Erosion Prevention Potential of an Over-the-Counter Stabilized SnF2 Dentifrice Compared to 5000 ppm F Prescription-Strength Products.

OBJECTIVE: To determine the relative ability of various F-containing products to protect enamel against the initiation and progression of tooth surface loss due to erosive acid challenges. METHODS: Cores of enamel were prepared from extracted human teeth, soaked in pooled human saliva (pellicle formation), and then treated in a 1:3 slurry (product:saliva) of either OTC level (1100 ppm F) or prescription level (5000 ppm F) products, followed by a standardized erosion cycling procedure (five days of cycling) that included 10-minute challenges with an erosive dietary acid (1% citric acid at pH 2.3) applied 60 minutes after each dentifrice treatment (repeated four times per day). Enamel surface loss was measured using transverse microradiography. Two studies were conducted. Study 1 included: A) 1100 ppm F as NaF; B) 1100 ppm F as stabilized SnF; C) 5000 ppm F as NaF; and D) 5000 ppm F as NaF + acidulated phosphate. Study 2 included: 1) 1100 ppm F as stabilized SnF; 2) 5000 ppm F as NaF + tricalcium phosphate; and 3) 1100 ppm F as NaF. RESULTS: Study 1: Treatment B (1100 ppm F as SnF), where specimens lost only 8.0 µm of the enamel surface, was significantly more effective than Treatments A, C, and D at protecting enamel against the initiation and progression of erosive acid damage (p < 0.05). Specimens treated with product A exhibited 22.8 (1.25) µm (mean ± sem) of enamel loss; 20.0 (0.71) µm of enamel loss with treatment C and 24.0 (1.4) µm of enamel loss with Treatment D. Study 2 also demonstrated significantly greater erosion protection with the stabilized SnF2 dentifrice (p < 0.05), with only 5.8 (1.93) µm of tooth surface loss, while groups 2 and 3 lost 19.8 (0.75) µm and 18.0 (2.16) µm, respectively. CONCLUSION: Results from both studies demonstrated the OTC dentifrice formulated with stabilized SnF2 provides significantly greater protection against erosive acid attack compared to some of the most popular prescription level (5000 ppm F) fluoride treatments available.

A new model for demonstrating enamel protection benefits relative to acid challenge.

OBJECTIVE: To determine the applicability of a modified US FDA Caries Monograph test method for measuring the protective benefits of fluoride (F) against erosive, dietary acids. METHODS: Acid-challenged teeth were treated in two studies with a dentifrice, rinsed, and then re-challenged in a series of tests using three dietary acids. Study 1 included dentifrices containing 1450 ppm F as sodium fluoride (NaF) + triclosan [A], 1450 ppm F (NaF) + potassium nitrate (KNO3) [B], 1000 ppm F as sodium monofluorophosphate (SMFP) [C], and 0 ppm F (placebo) [D]. Study 2 included dentifrices containing 1450 ppm F (NaF) [A]; and 0 ppm F (placebo) [B]. Acids were analyzed for phosphate removed during tooth challenges, with post-treatment results compared to baseline. Results were averaged and reported as a % protection value for each product, with higher values indicating greater protection. RESULTS: Study 1: % protection for A = 16.4; B = 13.0; C = 7.1; and D = -5.2. Study 2: A = 15.2; B = -10.5, with A = B > C > D: Study 1; and A > B: Study 2. In each study, p < 0.05, ANOVA. CONCLUSIONS: The model provides a viable tool for initially assessing the potential for fluoride-containing oral care products to protect teeth against erosive, dietary acids. This can then lead to further and more elaborate testing with reasonable expectations for outcomes.

Enamel protection from acid challenge--benefits of marketed fluoride dentifrices.

