Tooth Decay, Fluoride, and Hydroxyapatite

Tooth Decay, Fluoride, and Hydroxyapatite

In recent years, consumer perspectives around toothpaste have evolved dramatically. Once considered a toiletry for maintaining basic hygiene, toothpaste evolved into a premium beauty product and is now heralded as a wellness essential. Despite advances in technology and changing consumer desires, preventing tooth decay continues to be the core benefit of tooth brushing.

What causes tooth decay? You likely grew up hearing that consuming candy, soft drinks, and other sugary foods cause cavities. While this is a contributing factor, acid-producing bacteria are the real culprits. The oral microbiome is a very complex ecosystem, consisting of hundreds of species of bacteria and other microbes living in harmony. Many of these species find a home on the tooth surface, forming what is commonly known as the plaque biofilm. Among the residents of the plaque biofilm are a number of cariogenic species, species that consume dietary sugars and produce acids as waste products. When the balance shifts in favor of these species, the acids generated can dissolve the mineral structure of the tooth, creating demineralized lesions, ultimately leading to caries (cavities). Left unchecked, the plaque biofilm also causes inflammation of the surrounding tissue, which, over time, can lead to loss of the tooth.¹ Daily tooth brushing removes the plaque biofilm, creating an opportunity for remineralization of the tooth enamel.

The oral cavity has a natural process for maintaining homeostasis which is referred to as the demineralization-remineralization cycle, maintained by saliva. In an acidic environment, below pH 5.5, hydroxyapatite crystals dissolve, releasing calcium and phosphate ions from the dentition. This is referred to as demineralization and can be caused by bacterial metabolism of dietary sugars or direct exposure to acidic foods or beverages. Salivation introduces buffering proteins, calcium and phosphate ions, which causes the mouth to return to a healthy pH. Above pH 6.2, the saliva becomes supersaturated with calcium and phosphate ions, reverting from a demineralization phase to a remineralization phase. Calcium phosphate precipitates on the enamel surface, and demineralized crystallites act as a nucleation site for crystallization.^{2, 3}

In addition to physical removal of the plaque biofilm, toothpaste may contain ingredients that promote remineralization, and further help prevent tooth decay. The most common and well-studied ingredients are fluoride and hydroxyapatite.

Fluoride

Fluoride is a naturally occurring mineral found in trace amounts in many foods. The dental health benefits of fluoride were discovered due to low rates of dental decay and high incidence of dental fluorosis in isolated communities around naturally fluoridated water sources. This discovery led to the first public water fluoridation project in 1945, and the invention of fluoride toothpaste in 1955.

Fluoride ions react with calcium ions in saliva, depositing calcium fluoride on the surface of the tooth. Through cycles of demineralization and remineralization, fluoride is integrated into the outer layers of the tooth enamel creating a new mineral structure called fluorapatite. Fluorapatite is stronger and more acid resistant than hydroxyapatite, thus, brushing with a properly formulated fluoride toothpaste makes teeth stronger and more resistant to dental decay.⁴ There are four fluoride salts used in toothpaste: sodium fluoride, stannous fluoride, sodium monofluorophosphate, and amine fluoride. The primary mode of action for each of these ingredients is identical, however there are distinct differences that should be considered when selecting a fluoride source.

Sodium fluoride is the simplest, and arguably the easiest fluoride with which to formulate. It is inexpensive, tasteless, and readily soluble in water. For these reasons, sodium fluoride is the most prevalent source of fluoride used in toothpaste. However, it does lack any added functionality. Each of the remaining fluoride sources has unique attributes which are often perceived as advantageous, although they do not result in better protection from tooth decay.

Stannous fluoride is the first fluoride source that was used in a commercial toothpaste. It may present formulation challenges due to the reactivity of tin, but this counter-ion also offers several additional benefits including antibacterial properties. The stannous ions have antibacterial properties. The stannous ions can precipitate onto the tooth surface, resulting in both anti-erosion and anti-hypersensitivity benefits.⁵ However, these added benefits come at a cost. Tin has a distinct metallic taste and astringency which are challenging to mask. Additionally, regular use of stannous fluoride toothpaste can lead to tooth staining, which is harmless but also quite unsightly.

