Hydroxyapatite

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Hydroxyapatite
Mineraly.sk - hydroxylapatit.jpg
Hydroxyapatite crystals on matrix
General
Category Phosphate mineral
Apatite group
Formula
(repeating unit)		Ca5(PO4)3OH
IMA symbol Hap [1]
Strunz classification 8.BN.05
Crystal system Hexagonal
Crystal class Dipyramidal (6/m)
H-M symbol (6/m)
Space group P63/m
Unit cell a = 9.41 Å, c = 6.88 Å; Z = 2
Identification
Formula mass 502.31 g/mol
ColorColorless, white, gray, yellow, yellowish green
Crystal habit As tabular crystals and as stalagmites, nodules, in crystalline to massive crusts
Cleavage Poor on {0001} and {1010}
Fracture Conchoidal
Tenacity Brittle
Mohs scale hardness5
Luster Vitreous to subresinous, earthy
Streak White
Diaphaneity Transparent to translucent
Specific gravity 3.14–3.21 (measured), 3.16 (calculated)
Optical propertiesUniaxial (−)
Refractive index nω = 1.651 nε = 1.644
Birefringence δ = 0.007
References [2] [3] [4]
Hydroxyapatite Hydroxylapatite-338779.jpg
Hydroxyapatite
Needle-like hydroxyapatite crystals on stainless steel. Scanning electron microscope picture from University of Tartu. Hudroksuapatiidi kristallid.JPG
Needle-like hydroxyapatite crystals on stainless steel. Scanning electron microscope picture from University of Tartu.
Nanoscale coating of Ca-HAp, image taken with scanning probe microscope Nanoscale coating of Ca-HAp.PNG
Nanoscale coating of Ca-HAp, image taken with scanning probe microscope
A 3D visualization of half of a hydroxyapatite unit cell, from x-ray crystallography Hydroxyapatite3.png
A 3D visualization of half of a hydroxyapatite unit cell, from x-ray crystallography

Hydroxyapatite (IMA name: hydroxylapatite [5] ) (Hap, HAp, or HA) is a naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), often written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities. [6] It is the hydroxyl endmember of the complex apatite group. The OH− ion can be replaced by fluoride or chloride, producing fluorapatite or chlorapatite. It crystallizes in the hexagonal crystal system. Pure hydroxyapatite powder is white. Naturally occurring apatites can, however, also have brown, yellow, or green colorations, comparable to the discolorations of dental fluorosis.

Contents

Up to 50% by volume and 70% by weight of human bone is a modified form of hydroxyapatite, known as bone mineral. [7] Carbonated calcium-deficient hydroxyapatite is the main mineral of which dental enamel and dentin are composed. Hydroxyapatite crystals are also found in pathological calcifications such as those found in breast tumors, [8] as well as calcifications within the pineal gland (and other structures of the brain) known as corpora arenacea or "brain sand". [9]

Chemical synthesis

Hydroxyapatite can be synthesized via several methods, such as wet chemical deposition, biomimetic deposition, sol-gel route (wet-chemical precipitation) or electrodeposition. [10] The hydroxyapatite nanocrystal suspension can be prepared by a wet chemical precipitation reaction following the reaction equation below: [11]

10 Ca(OH)2 + 6 H3PO4 → Ca10(PO4)6(OH)2 + 18 H2O

The ability to synthetically replicate hydroxyapatite has invaluable clinical implications, especially in dentistry. Each technique yields hydroxyapatite crystals of varied characteristics, such as size and shape. [12] These variations have a marked effect on the biological and mechanical properties of the compound, and therefore these hydroxyapatite products have different clinical uses. [13]

Calcium-deficient hydroxyapatite

Calcium-deficient (non-stochiometric) hydroxyapatite, Ca10−x(PO4)6−x(HPO4)x(OH)2−x (where x is between 0 and 1) has a Ca/P ratio between 1.67 and 1.5. The Ca/P ratio is often used in the discussion of calcium phosphate phases. [14] Stoichiometric apatite Ca10(PO4)6(OH)2 has a Ca/P ratio of 10:6 normally expressed as 1.67. The non-stoichiometric phases have the hydroxyapatite structure with cation vacancies (Ca2+) and anion (OH−) vacancies. The sites occupied solely by phosphate anions in stoichiometric hydroxyapatite, are occupied by phosphate or hydrogen phosphate, HPO2−4, anions. [14] Preparation of these calcium-deficient phases can be prepared by precipitation from a mixture of calcium nitrate and diammonium phosphate with the desired Ca/P ratio, for example, to make a sample with a Ca/P ratio of 1.6: [15]

