Topical fluorides are fluoride-containing drugs indicated in prevention and treatment of
dental caries
Tooth decay, also known as cavities or caries, is the breakdown of teeth due to acids produced by bacteria. The cavities may be a number of different colors from yellow to black. Symptoms may include pain and difficulty with eating. Complicatio ...
, 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
In biogeochemistry, remineralisation (or remineralization) refers to the breakdown or transformation of organic matter (those molecules derived from a biological source) into its simplest Inorganic compound, inorganic forms. These transformations ...
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
Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...
reactions, neurotoxicity and
dental fluorosis
Dental fluorosis is a common disorder, characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation.
It appears as a range of visual changes in enamel causing degrees of intrinsic tooth d ...
.
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.
Medical uses
Topical fluoride formulations are effective measures for preventing and arresting the progression of dental caries, especially early childhood caries (ECC).
Domestic products such as toothpaste and mouthwash can be used on a regular basis at home, while silver diamine solution therapy can be administered by specialists in dental clinics.
Mechanism of action
Topical fluoride serves to prevent early dental caries primarily in three ways: promoting
remineralization
In biogeochemistry, remineralisation (or remineralization) refers to the breakdown or transformation of organic matter (those molecules derived from a biological source) into its simplest Inorganic compound, inorganic forms. These transformations ...
of decalcified enamel, inhibiting the cariogenic microbial processes in
dental plaque
Dental plaque is a biofilm of microorganisms (mostly bacteria, but also fungi) that grows on surfaces within the mouth. It is a sticky colorless deposit at first, but when it forms tartar, it is often brown or pale yellow. It is commonly found bet ...
and increasing tooth resistance to acid breakdown.
Promotion of remineralization of decalcified enamel
Fluoride has a high tendency to react with the calcium hydroxyapatite Ca10(PO4)6(OH)2 in tooth
enamel due to its high affinity to metals.
It subsequently replaces the hydroxide group in hydroxyapatite to precipitate calcium fluorapatite Ca5(PO4)3)F.
These fluorapatite precipitations scavenge excess phosphate and calcium in the saliva to form a supersaturated solution for remineralization.
Inhibition of the cariogenic microbial processes in dental plaque
Topical fluoride also serves as an
antimicrobial agent
An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...
to reduce demineralization by inhibiting the growth of tooth-erupting microorganisms in dental plaque.
Fluoride ions readily combine with hydrogen cations to produce hydrogen fluoride.
Hydrogen fluoride subsequently acidifies the bacterial
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
, inactivating the essential enzymes for bacterial metabolism, including enolase and proton releasing
adenosine triphosphatase.
As topical fluoride lowers the pH, bacteria have to consume more energy to maintain a neutral environment, leaving less energy for reproduction, and further generation of
polysaccharide
Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wa ...
s and acids.
These polysaccharides are necessary for adherence to
enamel, while these acids are essential for the synthesis of bacterial enzymes, for example,
immunoglobulin A protease.
These processes contribute to reducing the risk of dental caries by inhibiting microbial metabolism in the tooth plaque.
Increase in tooth resistance to acid dissolution
Topical fluoride can increase the resistance of enamel to acid.
Bacteria in enamel, including
Streptococcus
''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occurs ...
mutans, generate acids to maintain a low pH environment during
fermentation
Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...
.
These acids eventually dissociate the hydroxyapatite in teeth once the acidity falls below the critical pH (pH 5.5).
The fluorapatite formed by topical fluorides has lower critical pH (pH 4.5) than normal enamel, it is therefore more acid resistant and not prone to degrade even in an acidic environment.
This mechanism helps decelerate the rate of teeth demineralization.
Dosage forms
Toothpaste
![Charcoal Toothpaste](https://upload.wikimedia.org/wikipedia/commons/3/34/Charcoal_Toothpaste.jpg)
The daily use of fluoride-containing toothpaste is recognized as the key factor contributing to the global reduction in dental caries over recent decades. Fluoride-containing toothpaste can be classified into two types, namely low-fluoride and high-fluoride toothpaste.
