dentistry journal

Article

Effects of Amorphous Calcium Phosphate

Administration on Dental Sensitivity during In-Office and
At-Home Interventions
Giacomo Oldoini 1, Antonino Bruno 2,* , Anna Maria Genovesi 1,† and Luca Parisi 3,†
1
Stomatologic Institute of Tuscany, Foundation of Clinic, Research and Post Graduate Program,
55041 Camaiore (Lucca), Italy; [email protected] (G.O.); [email protected]
(A.M.G.)
2
Laboratory of Vascular Biology and Angiogenesis, Scientific and Technological Pole, IRCCS MultiMedica, 20138
Milan, Italy
3
Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, University of Milan, 20122 Milan,
Italy; [email protected]
* Correspondence: [email protected]; Tel.: +39-02-5540-6532 †
These authors contributed equally to this work.

Received: 4 July 2018; Accepted: 17 September 2018; Published: 1 October 2018

Abstract: Background. Tooth bleaching is the most frequently employed whitening procedure in clinics. The
major side effect of tooth bleaching is dental sensitivity during and after the treatment. Here, we evaluated
whether the administration of amorphous calcium phosphate (ACP), during in-office and at-home
procedures may impact on dental sensitivity. Methods. Eighty patients, responding to the study
requirements were enrolled according to the following criteria. Group 1
(n = 40), received in-office, 10% ACP prior to 30% professional hydrogen peroxide application. The
whitening procedure continued at home using 10% carbamide peroxide with 15% ACP for 15 days. Group 2
(n = 40) received only 30% hydrogen peroxide application and continued the whitening procedures at
home, using 10% carbamide hydroxide, without ACP- Casein phosphopeptides (CPP), for 15 days. Dental
sensitivity was recorded with a visual analogue scale (VAS) at baseline, immediately after, and at 15 days
after treatment in the two groups. Results. We observed that patients receiving ACP in the bleaching
mixture experienced decreased dental sensitivity (* p ≤ 0.05), as detected by VAS scale analysis
immediately following the procedures. Patients receiving ACP-CPP during at-home procedures showed a
statistically significant (*** p ≤ 0.0001) reduction of dental sensitivity. Conclusions. We demonstrated that
ACP-CPP administration, while exerting the same whitening effects as in control subjects receiving
potassium fluoride (PF), had an impact on the reduction of dental sensitivity, improving patient compliance.

Keywords: dental sensitivity; tooth bleaching; amorphous calcium phosphate; in-office procedures; at-
home procedures
1 . Introduction

Oral diseases are among the most prevalent chronic diseases worldwide, representing a burden to
health-care services. Treatments of dental diseases are expensive, accounting for between 5% and 10% of
total health-care expenditures in industrialized countries [1]. Demineralization is a process naturally
occurring within the oral cavity, as a consequence of a drop in pH that, if it persists, results in caries induction
and tooth loss [2]. Dentinal hypersensitivity is a common oral condition characterized by pain resulting from
dentine exposure to chemical, thermal, tactile or osmotic factors [3].