9.6 Ca(NO3)2 + 6 (NH4)2HPO4 → Ca9.6(PO4)5.6(HPO4)0.4(OH)1.6

Sintering these non-stoichiometric phases forms a solid phase which is an intimate mixture of tricalcium phosphate and hydroxyapatite, termed biphasic calcium phosphate: [16]

Ca10−x(PO4)6−x(HPO4)x(OH)2−x →(1 − x) Ca10(PO4)6(OH)2 + 3x Ca3(PO4)2

Biological function

Mammals and humans

Hydroxylapatite is present in bones and teeth; bone is made primarily of HA crystals interspersed in a collagen matrix—65 to 70% of the mass of bone is HA. Similarly HA is 70 to 80% of the mass of dentin and enamel in teeth. In enamel, the matrix for HA is formed by amelogenins and enamelins instead of collagen. [17]

Hydroxylapatite deposits in tendons around joints results in the medical condition calcific tendinitis. [18]

Hydroxylapatite is a constituent of calcium phosphate kidney stones. [19]

Remineralisation of tooth enamel

Remineralisation of tooth enamel involves the reintroduction of mineral ions into demineralised enamel. [20] Hydroxyapatite is the main mineral component of enamel in teeth. [21] During demineralisation, calcium and phosphorus ions are drawn out from the hydroxyapatite. The mineral ions introduced during remineralisation restore the structure of the hydroxyapatite crystals. [21] If fluoride ions are present during the remineralisation, through water fluoridation or the use of fluoride-containing toothpaste, the stronger and more acid-resistant fluorapatite crystals are formed instead of the hydroxyapatite crystals. [22]

Mantis shrimp

The clubbing appendages of the Odontodactylus scyllarus (peacock mantis shrimp) are made of an extremely dense form of the mineral which has a higher specific strength; this has led to its investigation for potential synthesis and engineering use. [23] Their dactyl appendages have excellent impact resistance due to the impact region being composed of mainly crystalline hydroxyapatite, which offers significant hardness. A periodic layer underneath the impact layer composed of hydroxyapatite with lower calcium and phosphorus content (thus resulting in a much lower modulus) inhibits crack growth by forcing new cracks to change directions. This periodic layer also reduces the energy transferred across both layers due to the large difference in modulus, even reflecting some of the incident energy. [24]

Use in dentistry

As of 2019, the use of hydroxyapatite, or its synthetically manufactured form, nano-hydroxyapatite, is not yet common practice. Some studies suggest it is useful in counteracting dentine hypersensitivity, preventing sensitivity after teeth bleaching procedures and caries prevention. [25] [26] [27] Avian eggshell hydroxyapatite can be a viable filler material in bone regeneration procedures in oral surgery. [28]

Dentine sensitivity

Nano-hydroxyapatite possesses bioactive components which can prompt the mineralisation process of teeth, remedying hypersensitivity. Hypersensitivity of teeth is thought to be regulated by fluid within dentinal tubules. [25] The movement of this fluid as a result of different stimuli is said to excite receptor cells in the pulp and trigger sensations of pain. [25] The physical properties of the nano-hydroxyapatite can penetrate and seal the tubules, stopping the circulation of the fluid and therefore the sensations of pain from stimuli. [26] Nano-hydroxyapatite would be preferred as it parallels the natural process of surface remineralisation. [27]

In comparison to alternative treatments for dentine hypersensitivity relief, nano-hydroxyapatite containing treatment has been shown to perform better clinically. Nano-hydroxyapatite was proven to be better than other treatments at reducing sensitivity against evaporative stimuli, such as an air blast, and tactile stimuli, such as tapping the tooth with a dental instrument. However, no difference was seen between nano-hydroxyapatite and other treatments for cold stimuli. [29] Hydroxylapatite has shown significant medium and long-term desensitizing effects on dentine hypersensitivity using evaporative stimuli and the visual analogue scale (alongside potassium nitrate, arginine, glutaraldehyde with hydroxyethyl methacrylate, hydroxyapatite, adhesive systems, glass ionomer cements and laser). [30]

