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Fluoride and its modalities

  2. Outline • Introduction • Mechanism of action of fluoride • Fluoride application in paediatric dentistry • Topical fluoride application • Professionally • Self • Silver diamine fluoride • Systemic fluoride application • Fluoride Hazard • Conclusion • References
  3. Introduction • Dental caries is the most common childhood disease. • It is an important public health problem across the world. The world health organization (WHO) emphasizes that the disease affects about 60–90% of school children. • Fluoride was introduced into dentistry over 70 years ago, and it is now recognized as the main factor responsible for the dramatic decline in caries prevalence that has been observed worldwide.
  4. Introduction • Fluorine is derived from the latin word “fluore” meaning “to flow”. • It is a member of the halogen family with atomic weight of 19 and atomic number of 9. • Is the most electronegative and reactive of all elements, hence it is never found in its elemental form in nature. • It is combined chemically in the form of fluorides.
  5. Introduction • Fluoride may occur in a wide variety of minerals in rock and soil including fluorspar, cryolite, apatite, mica, topaz, tourmaline. • Fluoride concentration in the soil increases with depth. • Waters with high fluoride content are usually found at the foot of high mountains and areas with geological deposits of marine origin.
  6. Introduction • All water contains fluorides in varying concentrations due to the presence of fluoride in the earths crust. • Water from lakes, rivers and artesian wells have a fluoride content below 0.5mg/l. • Sea water contains fluoride levels of 0.8-1.4mg/l. • Lake Nakuru in the rift valley in Kenya has the highest natural fluoride concentration of 2800mg/l.
  7. • Approximately 90% of the fluoride ingested each day is absorbed from the alimentary tract with higher proportions from liquids than solids. • Absorption across the oral cavity is limited and accounts for less than 1% of the daily intake. • Absorption from the stomach occurs readily and is inversely related to the ph of the gastric contents. • High concentrations of dietary calcium and other cat-ions form insoluble complexes with fluoride ion thus reducing fluoride absorption from the gastrointestinal tract.
  8. Introduction Dietary sources of fluoride include: • Unprocessed foods -low (0.1-2.5 mg/kg). • In plants - 2-20mg/g of dry weight. • Leafy vegetables -11-26 mg on dry weight basis. • Fish -20-40 ppm on dry weight basis
  9. Introduction • Approximately 99% of the body burden of fluoride is associated with the calcified tissues. • Approximately 55% will be retained by children and 36% by adults. The remainder of the absorbed fluoride will be excreted in urine. • The elimination of absorbed fluoride occurs almost exclusively via the kidneys and about 10% of the daily intake of fluoride is not absorbed and is excreted in the faeces.
  10. Mechanism of Action of Fluoride • The effect of fluoride in caries prevention can be considered under two headings. • Pre-eruptive effect • Post – eruptive effect
  11. Mechanism of Action of Fluoride • Until recently the major caries-inhibitory effect of fluoride was thought to be due to its incorporation in tooth minerals during the development of the tooth (systemic) prior to eruption. • There is now overwhelming evidence that the primary caries- preventive mechanisms of action of fluoride are post-eruptive (topical) effects for both children and adults.
  12. Pre-eruptive Effect • Improved crystallinity - Changes the crystalline structure of enamel making it less soluble. • Increased Crystal size • Less acid solubility • More rounded cusps and fissures • Overall effect is small because discontinuation of fluorides leads to loss of caries protection – constant servicing!!!
  13. • Changes the crystalline structure of enamel to make it less soluble. OLD CONCEPT • That major inhibitory effect was thought to be due to its incorporation in tooth mineral during the development of the tooth prior to eruption
  14. Post-Eruptive Effect • Recent evidences shows that the main effect of fluoride in caries prevention are the post-eruptive - through topical application. • Fluoride incorporated developmentally into the normal tooth mineral is insufficient to have a measurable effect on acid solubility. • Only when fluoride is concentrated into a new crystal surface during Re-mineralization, is it sufficient to alter solubility beneficially.
