4.17 ± 0.47
3.19 ± 0.34
3.14± 0.50
3.32 ± 0.36
Figure 41. Gingival color change was computed for each of the treatments. The combined treatment of Light +
peroxide produced a significantly greater color change than any of the other treatments.
74
Table 65. Evaluation of E in gingival color by ANCOVA for each of the 5 evaluation times. Values listed are
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
Light
0.43
0.76
0.27
0.57
0.86
Peroxide +
Light
Light
0.27
0.63
0.11
0.18
0.77
Peroxide +
Light
Light
0.64
0.09
0.21
0.19
0.39
Peroxide +
Light
Light
0.09
0.16
0.77
0.12
0.94
75
Peroxide
0.38
Peroxide
0.072
Peroxide
0.73
Peroxide
0.83
Hydrogen Sulfide Measurement
Hydrogen sulfide (H2S)is thought to be the volatile gas most responsible for halitosis. With
the development of a chairside method to measure H2S, it was hoped that a change in this
parameter would be a valuable measure of effect. Inspection of the data, however, revealed
that less that 0.1% of the samples were positive and as such, analysis was not included. It
was decided that either the subjects selected for this study have no H2S, which is possible
because they are not periodontal disease subjects, or the method is too insensitive to
measure H2S in subjects with little mouth odor.
Interleukin 1 β Measurement
The cytokine interleukin 1 β ( IL1β) is an inflammatory cytokine that is a potent bone
resorbing agent. The concentration of this cytokine in GCF has been associated with
periodontal disease and bone lose. Measurement of an effect on IL1β concentration would
be strong presumptive evidence for an anti-inflammatory effect of a therapy.
Initial IL1β values
Table 66.. Initial Pocket Depth of subjects participating in the study
N
Mean
SEM
StDev
Light + Peroxide
25
23.7
10.3
51.6
Light
26
19.3
6.6
33.7
Peroxide
25
17.8
4.6
23.0
Placebo
22
25.8
5.6
26.4
groups at baseline.
Table 67. ANOVA of baseline Pocket Depth values.
Source
TREAT
Error
Sum-of-Squares
df
Mean-Square
994.09353
1.19749E+05
331.3
1273.9
F-ratio
0.26
P
0.85
IL1β values for all visits
Table 68. Mean Pocket Depth (millimeters, ±SEM) of subjects participating in the study for all visits.
Treatment
Light + Peroxide
Light
Peroxide
Placebo
N
25
26
25
22
Baseline
23.7± 10.3
19.3± 6.6
17.8 ± 4.6
25.8 ± 5.6
1 Week
16.5 ± 3.9
23.6 ± 6.8
33.1 ± 17.6
26.8 ± 10.8
76
1 Month
26.0 ± 7.4
27.9 ± 10.2
26.4 ± 11.0
37.4 ± 18.4
6 Months
25.2 ± 6.0
32.3 ± 8.9
26.2 ± 5.8
26.1 ± 7.6
Figure 42. Concentration of IL1β in GCF of each group at each visit (mean + SEM). IL1β concentrations tend to
increase with increasing time, particularly the placebo at 1 month. None of these changes, however, are
statistically significant
These data and that of the following table provide no evidence to support an effect on
IL1β concentration in GCF.
Baseline vs. 1 Week
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Light
Peroxide
Placebo
Peroxide +
Light
0.59
0.24
0.54
Peroxide +
Light
0.85
0.87
0.63
Peroxide +
Light
0.52
0.99
0.939
77
Light
Peroxide
0.52
0.92
0.61
Light
Peroxide
0.98
0.76
0.74
Light
Peroxide
0.52
0.58
0.95
Microbiology Data
At the simplest level, the total number of bacteria was decreased by all treatments. This
was expected since tooth prophylaxis is a routine part of the procedure. This effect is
illustrated in the following figure.
Figure 43 Total number of bacteria on the tooth surfaces in each treatment group. The only statistically
significant effect is the elevation in total bacterial numbers at 6 months in the group treated by light.
This observation is in agreement with the plaque index which was also significantly elevated
at 6 months in the light treated group.
Numerous changes in the microbial population could be seen following each of the various
treatments. Some of those changes are indicated in the following figures illustrating the
change in microbial proportions of each of the 40 bacteria tested in each of the treatment
groups.
In these figures, bacteria are grouped into 7 complexes. The characteristics of these
complexes are as follows
1. Red complex : Includes all of the putative periodontal pathogens.
2. Orange complex: Bacteria associated with developing periodontitis.
78
3. Purple complex: Largely associated with gingivitis.
4. Other: A group of bacteria recently added to the panel. Their significance is not yet
certain.
5. Green complex:
including cancer.
Role largely unknown.
Often associated with oral pathology
6. Yellow complex: All streptococci. Probably beneficial.
7. Actinomycetes: Generally considered to be beneficial. Generally the numerically
largest component of periodontal plaque.
Considerable analysis may be conducted on this data. It would be of interest to determine
the degree of association between clinical measures and microbial changes. It would be
instructive to look at how the various therapies encourage growth of beneficial species. It is
important to determine what species proliferate 6-months following therapy with light alone.
These and other issues will have to be left to another time or this report will never get out.
79
80
81
82
83
84
Changes in P. gingivalis proportions were selected for detailed study as a representative
black-pigmented bacterium that would be expected to absorb light and at the same time an
acknowledged periodontal pathogen.
Changes in P. gingivalis proportions
The proportions of P. gingivalis in each treatment group over all visits is illustrated in the
following figure.