Low-fluoride toothpaste, depending on brand, generally contains 0.22% to 0.31% fluoride.
These fluorides are often manufactured in the form of sodium fluoride, stannous fluoride, or sodium monofluorophosphate (MFP).
High-fluoride toothpaste typically contains 1.1% sodium fluoride, namely four times more concentrated than low-fluoride toothpaste.
People using high-fluoride toothpaste should avoid eating or rinsing their mouth for at least 30 minutes after treatment for maximal therapeutic effect. Some fluoride-containing toothpaste incorporates extra chemical ingredients for additional purposes.
For instance, calcium carbonate and magnesium carbonate are added as
abrasives
An abrasive is a material, often a mineral, that is used to shape or finish a workpiece through rubbing which leads to part of the workpiece being worn away by friction. While finishing a material often means polishing it to gain a smooth, reflec ...
to remove dental plaque on teeth, while strontium chloride and potassium nitrate are added as anti-sensitive agents for individuals who have
teeth sensitivity.
Mouth rinse
Fluoride mouth rinse is usually used for adjunctive therapy with other topical fluoride products. It is generally prepared in the form of sodium chloride.
Sodium chloride is kept in the saliva after spitting out the mouth rinse, thus helping to prevent tooth decay.
0.02% fluoride mouth rinse rinse is commonly administered twice daily, while 0.05% is administered once daily at bedtime after thoroughly brushing teeth. People using high-fluoride toothpaste should avoid eating or rinsing their mouth for at least 30 minutes after administration for maximal therapeutic effect.
Silver diamine solution
![Dental Caries Cavity 2](https://upload.wikimedia.org/wikipedia/commons/2/2f/Dental_Caries_Cavity_2.JPG)
Silver diamine fluoride (SDF) is a transparent solution prepared by dissolving silver ions and fluoride ions in ammonia water.
It is approved in a few places, including Hong Kong, China, and the United States, for the prevention of
early childhood caries Early childhood caries (ECC), formerly known as nursing bottle caries, baby bottle tooth decay, night bottle mouth and night bottle caries, is a disease that affects teeth in children aged between birth and 71 months.American Academy of Pediatric De ...
(ECC) and relieving tooth sensitivity.
SDF has multiple advantages over traditional
fluoride varnish thearpy:
* SDF is a non-invasive treatment with higher acceptability among children and elderlies.
* The materials required for SDF are inexpensive, reducing the financial burden on patients.
* There is currently no evidence that SDF causes serious adverse reactions, for example, acute toxicity and infection of the
dental pulp
The pulp is the connective tissue, nerves, blood vessels, and odontoblasts that comprise the innermost layer of a tooth. The pulp's activity and signalling processes regulate its behaviour.
Anatomy
The pulp is the neurovascular bundle cent ...
, rendering it a safer therapy.
* SDF followed by stannous fluoride was proven to be more effective in reducing dental caries in children's primary
molars
The molars or molar teeth are large, flat teeth at the back of the mouth. They are more developed in mammals. They are used primarily to grind food during chewing. The name ''molar'' derives from Latin, ''molaris dens'', meaning "millstone to ...
.
However, the SDF solution results in permanent black staining on the teeth's decayed proportion. This may be unacceptable by some individuals with aesthetic concerns.
SDF, in addition to performing the functions of conventional topical fluorides, is suggested to have collagen-conserving properties and an additional antibacterial action owing to the presence of silver.
While multiple clinical trials demonstrate that 38% SDF is more effective than 5% sodium fluoride varnish in preventing ECC, it is currently unavailable in many countries due to insufficient research data.
Adverse effects
Increased exposure of fluoride may lead to certain adverse side effects, including
dental fluorosis
Dental fluorosis is a common disorder, characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation.
