FOCUS ON : UPDATE ON THE USE OF FOR THE PREVENTION OF DENTAL CARIES

Clifton M. Carey, BA, MS, PhD

SORT SCORE ABSTRACT A BCNA Improving the efficacy of fluoride therapies reduces dental caries and lowers SORT, Strength of Recommendation Taxonomy fluoride exposure.

LEVEL OF EVIDENCE Background 123 Fluoride is delivered to the teeth systemically or topically to aid in the prevention of See page A8 for complete details regarding SORT and dental caries. Systemic fluoride from ingested sources is in blood serum and can be LEVEL OF EVIDENCE grading system deposited only in teeth that are forming in children. Topical fluoride is from sources such as community water, processed foods, beverages, , mouthrinses, gels, foams, and varnishes. The United States Centers for Disease Control and Prevention (CDC) and the American Dental Association (ADA) have proposed changes in their long standing recommendations for the amount of fluoride in community drinking water in response to concerns about an increasing incidence of dental fluorosis in children. Current research is focused on the development of strategies to improve fluoride efficacy. The purpose of this update is to inform the reader about new research and policies related to the use of fluoride for the prevention of dental caries. Methods Reviews of the current research and recent evidence based systematic reviews on the topics of fluoride are presented. Topics discussed include: updates on com- munity water fluoridation research and policies; available fluoride in dentifrices; fluoride varnish compositions, use, and recommendations; and other fluoride containing dental products. This update provides insights into current research and discusses proposed policy changes for the use of fluoride for the prevention of dental caries.

University of Colorado, School Conclusions of Dental Medicine, Aurora, CO The dental profession is adjusting their recommendations for fluoride use based on 80045, USA current observations of the halo effect and subsequent outcomes. The research community is focused on improving the efficacy of fluoride therapies thus reducing Corresponding author. E-mail: clifton.carey@ dental caries and lowering the amount of fluoride required for efficacy. ucdenver.edu fl fl J Evid Base Dent Pract 2014;14S: Key words: Fluoride, uorosis, decay prevention, uoride delivery systems [95-102] 1532-3382/$36.00 INTRODUCTION ª 2014 Elsevier Inc. All rights reserved. here is no question about the importance of fluoride for the prevention of http://dx.doi.org/10.1016/j.jebdp.2014.02.004 Tdental caries as it is the first line of defense, along with education, for preventing the onset of caries. Fluoride is the only compound recognized by US Food and Drug Administration (FDA) for the prevention of dental caries; however, not all fluoride containing products are recognized by the FDA for caries protection. At this time fluoride for caries prevention comes primarily from fluoridated community water, toothpastes, and mouthrinses. The intake of water and processed beverages in the United States provides approximately 75% of a person’s fluoride intake.1