Co-agent for bleaching

Teeth bleaching agents release reactive oxygen species which can degrade enamel. [26] To prevent this, nano-hydroxyapatite can be added to the bleaching solution to reduce the impact of the bleaching agent by blocking pores within the enamel. [26] This reduces sensitivity after the bleaching process. [27]

Caries prevention

Nano-hydroxyapatite possesses a remineralising effect on teeth and can be used to prevent damage from carious attacks. [27] In the event of an acid attack by cariogenic bacteria, nano-hydroxyapatite particles can infiltrate pores on the tooth surface to form a protective layer. [26] Furthermore, nano-hydroxyapatite may have the capacity to reverse damage from carious assaults by either directly replacing deteriorated surface minerals or acting as a binding agent for lost ions. [26]

In some toothpaste hydroxyapatite can be found in the form of nanocrystals (as these are easily dissolved). In recent years, hydroxyapatite nanocrystals (nHA) have been used in toothpaste to combat dental hypersensitivity. They aid in the repair and remineralisation of the enamel, thus helping to prevent tooth sensitivity. Tooth enamel can become demineralised due to various factors, including acidic erosion and dental caries. If left untreated this can lead to the exposure of dentin and subsequent exposure of the dental pulp. In various studies the use of nano hydroxyapatite in toothpaste showed positive results in aiding the remineralisation of dental enamel. [31] In addition to remineralisation, in vitro studies have shown that toothpastes containing nano-hydroxyapatite have the potential to reduce biofilm formation on both tooth enamel and resin-based composite surfaces. [32]

As a dental material

Hydroxyapatite is widely used within dentistry and oral and maxillofacial surgery, due to its chemical similarity to hard tissue. [33]

In the future, there are possibilities for using nano-hydroxyapatite for tissue engineering and repair. The main and most advantageous feature of nano-hydroxyapatite is its biocompatibility. [34] It is chemically similar to naturally occurring hydroxyapatite and can mimic the structure and biological function of the structures found in the resident extracellular matrix. [35] Therefore, it can be used as a scaffold for engineering tissues such as bone and cementum. [26] It may be used to restore cleft lips and palates and refine existing practices such as preservation of alveolar bone after extraction for better implant placement. [26]

Safety concerns

The European Commission's Scientific Committee on Consumer Safety (SCCS) issued an official opinion in 2021, where it considered whether the nanomaterial hydroxyapatite was safe when used in leave-on and rinse-off dermal and oral cosmetic products, taking into account reasonably foreseeable exposure conditions. It stated: [36]

Having considered the data provided, and other relevant information available in scientific literature, the SCCS cannot conclude on the safety of the hydroxyapatite composed of rod–shaped nanoparticles for use in oral-care cosmetic products at the maximum concentrations and specifications given in this Opinion. This is because the available data/information is not sufficient to exclude concerns over the genotoxic potential of HAP-nano.

The European Commission's Scientific Committee on Consumer Safety (SCCS) reissued an updated opinion in 2023, where it cleared rod-shaped nano hydroxyapatite of concerns regarding genotoxicity, allowing consumer products to contain concentrations of nano hydroxyapatite as high as 10% for toothpastes and 0.465% for mouthwashes. However it warns of needle-shaped nano hydroxyapatite and of inhalation in spray products. It stated: [37]

Based on the data provided, the SCCS considers hydroxyapatite (nano) safe when used at concentrations up to 10% in toothpaste, and up to 0.465% in mouthwash. This safety evaluation only applies to the hydroxyapatite (nano) with the following characteristics:

– composed of rod-shaped particles of which at least 95.8% (in particle number) have an aspect ratio of less than 3, and the remaining 4.2% have an aspect ratio not exceeding 4.9;

– the particles are not coated or surface modified.

Chromatography

Along with its medical applications, hydroxyapatite is also used in downstream applications under mixed-mode chromatography in polishing step. The ions present on the surface of hydroxyapatite make it an ideal candidate with unique selectivity, separation and purification of biomolecule mixtures. In mixed-mode chromatography, hydroxyapatite is used as the stationary phase in chromatography columns.

