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Prevention of incipient carious lesions with various interventions during fixed and removable orthodontic treatment. A systematic review and meta-analysis


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Figure 1.

PRISMA flowchart presenting the study selection and identification process.
PRISMA flowchart presenting the study selection and identification process.

Figure 2.

Risk of bias summary of studies included in the meta-analysis.
Risk of bias summary of studies included in the meta-analysis.

Figure 3.

Meta-analysis of WSL risk reduction with fluoride interventions, using a random-effects model. The forest plot shows the pooled effect of fluoride on WSL incidence.
Meta-analysis of WSL risk reduction with fluoride interventions, using a random-effects model. The forest plot shows the pooled effect of fluoride on WSL incidence.

Figure 4.

Heterogeneity assessment.
Heterogeneity assessment.

Figure 5.

GRADE evidence profile: caries prevention during orthodontic treatment.
GRADE evidence profile: caries prevention during orthodontic treatment.

Figure 6.

Pooled risk difference obtained from a fixed-effects model.
Pooled risk difference obtained from a fixed-effects model.

Reasons for exclusion of studies included by previous SRs.

Authors Title Reason Exclusion stage
Adiaens et al. (1990) The use of ‘Fluor Protector®’, a fluoride varnish, as a caries prevention method under orthodontic molar bands. In vitro Title/abstract screen
Twetman et al. (1995) Effect of an antibacterial varnish on mutans streptococci in plaque from enamel adjacent to orthodontic appliances Surrogate outcome Title/abstract screen
Madléna et al. (2000) Effect of chlorhexidine varnish on bacterial levels in plaque and saliva during orthodontic treatment Surrogate outcome Title/abstract screen
Demito et al (2004) The efficacy of a fluoride varnish in reducing enamel demineralization adjacent to orthodontic brackets: an in vitro study. In vivo Title/abstract screen
Skold-Larsson, K. et al. (2004) Effect of topical applications of a chlorhexidine/thymol-containing varnish on fissure caries assessed by laser fluorescence Non RCT Title/abstract screen
Luther et al. (2005) Fluoride releasing glass beads in orthodontic treatment to reduce decay: a randomized, controlled clinical trial. Outcome not reported Title/abstract screen
Vivaldi-Rodrigues et al. (2006) The effectiveness of a fluoride varnish in preventing the development of white spot lesions Split mouth + <6 months Title/abstract screen
Farhadian N, et al (2008) Effect of fluoride varnish on enamel demineralization around brackets: an in-vivo study In vivo Title/abstract screen
Bailey et al. (2009) Regression of post-orthodontic lesions by a remineralizing cream Post-orthodontic Title/abstract screen
Beerens et al. (2010) Effects of casein phosphopeptide amorphous calcium fluoride phosphate paste on white spot lesions and dental plaque after orthodontic treatment: a 3-month follow-up < 6 months Title/abstract screen
Baeshen et al. (2011) Effect of fluoridated chewing sticks (Miswaks) on white spot lesions in postorthodontic patients Post-orthodontic Title/abstract screen
Brochner et al. (2011) Treatment of post-orthodontic white spot lesions with casein phosphopeptide-stabilised amorphous calcium phosphate Post-orthodontic Title/abstract screen
Enaia et al. (2011) White-spot lesions during multibracket appliance treatment: A challenge for clinical excellence. Non RCT Title/abstract screen
Richter et al. (2011) Incidence of caries lesions among patients treated with comprehensive orthodontics Retrospective Title/abstract screen
Robertson et al. (2011) MI Paste Plus to prevent demineralization in orthodontic patients: a prospective randomized controlled trial < 6 months Title/abstract screen
Shinaishin et al. (2011) Efficacy of light-activated sealant on enamel demineralization in orthodontic patients: an atomic force microscope evaluation Ex vivo Title/abstract screen
Akin et al. (2012) Can white spot lesions be treated effectively? Post-orthodontic Title/abstract screen
Du et al. (2012) Randomized controlled trial on fluoride varnish application for treatment of white spot lesion after fixed orthodontic treatment Post-orthodontic Title/abstract screen
Jumanca et al. (2012) Infiltration Therapy-an Alternative to Fluoride Varnish Application for Treatment of White Spot Lesion After Fixed Orthodontic Treatment. Post-orthodontic Title/abstract screen
Huang et al. (2013) Effectiveness of MI Paste Plus and PreviDent fluoride varnish for treatment of white spot lesions: a randomized controlled trial Post-orthodontic Title/abstract screen
Baroni et al. (2014) A SEM and non-contact surface white light profilometry in vivo study of the effect of a creme containing CPP-ACP and fluoride on young etched enamel In vivo Title/abstract screen
Restrepo et al. (2015) Control of white spot lesion adjacent to orthodontic bracket with use of fluoride varnish or chlorhexidine gel In vivo Title/abstract screen
He et al. (2016) Comparative assessment of fluoride varnish and fluoride film for remineralization of postorthodontic white spot lesions in adolescents and adults over a 6-month period: a single-center, randomized controlled clinical trial, Post-orthodontic Title/abstract screen
Restrepo et al. (2016) Control of White Spot Lesions with Use of Fluoride Varnish or Chlorhexidine Gel During Orthodontic Treatment A Randomized Clinical Trial. < 6 months Title/abstract screen
Kirschneck et al. (2016) Efficacy of fluoride varnish for preventing white spot lesions and gingivitis during orthodontic treatment with fixed appliances-a prospective randomized controlled trial < 6 months Title/abstract screen
Singh et al. (2016) Effects of various remineralizing agents on the outcome of post-orthodontic white spot lesions (WSLs): a clinical trial Post-orthodontic Title/abstract screen
Turska-Szybka et al. (2016) Randomised Clinical Trial on Resin Infiltration and Fluoride Varnish vs Fluoride Varnish Treatment Only of Smooth-surface Early Caries Lesions in Deciduous Teeth. Non-orthodontic Title/abstract screen
Bock et al. (2017) Changes in white spot lesions following post-orthodontic weekly application of 1.25 per cent fluoride gel over 6 months-a randomized placebo-controlled clinical trial. Part I: photographic data evaluation Post-orthodontic Title/abstract screen
Bock et al. (2017) Changes in white spot lesions following post-orthodontic weekly application of 1.25 per cent fluoride gel over 6 months-a randomized placebo-controlled clinical trial. Part II: clinical data evaluation Post-orthodontic Title/abstract screen
Ebrahimi et al. (2017) The effects of three remineralizing agents on regression of white spot lesions in children: a two week, single-blind, randomized clinical trial < 6 months Title/abstract screen
Karabekiroglu et al. (2017) Treatment of post-orthodontic white spot lesions with CPP-ACP paste: A three year follow up study Post-orthodontic Title/abstract screen
Beerens et al. (2018) 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 Post-orthodontic Title/abstract screen
Heravi et al. (2018) Effectiveness of MI Paste Plus and Remin Pro on remineralization and color improvement of postorthodontic white spot lesions Post-orthodontic Title/abstract screen