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In the last couple of years there has been a significant United States drink similar amounts of water and fluoridated reevaluation and proposed adjustment of public policies beverages. related to community water fluoridation. The proposed Studies have also shown that the fluoride intake of most changes are based on current research into fluoride availability children is supplemented from environmental sources. This in the environment as well as the increasing incidence of very fluoride from the environment, called the halo effect, includes mild and mild fluorosis. There is also new research into the sources such as processed foods and beverages, , mechanisms of fluoride for anticaries efficacy which may lead and to a small extent pesticides (Figure 1). The total fluoride to better prevention strategies. New and/or improved fluo- intake for the youngest members of the population can often ride products are entering the marketplace at an increased be higher than optimal which may lead to an increased rate; these products include: toothpastes, fluoride varnishes, incidence of very mild and mild fluorosis. Fluoride use in fluoride containing whitening agents, and other fluoride drinking water, dentifrice, and professional therapies has containing cleaning products. For some, if not most of these reduced caries incidence; however, indiscriminant use of new products, there is very little research to support their fluoride has led to an increase of fluoride in the efficacy. This update presents new evidence, implications, and environment. The fluoride halo is thought to be the cause strategies related to fluoride use in community water fluori- for the rapid increase in the rates of very mild and mild dation and for some fluoride based products for the pre- fluorosis (the lowest categories) over the last decade.2 vention of dental caries. Fluorosis occurs as a result of elevated amounts of fluoride Community during enamel formation before the tooth is erupted. The Community water fluoridation began 70 years ago and now elevated fluoride may lead to defects in the enamel ranging approximately 72% of the population of the United States has from white specks or white striations to rough and pitted sur- fluoridated water in their homes. In early 2011, after years of faces. Figure 2 shows examples of fluorosis from none, to very review and evaluation, the CDC, EPA, and the ADA pro- mild, and severe. Very mild fluorosis is often misdiagnosed and posed a modification to their recommendations for the thus may be over reported because there are other conditions amount of fluoride in drinking water to be 0.7 mg/mL (ppm) that appear similar. For instance, the use of antibiotics such as everywhere in the United States. The previous recommen- amoxicillin (in the b-lactam family of antibiotics which dations ranged from 0.7 ppm to 1.2 ppm fluoride and were includes penicillins, amoxicillins and cephalosporins) during climate dependent. Although the announcements of the childhood causes white spots on the tooth that could easily proposed changes in the recommendations were released for be mistaken for, but are not due to fluoride.3 It is interesting public comment, a large number of municipalities immediately to note that other antibiotics such as tetracycline also cause lowered the fluoride content of their water supply to which results in a dark colored stained 0.7 ppm. This means that although the proposed recom- striations that are easily distinguished from fluorosis. Since mendations have not been officially adopted by the CDC or anterior permanent teeth develop in children under the age ADA, the populations of those communities are already of 8, higher than optimal fluoride concentration exposure on receiving less fluoride than they did in the past. The municipal a consistent basis can result in fluorosis. Fluorosis is due to water providers are possibly putting their communities at risk fluoride deposited in the tooth as it is maturing, therefore the for increased incidence of dental caries. It may take several effects cannot be seen until the tooth erupts. Sources of years for any change in caries incidence to be noticed. fluoride during these early years can occur from ingestion of infant formula, drinking water that has higher than optimum The new proposed and previous water fluoridation recom- levels of fluoride, fluoride toothpaste ingestion, or from mendations are based on calculations of total fluoride intake inappropriately supervised fluoride supplements. by children under the age of 8 because this is the population most vulnerable to develop fluorosis from systemic fluoride. Powdered infant formula and infant formula concentrate are In the 1950’s the only source of fluoride for children was in particularly important contributing sources for higher amounts the drinking water so the calculations about fluoride intake of fluoride. Studies have shown that some brands contain estimated the amount of water that children drank and set the sufficient amounts of fluoride that when mixed with optimally recommendations accordingly. In the warmer southern re- fluoridated water result in greater than optimal amounts of gions the children drank more water; while in the colder fluoride in the formula.4 The CDC and ADA have varied their northern regions children drank less water. Thus, until 2011 recommendations about this in recent years. In 2006 the the CDC and the ADA recommended that the amount of CDC and ADA recommended that low-fluoride water be fluoride in drinking water should range from 0.7 ppm in used to reconstitute infant formula to guard against exposing warmer climates to 1.2 ppm in cooler climates. Reviews about the infant to excess amounts of fluoride. Recent evidence the drinking habits of children have shown that due to air reviewed by the CDC “suggests that mixing powdered or conditioning and other factors, children in all regions of the liquid infant formula concentrate with fluoridated water on a

