Nano-hydroxyapatite in dental products: Better than fluoride?

Tooth enamel is the most mineralized tissue of the human body and hydroxyapatite (HA) is its main component.¹ In 1970, a toothpaste containing HA was produced by NASA; shortly after, the Japanese company Sangi Co. Ltd. purchased the rights. In 1980, the company launched the world's first enamel restoration toothpaste, which is now considered the gold standard oral health ingredient in Japan.²

Nano-HA can be found in toothpaste and mouthwashes in Japan, the Netherlands, and Canada, among other places. Although nano-HA has been used in several nations for years, the FDA has yet to approve it in the United States. With several studies indicating that nano-HA could be a viable replacement for fluoride, we need to understand the benefits and drawbacks of this addition.

How it works in dental products

Since the 1980s, hydroxyapatite has been minimized to nano-HA with particles reduced to the size of 50 nanometers (nm) increasing the surface area to which proteins (amino acids and noncollagenous proteins) can bind to in addition to making it more effective in penetrating subsurface enamel, as well as with fragments of plaque and bacteria when contained in toothpastes.^1,2 Along with a strong ability to bond with proteins, when contained in toothpastes nano-HA can also bond with plaque and bacteria.¹ Due to the size of nano-HA, it acts as a filler by repairing small holes and depressions on enamel surfaces.¹ Hydroxyapatite is a calcium-phosphate compound found in enamel, bone, and saliva that occurs naturally in the human body. Nano-HA is a synthetic form that is derived either chemically or mechanically, yet it is nearly identical to the HA produced by the body, making it nontoxic to live tissues.³

Hydroxyapatite can be synthesized chemically by using chemical reagents or extracted from natural sources. Compared to synthetic HA, natural HA contains trace elements that make it similar to the chemical composition of human bone.³ There have been studies done over the past 20 years in extracting HA from mammals and aquatic/marine, shell, plant/algae, and mineral sources. Hydroxyapatite has been proven to be the most effective in promoting bone regeneration due to its composition of mostly calcium and phosphorus.³ The extraction of HA from natural sources can be considered an environmentally friendly process and can result in positive contributions to the environment and to general health.³

Significant remineralization effects

A survey completed in the United States found that “92% of adults aged 20-64 currently have or have had dental caries in their permanent teeth.”⁴ When enamel and dentin are only partially demineralized, there is still a chance to remineralize the tooth by restoring the lost mineral ions in the hydroxyapatite crystals. To date, fluoride has been used as one of the most effective remineralizing agents in caries prevention.² Research has shown that nano-HA demonstrates significant remineralization effects on both enamel and dentin due to its small particle size.¹ Studies show that there is not a significant difference between fluoride and nano-HA when it comes to remineralization.¹ However, for many there is a concern of high intake or even chronic low-level exposure of fluoride, making nano-HA an excellent alternative remineralizing agent due to its biomimetic and nontoxic properties.

More effective for hypersensitivity?

Dentinal hypersensitivity is one of the most common dental conditions among adults and has been extensively researched. Over the past few decades, there’s been extensive research on using dentin sealers, periodontal soft tissue grafts, lasers, ions and salts, and fluoride iontophoresis (an electric current technique) to clinically treat hypersensitivity.⁵ From these clinical studies, numerous kinds of toothpaste and other hygiene aids have been developed to reduce tooth hypersensitivity. The introduction of different components in dentifrices began with the goal of occluding opened dentinal tubules and creating a mineralized barrier to prevent fluid from entering these tubules.

It has been recently proposed that nano-HA can fight against tooth hypersensitivity more efficiently compared to conventional toothpaste with fluoride. Nano-hydroxyapatite’s mechanism of action is to biochemically bind HA and collagen to dentin and block fluid from entering the dentinal tubules. Due to the biological nature of HA and collagen, their nano-sized diameter provides better encapsulation and fills smaller tubules.

