Introduction: This study investigated the effectiveness of titanium tetrafluoride (TiF4) varnish compared to sodium fluoride (NaF) varnish for preventing and remineralizing white spot lesions (WSLs) in individuals undergoing orthodontic treatment. Methods: This randomized, placebo-controlled, and double-blinded study was conducted with sixty-five adolescents who were selected based on caries activity and then randomized into three parallel groups: G1 (placebo varnish), G2 (5% NaF varnish), and G3 (4% TiF4 varnish). Volunteers received varnish application weekly for the first 4 weeks, after 6 (T1) and 12 (T2) months. The measured outcomes included prevention of new WSLs and reversal/progression of WSLs, assessed by Nyvad and International Caries Detection and Assessment System (ICDAS) indices, as well as quantitative light-induced fluorescence. χ2, ANOVA, and Kruskall-Wallis tests were applied. The level of significance was set at 0.05, and post hoc Bonferroni test for p values was performed to correct for multiple comparisons. Results: 1,274 teeth were included; 70.5% were Nyvad 0, and 29.5% were Nyvad 1, with no differences between the groups at baseline (T0). Regarding ICDAS, 70.5% were ICDAS 0, 21.6% were ICDAS 1, and 7.9% were ICDAS 2. G1 showed an increasing prevalence of WSLs at T1 and maintained stable at T2; G2 exhibited a decline at T2, while G3 experienced a decrease at T1 and T2 (p < 0.01). Incidence of WSLs at T2 was 10.2% (G1), 5.6% (G2), and 1.4% (G3). The percentage of teeth initially scored as Nyvad 0 that progressed to Nyvad 1 was 13%, 6.8%, and 1% for G1, G2, and G3, respectively. Conversely, the percentage of teeth initially scored as Nyvad 1 that regressed to Nyvad 0 or Nyvad 2 (T0–T2) was 14%, 49.3%, and 74.4%, respectively (p < 0.001). As for the ICDAS index, regression was observed in 6.5%, 17.8%, and 24%, while progression was observed in 14.9%, 7.7% and 0.9% for G1, G2, and G3, respectively (p < 0.001). Significant differences among the 3 groups for integrated fluorescence loss (mean ± SD, G1: −14.28 ± 9.47, G2: −11.10 ± 11.49, and G3: −6.77 ± 11.00) were found at T2 (p < 0.01). Conclusion: Both varnishes demonstrated the ability to prevent and remineralize WSLs. However, TiF4 varnish exhibited the most effective control over WSLs during the 12-month orthodontic treatment.

This study examined the effectiveness of two fluoride varnishes, titanium tetrafluoride (TiF4) and sodium fluoride (NaF), in preventing and remineralizing white spot lesions (WSLs) in individuals undergoing orthodontic treatment. We conducted a double-blinded, placebo-controlled trial with 65 adolescents randomized into three groups: placebo, NaF, and TiF4 varnish. These varnishes were applied weekly for the first month and then at 6 and 12 months. Our findings indicate that TiF4 varnish was the most effective in preventing new WSLs and promoting the remineralization of existing ones. The incidence of WSLs after 12 months was lowest in the TiF4 group (1.4%), followed by the NaF group (5.6%), and highest in the placebo group (10.2%). The placebo group exhibited a continuous increase in WSLs, while the NaF group showed improvement only at 12 months, and the TiF4 group demonstrated improvement at both 6 and 12 months. All groups experienced reduced visible plaque, with no significant differences between the groups. In terms of remineralization, TiF4 varnish demonstrated substantial improvements, with the best results observed at 12 months. In conclusion, TiF4 varnish proved most effective in preventing and remineralizing WSLs in a 12-month follow-up during orthodontic treatment. These results suggest that TiF4 varnish offers promise in managing WSLs in orthodontic patients. This study’s findings have significant implications for the prevention and management of dental caries.

1.
Chapman
JA
,
Roberts
WE
,
Eckert
GJ
,
Kula
KS
,
Gonzalez-Cabezas
C
.