  15. Post-Eruptive Effect • Effect is seen when fluoride is present in plaque and saliva. • There is now clear evidence that caries reduction is most effective when a low concentration of fluoride is maintained consistently within the oral environment.
  16. Post-Eruptive Effect • Permanent enamel is an acellular tissue composed chiefly of minerals (calcium- deficient, carbonated hydroxyapatite (85% volume). • The hydroxyapatite molecules are arranged in long and thin apatite crystals that forms the enamel prism. • The spaces between the crystals is occupied by water (12%vol) and organic material (3% vol). • It is in this space filled with the enamel fluid that the demineralization and remineralization reactions take place.
  17. Post-Eruptive Effect • The dentine contains 47% apatite, 33% organic components and 20% water. • The organic matrix is composed mainly of collagen (90%), and other non- collagenous components. • The collagen forms the backbone of dentin and serves as a template for the deposition of apatite crystallites within the collagen matrix.
  18. Post-Eruptive Effect • The small apatite crystals provides a large surface area for acid interaction during acid attack. • Thus making the dentine surface more susceptible to caries attack than the enamel. • For dentinal caries to occur, there must be an initial dissolution of the mineral which in turn exposes the organic matrix to breakdown by bacterial- derived enzymes as well as by host derived enzymes such as matrix metalloproteinases present in dentin and saliva.
  19. Post-Eruptive Effect • The saliva under resting condition is a super saturated solution of calcium and phosphate ions. • Fluoride when present in the oral environment, reacts with the available calcium ion to form CaF₂. • The mineral of tooth tissue exists as a carbonated apatite which contains calcium, phosphate, and hydroxyl ions, making it a hydroxyapatite (Ca₁₀(PO4)₆(OH)₂). The carbonated portions weaken the structure and render the tissue susceptible to attack.
  20. Post-Eruptive Effect • In the presence of an acid attack and with a pH below 5.5 (the critical pH for hydroxyapatite demineralization), a net outward flow of calcium and phosphate ions from the enamel surface into plaque and saliva occurs. • As the pH returns to 7.0, remineralization occurs with a net inward flow of ions into the enamel surface. • Fluoride when present during remineralization, it is incorporated to form fluorapatite (Ca₁₀(PO4)₆F₂). which is more stable and resistant to further acid attacks
  21. Post-Eruptive Effect • This is now widely believed to be the most important preventive action of fluoride. • A constant post-eruptive supply of ionic fluoride is thought to be the most effective.
  22. Post-eruptive effect • Fluoride prevents demineralization. • Formation of fluorohydroxyapatite and inhibition of mineral loss from enamel. (critical ph is 3.5) • Fluoride enhances remineralization. • Through formation of a fluoride reservoir and creation of supersaturated solutions. • Fluoride aids in post eruptive maturation of enamel. • Fluoride reduces enamel solubility
  23. Post-eruptive effect • Fluoride inhibit plaque bacteria. • By blocking the enzyme enolase, needed in the glycolytic pathway of CHO metabolism • Also reduces the accumulation of intracellular and extra- cellular polysaccharides • At low pH, fluoride combines with hydrogen ions and diffuses into oral bacteria as hydrogen fluoride (HF) Inside the cell HF dissociates, acidifying the cell and releasing fluoride ions that inhibit glycolysis.
  24. Fluoride Application in Paediatric Dentistry
  25. Topical Fluoride • The term Topical Fluoride Therapy refers to the use of systems containing relatively large concentrations of fluoride that are applied locally, or topically to erupted tooth surfaces to prevent the formation of dental caries. • Thus this term encompasses the use of fluoride rinses, dentifrices, pastes, gels, and solutions that are applied in various manner.
  26. Rationale for Topical Fluoride • Topical fluorides hastens the process of fluoride acquisition by the teeth mineral. • Since immature and porous enamel acquires fluoride rapidly and the enamel surface of newly erupted teeth undergoes rapid maturation, its follows that the best time to apply topical fluorides is soon after eruption.