Dent. J. 2018, 6, 52; doi:10.3390/dj6040052 www.mdpi.com/journal/dentistry

Dent. J. 2018, 6, 52 2 of 16
Tooth bleaching is a safe and conservative treatment modality to improve the aesthetic appearance of
discolored teeth. Optimal results, along with the low costs for this procedure, have resulted in an increasing
use of tooth bleaching in clinical dentistry [4,5]. In association with this, a plethora of new bleaching agents
have been tested and introduced to the market. These are characterized by different percentages in the
composition of their active principles, such as carbamide peroxide and carbamide, diverse routes of
exposition to those agents and different disposal techniques.
Despite being a totally safe procedure, one of the major undesirable effects of bleaching is dentin
sensitivity, which may occur during and after treatment, thus representing a degree of biological damage
affecting the dentin–pulp complex [6].
Within the large number of techniques described in the literature concerning the external bleaching of
vital teeth, all are based on the direct use of hydrogen peroxide (H 2O2) or its precursor, carbamide peroxide
[7]. Hydrogen peroxide (H2O2) is employed as a whitening agent at concentrations ranging from 25% to 35%
[8,9]. Nevertheless, high concentrations of H 2O2, especially in patients with elevated enamel permeability, or
those where prolonged use of bleaching agents has been reported, resulted in increased dental sensitivity.
Dentinal hypersensitivity represents a very common effect following different whitening treatments.
The association of agents able to reduce dental sensitivity during bleaching procedures still represents a
major issue. The gold standard for professional products is not combined with products for the reduction of
post-treatment sensitivity, lacking dedicated protocols and entrusting the management of the problem to
the use of generic fluorine [10].
Treatment with 35% H2O2 has been associated with alteration of the nervous dentinal activities, both
when treatment has been performed with, or without, mineralizing calcium [11]. There are additional risks
that have been reported from in vitro studies, including tooth erosion, tooth mineral degradation, increased
susceptibility to demineralization, and pulpal damage [12].
Given these dental sensitivity issues, diverse manufacturers are investing their efforts into developing
bleaching gels with lower concentrations of H 2O2. This aims to minimize the side effects related to the
development of peroxide radicals [6,13], when using a bleaching agent with elevated peroxide content.
Along with dental sensitivity, another concern associated with bleaching procedures is represented by
the stability of the teeth color over time. Diverse strategies have been employed to overcome both of these
issues, including professional (referred as in-office) and in-house bleaching procedures.
In-house treatments aim at reducing adversities related to dentinal hypersensitivity. Jorgensen et al.
demonstrated that in-house treatments resulted in a decreased severe sensitivity. The population analyzed
showed that 50% of the subjects had low sensitivity, 10% moderate sensitivity and only 4% severe sensitivity
[14]. However, following two weeks of treatment, the hypersensitivity was completely abrogated in all the
subjects receiving the treatment [14].
Several studies showed that in 60–90% of cases, patients reported increased sensitivity when receiving
professional treatment. Therefore, to prevent and/or reduce the problems of sensitivity, different
approaches were employed, such as combination with 2-hydroxyethyl-glutaraldehyde (G2H) [15]. A study
comparing the effects of G2H against a placebo during in-office treatment, showed a significant reduction of
dentinal sensitivity, without considering the overall aesthetic effect on teeth color [16].
Casein phosphopeptides (CPP) represents another agent used for reducing dentinal sensitivity. CPP can
selectively deliver Ca2+, (PO4)3− ions and fluorine within the tooth enamel [17]. CPP can be associated with
carriers as for amorphous calcium phosphate (ACP). ACP has been largely used by dentists, given its
versatility and that it has been positively associated with caries inhibition [18], mineralizing activities [19],
the inhibition of caries-induced tooth enamel demineralization [18], and increased white spot [20,21].
An in vitro study investigated the ability of casein to inhibit tooth enamel demineralization as related to
fluoride [20]. One hundred and twenty (n = 120) blocks of tooth enamel were exposed to three different
solutions containing casein, fluoride or variable pH. The ACP-treated group showed significantly decreased (p
= 0.05) demineralization, as compared to those treated with fluoride, and the other two groups. Therefore,
the CPP-ACP combination was more effective in preserving the intact surface of the whitened tooth, as
confirmed by scanning electron microscopy (SEM) analysis [10].
A recent meta-analysis summarized major studies on the efficacy of fluorides and ACP-CPP vs fluorides
as monotherapy. Interestingly very few studies have reported on the impact of ACP-CPP administration to
dental sensitivity, suggesting the urgency of this poorly explored topic [22].
The quantity and quality of clinical trial evidence is insufficient to support the long-term effectiveness of
casein derivatives, specifically ACP-CPP, in preventing caries in vivo and treating dentin hypersensitivity or
Dent. J. 2018, 6, 52 3 of 16
dry mouth. We aim to investigate whether the use of ACP, combined with CPP can result in increased
comfort in patients, by reducing dental sensitivity through the treatment.