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Figure 1. Halo Effect Sources. Percentage source contribution to professionals.2 Nevertheless research shows that water total daily fluoride intake. drinking habits of the population have drastically changed over the last 70 years and fluoride availability in the environment (the halo effect) has increased; therefore, it is likely that there is an increase in very mild and mild fluorosis over the last decade in the US due to fluoride ingestion. Figure 3 shows a chart adapted from data published by H. Trendly Dean (1942)6,7 to show the relationship between fluoride concentration in drinking water and incidence of fluorosis and decayed-missing-filled teeth (DMFT) in chil- dren. This chart is used to help understand the potential ef- fects due to the change in fluoride concentration from 1 ppm to 0.7 ppm F. The x-axis of the Dean chart is modified to show the Equivalent Water Fluoride concentration which is Image from Environmental Protection Agency. Fluoride: Exposure and Relative Source fi fl Contribution Analysis. 2010, page 99.19 de ned as the sum of the community water uoride content and the net impact of the halo effect. The red arrow origi- nating from the reported percent of population affected by very mild dental fluorosis (approximately 40%) is projected to regular basis may increase the chance of a child developing the edge of the very mild fluorosis curve. The intersection of the faint, white markings of very mild or mild enamel fluo- the arrow and this curve is at 1.8 ppm equivalent community rosis.”5 Due in part to the proposed lower recommended water fluoride concentration. This concentration includes all concentrations of fluoride in community water, the ADA of the sources for fluoride such as water consumption and and CDC now recommend that fluoridated water be used the halo effect which contribute to the observed rate of mild to prepare infant formula. However, they caution that if the fluorosis. Note that the intersection is at the steepest portion child exclusively consumes infant formula reconstituted with of the fluorosis curve so that a very small change in the fluoridated water, there may be an increased chance for equivalent fluoride exposure should lead to a large change in mild dental fluorosis. To lessen this chance, the ADA and the fluorosis incidence. Thus, to reduce the very mild fluorosis CDC now state that parents can use low-fluoride bottled incidence by about 50% a reduction of only 0.3 ppm fluoride water some of the time to mix infant formula.4,5 Although this (from 1.8 ppm to 1.5 ppm) in the equivalent fluoride is statement seems vague, the relevant variable for fluoride needed as shown by the blue arrow. The caries experience intake is the size of the infant. If the infant is small then less curve (black curve) is nearly flat between these two points fluoride is needed and low fluoride bottled water could be (1.8 ppm–1.5 ppm) and thus this model predicts that there is used to reconstitute the infant formula for alternate meals. As little if any increased risk for caries with this change. Clearly, the infant grows fewer feedings of infant formula made with there are a number of assumptions inherent in using this low fluoride bottled water would be needed. model for setting the public policy. It is up to the dental profession to carefully monitor both caries and fluorosis Over the last couple of years there has been a significant incidence for the next 6–10 years as the effects of the change reevaluation and proposed adjustment of public policies in drinking water fluoride may reduce the impact of the halo related to community water fluoridation lead by the EPA and effect more greatly than anticipated. At this time, there are no CDC. This reevaluation came about because recent census plans for a national surveillance program to assess caries or surveys on oral health have reported a substantial increase in fluorosis incidence in children listed at the CDC. very mild and mild fluorosis. These reported increases are interpreted to mean that increasing numbers of children are ingesting more than optimal amounts of fluoride. However, it Potentially Available Fluoride in Toothpaste is possible that the increase in reported fluorosis by dental There are some recent studies where the amount of fluoride professionals is partly due to confusion in the differential made available in the oral cavity during tooth brushing diagnosis of very mild and mild fluorosis versus early caries (approximately 2 min) was measured.8 It seems that in such as white spot lesions, or white spots resulting from use of developing regions of the world there are toothpastes amoxicillin. Additionally, a new awareness of fluorosis has led marketed that contain the total fluoride as indicated on the to increased reporting when there was actually fluorosis in the label but which do not release sufficient fluoride during use past that was not reported. This observation is supported by to prevent caries. This is due to the composition of the the lack of similar increase in the incidence of greater degrees toothpaste which can render a significant amount of of fluorosis (moderate and severe) reported by dental the fluoride unavailable. Our studies have found that the

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Figure 2. Fluorosis – tooth hypomineralization resulting in a change in the appearance of teeth. Causes: long term ingestions of higher than optimal levels of fluoride during tooth mineralization; use of antibiotics (amoxicillin) during childhood ,6 years of age; genetic predisposition.

Images from “Centers for Disease Control and Prevention. Community Water Fluoridation, Images of Fluorosis. http://www.cdc.gov/fluoridation/faqs/dental_fluorosis/.”20

