Placebo Varnish Research Articles

Effectiveness of Fluoride Varnishes for White Spot Lesion Prevention and Remineralization during Orthodontic Treatment: A Randomized Controlled Trial.

This study investigated the effectiveness of titanium tetrafluoride (TiF4) varnish compared to sodium fluoride (NaF) varnish for preventing and remineralizing white spot lesions (WSLs) in individuals undergoing orthodontic treatment. This randomized, placebo-controlled, and double-blinded study was conducted with sixty-five adolescents who were selected based on caries activity and then randomized into three parallel groups: G1 (placebo varnish), G2 (5%-NaF varnish) and G3 (4%-TiF4 varnish). Volunteers received varnish application weekly for the first 4 weeks, after 6 (T1) and 12 (T2) months. The measured outcomes included: prevention of new WSLs, and reversal/progression of WSLs, assessed by Nyvad and ICDAS indices, as well as quantitative light-induced fluorescence (QLF). Chi-square, ANOVA, and Kruskall-Wallis tests were applied. The level of significance was set at 0.05, and post hoc Bonferroni test for p values were performed to correct for multiple comparisons. 1,274 teeth were included; 70.5% were Nyvad 0, and 29.5% were Nyvad 1, with no differences between the groups at baseline (T0). Regarding ICDAS, 70.5% were ICDAS 0, 21.6% were ICDAS 1, and 7.9% were ICDAS 2. G1 showed an increasing prevalence of WSLs at T1 and maintained stable at T2; G2 exhibited a decline at T2, while G3 experienced a decrease at T1 and T2 (p < 0.01). Incidence of WSLs at T2 was 10.2% (G1), 5.6% (G2) and 1.4% (G3). The percentage of teeth initially scored as Nyvad 0 that progressed to Nyvad 1 was 13%, 6.8%, and 1% for G1, G2, and G3, respectively. Conversely, the percentage of teeth initially scored as Nyvad 1 that regressed to Nyvad 0 or Nyvad 2 (T0-T2) was 14%, 49.3%, and 74.4%, respectively (p < 0.001). As for ICDAS index, regression was observed in 6.5%, 17.8% and 24%, while progression was observed in 14.9%, 7.7% and 0.9% for G1, G2 and G3, respectively (p < 0.001). Significant differences among the 3 groups for integrated fluorescence loss (mean±SD, G1: -14.28±9.47, G2: -11.10±11.49 and G3: -6.77±11.00) were found at T2 (p < 0.01). Both varnishes demonstrated the ability to prevent and remineralize WSLs. However, TiF4 varnish exhibited the most effective control over WSLs during the 12-month orthodontic treatment.

Analysis of dentin wear and biological properties promoted by experimental inoffice desensitizing materials

BackgroundThis study aimed to evaluate dentin wear and biological performance of desensitizing materials.MethodsSeventy bovine root dentin blocks were sectioned. Half of the surface of each specimen was untreated (control) and the other half was immersed in EDTA and treated with the following desensitizing materials: placebo varnish (PLA), fluoride varnish (FLU), sodium fluoride (NaF) varnish + sodium trimetaphosphate (TMP), universal adhesive (SBU), S-PRG varnish (SPRG), biosilicate (BIOS), and amelotin solution (AMTN). After application, the specimens were submitted to an erosive-abrasive challenge and the wear analyzed by optical profilometer. Serial dilutions of extracts obtained from the culture medium containing discs impregnated with those desensitizers were applied on fibroblasts and odontoblasts-like cells cultures. Cytotoxicity and production of total protein (TP) by colorimetric assays were determined after 24 h. Data were statistically analyzed using Kruskal-Wallis, Dunn’s, One-way ANOVA and Tukey tests (p ≤ 0.05).ResultsNo dentin wear was observed only for SBU. The lowest dentin wear was observed for AMTN and TMP. Cell viability was significantly reduced after treatment with undiluted extracts of PLA, FLU, TMP and SBU in fibroblasts and TMP and SBU in odontoblast-like cells. SPRG, BIOS and AMTN were cytocompatible at all dilutions tested. Considering TP results, no statistical difference was observed among the groups and high levels for TP were observed after TMP and FLU treatments.ConclusionsUniversal adhesive system may protect dentin with opened tubules from wear after challenge. Extracts of adhesive and fluoride varnishes presented cytotoxic mainly on fibroblasts. The enamel protein may be a future alternative to treat dentin with opened tubules because it may cause low wear under erosive-abrasive challenge with low cytotoxic effects.