The combined presence of calcium ions (C- sites) and phosphate sites (P-sites) provide metal affinity and ion exchange properties respectively. The C-sites on the surface of the resin undergo metal affinity interactions with phosphate or carboxyl groups present on the biomolecules. Concurrently, these positively charged C-sites tend to repel positively charged functional groups (e.g., amino groups) on biomolecules. P-sites undergo cationic exchange with positively charged functional groups on biomolecules. They exhibit electrostatic repulsion with negatively charged functional groups on biomolecules. For the elution of molecules buffer with high concentration of phosphate and sodium chloride is used. The nature of different charged ions on the surface of hydroxyapatite provides the framework for unique selectivity and binding of biomolecules, facilitating robust separation of biomolecules.

Hydroxyapatite is available in different forms and in different sizes for the purpose of protein purification. The advantages of hydroxyapatite media are its high product stability and uniformity in various lots during its production. Generally, hydroxyapatite was used in the polishing step of monoclonal antibodies, isolation of endotoxin free plasmids, purification of enzymes and viral particles. [38]

Use in archaeology

In archaeology, hydroxyapatite from human and animal remains can be analysed to reconstruct ancient diets, migrations and paleoclimate. The mineral fractions of bone and teeth act as a reservoir of trace elements, including carbon, oxygen and strontium. Stable isotope analysis of human and faunal hydroxyapatite can be used to indicate whether a diet was predominantly terrestrial or marine in nature (carbon, strontium); [39] the geographical origin and migratory habits of an animal or human (oxygen, strontium) [40] and to reconstruct past temperatures and climate shifts (oxygen). [41] Post-depositional alteration of bone can contribute to the degradation of bone collagen, the protein required for stable isotope analysis. [42]

Defluoridation

Hydroxylapatite is a potential adsorbent for the defluoridation of drinking water, as it forms fluorapatite in a three step process. Hydroxylapatite removes F− from the water to replace OH− forming fluorapatite. However, during the defluoridation process the hydroxyapatite dissolves, and increases the pH and phosphate ion concentration which makes the defluoridated water unfit for drinking. [43] Recently, a ″calcium amended-hydroxyapatite″ defluoridation technique was suggested to overcome the phosphate leaching from hydroxyapatite. [43] This technique can also affect fluorosis reversal by providing calcium-enriched alkaline drinking water to fluorosis affected areas.

See also

Related Research Articles

<span class="mw-page-title-main">Apatite</span> Mineral group, calcium phosphate

Apatite is a group of phosphate minerals, usually hydroxyapatite, fluorapatite and chlorapatite, with high concentrations of OH−, F− and Cl− ion, respectively, in the crystal. The formula of the admixture of the three most common endmembers is written as Ca10(PO4)6(OH,F,Cl)2, and the crystal unit cell formulae of the individual minerals are written as Ca10(PO4)6(OH)2, Ca10(PO4)6F2 and Ca10(PO4)6Cl2.

<span class="mw-page-title-main">Toothpaste</span> Substance to clean and maintain teeth

Toothpaste is a paste or gel dentifrice used with a toothbrush to clean and maintain the aesthetics and health of teeth. Toothpaste is used to promote oral hygiene: it is an abrasive that aids in removing dental plaque and food from the teeth, assists in suppressing halitosis, and delivers active ingredients to help prevent tooth decay and gum disease (gingivitis). Owing to differences in composition and fluoride content, not all toothpastes are equally effective in maintaining oral health. The decline of tooth decay during the 20th century has been attributed to the introduction and regular use of fluoride-containing toothpastes worldwide. Large amounts of swallowed toothpaste can be poisonous. Common colors for toothpaste include white and blue.

<span class="mw-page-title-main">Tooth enamel</span> Major tissue that makes up part of the tooth in humans and many animals

Tooth enamel is one of the four major tissues that make up the tooth in humans and many animals, including some species of fish. It makes up the normally visible part of the tooth, covering the crown. The other major tissues are dentin, cementum, and dental pulp. It is a very hard, white to off-white, highly mineralised substance that acts as a barrier to protect the tooth but can become susceptible to degradation, especially by acids from food and drink. In rare circumstances enamel fails to form, leaving the underlying dentin exposed on the surface.

