Interventions For Dental Fluorosis: A Systematic Review: Zurich Open Repository and Archive

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Year: 2018
Interventions for dental fluorosis: A systematic review
Di Giovanni, Tamara ; Eliades, Theodore ; Papageorgiou, Spyridon N
Abstract: OBJECTIVE Dental fluorosis has considerable implications on the patients’ quality of life.
The present study assesses the comparative effectiveness of the various interventions for the treatment
of fluorosed enamel. MATERIALS AND METHODS Nine databases were searched from inception to
December 2016 for randomized trials. After duplicate study selection, data extraction, and risk of bias
assessment, mean differences (MD) or Relative Risks and the corresponding 95% confidence intervals (CIs)
were calculated and assessed with the GRADE approach. RESULTS Six trials with a total of 348 patients
(at least 40% male/60% female) with a mean age of 17.7 years treated with bleaching, microabrasion,
or resin infiltration were included. Evidence of low quality indicated that microabrasion resulted in
smaller esthetic improvement compared to bleaching (MD = -2.9; 95% CI = -3.4 to -2.5). Evidence of
moderate quality indicated that compared to bleaching a greater esthetic improvement was seen with resin
infiltration (MD = 3.6; 95% CI = 2.7-4.6) or a combination of bleaching with resin infiltration (MD = 3.5;
2.8-3.7). However, all comparisons were supported from single trials and therefore caution is warranted.
CONCLUSIONS Based on the existing limited evidence, resin infiltration seems to be the most promising
treatment for dental fluorosis, followed by bleaching and microabrasion. CLINICAL SIGNIFICANCE
For this systematic review, which was registered beforehand in PROSPERO (CRD42016053492), we
synthesized evidence from existing randomized clinical trals on humans to see which treatment is most
effective for the esthetic rehabilitation of dental fluorosis, the prevalence of which is seeing a worldwide
steady increase. We found that resin infiltration seems to be the most effective treatment approach
for lesions of mild to moderate severity, followed by bleaching, and finally microabrasion. Our study’s
strengths are its a priori registration, wide search, quality check according to Cochrane guidelines, and
the use of a new robust analytic method to provide valid clinical recommendations according to the
principles of evidence-based medicine.
DOI: https://doi.org/10.1111/jerd.12408
Posted at the Zurich Open Repository and Archive, University of Zurich

ZORA URL: https://doi.org/10.5167/uzh-169505
Journal Article
Accepted Version
Originally published at:

Di Giovanni, Tamara; Eliades, Theodore; Papageorgiou, Spyridon N (2018). Interventions for dental
fluorosis: A systematic review. Journal of Esthetic and Restorative Dentistry, 30(6):502-508.
DOI: https://doi.org/10.1111/jerd.12408
Interventions for dental fluorosis: a systematic review
Tamara DiGiovanni1, Theodore Eliades, Dipl.DS, MS, Dr Med Sci, PhD, FIMMM, FRSC, FInstP1, Spyridon
N. Papageorgiou, DDS, Dr Med Dent1
1Clinic of Orthodontics and Pediatric Dentistry, Center of Dental Medicine, University of Zurich, Zurich,
Switzerland
Running title: interventions for dental fluorosis
Keywords Dental fluorosis • Adverse effects • Esthetic rehabilitation • Treatment • Randomized clinical
trials • Systematic review
Correspondence: Spyridon N. Papageorgiou, Clinic of Orthodontics and Pediatric Dentistry, Center of
Dental Medicine, University of Zurich, Plattenstrasse 11, Zurich 8032, Switzerland; Tel: +41 44 634 32 87
/ Fax: +41 44 634 43 35; e-mail: [email protected]
Conflict of Interest
The authors of this manuscript certify that they have no proprietary, financial, or other personal interest of
any nature or kind in any product, service, and/or company that is presented in this article.
1
Abstract
Objective: Dental fluorosis has considerable implications on the patients’ quality of life. The
present study assesses the comparative effectiveness of the various interventions for the
treatment of fluorosed enamel.
Materials and Methods: Nine databases were searched from inception to December 2016 for
randomized trials. After duplicate study selection, data extraction, and risk of bias assessment,
Mean Differences (MD) or Relative Risks (RR) and the corresponding 95% confidence intervals
(CIs) were calculated and assessed with the GRADE approach.
Results: Six trials with a total of 348 patients (at least 40% male/ 60% female) with a mean age
of 17.7 years treated with bleaching, microabrasion, or resin infiltration were included. Evidence
of low quality indicated that microabrasion resulted in smaller esthetic improvement compared to
bleaching (MD=-2.9; 95% CI=-3.4 to -2.5). Evidence of moderate quality indicated that compared
to bleaching a greater esthetic improvement was seen with resin infiltration (MD=3.6; 95% CI=2.7
to 4.6) or a combination of bleaching with resin infiltration (MD=3.5; 2.8 to 3.7). However, all
comparisons were supported from single trials and therefore caution is warranted.
Conclusions: Based on the existing limited evidence, resin infiltration seems to be the most
promising treatment for dental fluorosis, followed by bleaching and microabrasion.
2
TEXT
1 | INTRODUCTION
1.1 | Rationale
Dental fluorosis is a specific esthetic disturbance, which can be described as a chronic condition,
where enamel development is disrupted and the resulting enamel is hypomineralized.1
Concurrent with the worldwide decline of caries, the prevalence of enamel fluorosis has increased
in the last two decades.2,3 This can be explained by an excess of ingested fluoride originating
from caries prevention measures like toothpastes, mouthrinses, gels, or varnishes that is
incorporated in the enamel during tooth development. This leads to a disturbed enamel
formation,4 as fluoride reduces calcium ion concentration in the matrix, thus indirectly interfering
with protease activity and delaying or inhibiting enamel matrix protein degradation.1,5 An abnormal
growth of apatite crystals is seen, which has as consequences optical and physical tooth surface
changes.6
Optically, dental fluorosis is characterized by hypomineralization of tooth enamel, seen as
diffuse, symmetrical, discolored white opaque stains and striations.1 Enamel surface lesions, such
as pitting, porosity, and brownish areas often occur in the more severe forms of fluorosis.1
Depending on the amount of fluoride uptake, duration of fluoride exposure, and stage of
amelogenesis the severity of symptoms varies and requires different measures.7
Even though the esthetic perception of enamel mottling is variable across patients, this
may have considerable psychosocial effects on many patients and impact their quality of life.7,8
Therefore, considerable efforts have been put in identifying an effective means to treat fluorotic
stains that might be chosen according to lesion severity.1,9 A wide range of interventions of varying
invasiveness have been proposed to treat fluorotic enamel, including external bleaching,
microabrasion, dental veneers, or crowns2,10 or a combination of methods.11,12 Since patients with
enamel mottling are quite young, with a life expectancy of many decades, minimal-invasive, hard-
3
tissue sparing restorative approaches, such as microabrasion, external bleaching, or resin
infiltration have gained momentum.3,9 Microabrasion is based on the application of an etching gel
(mostly HCl) followed by pumicing with slow rotation handpiece. Bleaching of vital fluorotic teeth
with various kinds of acids (mostly H2O2) that produces peroxide ions to penetrate enamel and
dental tubules and reduce the contrast between white spotted lesions and sound enamel have
also been widely used. Finally, enamel infiltration with low-viscosity light-cured resins was initially
developed to inhibit incipient caries lesions, but has been applied recently in the masking of
fluorotic stains, due to the resin’s similar to enamel refractive index.
1.2 | Objectives
Although several treatment approaches have been suggested for the treatment of dental fluorosis,
their effectiveness has not yet been compared in an evidence-based fashion in order to formulate
clinical recommendations. Aim of the present systematic review was to identify and synthesize
according to the guidelines of evidence-based medicine all existing evidence from randomized
clinical trials in human patients of any age or sex with enamel fluorosis lesions being treated with
at least one intervention in any clinical setting.
2 | MATERIALS AND METHODS
2.1 | Protocol and registration
A review protocol was made a priori based on the PRISMA-P statement,13 registered in
PROSPERO (CRD42016053492), and all post hoc changes were appropriately noted. This
systematic review was conducted and reported according to Cochrane Handbook14 and PRISMA
statement,15 respectively.
2.2 | Eligibility criteria
4
According to the Participants-Intervention-Comparison-Outcomes-Study design schema
(PICOS), we included only randomized controlled trials on humans reporting in vivo any kind of
intervention to treat dental fluorosis. Any animal studies, case reports, ongoing trials, non-
randomized trials, trials without available full text, or non-relevant trials were excluded.
2.3 | Information sources and literature search
Literature search was carried out systematically by one author (SNP) in nine electronic, general,
open access, regional, and grey bibliographic databases, from inception up to December 15th,
2016 (Appendix S1). Additionally, four other sources (Directory of Open Access Journals (DOAJ),
Digital Dissertations, metaRegister of Controlled Trials, WHO trials search portal, and Google
Scholar) were screened manually for any additional trials. No search filters were applied other
than dentistry and trials on humans, where available. The reference lists and citation lists of
included trials and relevant reviews were manually searched as well.
2.4 | Study selection
For calibration a pilot study was conducted prior to the main study selection. Subsequently the
title, abstract, and full-text of identified studies were screened by one author (TDG) with a
subsequent duplicate independent checking for eligibility by a second author (SNP), while
conflicts were resolved by a third author (TE). All trials that were not excluded for any of the
abovementioned reasons were finally included in our review.
2.5 | Data collection
Characteristics of included trials and numerical data were extracted independently by two review
authors (TDG, SNP) using predetermined and piloted extraction forms. Piloting of the forms was
performed during the protocol stage until over 90 per cent agreement was reached. Missing or
5
unclear information was requested from the trial’s authors or re-analyzed first-hand, when
possible.
2.6 | Risk of bias in individual trials
The risk of bias of included trials was assessed using Cochrane’s risk of bias tool14 after initial
calibration.
2.7 | Data synthesis
Meta-analysis was planned to be performed, if similar interventions and control groups were
compared and similar outcomes were measured from at least two outcomes with MDs and RRs
for continuous and binary outcomes, respectively, and the corresponding 95% Confidence
Intervals (CIs). As no two trials on the same comparison were available for meta-analysis, the
MDs/RRs were calculated for all included trials and data synthesis was performed descriptively
according to the trial’s risk of bias and the results’ clinical relevance. A clinically relevant effect
was conventionally judged as an MD larger than half a standard deviation of the control response
or an RR larger than 1.30 (or smaller than 0.70). The overall quality of evidence was rated as very