Effect of Fluoride Varnish application on Primary Dentition among Preschool Children in Dharan: A Randomized Controlled Trial

Introduction: Topical application of fluoride varnish on the tooth surface prevents the dissolution rates of tooth materials and increases the re-precipitation of lost minerals. Objective: To assess the effectiveness of fluoride varnish application in primary dentition among preschool children at high risk of dental caries. Methods: A randomized controlled trial was conducted with two parallel-group, comprising 3–5-year-old children, 100 in each group (Fluoride varnish or Placebo varnish). Dental caries were recorded at baseline, three- and six-month using Caries Assessment and Treatment Instrument (CAST) scoring system. Statistical analysis was done using the Chi-square test for categorical data, Mann-Whitney U test, independent t-test, and Wilcoxon Signed Ranks test for quantitative data. The level of significance was set at p<0.05. Results: Overall, dental caries progression from baseline to three months and six months was more in placebo varnish group children than fluoride varnish (38.98% and 31.3% respectively). The proportion of children with new caries lesions was more in placebo group than that in the fluoride varnish group at every three months interval. The difference between the groups was statistically significant (p<0.05). Fluoride varnish treatment once in six months had a better treatment effect with a preventive fraction of 62.1% in comparison to three months (59.0%). Conclusions: Dental caries can be prevented effectively by the use of 5% sodium fluoride varnish. Fluoride varnish is efficacious when applied twice a year in children at high risk of dental caries.

Effect of theobromine based dental varnish on the enamel surface microhardness- an in vitro study

Introduction: Theobromine in recent years has been used as a remineralization agent. It demonstrates increased enamel hydroxyapatite crystal size that strengthens the enamel thus making it resistant to acid attack. Hence in the present study theobromine-based dental varnish was developed and its effect on enamel surface microhardness was assessed. Methods: In this in-vitro study, 45 freshly extracted healthy human first premolar teeth were randomly allocated into three groups of 15. Group 1 was Placebo varnish, Group 2 was Standard 5% Sodium fluoride varnish which was commercially available, and Group 3 was Novel theobromine nanoparticles containing dental Varnish. The enamel blocks were prepared from the randomly selected teeth. Baseline surface microhardness of the prepared enamel blocks were measured at three different points on the polished surface using both Vickers hardness tester and nano-indentation hardness tester. The prepared enamel blocks were immersed in a demineralizing solution for 7 days. At the end of the 7th day, the enamel blocks were removed and cleaned thoroughly. Again, the enamel blocks microhardness was recorded. After demineralization, all the enamel blocks were treated with three different varnishes for 28 days. After the 28th day, the readings were recorded using both Vickers hardness tester and nano-indentation hardness tester again. The results were analyzed by one-way analysis of variance (ANOVA), repeated measures ANOVA, and Bonferroni’s post hoc analysis. Results: The mean enamel surface microhardness between the three groups at baseline (P>0.001) and after demineralization (P>0.001) were not statistically significant whereas after application of dental varnishes the mean enamel surface microhardness values showed significant differences between the groups (P<0.001). Group 3 showed significantly more enamel surface microhardness values after its application on demineralized enamel surface as compared to Group 1 and Group 2 respectively. Conclusions: Theobromine nanoparticles containing dental varnish can significantly increase the enamel surface microhardness after its application on the demineralized early white spot lesion. Keywords: Theobromine, Remineralization, Nanoparticles, Surface microhardness

Root Caries Preventive Effect of Varnishes Containing Fluoride or Fluoride + Chlorhexidine/Cetylpyridinium Chloride In Vitro.