In most studies investigating nano-HA’s effectiveness on tooth hypersensitivity, nano-HA has been proven to show a better reduction in sensitivity when compared to controls like fluoride or potassium nitrate.^2,5 But with other desensitizing agents, some clinical trials have shown comparable results so there has been no consensus in literature with regard to dentinal hypersensitivity treatment utilizing nano-HA.

Fluoride, CHX, and nano-HA

The main causes for dental caries and periodontitis are the growth, metabolism, and presence of the oral biofilm. For preventing or reducing the risk of these oral diseases, the goal is to control oral bacterial biofilm. Brushing and flossing can greatly help with removing bacteria, and mouthwashes or toothpastes that contain antibacterial agents can be another means to do so.⁶

Fluoride is known to be an agent for preventing plaque formation, whereas chlorhexidine (CHX) is utilized as a microbiological agent added to mouthwash and toothpastes. However, side effects after long-term use of CHX such as decreased microbial diversity and extrinsic tooth discoloration have prompted researchers to seek additional biofilm management agents.

The ultimate goal of biofilm management is to achieve a homeostatic balance between helpful and harmful bacteria. Antimicrobial agents can cause a dysbiosis, or imbalance, of the microbiome by killing and/or halting the growth of beneficial bacteria. Unlike CHX, nano-HA's antiadhesive property prevents bacteria from adhering to the tooth surface rather than killing and inhibiting their growth. Nano-HA can bind to plaque and proteins in addition to bacteria, which reduces plaque development and accumulation.⁷

Although additional research on nano-HA in oral care is needed, a research review published in 2019 indicates that nano-HA is a promising oral care ingredient because it is comparable to CHX in its biofilm control without destroying bacteria.⁶

Nano-HA is a great alternative to fluoride because of its biomimetic and nontoxic properties. According to various studies, nano-HA is comparable to fluoride and/or CHX in terms of its effectiveness in remineralizing tooth structure, hypersensitivity, and biofilm control. Although the American Dental Association (ADA) has not yet given nano-HA its seal of approval, it can be found in dental care products developed and sold in the United States.

References

Pepla E, Besharat LK, Palaia G, Tenore G, Migliau G. Nano-hydroxyapatite and its applications in preventive, restorative and regenerative dentistry: a review of literature. Ann Stomatol (Roma). 2014;5(3):108-114.
Chen L, Al-Bayatee S, Khurshid Z, Shavandi A, Brunton P, Ratnayake J. Hydroxyapatite in oral care products—a review. Materials (Basel). 2021;14(17):4865. doi:10.3390/ma14174865
Pu'ad NASM, Koshy P, Abdullah HZ, Idris MI, Lee TC. Syntheses of hydroxyapatite from natural sources. Heliyon. Accessed March 13, 2022. https://www.sciencedirect.com/science/article/pii/S2405844018368944.
Dental caries (tooth decay) in adults (age 20 to 64). National Institute of Dental and Craniofacial Research. https://www.nidcr.nih.gov/research/data-statistics/dental-caries/adults#:~:text=92%25%20of%20adults%2020%20to,education%20have%20had%20more%20decay.
Kulal R, Jayanti I, Sambashivaiah S, Bilchodmath S. An in-vitro comparison of nano hydroxyapatite, novamin and proargin desensitizing toothpastes - a SEM study. J Clin Diagn Res. 2016;10(10):ZC51-ZC54. doi:10.7860/JCDR/2016/18991.8649
Meyer F, Enax J. Hydroxyapatite in Oral Biofilm Management. Eur J Dent. 2019;13(2):287-290. doi:10.1055/s-0039-1695657
Alencar Cde M, Paula BLFde, Ortiz MIG, Magno MB, Silva CM, Maia LC. Clinical efficacy of nano-hydroxyapatite in dentin hypersensitivity: A systematic review and meta-analysis. Journal of Dentistry. https://www.sciencedirect.com/science/article/abs/pii/S0300571218305487.