  27. Rationale for Topical Fluoride • Also the initial carious lesion, characterized by a white spot, is porous and accumulates fluoride at much higher concentrations than adjacent sound enamel. • Hence periodic applications of fluoride would enable vulnerable enamel sites that are partially demineralized to accumulate fluoride.
  28. Classification of Topical Fluoride • Professionally applied • Introduced by Bibby in 1942 • Dispensed by dental professionals in the dental office and usually involve the use of high fluoride concentration products ranging from 5000-19000 ppm. • which is equivalent to 5-9 mg F/ml • Self applied • Are low fluoride concentration products available for use at home. • Fl conc. ranges from 200-1000ppm or 0.2-1 mgF/ml • Include fluoride dentifrices, mouth rinses & gels
  29. Indications for Professional Topical Fluorides • High caries risk or caries active children i.e. those with past caries experience or those who develop new carious lesion on smooth tooth surfaces- severe ECC • Children shortly after periods of tooth eruption, especially those who are not carries free. • Medication to reduce salivary flow or had undergone head and neck radiation. • After periodontal surgery when roots of teeth have been exposed. • Patients with fixed or removable prosthesis and after placement or replacement of restorations. • Special health care need children.
  30. • Professional topical fluorides used in dentistry include: 1. Sodium fluoride: 2. Stannous fluoride 3. Acidulated phosphate fluoride
  31. Professionally Applied Fl • The professionally fluoride may be in the form of: • Varnish • Gel • Foam • Solution • Slow releasing device • These can be applied using the Paint on Technique or the Tray Technique.
  32. Knutson’s Technique - NaF • Named after Knutson JW in 1942. Because of his extensive work on topical fluoride. • This is a form of topical fluoride application with 2% Sodium Fluoride used at a pH of 7. • 2gm of NaF powder is dissolved in 100ml distilled water. • Stored in a plastic bottle, as it may react with the silica in a glass bottle to form Silicon-Fluoride thus; reducing the availability of free active fluoride for anti-caries action.
  33. Knutson’s Technique - NaF • The four visit procedure is recommended for ages 3,7,11 and 13 yrs, coinciding with the eruption of different groups of primary and permanent teeth. • Thus, most of the teeth will be treated soon after their eruption, maximizing the protection afforded by topical application. • There are 4 appointments for each visit spaced with a weekly interval.
  34. Technique • Teeth cleaned with aqueous pumice slurry, dry with compressed air and teeth isolated either by quadrant or by half mouth. • 2% NaF solution is painted on the teeth so that all surfaces are visibly wet and allow to air dry for 3-4 minutes. • Repeat for each of the isolated segments until all teeth are treated. • 2nd, 3rd and 4th NaF application is done, not preceded by a prophylaxis, is scheduled at intervals of approximately one week.
  35. Advantages • It is relatively stable when kept in a plastic container; • The taste is well accepted by patients; • The solution is non-irritating to the gingiva; • It does not cause discoloration of tooth structure; Disadvantages • One major disadvantage of the use of Knutson’s technique is that the patient must make 4 visits to the dentist within a relatively short time.
  36. Muhler’s Technique(stannous Fluoride) • It was so named because of the extensive done by Muhler et al in 1947. • They observed that stannous fluoride solution greatly reduced the rate of acid dissolution and is 3times more effective than NaF in preventing dissolution of Ca and P0₃ ions from the enamel. • Fluoride concentration of 19500ppm Stannous fluoride at 8% and 10% concentrations is used in Muhler’s technique. • A fresh solution of stannous fluoride is prepared for each patient as a result of the unstable nature. It forms tin hydroxide soon after mixing and becomes cloudy.