composition of the toothpaste is critical to the amount of to include in national and international standards. The diffi- fluoride that is potentially available. For instance, products culty in achieving the analytical methods is related to the large that contain sodium fluoride (NaF) as the active ingredient variety of ingredients used in toothpaste products and the also need to have sufficient detergent (typically sodium different forms of fluoride delivered during tooth brushing. lauryl sulfate, SLS) to prevent the fluoride ions from There are three categories of fluoride from toothpaste during reacting with the silica abrasives forming insoluble tooth brushing: free ionic fluoride which has the ability to fluorosilicates. At this time the literature is not clear about react with tooth structure, interfere with microbial meta- possible side effects of SLS in toothpastes. SLS is thought to bolism, absorb to the , and has anticaries efficacy; cause gingival inflammation and ulcers on the mucosal profluoride compounds that are delivered or precipitate in tissues in the mouth. A recent double blind crossover study the oral cavity during brushing, release ionic fluoride over in patients with recurrent aphthous (RAS) time, and contribute to anticaries efficacy; and unavailable followed clinical parameters including the number and fluoride compounds that do not release fluoride ions, are duration of ulcers and pain found that use of the SLS-free either spat out or swallowed, and have no anticaries efficacy. toothpastes reduced ulcer-healing time and reduced pain. Monofluorophosphate is an example of a profluoride com- There was no difference in the number of ulcers.9 Other pound that is hydrolyzed to release ionic fluoride through active ingredients such as monofluorophosphate (MFP), salivary enzyme action. Therefore potentially available fluoride stannous fluoride (SnF2), or amine fluorides (not available in is the sum of the ionic fluoride and the profluoride com- the United States) are also dependent on the abrasive, pounds that are available during the 2-min tooth brushing. A detergent, and other non-active ingredients combined in the single analytical method to measure both total fluoride and toothpaste to present sufficient available fluoride for efficacy. potentially available fluoride in the same sample is highly desirable for standardization purposes. The method should be Currently, there is a large effort by the American National able to quantify the total fluoride content and be able to Standards Institute (ADA/ANSI) and the International Orga- analyze both free fluoride ion as well as any profluoride nization for Standardization (ISO) to develop reliable fluoride compound that is deposited in the oral cavity during methods for the measurement of potentially available fluoride

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Figure 3. Relationship between equivalent fluoride in water and Figure 4. Salivary fluoride concentration 1 h after indicated fluorosis incidence and caries DMFT experience. The percent fluoride and calcium therapies. This comparison of the salivary caries experience (DMFT) and fluorosis was reported for 12–14 fluoride concentration after 1 h is for the following rinses or year old children in 21 communities. The categories for fluorosis toothpastes singly or in combination.11 The error bars are 95% are: Normal, white; Questionable (D) yellow; Very Mild (,) cyan; confidence intervals. The therapies are: None: no rinse baseline; Mild (>) green; Moderate (:) blue; and Severe (A) red areas. n 5 10; C–R: 20 mL of 150 mmol/L calcium lactate 60-s rinse; The caries experience in permanent teeth is reported as diseased, n 5 12; F–R: 20 mL of 228 ppm (12 mmol/L) NaF 60-s rinse; missing, or filled teeth (C) heavy black curve. The red arrow n 5 12; F–R/C–R: 20 mL of 228 ppm NaF 60-s rinse followed by shows the current incidence of very mild fluorosis, and the blue 20 mL of 150 mmol/L calcium lactate 60-s rinse; n 5 12; Fp/H2O: arrow shows the anticipated incidence of very mild fluorosis due 60-s brush with 1.5 g of 1100 ppm NaF toothpaste followed by a to the reduction of community water fluoride concentration by 10 s rinse with 10 mL H2O; n 5 12; C–R/Fp/H2O: 20 mL of 0.3 ppm F. 150 mmol/L calcium lactate 60-s rinse followed by a 60-s brush with 1.5 g of 1100 ppm NaF toothpaste and then followed by a 10 s rinse with 10 mL H2O; n 5 12; Cp/F–R: 60-s brush with 1.5 g of 5.6% (w/w) calcium glycerophosphate toothpaste followed by a 20 mL of 228 ppm NaF 60-s rinse; n 5 11; C–R/F–R: 20 mL of 150 mmol/L calcium lactate 60-s rinse followed by a 20 mL of 228 ppm NaF 60-s rinse, n 5 12.