low, low, moderate, or high using the GRADE approach16 by one author (SNP) and checked by
another (TD). The full study dataset was openly provided through Zenodo.17
2.8 | Risk of bias across studies and additional analyses
A number of additional analyses and sensitivity analyses for meta-analysis were planned during
the protocol stage, but could ultimately not be performed, as no meta-analysis was conducted.
3 | Results
3.1 | Study selection
6
A total of 572 papers were identified through the electronic and one through manual searches,
respectively (Figure 1). After removal of duplicates and initial screening 28 papers were assessed
for eligibility, from which six could be included in our review (Appendix S2).
3.2 | Study characteristics
The characteristics of the included papers can be seen in Table 1 and 2. All of the six studies
were randomized controlled trials from four countries, with 2 (33%) being within-persons
randomized trials and 4 (67%) being parallel randomized trials. A total of 348 patients were
included, (with 40% male and 60% female patients in the 4 trials that specified sex) and an
average age of 17.7 years (in the 3 trials that specified age). At least 1518 teeth with fluorotic
enamel were included, which were treated mostly for esthetic reasons. Fluorosis severity was
assessed in two trials with the Thylstrup-Fejerskov index, in one with the Tooth Surface Index of
Fluorosis, and in another two with Dean’s index, whereas in one trial no fluorosis index was
reported. Overall, the identified trials included mild forms of fluorosis, reaching from questionable
to moderate fluorosis. Interventions used in the identified trials included external bleaching,
microabrasion, resin infiltration with different application times, or combination of bleaching with
subsequent resin infiltration. The included trials assessed in all cases efficacy of treatment
(esthetic improvement or specific optical properties of the fluorotic lesions), while four of them
also assessed safety (tooth sensitivity or irritation of the gingiva) with an outcome measurement
timing ranging from directly post-treatment up to six months post-treatment.
3.3 | Risk of bias within studies
The risk of bias assessment for the included six trials is shown in Figure 2 and can be seen more
detailed in Appendix S3. Serious risk of bias was found in 4 of the trials (67%) for at least one
bias domain, with the most problematic domain being the blinding of outcome assessors (high
7
risk of bias in 67% of trials), followed by blinding of participants/personnel (high risk of bias in 50%
of trials).
3.4 | Results of individual studies and data synthesis
The treatment effects of all outcomes reported in the identified trials can be seen in Appendix S4.
Compared to no treatment, bleaching improved all colorimetric aspects according to the
International Commission on Illumination to a statistically and clinically significant extent. Although
fewer bleached fluorotic areas tended to have discernable color differences from healthy enamel
(RR=0.68; 95% CI=0.43 to 1.08), this did not reach statistical significance (P=0.04). The quality
of contributing evidence according to the Grading of Recommendations, Assessment,
Development and Evaluation (GRADE) approach was judged as low, due to bias and imprecision
(Table 3).
As far as direct comparisons between interventions are concerned, bleaching was
adopted as a reference intervention, since it contributed with the largest numbers of trials (Table
4). Compared to bleaching, microabrasion resulted in a significantly smaller esthetic improvement
of fluorotic stains 6 months after treatment, which was clinically relevant (MD=-2.9; 95% CI=-3.4
to -2.5). On the other side, no difference could be found post treatment in tooth sensitivity between
the microabrasion and bleaching. Both conclusions were however supported by evidence of low
quality according to GRADE, due to high risk of bias and imprecision (Table 4).
Furthermore, compared to bleaching, all other tested interventions, including resin
infiltration for 2’, resin infiltration for 3’, or bleaching followed by resin infiltration for 3’ lead to both
statistically and clinically greater esthetic improvements and greater improvements of the fluorotic
stains. This was supported by evidence of moderate quality according to GRADE, due to the
inclusion of a single trial with limited sample size (as in all cases). Finally, the esthetic
improvement was similar for all three listed interventions (MDs of 3.6, 3.6, and 3.5), which
8
indicated that increased times of resin infiltration (3’ instead of 2’) or combination with tooth
bleaching might not lead to better results.
3.5 | Risk of bias across studies and additional analyses
A number of additional analyses and sensitivity analyses for meta-analysis were planned during
the protocol stage, but could ultimately not be performed, as no meta-analysis was conducted.
4 | Discussion
The present systematic review summarizes clinical evidence from six available randomized
clinical trials on the treatment of mild to moderate dental fluorosis. According to evidence of low
quality, bleaching is effective in significantly improving the colorimetric properties of fluorosed
enamel (P<0.001; Appendix S4), although the discernable overall color difference between
bleached fluorotic and healthy enamel is not significantly different (P=0.10; Appendix S4).
Additionally, compared to bleaching, microabrasion seems to be associated with smaller esthetic
improvement, while resin infiltration for 2’ or 3’ and bleaching combined with resin infiltration seem
to be associated with greater esthetic improvements (P<0.001; Appendix S4).
As far as different interventions are compared, microabrasion was found to be significantly
less effective in the treatment of fluorotic enamel stains than McInnes bleaching (with a solution
of H2O2, HCl, and ether). Microabrasion has previously been suggested as an effective means to
remove enamel stains that are confined to superficial enamel layers, with possible underlying
mechanisms being a dissolution of the residual organic material (including pigmentations) and
loosely mineralized tissue by acids, allowing for a subsequent ‘correct’ remineralization by salivary
and fluoride minerals.3 Others report that it is difficult to determine which stains are sufficiently
superficial for correction with microabrasion.18 Additionally, there are reports that microabrasion
might be effective in removing mild fluorotic stains, but might be less effective against fluorotic
9
stains of even moderate severity.19 Furthermore, an identified trial that was not included in the
GRADE analysis11 compared microabrasion alone and microabrasion followed by home
bleaching, but found no added value from subsequent bleaching.
Additionally, resin infiltration with recommended application strategy (2’) or with increased
time of infiltrant application (3’) showed better results than bleaching in treating fluorotic enamel
stains.12 This might be expected, since resin infiltration has been previously suggested for the
treatment of post-orthodontic white spot lesions,20,21 which have many histological and optical
similarities to enamel fluorotic stains.22,23
As far as adverse effects are concerned, only a very mild transient tooth sensitivity was
recorded after the use of either microabrasion3,11 or bleaching,3,11 which was not clinically relevant
and subsided after about a month. Additionally, signs of minimal gingival irritation were observed
after microabrasion11 or microabrasion combined with bleaching,11 which were however transient.
However, some limitations are also present in this study. First and foremost, this
systematic review included mostly small trials with limited samples, which can influence their
results.24 Moreover, the limited number of included trials precluded robust assessments of
heterogeneity, subgroup analyses for many factors (including tooth type, fluorosis severity, and
operator’s experience), small-study effects, and reporting biases for all outcomes. Although
publication bias could not be tested statistically due to the small number of included studies, we
rate the possibility of publication bias as low due to our comprehensive literature screening that
included grey literature.
5 | CONCLUSIONS
According to existing evidence from randomized clinical trials in humans, resin infiltration seems
to be more effective in the esthetic treatment of mild to moderate fluorotic enamel stains than
bleaching and microabrasion. Additionally, no additional gains were found compared to
conventional resin infiltration by increased application time of the etchant on enamel or
10
combination with bleaching. Finally, no serious safety concerns were observed for any of the
assessed interventions. However, caution is warranted due to the limited available evidence with
moderate to high risk of bias.
11
REFERENCES
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man. J. Dent. Res. 69 Spec No, 692–700 (1990).