  37. Muhler’s Technique(stannous Fluoride) • To prepare 8% stannous fluoride solution, the content of one capsule which is 0.8 grams is dissolved in 10 ml of distilled water in a plastic container. Technique • Thorough prophylaxis with pumice including the proximal surfaces. • Isolation with cotton rolls and dry with compressed air. • A quadrant or half of the mouth can be treated at a time.
  38. • Apply freshly prepared 8% solution of SnF2 continuously to the teeth with cotton applicators. So that the teeth are kept moist with the solution for 4 minutes. • A reapplication of the solution to a particular tooth is done every 15-30 seconds. • Repeat applications are made every 6 months Advantages • Using an 8% stannous fluoride solution at 6 to 12 months intervals conforms to the practicing dentist’s usual patient – recall system.
  39. Muhler’s Technique(stannous Fluoride) Disadvantages • In aqueous solution the material is not stable • 8% solution is quite an astringent and disagreeable in taste, its application is unpleasant. • The solution occasionally causes a reversible tissue irritation manifested by gingival blanching. • Causes pigmentation of teeth which has a characteristic light brown colour especially hypocalcified areas and around margins of restorations.
  40. Brudevold’s Technique - APF • This follows the works done by Pameijer and Brudevold while comparing the effectiveness of a solution of neutral NaF with a acidulated phosphate fluoride (APF). • They reported APF to be 50% more effective than neutral NaF as a caries preventive agent. • To prepare, 20 grams of sodium fluoride is disolved in 1L of 0.1 M phosphoric acid and to this is added 50% hydrofluoric acid to adjust the ph at 3.0 and fluoride ion concentration at 1.23%. • The solution is also called Brudevold’s solution.
  41. Brudevold’s Technique • A gelling agent such as methylcellulose or hydroxyethyl cellulose is added to the solution. • The pH is to be adjusted between 4-5 Need for a gelling agent • teeth must be kept wet with solution for 4 minutes • APF solution is acidic and bitter in taste so repeated application necessitates the use of suction. • chair application by one dentist or auxiliary becomes difficult • increased chairside time • APF is recommended for application at 6 or 12 months interval
  42. • APF gel may be applied in the same manner as topical solution as described above. • It can also be used by self application and children can be trained for this. Using a variety of self re-usable or disposable trays in various sizes together with sponge like tray liners are available. Advantages • It is stable when stored in plastic container • No staining of teeth • Gels can be self applied • Requires only 2 applications in a year;
  43. Brudevold’s Technique Disadvantages • Repeated exposure of porcelain or composite to APF can lead to loss material, resulting in surface roughness and cosmetic changes • It is acidic, sour and bitter in taste • It cannot be stored in glass containers
  44. Fluoride Varnishes • A fluoride varnish is a professionally applied adherent material. • It is formulated to hold fluoride in close contact with the tooth for a period of time. • It permits the application of high fluoride concentrations in small amounts of material • Varnishes typically contain high concentrations of fluoride and are for professional application only.
  45. Fluoride Varnishes • When painted on the tooth surface, it act as fluoride depot from which Fl ions are continuously released. • It is also not quickly washed away by saliva. • This allow the Fl ion to interact with the hydroxyapatite crystal over a long period of time. • Hence leads to deeper penetration and significant anti-caries effect.
  46. Fluoride Varnishes • It is applied sparingly with a cotton bud and a small pea-size amount is sufficient for a full mouth application in children up to 6 years. • Fluoride varnishes are particularly useful in children with special need. • Also useful when fluoride is needed to target specific tooth surfaces e.g. exposed surfaces of roots, incipient carious lesions or the margins of restorations.
