A review of sodium fluoride varnish C.H. Chu, PhD, MAGD Edward C.M. Lo, PhD, MDS

Transcription

1 A review of sodium fluoride varnish C.H. Chu, PhD, MAGD Edward C.M. Lo, PhD, MDS Fluoride varnish was incorporated into clinical dentistry to reduce caries; its use in the U.S. has increased progressively since it was approved by the FDA in This paper reviewed clinical studies and found that fluoride varnish s effectiveness in caries prevention, ease of application, and safety give it an advantage over other types of topical fluoride treatments (such as gels and rinses) or other caries management methods. As a result, it is regarded as one of the superior topical fluoride agents for young children. Received: December 20, 2005 Accepted: April 13, 2006 Fluoride applications were incorporated into clinical dentistry in the 1940s to reduce dental caries. 1 Many fluoride products (such as sodium fluoride gels and stannous fluoride solutions) are aqueous agents. A non-aqueous form of topical fluoride was developed to promote a longer retention time; in 1964, the literature reported that a 2% sodium fluoride lacquer in an alcoholic solution of natural resins was being used. 2 This lacquer was a fluoride varnish, used to prolong the contact time between fluoride and enamel. The first clinical trial of fluoride varnish was published four years later and indicated that the product led to a significant effect in caries prevention. 3 Since then, a number of clinical trials have been reported as the manufacture and application of fluoride varnishes has developed. 4 The active ingredient of fluoride varnish usually is 5% sodium fluoride (NaF). The inactive ingredients in the varnish are there primarily for flavoring and to ensure that the fluoride sticks to the tooth surface. The most common ingredients usually include sodium saccharin (which is used as a sweetener), beeswax and ethanol (for the purpose of forming a gel-type structure to stabilize sodium ions), and shellac and mastic (to provide a flexible, permeable hard surface that prevents the varnish from dissolving rapidly in saliva). A flow enhancer such as kolophonium also is included. Duraphat (Colgate-Palmolive, Canton, MA; ), a 5% NaF preparation, was the first commercially available fluoride varnish. Although fluoride varnishes had been used widely in many countries for decades, the FDA did not approve the use of fluoride varnishes for dentistry in the United States until Three years later, Colgate began distributing Duraphat in tubes (containing 10 ml of varnish) for the United States. A number of clinical studies of Duraphat reported that the product was effective in preventing caries among children (see the table) At present, Duraphat is used in more than 40 countries. 2 Other common fluoride varnishes include Fluor Protector (Ivoclar/Vivadent, Amherst, NY; ), Duraflor (Pharma Science, Montreal, Canada; ), CavityShield (OMNII Oral Pharmaceuticals, West Palm Beach, FL; ), Bifluorid 12 (Voco, Cuxhaven, Germany; ) and Carex (Voss, Norway; ). Fluor Protector is a difluorosaline agent that was introduced in the mid-1970s; a 1983 study claimed that Fluor Protector could result in a high fluoride uptake by enamel. 11 Fluor Protector contains 0.7% fluoride in a polyurethane varnish and, unlike Duraphat, has acidic properties. It is available in 1.0 ml ampules and 0.4 ml single-unit doses. In the U.S., it is used in a 0.1% fluoride concentration and is marketed as a cavity varnish to seal and prevent the permeation of fluids and metal ions. Duraflor is a 5% NaF varnish that is available in 10 ml tubes. It includes xylitol (a sweetener) and bubblegum flavoring to increase patient acceptance. Reports have suggested it could prevent caries development and also could arrest caries progression. 12,13 CavityShield contains 5% NaF in a neutral resin and is packaged in single-use doses of 0.25 ml and 0.4 ml. The fluoride content is reported to be more uniform than that of Duraphat. 