Received: 8 February 2018 Revised: 8 June 2018 Accepted: 5 August 2018

DOI: 10.1111/jerd.12420

REVIEW ARTICLE

Dental hypomineralization treatment: A systematic review

Ana Sofia Estima da Cunha Coelho PhD1,2 | Pedro Carlos Machado Mata DDS3 |
Carolina Alves Lino DDS1 | Viviana Marisa Pereira Macho PhD3 |
Cristina Maria Ferreira Guimarães Pereira Areias PhD3 |
Ana Paula Mendes Alves Peixoto Norton PhD3 | Ana Paula Coelho Macedo Augusto PhD3

1
Dentistry Area, Faculty of Medicine,
University of Coimbra, Coimbra, Portugal Abstract
2
iCBR, Coimbra Institute of Clinical and Introduction: Defects in the maturation stage of amelogenesis result in a normal volume of
Biomedical Research, Faculty of Medicine, enamel but insufficient mineralization, called hypomineralization. Molar-incisor hypomineraliza-
University of Coimbra, Coimbra, Portugal
tion (MIH), amelogenesis imperfecta and dental fluorosis (DF) are examples of such defects.
3
Faculty of Dentistry, University of Oporto,
Objective: To evaluate the effectiveness of the treatments applied to the different forms of
Oporto, Portugal
dental hypomineralization.
Correspondence
 Materials and Methods: PubMed, Scopus, Cochrane Library, Web of Science, and Embase were
Dr Ana Sofia Estima da Cunha Coelho, Area de
Medicina Dentária Av. Bissaya Barreto, Bloco screened. The research was limited to studies published in English, Spanish, and Portuguese,
de Celas, 3000-075 Coimbra. until May 30, 2018. The research question was formulated following the Population, Interven-
Email: anasofiacoelho@gmail.com
tion, Comparison, Outcome strategy. The quality of the methodology of each article was evalu-
ated employing the Cochrane Handbook for Systematic Reviews.
Results: From the initial research, 7895 references were obtained, of which 33 were included in
the systematic review. The following treatments were reported: desensitizing and remineralizing
products, resin infiltration, restorations, fissure sealants, tooth bleaching, enamel microabrasion
and calcium, and vitamins supplements.
Conclusions: Although the results are suggestive, there is a clear need for a greater uniformity
of the methodologies, thus allowing for the development of clinical guidelines. Nevertheless, it
was possible to identify several effective treatments for teeth with MIH (arginine pastes or fluo-
ride varnishes) and DF (tooth bleaching and/or enamel microabrasion).
Clinical Significance: Because MIH, amelogenesis imperfecta, and DF are commonly seen in
dental daily practice, it is extremely important to analyze the literature regarding its treatment.

KEYWORDS

amelogenesis imperfecta, dental fluorosis, hypomineralization, molar-incisor

hypomineralization, treatment

1 | I N T RO D UC T I O N of fragile and quantitatively defective enamel (hypoplasia).2,3 Con-

versely, defects occurring during the maturation stage result in a
Dental enamel is a tissue composed of hydroxyapatite crystals (98%) normal volume of enamel but with insufficient mineralization
associated to a matrix composed of water and organic matter (2%) (hypomineralization).3–5 Within the dental hypomineralization defects,
1
arranged in an elongated hexagonal configuration. It is the hardest it is possible to include molar-incisor hypomineralization (MIH), amelo-
tissue of the human body and its formation is controlled by differenti- genesis imperfecta (the hypomaturated type and the hypocalcified
ated cells, the ameloblasts.1,2 The life cycle of these cells is comprised type), and dental fluorosis (DF).6–9
of 5 stages: presecretory, secretory, transition, maturation, and post- MIH is defined as a demarcated and qualitative enamel defect of
maturation.1 Generally, defects that occur during the secretory phase systemic origin that affects one or more permanent molars and may
result in minor matrix secretion and, consequently, in the production also affect the permanent incisors.8,10 Less frequently, MIH-like

26 © 2018 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/jerd J Esthet Restor Dent. 2019;31:26–39.

DA CUNHA COELHO ET AL. 27

defects have been described in permanent canines and premolars and The aim of this systematic review was to evaluate the effective-
in primary second molars. Although many studies have researched the ness of treatment methodologies applied to dental hypomineraliza-
potential factors involved in the occurrence of MIH, results have been tion: MIH, AI (hypomatured and hypocalcified type), and DF.
inconclusive. The most frequently suggested factors are neonatal
problems (prematurity and/or low birth weight), early childhood ill-
nesses (asthma or bronchitis), fever, hospitalization, oxygenation with-
2 | M A T E R I A L S A N D M ET H O D S
out intubation, and antibiotic therapy. Some authors have suggested a
genetic-based etiology.11–18 The prevalence of MIH in children and
For this systematic review, a database search was performed in
adolescents varies among different studies, with reported values
PubMed (www.ncbi.nlm.nih.gov/pubmed), Scopus (www.scopus.com),
between 2.8% and 40%.19 Clinically, MIH is characterized by variable-
Cochrane Library (www.cochranelibrary.com), Web of Science (www.
sized opacities, with a white to yellow/brownish staining and a
webofscience.com), and Embase (www.embase.com; Table 1). The
defined demarcation between healthy and affected enamel.20,21 Pos-
research was limited to articles in English, Spanish, and Portuguese,
teruptive breakdown may occur because of masticatory forces, either
published until May 30, 2018.
immediately or later, which facilitates the accumulation of bacterial
The research strategy was formulated following the Population,
plaque. These factors lead to a subclinical inflammatory response and
Intervention, Comparison, Outcome form36 (Table 2).
subsequent hypersensitivity.10,22
Only clinical trials on at least 10 human subjects having one or
Amelogenesis imperfecta (AI) represents a set of developmental
more teeth with enamel hypomineralization (because of MIH, AI, or
defects of genetic origin that interfere with the structure and clinical
DF) were included. The affected teeth had to be in need of treatment
appearance of the enamel of all or nearly all teeth.5,6 AI has a reported
and the results of at least 1 treatment method had to be reported.
prevalence up to 0.14%.23,24 Witkop25 recognizes 4 main types of AI
Articles evaluating the success of preventive treatments were also
based on their phenotype: hypoplastic, hypomatured, hypocalcified
included.
(hypomineralized), and hypomatured-hypoplastic. The hypocalcified
As so, during the selection process review articles, cell and animal
and hypomatured forms are the only types that can be classified as
studies, letters to the editor, clinical cases, and comments were
hypomineralization defects.1,25 The hypocalcified type is characterized
by enamel of normal thickness but with incomplete matrix mineraliza- excluded. Articles whose abstracts were unavailable online and stud-