  47. Fluoride Varnishes • Fluoride varnishes are safe because the amount of varnish usually used is 0.3 – 0.5 ml which delivers only 3-6 mg fluoride. • Patient should be instructed not to chew or brush for at least 1 hours after varnish application. • Many fluoride varnishes contain colophony which may cause a sensitivity reaction. • Hence, colophony-containing varnishes are contraindicated in unstable asthmatics, atopic children, and those allergic to Elastoplast (contains colophony)
  48. Fluoride Varnishes • Example of commercially available fluoride varnishes include: • 5% sodium fluoride(Duraphat) • 0.9% difluorosilane (fluor protector) • 6% sodium fluoride • 6% calcium fluoride (56,300 ppm F)
  49. Fluoride Varnishes Technique • Oral prophylaxis is done. • Teeth are dried and isolated. • First lower arch is taken up for application and then the upper arch - saliva collects rapidly on the lower arch. • Small amount of varnish is dispensed (0.3ml to 0.5ml, or 2 drops, for the entire dentition) to the applicator dish. • Varnish sets rapidly when they come in contact with saliva, hence no drying is necessary
  50. Fluoride Varnishes • Patient is made to sit with the mouth open for 4 minutes before spitting to allow the varnish set on teeth which is further enhanced by the moist environment created by saliva. • Patients should be clearly instructed not to rinse or drink anything for an hour.
  51. Slow Releasing Devices • In the past, many dental materials, such as amalgam, composites, cements, acrylics, and fissure sealants, have had fluoride added. • But either the fluoride release was short term • Or the properties of the materials were adversely affected. • Long term fluoride release by glass ionomer cement has been debated, even with its fluoride recharging ability. • The objective of a slow-release fluoride device is to produce a consistent level of fluoride intra-orally, over a long period of time (1-2 years) without the need for regular professional involvement or patient compliance.
  52. Slow Releasing Devices • There are three systems of slow-release F devices: • the copolymer membrane type - developed in the United States • and the glass bead - developed in the United Kingdom. • More recently, a third type, which consists in a mixture of sodium fluoride (NaF) and hydroxyapatite has been developed. • The devices are usually attached to the buccal surface of a posterior tooth either by direct bonding, or by means of an orthodontic band or plastic bracket.
  53. Slow Releasing Devices • Although, there is evidence from in vivo trials that slow release fluoride devices can produce a sustained increase in salivary fluoride levels (Toumba et al., 2009) • To date there is insufficient evidence from randomised control trials to determine the caries-inhibiting effect of slow-release fluoride devices (chong et al., 2014).
  54. A fluoride slow-release glass device attached to the buccal surface of the upper right first permanent molar tooth PAEDIATRIC DENTISTRY 5TH EDITION. Schematic cross-sectional view of the copolymer device, which originally had 8 mm in length, 3 mm in width, and 2 mm in tickness. Adapted from PESSAN et al 2008
  55. Self Applied Topical Fluorides • Dentifrices • Mouth rinses • Gels
  56. Fluoride Dentifrices • The first clinical trial of a fluoride dentifrices was initiated by Bibby in 1942. • The active agent was Sodium Fluoride which had been added to a conventional dentifrices containing Di-calcium phosphate as the abrasive. • In 1955, the stannous fluoride dentifrice became the first dentifrice recognized by FDA [Food and Drug Administration] as an effective tooth decay preventive product which was later accepted by ADA [American Dental Association].
  57. Fluoride Dentifrices • The various fluoride compounds used in dentifrices : • Sodium fluoride • Stannous fluoride • Monofluorophosphate • Amine fluoride • Brushing with fluoride toothpaste increases the fluoride concentration in saliva 100- to 1,000-fold. • This concentration returns to baseline levels within 1 to 2 hours
  58. • Fluoride toothpastes available contain fluoride concentration ranging between 1,000 to 1,500 ppm and 450-500ppm for children 3years or less. AAPD recommendations • Tooth brushing with fluoridated toothpaste significantly reduces dental caries prevalence in the primary dentition. • Children less than 3years of age should use a smear or rice-size amount of fluoridated toothpaste. (reduce the risk of fluorosis) • For children age 3-6 years, a pea-size fluoridated toothpaste is recommended. • They should have supervised tooth-brushing done twice daily. • Rinsing after brushing should be kept to a minimum or eliminated altogether.