14 An advertised advantage of CavityShield is that the unit dose can be mixed easily and applied to teeth, eliminating the concern of administering an unknown dose of fluoride. Bifluorid 12 contains both NaF (2.7% F) and calcium fluoride (CaF 2 ) (2.9% F). A 1995 study reported that this CaF 2 /NaF varnish deposited more fluoride on the surface of demineralized enamel than NaF varnish alone. 15 Carex was developed in Norway and contains 1.8% fluoride. A 1991 study indicated that Carex and Duraphat demonstrated a comparable efficacy among children. 16 Another experimental fluoride varnish is an NaF-ethanol varnish called CDB. In 1990, Acuna et al reported that using this experimental varnish led to a high fluoride uptake in both the enamel and dentine of extracted human canine teeth. 17 Sodium fluoride varnish is advocated for moderate and high-risk particularly children younger than 5, as well as for children who are receiving orthodontic treatment. 18 It also is used to prevent and arrest caries in children. 19 The manufacturer of Duraphat suggests using the product for preventing caries, promoting remineralization of caries, and treating tooth hypersensitivity. More than 90% of the municipal caries-preventive programs in Denmark provided fluoride varnish for children up to 18 years of age. 20 However, children who are at low risk, are caries-free, and live in a fluoridated community may not require fluoride varnish for caries prevention. 18 Sodium fluoride varnish can be applied topically two to four times a year. This regimen was the most common professionally applied fluoride measure in the Nordic countries for individuals at high risk for caries. 5,9,21-24 Pienihakkinen and Jokela conducted a three-year clinical study with young children in in which high-risk children received Duraphat four times a year for risk-based management of caries; this administration was determined to be effective and practical. 25 As there are no consistent Caries Prevention July-August

2 5-10, 18,22-24, Table. Oral summary of clinical studies on the use of sodium fluoride in children. Study Teeth (year of publication) Teeth present Chu Erupted et al (2002) Unerupted Impacted Missing teeth Congenitally Site Guangzhou, China Subjects 375 children 4.0 years) Duration (months) 30 Intervention Group 1: Silver fluoride once/year; Group 2: Duraphat 4x/year; Group 3: Lost antemortem Florio Lost postmortem et al (2001) Sao Paulo, Group 1: Vitremer Tooth position Brazil 6 sealant; Group 2: Malposition ; Crown morphology Group 3: 0.2% NaF Caries rinse weekly Zimmer Attrition, et abrasion, al erosion Hannover, 269 children 48 Duraphat vs. ; (1999) Atypical variations, enamel Germany pearls, peg (mean laterals, age = and so forth 7.1 years) Duraphat 4x/year Dentigenerous cyst Petersson Root morphology et al (1998) Size Shape Number Divergence of roots Dilaceration Root fracture Halland, 5,137 aged Fluor Protector vs ; Fluor Protector twice a year Bravo et al (1997) Andalucia, Hypercementosis Spain Root resorption Root hemisections Pulp chamber/root canal morphology Seppa et al (1995) Ylojarvi, 314 aged aged Group 1: Delton sealant; Group 2: Duraphat twice a year; Group 3: 36 Group 1: APF gel Main findings Groups 1 and 2 developed fewer new caries cases than Group 3 (p < 0.001); a statistically significant arrest of caries in Group 1 (p < 0.001) Statistically significant inactivation of caries activity in Group 1 (p < 0.05); no statistically significant differences in caries progression among these Test group showed a 37% caries reduction in decayed, missing, and filled teeth (DMFT) (p < 0.05) reduction in decayed fillings and surfaces in Fluor Protector group; 19 25% caries reduction in proximal lesions among Fluor Protector group (p < 0.05) 38% reduction in decayed, missing, and filled surfaces (DMFS) on permanent first molars in Duraphat group; 68% reduction in Delton sealant group (p < 0.01) reduction in DMFS between Duraphat and APF Seppa et al (1994) 247 aged x/year; Group 2: diluted (50%) Duraphat 3x/year reduction in DMFS