2. Aoba, T. & Fejerskov, O. Dental fluorosis: chemistry and biology. J. Clin. Epidemiol. 13,
155–170 (2002).
3. Bharath, K. et al. Comparison of relative efficacy of two techniques of enamel stain removal
on fluorosed teeth. An in vivo study. J. Clin. Pediatr. Dent. 38, 207–213 (2014).
4. Bronckers, A. L., Lyaruu, D. M. & DenBesten, P. K. The impact of fluoride on ameloblasts
and the mechanisms of enamel fluorosis. J. Dent. Res. 88, 877–893 (2009).
5. Robinson, C. et al. The effect of fluoride on the developing tooth. Caries Res. 38, 268–276
(2004).
6. Ng, F. & Manton, D. Aesthetic management of severely fluorosed incisors in an adolescent
female. Aust. Dent. J. 52, 243–248 (2007).
7. Bertassoni, L. E. et al. In-office dental bleaching and enamel microabrasion for fluorosis
treatment. J. Clin. Pediatr. Dent. 32, 185–187 (2008).
8. Celik, E. U., Yildiz, G. & Yazkan, B. Clinical evaluation of enamel microabrasion for the
aesthetic management of mild-to-severe dental fluorosis. J. Esthet. Restor. Dent. 25, 422–
430 (2013).
9. Khandelwal, V. et al. Aesthetic management of dental fluorosis. BMJ. Case Rep. 2013
(2013).
10. Akpata, E. S. Occurrence and management of dental fluorosis. Int. Dent. J. 51, 325–333
(2001).
11. Castro, K. S., et al. Acceptability, efficacy and safety of two treatment protocols for dental
fluorosis: A randomized clinical trial. J. Dent. 42, 938–944 (2014).
12
12. Gugnani, N. et al. Comparative evaluation of esthetic changes in nonpitted fluorosis stains
when treated with resin infiltration, in-office bleaching, and combination therapies. J. Esthet.
Restor. Dent. 29, 317–324 (2017).
13. Moher, D. et al. Preferred reporting items for systematic review and meta-analysis protocols
(PRISMA-P) 2015 statement. Syst. Rev. 4, 1 (2015).
14. Higgins, J. & Green, S. Cochrane Handbook for Systematic Reviews of Interventions
Version 5.1.0 [Internet]. The Cochrane Collaboration, 2011. Available from: www.cochrane-
handbook.org. Date accessed September 19, 2017.
15. Liberati, A. et al. The PRISMA statement for reporting systematic reviews and meta-
analyses of studies that evaluate healthcare interventions: explanation and elaboration.
BMJ. 339, b2700 (2009).
16. Guyatt, G. H. et al. GRADE guidelines: A new series of articles in the J Clin Epidemiol. J.
Clin. Epidemiol. 64, 380–382 (2011).
17. DiGiovani, T., Eliades, T. & Papageorgiou, S. N. Interventions for dental fluorosis: a
systematic review. http://doi.org/10.5281/zenodo.1213781
18. Croll, T. P. & Cavanaugh, R. R. Enamel color modification by controlled hydrochloric acid-
pumice abrasion. I. Technique and examples. Quintessence Int. 17, 81–87 (1986).
19. Train, T. E. et al. Examination of esthetic improvement and surface alteration following
microabrasion in fluorotic human incisors in vivo. Pediatr. Dent. 18, 353–362 (1996).
20. Paris, S. & Meyer-Lueckel, H. Masking of labial enamel white spot lesions by resin
infiltration: a clinical report. Quintessence Int. 40, 713–718 (2009).
21. Höchli, D. et al. Interventions for orthodontically induced white spot lesions: a systematic
review and meta-analysis. Eur. J. Orthod. 39,122–133 (2017).
22. Ontiveros, J. C. Commentary: alternative esthetic management of fluorosis and hypoplasia
stains: blending effect obtained with resin infiltration techniques. J. Esthet. Restor. Dent. 25,
40–41 (2013).
13
23. Torres, C. R. & Borges, A. B. Color masking of developmental enamel defects: a case
series. Operative Dent. 40, 25–33 (2015).
24. Cappelleri, J. C. et al. Large trials vs meta-analysis of smaller trials: how do their results
compare? JAMA. 276, :1332–1338 (1996).
14
Figure legends
Figure 1 Flow diagram for the identification and selection of eligible trials.
15
Figure 2 Summary of the risk of bias of included trials.
16
Table 1. Study design and patient characteristics of included trials
Study design;
Patients N of Tooth info
Study setting; Coun- Patient info
(M/F); agea teeth Fluorosis index; fluorosis severity; status
try
Bharath wpRCT; Uni; 30 (NR); 9-
objectionable esthetics 60 DFI; mild, moderate; caries-free
2014 IND 14 yrs
TF; mild, moderate; vital, caries-, defect-, fracture-,
70 (22/48); >15 yrs, good general/oral health,
Castro 2014 pRCT; Uni; BRA >280 malocclusion-free, restorations less than 1/6 of buc-
17.6 yrs non-smoker, not pregnant
cal Sf; orthodontic Tx
School children, good general/oral
Gugnani pRCT; Uni; 80 (NR); 6- TF; mild, moderate; nonpitted, fracture-, restoration-
health, no history of allergy towards 80
2017 IND 12 yrs free
dental material
18 (7/11); >14 yrs, Caucasian, good oral NR; mild, moderate; proximal caries-free, sufficient
Knosel 2008 pRCT; Uni; DEU 42
18.4 yrs health restorations
Loguercio wpRCT; Uni; 36 (19/17);
moderate-good oral health >144 DFI; questionable, very mild, mild
2007 BRA 10-12 yrs
good oral health, no bleaching ex-
Loyola-Ro- 114 (40/74); TSIF; <2/3 of tooth surface; caries-, restoration-free,
pRCT; Uni; MEX perience, no history of dental 912
driguez 2003 17.6 yrs tetracycline-stained-free, intact enamel
trauma
a when one value is given, this pertains to mean patient age; when this is not reported in the trial, the age range is given.
DFI Dean’s Fluorosis Index, FU follow-up after treatment administration, GH general health, Gp group, M/F mean/female, NR not reported, pRCT parallel
randomized clinical trial, Sf surface, smRCT split-mouth randomized clinical trial, TF Thylstrup and Fejerskov Index, Tx treatment, Uni university, wpRCT
within-persons randomized clinical trial, yrs years.
17
Table 2. Intervention and outcome characteristics of included trials
Study Tx; Application time; Application frequency FU Outcome
Gp1: McInnes Bleaching (36% HCL, 30% H2O2, Diethyle Ether); <5 min; NR 1, 3, 6 -esthetic improvement in VAS
Bharath 2014
Gp2: enamel microabrasion (18% HCL, pumice powder); <75 sec; <12-15 mos -tooth sensitivity
Gp1: enamel microabrasion (37% phosphoric acid, pumice); (n=23) 4 min, (n=12) -reduction in opacity with software
2 min; (n=23) 24, (n=12) 12 -esthetic improvement in VAS
Castro 2014 Gp2: enamel microabrasion (37% phosphoric acid, pumice), at-home bleaching 1 mos -participant satisfaction in VAS
(10% carbamide peroxide); (n=22) 56 h 4 min, (n=13) 56 h 2 min; (n=22) 38 -tooth sensitivity/gingiva irritation in
(n=13) 26 VAS
Gp1: in-office bleaching (35% H2O2); 8 min; 1
Gp2: resin infiltration (15% HCL gel, ethanol-drying agent, resin infiltrant); <10 - esthetic change in VAS
Immedi-
Gugnani 2017 min; 1 - improvement in opacity/stains in
ately
Gp3: resin infiltration with double application of infiltrant; <12 min; 1 VAS
Gp4: in-office bleaching (35% H2O2), resin infiltration; <18 min; 1
-tooth color, luminosity (colorimetry)
Gp1: external bleaching Illuminé office (30% hydrogen peroxide), Illuminé home - tooth sensitivity, enamel surface,
1 h; 14
Knosel 2008 (15% carbamide peroxide); 15 h; 15 gingival irritation in questionnaire
d; 28 d
Gp2: control -participant satisfaction in question-
naire
-esthetic improvement in VAS
Loguercio Gp1: enamel microabrasion PREMA; 10 min; 15
NR -participant satisfaction
2007 Gp2: enamel microabrasion Opalustre; 10 min; 15
-tooth surface
Gp1: external bleaching (10% carbamide peroxide); 56 h; 7 -esthetic improvement
Loyola-Rodri-
Gp2: external bleaching (20% carbamide peroxide); 56 h; 7 7d -tooth sensitivity
guez 2003
Gp3: external bleaching (7.5% hydrogen peroxide); 56 h; 7 -gingiva irritation
FU follow-up after treatment administration, GH general health, Gp group, M/F mean/female, min minutes, mos months, NR not reported, OH oral health,
sec seconds, Sf surface, TF Thylstrup and Fejerskov Index, TSIF Tooth Surface Index of Fluorosis, Tx treatment, Uni university, yrs years.
18
Table 3. GRADE Summary of Findings Table for meta-analyses of trials comparing bleaching to no treatment for fluorosed enamel
Anticipated absolute effects
Outcome Effect * Quality of the
Control Bleaching Difference What happens
Trials (patients) – follow up (95% CI) evidence (GRADE)a
ΔE(L*a*b*) >3.7 between Bleaching might make
RR: 0.68 52.0% 24.5% less  lowb,c
fluorosed and healthy enamel 76.5% fluorotic enamel less dis-
(0.43,1.08) (32.9%,82.6%) (43.6% less, 6.1% more) due to bias, imprecision
1 (18) – 1 month post Tx cernable
CI confidence interval, GRADE Grading of Recommendations Assessment, Development and Evaluation, RR relative risk, Tx treatment, ΔE(L*a*b) overall
color difference according to the International Commission on Illumination.
Treatment effects of interventions for enamel fluorosis.
Patient or population: Caucasian male & female adolescent/adult patients seeking treatment for fluorotic stains on teeth.
Settings: university clinics (Germany).
* Risk in the control group is based on the untreated control group of the single included study.
a Quality of evidence starts from high due to the inclusion of randomized studies.
b Downgraded by one due to risk of bias.
c Downgraded by one due to imprecision originating from the inclusion of a single study with limited sample size.
19
Table 4. GRADE Summary of Findings Table for meta-analyses of trials comparing bleaching to different treatments for fluorosed enamel