Caries preventive varnishes containing only fluoride might differ from those containing a combination of fluoride and antimicrobial components in terms of mineralization properties and their impact on the cariogenic biofilm. We compared a fluoride and a fluoride + chlorhexidine (CHX)/cetylpyridinium chloride (CPC) varnish on root caries formation in vitro. One hundred bovine root dentin samples were allocated to five groups (n = 20/group): (1) 7700 ppm fluoride varnish (Fluorprotector S (F)), (2) experimental placebo varnish for F (F-P), (3) 1400 ppm fluoride + 0.3% CHX/0.5% CPC varnish (Cervitec F (CF)), (4) experimental placebo varnish for CF (CF-P), (5) untreated control. Cariogenic challenge was provided using a multi-station, continuous-culture 3-species (Streptococcus mutans (SM), Lactobacillus rhamnosus (LR), Actinomyces naeslundii (AN)) biofilm model for 10 days. Mineral loss (ΔZ) was evaluated using transversal microradiography and bacterial counts in the biofilm assessed as colony-forming units. Fluorescence in situ hybridization (FISH) and confocal microscopy were performed to assess the three-dimensional biofilm architecture. Mean ± SD (vol% × μm) ΔZ was significantly lower for F (9133 ± 758) and CF (9835 ± 1677) compared to control (11362 ± 919) (p < 0.05), without significant differences between F and CF. SM counts were significantly lower and LR counts significantly higher in F- and CF-biofilms compared to control. AN counts were significantly higher in the F-biofilms than in all other groups. According to FISH, SM and LR invaded dentinal tubules only in the control-group. In the CF-group, the basal biofilm layer did not contain SM and AN. Both F and CF varnishes had similar caries-preventive effects and a considerable impact on biofilm structure and composition.

Protective effect of titanium tetrafluoride and silver diamine fluoride on radiation-induced dentin caries in vitro

This in vitro study evaluated the protective effect of titanium tetrafluoride (TiF4) varnish and silver diamine fluoride (SDF) solution on the radiation-induced dentin caries. Bovine root dentin samples were irradiated (70 Gy) and treated as follows: (6 h): 4% TiF4 varnish; 5.42% NaF varnish; 30% SDF solution; placebo varnish; or untreated (negative control). Microcosm biofilm was produced from human dental biofilm (from patients with head-neck cancer) mixed with McBain saliva for the first 8 h. After 16 h and from day 2 to day 5, McBain saliva (0.2% sucrose) was replaced daily (37 °C, 5% CO2) (biological triplicate). Demineralization was quantified by transverse microradiography (TMR), while biofilm was analyzed by using viability, colony-forming units (CFU) counting and lactic acid production assays. The data were statistically analyzed by ANOVA (p < 0.05). TiF4 and SDF were able to reduce mineral loss compared to placebo and the negative control. TiF4 and SDF significantly reduced the biofilm viability compared to negative control. TiF4 significantly reduced the CFU count of total microorganism, while only SDF affected total streptococci and mutans streptococci counts. The varnishes induced a reduction in lactic acid production compared to the negative control. TiF4 and SDF may be good alternatives to control the development of radiation-induced dentin caries.

Effect of xylitol varnishes on enamel remineralization of immature teeth: in vitro and in situ studies.

We evaluated the efficacy of xylitol varnishes on the remineralization of newly erupted permanent and deciduous teeth in vitro and in situ. Human enamel specimens were randomly allocated to 8 groups (n = 15/group). Artificial caries lesions were produced and enamel alterations were quantified by surface/subsurface hardness and transverse microradiography. The blocks were then treated with the following varnishes: DuraphatTM; 20 wt% xylitol (146 μm) varnish; 20 wt% milled xylitol (80 μm) varnish, and placebo varnish, and removed after 6 h of immersion in artificial saliva. The blocks were subjected to pH-cycles for 8 days. fifteen subjects wore palatal appliances containing four pre-demineralized and treated enamel specimens, for 5 days. Data were statistically analyzed by ANOVA/Tukey and Kruskal-Wallis/Tukey's test (p < 0.05). The %SHR in both studies was significantly increased by xylitol and Duraphat™ varnishes when compared to placebo. Considering subsurface remineralization, only the xylitol varnishes were able to significantly reduce the enamel lesion. Xylitol varnishes can be promising alternatives to promote enamel remineralization of newly erupted permanent and deciduous teeth.