between the two Skold et al (1994) Floda, 134 aged x/week, once a year; Group 2: Duraphat once a year 52% reduction in DMFS on permanent first molars in Group 1 (p < 0.001) Peyearon et al (1992) Malmo, 468 children aged Duraphat (4x/year) vs. Progression of proximal caries reduced 27% in the Duraphat group (p < 0.01) Haugejorden and Nord (1991) Voss, Norway 350 aged Carex 2x/year A comparable efficacy for Carex and Duraphat on posterior teeth Petersson et al (1991) Halmstad, times in one week once a year; Group 2: Group 1 showed a 46% reduction in progression of proximal caries (p < 0.05) Seppa and Tolonen, aged x/year; Group 2: reduction in DMFS between the two 248 General Dentistry

3 Table. Oral summary of clinical studies on the use of sodium fluoride in children. 5-10, 18,22-24, (continued from page 248) Study (year of publication) Lindquist et al (1989) Site Subjects Duration Gothenburg, years old, with >10 6 S. Mutans/mL in saliva Intervention (months) 24 Group 1: Chlorhexidine gel 4x/year; Group 2: Duraphat 4x/year; Group 3: ferric-aluminum fluoride 4x/year Main findings reduction in new decayed and filled surfaces for Duraphat and ferricaluminum fluoride; 51.7% caries reduction in chlorhexidine gel group, (p < 0.001) Clark et al (1987) Sherbrooke and Lac Megantic, Canada 549 aged Group 1: Fluor Protector 2x/year; Group 2: Durafluor 2x/year; Group 3: 27% reduction in DMFS in the Durafluor group (p < 0.05); no statistically significant caries reduction in the Fluor Protector group Seppa and Pollanen (1987) 204 aged Group 1: Fluoride rinse biweekly; Group 2: ; Group 3: Fluor Protector 2x/year DMFS increment in Group 1 was significantly more than that in Group 2 (p < 0.01); DMFS increment in Group 3 was significantly greater than that found in Group 2 (p < 0.05) Kirkegaard et al (1986) Horsens, Denmark 248 children 9.6 years) 60 Group 1: Duraphat 0.2% NaF rinse biweekly reduction between the two Petersson et al (1985) Uddevalla, 376 aged Group 1: fluoride tablet twice daily; Group 2: fluoride toothpaste; Group 3: ; Group 4: fluoride toothpaste plus reduction between Klimek et al (1985) Marburg, Germany 211 aged times plus five prophylaxes/year; Group 2: Group 1 showed 46% caries reduction in DFS (p < 0.001) Holm et al (1984) Eslov, Duraphat group showed 56% reduction in fissure caries (p < 0.05) Modeer et al (1984) Huddinge, x/year; Group 2: Duraphat group showed caries reduction of approximately 24% in new decayed and filled surfaces (p < 0.05). Tewari et al (1984) Chandigarh, India 1,335 aged years) 18 Group 1: NaF solution AFP solution 2x/year; Group 3: Duraphat 2x/year; Group 4: Caries reduction of 33 40% for DMFT and DMFS in Group 2 (p < 0.05); Group 3 showed caries reduction of 71 72% in DMFT and DMFS (p < ) van Eck et al (1984) Alkmaar, Netherlands years old 36 Group 1: Fluor Protector 1x/year; Group 2: reduction in DMFS between the two July-August

4 Table. Oral summary of clinical studies on the use of sodium fluoride in children. 5-10, 18,22-24, (continued from page 249) Study (year of publication) Seppa et al (1983) Site Subjects Duration 60 children with DMFS, aged Intervention (months) 36 Split-mouth design; vs. Main findings Approximately 44% reduction in rate of caries progression for teeth with Duraphat (p < 0.001) Grodzka et al (1982) Warsaw, Poland 322 aged 3 4 years 24 Duraphat (twice a year) vs. reduction in either DMFS or DMFT between the two Seppa et al (1982) 132 aged Split-mouth design: Group 1: Duraphat 2x/year; Group 2: Fluor Protector 2x/year Duraphat group reported 30% reduction of caries on DMFS (p < 0.001); no statistically significant caries reduction in the Fluor Protector group Kolehmainen (1981) Helsinki, 163 children 12.8 years) 24 Split month design: Fluor Protector (2x/year) vs. reduction for teeth with or without Fluor Protector treatment Holm (1979) Not stated Duraphat vs ; 44% caries reduction in the Duraphat group (p < 0.05) Koch et al (1979) Varnamo, % NaF rinse biweekly Duraphat group showed a 43% reduction in frank