Previous systematic reviews and meta-analyses.

Systematic reviews
Author Pre-registered? Intervention Studies used Risk of bias done? GRADE? Guideline? Comments
Derks (2004) N F, CHX, GIC RCTs and split mouth studies N N N Split mouth studies-clustering effect not considered (11/16 = 69% of included studies). Overall risk of bias not calculated.
Benson et al (2013) Y F RCTs Y Y N Cochrane review
Lapenaite et al (2016) N F and CPP-ACP RCTs and quasi-RCTs N N N No risk of bias assessment
Rahimi et al (2017) N F varnish RCTs, in vitro and in vivo N N N in vitro, in vivo studies used
Imani et al (2019) N CPP-ACP RCTs Y N N Post orthodontic WSL reduction.
Pithon et al (2019) Y CPP-ACP RCTS and non-RCTs Y N N Non-RCTs used
Sardana et al (2019) Y Self applied F RCTs and quasi-RCTs Y Y N During and post-orthodontic studies included without sub group analyses. Both control and intervention are F.

Data from studies included in the qualitative synthesis.

Study (year, country) Sample size Age of participants Intervention Control/Comparison
Ogaard et al. (1997, Sweden) 198 (101 experimental; 97 controls) 12-15 Fluoride varnish (Fluor Protector); Antimicrobial varnish (Cervitec) Placebo and F varnish
Alexander et al. (2000, US) 72 (22:25:25 – controls, 2*experimental groups) Mean 13.93 Group 1: Tooth brush instruction, high potency and frequency F gel; Group 2: Tooth brush instruction, high potency and frequency dentrifice Tooth brush instruction, low potency, high frequency F rinse
Weiss et al. (2005, Germany) 68 (34 per group) Mean 14.1 Chlorhexidine gel in chair and 2.26% NaF varnish 40% chlorhexidine varnish and 2.26% NaF varnish
Al Mulla et al. (2010, Saudi Arabia) 100 (51 experimentals; 49 controls) Mean 16.9 Modified F toothpaste technique: minimal rinsing of paste after brushing (1450 ppm F) Regular brushing (1450 ppm F)
Hoffman et al. (2015, USA) 48 (24 per group) Mean 15.6 in experimental group 15.3 in control 5000ppm NaF with 5% NovaMin paste 1500ppm F toothpaste
Suetenkov et al. (2015, Russia) 60 (30 per group) 12-13. Laser therapy (OPTODAN and FotoSan) with control goup regime Twice daily brushing with 1400ppm F paste, 0.05% CHX mouthrinse for 10 days, F gel
Esenlik et al. (2016, Turkey) 40 (20 per group) Mean 17 CPP-ACP paste No treatment
Alavi et al. (2018, Iran) 40 (10 in each group) Mean 23 Group 1: 0.2% CHX varnish; Group 2: 5% NaF varnish Group 3: placebo varnish; Group 4: control
Gomeza et al. (2018, Spain) 20 (10 per group) Mean 15.0 in experimental group 14.2 in control Photodynamic therapy – Methylene blue activated by laser at 670nm Ultrasonic scaler clean
Janatschke et al. (2001, Germany) 33 (18 experimentals; 15 controls) Median 15 40% chlorhexidine varnish Placebo
Ogaard et al. (2006, Sweden) 97 (50 experimentals; 47 controls) Mean 14.4 AmF/SnF2 (1400ppm F) toothpaste and 250ppm F rinse NaF (1400ppm F) toothpaste and 250ppm F rinse
Steckson-Blicks et al. (2007, Sweden) 257 (132 experimentals; 125 controls) 12-15. F varnish (0.1% F) Placebo varnish
Jiang et al. (2013, China) 95 (48 experimentals; 47 controls) 10-20. 1.23% APF foam Placebo foam
Fretty (2014, USA) 55 13 1.23% APF foam Placebo foam
Sonesson et al. (2014, Sweden) 391 (188 experimentals; 192 controls) 11-16. 5000ppm NaF paste 1450ppm NaF paste
van der Kaaij et al. (2015, Netherlands) 81 (36 experimentals; 45 controls) Mean 13.3 250ppm F rinse (100ppm AmF, 150ppm NaF) Placebo rinse
Zotti et al. (2016, Italy) 80 (40 per group) Mean 14.1 in study group 13.6 in control Whatsapp based reminder re OH No app based reminders