2. Materials and Methods

2.1. Patient Selection

Patients recruited within the study were enrolled after obtaining informed consent in an institutional
ethics committee-approved study. The study was performed under a clinically approved protocol (n◦421,
16-03-2016), by the Ethics Committee—Milan-Area B, Ospedale Maggiore, Fondazione IRCCS Ca Granda,
Ospedale Maggiore Policlinico Milano.
Investigations were carried out following the principles of the Declaration of Helsinki of 1975. Eighty
patients, responding to the study requirements were enrolled according to the following criteria.
Inclusion:
Age ≥ 18
Overall good healthy condition
With all the dentary settings Smokers
and non-smokers

Exclusion:
Dental hypersensitivity
Known periodontal problems
Subjected to bleaching within 1 year
Pregnancy
Bleeding On Probing (BOP) > 5%, Plaque Index (PI) > 18%

2.2. Study Groups

Patients were divided into two groups as follows: Group 1: 40 patients received, in-office, 15% ACP-CPP
prior to professional 30% hydrogen peroxide application. Group 1 continued the whitening procedures at
home using 10% carbamide-hydroxide with the 15% ACP-CPP for 15 days.
Group 2: 40 patients received, in office, only 30% hydrogen peroxide. Group 2 continued the whitening
procedures at home, using 10% carbamide peroxide without ACP-CPP for 15 days. Two independent
professionals enrolled the patients according to the indications from the literature.

2.3. Procedures
Two weeks prior to bleaching, all the patients received professional hygiene procedures using an
ultrasonic scaler (Mectron Combi Touch, Mectron s.p.a, Genova, Italy) and spherical powder based on
calcium carbonate (Prophylaxis Powder Smooth–Mectron s.p.a, Genova, Italy). The use of this powder seems
to be adapted for this scope to polish the teeth before a dental bleaching procedure. During the professional
hygiene procedures, several indicators were registered, such as the plaque and bleeding index. The at-home
hygiene procedures included the use of interdental brushes (Gum Soft Picks, regular to large size), sonic
toothbrush (Philips Sonicare, Seattle, WA, USA), toothpaste nano idrossiapatite (Biorepair-Cosweell, Bologna,
Italy), in association with ACP relief (Philiphs, Seattle, WA, USA) application (once per day). Patients were
monitored at 2 and 4 weeks following the first application. The VAS (visual analogue scale) system was used
to determine the dental sensitivity event [13,23] and every patient directly provided the VAS value. VAS
analysis was performed before treatment (T0), immediately following the treatment (T1), 15 days (T2) and
30 days (T3) following treatment. The variation in the dental color tone was evaluated at T0 and T3. The
indications for the at-home procedures were as follows:

• Sonicare Philips toothbrush

• Biorepair toothpaste containing nano-hydroxyapatite
• Use of an interdental toothbrush
Dent. J. 2018, 6, 52 4 of 16
2.4. Statistical Analysis
Data were analyzed using Graphpad-Prism7. t-test student for statistical analysis. Statistical significance
was considered at * p ≤ 0.05.

3. Results

3.1. Patient Characteristics

Forty patients received ACP-CPP supplementation and were compared with forty controls. Patients had
an average age of 36 ± 12.28 (mean ± sd), of which 44 were males and 36 females.

3.2. ACP-CPP Administration during Bleaching Procedures Reduces Dental Sensitivity Both in-Office and at
Home
We observed that patients receiving ACP-CPP in the bleaching mixture experienced decreased dental
sensitivity (* p ≤ 0.05), as detected by VAS scale analysis, immediately following the procedures (Figure 1).
We also found that patients receiving ACP-CPP during at-home procedures showed a highly statistically
significant (*** p ≤ 0.0001) reduction of dental sensitivity (Figure 2).
Finally, we determined that ACP-CPP can reduce dental sensitivity both in non-smoking (*** p ≤ 0.0001)
and smoking (*** p ≤ 0.0001) patients (Figure 3).