cavitation caries (p < 0.05) compared with a 29% reduction in proximal caries diagnosed with radiograph (p < 0.05) Maiwald et al (1978) Leipzig, Germany once/year; Group 2: Duraphat 3x/year; Group 3: Group 1 saw no significant effect on caries incidence; Group 2 saw a 46% reduction in DMFT (p < 0.05) Murray et al (1977) Chesham, England Split-mouth design: Duraphat (2x/year) vs. placebo (2x/year) Teeth treated with Duraphat showed a 37% caries reduction in DMFS (p < 0.001) Koch et al (1975) Jonkoping, Group 1: Duraphat twice/year; Group 2: Caries increment for Group 1 was 0.9, compared with 4.0 for Group 2 (p = 0.001) Wegner (1976) Putbus, Germany 87 diabetic 10 twice/year; Group 2: Group 1 demonstrated a 54% caries reduction in DMFT (p < 0.05) results of enhanced effectiveness of caries prevention with fluoride application every three months biannually, the frequency of sodium fluoride varnish application currently is under debate for cost-saving reasons. 4 Even so, two applications of fluoride varnish per year is the schedule recommended most commonly, possibly because it matches the standard dental office schedule of two recall visits per year. Fluoride varnish mode of action The mechanism of fluoride action in dental caries still is being researched, although it has been reported that the concentrated fluoride ions in fluoride varnish cause globules of a calcium fluoride-like material to form on the tooth surface. 26 These globules are stabilized by protein phosphate in the mouth and act as an insoluble reservoir of fluoride at neutral ph. When there is a cariogenic challenge such as sugar consumption, the ph is lowered and the dissolution rate of these globules increases. This response lowers the solubility constant of calcium and phosphate ions, releasing fluoride and increasing the saturation of calcium and phosphate ions in plaque fluid as a result. This reaction helps to prevent the dissolution of calcium and phosphate from the tooth mineral and/or increases the rate 250 General Dentistry

5 of remineralization or reprecipitation of the lost minerals. This mechanism can explain how topical application of a fluoride varnish two or three times a year can result in long-term caries reduction. 26 Advantages and disadvantages of fluoride varnish Fluoride varnish offers the theoretical advantage of prolonged contact time, acting as a slow-releasing reservoir to prevent the immediate loss of fluoride after application. 21 The varnish can be applied quickly and easily and sets rapidly on teeth; gagging and swallowing are unusual. 27 The simplicity of its application makes it suitable for special-needs populations including very young patients with autism, and patients with management problems (such as mental or physical disabilities) as well as for outreach dental services. A professional prophylaxis before varnish application has no additional effect on its caries prevention property and thus is not necessary; as a result, the chairside application time of fluoride varnish is short. 28 Application of fluoride varnish to four first molars may take less than half a minute. Warren et al reported that both patients and operators prefer fluoride varnish to fluoride gel. 29 More importantly, Bowden s 1998 study reported that fluoride varnishes are safe for young children. 30 Compared with other types of topical fluoride treatments (such as gels or rinses) or other caries management methods, fluoride varnishes offer effective caries prevention, ease of application, and safety. 4 A systematic review of caries management methods by Bader et al reported that fluoride varnish was fair at preventing dental caries, while the evidence for other methods, including sucrose-free gum and combined chlorhexidine-fluoride methods, was incomplete. 31 In addition, a recent review by Petersson found an average preventive fraction of 30% (0 69%) of fluoride varnish in children. 32 Fluoride varnishes have gained attention in terms of public health dentistry and it is likely that they will become the most common form of topical fluorides applied by dentists. 