tion, which results in a soft and fragile enamel. 26

In the hypomatura- ies that exclusively measured the participants’ quality of life were also

lized type, the enamel has a normal thickness but it is opaque and excluded.

brittle because of an irregularity that occurs during the hydroxyapatite All titles and abstracts were examined by 2 reviewers in order to

crystals development in the maturation phase. 26,27 select the relevant studies. Selection of the eligible studies was per-

Exposure of the developing enamel organ to excessive amounts formed by 2 reviewers and opinions of a third reviewer were called
7
of fluoride results in DF. The prevalence of children and adolescents upon in more ambiguous cases. Additional studies were selected by
with DF ranges between 4% and 70%, with the mild forms being the analyzing the references from the included articles. The methodology
28–30 applied during the article selection in the systematic review is outlined
most common. Mildly fluorosed enamel is characterized by nar-
row, diffuse, poorly demarcated and bilateral white lines, and by an in Figure 1.
31–33 The quality of each article’s methodology was assessed through
increase in the subsurface porosity. The more severe forms may
gain a yellow/brown coloration and the enamel may present preerup- the Cochrane Handbook for Systematic Reviews version 5.1.0.37 Each
tive or posteruptive breakdown, which leads to a greater susceptibility of the selected studies was determined as possessing a high risk of
to dental caries. DF can occur in both the primary and permanent bias (if 3 or more parameters were assessed with high risk of or
dentitions.4,30,34,35 unclear bias), medium risk (if 1 or 2 parameters were assessed with

TABLE 1 Databases consulted and their search formulas

Databases Search formulas

PubMed ((((((((((Hypominerali*) OR Hypocalcifi*) OR Hypomatur*) OR mottled enamel) OR ((MIH OR molar-incisor-hypominerali*)))
OR dental fluorosis[MeSH terms]) OR amelogenesis imperfecta[MeSH terms]))) AND ((((((((management) OR treatment)
OR rehabilitation[MeSH terms]) OR prevention) OR reminerali*) OR therapy) OR fluoride[MeSH terms])))
Scopus TITLE-ABS-KEY(hypomineralization OR hypocalcification OR hypomaturation OR “mottled enamel” OR MIH
OR “molar-incisor-hypomineralization” OR “dental fluorosis” OR “amelogenesis imperfecta”) AND
TITLE-ABS-KEY(management OR treatment OR rehabilitation OR prevention OR remineralization OR therapy OR fluoride)
Web of science (((((((Hypominerali*) OR Hypocalcifi*) OR Hypomatur*) OR mottled enamel) OR (MIH OR molar-incisor-hypominerali*))
OR fluorosis) OR amelogenesis imperfecta) AND TOPIC: (((((((management) OR treatment) OR rehabilitation)
OR prevention) OR reminerali*) OR therapy) OR fluoride)
Cochrane Library (((((((Hypomineralization) OR Hypocalcification) OR Hypomaturation) OR mottled enamel) OR fluorosis)
OR “Amelogenesis imperfecta”)) AND (((((((management) OR treatment) OR rehabilitation) OR prevention) OR
remineralization) OR therapy) OR fluoride)
Embase Hypomineralization OR hypocalcification OR hypomaturation OR mih OR “amelogenesis imperfecta”/exp OR “fluorosis”/exp
AND (“management”/exp OR treatment OR “rehabilitation”/exp OR “prevention”/exp OR “dental procedure”/exp
OR “therapy”/exp OR “fluoride”/exp OR remineralization)
28 DA CUNHA COELHO ET AL.

TABLE 2 PICO strategy used in the evaluation of scientific evidence

Parameter Evaluation
Population (P) Patients with enamel hypomineralization because of MIH, AI or DF
Intervention (I) Prevention, treatment of hipersensitivity and/or rehabilitation of affected teeth (through restorative, endodontic,
prosthetic, surgical or orthodontic methods)
Comparison (C) Placebo or without intervention;
Different treatment methods
Outcome (O) Successful prevention (no need for further interventions), improved esthetics and/or successful rehabilitation of affected teeth

