There is a growing need for effective methods in the management of early-stage carious
lesions. Therefore, the aim of this study was to evaluate the effect of combined casein
phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride on white spot lesions
(WSLs) compared to fluoride-only interventions. This meta-analysis was performed according
to PRISMA guidelines and registered in PROSPERO (CRD42021286245). The Medline, EMBASE
and Cochrane Central databases were searched until October 17, 2022. Eligible studies
were randomized controlled trials (RCTs). Outcome variables included Laser Fluorescence
(LF), Quantitative Light-Induced Fluorescence (QLF), and lesion area scores. The random-effects
model was used for analysis, and results were given as standardized mean difference
(SMD) and mean difference (MD) with a 95% Confidence Interval. Risk of Bias was assessed
using the RoB 2 tool, and the level of evidence with GRADE. Our systematic search
yielded 973 records after duplicate removal, 21 studies were included for qualitative
synthesis, and 15 studies were eligible for quantitative analysis. No significant
difference was found between CPP-ACP and fluoride versus fluoride alone in LF at 1,
3 and 6 months of use: SMD -0.30 (-0.64; 0.04); SMD -0.47 (-1.02; 0.07); SMD -0.49
(-1.13; 0.15), respectively. For QLF, the analysis did not demonstrate significant
differences between these two kinds of treatment at one and six months of use: MD
0.21 (-0.30;0.71); MD 0.60 (-1.70;2.90), but at three months higher QLF values were
found in the fluoride-only group compared to the CPP-ACP and fluoride combination
was shown regarding the WSLs: MD 0.58 (0.25;0.91). On the contrary, data showed a
small but statistically significant decrease in the lesion area in favor of the CPP-ACP
plus fluoride vs fluoride alone at six months MD -0.38 (-0.72; -0.04). None of these
observed changes indicated substantial clinical relevance. The combination of CPP-ACP
and fluoride did not overcome the effect of fluoride given alone. Our data suggest
that fluoride itself is effective in improving WSLs. However, the certainty of evidence
was very low. These results indicate that further studies and future development of
more effective than CPP-ACP are needed in addition to fluoride to achieve robust amelioration
of WSLs.
