2.3. Application method
The targeted area was first cleaned with a cotton
pellet. Then, the dentist mixed the powder with
the liquid for 15 s to obtain a paste that was
immediately applied on the treated areas with
a microbrush by gently brushing for 2 min (Fig.
1 to 4). In the same visit, both test and placebo
treatments were applied to each patient according
to a randomization list. Patients were then asked
to rinse their mouth, and within 15 min after the
treatment the blinded dentist applied the same air
blast stimuli under the same conditions to assess
pain scores after treatments (POST). Patients were
recalled for hypersensitivity assessment of the
treated areas after 1 week. At that time point, after
data collection, both dentist and patients were un-
blinded regarding the test or placebo treatment,
and the test treatment was applied to the area
that previously received the placebo compound.
Patients were then recalled after 1, 3 and 6 months
and at each recall the dentist assessed only tooth
areas that were treated with test compound since
the beginning of the trial.
Figure 2. Application of the tested DD on right maxillary
teeth (test site), same area depicted in Fig 1.
2.3. Statistical analysis
All statistical analyses were performed using
statistical software (JMP 10.0, SAS Institute Inc, Cary,
NC, USA). A preliminary check of the normality of
distribution and homogeneity of variances was
performed using Shapiro-Wilk’s and Levène’s tests
(p<0.0001 and p=0.0014, respectively). Since
data did not belong to continuous variable (0-10
ordinal VAS scores), were not normally distributed
and homoscedasticity was not respected, non-
parametrical
ANOVA
and
non-parametric
comparisons for each pair using Wilcoxon method
(p<0.05) were used to highlight significant
differences between groups.
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Figure 3. Dental occlusal erosions bilaterally on palatal
side of maxillary frontal and lateral teeth. Air blast test scored
8. Patient was referred to a gastroenterologist physician. He
was later diagnosed with gastroesophageal reflux disease
(GERD) and given treatment. Patient refused restorative
therapies, requesting treatment of pain symptoms only.
Figure 5. Box plot depicting the main findings of the study. The
minimum and maximum values and the 25th, 50th, and
75th percentiles are shown in red. Different superscript letters
indicate significant differences between groups (p<0.05) as
assessed by Wilcoxon method. The test DD was compared with a
placebo for up to 1 week, then its effect on reducing pain
perception was monitored for 6 months.
Figure 4. Application of the test DD on the same area as in Fig 3.
Figure 1. Patient requesting desensitization treatment for
vestibular areas of maxillary teeth. No presence of cervical
lesions or abrasions could be identified as well as other
lesions, yet upper right and upper left canines and premolars
scored 7 on VAS after air blast test.
CALCIUM PHOSPHATE NANOPARTICLES REDUCE DENTIN HYPERSENSITIVITY:
A RANDOMIZED, PLACEBO-CONTROLLED STUDY
3. Results
All 25 subjects completed the trial without requesting
alternative desensitization treatments or dropping
out from the trial. No adverse reactions were
reported. The results of the study are displayed in
Fig. 5. Both DD and placebo significantly decreased
VAS scores comparing POST and PRE (p<0.0001)
measurements, thus showing similar efficacy (35%
and 28%, respectively). DD application further
decreased scores after 1 week (63% in comparison
with PRE), while placebo application did not show
significant differences when compared to POST
(p=0.09). The scores from the areas treated with
the DD maintained, throughout the observational
period, the levels obtained after 1 week (maximum
decrease in scores = 69% after 3 months). At 6
months, a small, non-significant increase in VAS
scores was also observed.
4. Discussion
Dentin hypersensitivity is an increasing occurrence,
and dental materials or procedures able to reduce
the patient’s sensitivity are increasingly needed. A
variety of therapies are currently available, 2,4,6 but
the most modern and biocompatible approach
seems to be the one aiming at reconstituting
a barrier and closing the open orifices of the
tubules by using biomimetic materials and
techniques. 13,14,15,16
Stoma Edu J. 2017;4(2): 102-107
http://www.stomaeduj.com
In this study, we assessed the clinical efficacy,
expressed as pain reduction from hypersensitive
tooth areas, of a biomimetic, hydroxyapatite-
forming dentin desensitizer (DD) based on calcium
phosphate nanoparticles.