Anticipated absolute effects
Outcome Experi- Difference Quality of the What happens (with refer-
Ref (BLCH)*
Trials (patients) – follow up mental (95% CI) evidence (GRADE)a ence to bleaching)
MABR
Esthetic improvement +5.8 VAS1-7 pts MD: 2.9 pts less (2.5 to 3.4  lowb,c Smaller esthetic improvement
-
1(30) – 6 months post Tx improvement pts less) due to bias, imprecision with microabrasion
Tooth sensitivity MD: 0.1 pts less ( 0.4 pts  lowb,c Probably no difference in tooth
0.4 pts in SS0-3 -
1(30) – post Tx less to 0.2 pts more) due to bias, imprecision sensitivity.
RESINF (2’)
Esthetic improvement +1.9 VAS1-7pts MD: 3.6 pts more (3.0 to  moderatec Greater esthetic improvement
-
1(40) – post Tx improvement 4.2 pts more) due to imprecision with resin infiltration (2’).
Improvement of fluorosis
+1.5 VAS1-7pts MD: 3.5 pts more (2.8 to  moderatec Greater improvement of stains
stains -
improvement 4.1 pts more) due to imprecision with resin infiltration (2’).
1 (40) – post Tx
RESINF (3’)
Esthetic improvement +1.9 VAS1-7pts MD: 3.6 pts more (2.7 to  moderatec Greater esthetic improvement
-
1(40) – post Tx improvement 4.6 pts more) due to imprecision with resin infiltration (3’).
Improvement of fluorosis
+1.5 VAS1-7pts MD: 3.7 pts more (2.9 to  moderatec Greater improvement of stains
stains -
improvement 4.4 pts more) due to imprecision with resin infiltration (3’).
1 (40) – post Tx
BLCH &
RESINF (3’)
Greater esthetic improvement
Esthetic improvement +1.9 VAS1-7pts MD: 3.5 pts more (2.8 to  moderatec
- with bleaching + resin infiltra-
1(40) – post Tx improvement 3.7 pts more) due to imprecision
tion (3’).
BLCH bleaching, CI confidence interval, GRADE Grading of Recommendations Assessment, Development and Evaluation, MABR microabrasion, MD
mean difference, pts points, Ref referent intervention, RESINF resinfiltration (infiltration time indicated in parenthesis), SS0-3 sensitivity scale from 0 to 3
(greater values indicated greater tooth sensitivity), Tx treatment, VAS1-7 visual analogue scale from 1 to 7 (greater values indicated greater improvement).
Treatment effects of interventions for enamel fluorosis.
Patient or population: children with mild to moderate non-pitted fluorotic stains on teeth receiving treatment.
Settings: dental college (India).
* Reponse in the reference group is based on the single included study in each comparison.
a Quality of evidence starts from high due to the inclusion of randomized studies.
b Downgraded by one due to risk of bias.
c Downgraded by one due to imprecision originating from the inclusion of a single study with limited sample size.
20
Interventions for dental fluorosis: a systematic review
Supporting Information
Appendix S1. Literature databases searched with the used search strategies and their hits (search date December 20, 2016)
Nr Database Search Limit Hits
MEDLINE (via PubMed) (dent* OR teeth OR tooth) AND (fluorosis OR fluorosed OR fluorozed OR
1 Species: Human 156
https://www.ncbi.nlm.nih.gov/pubmed/ mottl*) AND random*
Cochrane Database of Systematic
2 Reviews (CDSR) (dent* OR teeth OR tooth) AND (fluorosis OR fluorosed OR fluorozed OR - 5
http://cochranelibrary.com/ mottl*)
Cochrane Central Register of Con-
3 trolled Trials (CENTRAL) (dent* OR teeth OR tooth) AND (fluorosis OR fluorosed OR fluorozed OR - 65
Cochrane Database of Abstracts of
4 Reviews of Effects (DARE) (dent* OR teeth OR tooth) AND (fluorosis OR fluorosed OR fluorozed OR - 7
Embase (dent* OR teeth OR tooth) AND (fluorosis OR fluorosed OR fluorozed OR
5 Human 95
https://embase.com/ mottl*) AND random*
Virtual Health Library (dent* OR teeth OR tooth) AND (fluorosis OR fluorosed OR fluorozed OR
6 - 49
http://bvsalud.org/en/ mottl*) AND random*
Scopus (dent* OR teeth OR tooth) AND (fluorosis OR fluorosed OR fluorozed OR
7 Dentistry; Human 98
https://scopus.com/ mottl*) AND random*
Web of Knowledge (dent* OR teeth OR tooth) AND (fluorosis OR fluorosed OR fluorozed OR DENTISTRY ORAL SUR-
8 89
https://login.webofknowledge.com/ mottl*) AND random* GERY MEDICINE
ClinicalTrials.gov (dental OR dentistry OR teeth OR tooth) AND (fluorosis OR fluorosed OR
9 8
https://clinicaltrials.gov/ fluorozed OR mottled OR mottling)
SUM 572
.
1
Appendix S2. List of identified studies with eligibility status.
Nr Paper Status
1 [No authors] A systematic review of public water fluoridation. Database of Abstracts of Reviews of Effects. 2000; 2:243. Excluded by title
2 {NCT01049503} Effect of pH and Fluoride Concentration of Dentifrices on Caries Control. Completed. Excluded by title
3 {NCT01568541} Fluoride Intake From Toothbrushig With Children's or Regular Toothpastes. Completed. Excluded by title
{NCT01571050} Systemic Fluoride Bioavailability From Toothpastes Containing Calcium Carbonate or Silica as Abrasives.
4 Excluded by title
Completed.
5 {NCT01589991} Anticaries Potential and Fluorosis Risk From Different Fluoride Toothpastes. Completed Excluded by title
6 {NCT01978041} Fluoride Bioavailability After Ingestion of Water or Foods Prepared With Fluoridated Water. Completed. Excluded by title
7 {NCT02958891} Dental Health Epidemiology Among Israel Defense Forces (IDF) Recruits. Active, not recruiting. Excluded by title
Aasenden R, Peebles T. Effects of fluoride supplementation from birth on dental caries and fluorosis in teenaged children. Ar-
8 Excluded by title
chives of oral biology. 1978; 23(2):[111-5 pp.].
Abuhaloob L, Abed Y. Dietary behaviours and dental fluorosis among Gaza Strip children. Eastern Mediterranean health journal
9 Excluded by title
= La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit. 2013;19(7):657-63.
Adair SM, Piscitelli WP, McKnight-Hanes C. Comparison of the use of a child and an adult dentifrice by a sample of preschool
10 Excluded by title
children. Pediatric dentistry. 1997;19(2):99-103.
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dren in Ibadan, Nigeria. The Nigerian postgraduate medical journal. 2012;19(2):102-6.
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dren in Kuwait: a non-fluoridated community. Community dentistry and oral epidemiology. 2014;42(3):224-33.
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miology. 2014;42(5):412-9.
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Excluded; trial reg-
istration-trial has
{NCT01733888} Resin Infiltration and Resin Infiltration With Bleaching in Improving the Esthetics for Fluorosis Stains. Com-
322 been completed
pleted
and added to ref-
erences
Excluded; trial reg-
323 {NCT02925780} Action of Infiltration Resin Icon in Fluorosis, Clinical Trial, Monitoring for 12 Month. Not yet recruiting. istration-trial still
ongoing
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11
Appendix S3. Details about the risk of bias assessment of included randomized trials with the Cochrane tool.
Other
Blinding of Blinding of outcome Selective outcome
Trial Sequence generation Allocation concealment Incomplete outcome data sources
participants/personnel assessors reporting
of bias
Low risk (for esthetic
improvement)– blinding of
outcome assessment in terms
Low risk – no drop-outs or
Unclear – of esthetic improvement is
patient losses are reported.
randomization adequate: „…assessment was Unclear – no protocol
High risk – no mention of All of the patients were in
description inadequate. Unclear – no mention done by four calibrated and exist for the trial.
blinding of participants follow-up for the esthetic
“Each subject had one throughout the paper; blinded examiners including a However, all in the Unclear –
throughout the paper. improvement assessment.
of their maxillary Highly probable that layperson.” Examiners were trial mentioned pre- residual
Bharath Risk of performance bias “…the pre- and post-operative
central incisors clinician knew about the checked for intra- and inter- specified outcomes, bias
2014 due to probable photographs of 30 subjects
randomly selected for allocation, as application rater reliability in advance. such as esthetic cannot be
knowledge of the were incorporated…” Number
micro-abrasion and the for the two procedures Unclear (for sensitivity)– In improvement and excluded.
allocated interventions by of patients which underwent
contralateral maxillary was different. terms of sensitivity, reported by tooth sensitivity, are
clinician. sensitivity assessment is not
central incisor for the patients, no blinding is reported.
mentioned, but patient loss
McInnes bleaching.” mentioned. Outcome is patient-
here is highly improbable.
reported and blinding of
patients has been assessed in
the previous domain.
Low risk (for esthetic
improvement)– photos were
Low risk – assessed by two calibrated and Unclear – no protocol
Unclear – The High risk – no mention of
randomization took blinded examiners. Software exist for the trial.
randomization table for blinding of participants
place with a and digital images were used to However, all in the
the allocation was throughout the paper.
randomization table to measure stained areas trial mentioned pre- Unclear –
prepared in advance “by Patients and clinicians