In-office (T0)
DentalSensitivity(VAS)
Dental
10
sensibility *
8
6
4
2
0

30% H2O2 30% H2O2

ACP-CPP PF
Figure 1. Effects of ACP-CPP combination on dental sensitivity, following in-office oral hygiene procedures.
ACP-CPP treatment significantly reduced dental sensitivity, as compared to the control group (PF),
immediately after treatment (T1). Results are showed as mean ± SEM, * p ≤ 0.05.

At-home (T 15 days)
DentalSensitivity(VAS)
Dental
10
***
8

0
10% Carbamide 10% Carbamide
Dent. J. 2018, 6, 52 5 of 16

ACP-CCP PF
Figure 2. Effects of ACP-CPP combination on dental sensitivity, following at-home oral hygiene procedures.
ACP-CPP treatment significantly reduced dental sensitivity as compared to control (PF) group, during the
following 15 (T15) days. Results are showed as mean ± SEM, *** p ≤ 0.0001.

At home G1 Vs G2/SMOKING HABITAt-home (T

15 days), smoking habits
DentalSensitivity(VAS)
Dental
sensitivityy
10
9
*** **
8
7
6
5
4
3
2
1
0

SMOKER - - + +
10% carbamide + + + +
ACP-CPP + - + PF
-+ -+
Figure 3. Effects of ACP-CPP administration on dental sensitivity, following at-home oral hygiene procedures
as related to smoking habits. ACP-CPP treatment resulted in decreased dental sensitivity, as compared with
the control (PF) group, both in non-smoker and smoker patients. Results are showed as mean ± SEM, ** p ≤
0.01; *** p ≤ 0.0001.
4. Discussion
Tooth bleaching (whitening) is one of the most common and economic methods to treat the
discoloration of teeth [24]. Dental aesthetics, especially tooth color, is of great importance for the majority of
people; and teeth discoloration can negatively influence the quality of life, especially from a social point of
view [25]. The increasing demand for tooth bleaching has driven many manufacturers and researchers to
develop whitening products to be used either in the dental office or at home [24]. However, as for any dental
procedure, bleaching involves risks that include increased tooth sensitivity and mild gingival irritation
[6,23,24,26,27]. The development of these side effects is directly related to the concentration of the
hydrogen peroxide bleach component, duration of the treatment, and the non-bleach composition of the
product used [28]. Therefore, strategies aimed at limiting bleaching-associated dental sensitivity during both
in-office and at-home procedures are urgently needed.
A systematic review and meta-analysis to evaluate the risk and intensity of tooth sensitivity during in-
office and at-home bleaching in adult patients revealed that no differences can be detected, either regarding
the risk/intensity of tooth sensitivity or the effectiveness of the bleaching treatment [29]. This comparison,
however, does not take into consideration variations in the protocols (daily usage time, number of bleaching
sessions, and product concentration) of the bleaching techniques in the studies included [29]. It is now clear
that the use of diverse agents combined with whitening compounds might impact on dental sensitivity and
can shift towards a significant difference in reducing this main concern related to dental whitening.
In line with this relevant issue, we investigated whether ACP-CPP administration might impact on dental
sensitivity, a major complication occurring during bleaching procedures. Dental sensitivity
Dent. J. 2018, 6, 52 6 of 16
was measured using the VAS scale, which is routinely employed in clinics. We first evaluated the effects of
ACP immediately following in-office bleaching procedures.
We showed that ACP supplementation during both in-office and at-home procedures significantly
decreased the dental sensitivity. Patients receiving ACP-CPP experienced reduced dental sensitivity both in
office, immediately following bleaching, and at home. Discomfort during bleaching procedures is a major
issue in the specific field [30], thus the combination of intervention procedures joining together rapid
aesthetic effects with reduced pain for the patients are urgently needed. In this view, aimed at limiting the
discomfort for the patients that must frequently attend in-office bleaching, we determined whether ACP-CPP
administration during at-home procedures might limit dental sensitivity. We found that the administration of
ACP-CPP during both in-office and at-home procedures reduced the dental sensitivity and minimized the use
of anti-inflammatory agents, which is otherwise necessary in cases of high dental sensitivity, improving
patient compliance.