Risk factors for incidence and severity of white spot lesions during treatment with fixed orthodontic appliances
.
Am J Orthod Dentofacial Orthop
.
2010
;
138
(
2
):
188
94
.
2.
Gwinnett
AJ
,
Ceen
RF
.
Plaque distribution on bonded brackets: a scanning microscope study
.
Am J Orthod
.
1979
;
75
(
6
):
667
77
.
3.
Roberts
WE
,
Mangum
JE
,
Schneider
PM
.
Pathophysiology of demineralization, Part II: enamel white spots, cavitated caries, and bone infection
.
Curr Osteoporos Rep
.
2022
;
20
(
1
):
106
19
.
4.
Ogaard
B
,
Rolla
G
,
Arends
J
.
Orthodontic appliances and enamel demineralization. Part 1. Lesion development
.
Am J Orthod Dentofacial Orthop
.
1988
;
94
(
1
):
68
73
.
5.
Ogaard
B
.
White spot lesions during orthodontic treatment: mechanisms and fluoride preventive aspects
.
Semin Orthod
.
2008
;
14
(
3
):
183
93
.
6.
Gorelick
L
,
Geiger
AM
,
Gwinnett
AJ
.
Incidence of white spot formation after bonding and banding
.
Am J Orthod
.
1982
;
81
(
2
):
93
8
.
7.
Sardana
D
,
Schwendicke
F
,
Kosan
E
,
Tufekci
E
.
White spot lesions in orthodontics: consensus statements for prevention and management
.
Angle Orthod
.
2023
;
93
(
6
):
621
8
.
8.
Sonesson
M
,
Twetman
S
.
Prevention of white spot lesions with fluoride varnish during orthodontic treatment with fixed appliances: a systematic review
.
Eur J Orthod
.
2023
;
45
(
5
):
485
90
.
9.
Erbe
C
,
Hartmann
L
,
Schmidtmann
I
,
Ohlendorf
D
,
Wehrbein
H
.
A novel method quantifying caries following orthodontic treatment
.
Sci Rep
.
2021
;
11
(
1
):
21347
.
10.
Mattousch
TJ
,
van der Veen
MH
,
Zentner
A
.
Caries lesions after orthodontic treatment followed by quantitative light-induced fluorescence: a 2-year follow-up
.
Eur J Orthod
.
2007
;
29
(
3
):
294
8
.
11.
Sonesson
M
,
Brechter
A
,
Lindman
R
,
Abdulraheem
S
,
Twetman
S
.
Fluoride varnish for white spot lesion prevention during orthodontic treatment: results of a randomized controlled trial 1 year after debonding
.
Eur J Orthod
.
2021
;
43
(
4
):
473
7
.
12.
Farhadian
N
,
Miresmaeili
A
,
Eslami
B
,
Mehrabi
S
.
Effect of fluoride varnish on enamel demineralization around brackets: an in-vivo study
.
Am J Orthod Dentofacial Orthop
.
2008
;
133
(
4 Suppl l
):
S95
8
.
13.
Al Mulla
AH
,
Kharsa
SA
,
Birkhed
D
.
Modified fluoride toothpaste technique reduces caries in orthodontic patients: a longitudinal, randomized clinical trial
.
Am J Orthod Dentofacial Orthop
.
2010
;
138
(
3
):
285
91
.
14.
Sonesson
M
,
Brechter
A
,
Abdulraheem
S
,
Lindman
R
,
Twetman
S
.
Fluoride varnish for the prevention of white spot lesions during orthodontic treatment with fixed appliances: a randomized controlled trial
.
Eur J Orthod
.
2020
;
42
(
3
):
326
30
.
15.
Sardana
D
,
Ekambaram
M
,
Yang
Y
,
McGrath
CP
,
Yiu
CKY
.
Caries-preventive effectiveness of two different fluoride varnishes: a randomised clinical trial in patients with multi-bracketed fixed orthodontic appliances
.
Int J Paediatr Dent
.
2023
;
33
(
1
):
50
62
.