allocate participants in objectively. Low risk – no drop-outs or specified outcomes, residual
an examiner not directly were most likely aware of
Castro 2014 each treatment group, Unclear (for sensitivity, patient losses. All patients such as esthetic bias
involved with the clinical the treatment, especially
prepared in advance by satisfaction, and esthetic attended the follow-up. improvement, patient cannot be
steps of the study”. It patients in the group with
an examiner not improvement, reported by the satisfaction, and excluded.
remains unclear if at-home bleaching had to
directly involved with patients)–no blinding is tooth/gingival
allocation was concealed be compliant and to know
the clinical steps of the mentioned. Outcome is patient- sensitivity, are
and how. what to do.
study. reported and blinding of reported.
patients has been assessed in
the previous domain.
Low risk – preoperative and
Low risk – allocation
Low risk – postoperative images were
concealment was
randomization took assessed by two independent Unclear – no protocol
ensured by using sealed
place by using block observers. “To ensure blinding exist for the trial.
envelopes, made by an
randomization. of the outcome evaluators, the However, all in the
independent person a Unclear – either only the Unclear –
“…children were preoperative and postoperative trial mentioned pre-
priori. “The sequence clinicians or only the residual
Gugnani randomly allocated in images were stored with a specified outcomes,
generation table was patients are single Unclear – not clearly reported. bias
2017 four different groups unique ID and the evaluators such as esthetic
kept sealed and secured blinded to the allocation cannot be
using block were not disclosed about the changes and
till the end of the study.” and the treatment. excluded.
randomization.” The participant’s treatment group.” improvement in
“The participants were
random sequence “Outcome evaluators were opacity/stains, are
allocated to different
generation happened blinded to avoid any bias during reported.
treatment groups by
web-based. the scoring of esthetic
independent personnel,
changes.”
12
not involved in the
sequence generation.”
High risk – no mention of High risk (for esthetic
blinding of participants improvement)– no mention of
High risk – no
throughout the paper. blinding throughout the paper.
protocol exist for the
Patients and clinicians Unclear (for patient-reported
trial. Main outcome Unclear –
Low risk – were most likely aware of outcomes) – In terms of
Unclear – no mention of reported in detail. residual
randomization took the treatment, especially sensitivity, satisfaction, and Low risk – no drop-outs or
Knosel 2008 concealment throughout Results of the patient bias
place by lot to either of patients in the group with enamel surface, reported by the patient losses are reported.
the paper. questionnaire are not cannot be
the two groups. at-home bleaching had to patients, no blinding is
fully reported, but excluded.
be compliant and to know mentioned. Outcome is patient-
only shortly
what to do. Patients in reported and blinding of
discussed.
control group never patients has been assessed in
received any treatment. the previous domain.
Unclear – unclear if
Low risk – outcome assessors
allocation concealment
Low risk – Unclear – no mention of were blinded. “Two blinded
was ensured. “All Unclear – not clearly reported.
randomization took blinding throughout the evaluators appraised both sides
participants were Even though all patients Unclear – no protocol
place by tossing a coin. paper. Blinding of of the mouth using a visual
informed of the nature attended all treatments, exist for the trial.
“For each subject, two patients is highly scale system.” Besides,
and objectives of this nothing is mentioned about However, all in the
compound systems probable (“however, they operators applying the Unclear –
study; however, they the follow-up. “All subjects trial mentioned pre-
were randomly were unaware of the bleaching agents and residual
Loguercio were unaware of the had three clinical treatments.” specified outcomes,
selected and location of each examiners, were different bias
2007 location of each “The clinical aspect resulted such as esthetic
designated “left” or material”), whereas people. Tooth sensitivity and cannot be
material.” “Two from the microabrasion improvement, patient
“right”. “A coin was operator most likely knew surface was assessed by the excluded.
uniformed examiners, technique, which was satisfaction, and
tossed to determine which bleaching agent patients themselves. Risk of
uniformed as to which evaluated at least 48 hours tooth surface, are
whether Opalustre or they were applying, as detection bias highly
product was used on after completion of the clinical reported in detail.
PREMA would be used blinding is not easily improbable, as patients were
which subjects, appointment…”
on the left or right side.” applicable. most likely blinded and
attempted to evaluate the
allocation concealed.
clinical performance…”
Low risk – no
Unclear – nothing
protocol exist for the
Unclear – precisely mentioned.
Low risk – patients and trial. However, all in
randomization Highly probable that
clinicians are blinded. “A the trial mentioned Unclear –
description inadequate. participants did not know High risk – no blinding of
Loyola- double blind clinical trial pre-specified residual
“…patients were assignment, as they did evaluators is mentioned, but
Rodriguez was done…” “Both Unclear – not clearly reported. outcomes, such as bias
randomized into three not know any treatment they were calibrated in
2003 subjects and dentist were esthetic cannot be
groups of treatment, resp. group. “Both advance.
unaware of which improvement, excluded.
sample size was 38 subjects and dentist were
treatment was involved. tooth/gingival
subjects per group.” unaware of which
sensitivity, are
treatment was involved.”
reported in detail.
13
Appendix S4. Results of all included trials.
Clinical rel-
Nr Trial Ref Exp Outcome Timing Clus MD (95% CI) P RR (95% CI) P
evance†
Apperance improve-
1 Bharath 2014 MAbr Bleach post tx yes 2.85 (2.36,3.35) <0.001 Yes
ment$
Apperance improve-
2 Bharath 2014 MAbr Bleach 6 mos yes 2.94 (2.48,3.40) <0.001 Yes
ment$
3 Bharath 2014 MAbr Bleach Tooth sensitivity post tx yes 0.10 (-0.17,0.37) 0.46 -
4 Bharath 2014 MAbr Bleach Tooth sensitivity 1 mo yes No sensitivity -
5 Bharath 2014 MAbr Bleach Tooth sensitivity 3 mos yes No sensitivity -
6 Bharath 2014 MAbr Bleach Tooth sensitivity 6 mos yes No sensitivity -
7 Castro 2014 MAbr Mabr/Bleach Lesion area 1 mo No -0.60 (-4.30,3.10) 0.75 -
8 Castro 2014 MAbr Mabr/Bleach Lesion area reduction 1 mo-BL No 0.00 (-3.03,3.03) 1.00 -
Apperance improvement
9 Castro 2014 MAbr Mabr/Bleach aft No 1.00 (-1.24,3.24) 0.38 -
(patients)
Apperance improvement
10 Castro 2014 MAbr Mabr/Bleach aft No 0.00 (-2.83,2.83) 1.00 -
(dentists)
Bleach
11 Gugnani 2017 Resin infiltration (2') Estethics improvement No 3.60 (3.00,4.20) <0.001 Yes
(HP35%)
Bleach
12 Gugnani 2017 Resin infiltration (3') Estethics improvement No 3.63 (2.67,4.59) <0.001 Yes
(HP35%)
Bleach Bleach (HP35%) +
13 Gugnani 2017 Estethics improvement No 3.45 (2.78,4.12) <0.001 Yes
(HP35%) resin infiltration (3')
Bleach Stain/opacities improve-
14 Gugnani 2017 Resin infiltration (2') No 3.45 (2.81,4.09) <0.001 Yes
(HP35%) ment
Bleach Stain/opacities improve-
15 Gugnani 2017 Resin infiltration (3') No 3.65 (2.92,4.39) <0.001 Yes
(HP35%) ment
Bleach Bleach (HP35%) + Stain/opacities improve-
16 Gugnani 2017 No 2.87 (2.03,3.71) <0.001 Yes
(HP35%) resin infiltration (3') ment
Fluorosed-to-healthy
17 Knosel 2008 Ctr Bleach BL 1.07 (0.82,1.39) 0.62 -
enamel DE>3
18 Knosel 2008 Ctr Bleach 1 mo 0.68 (0.47,0.98) 0.04 No
enamel DE>3
19 Knosel 2008 Ctr Bleach BL 1.25 (0.89,1.75) 0.20 -
enamel DE>3.7
20 Knosel 2008 Ctr Bleach 1 mo 0.68 (0.43,1.08) 0.10 -
enamel DE>3.7
L of fluorosed enamel
21 Knosel 2008 Ctr Bleach 1 mo-BL 4.24 (2.26,6.22) <0.001 Yes
change
a of fluorosed enamel
22 Knosel 2008 Ctr Bleach 1 mo-BL -0.99 (-1.42,-0.56) <0.001 Yes
change
b of fluorosed enamel
change
14
L of healthy enamel
24 Knosel 2008 Ctr Bleach 1 mo-BL 5.10 (2.83,7.37) <0.001 Yes
change
a of healthy enamel
25 Knosel 2008 Ctr Bleach 1 mo-BL -0.26 (-0.79,0.27) 0.33 -
change
b of healthy enamel
change
Loguercio MAbr Apperance improvement 1 wk after
27 MAbr (Opalustre) Yes 1.00 (0.72,1.28) <0.001 Yes
2007 (PREMA) (dentists) app1
Loguercio MAbr Apperance improvement 1 wk after
28 MAbr (Opalustre) Yes 0.40 (0.10,0.70) 0.009 No
2007 (PREMA) (dentists) app2
Loguercio MAbr Apperance improvement 1 wk after 0.20
29 MAbr (Opalustre) Yes 0.38 -
2007 (PREMA) (dentists) app3 (-0.24,0.64)
Loyola-Rodri- Bleach
30 Bleach (CP20%) Sum TSIF>20 bef-aft 1.50 (0.27,8.48) 0.65 Yes
guez 2003 (CP10%)
Loyola-Rodri- Bleach 15.50
31 Bleach (HP7.5%) Sum TSIF>20 bef-aft <0.001 Yes
guez 2003 (CP10%) (3.99,60.23)
† judged for statistically significant results as MD larger than half a standard deviation of the control response or RR larger than 30%
* medians converted to means for the analysis

