title: Interventions for orthodontically induced white spot lesions: a systematic review and meta-analysis.
abstract: Although orthodontic white spot lesions (WSLs) are one of the most often and most evident adverse effects of comprehensive fixed appliance treatment, the efficacy of interventions for WSLs has not yet been adequately assessed in an evidence-based manner.
  
  
  
  Aim of this systematic review was to assess the therapeutic and adverse effects of interventions to treat post-orthodontic WSLs from randomized trials in human patients.
  
  
  
  An unrestricted electronic search of eight databases from inception to May 2016.
  
  
  
  Randomized controlled trials assessing any interventions for post-orthodontic WSLs on human patients.
  
  
  
  After duplicate study selection, data extraction, and risk of bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MDs), standardized mean differences (SMDs), and odds ratios (ORs), including their 95% confidence intervals (CIs) were performed, followed by subgroup and sensitivity analyses.
  
  
  
  A total of 20 unique studies and a total of 942 (42 per cent male and 58% per cent female) patients were included, with an average age of 16.2 years and a mean number of 8.2 WSLs (range 2.2 to 45.4) per patient. These were allocated to adjunct treatment with casein phosphopeptide-stabilized amorphous calcium phosphate creams, external tooth bleaching, low- or high-concentration fluoride films, gels, mouthrinses or varnishes, resin infiltration, miswak chewing sticks, bioactive glass toothpastse, or to no adjunct treatment (i.e. conventional oral hygiene). The monthly use of fluoride varnish was the best supplement to improve WSLs in terms of lesion area (1 trial; MD = -0.80 mm2; 95% CI = -1.10, -0.50 mm2; P < 0.05; high quality) and enamel fluorescence (3 trials; SMD = -0.92; 95% CI = -1.32, -0.52; P < 0.05; high quality), followed by the use of fluoride film. WSL treatment did not provide a considerable improvement in their clinical evaluation (3 trials; OR = 0.97; 95% CI = 0.60, 1.56; P > 0.05; moderate quality), with imprecision due to small sample size being the main limitation of existing evidence.
  
  
  
  Based on the existing trials, interventions for post-orthodontic WSLs, mainly fluoride varnish, seem to be effective, but further research is needed to elucidate their clinical relevance.
  
  
  
  PROSPERO (CRD42016037538).
authors.affiliation: Clinic of Orthodontics and Pediatric Dentistry, Center of Dental Medicine, Faculty of Medicine, University of Zurich, Switzerland.
authors.forename: Damian
authors.initials: D
authors.lastname: Höchli
authors.affiliation: Clinic of Orthodontics and Pediatric Dentistry, Center of Dental Medicine, Faculty of Medicine, University of Zurich, Switzerland.
authors.forename: Monika
authors.initials: M
authors.lastname: Hersberger-Zurfluh
authors.affiliation: Clinic of Orthodontics and Pediatric Dentistry, Center of Dental Medicine, Faculty of Medicine, University of Zurich, Switzerland.|Department of Oral Technology, School of Dentistry, University of Bonn, Germany.
authors.forename: Spyridon N
authors.initials: SN
authors.lastname: Papageorgiou
authors.affiliation: Clinic of Orthodontics and Pediatric Dentistry, Center of Dental Medicine, Faculty of Medicine, University of Zurich, Switzerland.
authors.forename: Theodore
authors.initials: T
authors.lastname: Eliades
mesh_terms: D002130:Calcium Phosphates / Q000627:therapeutic use; D002327:Cariostatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003731:Dental Caries / Q000209:etiology / Q000628:therapy*; D019317:Evidence-Based Medicine / Q000379:methods; D005460:Fluorides, Topical / Q000627:therapeutic use; D006801:Humans; D009910:Oral Hygiene; D016910:Orthodontic Brackets / Q000009:adverse effects*; D014089:Tooth Remineralization / Q000379:methods*
chemical_list: D002130:Calcium Phosphates; D002327:Cariostatic Agents; D005460:Fluorides, Topical; C020243:calcium phosphate