Effect of TiF4 varnish after pre-treatment with proanthocyanidin or chlorhexidine on the progression of erosive dentin loss in the presence or absence of the demineralized organic matrix

This study evaluated the protective effect of TiF4 varnish, after pre-treatment with proantocyanidin or chlorhexidine, on the progression of erosive dentin loss (EDL), under the presence or absence of the demineralized organic matrix (DOM). Bovine root dentin samples were eroded for 30 min (0.1% citric acid, pH 2.5) and the loss was measured by profilometry. Half of them were subjected to the DOM removal using collagenase for 4 days, while the other half remained immersed in water. The removal of DOM was checked by profilometry. Samples were divided into 24 groups (n = 15) according to the factors: 1– With or without DOM; 2– Pre-treatment with 0.012% chlorhexidine gel, 10% proanthocyanidin gel or untreated for 1 min; 3–Final Treatment with TiF4 varnish, NaF varnish, placebo varnish or untreated for 6 h. The samples were submitted to a pH cycling for 5 days: 0.1% citric acid (4 × 90s/day) and artificial saliva between the challenges. The final profile was obtained for the calculation of EDL (μm, three-way ANOVA/Tukey test). When DOM was preserved, the EDL was lower compared to the condition without DOM (7.08 ± 4.03 μm and 9.80 ± 3.79 μm, p < 0.001, respectively), regardless of the treatments. The pre-treatment had no influence on the progression of EDL (p = 0.637), while the final treatment (TiF4 varnish only, 6.77 ± 4.08 μm) was effective in reducing the progression of EDL (NaF varnish: 9.52 ± 4.02 μm; Placebo varnish: 8.64 ± 4.06 μm and no treatment: 8.80 ± 3.95 μm). It can be concluded that DOM has important protective effect on the progression of EDL. TiF4 was the unique treatment capable of reducing EDL progression, regardless of the pre-treatment of DOM.

Efficacy of P11-4 for the treatment of initial buccal caries: a randomized clinical trial

To investigate the safety and efficacy of Self-Assembling Peptide P11-4 (SAP P11-4) compared to placebo or fluoride varnish (FV), a randomized, controlled, blinded, split-mouth study with sequential design was conducted. Subjects presenting two teeth with White-Spot-Lesions (WSLs) were included and teeth were randomly assigned to test or control. Control received placebo at baseline (D0) and test SAP P11-4, all received FV at Day 90 (D90). Standardized photographs were taken at each visit, and WSL size changes were morphometrically assessed. Hierarchical Linear Modelling, considering paired and sequential design, was used to test four hypotheses. SAP P11-4 lesions (test, D90–D0) showed significant WSL size reduction compared to placebo (control, D90–D0; p = 0.008) or FV (control, D180–D90; p = 0.001). Combination of SAP P11-4 and delayed FV after 90 days (test, D180–D0), showed a significant difference compared to FV alone (control D270–D90; p = 0.003). No significant difference on FV efficacy was found when SAP P11-4 was applied 3 months before FV (test D270–D90; control D270–D90, p = 0.70). SAP P11-4 treatment resulted in superior caries regression compared to either placebo or FV, and FV efficacy seems not to be affected by SAP P11-4. SAP P11-4 was found to be a safe and effective WSL treatment.