16.
Stecksen-Blicks
C
,
Renfors
G
,
Oscarson
ND
,
Bergstrand
F
,
Twetman
S
.
Caries-preventive effectiveness of a fluoride varnish: a randomized controlled trial in adolescents with fixed orthodontic appliances
.
Caries Res
.
2007
;
41
(
6
):
455
9
.
17.
Sonesson
M
,
Twetman
S
,
Bondemark
L
.
Effectiveness of high-fluoride toothpaste on enamel demineralization during orthodontic treatment-a multicenter randomized controlled trial
.
Eur J Orthod
.
2014
;
36
(
6
):
678
82
.
18.
Benson
PE
,
Parkin
N
,
Dyer
F
,
Millett
DT
,
Germain
P
.
Fluorides for preventing early tooth decay (demineralised lesions) during fixed brace treatment
.
Cochrane Database Syst Rev
.
2019
;
2019
(
11
):
CD003809
.
19.
Recommendations for using fluoride to prevent and control dental caries in the United States. Centers for Disease Control and Prevention
.
MMWR Recomm Rep
.
2001
;
50
(
RR-14
):
1
42
.
20.
Chevitarese
AB
,
Leite
KLF
,
Dutra
PB
,
Pithon
MM
,
Faria
LCM
,
Ruellas
ACO
.
Effect of an aqueous 4% titanium tetrafluoride solution on preventing caries in orthodontic patients: a controlled clinical trial
.
Dental Press J Orthod
.
2023
;
28
(
1
):
e2321304
.
21.
Dos Santos
DMS
,
Pires
JG
,
Silva
AB
,
Salomao
PMA
,
Buzalaf
MAR
,
Magalhaes
AC
.
Protective effect of 4% titanium tetrafluoride varnish on dentin demineralization using a microcosm biofilm model
.
Caries Res
.
2019
;
53
(
5
):
576
83
.
22.
Comar
LP
,
Wiegand
A
,
Moron
BM
,
Rios
D
,
Buzalaf
MA
,
Buchalla
W
, et al
.
In situ effect of sodium fluoride or titanium tetrafluoride varnish and solution on carious demineralization of enamel
.
Eur J Oral Sci
.
2012
;
120
(
4
):
342
8
.
23.
Comar
LP
,
Souza
BM
,
Martins
J
,
Santos
MG
,
Buzalaf
MAR
,
Magalhaes
AC
.
Response of carious enamel to TiF(4) varnish treatment under diverse cariogenic activities in situ
.
J Dent
.
2017
;
63
:
81
4
.
24.
Alexandria
AK
,
Nassur
C
,
Nobrega
CBC
,
Branco-de-Almeida
LS
,
Dos Santos
KRN
,
Vieira
AR
, et al
.
Effect of TiF(4) varnish on microbiological changes and caries prevention: in situ and in vivo models
.
Clin Oral Investig
.
2019
;
23
(
6
):
2583
91
.
25.
Magalhaes
AC
,
Comar
LP
,
Rios
D
,
Delbem
AC
,
Buzalaf
MA
.
Effect of a 4% Titanium Tetrafluoride (TiF4) varnish on demineralisation and remineralisation of bovine enamel in vitro
.
J Dent
.
2008
;
36
(
2
):
158
62
.
26.
Souza
BM
,
Silva
MS
,
Braga
AS
,
Santos
D
,
Carvalho
TS
,
Santos
NMD
, et al
.
Acceptability and effect of TiF4 on dental caries: a randomized controlled clinical trial
.
Braz Oral Res
.
2021
;
35
:
e121
.
27.
Gao
SS
,
Zhang
S
,
Mei
ML
,
Lo
EC
,
Chu
CH
.
Caries remineralisation and arresting effect in children by professionally applied fluoride treatment: a systematic review
.
BMC oral health
.
2016
;
16
:
12
.
28.
Comar
LP
,
Souza
BM
,
Al-Ahj
LP
,
Martins
J
,
Grizzo
LT
,
Piasentim
IS
, et al
.
