Fluoride Action Network


Dental caries is still one of the most prevalent diseases worldwide. Research has shown that fluoride has a role in caries prevention. For many reasons there are concerns about young children using fluoride-containing oral care products. Consequently, there is a need to identify effective fluoride-free products. A large body of literature now exists on the use of biomimetic hydroxyapatite (HAP) as an active ingredient in oral care products to combat caries.


To conduct a systematic review of the clinical evidence of the effects of HAP-based fluoride-free oral care products in caries reduction and conduct a meta-analysis of available randomized clinical trials (RCTs).


Using the PICO question “In individuals of all ages (P), do fluoride-free oral care products containing HAP as the anti-caries agent (I), compared to products with fluoride or without caries control products (C), reduce the risk of dental caries (O)?” Ovid MEDLINE (PubMed), Scopus, EMBASE, and Web of Science databases were searched using the following keywords: apatite, hydroxyapatite, caries, dental decay, dentin(e), enamel, toothpaste, dentifrice, mouthwash, gels, biofilm, (dental) plaque, ero(de, ded, sion), (de, re)mineral(ise, ized, ised, ization, isation). Reviews, tooth whitening, tooth sensitivity, and in vitro studies were excluded. PRISMA was used for the search and GRADE was used to assess quality. Clinical trials were subjected to the Cochrane Risk of Bias assessment followed by meta-analysis.


291 studies were retrieved; 22 were suitable for systematic review, 5 were clinical caries trials and 4 were RCTs. A meta-analysis of 3 RCTs was possible showing HAP provided 17% protection against caries. The other 17 trials had simpler proxy outcomes for anticaries effects. Some trials showed non-inferior performance of HAP products compared to those with fluoride.


There is good evidence that hydroxyapatite in oral care products in the absence of fluoride effectively reduces caries.

Keywords: caries, caries prevention, dentin, early childhood caries, enamel, hydroxyapatite, meta-analysis, primary teeth, randomized clinical trial, systematic review, toothpaste


  • Studies show that biomimetic hydroxyapatite-containing, fluoride-free oral care products are effective in reducing dental decay.

  • Dental hygienists can recommend fluoride-free, hydroxyapatite-containing oral care products to their clients to effectively reduce their risk of dental decay.

  • For families seeking to limit their children’s exposure to fluoridated oral products, dental hygienists can recommend fluoride-free, hydroxyapatite-containing toothpastes specially formulated for toddlers and preschool children.

*Abstract and full-text study online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641555/


For decades, fluoride has been the pre-eminent ingredient in consumer products to prevent dental caries. The evidence that fluoridated toothpaste significantly reduces caries is well documented. , It is now widely accepted that fluoride prevents dental decay by encouraging topical remineralization of early white spot, incipient lesions. New non-fluoride remineralization strategies have emerged that seem to be promising.

The primary concern with fluoridated toothpastes used by children under age 6 is the increased risk of dental fluorosis from fluoride ingestion. , It was established years ago that children under age 3 are unable to expectorate toothpaste efficiently and they tend to swallow significant proportions of the toothpaste placed in their mouth. A recent update by the Centers for Disease Control and Prevention in the United States showed that preschoolers and toddlers were still being exposed to greater than recommended amounts of fluoridated toothpaste early in life. Ingestion of fluoride during development of the permanent teeth (birth to age 6 years) results in varying degrees of dental fluorosis. , Dental professionals routinely advise their clients that fluoridated toothpaste use should be limited to a pea-sized amount in 3 year olds and even less for babies and toddlers. , A pea-sized amount is approximately 0.25 g of toothpaste but children still use more toothpaste, and the majority of those ages <3 years use it 2 times a day or more often. There is no direct evidence that these smaller amounts of toothpaste can prevent cavities: the “rice-sized smear” may even be ineffective in preventing caries formation. There is not only concern about dental fluorosis from, too much fluoride ingestion from all sources in early developmental ages, but recent studies indicate that there may also be concern about fluoride’s potential neurotoxicity on developing brains.

Dental manufacturers are continually improving dental products for use by consumers at home. Old formulations are refined and new formulations developed with the goal of improving the oral health of the population. Toothpaste manufacturers have reformulated and rebranded their products to focus on trends in cosmetic and preventive oral health care. These include antiplaque, antitartar, antigingivitis, remineralization, whitening, breath freshening, antisensitivity, and anti-erosion claims. However, most of these products continue to contain fluoride for basic caries prevention. Products validated by the Canadian Dental Association are listed on the Canadian Dental Association’s website.

Hydroxyapatite (HAP) is the primary calcium phosphate mineral in human mineralized tissues, i.e., teeth and bones. Calcium phosphate crystallites, including HAP, have been extensively studied and determined to be biocompatible in humans. They are non-toxic when swallowed, at least in doses that are normally applied during toothbrushing. HAP has been successfully used as a biocompatible (biomimetic) active mineral to encourage better bone healing and implant placement. Biomimetic means that the synthesized material exhibits chemical–physical features close to those found in the human body. Hydroxyapatite crystals can be synthesized to the same formulation as found in the mineralized tissues of dentin and enamel and can be made to resemble the same crystal structure. However, not all hydroxyapatite-based materials are biomimetic. Since HAP generally is biocompatible with and beneficial to mineralized tissues it would seem logical to add it to toothpaste to benefit tooth enamel and dentin. After thorough testing, HAP-containing toothpastes were first approved for sale in Japan in the 1980s to treat dentin hypersensitivity and for caries prevention.

One of the roles of dental hygienists is to provide evidence-based recommendations in their practice to improve oral health. The purpose of this systematic review is to highlight the extent of the literature and, in particular, the state of the evidence from clinical trials on the oral health benefits of biomimetic hydroxyapatite. In addition, this review is the first meta-analysis of clinical caries trials on HAP toothpaste. As fluoride has been determined to be a suitable anticaries agent for all ages, this study sought to examine the literature on HAP’s anticaries effects in clients of any age to determine its universal application. Of particular interest, though, was the evidence for its benefit in children so that fluoride-free oral care products specifically formulated for young children (toddlers, preschoolers, and children in grade school) might be recommended.


The PICO framework

The PICO framework was used to guide the focus of this review.

P ( Patient, Problem, Population ): clients of all ages, with primary, mixed or permanent dentitions.

I ( Intervention ): the introduction of one of the following oral care products containing biomimetic hydroxyapatite as an active ingredient: toothpaste, mouthwash or gel.

C ( Comparison, Control ): hydroxyapatite free oral care products versus fluoride-containing products, placebo or no intervention.

O ( Outcome ): a measurable oral health effect that is either a direct measurement of reduced dental decay or a suitable proxy for reduced caries risk.

Associated Data

Supplementary Table #1.
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Supplementary Table #2.
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Supplementary Table #3.
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Supplementary Table #4.
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