Rechmann et al. (2018, USA) 37 (19 experimentals, 18 controls) Mean 15.9 1100ppm F paste with MI Varnish (10% w/v CPP-ACP, 5% NaF) and MI Paste Plus (10% w/v CPP-ACP, 0.2% 900ppm NaF) 1100ppm F paste with 0.05% NaF rinse

Reasons for exclusion following full-text assessment.

Study Reason for exclusion
Dimitriadis AG, Sassouni V, and Draus FJ (1974). Non randomised
Boyd RL (1992). Non randomised
Boyd RL (1993). Non randomised
Turner PJ (1993). Non randomised
Banks PA and Richmond S (1994). Split mouth
Boyd RL and Rose CM (1994). Non randomised
Silverman E, Cohen M, Demke RS, and Silverman M (1995). Non randomised
Trimpeneers LM and Dermaut LR (1996). Non randomised
Marini I, Pellicioni GA, Vecchiet F, Bonetti GA, Checchi L. (1999). Baseline data not available
Wenderoth CJ, Weinstein M, and Borislow AJ (1999). Split mouth
Banks PA, Chadwick SM, Asher-McDade C, Wright JL (2000). Baseline data not available
Hsu CYS, Jordan TH, Dederich DN, and Wefel JS (2000). Non randomised
Harazaki M, Hayakawa K, Fukui T, Isshiki Y, and Powell LG (2001). Non randomised
Ogaard B, Larsson E, Henriksson T, Birkhed D, and Bishara SE (2001). Baseline data not available
Donly KJ (2003). Ex-vivo
Zimmer BW and Rottwinkel Y (2004). Non randomised
Abdullah AZ, Stafford SM, Brookes SJ, and Duggal MS (2006). In-vitro
Miura KK, Ito IY, Enoki C, Elias AM, and Matsumoto MAN (2007). < 6 months
Shafi I (2008). Non-randomised
Dong YN, Chen M, and Ren XM (2009). Split mouth
Tenuta LMA, Zamataro CB, Del Bel Cury AA, Tabchoury CPM, and Cury JA (2009). Split mouth
Akkurt MD, Amasyali M, Ozcan S, Yagci A, Basak F, and Sagdic D (2011). < 6 months
Buck T, Pellegrini P, Sauerwein R, Leo MC, Covell Jr DA, Maier T, and Machida CA (2011). Split mouth
Demito CF, Rodrigues GV, Ramos AL, and Bowman SJ (2011). Split mouth
Najibfard K, Chedjieu I, Ramalingam K, and Amaechi BT (2011). < 6 months
Stafford GL (2011). Non-randomised
Sollenius O, Karlsson L, Petersson LG, and Twetman S (2013). < 6 months
Atwa ALDA,. AbuShahba RY, Mostafa M, and Hashem MI (2014). < 6 months
Melo MA, Morais WA, Passos VF, Lima JP, and Rodrigues LK (2014). In-vitro
Ghajari MF, Eslamian L, Rad AN, and Morovati SP (2015). Baseline data not available
Masoud MI, Allarakia R, Alamoudi NM, Nalliah R, and Allareddy V (2015). Outcome data not available
Paschoal MA, Moura CMZ, Jeremias F, Souza JF, Bagnato VS, Giusti JSM, and Santos-Pinto L (2015). < 6 months
Restrepo M, Bussaneli DG, Jeremias F, Cordeiro RCL, Magalhaes AC, Palomari Spolidorio DM, and Santos-Pinto L (2015). Ex-vivo
Zhang N, Chen C, Weir MD, Bai Y, and Xu HH (2015). Ex-vivo
Bussaneli DG, Jeremias F, Cordeiro RC, Raveli DB, Magalhaes AC, Candolo C, and Santos-Pinto L (2016). < 6 months
Gizani S, Petsi G, Twetman S, Caroni C, Makou M, Papagianoulis L (2016). Baseline data not available
Hammad S and Abdellatif A (2016). Baseline data not available
Miller CC, Burnside G, Higham SM, Flannigan NL (2016). Baseline data not available
Oosterkamp BCM, Wafae A, Schols JGJH, van der Sanden WJM, and Wensing M (2016). Different topic
Korkmaz YN and Yagci A (2018). < 6 months
Liptak L, Szabo K, Nagy G, Marton S, and Madlena M (2018). Split mouth
Benson PE, Alexander-Abt J, Cotter S, Dyer F, Fenesha F, Patel A, Campbell C, Crowley N & Millett D (2019). Baseline data not available
Enerback H, Moller M, Nylen C, Odman Bresin C, Ostman Ros I, and Westerlund A (2019). Different topic
Sonesson M, Brechter A, Abdulraheem S, Lindman R, Twetman S (2019). Baseline data not available

