Remineralising efficacy of bioactive glass and casein phosphopeptide amorphous calcium phosphate in white spot lesions or early enamel caries: A systematic review of randomised controlled trials

Fluoride has always been used as a gold standard in preventing early enamel caries, however due to its demerits, newer remineralising agents such as casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and bioactive glass (BAG) have been developed to either substitute or as an adjuvant to fluoride in managing white spot lesions (WSLs). A systematic search of five databases was conducted up to August 2025 following PRISMA guidelines. Eligible RCTs evaluated CPP-ACP or BAG in permanent teeth with WSLs or early enamel caries. Risk of bias was assessed using the Cochrane RoB-2 tool, and certainty of evidence with GRADE. Sixteen RCTs were included (3 BAG, 13 CPP-ACP). BAG showed greater remineralisation than fluoride and CPP-ACP in two studies. Five studies favored CPP-ACP over fluoride. Formulations containing CPP-ACP with fluoride showed slight advantages over CPP-ACP alone. Considerable heterogeneity in outcome measures and a high or unclear risk of bias was identified across most studies. Certainty of evidence was rated low to moderate. Both BAG and CPP-ACP demonstrate remineralising potential, with BAG particularly fluoride-containing formulations showing more consistent results. Current evidence remains insufficient to replace fluoride as the standard. High-quality multicentre RCTs with standardised outcomes are needed.