Sodium monofluorophosphate has one major advantage over the other fluoride sources, in that it is compatible with calcium-based abrasives like calcium carbonate, dicalcium phosphate, and calcium pyrophosphate. The reason sodium monofluorophosphate is relatively stable in these conditions is because the fluoride is covalently bound, making it unavailable to react with any free calcium in the product. This makes sodium monofluorophosphate the most flexible option in terms of compatibility with a broad range of abrasive agents. That said, the covalency of the chemical bond is not without drawbacks. Since sodium monofluorophosphate does not readily bind with calcium ions, it is thought to be less acid resistant when deposited on the enamel surface.

Amine fluoride is the last and most likely the least known fluoride source for toothpaste. It can be found in many European countries but is not approved for use in the United States. Amine fluoride functions as a surfactant, forming a film on the tooth surface that can deter deposition of the plaque biofilm. Amine fluoride can be perceived as tasting soapy and may be tricky to formulate because the amine can react with other functional groups.

In the United States, anti-cavity [fluoride] toothpaste is regulated as an over-the-counter drug requiring strict compliance with the FDA Anticaries Drug Products for Over-the-Counter Human Use monograph. The monograph dictates the concentrations of fluoride that can be used, required testing to demonstrate the fluoride is effective, and exact language for performance claims related to prevention of dental decay or cavities.⁶ In most other countries, fluoride toothpaste is regulated as a cosmetic product, and there is a maximum amount of fluoride permitted to ensure product safety.

Formulators have several fluoride sources to choose from, each with distinct advantages and disadvantages. Despite the apparent differences between these compounds, when formulated to the same fluoride concentration, they provide comparable protection against tooth decay in the clinical setting.

Hydroxyapatite

Hydroxyapatite is a form of calcium phosphate and is the primary component of animal teeth and bones. The idea of using a hydroxyapatite precursor in toothpaste to repair teeth was first proposed by NASA in a patent that was granted in 1972. Two years later, the rights were acquired by Japanese company Sangi Co. Ltd. The first toothpaste containing hydroxyapatite, Apadent, was launched in Japan in 1980. Japan officially approved hydroxyapatite as an anti-cavity agent in 1993.

Hydroxyapatite promotes enamel remineralization and impedes dental decay through several mechanics. Hydroxyapatite exhibits buffering capacity which aids in the recovery of saliva to a healthy pH. It also causes the saliva to be supersaturated with calcium and phosphate ions which leads to the deposition of calcium phosphate onto the enamel surface. Hydroxyapatite itself has an affinity to the tooth surface (via the acquired pellicle), causing particles to be retained on the tooth after brushing. Hydroxyapatite on the tooth surface can act as a sacrificial layer during acid challenges, neutralizing the acid and allowing the crystalline enamel to remain intact. Furthermore, hydroxyapatite on the surface can be integrated into the enamel through the natural demineralization-remineralization cycle.⁷ Unlike fluoride, hydroxyapatite does not alter the mineral structure of the tooth.

Hydroxyapatite is often classified by particle size, morphology, or origin. The most common distinction is nanocrystalline hydroxyapatite (nHA) or microcrystalline hydroxyapatite (mHA). Both nHA and mHA have a similar crystalline structure to the hydroxyapatite that comprises tooth enamel. Nano-hydroxyapatite particles typically range from 20 to 100 nm whereas mHA particles typically range from 200 nm to 10 microns.

Nano-hydroxyapatite is a synthetic material typically made by reacting calcium hydroxide and phosphoric acid. Reaction variables can be adjusted to produce hydroxyapatite crystals of different shapes and sizes. Nano-hydroxyapatite particles are purported to fill microscopic cracks and gaps in the enamel surface, quickly integrating with the enamel and repairing defects.⁸ However, the small size of these particles raises concerns about their long-term safety. Nano-particle hydroxyapatite is small enough to enter human cells, and there is not currently a clear understanding of how these particles may disrupt cellular processes. In 2023, the European Commission’s Scientific Committee on Consumer Safety updated their opinion on the safety of nHA, and currently recognizes “rod-shaped” nHA particles to be safe for use in toothpaste and mouthwash.⁹ Despite this recognition of safety, “nanophobia” remains prevalent among consumers.