Light + Peroxide
Light
Peroxide
Placebo
Baseline
0
10
20
30 40
V0
50
60
70
0
10
20
30 40
V0
50
60
70
0
10
20
30 40
V0
50
60
70
0
10
20
30 40
V0
50
60
70
0
10
20
30 40
V1
50
60
70
0
10
20
30 40
V1
50
60
70
0
10
20
30 40
V1
50
60
70
0
10
20
30 40
V1
50
60
70
0
10
20
30 40
V2
50
60
70
0
10
20
30 40
V2
50
60
70
0
10
20
30 40
V2
50
60
70
0
10
20
30 40
V2
50
60
70
0
10
20
30 40
V3
50
60
70
0
10
20
30 40
V3
50
60
70
0
10
20
30 40
V3
50
60
70
0
10
20
30 40
V3
50
60
70
0
10
20
30 40
V4
50
60
70
0
10
20
30 40
V4
50
60
70
0
10
20
30 40
V4
50
60
70
0
10
20
30 40
V4
50
60
70
PostTreatment
1-Week
1-Month
6-Months
Figure 44. The distribution of proportions of P. gingivalis from subjects of each treatment group over all visits.
Each dot represents the average proportion of P. gingivalis for each subject.
These data indicate that subjects were entered into the study with proportions of from 0 to
5% of the total microbiota. Following treatment, Peroxide + Light and Light alone
substantially reduced the proportions of P. gingivalis whereas Peroxide and Placebo
treatments were less effective. Over the months that followed the proportion of P. gingivalis
increased in all therapies. Clearly, the best effects were seen in 1-week. After 1-week
subjects were found to have increasing proportions of P. gingivalis in their periodontal
plaques. This was particularly true of the Placebo treated group where three subjects are
seen to have levels greater than 5% and one individual was found to have an extraordinary
66% P. gingivalis.
85
This proliferation of a recognized periodontal pathogen in 14% of the Placebo-treated
subject group is approximately the expected level of new periodontal disease occurrence. It
doesn’t occur in everybody, only in disease-susceptible individuals who comprise
approximately 25% of the population. With a limited dataset of 6 subjects who have an
average P. gingivalis population of greater than 5% of the total bacteria, the following figure
suggests that the occurrence is associated with both increased visible plaque and increased
resting gingival fluid volume. This is illustrated in the following figure.
0.45
0.4
0.35
0.3
0.25
PL
0.2
Vr
0.15
0.1
0.05
0
Baseline
1-Week
1-Month
6-Months
Figure 45. Plaque index (PL) and resting gingival fluid volume (Vr, l) of six subjects with P.
gingivalis proportions greater than 5% at 6-Months. None of these differences are
Analysis of the treatment data by ANOVA reveals a strong association between treatment
and suppression of the percent P.g. in periodontal plaque. This is illustrated in the following
figure.
86
8
5
P. gingivalis
Proportion
(%)
2
0
Light + Light
Peroxide
Peroxide Placebo
Figure 46. The proportion of P. gingivalis in periodontal plaque of subjects in each of 4 treatment groups 6months after treatment.
Analysis of 6-Month data by ANOVA produced the following result.
Source
TREAT$
Error
Sum-of-Squares
372.09375
4900.09210
df
3
91
Mean-Square
124.03125
53.84717
F-ratio
2.30339
P
0.08222
The associated probability matrix from post-hoc testing is listed in the following table.
Light
Peroxide
Placebo
Peroxide +
Light
0.90451
0.95620
0.03444
Light
0.86032
0.02357
Peroxide
0.03904
These data suggest that with treatment of either Light + Peroxide, Peroxide alone or Light
alone, the mean P. gingivalis proportions in periodontal plaque can be maintained below
2%. In contrast, P. gingivalis more than doubled in placebo treated subjects (5%) over the
same period of time. Note that this analysis does not separate the light and peroxide
effects, it analyzes the treatment groups per se.
87
Changes in P. gingivalis proportions by factorial analysis
The observation that P. gingivalis increased through 6 months in a subset of placebo-treated
subjects suggests the effect of Light and peroxide could be investigated using the factorial
design of the study to determine the relative effects of each. By this analysis, the effects of
peroxide and light alone can be combined with the effects of peroxide + light effectively
doubling the number of subjects for each test and allowing us to separate the effects of light
and peroxide on control of P. gingivalis proliferation. The following table represents the
adjusted least squares mean computed at each visit for those subjects treated with peroxide
(either peroxide alone or peroxide + light) and those subjects treated with light (either light
alone or peroxide + light). These values represent a least squares estimate of the effect of
each of these single therapies at each visit. The independence of Light and peroxide was
investigated by introducing the Light*Peroxide interaction into the analysis. This effect not
significant at any of the visits suggesting that peroxide and light work independently in their
ability to effect tooth lightness.
Evaluation of changes in P. gingivalis by factorial analysis produced the following data.
Table 70. Least squares means of proportions of P. gingivalis in periodontal plaque at each visit associated with
treatment (1) and no treatment (0) by Light and Peroxide.
Treatment
Adj.LS Mean
SE
N
Difference
Post-Therapy
LIGHT(0)
1.46898
0.187
45
LIGHT(1)
1.28241
0.1765
50
PEROXIDE(0)
1.37372
0.1855
46
PEROXIDE(1)
1.37767
0.1782
49
0.18657
-0.00395
1-week
LIGHT(0)
1.08719
0.1293
45
LIGHT(1)
0.7758
0.122
50
PEROXIDE(0)
1.03594
0.1282
46
PEROXIDE(1)
0.82705
0.1232
49
0.31139
0.20889
1-month
LIGHT(0)
1.46145
0.2397
45
LIGHT(1)
0.87758
0.2263
50
PEROXIDE(0)
1.13547
0.2377
46
PEROXIDE(1)
1.20356
0.2285
49
0.58387
-0.06809
6-months
LIGHT(0)
3.46543
1.097
45
LIGHT(1)
1.12084
1.0354
50
PEROXIDE(0)
3.35025
1.0878
46
PEROXIDE(1)
1.23602
1.0454
49
88
2.34459
2.11423
Figure 47. Proportion of P. gingivalis in periodontal plaque with and without either light or peroxide by factorial
analysis. Values are adjusted least squares means.
Essentially no effect of either light or peroxide was seen at the immediate Post-therapy visit.