high risk of or unclear bias), or low risk (if all the parameters were eval- studied the effect of casein phosphopeptides and amorphous calcium
uated with low risk of bias). phosphate (CPP-ACP) pastes. Grossi et al.43 used the atraumatic restor-
Given the methodological variability present in the studies ative treatment (ART) protocol and a glass hybrid restorative system
included in the systematic review it was not possible to perform a whereas Sönmez and Saat48 restored the affected teeth with a resin
quantitative analysis (meta-analysis). composite and evaluated the effects of deproteinization of the hypomi-
neralized enamel and of different cavity forms. Bekes et al.39,44
employed an arginine paste and Lygidakis et al.44 used fissure sealants.
3 | RESULTS Of the 12 studies, 939,41–46,48,49 only performed a visual assessment,
using different methods and indices, whereas Bakkal et al.38 and Biondi
The initial survey resulted in 7895 references of which 2008 were et al.40 used laser fluorescence, and Restrepo et al.47 analyzed the quan-
deleted because of duplication. After analysis of titles and abstracts, titative light-induced fluorescence.
56 articles were considered for full text analysis. Thirty-three studies Regarding DF, 850,53,57,60,62,65,67,68 of the selected studies
were included in the systematic review. Of these, 12 were related to assessed the bleaching of the affected teeth, 951,52,54–56,63,64,69,70
MIH and 21 to DF. No AI studies met the inclusion criteria. analyzed the effects of enamel microabrasion, 452,54,56,60 evaluated
The results for MIH and DF are presented in Tables 3 and 4, the effect of a combined treatment (tooth bleaching and enamel
respectively. microabrasion) and Gugnani et al.58 used a resin infiltrant. Gupta
40 45
Among the MIH studies, Biondi et al., Ozgul et al., and Restrepo et al.59 and Mehta et al.66 studied the effect of oral administration of
et al.47 applied fluoride varnish, whereas Fragelli et al.41,42 and Souza calcium and vitamins in reducing lesion size whereas Hasanuddin
et al.49 applied fluoride varnish and then restored/sealed the affected et al.61 applied fissure sealants to molars with DF. All authors analyzed
38 40 45 46
teeth. Bakkal et al., Biondi et al., Ozgul et al., and Pasini et al. the effectiveness of the treatments through a visual evaluation. Of

7895 References from the initial search

(Pubmed = 2641; Cochrane Library = 93; Web of Science = 2772; SCOPUS = 1724;
Embase = 665)

7839 Articles excluded for being duplicates or

after analysis of titles and abstracts

56 Articles selected for full text

examination

23 Studies excluded after reviewing the full text:

No group stratification by type of lesion (n=11)
Sample < 10 (n=4)
Case-report (n=4)
Unequal follow-up between groups (n=3)
Not an intervention study (n=1)

33 Articles included in the review

FIGURE 1 Flow diagram of the study selection process for the systematic review
TABLE 3 Studies included in the systematic review for the treatment of incisor-molar hypomineralization

Authors Age
(year) Participants (n) (years) Intervention Measurement Follow-up Results Comments
Bakkal 38 teeth 7-12 I: CPP-ACP LF 30 d I: T0: 3.739  2.911; T1: 1.826  1.775a;
et al.38 II: CPP-ACFP II: T0: 5.267  2.815; T1: 2.667  2.320b
Bekes 12 6-14 2 applications of an arginine SCASS, WBFS 8 wk Air blast sensitivity (SCASS) Each participant was given a toothpaste, a
et al.39 paste T0: 2.1  0.3; T1: 0.8  0.9a toothbrush and a mouthwash
DA CUNHA COELHO ET AL.

Tactile sensitivity (WBFS)

T0: 2.1  2.6; T1: 0.6  1.1a
Biondi 55 6-17 I: fluoride varnish (3× 1 min); II: LF 45 d Mild lesions All participants received dietary and oral hygiene
et al.40 CPP-ACP; III: fluoride varnish I: T0: 18.57 5.88; T1: 14.59  4.88c; instructions. Open caries lesions were
containing tricalcium II: T0: 17.37  7.22; T1: 15.15  5.19c; inactivated with a reinforced zinc oxide-
phosphate III: T0: 20.04  5.07; T1: 14.18  3.65c; eugenol material
Moderate lesions
I: T0: 56.88  15.71; T1: 31  11.97;
II: T0: 29.53  17.85; T1: 27.31  15.77;
III: T0: 28.85  8.99; T1: 23.1  7.74
Fragelli 21 6-9 1 mo of weekly applications of Photographs + 12 mo Survival rate: All participants received oral hygiene instructions
et al.41 (48 teeth) fluoride varnish + glass impressions T1: 35/45 (78.8%)
ionomer restoration
Fragelli 25 (MIH) + 16 6-8 4 weekly applications of fluoride USPHS 18 mo Success rate:
et al.42 (control) varnish + resin fissure sealant I: 72%; II: 62%
Grossi 44 7-13 Glass hybrid restorative system Clinical 12 mo Success rate: Success: present and satisfactory or with
et al.43 (60 teeth) (ART protocol) evaluation 98.3% deficiency at cavity margin less <0.5 mm
Lygidakis 47 6-7 I: fissure sealants with double Clinical 4y Fully sealed (%): I: 70.2; II: 25.5b All participants received oral hygiene instructions
et al.44 adhesive II: fissure sealants evaluation Partially sealed (%): I: 29.7; II: 44.6b + fluoride varnish every 6 mo
without adhesive Unsealed (%): I: 0; II: 29.7b
Ozgul 33 7-12 Ia: fluoride varnish; Ib: VAS (0, no 3 mo Ia: 3.21 (2.15)c; Ib: 2.93 (3.10)c Participants received toothbrushes, toothpastes
et al.45 ozone + fluoride varnish; IIa: pain after IIa: 4.53 (3.16)c; IIb: 4.87 (2.47)c and oral hygiene instructions
CPP-ACP; IIb: cold stimuli; IIIa: 3.92 (2.43)c; IIIb: 3.62 (2.84)c
ozone + CPP-ACP; IIIa: 10, worst Unit—difference with baseline (sum of squares)
CPP-ACFP; IIIb: pain)
ozone + CPP-ACFP
Protocol repeated after 4 wk
Pasini 40 8-13 I: CCP-ACP SCASS + VAS 120 d SCASS: I: T0: 2.4  0.6; T1: 1.1  0.4a; II: T0: Each patient used a fluoride toothpaste 3 times a
et al.46 II: fluoride toothpaste + fluoride (0, no pain; 2.3  0.5; T1: 2.2  0.4 day
varnish after 120 d or 10, worst VAS: I: T0: 7.8  1; T1: 3.8  0.6a;
composite restoration in pain) II: T0: 7.5  1.5; T1: 7.2  0.8
severely damage teeth
Restrepo 51 9-12 I: 4 weekly applications of QLF 4 wk T0: I: −7.47  0.43; II: −7.22  0.40; T1: Participants received dietary and oral hygiene
et al.47 (I: 26, II: 25) fluoride varnish; II: negative I: −6.32  0.50; II: −6.43  0.64 (ΔF, %) instructions
control
Sönmez 95 teeth 8-12 Composite restoration: USPHS 2y Retention rates:
and (MIH) + 31 I: cavity form Id; II: cavity form I: 81.3%;
Saat48 (control) IIe; III: cavity form IIe + 5% II: 58.1%c;
sodium hypochlorite (60 s) III: 78.1%; IV: 87.1%
after etching; IV: conventional
cavities (non-MIH teeth)
(Continues)
29
 30 DA CUNHA COELHO ET AL.