30 One disadvantage of Duraphat is its poor esthetic effect. A yellow film of varnish remains on the teeth for several hours after application unless it is removed by brushing; in addition, there is a temporary discoloration of teeth after varnish application. 29 While the majority of patients find the presence of varnish on their teeth acceptable, it is the authors experience that some patients dislike its presence as a thin film on their teeth or they find the taste of the varnish objectionable. Safety of fluoride varnish Duraphat varnish contains either a 5% NaF ion or 2.26% fluoride ion. It is considered to be a concentrated fluoride therapeutic agent delivered by dental professionals. Ingestion of excessive fluoride can be a hazard to patients (especially preschool children) who are receiving topical fluoride treatment. According to a fluoride toxicity report by Shulman and Wells, a child weighing 10 kg who ingests 50 mg of fluoride probably will have ingested a toxic dose. 33 Roberts and Longhurst conducted a clinical evaluation on the amount of fluoride applied to children with Duraphat in the United Kingdom and found that the amount of fluoride applied on average was 5.2 mg per child; this amount varied little regardless of the children s ages and no child received the level of fluoride ion quoted for toxicity. 34 Fluoride varnish sets rapidly when applied to teeth and most of the sodium fluoride applied will stay on the tooth surfaces in the natural resins. A study of Swedish children by Ekstrand et al showed a plasma fluoride peak level of μmol/l after fluoride varnish was applied. 35 By contrast, a later study noted that a four-minute acidulated phosphate fluoride (APF) gel application produced a plasma fluoride peak of μmol/l. 36 By comparison, a 1983 study on preschool children reported that the mean plasma fluoride peak level after brushing with fluoride toothpaste was 3.6 μmol/l, while ingesting a 1.0 mg fluoride tablet produced a peak level of 4.5 μmol/l. 37 Two cases of contact allergy to Duraphat varnish have been reported in the literature; the first caused dermatitis in a dental assistant s hand, while the second caused stomatitis in a patient. 38 It has been suggested that these allergic responses were related to the varnish s colophony component. 39 According to the manufacturer, edematous swelling and vomiting by patients with sensitive stomachs have been reported as rare side effects. 40 Recent reviews indicate that fluoride varnish is safe for dental care and that risk of acute toxic reactions from fluoride varnish is minimal. 4,30,39 In addition, the risk of dental fluorosis is minimal because children are not exposed to fluoride varnishes as frequently as they are to fluoride supplements. 4,39 Clinical studies of fluoride varnish on caries As the most commonly used fluoride varnish in dentistry, Duraphat has been the subject of many reviews. 4,41-48 The table provides a summary of clinical studies concerning fluoride varnishes in children. In most clinical trials, Duraphat was reported to be effective for preventing caries, with an average reduction of approximately 30%. 32 Meta-analysis has been conducted using a fitted fixed and a random effects model. The overall effect size of caries reduction was approximately 0.38 in both models. 49,50 Fluor Protector deposited more fluoride in and on the enamel and protected the enamel more effectively in situ than Duraphat; however, it was not proven clinically to be more effective. 43,46 Some studies found NaF more effective than difluorosaline, while others reported that both were equally effective at reducing caries. 26 Topical application of a sodium fluoride varnish is carried out using a small brush and a very small amount of varnish (especially for young children). One study found that an average of 0.17 ml of Duraphat was used in each topical application. 51 The teeth do not have to be very dry and the patient should not eat for approximately two hours after application. 4 Since toothbrushing can remove fluoride varnish, the varnish should be left on the teeth and brushing on the day of application should be avoided whenever possible. 4 In a two-year randomized study in, Seppa and Tolonen studied 300 children at risk of caries and did not find any significant difference in the increment of caries experience between those who received two applications of sodium fluoride varnish per year and those who received four applications. 52 The study also reported that children with a very July-August

