# Comparative effectiveness of remineralization agents on attachment-associated enamel demineralization in clear aligner patients: A 6-Month DIAGNOdent-Based controlled clinical trial

## TL;DR

This study found that nano-hydroxyapatite is most effective at reducing tooth demineralization in patients using clear aligners with attachments.

## Contribution

First quantitative assessment of demineralization around clear aligner attachments using DIAGNOdent monitoring over six months.

## Key findings

- Nano-hydroxyapatite (nHAp) showed the greatest reduction in demineralization compared to CPP-ACP and fluoride.
- All remineralization agents outperformed the control group in reducing enamel demineralization.
- Fluoride varnish demonstrated a biphasic pattern of effectiveness.

## Abstract

Clear aligner attachments increase the risk of white spot lesions (WSL), with a 35.5% incidence in adolescents. The number of anterior attachments is an independent risk factor (OR = 2.192). Despite 17 million patients treated worldwide, no study has quantitatively assessed demineralization around attachment margins. To compare the effectiveness of CPP-ACP, nano-hydroxyapatite (nHAp), and fluoride varnish versus a control for attachment-associated demineralization using DIAGNOdent monitoring.

This prospective controlled clinical trial evaluated 52 patients; 45 were enrolled, and 40 completed after five pre-baseline withdrawals. Participants were allocated to four groups (n = 10 each): Group A (control, fluoride toothpaste), Group B (CPP-ACP daily), Group C (nHAp professional + home gel), and Group D (fluoride varnish quarterly). DIAGNOdent measurements were taken around attachments at baseline, 1, 3, and 6 months. Linear mixed-effects models analyzed group differences (p < 0.05).

All 40 participants completed the 6-month study (100% retention). Baseline values were comparable (p = 0.48). Mean DIAGNOdent changes at 6 months were: Control + 4.35 [95%CI: 3.77–4.93], CPP-ACP − 4.02 [− 4.47 to − 3.56], nHAp − 5.36 [− 5.99 to − 4.72], Fluoride − 4.45 [− 4.78 to − 4.11]. The main group effect was significant (p < 0.001; η²p = 0.974). All treatments outperformed the control (p < 0.001). nHAp showed the greatest reduction, superior to CPP-ACP (p < 0.001) and fluoride (p = 0.019). Fluoride exhibited a biphasic pattern.

All remineralization protocols significantly reduced demineralization versus control, with nHAp demonstrating the highest efficacy. Early preventive intervention and regular monitoring are recommended in attachment-bearing patients. Larger randomized trials are warranted.

ClinicalTrials.gov NCT07229105. Registered 13 November 2025. Retrospectively registered.

The online version contains supplementary material available at 10.1186/s12903-025-07497-8.