  59. Smear and pea-sized toothpaste sizes. AAPD Best practice guidelines – fluoride therapy 2018
  60. Mouth rinses • Concentration of fluoride in home mouth rinses varies from 225ppm- 900ppm. • It can be used daily or weekly • The AAPD in its guidelines refers to randomized trials supporting the use of 0.2% sodium fluoride mouth rinse (900ppm F) to reduce caries as part of a preventive regimen.
  61. Mouth rinses • The EAPD stipulates that supervised rinsing is more efficacious than unsupervised rinsing. • The children using the fluoride rinse should be older than 6 years. (risk of swallowing) • The rinse should be held in the mouth for 1 minute and then expectorated. • That there is no evidence to support the efficacy of fluoride rinse in primary teeth. • In permanent teeth the rinse is efficacious in preventing caries.
  62. Mouth rinses • Fluoride rinses should be at a different time to tooth brushing inorder to increase the frequency of fluoride exposure. • Tooth brushing and rinsing with fluoride has been shown to be additive. • All orthodontic patients should be use a daily fluoride rinse to minimize the risk of demineralization and white spot lesions.
  63. Other Fluoride Topical therapy - Silver diamine fluoride • SDF is a colourless solution with an alkaline pH (pH 8–10). • Its main components are • Silver – antimicrobial agent • fluoride – aids remineralization • and ammonia. – stabilizes the solution • It offers a therapeutic and preventive effect in the management of dental caries in paediatric patient.
  64. SDF • These components have the following synergistic activity • a bactericidal action on cariogenic microorganisms, • promotion of mineralization, • inhibition of demineralization of tooth hard tissues, and • decrease of the destruction of the organic portion of the dentin
  65. SDF • On application to a carious lesion, two compounds are formed: calcium fluoride and fluoroapatite. • Calcium fluoride is loosely bound to the teeth and it can be considered a reservoir of fluoride that will be released if a pH drop occurs. • Silver phosphate can also act as a reservoir of phosphate ions for the next caries challenge
  66. SDF • The fluorhyapatite is formed when fluoride is incorporated into the hydroxyapatite crystals. • It helps remineralization and makes the tooth more resistant to further demineralization. • Also, high concentration of fluorides can inhibit the formation of biofilm, since fluoride can influence the carbohydrate metabolism and the sugar uptake of the microorganisms
  67. SDF • The silver ions (Ag+) exert a great antimicrobial effect, killing or interfering in the microorganisms’ metabolic processes. Drawback • The only reported side effects of SDF are that caries lesions stain black after treatment, and it will temporarily stain the skin and mucosa with contact.
  68. Systemic fluoride • They are ingested and circulate through the blood stream. • They are incorporated into the developing teeth and provide a low concentration of fluoride over a long period of time. • Ingested fluoride such as fluoridated water and dietary supplements, may contribute to a topical effect on erupted teeth. • Before it is swallowed, while in he oral cavity, • as well as a topical effect due to increasing salivary and gingival crevicular fluoride secretion
  69. Systemic fluoride • The different types of Systemic fluorides are: • Water Fluoridation • Community Water Fluoridation • School Water Fluoridation • Salt Fluoridation • Milk Fluoridation • Fluoride tablets/ drops/ lozenges
  70. Systemic fluoride • Water fluoridation is the controlled addition of fluoride to a public water supply to an optimum level for the prevention of dental caries. • It is socially equitable, in that it is available to all social groups and ages. • One of the most important and successful public health intervention. • Other fluoride supplements such as fluoride in milk and salt, fluoride tablet, lozanges and drops are recommended for children who are not exposed to fluoridated water
  71. AAPD guidelines on dietary fluoride supplementation schedule AGE FLUORIDE IN DRINKING <0.3 ppm F 0.3 to 0.6 ppm F >0.6 ppm F Birth to 6 months 0 0 0 6months to 3years 0.25mg 0 0 3 to 6 years 0.50mg 0.25mg 0 6 to at least 16 years 1.00mg 0.5mg 0
  72. POTENTIAL HAZARDS OF FLUORIDE • Fluoride is often called a double-edged sword. • This is because inadequate ingestion of fluoride will not prevent dental caries and an excessive intake of fluoride can lead to dental and skeletal fluorosis.
