Non-Cochrane · intervention · PM31888600

Evaluation of the efficacy of casein phosphopeptide-amorphous calcium phosphate on remineralization of white spot lesions in vitro and clinical research: a systematic review and meta-analysis.

Ma Xueling, Lin Xuandong, Zhong Tengfei, et al. · BMC oral health · 2019 · PubMed · doi:10.1186/s12903-019-0977-0

Oral HealthDental cariesAMSTAR 2: critically low (both extractors)
Full textEvery question was extracted from the full text, figures and supplements by two independent LLM extractors, disagreements adjudicated. Rows cite where in the review the value comes from.
Questions
6
current version
GRADE rated
0
No studies
0
Included studies
12
linked below
No studies 0 · 0%Ungraded 6 · 100%Very low 0 · 0%Low 0 · 0%Moderate 0 · 0%High 0 · 0%

Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.

Review question

ElementPlanned (methods)Found (results)
PopulationPatients with early enamel carious/white spot lesions (clinical); extracted human teeth free of enamel defects, microcracks or caries (in vitro)Children/adolescents with white spot lesions (clinical, n=2 studies, 129 patients aged 2.5-18 y); extracted human teeth with early/artificial enamel lesions (in vitro, n=10 studies)
InterventionRemineralizing agents based on CPP-ACP (any CPP-ACP product, e.g., MI Paste or Tooth Mousse)CPP-ACP pastes: GC Tooth Mousse, tooth mousse, GC Tooth Mousse Plus, MI Paste Plus (n=12)
ComparisonNon-CPP-ACP therapy: blank (no treatment), negative (placebo/deionized water), or positive (other intervention, e.g., fluoride toothpaste)Placebo/standard fluoride toothpaste (clinical); no treatment, soft drink, deionized water or remineralizing solutions (in vitro); baseline (clinical supplementary)
OutcomesRemineralization efficacy in clinical research; average surface roughness and surface microhardness in vitroQLF fluorescence loss (clinical, n=2); average surface roughness (in vitro, n=3); surface microhardness (in vitro, n=8: Vickers n=5, Knoop n=3)
Study designsRCTs, retrospective and prospective placebo-/blank-controlled parallel-group studies (clinical and in vitro)RCTs (clinical, n=2); in vitro experimental studies (n=10)
TimingNot specified4 weeks to 1 year (clinical); 6 hours to 30 days (in vitro)

Search date: May 20, 2019. Databases: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Ovid

Questions and results

CPP-ACP paste (casein phosphopeptide-amorphous calcium phosphate; e.g., Tooth Mousse/MI Paste) vs Placebo paste without CPP-ACP (fluoride toothpaste control)

Population: Patients with early enamel white spot lesions (children/adolescents, ages 2.5-18 years)
1 question
OutcomeEffectEvidenceStatus / GRADE
Quantitative light-induced fluorescence (QLF), fluorescence loss
4 weeks to 1 year
CPP-ACP toothpaste did not differ significantly from placebo paste (fluoride control) for white spot lesion remineralization on QLF (MD 0.08, 95% CI -0.91 to 1.08; ungraded).
Source: Results 'QLF detection from in clinical experimentation'; Fig. 3a; Abstract · same question in other reviews
MD 0.08 [-0.91, 1.08]2 studies · 129 participantsUngraded

CPP-ACP paste (casein phosphopeptide-amorphous calcium phosphate) vs Baseline (same subjects, pre-treatment)

Population: Patients with white spot lesions (children/adolescents)
1 question
OutcomeEffectEvidenceStatus / GRADE
Quantitative light-induced fluorescence (QLF), fluorescence loss
4 weeks to 1 year · CPP-ACP vs baseline
Compared with baseline, CPP-ACP significantly improved white spot lesions on QLF (SMD -0.43, 95% CI -0.79 to -0.07; ungraded).
Source: Discussion (supplementary QLF vs baseline analysis); Fig. 3d; Abstract · same question in other reviews
SMD -0.43 [-0.79, -0.07]2 studies · 62 participantsUngraded

CPP-ACP agent (e.g., GC Tooth Mousse, GC Tooth Mousse Plus, MI Paste Plus) vs Control (no treatment / negative control)