Adapted from data published by Dean.6,7 tooth brushing. Studies in our laboratory to develop a single method that can be used for all dentifrices are near completion. An important feature of this method is that the total and potentially available fluoride can be determined from a single toothpaste slurry. in our labs is developing a toothpaste that provides calcium ions and profluoride compounds. After approximately 30 s fl The amount and persistence of uoride ion available in the of brushing, ionic fluoride is released and then reacts with oral cavity during brushing and after brushing is an important the calcium ions to form calcium fluoride reservoirs. parameter for anticaries efficacy. New strategies are being tested where profluoride compounds, such as calcium fluo- ride, are precipitated during brushing, resulting in longer ex- Fluoride Rinses posures to fluoride than what is achieved in tooth brushing The new strategy being designed for toothpastes can also be alone. A new generation of toothpastes based on these applied for oral rinses. A new generation of fluoride rinses is strategies are anticipated that will optimize the precipitation of anticipated that will contain soluble calcium salts that help profluoride compounds into the oral cavity.10 One method is retain fluoride in the oral cavity to be released over time.10 to flood the oral cavity with an abundance of soluble calcium The concept of including soluble calcium in a pre-rinse ions in a non-fluoride rinse followed immediately by a fluoride prior to a fluoride rinse has been shown to increase the toothpaste. This strategy has been shown to form calcium amount of fluoride in saliva nearly five-fold at 1 h after rinsing, fluoride reservoirs that release fluoride over time such that in comparison to a NaF containing rinse at the same fluoride the amount of fluoride in saliva at 1 h after brushing is concentration.11 Figure 5 shows the overnight persistence of doubled in comparison to a NaF containing toothpaste at the salivary fluoride after the calcium pre-rinse/fluoride rinse same fluoride concentration.10 Figure 4 shows the salivary sequence. The calcium pre-rinse provides large amounts of fluoride concentration 1 h after several different calcium ions in situ which, when followed by a fluoride rinse, combinations of fluoride and calcium applications by rinse precipitates large amounts of calcium-fluoride reserves. These or toothpaste. This strategy seems effective but has the reserves dissolve into saliva over time such that the salivary difficulty of requiring two separate steps. Current research fluoride concentration is more than quadruple that of a NaF

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Figure 5. Comparison of fluoride concentrations in overnight Figure 6. Fluoride uptake into after 3 h exposure salivary samples after a calcium pre-rinse or a fluoride rinse. to F-varnishes of varying concentration of sodium fluoride.18 Fluoride concentration in saliva samples obtained overnight after 60-s 20 mL rinse as follows: Baseline distilled water (H2O), 228 ppm fluoride (F-R Lo), 912 ppm fluoride (F-R Hi), or 150 mmol/L calcium lactate pre-rinse immediately followed by a 228 ppm fluoride rinse. All fluoride was from sodium fluoride. The error bars are standard errors (N 5 12) statistical differences (p , 0.05, Holm–Sidak pairwise multiple comparison test) are indicated by the letters.

have anticaries efficacy or are synergistic with the fluoride in the product. Therefore the FDA does not have sufficient fl Data adapted from Vogel et al (2008).21 information to describe the requirements needed for uoride varnish efficacy. Current studies have not demonstrated that anticaries efficacy is due to the fluoride content as opposed to fl 10 rinse at the same uoride concentration. It is conceivable some other component of the product. Nor have there been fi that these new rinses and dentifrices may provide suf cient studies that demonstrate the mechanism of action to explain fi ’ anticaries ef cacy to the point that a children s toothpaste how a therapy that has duration of 2–24 h can have anticaries fl with a lower uoride concentration could be developed. effects for 6 months. This lack of information has hampered fl This would help lower the body burden of uoride for the use of F-varnish for community prevention programs. In fl children and may reduce the incidence of uorosis. spite of this there are community based programs that have The recent systematic review of topical fluoride for caries clear success in reducing the amount of dental caries in chil- prevention presents recommendations in favor of the use of dren. A notable example is the ongoing program in Clark 0.09 percent fluoride (900 ppm F) mouth rinse at least weekly County, Kentucky (USA) under the private Clark County for children aged 6–18 years. The recommendation of at least Dental Health Initiative, where the application of a calcium- weekly use for older than 18 years or for root caries pre- phosphate containing F-varnish has reduced the caries inci- vention is based on ‘Expert Opinion’ because the scientific dence over five years from over 50%–11% in a population of 15 evidence is lacking.12 over 6000 elementary students. While this community health program is not a robust mechanistic study, the Fluoride Releasing Varnish observations are impressive and important for the scientific community to witness. The ADA has recommended the use of fluoride releasing varnish (F-varnish) for caries prevention in young patients at There is a critical need to develop the scientific knowledge moderate and high risk. There is strong clinical evidence that and mechanism of action to understand how F-varnishes can indicates anticaries efficacy of F-varnish for high-risk pop- give 6 months of anticaries efficacy from a single application. ulations.13 Recent studies have found that F-varnish has long The basic technology inherent in the F-varnish design is to lasting efficacy to prevent caries.14 However, it seems apply a very high concentration of fluoride salt, usually at inconsistent that the FDA has not approved F-varnish for 50,000 ppm NaF (22,600 ppm F), in a resin varnish which will caries prevention. The reticence of the FDA to approve F- reside on the tooth surface for several hours. During the varnish is because clinical efficacy caries trials have been residence time, saliva bathes the varnish and dissolves the equivocal or at best product based. There is insufficient fluoride salt, allowing fluoride ions to diffuse out of the varnish science demonstrating mechanism of action or identifying and become absorbed into fluoride reservoirs within oral soft the significant compositional variables for anticaries activity. tissues, plaque, and teeth. Over time the fluoride ions are re- It is possible that non-fluoride components of the varnish released from these reservoirs. The commonly recited products such as the varnish resin, flavoring, or other additives mechanism presumes that abundant calcium ion is available