these, 1451,52,54–58,63–65,67–70 resorted to photographs and 253,62

fluoride phosphate; LF, laser fluorescence; QLF, quantitative light-induced fluorescence; SCASS, Schiff Cold Air Sensitivity Scale; SEA, self-etching adhesive; T0, baseline; T1, follow-up; TEA, total-etch adhesive; USPHS,
Abbreviations: ΔF, deviation of fluorescence; ART, atraumatic restorative treatment; CPP-ACP, casein phosphopeptides and amorphous calcium phosphate; CPP-ACFP, casein phosphopeptides and amorphous calcium
All participants received dietary and oral hygiene
used a chromameter.

instructions + fluoride gel application every

Several studies39,41,43,50,53,55,57,59,63,67,68,70 did not have a
comparative group and were therefore categorized as having a
high risk of bias. The risk of bias for each remaining study was ana-
lyzed and the results are shown in Table 5. Four studies47,49,54,58
were assessed as having a medium risk of bias. The final 17
studies38,40,42,44–46,48,51,52,56,60–62,64–66,69 were evaluated as pos-
sessing a high risk of bias.
Comments

Cavity form II: soft carious tissue and porous enamel surrounding cavity margins were removed until the bur met with significant resistance from the hypomineralized enamel.
4 | DI SCU SSION
6 mo

Bekes et al.39 proposed the application of an arginine paste to MIH-

affected teeth in order to reduce the associated hypersensitivity. Argi-
nine promotes the sealing of the dentinal tubules, decreasing the
number of sensory afferents exposed, thus blocking the hydrodynamic
pain mechanism.71,72 Yang et al.72 performed a meta-analysis on the
application of arginine toothpaste as a desensitizing agent and con-
cluded that an 8-week use decreased dental hypersensitivity. The
results are consistent with Bekes et al.39 who reported a significant
Cavity form I: soft carious tissue and surrounding hypomineralized enamel were removed until cavity margins ended in sound enamel.

decrease in hypersensitivity 8 weeks after 2 applications of an argi-

nine desensitizing paste on teeth with MIH. Such results suggest that
II: 12/22 (54.6%)
I: 13/19 (68.4%)

arginine paste can be recommended as a desensitizing agent for teeth

Survival rate:

affected with MIH.

Results

Restrepo et al.47 and Ozgul et al.45 reported the reduction of

dental hypersensitivity in MIH-affected teeth after application of
fluoride varnish. These results are similar to those found by other
Follow-up

authors73–77 in patients without MIH, who reported a decrease in

18 mo

dental hypersensitivity after the use of fluoride varnishes. Thus, fluo-

ride varnish treatments may be considered a therapeutic option in
Measurement

cases of MIH-related dental hypersensitivity.

Though Biondi et al.40, Ozgul et al.,45 Bakkal et al.,38 and Pasini
USPHS

et al.46 reported positive results after applying CPP-APC pastes, its

effectiveness as desensitizing and remineralizing agent has been
questioned74,78–82 and long-term clinical trials with large samples are
II: resin composite with TEA
I: resin composite with SEA

needed to validate the results before its widespread recommendation.

(1 mo) + glass ionomer
Weekly fluoride varnish

It is of particular importance for patients with MIH the identifica-

restoration (2 mo) +

United States Public Health Service; WBFS, Wong Baker Faces Scale.

tion of effective agents in the treatment of dental hypersensitivity

Comparison with baseline is statistically significant at P < 0.001.
Comparison with baseline is statistically significant at P < 0.01.