  73. Acute Toxicity • Acute fluoride toxicity results from rapid excessive ingestion of fluoride. • The speed and severity of the response are dependent on the amount of fluoride ingested and the weight and age of the child. • Studies have found that a single ingestion of just 0.1-0.3 mg/kg. • A child weighing 10 kilograms, therefore, can suffer symptoms of acute toxicity by ingesting just 1 to 3 milligrams of fluoride in a single sitting. • 1 to 3 mgs of fluoride is found in just 1 to 3 grams of toothpaste (less than 3% of the tube) • Acute lethal dose is 15mg/kg body weight.
  74. Symptoms symptoms of ACUTE fluoride toxicity include: • Nausea • Abdominal cramps. • Vomiting • Diarrhoea • Increased salivation • Dehydration and thirst.
  75. Management • Induce vomiting with emetics. • Reduce bioavailability: 1% calcium chloride Calcium gluconate Milk
  76. Chronic Toxicity • Chronic fluoride toxicity results from long term ingestion of small amounts of fluoride. • The effect of chronic fluoride toxicity on enamel is dental fluorosis. • Other problems such as skeletal fluorosis may also occur. • Effect dosages duration: • Dental fluorosis >2 times optimal until 5 years • Skeletal fluorosis 10-25 mg/day 10-20 years.
  77. Conclusion • Fluoride has been contributing to the improvement of the dental health of persons all over the world. • Fluoride when used appropriately, is a safe and effective agent that can be used to prevent and control dental caries. • Practitioners should concentrate on recommending for their patients, agents or methods that provide frequent low moderate fluoride concentration rather than rely on infrequently applied high concentrations of fluoride.
  78. References • Buzalafa, Pessan, Honório, Cate Mechanisms of Action of Fluoride for Caries Control. Monogr Oral Sci. Basel, Karger, 2011, vol 22, pp 97–114 • Ten Cate JM. Current concepts on the theories of the mechanism of action of fluoride. Acta Odontol Scand 1999;57:325–329. Oslo. ISSN 0001-6357 • Manal Al Halabi Current Guidelines for the Use of Fluoride in Pediatric Dentistry, A Review. Applied Clinical Research, Clinical Trials & Regulatory Affairs, 2014, 1, 000-000 • American Academy of Pediatric Dentistry. Fluoride therapy. The Reference Manual of Pediatric Dentistry. Chicago, Ill.: American Academy of Pediatric Dentistry; 2020:288-91. • Textbook of paediatric dentistry. Welbury, Duggal and Hossey. 5th edition. Oxford University Press 2018 • Fluoride and oral health D.M. O’mullane1 , R.J. Baez, S. Jones, M.A. Lennon , P.E. Petersen , A.J. Rugggunn , H. Whelton and G.M. Whitford
  79. References • Contemporary perspective on the use of fluoride products in caries prevention J. M. Ten cate • Heozor-ejiofor Z, worthington HV, walsh T, o'malley L, clarkson JE, macey R, alam R, tugwell P, welch V, glenny A. Water fluoridation for the prevention of dental caries. Cochrane database of systematic reviews 2015, issue 6. Art. No.: Cd010856. Doi: 10.1002/14651858.Cd010856.Pub2 • Guidelines on the use of fluoride in children: an EAPD policy document. • Fluoride toothpaste use for young children the journal of the american dental association , volume 145 , issue 2 , 190 – 191 • Marinho VCC, Higgins JPT, Logan S, Sheiham A . Topical fluoride (toothpastes, mouthrinses, gels or varnishes) for preventing dental caries in children and adolescents (Review). The cochrane collaboration
  80. Thank You