Mechanism of action of TiF4 on dental enamel surface: SEM/EDX, KOH-soluble F, and X-ray diffraction analysis
.
Caries Res
.
2017
;
51
(
6
):
554
67
.
29.
Fejerskov
O
,
Thylstrup
A
,
Larsen
MJ
.
Rational use of fluorides in caries prevention. A concept based on possible cariostatic mechanisms
.
Acta Odontol Scand
.
1981
;
39
(
4
):
241
9
.
30.
Ribeiro
CC
,
Gibson
I
,
Barbosa
MA
.
The uptake of titanium ions by hydroxyapatite particles-structural changes and possible mechanisms
.
Biomaterials
.
2006
;
27
(
9
):
1749
61
.
31.
Schulz
KF
,
Altman
DG
,
Moher
D
;
CONSORT Group
.
CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials
.
BMJ
.
2010
;
340
:
c332
.
32.
Nyvad
B
,
Machiulskiene
V
,
Baelum
V
.
Construct and predictive validity of clinical caries diagnostic criteria assessing lesion activity
.
J Dent Res
.
2003
;
82
(
2
):
117
22
.
33.
Pitts
NB
,
Ekstrand
KR
;
ICDAS Foundation
.
International Caries Detection and Assessment System (ICDAS) and its International Caries Classification and Management System (ICCMS): methods for staging of the caries process and enabling dentists to manage caries
.
Community Dent Oral Epidemiol
.
2013
;
41
(
1
):
e41
52
.
34.
Moraes
SM
,
Koshino
LA
,
Carvalho
TS
,
Souza
BM
,
Honório
HM
,
Garib
DG
, et al
.
TiF4 varnish in the prevention and remineralization of white spot lesions during orthodontic treatment
. 69th ORCA Congress June 29 - July 2, 2022;
Cagliari, Sardinia, Italy
:
Caries Research
;
2022
. p.
245
.
35.
Almeida
MQ
,
Costa
OX
,
Ferreira
JM
,
Menezes
VA
,
Leal
RB
,
Sampaio
FC
.
Therapeutic potential of Brazilian fluoride varnishes: an in vivo study
.
Braz Dent J
.
2011
;
22
(
3
):
193
7
.
36.
Ferreira
JM
,
Aragao
AK
,
Rosa
AD
,
Sampaio
FC
,
Menezes
VA
.
Therapeutic effect of two fluoride varnishes on white spot lesions: a randomized clinical trial
.
Braz Oral Res
.
2009
;
23
(
4
):
446
51
.
37.
Ainamo
J
,
Bay
I
.
Problems and proposals for recording gingivitis and plaque
.
Int Dent J
.
1975
;
25
(
4
):
229
35
.
38.
Zero
DT
.
Dental caries process
.
Dent Clin North Am
.
1999
;
43
(
4
):
635
64
.
39.
Thylstrup
A
,
Bruun
C
,
Holmen
L
.
In vivo caries models: mechanisms for caries initiation and arrestment
.
Adv Dent Res
.
1994
;
8
(
2
):
144
57
.
40.
Tranaeus
S
,
Al-Khateeb
S
,
Bjorkman
S
,
Twetman
S
,
Angmar-Mansson
B
.
Application of quantitative light-induced fluorescence to monitor incipient lesions in caries-active children. A comparative study of remineralisation by fluoride varnish and professional cleaning
.
Eur J Oral Sci
.
2001
;
109
(
2
):
71
5
.
41.
Sitthisettapong
T
,
Doi
T
,
Nishida
Y
,
Kambara
M
,
Phantumvanit
P
.
Effect of CPP-ACP paste on enamel carious lesion of primary upper anterior teeth assessed by quantitative light-induced fluorescence: a one-year clinical trial
.
Caries Res
.
2015
;
49
(
4
):
434
41
.
42.
BASS
CC
.
An effective method of personal oral hygiene
.
J La State Med Soc
.
1954
;
106
(
2
):
57
.
43.