Comparison with baseline is statistically significant at P < 0.05.

because of the impact that this condition has on their quality of life. It
Intervention

has further been described that this hypersensitivity weakens the

action of anesthetic agents, which makes pain control difficult and
reduces patient comfort during dental appointments.10,22
Fragelli et al.42 and Lygidakis et al.44 suggested that fissure seal-
ants may be an effective preventive treatment for MIH teeth. Lygida-
(years)

kis et al.44 reported that fissure sealants applied using an adhesive

Age

6-8

system had a higher retention rate than those that were applied with-
out it. However, results regarding the use of an adhesive prior to fis-
Participants (n)

sure sealant application are conflicting.83–86 In 2015 a meta-analysis

II: 22 teeth)
(I: 19 teeth,
(Continued)

carried out by Botton et al.87 concluded that the nonuse of an adhe-

sive resulted in a higher retention rate of fissure sealants in teeth
18

without hypomineralization. As so, further studies are needed in order

et al.49

to confirm the results reported by Lygidakis et al.44

Authors
TABLE 3

Souza
(year)

Fragelli et al.41 evaluated the success of glass ionomer restora-

tions in teeth affected with MIH, reporting a success rate of 78.8% at
b

d
e
a

c
TABLE 4 Studies included in the systematic review for the treatment of DF

Authors (year) Participants (n) Age (years) Intervention Measurement Follow-up Results Comments
50
Bailey et al. 14 20-46 30% hydrogen peroxide +36% Visual – Success rate: Transient increased thermal
hydrochloric acid (4× maximum) 14/14 sensitivity in 1 case
Bezerra et al.51 15 8-13 I: 37% phosphoric acid (6×) Photographs 1 mo Opacity area (%)
II: 18% hydrochloric acid (4×) T0: I: 55.10  19.83; II:
53.74  22.26
DA CUNHA COELHO ET AL.

T1: I: 8.14  8.28a; II:

5.68  6.17a
Bharath et al.52 30 9-14 I: 36% hydrochloric acid +30% Photographs (VAS: 1, no 6 mo 6 mob: The sensitivity reported after
hydrogen peroxide (5 min improvement; 7— I: 5.77  0.54a; II: 2.83  1.17a both techniques was
maximum) + APF exceptional improvement) transient and decreased up
II: 18% hydrochloric acid (15× to 1 mo after treatment
maximum) + APF
Cardénas 33 8-12 5% sodium hypochlorite + fissure Chromameter – L* parameter—T0: 68.95  5.01;
Flores et al.53 sealant immediately after:
(prior etching with 37% phosphoric 72.30  3.74c
acid) a* parameter—T0: 1.65  2.43;
immediately after:
−0.04  2.14c; b*
parameter—T0: 12.80  3.95;
immediately after:
12.31  2.83;
DE—T0: 70.32  4.61;
immediately after:
73.42  3.70c
Castro et al.54 70 15-39 I: 37% phosphoric acid Photographs 1 mo Fluorosis staining areas (mmd) Participants received a
(I: 35, II: 35) (1-2 sessions of 12 applications) T0: I—32.0  10.1; II— toothbrush and a fluoridated
II: I + 10% carbamide peroxide, 31.4  9.3 non-whitening toothpaste
at-home, 4 h/d, 2 wk) T1: I—20.4  7.8a; II—
19.8  8.0a
Celik et al55 14 19-38 6.6% hydrochloric acid Photographs (VAS: 1, no 24 h Esthetic improvement—I: 3 patients presented mild or
(5-10×) + 5 min of fluoride gel improvement; 7— 5.7  0.7; moderate dental
exceptional improvement) II: 4.1  1.5; III: 3.3  1.4; hypersensitivity
I vs IIc, II vs IIIc; I vs IIId
Changes in opaque areas—I: Severity (DFI):
5.8  1.1; Group I: mild;
II: 3.4  0.9; III: 3.12  0.9; I vs Group II: moderate
IId, I vs IIId Group III: severe
Changes in brown stains—II:
4.9  1.8;
III: 4.1  1.3
Celik et al56 10 18-41 I: 6.6% hydrochloric acid (5 to Photographs (VAS: 1—no I: 24 h Esthetic improvementb: I had less dental sensitivity than
10×) + 5 min fluoride gel improvement; 7— II: 48 h I: 3.4  1.4; II: 5.8  1.4 IIb
II: I + 38% hydrogen exceptional improvement) Changes in opaque areasb:
peroxide + 5 min fluoride gel I: 4.8  1.5; II: 6.5  0.9
Changes in brown stainsb:
I: 4.2  1.4; II: 5.5  1.2.
Chandra et al57 22 <30 36% hydrochloric acid +30% Photographs – Success rate:
hydrogen peroxide + abrasive 22/22
disc
31

(Continues)
TABLE 4 (Continued)
32

Authors (year) Participants (n) Age (years) Intervention Measurement Follow-up Results Comments
58
Gugnani et al 80 6-12 I: 35% hydrogen peroxide (8 min); II: Photographs VAS Change in esthetics:
resin infiltration (3 + 1 min); (1-7) I: 1.90  0.954; II: 5.50  1.00;
III: resin infiltration (3 + 3 min) III: 5.53  1.97; IV:
IV: I + III 5.35  1.21; I vs IIb; I vs IIIb; I
vs IVb
Improvement in opacities/
stainsb:
I: 1.53  0.07; II: 4.98  0.98;
III: 5.18  1.29; IV:
4.40  1.59; I vs IIb; I vs IIIb; I
vs IVb
Gupta et al.59 29 3-12 Vitamin C + calcium + vitamin D3, Visual 59 d Improvement:
(I: 14; II: 15) orally, 1× day. After 44 d, 15 29/29a
participants have the vitamin C
dose increased
Gupta et al.60 90 10-17 I: 35% hydrogen peroxide Photographs 3 mo Color change: Cases in which satisfactory
(3 × 15 min); II: 15% hydrochloric I: 14.03  8.15a results were not obtained,
acid (3 × 60 s maximum) + 44% II: 16.29  7.89a; III: the respective procedure
carbamide peroxide (3 × 20 min 8.83  5.70a was repeated in further
maximum); III: 5% sodium appointments as necessary
hypochlorite (20 min maximum)
Hasanuddin et 80 7-10 Ia: resin composite fissure sealant; Visual 12 mo Retention rate: Ia: 1.55  0.60; All participants received oral
al.61 (I: 40; II: 40) Ib: Ia + enameloplasty; Ib: 1.70  0.56 hygiene instructions
IIa: glass ionomer fissure sealant; IIb: IIa: 0.58  0.68; IIb: 1.25  0.71
IIa + enameloplasty IIa vs IIbc; I vs IIa; Ia vs IIaa; Ib vs
IIba
Mean of retention (0—total loss;
2—total retention)
Knosel et al.62 18 18.4  4.3 I: 30% hydrogen peroxide (1 h, Chromameter 28 d L* parameter—T0: I:
in-office) + 15% carbamide 75.39  5.19;
peroxide (at-home, 1 h per day, II: 78.46  4.30; T1: I:
14 d) 79.77  4.44d;
II: negative control II: 78.60  4.21; a* parameter—
T 0:
I: −0.29  1.07; II:
−0.82  0.98; T1:
I: −1.04  0.89c; II:
−0.58  1.00; b* parameter—
T0: I: 10.59  6.33; II:
11.56  4.49;
T1: I: 4.62  3.43a; II:
10.79  4.92
Limeback et al.63 14 8-21 Microabrasion with diamond bur (VAS) – Esthetics significantly improved
after treatmenta
(Continues)
DA CUNHA COELHO ET AL.
TABLE 4 (Continued)