Micro-hydroxyapatite can be natural, naturally derived, or synthetic. Natural sources are typically pulverized animal bones. The advantages of natural mHA is that it is an upcycled material and contains the same ratios of macronutrients as biological hydroxyapatite, however, animal derived sources are not commonly used in the personal care industry due to the complexity of consumer attitudes towards animal cruelty, vegetarianism/veganism, etc. Synthetic mHA is pure HA composed only of calcium phosphate crystals and is produced using the same techniques as nHA with the reaction parameters adjusted to grow larger crystals. Naturally derived sources are manufactured using natural feedstocks such as limestone and natural phosphoric acid.

Nano-hydroxyapatite is often perceived to be a more effective remineralization agent than mHA due to its smaller particle size. The main advantage being that the particles have a larger surface area, and thus a greater affinity to the enamel surface. It has been demonstrated in vitro that nanoparticles can fill microscopic defects in the enamel and quickly incorporate into the structure of the dentition.⁸ However, in clinical studies, both nHA and mHA have been demonstrated to be effective remineralization agents. In practical application, hydroxyapatite nanoparticles have a tendency to aggregate into larger structures functionally equivalent to mHA particles.¹⁰ Furthermore, studies have found hydroxyapatite clusters up to 4 microns adhered to oral surfaces. Despite differences in particle size, morphology, and origin, nanocrystalline and microcrystalline hydroxyapatite provide comparable protection against tooth decay in the clinical setting.¹¹ The concentration of hydroxyapatite is the primary factor impacting the extent of the benefit.

Hydroxyapatite is an approved active ingredient in both Japan and Canada, but in most other countries it is still regulated as a cosmetic ingredient. This can limit the claims that brands can make regarding the efficacy of the product against tooth decay. It can also make it challenging for consumers to identify which products contain a suitable concentration of hydroxyapatite to provide a remineralization benefit above and beyond the mechanical action of removing the plaque biofilm.

Fluoride versus Hydroxyapatite 

Fluoride and hydroxyapatite are both clinically proven to aid in remineralization and the prevention of tooth decay, but there are vast differences between the two technologies. Fluoride is by far the most studied ingredient for this purpose, with over 80 years of research supporting the dental benefits of fluoride. Fluoride is also inexpensive and effective at a very low usage level. Toothpaste containing 1000 to 1500 ppm fluoride (0.10 to 0.15%, by mass) is proven to help prevent dental decay. Documented long-term negative effects of excessive fluoride exposure include both dental and skeletal fluorosis. More recently, excessive fluoride exposure has been associated with lower intelligence quotient (IQ) in children. This has increased public scrutiny of water fluoridation programs. Most countries do not allow greater than 1500 ppm fluoride in a toothpaste as a means to prevent fluoride toxicity.

Hydroxyapatite is a younger technology, developed just over 50 years ago. It is more expensive to produce than fluoride and requires higher usage levels to be effective. Products containing 10% hydroxyapatite have been found to provide similar clinical results to fluoride.^{11, 12} However, there are no identified safety concerns about exposure to HA. Hydroxyapatite is a naturally occurring material in human teeth and bones, making it both nontoxic and biocompatible.¹² Hydroxyapatite is also safe in the environment and is a source of bioavailable calcium to many life forms. Unlike fluoride, hydroxyapatite does not change the chemical composition of the outermost layers of the dentition.

The evolution of toothpaste from a basic hygiene product to a wellness essential reflects changing consumer priorities and scientific advancements. One place this can be observed is in the fluoride-free toothpaste segment. Fluoride-free toothpastes have always been available to consumers weary of potential health risks of fluoride. Historically, these fluoride-free products did not provide any alternative remineralization ingredients. Over the past decade, as more studies demonstrating the efficacy of hydroxyapatite have become available, use of hydroxyapatite as an alternative remineralization agent in fluoride-free toothpastes has consistently increased. For the past 3 years, most new fluoride-free toothpastes contain hydroxyapatite (figure 1).