Volume 14, Supplement 1 100 JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE SPECIAL ISSUE—ANNUAL REPORT ON DENTAL HYGIENE and that large quantities of calcium-fluoride are precipitated applications at least every three to six months for all children on the tooth surface. The reservoirs then slowly dissolve, younger than 18 years of age.12 This same review found that releasing fluoride ion, which in turn acts to protect the the evidence is lacking for use of F-varnish for adults 18 and tooth.16 This oft-cited mechanism cannot explain the long older or for prevention of root caries, however, expert period of efficacy because calcium fluoride precipitates are opinion is in favor of these uses to prevent caries. not long lasting reservoirs and are thought to be less impor- tant than fluoride uptake into enamel.17 Another possible mechanism of F-varnishes could be antibacterial; however, it SUMMARY has been reported that F-varnish did not affect the levels of Research has developed significant improvements in the use S. mutans in saliva or dental plaque.16 Thus the primary of fluoride in toothpaste and oral rinses, and insights into the cariostatic effect of F-varnish is probably due to the action mechanism for F-varnish efficacy. New systematic reviews of of fluoride on the chemical stability of tooth mineral the literature have provided the basis for updated recom- converting enamel to fluoroapatite which is much less mendations from the profession on how topical fluoride can susceptible to acid attack than enamel. Additionally, the NaF be used to prevent caries. Finally, the adjustment of policy concentration in the F-varnish that yields optimal fluoride recommendations for community water fluoridation ad- enamel uptake and anti-caries efficacy is unknown. dresses changes in water drinking habits of children and the effects of the halo effect on fluoride exposure. We have launched a systematic series of studies to establish the mechanism by which F-varnish affords long-term caries Abbreviations: protection and to identify the optimal fluoride concentration ADA – American Dental Association fi ADA/ANSI – American National Standards Institute for anticaries ef cacy of the F-varnish. Our in vitro studies – show that F-varnish saturates the fluoride binding sites of CDC United States Health and Human Services Centers for Disease fl Control and Prevention enamel by ooding the tooth surface with high concentra- DMFT – diseased, missing or filled teeth tions of fluoride ion for several hours. Our study also shows EPA – United States Environmental Protection Agency that very high concentrations of fluoride in contact with the ISO – International Organization of Standards – fl tooth for extended time are required to overcome the slow MFP Mono uorophosphate NaF – sodium fluoride rate of fluoride binding to enamel binding sites. Figure 6 – fl SLS sodium lauryl sulfate shows the uoride uptake into hydroxyapatite discs (a SnF2 – stannous fluoride mineral model for ) as a function of the fluoride concentration in F-varnish at 3 h exposure. We REFERENCES measured both tightly bound fluoride, which gives long 1. Centers for Disease Control and Prevention. Recommendations for term protection by preventing dissolution and loosely using fluoride to prevent and control dental caries in the United States. bound fluoride, which gives short term protection by MMWR 2001;50(No. RR-14):1-42. inducing surface stability and through antimicrobial 2. Beltrán-Aguilar ED, Barker L, Dye BD. Prevalence and severity of dental mechanisms. Both the loosely bound and tightly bound F fluorosis in the United States, 1999–2004. NCHS Data Brief November uptake into the hydroxyapatite disc is a non-linear function 2010;(53). of NaF concentration in the varnish. The fluoride saturates the 3. Hong L, Levy SM, Warren JJ, Broffitt B. Amoxicillin use during early binding sites at 2.5% NaF, thus the uptake does not increase childhood and fluorosis of later developing tooth zones. J Public Health above this concentration. In our study we have found that the Dent 2011;71:229-35. number of fluoride binding sites on the hydroxyapatite disc is 4. Berg J, Gerweck C, Hujoel PP, et al. American Dental Association limited and there is an optimal NaF concentration at 2.5% that Council on Scientific Affairs Expert Panel on fluoride intake from infant fl saturates the binding sites. Saturation of fluoride binding sites formula and uorosis. J Am Dent Assoc 2011;142:79-87. 18 gives maximal protection against demineralization. 5. Centers for Disease Control and Prevention. Infant Formula and Fluorosis. http://www.cdc.gov/fluoridation/safety/infant_formula.htm; The ADA has performed several systematic reviews of the Accessed 12.04.13. literature on F-varnish efficacy for caries protection and has fi 6. Dean HT. The investigation of physiological effects by the epidemio- concluded that there is suf cient evidence to recommend logical method. In: Moulton FR, ed. and Dental Health. twice a year use of F-varnish for children who are at moderate Washington, DC: American Association for the Advancement of Sci- and high caries risk. Application of F-varnish at six month in- ence; 1942:23-31. Publication No. 19. tervals is recommended for caries prevention in permanent 7. Dean HT, Arnold FA, Elvove E. Domestic water and dental caries. Public fi teeth. Children who are not at caries risk may not bene t Health Rep 1942;57(32):1155-79. from F-varnish applications; however, the risks from the fi 8. Benzian H, Holmgren C, Buijs M, van Loveren C, van der Weijden F, van therapy are negligible and the bene ts have been judged to Palenstein Helderman W. Total and free available fluoride in toothpastes outweigh the risks. The most recent systematic review on in Brunei, Cambodia, Laos, the Netherlands and Suriname. Int Dent J topical fluoride indicates that the evidence favors F-varnish 2012;62:213-21.

