Comparison of hydroxyapatite and fluoride oral care gels for remineralization of initial caries: a pH-cycling study

Dental caries is a prevalent global health problem affecting millions. While fluoride treatments are common, their effectiveness is limited, especially in high-risk patients, and concerns exist regarding fluorosis in children. The study explores the potential of hydroxyapatite (HAP), a biocompatible calcium phosphate similar to tooth mineral, as an alternative remineralizing agent. Previous research suggests that HAP-based products are effective in remineralization and inhibiting demineralization, demonstrating comparable efficacy to fluoride in some studies. This study investigates whether a daily application of a 15% HAP gel is as effective as a weekly application of a high-concentration fluoride gel (12,500 ppm F) in remineralizing early caries lesions. The use of a pH-cycling model mimics the natural alternation of demineralization and remineralization in the oral cavity, providing a clinically relevant *in vitro* environment for the comparison.

Numerous studies highlight the prevalence and impact of dental caries globally. The limitations of fluoride-based treatments, particularly regarding fluorosis risk in children and insufficient efficacy in high-risk patients, are well-documented in literature. Research on alternative remineralization strategies focuses on biomimetic approaches using calcium phosphates, such as HAP. Several *in situ* and clinical trials have shown the caries-preventing and remineralizing effects of HAP-based toothpastes and mouthwashes. The biocompatibility and anti-adhesive properties of HAP make it a promising agent for all age groups. However, direct comparisons between HAP and high-concentration fluoride gels in a pH-cycling model, simulating daily oral conditions, are lacking. This study addresses this gap by directly comparing remineralization effectiveness under controlled, clinically relevant conditions.

Sixty bovine teeth were used to create three tooth blocks each. Caries-like lesions were created on each block using a 4-day demineralization process in acidified gel. The blocks were randomly assigned to three groups (n=20): 15% HAP gel (daily application), 12,500 ppm F gel (weekly application), and artificial saliva (control). A 28-day pH-cycling model was employed, with a 2-hour demineralization period daily, followed by a 3-minute application of the respective gel or artificial saliva. Microradiography was used to quantify mineral loss at baseline and post-treatment (day 28). Paired *t*-tests assessed intra-group changes, while Games-Howell's multiple comparison test compared inter-group differences. Power analysis using nQuery Advisor software determined the appropriate sample size (20 blocks per group). Statistical analysis was performed using STATA software version 10.0. Non-inferiority analysis was conducted to compare HAP gel to the fluoride gel, using a non-inferiority margin of ≤20%.

Paired *t*-tests showed significant remineralization (*p* < 0.0001) in all three groups. Games-Howell's multiple comparison test revealed no significant difference in remineralization between the 15% HAP gel (39 ± 7% mineral gain) and the 12,500 ppm F gel (41 ± 11% mineral gain). However, both gels exhibited significantly higher mineral gain compared to the artificial saliva control group (6 ± 2%) (*p* < 0.001). Microradiographic images showed homogenous remineralization throughout the lesion with the HAP gel, while the fluoride gel primarily remineralized the outer layer of the lesion. The non-inferiority analysis confirmed that the HAP gel was not inferior to the fluoride gel, showing no clinically relevant difference in remineralization efficacy. Confidence intervals confirmed the superiority of both gels over the artificial saliva control.

The findings demonstrate that the fluoride-free 15% HAP gel is equally effective as the high-concentration fluoride gel in remineralizing initial caries lesions. This supports the potential of HAP as a safe and effective alternative to high-fluoride treatments, particularly in age groups susceptible to fluorosis. The homogenous remineralization pattern observed with the HAP gel suggests its potential to achieve more complete lesion repair compared to the surface-limited effect of the fluoride gel. The significantly greater remineralization observed in both test groups compared to artificial saliva alone highlights the significant impact of both fluoride and HAP in promoting remineralization. The study’s use of a clinically relevant pH-cycling model enhances the generalizability of the findings.

This study demonstrates the non-inferiority of a 15% HAP gel to a high-concentration fluoride gel (12,500 ppm F) in remineralizing initial caries lesions. Both agents significantly outperformed the artificial saliva control. The biocompatibility and lack of fluorosis risk associated with HAP suggest its potential as a valuable alternative or complementary agent in caries prevention and management. Future clinical trials are warranted to confirm these findings in vivo.

The study's *in vitro* nature, using a pH-cycling model that lacks the complexity of the oral environment (including the cariogenic biofilm), is a limitation. The model's more aggressive demineralization cycles compared to natural conditions may also affect the generalizability of the findings. Future clinical studies are needed to fully validate the results in a real-world setting.