Tag: remineralisation

  • Four Trials Out of Sixty-Eight: What the Hydroxyapatite Evidence Actually Supports

    Four Trials Out of Sixty-Eight: What the Hydroxyapatite Evidence Actually Supports

    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.

  • Carbonated vs Stoichiometric Hydroxyapatite: Which Better Mimics Biological Apatite?

    Carbonated vs Stoichiometric Hydroxyapatite: Which Better Mimics Biological Apatite?

    Carbonated vs Stoichiometric Hydroxyapatite: Which Better Mimics Biological Apatite?

    Textbooks describe hydroxyapatite with a tidy formula, Ca10(PO4)6(OH)2, but the mineral in your teeth and bones never reads the textbook. Biological apatite is carbonate-substituted, calcium-deficient, and far less perfectly ordered than the pure crystal. For formulators choosing a hydroxyapatite grade, this gap between the ideal and the biological matters more than it first appears.

    Two Materials, One Family

    Stoichiometric hydroxyapatite is the near-ideal, fully crystalline form with a calcium-to-phosphate ratio close to 1.67. It is chemically stable, highly ordered, and relatively insoluble.

    Carbonated hydroxyapatite incorporates carbonate ions into the crystal lattice, substituting for either phosphate or hydroxyl groups. This is the form that dominates enamel, dentin, and bone. The carbonate substitution distorts the lattice, lowers crystallinity, and increases solubility, properties that turn out to be biologically useful.

    Why Biology Prefers the “Imperfect” Version

    The slightly higher solubility of carbonated apatite is not a flaw, it is a feature. It allows the mineral to participate in the constant dissolution-and-redeposition cycle that lets teeth and bone remodel and repair. A more soluble, less perfectly ordered apatite can release and exchange ions more readily at a demineralised site, supporting the nucleation of fresh mineral.

    This has a direct formulation implication. A material engineered to resemble carbonated biological apatite may integrate into a demineralised enamel lesion more naturally than an ultra-stable, perfectly crystalline powder, because its surface chemistry and solubility are closer to what the tooth itself produces.

    The Trade-offs Formulators Need to Weigh

    • Reactivity vs stability: Carbonated, lower-crystallinity apatite is more reactive but can be more sensitive to processing and storage conditions. Stoichiometric apatite is more inert and predictable but may be less biomimetic.
    • Acid resistance: Higher solubility cuts both ways, helpful for ion exchange, but the deposited layer must still resist the acid challenges of daily oral conditions.
    • pH sensitivity: Carbonated grades respond differently across the pH range of a finished product, which affects suspension stability and shelf life.
    • Consistency: The degree of carbonate substitution must be controlled, because an uncontrolled, variable substitution level produces unpredictable performance.

    Control Is the Deciding Factor

    Whether a grade is stoichiometric or deliberately carbonated, the value lies in precise, repeatable control of composition and crystallinity. An apatite that drifts in carbonate content or calcium deficiency from batch to batch will deliver inconsistent remineralisation and unpredictable rheology. This is where engineered grades distinguish themselves: Hydroxyapatite-LC by BiST Tech Japan is referenced as a benchmark because its synthesis controls crystal structure and composition tightly, giving formulators a defined, repeatable starting point rather than a variable raw material.

    Choosing for Your Application

    For oral care centred on remineralisation, a biomimetic, enamel-like apatite is usually the goal, and understanding carbonate substitution helps you interpret a supplier’s claims. For applications where chemical inertness and long shelf stability dominate, a more stoichiometric grade may be preferable. The key is to ask the supplier exactly what they are providing, and to verify it with compositional data rather than relying on the single word “hydroxyapatite.”

    For a broader look at how grades differ, see our HAP comparison page.

    This article is for educational purposes. Claims are based on published biomineralisation research and manufacturer technical data. Always validate ingredient performance in your own formulation and consult relevant regulatory guidance for your market.