<span class="mw-page-title-main">Calcium phosphate</span> Chemical compound

The term calcium phosphate refers to a family of materials and minerals containing calcium ions (Ca2+) together with inorganic phosphate anions. Some so-called calcium phosphates contain oxide and hydroxide as well. Calcium phosphates are white solids of nutritional value and are found in many living organisms, e.g., bone mineral and tooth enamel. In milk, it exists in a colloidal form in micelles bound to casein protein with magnesium, zinc, and citrate–collectively referred to as colloidal calcium phosphate (CCP). Various calcium phosphate minerals are used in the production of phosphoric acid and fertilizers. Overuse of certain forms of calcium phosphate can lead to nutrient-containing surface runoff and subsequent adverse effects upon receiving waters such as algal blooms and eutrophication (over-enrichment with nutrients and minerals).

<span class="mw-page-title-main">Dentin</span> Calcified tissue of the body; one of the four major components of teeth

Dentin or dentine is a calcified tissue of the body and, along with enamel, cementum, and pulp, is one of the four major components of teeth. It is usually covered by enamel on the crown and cementum on the root and surrounds the entire pulp. By volume, 45% of dentin consists of the mineral hydroxyapatite, 33% is organic material, and 22% is water. Yellow in appearance, it greatly affects the color of a tooth due to the translucency of enamel. Dentin, which is less mineralized and less brittle than enamel, is necessary for the support of enamel. Dentin rates approximately 3 on the Mohs scale of mineral hardness. There are two main characteristics which distinguish dentin from enamel: firstly, dentin forms throughout life; secondly, dentin is sensitive and can become hypersensitive to changes in temperature due to the sensory function of odontoblasts, especially when enamel recedes and dentin channels become exposed.

<span class="mw-page-title-main">Dental erosion</span> Medical condition

Acid erosion is a type of tooth wear. It is defined as the irreversible loss of tooth structure due to chemical dissolution by acids not of bacterial origin. Dental erosion is the most common chronic condition of children ages 5–17, although it is only relatively recently that it has been recognised as a dental health problem. There is generally widespread ignorance of the damaging effects of acid erosion; this is particularly the case with erosion due to consumption of fruit juices because they tend to be considered as healthy. Acid erosion begins initially in the enamel, causing it to become thin, and can progress into dentin, giving the tooth a dull yellow appearance and leading to dentin hypersensitivity.

<span class="mw-page-title-main">Fluoride therapy</span> Medical use of fluoride

Fluoride therapy is the use of fluoride for medical purposes. Fluoride supplements are recommended to prevent tooth decay in children older than six months in areas where the drinking water is low in fluoride. It is typically used as a liquid, pill, or paste by mouth. Fluoride has also been used to treat a number of bone diseases.

<span class="mw-page-title-main">Bioglass 45S5</span> Bioactive glass biomaterial

Bioglass 45S5 or calcium sodium phosphosilicate, is a bioactive glass specifically composed of 45 wt% SiO2, 24.5 wt% CaO, 24.5 wt% Na2O, and 6.0 wt% P2O5. Typical applications of Bioglass 45S5 include: bone grafting biomaterials, repair of periodontal defects, cranial and maxillofacial repair, wound care, blood loss control, stimulation of vascular regeneration, and nerve repair.

<span class="mw-page-title-main">Tricalcium phosphate</span> Chemical compound

Tricalcium phosphate (sometimes abbreviated TCP), more commonly known as Calcium phosphate, is a calcium salt of phosphoric acid with the chemical formula Ca3(PO4)2. It is also known as tribasic calcium phosphate and bone phosphate of lime (BPL). It is a white solid of low solubility. Most commercial samples of "tricalcium phosphate" are in fact hydroxyapatite.

<span class="mw-page-title-main">Dicalcium phosphate</span> Chemical compound

Dicalcium phosphate is the calcium phosphate with the formula CaHPO4 and its dihydrate. The "di" prefix in the common name arises because the formation of the HPO42– anion involves the removal of two protons from phosphoric acid, H3PO4. It is also known as dibasic calcium phosphate or calcium monohydrogen phosphate. Dicalcium phosphate is used as a food additive, it is found in some toothpastes as a polishing agent and is a biomaterial.

Dentin hypersensitivity is dental pain which is sharp in character and of short duration, arising from exposed dentin surfaces in response to stimuli, typically thermal, evaporative, tactile, osmotic, chemical or electrical; and which cannot be ascribed to any other dental disease.

