White spot lesions – treatment options


White spot lesions or early caries lesions can be classified in the range 1-2 of the International Caries Detection and Assessment System (ICDAS) II. White spot lesions (WSLs) are commonly seen during orthodontic treatment and prevention and remineralisation of these early lesions is possible. Fluoride-based strategies are the main strategies but recently casein phosphopeptides (CPP), amorphous calcium phosphate (ACP), self-assembling peptide P11-4(SAP P11-4) and resin infiltration (RI) have been studies.

The aim of this review and network meta-analysis was to compare the efficacy of seven treatments for white spot lesions.


A protocol was registered on PROSPERO. Searches were conducted in the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PubMed, and Web of Science databases for 2007 to 2022.Two reviewers independently searched for, and selected studies extracted data as assessed risk of bias using the Cochrane RoB2 tool . Randomised controlled trials (RCTs) of treatment for WSLs (in vitro/clinical) were considered. Outcomes of interest were changes in QLF (quantitative photo-induced fluorescence), laser fluorescence (LF), and lesion area, A network meta-analysis (NMA) was conducted.


  • 42 studies (36 clinical, 6 in-vitro) met the inclusion criteria with 31 contributing to the NMA.
  • Active treatments included casein phosphor peptides- amorphous calcium phosphate (CPP-ACP), CPP-amorphous calcium fluoride phosphate (CPP-ACFP), fluoride varnish (FV) self-assembling peptide P11-4 and resin infiltration (RI).
  • Of the 36 clinical studies 22 were considered to be at moderate risk of bias and 12 at low risk with 2 at high risk.
  • 2 of the 6 in-vitro studies were assessed as at low risk of bias and 4 at moderate risk.
  • NMA showed a statistically significant difference in standard mean difference for P11-4, P11-4+FV, and RI. These are shown in the table below together with the SUCRA value (the higher SUCRA the value the higher the ranking).
Treatment Effect size (95%CI) SUCRA
P11-4 + FV -0.96 (-1.44 to -0.48) 89.7
RI -0.94 (-1.46 to -0.43) 88.7
P11-4 -0.56 (-0.96 to -0.15) 61.9
CPP-ACFP -0.42 (-0.84 to 0.00) 50.5
FV -0.25 (-0.51 to 0.02) 31.9
CPP-ACP -0.18 (-0.49 to 0.14) 24.0
Control N/A 3.3


The authors concluded: –

Our study compared and evaluated the effects of the treatment for WSLs. Both resin infiltration and SAP P11-4 have a positive therapeutic effect on WSLs. The clinical efficacy of both CPP-ACP-based and fluoride- based drugs is not significant. The combination of SAP P11-4 and fluoride varnish is a better strategy for treating WSLs.


Treatment of WSLs is a topic on which we have summarised numerous reviews (Dental Elf – White Spot Lesions -Blogs). The new review and NMA used a pre-registered protocol and searched a good range of databases but restricted to papers published between 2007 and 2020. A high proportion of the included studies have used digital measurements as outcome measures, but it is a point of discussion as to whether this is clinically relevant and meaningful to patients and clinicians. The recent Cochrane review on this topic (Dental Elf – 27th Nov 2019) suggested the use of standardised images and the use of more than one assessor. Only 12 of the 36 included clinical studies were considered to be at low risk of bias with only 5 having sample sizes of 100 or more patients and follow-up periods ranging from 3 weeks to 36 months. While this NMA is suggestive of beneficial effects from newer interventions the quality of evidence is limited. Future studies would benefit from the use of common outcomes measures and being conducted and reported in line with SPIRIT and CONSORT guidelines.


Primary Paper

Xie Z, Yu L, Li S, Li J, Liu Y. Comparison of therapies of white spot lesions: a systematic review and network meta-analysis. BMC Oral Health. 2023 Jun 1;23(1):346. doi: 10.1186/s12903-023-03076-x. PMID: 37264364; PMCID: PMC10233982.

Review protocol on PROSPERO

Other references

Dental Elf – 27th Nov 2019

White spot lesions: Topical fluoride for prevention during fixed orthodontic treatment

Dental Elf – White Spot Lesions -Blogs


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