$ all raters pooled together for the analysis
Ref, referent intervention; Exp, experimental group; Clus, clustered data; MD, mean difference; CI, confidence interval; RR, relative risk; MAbr, microabrasion; HP, hydrogen
peroxide; Ctr, control (untreated); CP, carbamide peroxide.
15
Appendix S5. Further details to the review and deviations from protocol.
Author contributions
SNP conceived the idea and TDG wrote the first draft of the protocol. TDG, SNP, and TE revised the
protocol. SNP performed the literature searches, while TDG extracted search hits, and did screening by
title, abstract, fulltext, data extraction, and risk of bias assessment, while SNP checked all procedures
afterwards in duplicate, and TE resolved discrepancies. SNP handled communications with trialists,
performed the statistical analysis, and graded the quality of evidence with GRADE, while TDG checked
this. TDG wrote the first draft of the manuscript. SNP and TE assisted in the interpretation of the results
and revised the manuscript draft. SNP submitted the manuscript, is the guarantor and responsible for the
accuracy of the data and for future updates of the review.
Deviations from protocol
 Additional analyses including subgroup analyses, meta-regressions, sensitivity analyses, and
analyses of reporting bias were originally planned in the protocol, but could not be performed due
to the limited number of available studies.
 The possibility of using network meta-analysis to directly compare all available interventions was
considered during the protocol stage. This was however not possible due to the small number of
interventions being compared in the identified trials and the sparse connections in the network.
 The Number Needed to Treat was planned to be used to clinically translate statistically significant
RRs, but no such instance was encountered.
Acknowledgements
None.
Conflict of Interest
The authors of this manuscript certify that they have no proprietary, financial, or other personal interest of
any nature or kind in any product, service, and/or company that is presented in this article.
16

