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How does hydroxyapatite toothpaste compare to 500 ppm fluoride in promoting remineralization and inhibiting caries development?


These excerpts are taken from the open-access article published in the British Dental Journal Comparative efficacy of a hydroxyapatite and a fluoride toothpaste for prevention and remineralization of dental caries in children (PDF)

Although fluoride interventions seem to have the most consistent benefit in preventing caries development and remineralizing initial lesions with the highest level of supporting evidence,6–8 caries still develop in high risk individuals of all ages, irrespective of the dose of fluoride used. (1,2)

There are limitations to what application of fluoride alone can achieve in relation to caries prevention and remineralization.(3) The effect of dose limitation on fluoride effectiveness may be more pronounced in children below 6 years, since the fluoride dose recommended for this group is even lower than the regulatory 1000–1500 ppm fluoride concentration in non-prescription toothpastes, and as such probably suboptimal for effective remineralization of initial lesions.

The objective of this in situ study is to compare the effectiveness of two toothpastes containing hydroxyapatite or 500 ppm fluoride in promoting remineralization and inhibiting caries development.

This is a two-arm double-blind randomized crossover study in which each arm of the study lasted 14 days. The authors exposed two enamel blocks (human primary teeth), one sound and one with artificially-produced caries lesion, to toothpaste containing either 10% hydroxyapatite or 500 ppm F− (amine fluoride) via intra-oral appliance worn by 30 adults.

Baseline and post-test mineral loss and lesion depth (LD) were quantified using microradiography. One-sided t-test of one group mean was used for intragroup comparison (baseline vs. post-test), while two-sided t-test of two independent means was used to compare the two toothpaste groups.

Clinical Implication

The study confirmed hydroxyapatite toothpaste is equivalent or non-inferior to the fluoride toothpaste with respect to remineralization of initial caries lesions and prevention of carious lesion development.


The findings of this study accepted the two hypotheses that each of the two toothpaste formulations promotes remineralization and lesion depth reduction and that neither toothpaste is inferior to the other with respect to promoting the remineralization and inhibiting the development of initial caries lesions.

  • Despite being a preventable disease and amid the presence of fluoride in oral dentifrices, dental caries prevalence in children continues to increase globally,(4) and at a faster rate among children from low socioeconomic backgrounds.(21) This indicates that although fluoride interventions have the highest level of supporting evidence as having the most consistent benefit in preventing caries and remineralizing initial caries lesions; (5-7) additional remineralizing and preventive agents are often needed to enhance fluoride effects in high caries risk individuals.(1,2)
  • One may suggest increasing the dose of fluoride since its effectiveness is dose-dependent, (6) unfortunately, there is a limit to fluoride dose allowed in oral care products to avoid the risk of fluorosis in children (8) and toxicity in all ages.(9,10)
  • Effectiveness of amine fluoride (AMF) in these reports and this study is in agreement with the long-established fact that fluoride in varying concentrations are effective in preventing caries development and remineralizing initial caries,9,39,40 and that the various fluoride salts were equally effective. (11)
  • The effectiveness of the hydroxyapatite (HAP) toothpaste in this study is in agreement with previous clinical and in vitro studies, and it is not surprising considering the various mechanisms through which HAP has been demonstrated to effect remineralization of initial caries. (12,13,14,15,16-20)
  • The absence of any evidence of demineralization in all the sound tooth blocks following intra-oral exposure to either HAP or AMF toothpaste further demonstrated the inhibition of demineralization by both toothpastes.
  • Based on the findings of the study, one may suggest that HAP-containing toothpaste may be a better choice for children and individuals at high caries risk since the dosage can be increased to obtain higher efficacy without any safety issue such as the risk of fluorosis in children associated with high fluoride dose.
  • The use of HAP in oral care products may eliminate the need of combining fluoride and antimicrobials in a dentifrice, as well as having different dosages for infants, children and adults.
  • It is logical but scientific that since the remineralizing efficacy of topical fluorides is strictly dependent on the availability of calcium and phosphate ions, HAP dentifrices may be a more effective for xerostomic patients with diminished amounts of saliva. This may need to be confirm through a clinical trial on patients suffering from xerostomia.


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  3. Bjarnason, S. & Finnbogason, S. Y. Effect of different fluoride levels in dentifrice on the development of approximal caries. Caries Res. 25, 207–212 (1991).
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  13. Najibfard, K., Ramalingam, K., Chedjieu, I. & Amaechi, B. T. Remineralization of early caries by nano-hydroxyapatite dentifrice. J. Clin. Dent. 22, 139–143 (2011).
  14. Juntavee, N., Juntavee, A. & Plongniras, P. Remineralization potential of nanohydroxyapatite on enamel and cementum surrounding margin of computeraided design and computer-aided manufacturing ceramic restoration. Int J. Nanomed. 8, 2755–2765 (2018).
  15. Schlagenhauf, U. et al. Impact of a non-fluoridated microcrystalline hydroxyapatite dentifrice on enamel caries progression in highly caries-susceptible orthodontic patients: a randomized, controlled 6-month trial. J. Investig. Clin. Dent. 10, e12399 (2019).
  16. Huang, S., Gao, S., Cheng, L. & Yu, H. Remineralization potential of nanohydroxyapatite on initial enamel lesions: an in vitro study. Caries Res. 45, 460–468 (2011).
  17. de Carvalho, F. G. et al. In vitro effects of nano-hydroxyapatite paste on initial enamel carious lesions. Pediatr. Dent. 36, 85–89 (2014).
  18. Kim, M. Y., Kwon, H. K., Choi, C. H. & Kim, B. I. Combined effects of nanohydroxyapatite and NaF on remineralization of early caries lesion. Key Eng. Mater. 330, 1347–1350 (2007).
  19. Venegas, S. C., Palacios, J. M., Apella, M. C., Morando, P. J. & Blesa, M. A. Calciummodulates interactions between bacteria and hydroxyapatite. J. Dent. Res. 85, 1124–1128 (2006).
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