6 high caries experience would not benefit from more frequent fluoride application. Conversely, Modeer et al investigated the progression of proximal caries lesions in premolars and molars using Duraphat varnish four times per year; they reported a significant caries reduction among their patient population of 194 teenagers. 22 Ripa and Newbrun both recommended four applications of fluoride treatment a year for patients at high risk for caries. 53,54 Summary Fluoride varnish can be an effective agent in caries management. Fluoride varnish is regarded as a superior topical fluoride agent for young children and there are several advantages to using it instead of other fluoride agents. The contemporary view of fluoride varnish is that it is simple to use, takes only a few seconds to apply, and is safe for children and other special needs. Disclaimer The authors have no financial, economic, commercial, and/or professional interests with any of the products or manufacturers listed in this article. Author information Dr. Chu is in charge of the dental unit, Health Service, University of Hong Kong, where Dr. Lo is a professor, Faculty of Dentistry. References 1. Knutson JW, Armstrong W. The effect of topically applied sodium fluoride on dental caries experience. Publ Health Rep 1943;58: Newbrun E. Evolution of professionally applied topical fluoride therapies. Compend Contin Educ Dent 1999;20 (Suppl 1): Heuser H, Schmidt HF. Dental caries prophylaxis by deep impregnation of the dental enamel with fluorine lac [article in German]. Stoma (Heidelb) 1968;21: Seppa L. Efficacy and safety of fluoride varnishes. Compend Contin Educ Dent 1999;20: Zimmer S, Robke FJ, Roulet JF. Caries prevention with fluoride varnish in a socially deprived community. Community Dent Oral Epidemiol 1999;27: Peyearon M, Matsson L, Birkhed D. Progression of approximal caries in primary molars and the effect of Duraphat treatment. Scand J Dent Res 1992;100: Holm GB, Holst K, Mejare I. The cariespreventive effect of a fluoride varnish in the fissures of the first permanent molar. Acta Odontol Scand 1984;42: Klimek J, Prinz H, Hellwig E, Ahrens G. Effect of a preventive program based on professional toothcleaning and fluoride application on caries and gingivitis. Community Dent Oral Epidemiol 1985;13: Maiwald HJ, Kunzel W, Weatherell J. The use of a fluoride varnish in caries prevention. J Int Assoc Dent Child 1978;9: Wegner H. The clinical effect of application of fluoride varnish. Caries Res 1976; 10: Retief DH, Bradley EL, Holbrook M, Switzer P. Enamel fluoride uptake, distribution and retention from topical fluoride agents. Caries Res 1983;17: Milgrom P, Rothen M, Spadafora A, Skaret E. A case report: Arresting dental caries. J Dent Hyg 2001;75: Fontana M, Gonzalez Cabezas C. Topical application of stannous fluoride inside of cavity preparations: A review of the literature. J Indiana Dent Assoc 1995;74: Shen C, Autio-Gold J. Assessing fluoride concentration uniformity and fluoride release from three varnishes. J Am Dent Assoc 2002;133: Attin T, Hartmann O, Hilgers RD, Hellwig E. Fluoride retention of incipient enamel lesions after treatment with a calcium fluoride varnish in vivo. Arch Oral Biol 1995;40: Haugejorden O, Nord A. Caries incidence after topical application of varnishes containing different concentrations of sodium fluoride: 3-year results. Scand J Dent Res 1991;99: Acuna V, von Beetzen