The effect of suppression of proportions of P. gingivalis in periodontal plaque attributed to
light therapy appears to progressively increase through 6-months. The effect attributed to
Peroxide appears only at 6 months, the difference between treatment and no treatment
being small for all visits through 1-month. These effects can be visually appreciated by
study of the following figure.
89
Figure 48. Adjusted Least Squares means describing the change in proportions of P. gingivalis at each visit
associated with treatment (1) or no treatment (0) by Light and Peroxide.
The significance of these patterns can be evaluated by reviewing the GLM parameters of
the fitted factorial model listed in the following table.
90
Table 71. Factorial analysis evaluating the effect of Light and Peroxide on the proportions of P. gingivalis at
periodontal sites in subjects at all visits.
Source
Sum-of-Squares
df
Mean-Square
F-ratio
P
Post-Therapy
LIGHT
0.81193
1
0.81193
0.52428
0.4709
PEROXIDE
0.00036
1
0.00036
0.00023
0.9878
331.53539
1
331.53539
214.0802
< 0.001
0.21797
1
0.21797
0.14075
0.7084
139.37851
90
1.54865
V0
LIGHT*PEROXIDE
Error
1-week
LIGHT
2.26154
1
2.26154
3.05498
0.0839
PEROXIDE
1.01708
1
1.01708
1.37391
0.2442
V0
21.14827
1
21.14827
28.56789
< 0.001
LIGHT*PEROXIDE
0.26684
1
0.26684
0.36046
0.5498
Error
66.6253
90
0.74028
1-month
LIGHT
7.95119
1
7.95119
3.12424
0.0805
PEROXIDE
0.10805
1
0.10805
0.04245
0.8372
V0
2.80375
1
2.80375
1.10167
0.2967
LIGHT*PEROXIDE
1.19201
1
1.19201
0.46837
0.4955
229.05009
90
2.545
Error
6-months
LIGHT
128.21459
1
128.21459
2.40634
0.1244
PEROXIDE
104.18348
1
104.18348
1.95532
0.1655
V0
34.11882
1
34.11882
0.64034
0.4257
LIGHT*PEROXIDE
153.79579
1
153.79579
2.88645
0.0928
Error
4795.37703
90
53.28197
These data indicate that light has a borderline significant effect on reducing the percentage
of P. gingivalis at a periodontal site (P=0.08). Interestingly, the initial percentage of P.
gingivalis was highly significant at 1 week but not at 1 month and 6 months. Peroxide alone
was never even close to statistical significance in reducing the P.g. percentage The
interaction Light*Peroxide was never significant although it approached significance at 6
months (p=O.09). We can conclude from this analysis that Light alone apparently has an
effect in decreasing the percentage of P. g. in periodontal plaque and that effect is most
prominent 1 week after treatment.
91
Questionnaire Data
Post-Treatment Evaluation
1
2
3
4
5
6
How much did the product increase the whiteness of your teeth?
Not at all
Slightly
Moderately Greatly
Did the test product reduce the yellowness of your teeth?
Not at all
Slightly
Moderately Greatly
Did you feel any discomfort during the procedure?
Not at all
Slightly
Moderately Greatly
Did your teeth feel sensitive before the procedure?
Not at all
Slightly
Moderately Greatly
Did your teeth feel sensitive after the procedure?
Not at all
Slightly
Moderately Greatly
Would you recommend this procedure to your friends?
Not at all
Maybe
Yes
Q1 How much did the product increase the whiteness of your teeth?
Table 72. Post-Treatment question 1 response
Not at
Slightly Moderately
all
Light + Peroxide
0
1
8
Light
5
10
11
Peroxide
4
16
5
Placebo
10
9
3
Total
19
36
27
Greatly
Table 73. Pooled Post-Treatment question 1 response.
Not at all – Slightly Moderately - Greatly
Light + Peroxide
1
24
Light
15
11
Peroxide
20
5
Placebo
19
3
Total
55
43
Table 74. Post-Treatment question 1 2x2 probability matrix.
Peroxide
Light
Peroxide
+ Light
Light
0.00004
Peroxide
0.00000
0.08610
Placebo
0.00000
0.02944
0.56243
92
16
0
0
0
16
Total
25
26
25
22
98
Total
25
26
25
22
98
These data indicate that based on the immediate post-treatment questionnaire, 96% of
the peroxide + light treated subjects (25/25) reported a moderate-great increase in tooth
whiteness. The probability matrix indicates that peroxide + light treatment received a
greater positive subject response than any of the other treatments. Light alone
received 42% (11/26) positive responses, significantly more than peroxide alone (20%,
5/25) or placebo (14%, 3/22). Responses to peroxide alone were not different than
placebo. It is interesting to note that 55% (12/22) placebo-treated subjects reported
some degree of tooth whitening.
Q2 Did the test product reduce the yellowness of your teeth?
Not at
Slightly Moderately
all
Light + Peroxide
0
1
9
Light
3
14
8
Peroxide
2
17
6
Placebo
11
9
2
Total
16
41
25
Greatly
Light + Peroxide
1
24
Light
17
9
Peroxide
19
6
Placebo
20
2
Total
57
41
15
1
0
0
16
Total
25
26
25
22
98
Total
25
26
25
22
98
Peroxide
Light
Peroxide
+ Light
Light
0.00000
Peroxide
0.00000
0.40556
Placebo
0.00000
0.03604
0.17476
These data were almost identical to the responses in Q1. They indicate that based on
the immediate post-treatment questionnaire, 96% of the peroxide + light treated
subjects (24/25) reported a moderate-great reduction in tooth yellowness. The
probability matrix indicates that peroxide + light treatment received a greater positive
subject response than any of the other treatments. Light alone received 35% (9/26)
positive responses, significantly more than peroxide alone (24%, 6/25) or placebo (9%,
2/22). Responses to peroxide alone were not different than placebo.
93
Q3 Did you feel any discomfort during the procedure?
