Hydroxyapatite-Fluoride Toothpastes on Caries Activity: A Triple-Blind Randomized Clinical Trial

Published In: International Dental Journal
Publication Year: 2025

Study Design

This study is a triple-blind randomized clinical trial conducted over 24 months to compare the effectiveness of hydroxyapatite-fluoride (HAF) toothpastes versus standard fluoride (NaMFP) toothpastes in managing caries activity in children.

Funding Sources

The study was funded by:

• Department of Surgery, Microsurgery and Medicine Science—School of Dentistry, University of Sassari, Italy

• Curasept S.p.A (Milan, Italy)

The funders had no role in the design, data analysis, interpretation, or publication decisions.

PICO Framework - what was studied and how?

Population:
Children aged 4–7 years with at least one active caries lesion in primary teeth.

Intervention:
Toothpaste containing biomimetic hydroxyapatite (HAF) + fluoride (1000 ppmF or 1450 ppmF), including magnesium-, strontium-, and carbonate-substituted HA in a chitosan matrix.

Comparison:
Standard fluoride toothpaste (NaMFP) at matching concentrations (1000 ppmF or 1450 ppmF) without additional active agents.

Outcomes:

• Change in caries lesion activity (from active to inactive or filled)

• Enamel remineralization

• Arrest of dentinal lesion progression

In Paragraph Form:
The study evaluated children aged 4–7 with at least one active caries lesion to compare the effects of hydroxyapatite-fluoride toothpaste versus traditional fluoride toothpaste. The trial measured changes in lesion activity (progression, arrest, or reversal) over 24 months, focusing on both enamel and dentinal caries in primary teeth.

Inclusion and Exclusion Criteria

Inclusion Criteria:

• Children aged 4–7 with at least one active caries lesion

• Good general health

• Agreement not to use other oral hygiene products

Exclusion Criteria:

• Ongoing dental treatment (except emergencies)

• Allergies to oral hygiene products

• Participation in another clinical trial in the past 30 days

• Recent antibiotic use (within 3 months)

Demographics and Sample Sizes

• Total enrolled: 610 children

• Completed trial (per-protocol analysis): 518 children

• Group Sizes:

  • HAF group: 259 children

  • NaMFP group: 259 children

Each group included two concentrations (1000 ppmF and 1450 ppmF), randomized equally within two age brackets (4–5 and 6–7 years).

Primary Outcome Variables and Results

Outcome: Caries lesion activity in primary enamel and dentine at 24 months

Key Findings (Primary Teeth):

• Enamel Lesions:
  HAF group had a statistically significant higher proportion of inactive lesions compared to NaMFP (P < .01).

• Dentinal Lesions:
  Although both groups had similar rates of filled lesions, HAF resulted in significantly more inactive lesions than NaMFP (27.8% vs <10%, P = .03).

• Progression to Filling:
  Fewer lesions in HAF needed fillings compared to NaMFP.

Conclusions

The use of hydroxyapatite-fluoride toothpaste:

• Led to significantly higher remineralization and inactivation of early enamel lesions

• Was more effective than standard fluoride toothpaste in arresting caries progression in children with active lesions

• Could represent a superior non-invasive caries management strategy in primary dentition

Discussion: Strengths and Limitations

Strengths:

• Large sample size (518 completed cases)

• Triple-blind design with strong randomization

• Real-world, school-based application

• High examiner calibration and reliability (Cohen’s kappa > 0.85)

Limitations:

• COVID-19 disrupted follow-ups and data collection

• ITT analysis limitations due to changing dentition phases

• No subgroup analysis by fluoride concentration

• Long-term outcomes beyond 2 years not assessed

• No formal cost-effectiveness or health-economic evaluation

Citation

Cocco F, Salerno C, Wierichs RJ, et al. Hydroxyapatite-Fluoride Toothpastes on Caries Activity: A Triple-Blind Randomized Clinical Trial. Int Dent J. 2025;75(4):632–642.
https://pubmed.ncbi.nlm.nih.gov/

Visual Aids

Simple Chart: Caries Lesion Status Change (Primary Enamel and Dentine at 24 Months)