Toumba
KJ
,
Twetman
S
,
Splieth
C
,
Parnell
C
,
van Loveren
C
,
Lygidakis
N
.
Guidelines on the use of fluoride for caries prevention in children: an updated EAPD policy document
.
Eur Arch Paediatr Dent
.
2019
;
20
(
6
):
507
16
.
44.
Zanatta
FB
,
Moreira
CH
,
Rosing
CK
.
Association between dental floss use and gingival conditions in orthodontic patients
.
Am J Orthod Dentofacial Orthop
.
2011
;
140
(
6
):
812
21
.
45.
Little
RJ
,
D'Agostino
R
,
Cohen
ML
,
Dickersin
K
,
Emerson
SS
,
Farrar
JT
, et al
.
The prevention and treatment of missing data in clinical trials
.
N Engl J Med
.
2012
;
367
(
14
):
1355
60
.
46.
Carvalho
RN
,
Letieri
ADS
,
Vieira
TI
,
Santos
T
,
Lopes
RT
,
Neves
AA
, et al
.
Accuracy of visual and image-based ICDAS criteria compared with a micro-CT gold standard for caries detection on occlusal surfaces
.
Braz Oral Res
.
2018
;
32
:
e60
.
47.
Gomez
J
,
Zakian
C
,
Salsone
S
,
Pinto
SC
,
Taylor
A
,
Pretty
IA
, et al
.
In vitro performance of different methods in detecting occlusal caries lesions
.
J Dent
.
2013
;
41
(
2
):
180
6
.
48.
Al Maaitah
EF
,
Adeyemi
AA
,
Higham
SM
,
Pender
N
,
Harrison
JE
.
Factors affecting demineralization during orthodontic treatment: a post-hoc analysis of RCT recruits
.
Am J Orthod Dentofacial Orthop
.
2011
;
139
(
2
):
181
91
.
49.
Beerens
MW
,
Ten Cate
JM
,
Buijs
MJ
,
van der Veen
MH
.
Long-term remineralizing effect of MI Paste Plus on regression of early caries after orthodontic fixed appliance treatment: a 12-month follow-up randomized controlled trial
.
Eur J Orthod
.
2018
;
40
(
5
):
457
64
.
50.
Beerens
MW
,
van der Veen
MH
,
van Beek
H
,
ten Cate
JM
.
Effects of casein phosphopeptide amorphous calcium fluoride phosphate paste on white spot lesions and dental plaque after orthodontic treatment: a 3-month follow-up
.
Eur J Oral Sci
.
2010
;
118
(
6
):
610
7
.
51.
Silva
VM
,
Massaro
C
,
Buzalaf
MAR
,
Janson
G
,
Garib
D
.
Prevention of non-cavitated lesions with fluoride and xylitol varnishes during orthodontic treatment: a randomized clinical trial
.
Clin Oral Investig
.
2021
;
25
(
6
):
3421
30
.
52.
Atilla
AO
,
Ozturk
T
,
Eruz
MM
,
Yagci
A
.
A comparative assessment of orthodontic treatment outcomes using the Quantitative Light-induced Fluorescence (QLF) method between direct bonding and indirect bonding techniques in adolescents: a single-centre, single-blind randomized controlled trial
.
Eur J Orthod
.
2020
;
42
(
4
):
441
53
.
53.
Benson
PE
,
Pender
N
,
Higham
SM
.
Quantifying enamel demineralization from teeth with orthodontic brackets: a comparison of two methods. Part 2: validity
.
Eur J Orthod
.
2003
;
25
(
2
):
159
65
.
54.
Benson
PE
,
Pender
N
,
Higham
SM
.
Quantifying enamel demineralization from teeth with orthodontic brackets: a comparison of two methods. Part 1: repeatability and agreement
.
Eur J Orthod
.
2003
;
25
(
2
):
149
58
.
55.
Boersma
JG
,
van der Veen
MH
,
Lagerweij
MD
,
Bokhout
B
,
Prahl-Andersen
B
.