Not at
Slightly Moderately
all
Light + Peroxide
8
14
3
Light
14
9
3
Peroxide
10
12
2
Placebo
7
11
3
Total
39
46
11
Greatly
Total
0
0
1
1
2
25
26
25
22
98
Light + Peroxide
22
3
Light
23
3
Peroxide
22
3
Placebo
18
4
Total
85
13
Total
25
26
25
22
98
Table 80 Post-Treatment question 3 2x2 probability matrix.
Peroxide
Light
Peroxide
+ Light
Light
0.95921
Peroxide
1.00000
0.95921
Placebo
0.55253
0.51584
0.55253
There were no significant differences between treatments in response to this question
concerning procedure discomfort. 87% of subjects experienced none to slight
discomfort. Two subjects, one in the light alone group and one in the placebo group
experienced great discomfort during the procedure.
Q4 Did your teeth feel sensitive before the procedure?
Not at all
Slightly
Total
Light + Peroxide
20
5
25
Light
24
2
26
Peroxide
22
3
25
Placebo
20
2
22
Total
86
12
98
Table 82 Post-Treatment question 4 probability.
Test statistic Value
Pearson Chi-square
2.10578
df
3.00000
Prob
0.55075
88% of subjects(86/98) reported that they had no tooth sensitivity before the study.
There was no significant difference between treatment groups in this response
94
Q5 Did your teeth feel sensitive after the procedure?
Not at all
Slightly Moderately
Light + Peroxide
18
7
0
Light
22
4
0
Peroxide
18
6
1
Placebo
16
5
1
Total
74
22
2
Total
25
26
25
22
98
Not at all – Slightly
Moderately - Greatly
Light + Peroxide
25
0
Light
26
0
Peroxide
24
1
Placebo
21
1
Total
96
2
Total
25
26
25
22
98
Table 85 Post-Treatment question 5 2x2 probability matrix.
Peroxide
Light
Peroxide
+ Light
Light
0.9999
Peroxide
0.31242
0.30303
Placebo
0.28124
0.27193
0.92635
98% of subjects (96/98) did not feel increased tooth sensitivity immediately following
treatment. No subjects experienced a great increase in tooth sensitivity and only 2
experienced a moderate increase (one treated by light alone and one treated by
placebo).
Q6 Would you recommend this procedure to your friends?
Not at all
Maybe
Light + Peroxide
1
5
Light
0
12
Peroxide
1
13
Placebo
3
10
Total
5
40
Yes
19
14
11
9
53
Total
25
26
25
22
98
Table 87.. Pooled Post-Treatment question 6 response.
Not at all – Maybe
Yes
Total
Light + Peroxide
6
19
25
Light
12
14
26
Peroxide
14
11
25
Placebo
13
9
22
Total
45
53
98
95
Peroxide
Light
Peroxide
+ Light
Light
0.09792
Peroxide
0.02092
0.48196
Placebo
0.01444
0.37134
0.83066
In this question response, overall 54% (53/98) would have recommended this
procedure to a friend. In the Light + Peroxide group, 76% (19/25) would have
recommended the treatment. In the light alone treated group, 54% (14/26) would have
recommended the treatment. This was not significantly different than the Light +
Peroxide treated group (p=0.1). In the peroxide alone group, 44% (11/25) would have
recommended the treatment. This response was significantly different than the Light +
Peroxide treated group (p=0.02). In the placebo-treated group, 41% (9/22) would have
Peroxide treated group (p=0.01). The response following treatment by peroxide alone
was not different than the response from subjects treated by placebo alone (p=0.8).
96
One-Week follow up Survey
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
How would you rate your overall experience with the whitening procedure?
Excellent
Very good Fair
Poor
Compared to your appearance immediately after the treatment, do you think that
the whiteness of your teeth has decreased?
Not at all
Slightly
Moderately Greatly
Compared to your appearance immediately after the treatment, do you think that
the yellowness of your teeth has increased?
Not at all
Slightly
Moderately Greatly
Have your sleeping habits changed?
No
Yes
If your sleeping habits changed, Please indicate:
Less Sleep More Sleep Frequent Awakening Other / No Answer
Have your eating habits changed?
No
Yes
If your eating habits changed, Please indicate:
Avoidance of certain foods Less frequent meals
More frequent meals
Other/No Answer
Did you experience Tooth Pain during the past week?
None
Mild
Moderate
Severe
Did you experience Bleeding during the past week?
None
Mild
Moderate
Severe
Did you experience Drooling during the past week?
None
Mild
Moderate
Severe
Did you experience Choking during the past week?
None
Mild
Moderate
Severe
Did you experience Dry Mouth during the past week?
None
Mild
Moderate
Severe
Did you experience Bad Taste during the past week?
None
Mild
Moderate
Severe
Did you experience Tooth Sensitivity - Hot during the past week?
None
Mild
Moderate
Severe
Did you experience Tooth Sensitivity - Cold during the past week
None
Mild
Moderate
Severe
Please tell us if you experienced discomfort in your lips.
None
Mild
Moderate
Severe
Please tell us if you experienced discomfort in your gums.
None
Mild
Moderate
Severe
Please tell us if you experienced discomfort in your jaws.
None
Mild
Moderate
Severe
Did you take medication to control oral discomfort?
No
Yes
If yes, did medication control discomfort?
Well-controlled
Moderately well-controlled Not controlled at all
97
Q1 How would you rate your overall experience with the whitening procedure?
Table 89. One-week follow up question 1 response
Excellent
Very good
Fair
Light + Peroxide
14
11
0
Light
6
10
9
Peroxide
4
13
8
Placebo
4
11
6
Total
28
45
23
Poor
0
1
0
1
2
Table 90. Pooled One-week follow up question 1 response.
Excellent – Very good Fair - Poor
Light + Peroxide
25
0
Light
16
10
Peroxide
17
8
Placebo
15
7
Total
73
25
Total
25
26
25
22
98
Total
25
26
25
22
98
Table 91. One-week follow up question 1 2x2 probability matrix.