OBJECTIVE: To determine the ability of various marketed dentifrices containing stabilized stannous fluoride (SnF2), sodium fluoride (NaF), or sodium monofluorophosphate (SMFP) to protect enamel against the earliest stages of erosive dietary acid damage using an in vitro enamel protection model. METHODS: Acid-challenged, extracted human teeth were treated with a 1:3 dilution of dentifrice, rinsed, and then challenged in a controlled series of tests using four dietary acids considered potentially erosive to teeth. Each acid was collected and analyzed to determine the level of mineral (phosphorous) removed from the teeth during the challenge. Post-treatment results were compared to baseline values for each acid. Results for the four acids were averaged and reported as an average percent protection value for each of the dentifrices tested, with higher values representing greater acid protection. The study included six dentifrices formulated with (A) sodium fluoride (NaF), (B) stabilized stannous fluoride (SnF2), (C,D) NaF plus 5% potassium nitrate (KNO3), (E) sodium monofluorophosphate (SMFP), or (F) SMFP plus 8% arginine bicarbonate. RESULTS: The stabilized SnF2 dentifrice demonstrated an average protection score of 39.3%, while products formulated with NaF resulted in protection scores between 11 and 13%. The SMFP dentifrice was rated at -3.5%, and the SMFP + arginine bicarbonate dentifrice resulted in a net average score of -5.0%. Results of this test were statistically significant (p < 0.05, ANOVA: B > A = C = D > E = F), in favor of the stabilized SnF2 dentifrice. CONCLUSIONS: These results suggest the stabilized SnF2 dentifrice has the potential to provide significantly better overall acid protection versus any of the other dentifrices included in the study.

Anticaries potential of commercial fluoride rinses as determined by fluoridation and remineralization efficiency.

OBJECTIVE: The objective of this work was to compare the anticaries potential of several currently marketed fluoride-containing mouthrinse products using two in vitro approaches: 1) fluoride uptake studies of demineralized human enamel samples after exposure to rinse products; and 2) microhardness studies of sound enamel samples after exposure to the rinse products and demineralizing agents. METHODS: Four currently marketed rinse products, formulated at 100 ppm F, were evaluated in fluoride uptake studies relative to a negative (water) rinse control (Study 1). The same rinse products were evaluated in microhardness studies (Study 2) against a positive control, ACT Anticavity rinse, which is formulated with 225 ppm F and carries the ADA Seal of Acceptance as an effective anticavity mouthrinse. Test products included ACT Total Care rinse (pH = 6.34), Listerine Total Care rinse (pH = 3.57), Crest Pro-Health for Me rinse (pH = 3.33), and Crest Pro-Health Complete rinse (pH = 3.43). RESULTS: Study 1-Samples treated with any of the fluoride-containing rinses showed significantly higher (p < 0.05) levels of fluoride uptake than the negative (water) control. Two of the products (Crest Pro-Health for Me and Crest Pro-Health Complete) showed significantly higher (p < 0.05) levels of fluoride uptake into demineralized enamel than the other marketed rinses (Listerine Total Care and ACT Total Care). Study 2-Samples treated with the same two rinse products (Crest Pro-Health For Me and Crest Pro-Health Complete) showed significantly lower mineral loss than the other rinse products, as well as the positive control. CONCLUSION: Results of these in vitro studies indicate that the Crest mouthrinse products evaluated here are capable of providing significantly better fluoridation of demineralized enamel, as well as significantly better protection against the initiation and progression of demineralization, compared to the other marketed fluoride-containing mouthrinse products tested.

Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year.

There is limited evidence from clinical trials on the dose response of sodium fluoride dentifrices at concentrations above 1100 ppm fluoride ion, with respect to caries efficacy. This randomized, double-blind study examined the anti-caries effectiveness of sodium fluoride dentifrices containing 1700 ppm, 2200 ppm and 2800 ppm fluoride ion relative to an 1100 ppm fluoride ion control. A population of 5439 elementary schoolchildren, aged 6-15 years, was recruited from an urban central Ohio area with a low fluoride content water supply (<0.3 ppm). Subjects were examined by visual-tactile and radiographic examination at baseline and after 1, 2, and 3 years of using the sodium fluoride dentifrices. Subjects were stratified according to gender, age and baseline DMFS scores derived from the visual-tactile baseline examination and randomly assigned to one of four treatment groups: 0.243% sodium fluoride (1100 ppm fluoride ion), 0.376% sodium fluoride (1700 ppm fluoride ion), 0.486% sodium fluoride (2200 ppm fluoride ion), and 0.619% sodium fluoride (2800 ppm fluoride ion). All products were formulated with the same fluoride compatible silica abrasive. Results after 1 year provided evidence of a positive sodium fluoride dose response. Compared to the 1100 ppm fluoride treatment group, the 1700 ppm fluoride treatment group had an 11.0% reduction in DMFS that was not statistically significant, while the 2200 ppm and 2800 ppm fluoride treatment groups showed statistically significant (P<0.05) reductions of 18.6% and 20.4%, respectively. The reductions in caries delivered by the higher fluoride dentifrices were present across all tooth surface types, but were most pronounced for occlusal surfaces. Results at years 2 and 3 were confounded by a concurrent fluoride rinse program, which involved portions of the study population. While the trends for the higher fluoride dentifrices observed at year 1 remained at years 2 and 3, the difference observed between treatments were substantially less and failed to reach statistical significance (P<0.05). Collectively, the data demonstrate that the 2200 ppm and the 2800 ppm fluoride treatments delivered statistically significantly greater caries efficacy than the 1100 ppm fluoride treatment. This large-scale clinical trial provides evidence of a positive statistically significant dose relationship between dental caries and sodium fluoride in a dentifrice at levels above 1100 ppm fluoride at year 1.

