Poor oral hygiene, bacteria and orthodontic appliances mainly lead to early demineralized lesions where early detection and diagnosis of the lesion is a must so that it can be assessed and cured with the least invasive treatment. The objective was to evaluate the effect of nano-hydroxyapatite (nano-HA) and casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) on early demineralized enamel using DIAGNOdent pen and energy dispersive X-ray analysis (EDX). Materials and methods: A total of 60 enamel specimens were divided into four groups (n=15), where Group A: experimental; treated with nano-HA tooth paste, Group B: self-control for group A, Group C: experimental; treated with CPP-ACPF paste, and Group D: self-control for Group C. Control specimens were treated with fluoride varnish. All specimens were exposed to artificial demineralization followed by application of the respective agent for each and stored in artificial saliva. For normally distributed data, comparison between more than two population were analyzed using F-test (ANOVA) and One way analysis of variance (ANOVA) was performed for comparison between more than two groups. The significance level was set at p ≤0.05. Results: There was statistical significant difference regarding DIAGNOdent pen readings and mineral count of calcium and phosphate at different periods in all groups (P \u3c 0.05). There was no statistical significant difference between groups A and B and between groups C and D regarding DIAGNOdent pen readings and mineral count of calcium and phosphate at all periods (P \u3e 0.05). Conclusion: Nano-HA and CPP-ACPF had similar potential in remineralizing initial enamel lesion as fluoride varnish and can reverse a lesion into a sound tooth structure with higher net mineral gain. DIAGNOdent pen was found to be a non-highly specific and relevant tool in the assessment of enamel mineralization
