The tube design is finished. The claim line sits under the brand mark, six words long, and legal has asked the only question that matters: what are we citing for that?
It sounds like a small ask. Hydroxyapatite has been studied in oral care for decades; the literature runs to thousands of papers. Surely one of them says the thing on the tube.
Sixty-eight papers, four trials
In March 2025, a team led by Chatzidimitriou published a systematic review and meta-analysis in the Journal of Dentistry asking exactly that question: do hydroxyapatite toothpastes prevent and remineralise early caries lesions? They searched the literature and retrieved 68 studies. After applying their eligibility criteria, four remained.
Four randomised controlled trials. That is the evidence base, pooled.
The pooled result was not what either side of the fluoride argument tends to claim. On the development of new lesions and the progression of existing ones, the review reported “no significant differences between HAP and fluoride toothpastes” — a risk ratio of 0.98 (95% CI 0.85–1.12, p = 0.61) and an odds ratio of 0.90 (95% CI 0.57–1.42, p = 0.68). Confidence intervals straddling 1.0 in both cases.
What “no difference” bought
That reads like a null result. It is better understood as a pass mark on a different exam.
The largest adult trial in the field was designed on precisely that logic. Paszynska and colleagues ran an 18-month double-blinded randomised controlled trial across two centres in Poland, powered as a non-inferiority study — 189 adults in the intention-to-treat analysis, 171 completing per protocol. After 18 months, no increase in the DMFS index was observed in 89.3% of the hydroxyapatite group against 87.4% of the fluoride group. The authors concluded that hydroxyapatite “was proven to be a safe and efficient anticaries agent in oral care.”
Non-inferiority is a real finding. It is also a narrow one: it licenses as good as, not better than.
The trial that did find a difference
And then there is the one that found superiority. In 2025, Cocco, Campus and colleagues published a triple-blind randomised trial in the International Dental Journal: 610 children enrolled, 518 completing, followed for 24 months. The hydroxyapatite arm showed a statistically significant reduction in enamel lesions against the mono-fluoridated comparator (P < .01); of 78 active lesions in that arm at baseline, close to 75% were inactive at follow-up.
Read the arms carefully, though. That trial did not test hydroxyapatite against fluoride. It tested magnesium-, strontium- and carbonate-substituted hydroxyapatite in a chitosan matrix, with fluoride, against fluoride alone. A different material, answering a different question.
So the six words on the tube depend entirely on which comparison your grade was actually in. “As effective as fluoride” has four trials behind it. “More effective than fluoride” has one — and only for a substituted, fluoride-containing, chitosan-carried material that a generic powder is not.
Which is the uncomfortable part for anyone sourcing. None of this evidence transfers to a material by name. It transfers to a material by specification — substitution chemistry, carrier, particle characteristics, the lot-to-lot consistency that makes your product the thing that was tested rather than something that shares its INCI entry. The claim is only as defensible as the sameness of what goes into the tube.
Sources
Chatzidimitriou K, Theodorou K, Seremidi K, Kloukos D, Gizani S, Papaioannou W. “The role of hydroxyapatite-based, fluoride-free toothpastes on the prevention and the remineralization of initial caries lesions: A systematic review and meta-analysis.” Journal of Dentistry, 2025 — pubmed.ncbi.nlm.nih.gov/40107597. Paszynska E, Pawinska M, Enax J, Meyer F, et al. “Caries-preventing effect of a hydroxyapatite-toothpaste in adults: an 18-month double-blinded randomized clinical trial.” Frontiers in Public Health, 2023 (open access) — doi.org/10.3389/fpubh.2023.1199728. Cocco F, Salerno C, Wierichs RJ, Wolf TG, Arghittu A, Cagetti MG, Campus G. “Hydroxyapatite-Fluoride Toothpastes on Caries Activity: A Triple-Blind Randomized Clinical Trial.” International Dental Journal, 2025 — pubmed.ncbi.nlm.nih.gov/39971658.