Reduction in dental caries with four concentrations of sodium fluoride in a dentifrice: a meta-analysis evaluation.

Information on the effects of fluoride concentrations above 1,100 ppm in dentifrices is not extensive in the literature. The objective of this meta-analysis was to examine and compare the anticaries effectiveness (in terms of DMFS scores) of 1,700 ppm, 2,200 ppm and 2,800 ppm F- ion (as sodium fluoride) dentifrices vs. an 1,100 ppm F- ion (as sodium fluoride) control dentifrice based on results from six double-blind, randomized clinical studies, each conducted over a two- to three-year period. The studies each enrolled approximately 1,200-2,000 male and female school children per treatment group in grades I through 8, and were conducted in areas with low fluoride content water supplies in the states of Indiana, Pennsylvania, Ohio and Oregon. Separate meta-analyses were performed on the study results (DMFS increment scores determined by visual-tactile examinations supplemented with radiographs) for the one-year, two-year and three-year examinations. Comparisons of the 1,700 ppm F-, 2,200 ppm F-, and 2,800 ppm F- groups vs. the 1,100 ppm F- group were based on pooling the effect sizes for these comparisons from the individual studies. The effect sizes were calculated in two different ways, reflecting the analyses that were performed in the original studies: 1) effects based on the sample means and variances; and 2) effects based on the adjusted sample means and mean squared error from an analysis of covariance. The results obtained from this meta-analysis provide evidence that the use of a 2,800 ppm F- ion, as sodium fluoride, dentifrice results in statistically significantly lower caries increment than the use of an 1,100 ppm F- ion, as sodium fluoride, dentifrice. This result was noted after one, two, and three years of dentifrice use. The 1,700 ppm F- and 2,200 ppm F- dentifrice groups showed some directional advantages over the 1,100 ppm F- dentifrice group, however the analysis did not establish these groups as statistically significantly better than 1,100 ppm F-. The meta-analysis based on analysis of covariance results was somewhat more sensitive to treatment group differences than the analysis based on sample means and variances, as was expected.

Reversal of incipient and radiographic caries through the use of sodium and stannous fluoride dentifrices in a clinical trial.

Experimental evidence has clearly demonstrated that the early stages of lesion formation (enamel demineralization) are reversible following exposure to saliva and/or fluoride. Clinical evidence for remineralization has also been reported extensively in the literature. However, the literature is lacking with respect to data from well-controlled clinical studies regarding the quantitative contribution of remineralization to arrestment and reversal of caries. Retrospective analysis of an existing clinical trial database provided an opportunity to examine the incidence of clinical lesion reversals in a placebo-controlled, double-blinded caries clinical study. The clinical study examined three treatment groups: 1) 0.243% sodium fluoride/silica dentifrice, 2) 0.4% stannous fluoride/calcium pyrophosphate (positive control) dentifrice and 3) non-fluoridated placebo/calcium pyrophosphate (negative control) dentifrice. Clinical measures in this study included both radiographic and visual-tactile assessments of caries. Examination of all subjects revealed a statistically greater frequency for caries reversals in the sodium fluoride group as compared to the placebo group at Year 3, for both total and radiographic caries. In contrast, while caries reversals in the stannous fluoride group occurred with greater frequency than in the placebo group at Year 3, for both total and radiographic caries, the differences were not statistically significant. When only subjects who were "at risk" for potential reversals (i.e., those with a minimum of one carious lesion at baseline) were examined, a statistically greater frequency in caries reversals was observed in both the sodium fluoride (total, incipient, and radiographic caries) and stannous fluoride (total and radiographic caries) groups as compared to the placebo group at Year 3. Collectively, these data confirm the ability of both 0.243% sodium fluoride/silica and 0.4% stannous fluoride/calcium pyrophosphate dentifrices to clinically reverse caries. The results suggest that sodium fluoride may deliver a greater frequency of caries reversals than stannous fluoride, although these treatments were not found to be significantly different.