Figure 1: Graph of new oral hygiene products cataloged in Mintel NPD between January 1, 2014 and December 31, 2024 featuring either (a) the ingredient hydroxyapatite or (b) a “free from fluoride” or “fluoride-free” claim.¹³

Today, consumers have more choices, and more education available to guide them, than ever before. While preventing tooth decay remains the primary goal of brushing, the choice between fluoride and hydroxyapatite-based formulations offers consumers a more personal approach to oral health. Fluoride has decades of research supporting its safety and effectiveness. The biomimetic nature and enhanced safety profile of hydroxyapatite, coupled with a mounting body of evidence supporting its efficacy, are forces driving interest in its incorporation into toothpaste as an alternative to fluoride, especially within the children’s and natural segments. However, it should be noted that any toothpaste product marketed in the US and claiming to aid in the prevention of dental caries, cavities or decay must be compliant with the FDA Anticaries Drug Products for Over-the-Counter Human Use monograph.

References

1. Kilian, M., Chapple, I., Hannig, M. et al. The oral microbiome – an update for oral healthcare professionals. Br Dent J 221, 657–666 (2016). https://doi.org/10.1038/sj.bdj.2016.865
2. Chen L, Al-Bayatee S, Khurshid Z, Shavandi A, Brunton P, Ratnayake J. Hydroxyapatite in Oral Care Products-A Review. Materials (Basel). 2021 Aug 27;14(17):4865. https://doi.org/10.3390/ma14174865.
3. Farooq I, Bugshan A. The role of salivary contents and modern technologies in the remineralization of dental enamel: a narrative review. F1000Res. 2020 Mar 9;9:171. https://doi.org/10.12688/f1000research.22499.3.
4. Talwar M, Borzabadi-Farahani A, Lynch E, Borsboom P, Ruben J. Remineralization of Demineralized Enamel and Dentine Using 3 Dentifrices-An InVitro Study. Dent J (Basel). 2019 Sep 2;7(3):91. https://doi.org/10.3390/dj7030091.
5. Nicholson, J.W. Stannous Fluoride in Toothpastes: A Review of Its Clinical Effects and Likely Mechanisms of Action. J. Funct. Biomater.2025, 16, 73. https://doi.org/10.3390/jfb16030073
6. 21 CFR Parts 310, 355, and 369 (1995). Anticaries Drug Products for Over-the-Counter Human Use; Final Monograph
7. Enax J, Fabritius H, Fabritius-Vilpoux K, Amaechi BT, Meyer F, Modes of Action and Clinical Efficacy of Particulate Hydroxyapatite in Preventive Oral Health Care − State of the Art, The Open Dentistry Journal, Volume 13, 2019, Pages 274-287, ISSN 1874-2106, https://doi.org/10.2174/1874210601913010274.
8. Chen, L.; Al-Bayatee, S.; Khurshid, Z.; Shavandi, A.; Brunton, P.; Ratnayake, J. Hydroxyapatite in Oral Care Products—A Review. Materials 2021, 14, 4865. https://doi. org/10.3390/ma14174865
9. SCCS (2023): SCCS Opinion on Hydroxyapatite (nano). SCCS/1648/22 – Final Opinion.
10. Nobre CMG, Pütz N, Hannig M, Adhesion of Hydroxyapatite Nanoparticles to Dental Materials under Oral Conditions, Scanning, 2020, 6065739, 12 pages, 2020. https://doi.org/10.1155/2020/6065739
11. O’Hagan-Wong, K., Enax, J., Meyer, F. et al. The use of hydroxyapatite toothpaste to prevent dental caries. Odontology 110, 223–230 (2022). https://doi.org/10.1007/s10266-021-00675-4
12. Pawinska M, Paszynska E, Amaechi BT, Meyer F, Enax J, Limeback H, Clinical evidence of caries prevention by hydroxyapatite: An updated systematic review and meta-analysis, Journal of Dentistry, Volume 151, 2024, 105429, ISSN 0300-5712, https://doi.org/10.1016/j.jdent.2024.105429.
13. Nesta, J. (2025, January). New Products Database search. Mintel.

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Jason Nesta is an oral care veteran with over 12 years of practical experience formulating toothpaste, mouthwash, and specialty oral care products. During that time, he led the development and commercialization of dozens of oral hygiene products, many of which can still be found on store shelves or in pharmacies. Jason has presented at the International Association of Dental Research, published in peer reviewed journals, and been awarded more than 10 composition of matter patents in the art. He received his bachelor’s degree in biological sciences and a Master of Arts for Teachers from Fairleigh Dickinson University. Jason is currently the Consumer Goods Market Development & Innovation Manager at Omya Inc.