Population: Extracted human teeth with early/artificial enamel lesions (in vitro)
4 questions
OutcomeEffectEvidenceStatus / GRADE
Enamel surface microhardness
6 hours to 30 days
In vitro, CPP-ACP significantly increased enamel surface microhardness versus control (SMD 2.07, 95% CI 1.24 to 2.89; ungraded).
Source: Results 'SMH from in vitro experimentation'; Fig. 3c · same question in other reviews
SMD 2.07 [1.24, 2.89]8 studies · 170 participantsUngraded
Average enamel surface roughness
24 hours to 28 days
In vitro, CPP-ACP markedly reduced enamel surface roughness versus control (SMD -8.21, 95% CI -10.37 to -6.04; ungraded).
Source: Results 'Average surface roughness from in vitro experimentation'; Fig. 3b · same question in other reviews
SMD -8.21 [-10.37, -6.04]3 studies · 56 participantsUngraded
Enamel surface microhardness
6 hours to 30 days · Vickers microhardness
In vitro, CPP-ACP increased Vickers microhardness versus control (SMD 1.19, 95% CI 0.72 to 1.66; ungraded).
Source: Results 'SMH from in vitro experimentation'; Fig. 3c subgroup 1.1.1 · same question in other reviews
SMD 1.19 [0.72, 1.66]5 studies · 106 participantsUngraded
Enamel surface microhardness
5 to 7 days · Knoop microhardness
In vitro, CPP-ACP increased Knoop microhardness versus control (SMD 3.52, 95% CI 2.68 to 4.36; ungraded).
Source: Results 'SMH from in vitro experimentation'; Fig. 3c subgroup 1.1.2 · same question in other reviews
SMD 3.52 [2.68, 4.36]3 studies · 64 participantsUngraded

AMSTAR 2 appraisal

Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.

ItemExtractor AExtractor BAgree
1Research question includes PICO componentsYesYesyes
2Protocol established before the reviewcriticalNoNoyes
3Choice of study designs explainedNoYesno
4Comprehensive literature searchcriticalPartial YesPartial Yesyes
5Study selection in duplicateYesYesyes
6Data extraction in duplicateYesYesyes
7List of excluded studies with reasonscriticalNoNoyes
8Included studies described in detailYesYesyes
9Risk of bias assessed satisfactorilycriticalRCT: Yes · NRSI: N/ANRSI: No · RCT: Yesno
10Funding of included studies reportedNoNoyes
11Appropriate meta-analysis methodscriticalRCT: Yes · NRSI: N/ANRSI: No · RCT: Yesno
12Impact of risk of bias on the pooled resultsNoNoyes
13Risk of bias accounted for in interpretationcriticalYesYesyes
14Heterogeneity explainedYesYesyes
15Publication bias investigatedcriticalNoN/Ano
16Conflicts of interest reportedYesYesyes
OverallCritically LowCritically Lowyes

Included primary studies 12

Open as a trial list
StudyAlso included byOutcomes it informs hereTrial PICOResults
Bröchner 2014
Treatment of post-orthodontic white spot lesions with casein phosphopeptide-stabilised amorphous calcium phosphate
DOI:10.1007/s00784-010-0401-2
1 other reviewQuantitative light-induced fluorescence (QLF), fluorescence lossnot extracted yetnot extracted yet
Carvalho 2013
Protective effect of calcium nanophosphate and CPP-ACP agents on enamel erosion
DOI:10.1590/s1806-83242013000600004
this review onlyEnamel surface microhardnessnot extracted yetnot extracted yet
Carvalho 2014
matched by author and year (probable)
this review onlyEnamel surface microhardnessnot extracted yetnot extracted yet
Kargul 2012
matched by author and year (probable)
this review onlyEnamel surface microhardnessnot extracted yetnot extracted yet
Memarpour 2015
Efficacy of calcium‐ and fluoride‐containing materials for the remineralization of primary teeth with early enamel lesion
DOI:10.1002/jemt.22543
this review onlyAverage enamel surface roughnessnot extracted yetnot extracted yet
Poggio 2009
Protective effect on enamel demineralization of a CPP–ACP paste: an AFM in vitro study
DOI:10.1016/j.jdent.2009.07.011
this review onlyAverage enamel surface roughnessnot extracted yetnot extracted yet
Rallan 2013
Effect of various remineralising agents on human eroded enamel of primary teeth
DOI:10.1007/s40368-013-0085-9
this review onlyEnamel surface microhardnessnot extracted yetnot extracted yet
Rirattanapong 2012
matched by author and year (probable)
this review onlyEnamel surface microhardnessnot extracted yetnot extracted yet
Sitthisettapong 2014
Effect of CPP-ACP Paste on Enamel Carious Lesion of Primary Upper Anterior Teeth Assessed by Quantitative Light-Induced Fluorescence: A…
DOI:10.1159/000434728
this review onlyQuantitative light-induced fluorescence (QLF), fluorescence lossnot extracted yetnot extracted yet
Soares 2017
Assessment of Enamel Remineralisation After Treatment with Four Different Remineralising Agents: A Scanning Electron Microscopy (SEM) Study.
PMID:28571281
this review onlyEnamel surface microhardnessnot extracted yetnot extracted yet
Vyavhare 2015
Effect of Three Different Pastes on Remineralization of Initial Enamel Lesion: An in Vitro Study
DOI:10.17796/jcpd.39.2.yn2r54nw24l03741
this review onlyEnamel surface microhardnessnot extracted yetnot extracted yet
Zhou 2014
Casein phosphopeptide–amorphous calcium phosphate remineralization of primary teeth early enamel lesions
DOI:10.1016/j.jdent.2013.11.005
this review onlyAverage enamel surface roughnessnot extracted yetnot extracted yet

Overlap with other reviews

Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match).