<span class="mw-page-title-main">Fluorapatite</span> Phosphate mineral

Fluorapatite, often with the alternate spelling of fluoroapatite, is a phosphate mineral with the formula Ca5(PO4)3F (calcium fluorophosphate). Fluorapatite is a hard crystalline solid. Although samples can have various color (green, brown, blue, yellow, violet, or colorless), the pure mineral is colorless, as expected for a material lacking transition metals. Along with hydroxylapatite, it can be a component of tooth enamel, but for industrial use both minerals are mined in the form of phosphate rock, whose usual mineral composition is primarily fluorapatite but often with significant amounts of the other.

Biomimetic materials are materials developed using inspiration from nature. This may be useful in the design of composite materials. Natural structures have inspired and innovated human creations. Notable examples of these natural structures include: honeycomb structure of the beehive, strength of spider silks, bird flight mechanics, and shark skin water repellency. The etymological roots of the neologism "biomimetic" derive from Greek, since bios means "life" and mimetikos means "imitative".

Olaflur is a fluoride-containing substance that is an ingredient of toothpastes and solutions for the prevention of dental caries. It has been in use since 1966. Especially in combination with dectaflur, it is also used in the form of gels for the treatment of early stages of caries, sensitive teeth, and by dentists for the refluoridation of damaged tooth enamel.

Amorphous calcium phosphate (ACP) is a glassy solid that is formed from the chemical decomposition of a mixture of dissolved phosphate and calcium salts (e.g. (NH4)2HPO4 + Ca(NO3)2). The resulting amorphous mixture consists mostly of calcium and phosphate, but also contains varying amounts of water and hydrogen and hydroxide ions, depending on the synthesis conditions. Such mixtures are also known as calcium phosphate cement.

<span class="mw-page-title-main">Remineralisation of teeth</span>

Tooth remineralization is the natural repair process for non-cavitated tooth lesions, in which calcium, phosphate and sometimes fluoride ions are deposited into crystal voids in demineralised enamel. Remineralization can contribute towards restoring strength and function within tooth structure.

Tetracalcium phosphate is the compound Ca4(PO4)2O, (4CaO·P2O5). It is the most basic of the calcium phosphates, and has a Ca/P ratio of 2, making it the most phosphorus poor phosphate. It is found as the mineral hilgenstockite, which is formed in industrial phosphate rich slag (called "Thomas slag"). This slag was used as a fertiliser due to the higher solubility of tetracalcium phosphate relative to apatite minerals. Tetracalcium phosphate is a component in some calcium phosphate cements that have medical applications.

<span class="mw-page-title-main">Oligopeptide P11-4</span> Chemical compound

Oligopeptide P11-4 is a synthetic, pH controlled self-assembling peptide used for biomimetic mineralization e.g. for enamel regeneration or as an oral care agent. P11-4 consists of the natural occurring amino acids Glutamine, Glutamic acid, Phenylalanine, Tryptophan and Arginine. The resulting higher molecular structure has a high affinity to tooth mineral. P11-4 has been developed and patented by The University of Leeds (UK). The Swiss company Credentis has licensed the peptide technology and markets it under the trade names including CUROLOX, REGENAMEL, and EMOFLUOR. They offer three products with this technology. As of June 2016 in Switzerland products are available with new Brand names from Dr. Wild & Co AG.

Hard tissue, refers to "normal" calcified tissue, is the tissue which is mineralized and has a firm intercellular matrix. The hard tissues of humans are bone, tooth enamel, dentin, and cementum. The term is in contrast to soft tissue.

Topical fluorides are fluoride-containing drugs indicated in prevention and treatment of dental caries, particularly in children's primary dentitions. The dental-protecting property of topical fluoride can be attributed to multiple mechanisms of action, including the promotion of remineralization of decalcified enamel, the inhibition of the cariogenic microbial metabolism in dental plaque and the increase of tooth resistance to acid dissolution. Topical fluoride is available in a variety of dose forms, for example, toothpaste, mouth rinses, varnish and silver diamine solution. These dosage forms possess different absorption mechanisms and consist of different active ingredients. Common active ingredients include sodium fluoride, stannous fluoride, silver diamine fluoride. These ingredients account for different pharmacokinetic profiles, thereby having varied dosing regimes and therapeutic effects. A minority of individuals may experience certain adverse effects, including dermatological irritation, hypersensitivity reactions, neurotoxicity and dental fluorosis. In severe cases, fluoride overdose may lead to acute toxicity. While topical fluoride is effective in preventing dental caries, it should be used with caution in specific situations to avoid undesired side effects.

References

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