5. Conclusions
Our work demonstrated that the use of ACP-CPP during at-home bleaching procedures, by improving
the patient compliance, reduced both patient discomfort during long and frequent in-office
treatments/visits, as well as the costs, whilst making aesthetic treatment more easily available.

Author Contributions: Conceptualization: G.O., A.B.; A.M.G., L.P.; Methodology: G.O., A.B., L.P.; Statistical analysis: A.B.;
Project administration: A.B., L.P.; Paper drafting: A.B., A.M.G.; Paper reviewing: A.B., A.M.G., L.P. Funding: This research
received no external funding.
Acknowledgments: A.B. has been funded by a Post-Doctoral Fellowship from the Fondazione Umberto Veronesi (FUV)
for the year 2016 until May 2017.
Conflicts of Interest: We wish to confirm that there are no known conflicts of interest associated with this publication
and there has been no significant financial support for this work that could have influenced its outcome.
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© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution (CC BY)
license (http://creativecommons.org/licenses/by/4.0/).
Dent. J. 2018, 6, 52 8 of 16
No Paragraf dan Halaman Kalimat Verb Subject
1 H.1 P.1 Tooth bleaching is the most Is
frequently employed whitening Employed
procedure in clinics
2 H.1 P.1 Eighty patients, responding to Were Responding
the study requirements were Study
enrolled according to the Enrolled
following criteria.
3 H.1 P.1 Group 2 (n = 40) received only Procedures
30% hydrogen peroxide Using
application and continued the
whitening procedures at home,
using 10% carbamide
hydroxide, without ACP- Casein
phosphopeptides (CPP), for 15
days.
4 H1 P1 Dental sensitivity was recorded Was Recorded
with a visual analogue scale
(VAS) at baseline, immediately
after, and at 15 days after
treatment in the two groups.
Results.
5 H1 P1 We observed that patients Patients
receiving ACP in the bleaching Experienced
mixture experienced decreased Procedures
dental sensitivity (* p ≤ 0.05),
as detected by VAS scale
analysis immediately following
the procedures.
6 H1 P1 We demonstrated that ACP- Same Whitening
CPP administration, while Receiving
exerting the same whitening
effects as in control subjects
receiving potassium fluoride
(PF), had an impact on the
reduction of dental sensitivity,
improving patient compliance.

7 H1 P2 dental sensitivity; tooth Procedures

bleaching; amorphous calcium Procedures
phosphate; in-office
procedures; at-home
procedures
8 H1 P3 Oral diseases are among the Are Diseases
most prevalent chronic diseases Representing Services
worldwide, representing a
burden to health-care services.
9 H1 P3 Treatments of dental diseases Are Expenditures
are expensive, accounting for
between 5% and 10% of total
health-care expenditures in
Dent. J. 2018, 6, 52 9 of 16
industrialized countries [1].
10 H1 P3 Demineralization is a process Results
naturally occurring within the Caries
oral cavity, as a consequence of
a drop in pH that, if it persists,
results in caries induction and
tooth loss [2].
11 H1 P3 Dentinal hypersensitivity is a Resulting
common oral condition
characterized by pain resulting
from dentine exposure to
chemical, thermal, tactile or
osmotic factors[3]
12 H2 P1 Tooth bleaching is a safe and Bleaching Tooth
conservative treatment Improve
modality to improve the Appearance
aesthetic appearance of
discolored teeth.
13 H2 P1 Optimal results, along with the Increasing Optimal results
low costs for this procedure, Use
have resulted in an increasing
use of tooth bleaching in
clinical dentistry [4,5].
14 H2 P1 In association with this, a introduced In association with
plethora of new bleaching this
agents have been tested and
introduced to the market.
15 H2 P1 These are characterized by These are
different percentages in the characterized
composition of their active
principles, such as carbamide
peroxide and carbamide,
diverse routes of exposition to
those agents and different
disposal techniques.