Peroxide
Light
Peroxide
+ Light
Light
0.00054
Peroxide
0.00203
0.62930
Placebo
0.00223
0.63157
0.98935
In this questionnaire, taken one-week after treatment, 74% (73/98) felt their overall
experience in tooth whitening was excellent to very good. Two subjects (one treated by light
alone and one treated by placebo) considered their response poor. In the Light + Peroxide
treated group, 100% (25/25) considered the experience excellent to very good. This
response was significantly better than with any of the other groups. In the light alone group,
38% (10/26) considered the experience excellent to very good. In the peroxide alone group,
32% (8/25) considered the experience excellent to very good. In the placebo treated group,
32% (7/22) considered the experience excellent to very good. There was no significant
difference in responses from subjects treated by light alone, peroxide alone or placebo
alone.
98
Q2 Compared to your appearance immediately after the treatment, do you think
that the whiteness of your teeth has decreased?
Light + Peroxide
Light
Peroxide
Placebo
Total
Not at all
Slightly
8
10
8
13
39
13
8
9
3
33
Moderately
Greatly
1
3
3
1
8
2
0
1
1
4
Not
Applicable
1
5
4
4
14
– Not Applicable0
Light + Peroxide
22
3
Light
23
3
Peroxide
21
4
Placebo
20
2
Total
86
12
Total
25
26
25
22
98
Total
25
26
25
22
98
Table 94. One-week follow up question 2 2x2 probability matrix.
Peroxide
Light
Peroxide
+ Light
Light
0.95921
Peroxide
0.68359
0.64346
Placebo
0.74688
0.78210
0.47879
In this response, 1-week after treatment, 88% (86/98) of subjects felt that the whiteness had
not decreased. There were no significant differences between treatment groups in this
response.
Q3 Compared to your appearance immediately after the treatment, do you think
that the yellowness of your teeth has increased?
Not at all
Light + Peroxide
Light
Peroxide
Placebo
Total
11
12
12
15
50
Slightly Moderately
10
7
5
2
24
1
3
3
0
7
99
Greatly
1
0
1
1
3
Not
Applicable
2
4
4
4
14
Total
25
26
25
22
98
– Not Applicable0
Light + Peroxide
23
2
Light
23
3
Peroxide
21
4
Placebo
21
1
Total
88
10
Total
25
26
25
22
98
Table 97 One-week follow up question 3 2x2 probability matrix.
Peroxide
Light
Peroxide
+ Light
Light
0.67098
Peroxide
0.38409
0.64346
Placebo
0.62879
0.38243
0.20378
The response to this question was almost identical to that of Q2. In this response, 1-week
after treatment, 90% (88/98) of subjects felt that the whiteness had not decreased. There
were no significant differences between treatment groups in this response.
Q4 Have your sleeping habits changed?
No
Yes
Total
Light + Peroxide
24
1
25
Light
26
0
26
Peroxide
24
1
25
Placebo
20
2
22
Total
94
4
98
Table 99. One-week follow up question 4 probability.
Pearson Chi-square
2.51729
df
3.00000
Prob
0.47217
96% (94/98) subjects answered no to this question. There were no significant changes in
sleeping habits resulting from the treatment.
100
Q5 If your sleeping habits changed, Please indicate:
Other /
Less Sleep
No Answer
Light + Peroxide
24
0
Light
26
0
Peroxide
24
1
Placebo
20
2
Total
94
3
Frequent
Awakening
1
0
0
0
1
Table 101. One-week follow up question 5 probability.
df
Pearson Chi-square
7.26881
6.00000
Tota
25
26
25
22
98
Prob
0.29670
96% of subjects (94/98) did not respond to this question. There were no difference between
treatments in those who responded.
Q6 Have your eating habits changed?
No
Yes
Total
Light + Peroxide
21
4
25
Light
25
1
26
Peroxide
25
0
25
Placebo
21
1
22
Total
92
6
98
94% of individuals (92/98) responded negatively to this question. None of the treatments
appear to have significantly altered eating habits.
Q7 If your eating habits changed, Please indicate:
Table 103. One-week follow up question 7response
Light + Peroxide
Light
Peroxide
Placebo
Total
Other /
No Answer
Avoidance of
Certain Foods
21
25
25
21
92
4
1
0
0
5
Less
Frequent
Meals
0
0
0
1
1
Total
25
26
25
22
98
94% of individuals (92/98) responded negatively to this question. None of the treatments
appear to have significantly altered eating habits.
101
Q8 Did you experience Tooth Pain during the past week?
None
Mild
Moderate
Light + Peroxide
15
5
5
Light
24
2
0
Peroxide
23
2
0
Placebo
20
2
0
Total
82
11
5
Total
25
26
25
22
98
None - Mild
Moderate - Severe
Total
Light + Peroxide
20
5
25
Light
26
0
26
Peroxide
25
0
25
Placebo
22
0
22
Total
93
5
98
Table 106 One-week follow up question 8 2x2 probability matrix.
Peroxide
Light
Peroxide
+ Light
Light
0.01635
Peroxide
0.01842
Placebo
0.02649
In this response, 95% (93/98) experienced none to mild pain. None experienced severe
pain. 5 subjects (20%) treated by Light + Peroxide reported moderate pain. None of the
subjects with other treatments experienced moderate pain. This difference was statistically
significant (p=0.01).
Q9 Did you experience Bleeding during the past week?
None
Mild
Total
Light + Peroxide
23
2
25
Light
22
4
26
Peroxide
23
2
25
Placebo
17
5
22
Total
85
13
98
102
Table 108 One-week follow up question 9 probability.
Pearson Chi-square
3.01816
df
3.00000
Prob
0.38883
13% (13/98) of subjects reported bleeding in response to this question. The most frequent
report was from placebo treated subjects (23%, 5/22). There was no statistically significant
association of this report with any treatment category.
Q10 Did you experience Drooling during the past week?
