Remineralizing effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on enamel affected by molar-incisor hypomineralization (MIH): a systematic review and meta-analysis

Background: Molar-Incisor Hypomineralization (MIH) is a developmental disorder of the dental enamel with significant oral health implications, including caries, dentin hypersensitivity, aesthetic impairment, and pulpitis, driving a high clinical need for in-tervention. Current non-invasive approaches include Fluoride, Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP), and Calcium Glycerophosphate (CaGP). This meta-analysis aims to evaluate the effectiveness of CPP-ACP on MIH-affected teeth. Methods: A systematic review and meta-analysis were conducted. The search was carried out in four databases (PubMed, Cochrane, Embase, Google Scholar) and manual searches were utilized to identify studies published up to December 2025, with no restrictions on the publication date. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review and meta-analysis were conducted using a Population, Intervention, Comparison, and Outcome (PICO)-based search strategy. Relevant studies were selected based on titles and abstracts, and the full texts were retrieved. The meta-analysis was conducted using Stata version 16.0. Results: A total of 18 studies were eligible for the systematic review, and 8 studies were included in the meta-analysis. The systematic review indicated that CPP-ACP may be effective in promoting remineralization, reducing hypersensitivity, improving microhardness, and altering salivary characteristics. Meta-analysis revealed that Casein Phosphopeptide-Amorphous Calcium Phosphate Fluoride (CPP-ACPF) significantly enhanced remineralization after one month of use, whereas the efficacy of CPP-ACP was not statistically significant. The prognosis for microstructural recovery in MIH enamel is dependent on the initial defect. While white spots can nearly recover to their original structure, yellow-brown lesions may require more aggressive and long-term intervention strategies. Conclusions: Adding fluoride to CPP-ACP (CPP-ACPF) may accelerate the remineralizing effect, since this integration promotes the development of acid-resistant fluorapatite, which reduces hypersensitivity and shows potential for mitigating the risk of enamel breakdown. The PROSPERO Registration: CRD420251103933.

MIH; CPP-ACP; Remineralization; Dentin hypersensitivity; Microhardness; Salivary buffer

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