Caries prevalence measured with QLF after treatment with fixed orthodontic appliances: influencing factors
.
Caries Res
.
2005
;
39
(
1
):
41
7
.
56.
Zarif Najafi
H
,
Shavakhi
M
,
Pakshir
HR
.
Evaluation of the preventive effect of two concentrations of xylitol varnish versus fluoride varnish on enamel demineralization around orthodontic brackets: a randomized controlled trial
.
Eur J Orthod
.
2022
;
44
(
3
):
243
51
.
57.
Ten Cate
JM
.
Fluorides in caries prevention and control: empiricism or science
.
Caries Res
.
2004
;
38
(
3
):
254
7
.
58.
Buzalaf
MAR
,
Pessan
JP
,
Honorio
HM
,
Ten Cate
JM
.
Mechanisms of action of fluoride for caries control
.
Monogr Oral Sci
.
2011
;
22
:
97
114
.
59.
de Almeida Baldini Cardoso
C
,
Mangueira
DF
,
Olympio
KP
,
Magalhaes
AC
,
Rios
D
,
Honorio
HM
, et al
.
The effect of pH and fluoride concentration of liquid dentifrices on caries progression
.
Clin Oral Investig
.
2014
;
18
(
3
):
761
7
.
60.
Yagci
A
,
Seker
ED
,
Demirsoy
KK
,
Ramoglu
SI
.
Do total or partial etching procedures effect the rate of white spot lesion formation? A single-center, randomized, controlled clinical trial
.
Angle Orthod
.
2019
;
89
(
1
):
16
24
.
61.
Bevinagidad
S
,
Setty
S
,
Patil
A
,
Thakur
S
.
Estimation and correlation of salivary calcium, phosphorous, alkaline phosphatase, pH, white spot lesions, and oral hygiene status among orthodontic patients
.
J Indian Soc Periodontol
.
2020
;
24
(
2
):
117
21
.
62.
Flynn
LN
,
Julien
K
,
Noureldin
A
,
Buschang
PH
.
The efficacy of fluoride varnish vs a filled resin sealant for preventing white spot lesions during orthodontic treatment
.
Angle Orthod
.
2022
;
92
(
2
):
204
12
.
63.
Rechmann
P
,
Bekmezian
S
,
Rechmann
BMT
,
Chaffee
BW
,
Featherstone
JDB
.
MI Varnish and MI Paste Plus in a caries prevention and remineralization study: a randomized controlled trial
.
Clin Oral Investig
.
2018
;
22
(
6
):
2229
39
.
64.
van der Kaaij
NCW
,
Faaij
MJ
,
Ten Cate
JM
,
van der Veen
MH
.
The reproducibility of assessment of white spot lesions adjacent to orthodontic brackets, with a quantitative light induced fluorescence digital camera at different rotations of teeth: an in vitro study
.
BMC oral health
.
2018
;
18
(
1
):
209
.
65.
Wang
Y
,
Qin
D
,
Guo
F
,
Levey
C
,
Huang
G
,
Ngan
P
, et al
.
Outcomes used in trials regarding the prevention and treatment of orthodontically induced white spot lesions: a scoping review
.
Am J Orthod Dentofacial Orthop
.
2021
;
160
(
5
):
659
70.e7
.
66.
Trudeau
T
.
The Hawthorne study revisited
.
Hosp Top
.
1982
;
60
(
6
):
17
.
67.
Enaia
M
,
Bock
N
,
Ruf
S
.
White-spot lesions during multibracket appliance treatment: a challenge for clinical excellence
.
Am J Orthod Dentofacial Orthop
.
2011
;
140
(
1
):
e17
24
.
68.
Migliorati
M
,
Isaia
L
,
Cassaro
A
,
Rivetti
A
,
Silvestrini-Biavati
F
,
Gastaldo
L
, et al
.
Efficacy of professional hygiene and prophylaxis on preventing plaque increase in orthodontic patients with multibracket appliances: a systematic review
.
Eur J Orthod
.
2015
;
37
(
3
):
297
307
.
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