None
Mild
Total
Light + Peroxide
25
0
25
Light
26
0
26
Peroxide
24
1
25
Placebo
22
0
22
Total
97
1
98
df
Pearson Chi-square
2.95010
3.00000
Prob
0.39938
Only one subject reported this effect. There were no statistically significant associations of
this condition with any treatment.
Q11 Did you experience choking during the past week?
None
Total
Light + Peroxide
25
25
Light
26
26
Peroxide
25
25
Placebo
22
22
Total
98
98
None of the subjects experienced choking during the past week.
103
Q12 Did you experience Dry Mouth during the past week?
Light +
Peroxide
Light
Peroxide
Placebo
Total
None
Mild
Moderate
Total
23
2
0
25
23
24
20
90
3
0
1
6
0
1
1
2
26
25
22
98
Test statistic
Pearson Chi-square
Value
5.27845
df
6.00000
Prob
0.50863
8% of subjects (8/98) reported mild to moderate dry mouth during the week following
treatment. None of these reports were significantly associated with any particular treatment.
Q13 Did you experience Bad Taste during the past week?
None
Mild
Total
Light + Peroxide
25
0
25
Light
24
2
26
Peroxide
25
0
25
Placebo
20
2
22
Total
94
4
98
df
Pearson Chi-square
4.40351
3.00000
Prob
0.22106
4% (4/98) subjects experienced bad taste in their mouth during the week following
treatment. None of these reports were significantly associated with any particular treatment.
104
Q14 Did you experience Tooth Sensitivity - Hot during the past week?
None
Mild Moderate
Light + Peroxide
19
5
1
Light
26
0
0
Peroxide
24
1
0
Placebo
20
2
0
Total
89
8
1
Pearson Chi-square
10.80703
Total
25
26
25
22
98
df
6.00000
Prob
0.09453
91 % (89/98) of subjects did not experience tooth sensitivity to hot stimulus n the week
between treatment and recall. Only 1 subject (Light + Peroxide treated) exhibited moderate
tooth sensitivity. None of the reported tooth sensitivity was significantly associated with any
particular treatment. The majority of Mild + Moderate reports were following Light +
Peroxide treatment.
Q15 Did you experience Tooth Sensitivity - Cold during the past week
None
Mild Moderate
Light + Peroxide
17
7
1
Light
24
2
0
Peroxide
22
3
0
Placebo
17
4
1
Total
80
16
2
Total
25
26
25
22
98
df
Pearson Chi-square
6.90163
6.00000
Prob
0.33004
82 % (80/98) of subjects did not experience tooth sensitivity to cold stimulus n the week
between treatment and recall. Only 2 subjects (one Light + Peroxide treated and one
placebo treated) exhibited moderate tooth sensitivity. None of the reported tooth sensitivity
was significantly associated with any particular treatment. The majority of Mild + Moderate
reports were following Light + Peroxide treatment
105
Q16 Please tell us if you experienced discomfort in your lips.
None
Mild Moderate
Light +
24
1
0
Peroxide
Light
25
0
1
Peroxide
23
2
0
Placebo
19
3
0
Total
91
6
1
Total
25
26
25
22
98
df
Pearson Chi-square
6.87662
6.00000
Prob
0.33241
93 % (91/98) of subjects did not experience tooth sensitivity to cold stimulus in the week
between treatment and recall. Only 1 subject (Light + Peroxide treated) exhibited moderate
lip discomfort. None of the reported lip discomfort was significantly associated with any
particular treatment.
Q17 Please tell us if you experienced discomfort in your gums.
None
Mild Moderate
Light +
23
1
1
Peroxide
Light
26
0
0
Peroxide
25
0
0
Placebo
22
0
0
Total
96
1
1
Total
25
26
25
22
98
df
Pearson Chi-square
5.96167
6.00000
Prob
0.42750
98 % (96/98) of subjects did not experience periodontal discomfort in the week between
treatment and recall. Only 1 subject (Light + Peroxide treated) exhibited moderate
periodontal discomfort. None of the reported periodontal discomfort was significantly
associated with any particular treatment.
106
Q18 Please tell us if you experienced discomfort in your jaws.
Light + Peroxide
Light
Peroxide
Placebo
Total
None
Mild
24
25
24
19
92
1
1
0
3
5
Moderate
Total
0
0
1
0
1
25
26
25
22
98
Table @ One-week follow up question 18 probability.
Pearson Chi-square
7.64668
df
6.00000
Prob
0.26515
94 % (92/98) of subjects did not experience jaw discomfort in the week between treatment
and recall. Only 1 subject (Peroxide treated) exhibited moderate jaw discomfort. None of
the reported jaw discomfort was significantly associated with any particular treatment.
Q19 Did you take medication to control oral discomfort?
No
Yes
Total
Light + Peroxide
18
7
25
Light
26
0
26
Peroxide
25
0
25
Placebo
21
1
22
Total
90
8
98
Peroxide
Light
Peroxide
+ Light
Light
0.00367
Peroxide
0.00433
Placebo
0.03277
0.27193
0.28124
8 % (8/98) of subjects overalltook medication to control oral discomfort in the week between
treatment and recall. Of the subjects treated by Peroxide + Light, 28% (7/25) took
medication. This represents a highly significant difference compared to the other treatment
groups.
107
Q20 If yes, did medication control discomfort?
Very
Moderately
N/A
well-controlled
well-controlled
Light + Peroxide
18
4
3
Light
26
0
0
Peroxide
25
0
0
Placebo
21
1
0
Total
90
5
3
Total
25
26
25
22
98
Of the 8 individuals taking medication it was very well controlled in 63% (5/8) and
moderately well controlled in 38% (3/8).
Subject Recall Questionnaire
1
2
3
4
5
6
Compared to after treatment, has whiteness of your teeth decreased?
Not at all
Slightly
Moderately Greatly
Not Applicable
Compared to after treatment, has yellowness of your teeth increased?
Not at all
Slightly
Moderately Greatly
Not Applicable
Did your teeth feel sensitive before the procedure?