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9. Shim YJ, Choi JH, Ahn HJ, Kwon JS. Effect of sodium lauryl sulfate on centralkynews.com/winchestersun/news/local/clark-county-dental-health- recurrent : a randomized controlled clinical trial. Oral initiative-honored-by-national-health-organization/article_87acf502-5768- Dis 2012;18:655-60. 5724-922b-74080ca89a92.html. 10. Vogel GL. Oral fluoride reservoirs and the prevention of dental caries. In: 16. Beltrán-Aguilar ED, Goldstein JW, Lockwood SA. Fluoride varnishes. A Buzalaf MAR, ed. Fluoride and the Oral Environment. Basel: Karger review of their clinical use, cariostatic mechanism, efficacy and safety. Monogr Oral Sci 2011;22:146–157. J Am Dent Assoc 2000;131:589-96. 11. Vogel GL, Shim D, Schumacher GE, Carey CM, Chow LC, Takagi S. 17. Schemehorn BR, Wood GD, McHale W, Winston AE. Comparison Salivary fluoride from fluoride dentifrices or rinses after use of a calcium of fluoride uptake into tooth enamel from two fluoride varnishes pre-rinse or calcium dentifrice. Caries Res 2006;40:449-54. containing different calcium phosphate sources. J Clin Dent 2011;22: 51-4. 12. Weyant RJ, Tracy SL, Anselmo T, et al. Topical fluoride for caries pre- vention: executive summary of the updated clinical recommendations 18. Ahmed I, Coleman S, Carey C. Fluoride release and uptake into hy- and supporting systematic review. J Am Dent Assoc 2013;144:1279-91. droxyapatite from experimental dental varnish. J Dent Res 2013;92(spec iss A):3259. 13. American Dental Association Council on Scientific Affairs. Professionally applied topical fluoride, evidence-based clinical recommendation. J Am 19. Environmental Protection Agency. Fluoride: Exposure and Relative Dent Assoc 2006;137:1151-9. Source Contribution Analysis; 2010;99. 14. Arruda AO, Senthamarai Kannan R, Inglehart MR, Rezende CT, Sohn W. 20. Centers for Disease Control and Prevention. Community Water Fluo- Effect of 5% fluoride varnish application on caries among school children ridation, Images of Fluorosis, Dental Fluorosis FAQs. http://www.cdc. in rural Brazil: a randomized controlled trial. Community Dent Oral gov/fluoridation/faqs/dental_fluorosis; Accessed 12.04.13. Epidemiol 2012;40:267-76. 21. Vogel GL, Chow LC, Carey CM. Calcium pre-rinse greatly increases 15. Mann J. Clark County Dental Health Initiative Honored by National overnight salivary fluoride after a 228 ppm fluoride rinse. Caries Res Health Organization. Winchester Sun. Accessed 12.04.13, http://www. 2008;42:401-4.

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