Electron probe microanalysis and transverse microradiography studies of artificial lesions in enamel and dentin: a comparative study.

In cardiology and research involving the interactions between restorative materials and dental hard tissues, it is important for small changes in tooth mineral content to be measurable. Currently, transverse microradiography (TMR) is the most accepted tool for the above purpose. Electron Probe Microanalysis (EPMA) can yield both qualitative identification of elements and quantitative compositional information. The purpose of this study was to compare the mineral distribution in well-defined artificial lesions, in dentin and enamel, by the use of both TMR and EPMA on the same sample. The good correlation between the two sets of data validates EPMA as a technique and helps in the interpretation of its results. The data from TMR analysis are expressed as vol% of mineral, while EPMA gives the levels of Ca and phosphate in wt%. The conversion between the two sets of data is complicated by the fact that local density is, as yet, unknown.

The application of in situ models for evaluation of new fluoride-containing systems.

Many in situ models have assessed the anticaries potential of fluoride-containing systems (Stookey et al., 1985; Mellberg et al., 1986, 1992a,b; Corpron et al., 1986; Featherstone and Zero, 1992; Ogaard and Rolla, 1992; Stephen et al., 1992). Several models have reportedly been validated according to guidelines proposed by Proskin et all. (1992). The proposed guidelines cover only dentifrices containing sodium fluoride (NaF) or sodium monofluorophosphate (SMFP) as active ingredients. These compounds are the most widely used sources of fluoride in dentifrices, and dose-response clinical standards are available for both. Other fluoride compounds, such as amine fluoride (AmF) and stannous fluoride (SnF2), have also been proven effective in reducing caries (Muehler et al., 1957, 1958; Marthaler, 1968; Lu et al., 1980; Cahen et al., 1982). Profile standards for these fluorides were not included in the proposed guidelines, primarily due to the lack of clinical data necessary to establish a dose response for these ingredients. Criteria for demonstrating the efficacy of these ingredients, along with methods to assess new fluoride compounds, need to be established. In situ models are used to evaluate the anticaries potential of new compounds added to mouthrinses, gums, slow-release devices, etc. (Creanor et al., 1992; Manning and Edgar, 1992; Lamb et al., 1993; Toumba and Curzon, 1993; Wang et al., 1993). Ingredients are often added to dentifrices previously proven effective against caries in order to provide additional benefits of gum health, tartar control, cleaning, etc. Proposals are made regarding the in situ testing of new dentifrices containing clinically proven fluoride compounds other than NaF and SMFP, as well as alternative delivery systems, in order to assist in their evaluation.

De/remineralization from sodium fluoride dentifrices.

PURPOSE: To test the demineralization/remineralization effects of sodium fluoride dentifrices using an in situ single-section crown model system. MATERIALS AND METHODS: A fluoride dose response was evaluated using 0, 1100 and 2800 ppm F-, along with the effects of an enhanced fluoride delivery system (polyampholyte-NaF). The single-section crown model was employed with supervised toothbrushing twice a day. At the end of each 1-month study leg, sections were removed and replaced with new sections for the next leg. Both before and after the double-blind, crossover portion of the study, sections were evaluated by polarized light microscopy and microradiography. The change in mineral content of the enamel and root lesions was analyzed by ANOVA with a Waller-Duncan K-Ratio Test post hoc. RESULTS: The placebo dentifrice group showed a loss of mineral and was statistically different from all groups. The fluoride dentifrices showed increasing amounts of enamel mineral gain, with increasing fluoride concentration. The polyampholyte-NaF delivery system with 1100 ppm F- was equivalent to the 2800 ppm F- dentifrice. Root lesions gave similar rank-order results although all treatments showed demineralization or mineral loss.

Anticaries efficacy of an improved stannous fluoride toothpaste.

A series of laboratory and animal studies were conducted to confirm the anticaries potential of a new, stabilized stannous fluoride (SnF2) dentifrice relative to clinically proven SnF2 controls. Included in this series of assessments were fluoride uptake into demineralized human enamel, remineralization/inhibition of demineralization for both human enamel and roots, and animal caries studies. Each of these studies demonstrate the new, stabilized SnF2 dentifrice (Crest Gum Care toothpaste) is effective at inhibiting and reversing the caries process. These data confirm that this new dentifrice, formulated with a combination of SnF2, and hydrated silica, is predicted to be highly effective against caries. These tests predict that this new stabilized SnF2 dentifrice (Crest Gum Care toothpaste) provides a level of anticaries activity that is equivalent to Crest Regular toothpaste, a sodium fluoride (NaF)/silica product. The data suggest that this new formulation provides enhanced anticaries efficacy relative to previous, unstabilized SnF2 formulations as a result of improved fluoride bioavailability.