It appears as a range of visual changes in enamel causing degrees of intrinsic tooth d ...
and developmental
neurotoxicity
Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...
.
Other rare side effects include
skin rash
A rash is a change of the human skin which affects its color, appearance, or texture.
A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...
and
hypersensitivity
Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...
reactions.
In severe cases, fluoride overdose may lead to acute toxicity.
Dental fluorosis
Dental fluorosis
Dental fluorosis is a common disorder, characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation.
It appears as a range of visual changes in enamel causing degrees of intrinsic tooth d ...
is a dose-dependent adverse drug effect featured by temporary white marks.
It can be induced by increased fluoride exposure, typically from stannous fluoride-containing products or fluoridated water.
Excess intake of fluoride leads to overabundance of structurally-weak fluorapatite formed inside the enamel, resulting in increased brittleness of teeth. In severe dental fluorosis, brown or yellow staining may appear on teeth.
Children under the age of eight are susceptible to dental fluorosis.
Developmental neurotoxicity
Overdose of fluoride can potentially cause neurotoxicity during early development.
While the exact pathophysiology of fluoride-induced developmental toxicity is not completely understood, most research suggested that excessive fluoride intake may result in formation of aluminium fluoride (AlF3 or AlF4).
Aluminium fluoride structurally mimics phosphate, thus is capable of crossing the blood-brain barrier via phosphate transporters.
These fluorides in the brain may cause neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and IQ declination.
Nevertheless, topical fluoride was less likely to cause developmental neurotoxicity than
fluoridated water
Water fluoridation is the controlled adjustment of fluoride to a public water supply solely to reduce tooth decay. Fluoridated water contains fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding ...
.
Acute fluoride toxicity
Fluoride overdose may cause acute toxicity.
While the underlying mechanism of fluoride toxicity is unclear, most studies ascribe fluoride toxicity to its capacity to inhibit
metalloprotein
Metalloprotein is a generic term for a protein that contains a metal ion Cofactor (biochemistry), cofactor. A large proportion of all proteins are part of this category. For instance, at least 1000 human proteins (out of ~20,000) contain zinc-bi ...
s by imitating metallofluoride substrate.
Inhibition of metalloproteins slows down multiple
signalling pathways
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately re ...
and disrupts cellular
organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
s, subsequently producing oxidative stress and cell cycle arrest.
Fluoride overload is suggested to be linked to pH and electrolyte imbalances, creating an environment unfavourable for cell living.
These mechanisms can ultimately result in cellular malfunction and cell death.
Cautions
Toothpaste, cream, mouthrinse and varnish
* Most topical fluoride preparations with a concentration exceeding 0.6 ppm should be avoided to reduce risk of dental fluorosis if drinking water has already been
fluoridated.
* Swallowing of topical fluoride products should be avoided in order to avoid systemic adverse effects, for example,
skeletal fluorosis
Skeletal fluorosis is a bone disease caused by excessive accumulation of fluoride leading to weakened bones. In advanced cases, skeletal fluorosis causes painful damage to bones and joints.
Symptoms
Symptoms are mainly promoted in the bone structu ...
.
* While an appropriate amount of fluoride consumption during pregnancy is beneficial to prevent early childhood caries (ECC), pregnant women should avoid excessive fluoride exposure since it may predispose their children to skeletal fluorosis in later childhood.
* Most topical fluoride preparations containing more than 1.1ppm should be avoided in children younger than 6 years of age, unless otherwise instructed by a healthcare practitioner.
* Topical fluoride preparation containing benzyl alcohol derivative, polysorbate 80 and propylene glycol should be used in caution. These ingredients may precipitate severe adverse effects in neonates.
Silver diamine fluoride
* Silver diamine fluoride is contraindicated in patients having silver allergy,
oral ulcerations and severe gum disease.
These diseases can cause painful responses when associated with the acid or ammonia in SDF.
References
{{ci, date=June 2022
Fluorides
Dentistry