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Interventions for dental fluorosis: A systematic review

Di Giovanni, Tamara ; Eliades, Theodore ; Papageorgiou, Spyridon N

Posted at the Zurich Open Repository and Archive, University of Zurich

Originally published at:

N. Papageorgiou, DDS, Dr Med Dent1

Running title: interventions for dental fluorosis

trials • Systematic review

Correspondence: Spyridon N. Papageorgiou, Clinic of Orthodontics and Pediatric Dentistry, Center of

/ Fax: +41 44 634 43 35; e-mail: [email protected]

treatment of fluorosed enamel.

(CIs) were calculated and assessed with the GRADE approach.

promising treatment for dental fluorosis, followed by bleaching and microabrasion.

where enamel development is disrupted and the resulting enamel is hypomineralized.1

Optically, dental fluorosis is characterized by hypomineralization of tooth enamel, seen as

amelogenesis the severity of symptoms varies and requires different measures.7

microabrasion, dental veneers, or crowns2,10 or a combination of methods.11,12 Since patients with

fluorotic stains, due to the resin’s similar to enamel refractive index.

at least one intervention in any clinical setting.

2 | MATERIALS AND METHODS

2.1 | Protocol and registration

2.2 | Eligibility criteria

2.3 | Information sources and literature search

included trials and relevant reviews were manually searched as well.

2.4 | Study selection

abovementioned reasons were finally included in our review.

2.5 | Data collection

2.6 | Risk of bias in individual trials

2.7 | Data synthesis

2.8 | Risk of bias across studies and additional analyses

3.1 | Study selection

3.2 | Study characteristics

timing ranging from directly post-treatment up to six months post-treatment.

3.3 | Risk of bias within studies

3.4 | Results of individual studies and data synthesis

Compared to no treatment, bleaching improved all colorimetric aspects according to the

International Commission on Illumination to a statistically and clinically significant extent. Although

of contributing evidence according to the Grading of Recommendations, Assessment,

As far as direct comparisons between interventions are concerned, bleaching was

4). Compared to bleaching, microabrasion resulted in a significantly smaller esthetic improvement

Furthermore, compared to bleaching, all other tested interventions, including resin

bleaching might not lead to better results.

3.5 | Risk of bias across studies and additional analyses

quality, bleaching is effective in significantly improving the colorimetric properties of fluorosed

Additionally, compared to bleaching, microabrasion seems to be associated with smaller esthetic

to be associated with greater esthetic improvements (P<0.001; Appendix S4).

As far as different interventions are compared, microabrasion was found to be significantly

GRADE analysis11 compared microabrasion alone and microabrasion followed by home

bleaching, but found no added value from subsequent bleaching.

similarities to enamel fluorotic stains.22,23

included grey literature.

bleaching and microabrasion. Additionally, no additional gains were found compared to

conventional resin infiltration by increased application time of the etchant on enamel or

moderate to high risk of bias.

man. J. Dent. Res. 69 Spec No, 692–700 (1990).

4. Bronckers, A. L., Lyaruu, D. M. & DenBesten, P. K. The impact of fluoride on ameloblasts

6. Ng, F. & Manton, D. Aesthetic management of severely fluorosed incisors in an adolescent