16 H2 P2 Despite being a totally safe Bleaching Despite

procedure, one of the major Occur
undesirable effects of bleaching damage
is dentin sensitivity, which may
occur during and after
treatment, thus representing a
degree of biological damage
affecting the dentin–pulp
complex [6].
17 H2 P3 Within the large number of Use Within the large
techniques described in the number of
literature concerning the techniques
external bleaching of vital described in the
teeth, all are based on the
literature
direct use of hydrogen peroxide
concerning the
(H2O2) or its precursor,
carbamide peroxide [7]. external bleaching
Dent. J. 2018, 6, 52 10 of 16
of vital teeth
Hydrogen
Peroxide
18 H2 P3 Hydrogen peroxide (H2O2) is Employed
employed as a whitening agent Concentrations
at concentrations ranging from
25% to 35% [8,9].
19 H2 P3 Nevertheless,high Use Nevertheless,high
concentrations of H 2O 2, Bleaching concentrations of
especially in patients with increassed H 2O 2
elevated enamel permeability,
or those where prolonged use
of bleaching agents has been
reported, resulted in increased
dental sensitivity.

20 H2 P4 Dentinal hypersensitivity Dentinal

represents a very common hypersensitivity
effect following different represents
whitening treatments.
H2 P4 The association of agents able Bleaching The association of
to reduce dental sensitivity agents
during bleaching procedures
still represents a major issue.
H2 P4 The gold standard for Use The gold standard
professional products is not
combined with products for the
reduction of post-treatment
sensitivity, lacking dedicated
protocols and entrusting the
management of the problem to
the use of generic fluorine [10].

H2 P5 Treatment with 35% H2O2 has Treatment with

been associated with alteration 35% H2O2
of the nervous dentinal
activities, both when treatment
has been performed with, or
without, mineralizing calcium
[11].
H2 P5 There are additional risks that Studies There are
have been reported from in Including additional risks
vitro studies, including tooth Increased
erosion, tooth mineral
damage
degradation, increased
susceptibility to
demineralization, and pulpal
damage [12].
H2 P6 Given these dental sensitivity Bleaching Given these dental
issues, diverse manufacturers Concentrations sensitivity issues
are investing their efforts into
developing bleaching gels with
lower concentrations of H2O2.
Dent. J. 2018, 6, 52 11 of 16
H2 P6 This aims to minimize the side Using
effects related to the Bleaching
development of peroxide
radicals [6,13], when using a
bleaching agent with elevated
peroxide content.
H2 P7 Along with dental sensitivity, Concern Along with dental
another concern associated Bleaching sensitivity
with bleaching procedures is
represented by the stability of
the teeth color over time.
H2 P7 Diverse strategies have been Employed Diverse
employed to overcome both of Including Strategies
these issues, including Bleaching
professional (referred as in-
office) and in-house bleaching
procedures.

H2 P8 In-house treatments aim at In-house

reducing adversities related to treatments aim
dentinal hypersensitivity. Jorgensen et al
Jorgensen et al.

H2 P8 The population analyzed The population

showed that 50% of the analyzed
subjects had low sensitivity,
10% moderate sensitivity and
only 4% severe sensitivity [14].
H2 P8 However, following two weeks However,
of treatment, the following two
hypersensitivity was completely weeks of
abrogated in all the subjects treatment
receiving the treatment [14
H2 P9 Several studies showed that in Increased Several studies
60–90% of cases, patients receiving
reported increased sensitivity
when receiving professional
treatment

H2 P9 Therefore, to prevent and/or Employed

reduce the problems of
sensitivity, different approaches
were employed, such as
combination with 2-
hydroxyethyl-glutaraldehyde
(G2H) [15].
H2 P9 A study comparing the effects considering A study
of G2H against a placebo during
in-office treatment, showed a
significant reduction of dentinal
sensitivity, without considering
the overall aesthetic effect on
Dent. J. 2018, 6, 52 12 of 16
teeth color [16].