The first null hypothesis could not be fully
rejected, since immediately after application
there was no significant difference between DD
under investigation and placebo, meaning that
the reaction to the test DD immediately after
application could not be due to its activity, but
simply to a placebo effect. After one week, however,
there was a highly significant difference between
placebo and test DD. In fact, the test DD required
1 week to reach the significantly lowest scores of
pain perception, and this level was maintained for
up to 6 months. The second null hypothesis could,
therefore, be rejected.
The tested DD is a biomimetic desensitizing
compound based on the reaction between
tetracalcium phosphate and dicalcium phosphate
anhydrous in the presence of fluoride ions.
Once water is added, the reaction produces
hydroxyapatite and small parts of fluorapatite
nanoparticles that precipitate as an amorphous
layer on the tooth structures. Since nanocrystal
deposition on enamel and dentin structures is
driven by collagen backbone structures, one may
speculate that the presence of these structures
inside dentine tubules may help organize
deposition of hydroxyapatite and fluorapatite.
Thanatvarakorn et al. in 2013 17 provided some data
in support of this hypothesis. They showed that the
tested DD developed an immediate reduction in
dentin permeability and an effective integration
of the calcium phosphate rich layer with dentin
surfaces, enhancing mineralization under oral
Stomatology Edu Journal
conditions. 17 The data obtained in this study
could convey some indirect hints regarding the
activity of the compound. It seems clear that the
deposition of an amorphous layer of nanocrystals
on the hypersensitive tooth surfaces does not
lead to a reduction in pain perception greater
than placebo effect. It is very likely, however,
that hydroxyapatite and fluorapatite deposition
inside dentinal tubules takes place at least over
a one-week time period after application and is
responsible for the significant reduction in pain
perception when confronted to the placebo at 1
week or to the initial values. Our results confirm
the assumptions of Zhou et al. 10 thus providing
a clinical confirmation of their in vitro results. In
their study, the effectiveness of the same DD was
evaluated in reducing dentin permeability and
tubule orifice occlusion. It was found that the two
parameters improved depending on the time
until maximum values in permeability reduction
and tubules occlusion were found after one week
[10]. These results are in good correlation with
those of the present study, meaning that dentine
permeability and occlusion of tubuli orifices
(>50%) can be good indicators of reduction in
pain perception.
In our study, it was found that the reduction in
pain perception due to the test DD did not remain
significantly different between the different time
points starting from 1 week for up to 6 months. This
means that the effects obtained by the tested DD
(remineralization, reduction in dentin permeability
and tubule occlusion 10,17 ) are long-lasting, however
additional studies are needed to ascertain if the
test DD may express its activity over extended
observation times up to one or several years.
The study was performed under conditions as
close as possible with those of similar studies 14,15
in order to evaluate possible differences yielded
from geographical areas or pain perception. The
tested DD compound was the same as the one
used by Mehta et al. in 2014 14 and similar to the
one tested by the same research group one year
after. 15 The study design was the same as in Mehta
et al., 2015, 15 except for the placebo follow-up that
was stopped after 1 week in the present study. The
statistical analysis was different in methodology,
since in the present study no parametric analysis of
data could be applied. One would speculate that,
given that the material, the study design and the
patient recruitment were very similar among these
studies, similar results would be obtained. A first
observation can be made comparing the initial pain
scores to those after treatment and 1-week follow-
up. The initial scores in the present study were higher
than those from Mehta et al., 14,15 and reduction in
pain perception after at least one week of treatment
was higher than the results of Mehta et al., 15 but
similar to the results the same Authors obtained one
year earlier. 14
Many different explanations for these results may
be provided, including the fact that pain remains an
extremely subjective perception being influenced
CALCIUM PHOSPHATE NANOPARTICLES REDUCE DENTIN HYPERSENSITIVITY:
A RANDOMIZED, PLACEBO-CONTROLLED STUDY
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