M, Caracatsanis M, Sundstrom F. In vitro fluoride uptake by enamel and dentin. A comparative study of two varnishes. Acta Odontol Scand 1990;48: Donly KJ. Fluoride varnishes. J Calif Dent Assoc 2003;31: Chu CH, Lo EC, Lin HC. Effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting dentin caries in Chinese pre-school children. J Dent Res 2002;81: Arnbjerg D. Use of professionally administered fluoride among Danish children. Acta Odontol Scand 1992;50: Ogard B, Seppa L, Rolla G. Professional topical fluoride applications Clinical efficacy and mechanism of action. Adv Dent Res 1994;8: Modeer T, Twetman S, Bergstrand F. Three-year study of the effect of fluoride varnish (Duraphat) on proximal caries progression in teenagers. Scand J Dent Res 1984;92: Seppa L, Pollanen L, Hausen H. Cariespreventive effect of fluoride varnish with different fluoride concentrations. Caries Res 1994;28: Lindquist B, Edward S, Torell P, Krasse B. Effect of different carriers preventive measures in children highly infected with mutans streptococci. Scand J Dent Res 1989;97: Pienihakkinen K, Jokela J. Clinical outcomes of risk-based caries prevention in preschool-aged children. Community Dent Oral Epidemiol 2002;30: Ogaard B. The cariostatic mechanism of fluoride. Compend Contin Educ Dent 1999;20 (1 Suppl): Blinkhorn A, Davis R. Using fluoride varnish in the practice. Br Dent J 1998;185: Seppa L. Effect of dental plaque on fluoride uptake by enamel from a sodium fluoride varnish in vivo. Caries Res 1983; Warren DP, Henson HA, Chan JT. Dental hygienist and patient comparisons of fluoride varnishes to fluoride gels. J Dent Hyg 2000;74: Bawden JW. Fluoride varnish: A useful new tool for public health dentistry. J Public Health Dent 1998;58: Bader JD, Shugars DA, Bonito AJ. Systematic reviews of selected dental caries diagnostic and management methods. J Dent Educ 2001;65: Petersson LG, Twetman S. Dahlgren H, Norlund A, Holm AK, Nordenram G, Lagerlof F, Soder B, Kallestal C, Mejare I, Axelsson S, Lingstrom P. Professional fluoride varnish treatment for caries : A systematic review of clinical trials. Acta Odontol Scand 2004;62: Shulman JD, Wells LM. Acute fluoride toxicity from ingesting home-use dental products in birth to 6 years of age. J Public Health Dent 1998;57: Roberts JF, Longhurst P. A clinical estimation of the fluoride used during application of a fluoride varnish. Br Dent J 1987;162: Ekstrand J, Koch G, Petersson LG. Plasma fluoride concentration and urinary fluoride excretion in children following application of the fluoride-containing varnish Duraphat. Caries Res 1980;14: Ekstrand J, Koch G, Lindgren LE, Petersson LG. Pharmacokinetics of fluoride gels in children and adults. Caries Res 1981;15: Ekstrand J, Koch G, Petersson LG. Plasma fluoride concentrations in pre-school children after ingestion of fluoride tablets and toothpaste. Caries Res 1983;17: General Dentistry

7 38. Isaksson M, Bruze M, Bjorkner B, Niklasson B. Contact allergy to Duraphat. Scand J Dent Res 1993;101: Beltran-Aguilar ED, Goldstein JW, Lockwood SA. Fluoride varnishes. A review of their clinical use, cariostatic mechanism, efficacy and safety. J Am Dent Assoc 2000;131: Duraphat [package insert]. Canton, MA: Colgate-Palmolive; Clark DC. A review on fluoride varnishes: An alternative topical fluoride treatment. Community Dent Oral Epidemiol 1982; 10: Seppa L. Fluoride varnishes in caries prevention. Proc Finn Dent Soc 1982;78 Suppl 8: Seppa L. Studies of fluoride varnishes in. Proc Finn Dent Soc 1991;87: Yanover L. Fluoride varnishes as cariostatic agents: A review. J Can Dent Assoc 1982;48: Primosch RE. A report on the efficacy of fluoridated varnishes in dental caries prevention. Clin Prev Dent 1985;7: de Bruyn H, Arends J. Fluoride varnishes A review. J Biol Buccale 1987;15: Petersson LG. Fluoride mouthrinses and fluoride varnishes. Caries Res 1993;27 Suppl 1: Strohmenger L, Brambilla E. The use of fluoride varnishes in the prevention of dental caries: A short review. Oral Dis 2001;7: Helfenstein U, Steiner