H2 P10 Casein phosphopeptides (CPP) Used Casein

represents another agent used Deliver phosphopeptides
for reducing dentinal CPP
sensitivity. CPP can selectively
deliver Ca2+, (PO4)3− ions and
fluorine within the tooth
enamel [17]. CPP can be
associated with carriers as for
amorphous calcium phosphate
(ACP).

H2 P10 ACP has been largely used by Used ACP

dentists, given its versatility and Increased
that it has been positively
associated with caries inhibition
[18], mineralizing activities [19],
the inhibition of caries-induced
tooth enamel demineralization
[18], and increased white spot
[20,21].
H2 P11 An in vitro study investigated An in vitro study
the ability of casein to inhibit
tooth enamel demineralization
as related to fluoride [20]. One
hundred and twenty (n = 120)
blocks of tooth enamel were
exposed to three different
solutions containing casein,
fluoride or variable pH
H2 P11 The ACP-treated group showed Compared The ACP-treated
significantly decreased (p = group
0.05) demineralization, as the CPP-ACP
compared to those treated with
fluoride, and the other two
groups. Therefore, the CPP-ACP
combination was more
effective in preserving the
intact surface of the whitened
tooth, as confirmed by scanning
electron microscopy (SEM)
analysis [10].
H2 P12 A recent meta-analysis A recent meta-
summarized major studies on analysis
the efficacy of fluorides and Interestingly very
ACP-CPP vs fluorides as few studies
monotherapy. Interestingly
very few studies have reported
on the impact of ACP-CPP
administration to dental
sensitivity, suggesting the
urgency of this poorly explored
Dent. J. 2018, 6, 52 13 of 16
topic [22].
H3 P13 The quantity and quality of Support
clinical trial evidence is Preventing
insufficient to support the long- Treating
term effectiveness of casein
derivatives, specifically ACP-
CPP, in preventing caries in vivo
and treating dentin
hypersensitivity or dry mouth.
H3 P13 We aim to investigate whether Aim We
the use of ACP, combined with Use
CPP can result in increased Comfort
comfort in patients, by reducing
treatment
dental sensitivity through the
treatment.

H3 P1 2.1 Patients recruited within Study Patients

the study were enrolled after Enrolled
obtaining informed consent in
an institutional ethics
committee-approved study
H3 P1 The study was performed under The study
a clinically approved protocol
(n◦421,
16-03-2016), by the Ethics
Committee—Milan-Area B,
Ospedale Maggiore,
Fondazione IRCCS Ca Granda,
Ospedale Maggiore Policlinico
Milano.
H3 P2 Investigations were carried out Following
following the principles of the Responding
Declaration of Helsinki of 1975. The study
Eighty patients, responding to following
the study requirements were
enrolled according to the
following criteria
H3 P1 2.2 Patients were divided into Patients
two groups as follows: Group 1: Patients received
40 patients received, in-office,
15% ACP-CPP prior to
professional 30% hydrogen
peroxide application
H3 P1 Group 1 continued the Continued Group 1
whitening procedures at home
using 10% carbamide-hydroxide
with the 15% ACP-CPP for 15
days.
H3 P2 Group 2 continued the continued Two independent
whitening procedures at home, professionals
using 10% carbamide peroxide
without ACP-CPP for 15 days.
Dent. J. 2018, 6, 52 14 of 16
Two independent professionals
enrolled the patients according
to the indications from the
literature
H3 P1 2.3 Two weeks prior to Using The patients
bleaching, all the patients
received professional hygiene
procedures using an ultrasonic
scaler (Mectron Combi Touch,
Mectron s.p.a, Genova, Italy)
and spherical powder based on
calcium carbonate (Prophylaxis
Powder Smooth–Mectron s.p.a,
Genova, Italy).
H3 P1 The use of this powder seems The use
to be adapted for this scope to Seems
polish the teeth before a dental Adapted
bleaching procedure.
H3 P1 Patients were monitored at 2 Following
and 4 weeks following the first
application
H3 P1 The VAS (visual analogue scale) Used The VAS [visual
system was used to determine Determine analogue scale]
the dental sensitivity event
[13,23] and every patient
directly provided the VAS value
H3 P1 VAS analysis was performed Performed
before treatment (T0), Treatment
immediately following the
treatment (T1), 15 days (T2)
and 30 days (T3) following
treatment
H4 P1 2.4 Data were analyzed using Were
Graphpad-Prism7. t-test
student for statistical analysis.
Statistical significance was
considered at * p ≤ 0.05.