Not at all
Slightly
Moderately Greatly
Not Applicable
Do your teeth feel sensitive now?
Not at all
Slightly
Moderately Greatly
Not Applicable
Did you have sensitive teeth at any time after the procedure?
Not at all
Slightly
Moderately Greatly
Not Applicable
Would you recommend this procedure to your friends?
Not at all
Maybe
Yes
108
Q1 Compared to after treatment, has whiteness of your teeth decreased?
Table 128. Subject Recall question 1 response
Not at all
Slightly Moderately
Light + Peroxide
4
12
9
Light
13
8
3
Peroxide
13
10
2
Placebo
15
6
1
Total
45
36
15
Greatly
0
2
0
0
2
Table 129. Pooled Subject Recall question 1 response.
Light + Peroxide
16
9
Light
21
5
Peroxide
23
2
Placebo
21
1
Total
81
17
Total
25
26
25
22
98
Total
25
26
25
22
98
Peroxide
Light
Peroxide
+ Light
Light
0.17976
Peroxide
0.01686
0.24396
Placebo
0.00856
0.12531
0.62879
Six months after treatment, 17% of subjects (17/98) reported that whiteness of teeth had
decreased. Of those subjects treated by Light + Peroxide, 36% (9/25) reported detectable
whiteness decrease. Of those subjects treated by light alone 12% (3/26) reported
detectable whiteness decrease. Of those subjects treated by peroxide alone 8% (2/25)
reported detectable whiteness decrease. Of those subjects treated by placebo 5% (1/22)
reported detectable whiteness decrease. The difference in whiteness reduction was clearly
associated with the highest level of initial response (Light + Peroxide treatment).
Q2 Compared to after treatment, has yellowness of your teeth increased?
Light + Peroxide
Light
Peroxide
Placebo
Total
Not at all
Slightly
10
14
13
15
52
10
8
11
7
36
Moderately
4
3
1
0
8
109
Greatly
Total
1
1
0
0
2
25
26
25
22
98
Light + Peroxide
Light
Peroxide
Placebo
Total
20
5
22
4
24
1
22
0
88
10
Total
25
26
25
22
98
Table 133. Subject Recall question 2 2x2 probability matrix.
Peroxide
Light
Peroxide
+ Light
Light
0.66558
Peroxide
0.08172
0.17170
Placebo
0.02649
0.05466
0.34301
Six months after treatment, 10% of subjects (10/98) reported that yellowness of teeth had
increased. Of those subjects treated by Light + Peroxide, 20% (5/25) reported detectable
whiteness increase. Of those subjects treated by light alone 15% (4/26) reported detectable
yellowness increase. Of those subjects treated by peroxide alone 2% (1/25) reported
detectable yellowness increase. Of those subjects treated by placebo 0% (0/22) reported
detectable yellowness increase. The difference in yellowness increase was clearly
associated with the highest level of initial response (Light + Peroxide treatment).
Q3 Did your teeth feel sensitive before the procedure?
Not at all Slightly Moderately
Light + Peroxide
17
7
1
Light
21
4
1
Peroxide
20
5
0
Placebo
17
4
1
Total
75
20
3
Total
25
26
25
22
98
Light + Peroxide
24
1
Light
25
1
Peroxide
25
0
Placebo
21
1
Total
95
3
Peroxide
Light
Peroxide
+ Light
Light
0.97743
Peroxide
0.31242
0.32201
Placebo
0.92635
0.90384
0.28124
110
Total
25
26
25
22
98
77% of subjects(75/98) reported that they had no tooth sensitivity before the study.
There was no significant difference between treatment groups in this response
Q4 Do your teeth feel sensitive now?
Not at all
Slight Moderately
Light + Peroxide
17
7
1
Light
22
4
0
Peroxide
17
8
0
Placebo
17
5
0
Total
73
24
1
Total
25
26
25
22
98
BS
24
1
L
26
0
P
25
0
C
22
0
Total
97
1
Total
25
26
25
22
98
Only one subject reported moderate tooth sensitivity. This subject was in the Light +
Peroxide treatment group.
Q5 Did you have sensitive teeth at any time after the procedure?
Not at
Slightly Moderately
all
Light + Peroxide
8
14
3
Light
20
4
2
Peroxide
15
10
0
Placebo
16
5
1
Total
59
33
6
Total
Light + Peroxide
22
3
Light
24
2
Peroxide
25
0
Placebo
21
1
Total
92
6
111
25
26
25
22
98
Total
25
26
25
22
98
Light
Peroxide
Placebo
Peroxide
+ Light
0.60505
0.07402
0.36078
Light
Peroxide
0.15714
0.65359
0.28124
94% of subjects (92/98) had non e to slight tooth sensitivity immediately following
treatment. No subjects experienced a great increase in tooth sensitivity and 6
experienced a moderate increase (three treated by Light + Peroxide, two treated by
light alone and one treated by placebo).
Q6 Would you recommend this procedure to your friends?
Not at all
Maybe
Light + Peroxide
1
2
Light
3
8
Peroxide
0
11
Placebo
4
8
Total
8
29
Yes
22
15
14
10
61
Not at all – Maybe
Yes
Light + Peroxide
3
22
Light
11
15
Peroxide
11
14
Placebo
12
10
Total
37
61
Total
25
26
25
22
98
Total
25
26
25
22
98
Peroxide
Light
Peroxide
+ Light
Light
0.01533
Peroxide
0.01174
0.90291
Placebo
0.00179
0.39775
0.47051
In this question response, overall 62% (61/98) would have recommended this
procedure to a friend. In the Light + Peroxide group, 88% (22/25) would have
recommended the treatment. In the light alone treated group, 58% (15/26) would have
recommended the treatment. This was significantly different than the Light + Peroxide
treated group (p=0.02). In the peroxide alone group, 56% (14/25) would have
Peroxide treated group (p=0.01). In the placebo-treated group, 45% (10/22) would
have recommended the treatment. This response was significantly different than the
Light + Peroxide treated group (p=0.02). Treatment response from light alone was not
different from peroxide (p=0.9) or placebo (p-0.4). The response following treatment by
peroxide alone was not different than the response from subjects treated by placebo
112
alone (p=0.5). The treatment of Peroxide + Light was significantly more frequently
recognized as a treatment to be recommended than any other therapy.