Mode of action of fluoride: application of new techniques and test methods to the examination of the mechanism of action of topical fluoride.

Modern techniques in dental research continue to assist in the study of the mode of (anticaries) action of topical fluorides. The Plaque Glycolysis and Regrowth Model (PGRM) facilitates the standardized assessments of antimicrobial effects on plaque following use of test formulations in vivo without complications arising from coincident mineral reactivity. In vivo plaque glycolysis testing demonstrates that topically applied fluoride, at conventional levels found in dentifrices, has only modest effects on the metabolic (acid-producing) activity of dental plaque. Any 'plaque' contribution to fluoride efficacy must come from more subtle effects on plaque acidogenicity than those measured in PGRM. The 19-FMAS NMR (Magic Angle Spinning Nuclear Magnetic Resonance) technique provides unambiguous measures of the reaction products of F-enamel interactions. Studies have revealed a new 'reaction product' of fluoride-enamel interactions--designated as Non-Specifically-Adsorbed Fluoride, NSAF. This species, along with FAP (fluoroapatite), FHAP (fluorohydroxyapatite), and CaF2 (calcium fluoride), contributes to the remineralization/demineralization benefits of fluoride. pH cycling and in situ denture chip studies permit quantitative assessments to be made of the relative benefits of fluoride in promoting remineralization and in inhibiting demineralization. Results from pH cycling/in situ experiments are strongly supportive of Koulourides' 'Acquired Acid Resistance' concept, describing fluoride's decay-preventive effects. The continued application of new analytical/physical techniques and testing regimens to the study of fluoride anticaries mechanisms may lead to the development of improved fluoride agents/treatment modalities for the prevention of dental caries.

Demineralization and remineralization evaluation techniques--added considerations.

Methods used for the analysis of tooth de- and remineralization include techniques with various degrees of sophistication and quantitative capabilities, ranging from direct measures of mineral gain/loss (e.g., microradiography) to indirect measures (e.g., iodide permeability) of changes in tooth mineral properties. In all instances, the capabilities of methods for accurate determination of changes in tooth mineral properties are affected by procedures used in the preparation of specimens for analysis, the magnitude of change taking place in the test (vs. the detection limits of the techniques), and protocols for specimen analysis. In specific instances, such as in the case of dentin, unique specimen-handling and analysis procedures must be used to prevent artifacts. The choice of techniques for the assessment of de- and remineralization depends strongly upon study protocols and laboratory capabilities; however, 'quantitative' measures of mineral gain and loss are possible only if direct chemical or radiographic techniques are used. Either radiographic, cross-sectioned microhardness or polarized light can be used for the determination of lesion depth. Porosity, light-scattering, and surface microhardness are indirect techniques which complement direct measures of mineral gain and loss. Whatever methods are used in the analysis of de- and remineralization, researchers must take care to differentiate accurately among the quantitative capabilities of techniques used in analysis.

19F MAS-NMR and solution chemical characterization of the reactions of fluoride with hydroxyapatite and powdered enamel.

Solution chemical and 19F magic angle spinning-nuclear magnetic resonance (MAS-NMR) methods have been utilized to study the effects of fluoride dose, fluoridating pH, and mineral surface area on the dynamics of fluoride reactivity with hydroxyapatite and powdered human dental enamel in vitro. Both solution chemical fluoride uptake and NMR measurements demonstrated that the reaction products of ionic fluoride with apatite include mixtures of FAP, FHAP, and CaF2, with increased amounts of CaF2 promoted by increased F concentration or decreased pH. NMR analysis showed FAP or FHAP as a reaction product of fluoride uptake under all conditions, regardless of whether CaF2 was formed, unambiguously demonstrating fluorite as an additive rather than substitute form of F reactivity. pH stat measurements demonstrated the release of OH- during F reactivity with apatites corresponding to ion exchange formation of FAP/FHAP or dissolution/reprecipitation formation of CaF2. Phosphate release into solution accompanied fluoride uptake under all conditions, including regions where ion exchange predominated. Whereas powdered dental enamel demonstrated fluoride uptake behavior similar to that of synthetic apatite, the resulting reaction products differed as analyzed by 19F MAS-NMR.