H4 P1 3.1 Forty patients received ACP- Were

CPP supplementation and were
compared with forty controls.

H4 P1 Patients had an average age of Had

36 ± 12.28 (mean ± sd), of Were
which 44 were males and 36
females.
H4 P1 3.2 We observed that patients We observed
receiving ACP-CPP in the Bleaching
bleaching mixture experienced Experienced
decreased dental sensitivity (*
Dent. J. 2018, 6, 52 15 of 16

p ≤ 0.05), as detected by VAS Following

scale analysis, immediately
following the procedures
(Figure 1).
H4 P1 We also found that patients We
receiving ACP-CPP during at- Significant
home procedures showed a
highly statistically significant
(*** p ≤ 0.0001) reduction of
dental sensitivity (Figure 2).

H4 P2 Finally, we determined that We

ACP-CPP can reduce dental
sensitivity both in non-smoking
(*** p ≤ 0.0001) and smoking
(*** p ≤ 0.0001) patients
(Figure 3).

H5 P1 Tooth bleaching (whitening) is Is Tooth bleaching

one of the most common and (Whitening)
economic methods to treat the Dental aesthetics
discoloration of teeth [24].
Dental aesthetics, especially
tooth color, is of great
importance for the majority of
people; and teeth discoloration
can negatively influence the
quality of life, especially from a
social point of view [25].
H5 P1 The development of these side Is The development
effects is directly related to the
concentration of the hydrogen
peroxide bleach component,
duration of the treatment, and
the non-bleach composition of
the product used [28].
H5 P2 It is now clear that the use of Use It
diverse agents combined with Is
whitening compounds might
impact on dental sensitivity and
can shift towards a significant
difference in reducing this main
concern related to dental
whitening.

H5 P3 In line with this relevant issue, investigated We

we investigated whether ACP-
CPP administration might
impact on dental sensitivity, a
major complication occurring
during bleaching procedures
H6 P3 We first evaluated the effects of Evaluated We
Dent. J. 2018, 6, 52 16 of 16
ACP immediately following in-
office bleaching procedures.
H6 P4 We showed that ACP Showed we
supplementation during both
in-office and at-home
procedures significantly
decreased the dental sensitivity
H6 P4 In this view, aimed at limiting View we
the discomfort for the patients Attend
that must frequently attend in- Administration
office bleaching, we determined
whether ACP-CPP
administration during at-home
procedures might limit dental
sensitivity.
H6 P4 We found that the Administration We
administration of ACP-CPP Found
during both in-office and at-
home procedures reduced the
dental sensitivity and minimized
the use of anti-inflammatory
agents, which is otherwise
necessary in cases of high
dental sensitivity, improving
patient compliance.
H6 P1 5. Our work demonstrated that Work
the use of ACP-CPP during at- Use
home bleaching procedures, by Treatments/visits
improving the patient
compliance, reduced both
patient discomfort during long
and frequent in-office
treatments/visits, as well as the
costs, whilst making aesthetic
treatment more easily available