113
Section
5
Discussion
Tooth Shade: As previously demonstrated, the combination of peroxide and light produced
a greater reduction in shade than either peroxide alone or light alone. The average posttreatment reduction was 4.9 shade units in a group that were enrolled with an average of
6.4 shade units. By six months, 73% of this shade reduction was maintained. Also, as
previously demonstrated, light alone produced a reduction in shade although by six months,
the light effect on tooth shade was no longer statistically significant. The effect of peroxide in
this study was only slightly better than light alone, a difference that was never statistically
significant.
Tooth Color: Effects of tooth whitening on changes in lightness (L*) were seen principally
on either peroxide alone treated subjects or those treated by the combination of peroxide
and light. In this data set, it appeared that light alone had little effect on increase in the
lightness parameter. Factorial analysis of these data identified the relative contributions of
peroxide and light to increased lightness. This evaluation indicated that the effect of light
alone was only seen in the immediate post-therapy period whereas the peroxide effect
persisted for 6 months. It has been suggested that this effect of light may be the result of
transient desiccation of the teeth.
Effects of tooth whitening on changes in yellowness (b*) were seen with both peroxide and
light treatments. Factorial analysis of these data identified the relative contributions of
peroxide and light to increased lightness, peroxide being only slightly greater than light. This
change indicated that the effect of light alone and peroxide alone were seen through 6
months. These data indicate that tooth whitening involves both increase in L*, principally a
peroxide effect and decrease in b*, an effect of both peroxide and light. Significant
synergistic effects between light and peroxide appeared to persist only for one week in
reduction of yellowness (b*) and not at all for increase in lightness (L*)/
Placebo Effects: The creation of a placebo light was a difficult quandary. How does
one test a light and, as a control, test the absence of a light. This was addressed by
creating a ruse. The subject was seated in a dental chair, all the materials were applied
including lip balm, opaldam, cheek retractors and placebo gel. The protective glasses
were then placed, the fan on the BriteSmile light was turned on, an audible timer was
set for each 20 minute segment but the light was never turned on. The quality of this
placebo light may be judged by the fact that 41% (9/22) placebo treated subjects would
have recommended the procedure to their friends (see response to question #6 of the
post-treatment questionnaire) and 55% 12/22 reported some degree of tooth whitening
(.see response to question #1 of the post-treatment questionnaire)
114
More than 50% of the reduction in gingival index seen following BriteSmiles treatment was
also seen with placebo treatment. Plaque index , a measure of home care, was reduced by
approximately one-half from baseline in all groups to the same degree and maintained at a
low level throughout the study. The Eastman Dental Bleeding Index (EDBI), Gingival
Crevice Fluid Flow (GCF flow) and GCF resting volume were reduced to the same extent by
both BriteSmile and Placebo treatments. From these observations we may conclude that
the BriteSmile treatment process, even without the tooth whitening is a powerful stimulus to
improve home care and gingival health.
Effects on Measures of Inflammation: In general, all measures of inflammation that
changed were reduced by all groups including placebo. This was true of Gingival Index,
EDBI , GCF flow and volume, Several measures did not appreciably change. This
included pocket depth, bleeding on probing, gingival color measures and IL1β. It is
assumed that the failure of these measures to change is related to insensitivity.
The Oral Microbiology of BriteSmiles Therapy: The BriteSmiles treatment reduces the
number of bacteria on teeth and changes the bacterial composition. One example studied
in detail was the change in proportions of P. gingivalis over the course of the study. This
may be the first recorded instance of having measured the formation of new periodontal
disease lesions. Considering the four treatment groups, treatment with light and/or peroxide
always reduced the number of individuals with high proportions of P. gingivalis. In the
placebo treated group, irrespective of the demonstrated increase in homecare effectiveness,
there appeared to be a proliferation of this periodontal pathogen. Although this occurred
only in a small number of individuals, this is our expectation. Periodontal disease starts at a
few sites only in susceptible individuals.
With investigation of the effect of each therapy by factoral analysis, it was found that light
alone decreased the proportion of P. gingivalis and the effect was most prominent 1 week
after treatment.
115
Section
6
Conclusions
From this study we may conclude the following:
1. The improvement in gingival health detected in previous studies may be largely
explained by the ability of the therapy to motivate subjects to achieve higher
levels of oral hygiene through intensified homecare.
2. The reduction of Gingival Index and proportions of P. gingivalis in periodontal by
light suggest that added direct benefit may be realized from this form of therapy.
3. Tooth whitening by the Britesmiles system occurs primarily by a decrease in
yellowness (a combined light and peroxide effect) and secondarily by an increase
in lightness (a pure peroxide effect).
4. All elements of BriteSmile therapy impact on the oral microbiology. This
interaction is complex and in no way completely explained or described by this
document.
References
Berger-Schunn,A. (1994) Practical color measurement. New York, N.Y.: John Wiley &
sons.
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Associations between bleeding and visual signs of interdental gingival
inflammation. J. Periodontol. 59 (11), 722-727.
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Associations between bleeding and visual signs of interdental gingival
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Schulte, J.R., Morrissette, D.B., Gasior, E.J., Czajewski, MV. (1993) Clinical changes in
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oral hygiene and periodontal condition. Acta Odont. Scand 22: 121-135.
Socransky, SS, Smith, C, Martin, L, Paster, BJ, Dewhirst, FED and Levin, AE (1994)
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specfies to clinical status at the sampled site. J. Clin. Periodontol 1991; 18:766775.
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117

Gingival Health Changes Associated with BriteSmile Tooth

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