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
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
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients 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) |
| Intervention | Remineralizing 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) |
| Comparison | Non-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) |
| Outcomes | Remineralization efficacy in clinical research; average surface roughness and surface microhardness in vitro | QLF 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 designs | RCTs, retrospective and prospective placebo-/blank-controlled parallel-group studies (clinical and in vitro) | RCTs (clinical, n=2); in vitro experimental studies (n=10) |
| Timing | Not specified | 4 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)
| Outcome | Effect | Evidence | Status / 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 participants | Ungraded |
CPP-ACP paste (casein phosphopeptide-amorphous calcium phosphate) vs Baseline (same subjects, pre-treatment)
| Outcome | Effect | Evidence | Status / 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 participants | Ungraded |
CPP-ACP agent (e.g., GC Tooth Mousse, GC Tooth Mousse Plus, MI Paste Plus) vs Control (no treatment / negative control)
| Outcome | Effect | Evidence | Status / 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 participants | Ungraded |
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 participants | Ungraded |
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 participants | Ungraded |
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 participants | Ungraded |
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.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | No | No | yes |
| 3Choice of study designs explained | No | Yes | no |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Yes | Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: N/A | NRSI: No · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: Yes · NRSI: N/A | NRSI: No · RCT: Yes | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | No | N/A | no |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |
Included primary studies 12
Open as a trial list| Study | Also included by | Outcomes it informs here | Trial PICO | Results |
|---|---|---|---|---|
| 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 review | Quantitative light-induced fluorescence (QLF), fluorescence loss | not extracted yet | not extracted yet |
| Carvalho 2013 Protective effect of calcium nanophosphate and CPP-ACP agents on enamel erosion DOI:10.1590/s1806-83242013000600004 | this review only | Enamel surface microhardness | not extracted yet | not extracted yet |
| Carvalho 2014 matched by author and year (probable) | this review only | Enamel surface microhardness | not extracted yet | not extracted yet |
| Kargul 2012 matched by author and year (probable) | this review only | Enamel surface microhardness | not extracted yet | not 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 only | Average enamel surface roughness | not extracted yet | not 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 only | Average enamel surface roughness | not extracted yet | not 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 only | Enamel surface microhardness | not extracted yet | not extracted yet |
| Rirattanapong 2012 matched by author and year (probable) | this review only | Enamel surface microhardness | not extracted yet | not 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 only | Quantitative light-induced fluorescence (QLF), fluorescence loss | not extracted yet | not 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 only | Enamel surface microhardness | not extracted yet | not 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 only | Enamel surface microhardness | not extracted yet | not 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 only | Average enamel surface roughness | not extracted yet | not 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).
| Review | Shared studies | Jaccard |
|---|---|---|
| Efficacy of fluorides and CPP-ACP vs fluorides monotherapy on early caries lesions: A systematic review and meta-analysis. (2018) | 1 | 0.05 |