Authors (year) Participants (n) Age (years) Intervention Measurement Follow-up Results Comments
64 a a
Loguercio et al. 36 10-12 I: 10% hydrochloric acid Photographs (VAS: 0, no 1 wk I: 5.1  0.8 ; II: 5.3  1.1 All participants received oral
(5×) + 4 min of fluoride gel (3 improvement; 7, (77.7% considered the area hygiene instructions
sessions) exceptional improvement) treated with 6.6%
II: 6.6% hydrochloric acid (5×, 3 hydrochloric acid to be
sessions) rougher than that treated with
the concentration of 10%)
DA CUNHA COELHO ET AL.

Loyola-Rodriguez 114 12-29 7 nights of NVBT: Photographs 1 wk I versus IIIe (I more effective);
et al.65 (I: 38; II: 38; III: I: 10% carbamide peroxide; II versus III5 (II more effective)
38) II: 20% carbamide peroxide;
III: 7.5% hydrogen peroxide
Mehta and Shah66 30 8-17 I: calcium (daily) + vitamin D3 TSIF 3 mo No change in DF lesions was
(I: 10; II: 10; III: (weekly); II: ascorbic acid observed in the 3 groups of
10) (daily) + vitamin D3 (weekly) participants
III: chlorhexidine mouthwash
Seale and Thrash67 20 8-43 35% hydrogen peroxide (maximum Photographs – The results were better the
4× per session) younger the patientsc, the
yellower the lesionsc and the
longer the bleaching sessiond
Shanbhag et al.68 60 14-17 35% hydrogen peroxide + fluoride Photographs (1, the brightest 6 mo T0—I: 5.25  1.8028; II: Severity (DFI):
(I: 20; II: 20; III: varnish spectrum of the vita scale; 4.65  1.4965; Group I: very mild
20) (severe cases were previously 16—the darkest) III: 5.00  1.8064 Group II: mild
etched with 37% phosphoric acid) T1—I: 3.75  0.7864a; II: Group III: moderate
3.35  0.6708a;
III: 3.70  0.6569d
Sinha et al.69 30 7-14 CPP-ACP paste (15 min) after 4 Photographs + impressions 1 mo Improvement in white spots (T1) Severity (DFI):
(I: 10; II: 10; III: applications of 5 s of: and SEM analysis Ia: 61.3%; Ib: 70.9%; IIa: 55.05%; Group I: very mild, mild
10) Ia: 18% hydrochloric acid or IIb: 67.6%; IIIa: 40.34%; IIIb: Group II: moderate
Ib: 37% phosphoric acid or 46.6% Group III: severe
IIa: 18% hydrochloric acid or Improvement in intensity of stain
IIb: 37% phosphoric acid or (T1)
IIIa: 18% hydrochloric acid or Ia: 66.4%; Ib: 62.7%; IIa: 59%;
IIIb: 37% phosphoric acid IIb: 73.4%; IIIa: 49.7%; IIIb:
51.4%
Improvement in area of stain (T1)
Ia: 71.4%; Ib: 81.9%; IIa: 62.8%;
IIb: 72.6%; IIIa: 43%; IIIb:
48.7%
Improvement in affected area
(immediately after)—Ia: 45%;
Ib: 52%; IIa: 50%; IIb: 50%;
IIIa: 46%; IIIb: 56%

(Continues)
33
TABLE 4 (Continued)
34

Authors (year) Participants (n) Age (years) Intervention Measurement Follow-up Results Comments
70
Train et al. 41 – 15% hydrochloric acid (20× Photographs+ 4d White spot (0-5) Severity (DFI):
(I: 15; II: 15; III: maximum) Impressions and SEM T0—I: 2.47  1.164; II: Group I: very mild, mild
11) analysis 3.63 1.273; III: Grupo II: moderate
4.40  1.231; T1—I: Group III: severe
1.66  0.653d; II:
3.20  1.270d; III:
4.05  1.356d
Area of stain (0-3)
T0—I: 0.06  0.246; II:
0.67  0.547; III:
1.60  0.883; T1—I:
0.00  0.000d; II:
0.27  0.521d; III:
1.50  0.875d
Intensity of stain (0-2)
T0—I: 0.06  0.246; II:
0.70  0.596; III:
1.55  0.510; T1—I:
0.00  0.000d; II:
0.23  0.430d; III:
1.20  0.768d
Affected area (1-4)
T0—I: 1.60  1.429; II:
1.39  1.257;
III: 1.06  0.929; 2 treatments
(immediately after)—I:
1.47  1.106; II:
2.29  1.049d;
III: 1.50  1.3171; 4 treatments
(immediately after)—I:
1.37  1.159; II:
2.11  1.166d; III:
1.63  1.088c