Risk of bias assessment of RCTs included in the qualitative analysis.

Trial Bias from randomisation process Bias from deviations from intended interventions Bias from missing outcome data Bias from measurement of the outcome Bias from selection of the reported result Overall bias
Ogaard et al. (1997) High Low Low Some concerns Low High
Alexander et al. (2000) High Some concerns Low Some concerns Low High
Jenatschke et al. (2001) Some concerns Low Low Some concerns Some concerns Some concerns
Weiss et al. (2005) Some concerns Some concerns Low High Some concerns High
Ogaard et al. (2006) Some concerns Low Low Low Low Some concerns
Steckson-Blicks et al. (2007) Some concerns Low Low Low Some concerns Some concerns
Al Mulla et al. (2010) Some concerns Low Low High Some concerns High
Jiang et al. (2013) Low Low Low Low Some concerns Some concerns
Fretty (2014) Low Low Low High Some concerns High
Sonesson et al. (2014) Low Some concerns Low Low Some concerns Some concerns
Hoffman et al. (2015) Some concerns Low High High Some concerns High
Suetenkov et al. (2015) Some concerns Some concerns Low High Some concerns High
van der Kaaij et al. (2015) Low Low Low Low Some concerns Some concerns
Esenlik et al. (2016) High Some concerns High High Some concerns High
Zotti et al. (2016) Low Low Low Low Some concerns Some concerns
Alavi et al. (2018) Some concerns Some concerns High High Some concerns High
Gómez et al. (2018) High Low Some concerns Low Some concerns High
Rechmann et al. (2018) Low Some concerns Low Low Low Some concerns

MEDLINE OVID search strategy.

Search key words
1 Prevent*
2 Fluoride* or toothpaste* or tooth paste or mouthrinse* or mouth rinse* or mouth wash* or gel or varnish or NaF or SMFP
or SnF or APF or amine F or f releas* or dentrific*
3 tooth brushing or dental devices, home care/
4 Exp cariostatic agents/or cariostatic
5 Chlorhexidine or chlor hexidine
6 CPP ACP or casein phosphopeptide amorphous calcium phosphate
7 RMGI or resin modified glass ionomer*
8 SAP or self assembling peptide*
9 Oral hygiene or OHI
10 Or/1-9
11 caries or incipient lesion* or WSL or cavity or cavities or white spot
12 demineralization or demineralisation
13 or/11-12
14 fixed or orthodont* or brace* or edgewise or begg
15 removable or removed or appliance*
16 exp orthodontics/
17 or/14 -16
18 10 AND 13 AND 17
19 randomized controlled trial.pt
20 controlled clinical trial.pt
21 random* or blind*
22 trial or trials
23 or/19 – 22
24 18 AND 23
25 limit 24 to English language
eISSN:
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Sprache:
Englisch
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