Comparative Effectiveness of Remineralization Agents on Attachment-Associated Demineralization in Clear Aligner Patients

Comparative Effectiveness of Remineralization Agents on Attachment-Associated Demineralization in Clear Aligner Patients: A 6-Month DIAGNOdent-Based Observational Study

Background/ Objectives: 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.

Methods: This prospective observational study 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).

Study Overview

• Status: Completed
• Conditions: Dental Caries; Orthodontic Treatment; White Spot Lesions; Demineralization
• Intervention / Treatment: Device: GC Tooth Mousse; Device: Nano-Hydroxyapatite Gel; Drug: Sodium Fluoride varnish

Detailed Description

DIAGNOdent Measurement Protocol Calibration and Standardization The DIAGNOdent pen (KaVo, Biberach, Germany) was calibrated before each measurement session according to the manufacturer's instructions using a ceramic standard[18]. A single calibrated examiner performed all measurements to ensure consistency. Intra-examiner reliability was assessed using intraclass correlation coefficient (ICC) with two-way mixed model, absolute agreement, calculated from 30 repeated measurements at 10 randomly selected attachment sites (ICC = 0.85, 95% CI: 0.79-0.91).

Measurement Technique A standardized measurement protocol was employed for all DIAGNOdent assessments. Teeth were air-dried for 5 seconds prior to measurement, and the probe tip was positioned perpendicular to the enamel surface to ensure consistent readings. Four measurements were obtained per attachment site at the mesial, distal, gingival, and occlusal margins. Three measurement passes were performed at each site, with the maximum value recorded to represent the most advanced demineralization present. Measurements were conducted at four timepoints: baseline (T0), 1 month (T1), 3 months (T2), and 6 months (T3).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • Bezmialem Vakif University, Faculty of Dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 16-45 years
• Active clear aligner treatment with minimum 6 months remaining
• Presence of ≥10 attachments on anterior teeth and premolars
• Good general health
• Commitment to prescribed aligner wear (20-22 hours/day)

Exclusion Criteria:

• Active carious lesions
• Periodontal disease
• Fluorosis or enamel hypoplasia
• Current fluoride supplement use beyond standard toothpaste
• Pregnancy or lactation
• Systemic conditions affecting salivary flow

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group A: Control; The participants used standard fluoride toothpaste (1450 ppm) twice daily, with no additional remineralization protocol.
Experimental: Group B: Casein Phosphopeptide-Amorphous Calcium Phosphate; In addition to standard fluoride toothpaste, participants applied GC Tooth Mousse (CPP-ACP) to their clear aligners once daily for 15 minutes before bedtime.	Device: GC Tooth Mousse; Participants applied a pea-sized amount of GC Tooth Mousse into each aligner once daily before bedtime. They wore the aligners with the mousse for 15 minutes and were instructed not to rinse for 30 minutes post-application.; Other Names: CPP-ACP Paste
Experimental: Group C: Nano-Hydroxyapatite; Professional in-office application of 5% nHAp gel at baseline, 1, and 3 months, combined with daily home application of 1% nHAp gel into aligners.	Device: Nano-Hydroxyapatite Gel; A combined protocol involving: 1) Professional in-office application of 5% nHAp gel (BioWhiten ProOffice) at baseline, 1 month, and 3 months; and 2) Daily home application of 1% nHAp gel (Biowhiten Nanocare) into aligners every night before sleep.; Other Names: BioWhiten ProOffice and Nanocare
Experimental: Group D: Professional Fluoride Varnish; Professional application of 5% sodium fluoride varnish (ProShield) applied to attachment margins at baseline and 3 months.	Drug: Sodium Fluoride varnish; Professional application of 5% sodium fluoride varnish (ProShield) to all tooth surfaces, with special attention to attachment margins, at baseline and 3 months. The varnish was left for 1 minute contact time before removal, with instructions not to eat/drink for 2 hours.; Other Names: ProShield Varnish

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Enamel Demineralization (DIAGNOdent values).	Measurements taken using DIAGNOdent pen around attachment margins. Validated cut-off values: 0-12 sound, 13-24 initial, >25 advanced.	Baseline (T0) to 6 months (T3).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporal Changes in Enamel Mineralization	Evaluation of DIAGNOdent values at intermediate time points to assess the progression or regression patterns (e.g., continuous improvement vs. biphasic response) of demineralization.	1 month (T1) and 3 months (T2)

Collaborators and Investigators

• Sponsor: Bezmialem Vakif University

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2024
• Primary Completion (Actual): March 28, 2025
• Study Completion (Actual): March 28, 2025

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 13, 2025
• First Posted (Estimated): November 14, 2025

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: White Spot Lesions; DIAGNOdent; White Spot Lesion; clear aligners; Orthodontic Attachments
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Diseases; Tooth Demineralization; Dental Caries; Bifluorid 12
• Other Study ID Numbers: 09/15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.
• IPD Sharing Time Frame: Immediately following publication
• IPD Sharing Access Criteria: Researchers can contact the corresponding author.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No