Abbreviation: APF, acidulated phosphate fluoride; CPP-ACP, casein phosphopeptides and amorphous calcium phosphate; DE, delta equation; DFI, Dean’s Fluorosis Index; NVBT, Nightguard Vital Bleaching Technique;
SEM, scanning electron microscope; SCASS, Schiff Cold Air Sensitivity Scale; T0, baseline; T1, follow-up; TFI, Thylstrup–Fejerskov Index; TSIF, Tooth Surface Index of Fluorosis; IU, international units; VAS, visual analog
scale.
a
Comparison with baseline is statistically significant at P < 0.001.
b
Comparison between groups is statistically significant at P < 0.001.
c
Comparison with baseline is statistically significant at P < 0.05.
d
Comparison with baseline is statistically significant at P < 0.01.
e
Comparison between groups is statistically significant at P < 0.05.
DA CUNHA COELHO ET AL.
DA CUNHA COELHO ET AL. 35

TABLE 5 Risk of bias assessment for the studies included in the systematic review

Random sequence Allocation Blinding of participants Blinding of outcome Incomplete Selective Other Risk
Author generation concealment and personnel assessment outcome data reporting bias of bias
Bakkal et al.38 High High High Low Unclear Low Low High
Bezerra et al.51 Unclear Unclear Unclear Low Low Low Low High
Bharath et al.52 Unclear Unclear Unclear Low Low Low Low High
40
Biondi et al. High High High Unclear Unclear Low Low High
Castro et al.54 Low Low High Low Low Low Low Medium
Celik et al.56 High Unclear High High Low Low Unclear High
Fragelli et al.42 Unclear Unclear Low Low Unclear Low Low High
58
Gugnani et al. Low Low Low Low Low Low Unclear Medium
Gupta et al.60 Unclear Unclear Low Unclear Low Low Low High
Hasanuddin et al.61 Unclear Unclear Unclear Unclear Low Low Low High
Knosel et al.62 Unclear Unclear High Low Low Low Low High
64
Loguercio et al. Unclear Unclear High High Unclear Low Unclear High
Loyola-Rodriguez et al.65 Unclear Unclear Low Low Low High Low High
Lygidakis et al.44 Unclear Unclear Unclear Low High Low Low High
Mehta et al.66 Unclear Unclear High High High High Unclear High
Ozgul et al.45 High High Unclear Unclear Low Low Low High
Pasini et al.46 Unclear Unclear Unclear Low Unclear Low Low High
Restrepo et al.47 Low Unclear High Low Low Low Low Medium
Sinha et al.69 Unclear Unclear High Low Low Low Low High
48
Sönmez and Saat Unclear Unclear Low Unclear Low Low Low High
Souza et al.49 Low High Unclear Low Low Low Low Medium

12 months. Using the ART protocol and a glass hybrid restorative sys- and Christen50 applied hydrogen peroxide, whereas Gupta et al.60,
43
tem Grossi et al. reported a higher success rate (98.3%) at Loyola-Rodriguez et al.,65 and Knosel et al.62 also employed a carbam-
12 months. Though the authors reported positive results there is a ide peroxide solution. Although the authors used different product
clear need for the patients to be controlled because there is a lack of concentrations, all of them reported an esthetic improvement.
information regarding the effectiveness of the ART protocol in perma- Shanbhag et al.68 also reported an esthetic improvement in DF
88
nent teeth, especially those affected with MIH. lesions 6 months after bleaching with 35% hydrogen peroxide with a
Souza et al.49 evaluated the success of resin composite restora- prior etching with 37% phosphoric acid. The combination of these
tions and reported a lower success rate at 18 months: 68.4% when 2 techniques is described in the literature as prior etching allows a
restorations were performed with a self-etch adhesive and 54.6% greater diffusion of hydrogen peroxide.94,95
when performed with a total-etch adhesive. Such results may be justi- Gupta et al.60 used 5% sodium hypochlorite to remove fluorosis
fied by the hypomineralization of the affected teeth, which compro- stains but it was only effective in removing mild stains and better
89,90
mises the resin adhesion to the dental surface. In fact, Sönmez results were reported when using hydrogen peroxide or hydrochloric
and Saat48 restored hypomineralized teeth with a resin composite and acid. The use of sodium hypochlorite to remove fluorosis stains has
reported that the removal of whole affected enamel (group I) signifi- been described in the literature.60,96–98 However, care must be exer-
cantly increased the success of the treatment compared with noninva- cised when using sodium hypochlorite because it oxidizes the tissues
sive techniques without removal of all clinically defective tissue that it comes in contact with resulting in hemolysis, ulceration, inhibi-
(group II). These results corroborate those of William et al.90 who tion of neutrophil migration, and destruction of endothelial cells and
reported a lower marginal adhesion of the resin composite to hypomi- fibroblasts.99,100
neralized enamel in an in vitro study. Microabrasion consists of the removal of defects, through an
Sönmez and Saat48 suggested deproteinization using 5% sodium abrasion and a chemical erosion of the superficial layer of the enamel,
hypochlorite postacid conditioning (group III). The authors reported a being considered a safe and minimally invasive technique.101 The loca-
statistically significant difference between group II (restoration with- tion and depth of the stain or spot are the most important factors for
out deproteinization) and group III, which suggests that in cavities a successful treatment. As so, this procedure should be restricted to
without removal of all hypomineralized enamel sodium hypochlorite more superficial enamel and deeper lesions may require additional
may help in achieving better bond strength although preventing major treatment.101–103
tissue loss. However, further research is required in order to evaluate Although hydrochloric acid is presently used as a component of
the clinical efficacy of this technique because just a few studies on microabrasion pastes in concentrations up to 18%, its use at 36% as
this topic have been conducted.91–93 suggested by Chandra and Chawla57 is not currently advocated given
Several authors50,57,60,62,67,68 used dental bleaching in order to the loss of tooth structure caused by high concentrations of hydro-
improve the esthetics of DF lesions. Seale and Thrash67 and Bailey chloric acid.102,104,105
36 DA CUNHA COELHO ET AL.