M. Fluoride varnishes (Duraphat): A meta-analysis. Community Dent Oral Epidemiol 1994;22: Helfenstein U, Steiner M. A note concerning the caries preventive effect of Duraphat. Community Dent Oral Epidemiol 1994; 22: Chu CH. Effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting dentine caries [Ph.D thesis]. University of Hong Kong; Seppa L, Tolonen T. Caries preventive effect of fluoride varnish applications performed two or four times a year. Scand J Dent Res 1990;98: Ripa LW. A critique of topical fluoride methods (dentifrices, mouthrinses, operator-, and self-applied gels) in an era of decreased caries and increased fluorosis prevalence. J Public Health Dent 1991;51: Newbrun E. Current treatment modalities of oral problems of patients with Sjogren s syndrome: Caries prevention. Adv Dent Res 1996;10: Florio FM, Pereira AC, Meneghim Mde C, Ramacciato JC. Evaluation of non-invasive treatment applied to occlusal surfaces. ASDC J Dent Child 2001;68: , Petersson LG, Twetman S, Pakhomov GN. The efficiency of semiannual silane fluoride varnish applications: A two-year clinical study in preschool children. J Public Health Dent 1998;58: Bravo M, Baca P, Llodra JC, Osorio E. A 24-month study comparing sealant and fluoride varnish in caries reduction on different permanent first molar surfaces. J Public Health Dent 57: Seppa L, Leppanen T, Hausen H. Fluoride varnish versus acidulated phosphate fluoride gel: A 3-year clinical trial. Caries Res 1995;29: Skold L, Sundquist B, Eriksson B, Edeland C. Four-year study of caries inhibition of intensive Duraphat application in year-old children. Community Dent Oral Epidemiol 1994;22: Petersson LG, Arthursson L, Ostberg C, Jonsson G, Gleerup A. Caries-inhibiting effects of different modes of Duraphat varnish reapplication: A 3-year radiographic study. Caries Res 1991;25: Clark DC, Stamm JW, Tessier C, Robert G. The final results of the Sherbrooke-Lac Megantic fluoride varnish study. J Can Dent Assoc 1987;53: Seppa L, Pollanen L. Caries preventive effect of two fluoride varnishes and a fluoride mouthrinse. Caries Res 1987;21: Kirkegaard E, Petersen G, Poulsen S, Holm SA, Heidmann J. Caries-preventive effect of Duraphat varnish applications versus fluoride mouthrinses: 5-year data. Caries Res 1986;20: Petersson LG, Koch G, Rasmusson CG, Stanke H. Effect on caries of different fluoride prophylactic programs in preschool children. A two year clinical study. Swed Dent J 1985;9: Tewari A, Chawla HS, Utreja A. Caries preventive effect of three topical fluorides. J Int Assoc Dent Child 1984;15: van Eck AA, Theuns HM, Groeneveld A. Effect of annual application of polyurethane lacquer containing silanefluoride. Community Dent Oral Epidemiol 1984;12: Seppa L, Hausen H, Tuutti H, Luoma H. Effect of a sodium fluoride varnish on the progress of initial caries lesions. Scand J Dent Res 1983;91: Grodzka K, Augustyniak L, Budny J, Czarnocka K, Janicha J, Mlosek K, Moszczenska B, Szpringer M, Wacinska M, Petersson L, Frostell G. Caries increment in primary teeth after application of Duraphat fluoride varnish. Community Dent Oral Epidemiol 1982;10: Seppa L, Tuutti H, Luoma H. Three-year report on caries prevention of using fluoride varnishes for caries risk children in a community with fluoridated water. Scand J Dent Res 1982;90: Kolehmainen L. Evaluation of a fluoridecontaining varnish in children with low caries incidence. Scand J Dent Res 1981;89: Holm AK. Effect of fluoride varnish (Duraphat) in preschool children. Community Dent Oral Epidemiol 1979;7: Koch G, Petersson LG, Ryden H. Effect of flouride varnish (Duraphat) treatment every six months compared with weekly mouthrinses with 0.2 per cent NaF solution on dental caries. Swed Dent J 1979;3: Murray JJ, Winter GB, Hurst CP. Duraphat fluoride varnish. A 2-year clinical trial in 5-year-old children. Br Dent J 1977;143: Koch G, Petersson LG. Caries preventive effect of a fluoride-containing varnish (Duraphat) after 1 year s study. Community Dent Oral Epidemiol 1975;3: July-August