Loguercio et al.64 resorted to enamel microabrasion with 10% in the resin composites adhesion to hypomineralized enamel affected
hydrochloric acid, comparing it with the application of the same prod- with DF.114–117
uct at 6.6%. Although the authors did not find differences between Even though only some treatments were analyzed in this review
the groups, esthetic improvement was reported. Similarly, Train (considering the inclusion and exclusion criteria), there are some
et al.70 and Gupta et al.60 reported an esthetic improvement after guidelines and case reports that suggest different approaches.118–122
51
microabrasion with 15% hydrochloric acid. In addition, Bezerra et al. Regarding young patients with severe hypomineralized molars, stain-
and Sinha et al.69 reported a reduction of the total area and of the less steel crowns may be used to prevent further tooth loss whereas
intensity of DF stains after the application of 18% hydrochloric acid controlling hypersensitivity and establishing interproximal and occlusal
or 37% phosphoric acid. However, Sinha et al.69 did not perform a sta- contacts and often provide an effective medium-term solu-
tistical analysis of the results, which would be imperative for a correct
tion.118,123,124 Glass-ionomer cement is also commonly used in situa-
interpretation of the data.
tions where a moisture control is inadequate (because of an
Celik et al.55 reported that the esthetic improvement because of
incomplete tooth eruption) as an intermediate restoration.119,122 In
microabrasion with 6.6% hydrochloric acid were significantly lower in
severe MIH situations the extraction of the first 4 molars associated
teeth presenting severe lesions than in mild or moderate lesions.
with orthodontic treatment has also been reported.103,121,125
These results are similar to those of Sinha et al.69 and Train et al.,70
Although the evolution of the techniques and materials used to
who reported that the need for additional treatment was higher in
manage hypomineralized teeth has been able to improve patients’ qual-
teeth with more severe DF lesions. The enamel microabrasion tech-
ity of life, the treatment of these teeth remains a challenge for dentists.
nique can be combined with dental bleaching in order to attain higher
Nowadays, the recommended treatments aim to prevent the destruc-
esthetic results. In fact, prior etching allows the opening of the den-
95,101 tion and/or loss of the affected teeth, to offer an esthetic and functional
tinal tubules, favoring the diffusion of the bleaching solution.
rehabilitation and to treat dental hypersensitivity.132, 134, 136
However,
Enamel microabrasion is a viable treatment to be applied to teeth
with mild DF lesions but may be insufficient in moderate or severe an early diagnosis combined with the evaluation of the severity of the

fluorosis lesions. As such, there is a clear need for a correct diagnosis condition and the patients’ dental age and expectation is imperative.132

so treatments can be performed with foreseeable results and a good

prognosis.
Limeback et al.63 reported an esthetic improvement of DF lesions 5 | CONC LU SION
through physical enamel abrasion with a diamond bur. This mechanical
Comparison of the reported results provided by the different studies
removal of pigmented enamel has been described in the
literature.106–108 The advantage of this technique is in its celerity in was difficult given the variability of the methodology. Thus, it is

reaching the desired esthetic in cases of mild or moderate imperative to carry out further intervention studies aimed at compar-
DF. However, these procedures employ a high-speed rotary instrument, ing the different treatments and based on the existing scientific
which can lead to excessive removal of the dental structure. 107,109 evidence.
Gugnani et al.58 suggested the use of a resin infiltrant to estheti- It is also worth noting the absence of controlled studies on types
cally improve DF stains. The efficacy of resin infiltration in arresting II and III of AI, which makes it impossible to develop guidelines for its
noncavitated caries lesions has been proven.110 Though resin infiltra- treatment.
tion may be considered a feasable alternative for blending mild and Nevertheless, it was possible to identify several effective treat-
moderate fluorosis, there is a need for long-term clinical trials with ments for teeth with MIH (arginine pastes or Fluoride varnishes to
large samples so the stability of the esthetic changes can be evaluated. treat hypersensitivity) and for DF (tooth bleaching and/or enamel
The use of resin infiltration in different kinds of stains and oppacities microabrasion).
should also be studied.
Gupta et al.59 reported an esthetic improvement of DF lesions
after daily oral administrations of a vitamin C, vitamin D3, and calcium DISC LOSURE
solution. However, this study presents a high risk of bias, given the The authors do not have any financial interest in the companies
lack of randomness in sequence generation, the absence of blinding of
whose materials are included in this article.
outcome assessment and professionals and the nonexistence of a con-
trol group. Mehta et al.66 developed a similar study but did not find
ORCID
statistical significant differences in the DF lesions. In fact, the irrevers-
ibility of DF lesions has been described in the literature. 7,111,112 Ana Sofia Estima da Cunha Coelho https://orcid.org/0000-0002-
Hasanuddin et al.61 evaluated the retention of fissure sealants in 2924-7926
DF permanent molars, reporting significantly higher sealant retention
when applying resin composite than when using glass ionomer seal-
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