Arresting early childhood caries using silver and fluoride products – A randomised trial

ObjectiveThe aim of this randomised non-inferiority clinical trial was to compare the effectiveness of semi-annual (every six months) applications of 25 % silver nitrate (AgNO3) solution followed by 5 % sodium fluoride (NaF) varnish to semi-annual applications of 38 % silver diamine fluoride (SDF) solution in arresting early childhood caries (ECC). MethodsThree-year-old children with active cavitated carious lesions were recruited and randomly assigned to two intervention groups. Children in Group A received semi-annual applications of 25 % AgNO3 solution followed by 5 % NaF varnish on carious lesions. Children in Group B received semi-annual applications of 38 % SDF solution followed by a placebo varnish. One trained dentist assessed ECC status at baseline and in all follow-up examinations. An independent operator performed the interventions. The dentist, the children, and their caretakers were blinded to the intervention allocation. Data were analysed using a non-inferiority test. Group A’s non-inferiority would be accepted if the lower limit of the 95 % confidence interval (CI) for the difference in the mean number of arrested decayed surfaces (ds) was greater than −0.5. ResultsAt baseline, 1,070 children were recruited, and 535 children were assigned to each group. After 30 months, the mean arrested ds in Groups A (n = 447) and B (n = 433) were 3.7 ± 3.6 and 3.6 ± 3.7, respectively (p = 0.694). The difference in the mean arrested ds between the two groups was 0.088 (95 % CI: -0.351 to 0.526). ConclusionSemi-annual application of 25 % AgNO3 followed by 5 % NaF is at least as effective as the semi-annual application of 38 % SDF in arresting ECC. Clinical significanceSilver and fluoride products are effective in arresting caries. As a simple, non-invasive, and inexpensive strategy, it can be used in young children, elderly adults, and people with special needs.

Fluoride varnish for white spot lesion prevention during orthodontic treatment: results of a randomized controlled trial 1 year after debonding.

Topical fluorides are commonly recommended to prevent the development of white spot lesion (WSL) during treatment with fixed orthodontic appliances (FOAs), but the certainty of evidence is low, and long-term effects of fluoride preventive methods to reduce lesions seem to be rare. To evaluate the long-term effectiveness of professional applications of a fluoride varnish containing 1.5% ammonium fluoride in preventing WSL development in adolescents undergoing multi-bracket orthodontic treatment. We performed a randomized controlled trial in which 166 healthy adolescents (12-18 years) from three different clinics were enrolled and randomly allocated to a test or a placebo group. The randomization was performed by a computer program, generating sequence numbers in blocks of 15. The fluoride varnish or the non-fluoride placebo varnish was applied in a thin layer around the bracket base every sixth week during the course of the orthodontic treatment (mean duration 1.7 years). We scored the prevalence of WSL on the labial surfaces of the maxillary incisors, canines and premolars immediately after debonding (baseline) and approximately 1 year after debonding, from digital photos with aid of a four-step score. The examiners were not involved in the treatment of the patients and blinded for the group assignment. One hundred and forty-eight patients were available at debonding and 142 of them could be re-examined after 1 year (71 in the test and 71 in the placebo group). The 1-year attrition rate was 4.0%. On patient level, the prevalence of post-orthodontic WSLs (score ≥ 2) dropped by over 50% during the follow-up with no significant difference between the groups. On surface level, there were significantly fewer remaining WSLs in the test group compared with the placebo group (4.5% versus 10.4%; relative risk 0.44, 95% confidence interval 0.28-0.68). The compliance with fluoride toothpaste was not checked, and the patients' general dentists may have instigated additional risk-based preventive measures. No cost-benefit analysis was carried out. This follow-up study displayed a small beneficial long-term effect of fluoride varnish in reducing WSL development during treatment with FOA. NCT03725020. The protocol was not published before trial commencement.

Remineralization and fluoride uptake of white spot lesions under dental varnishes.

The aim of this study was to evaluate white spot lesion (WSL) remineralization and fluoride uptake by the application of fluoride varnishes directly onto artificial WSLs in vitro. MI varnish containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and 2.26% fluoride and Duraphat varnish containing 2.26% fluoride (no added calcium) were compared with a placebo varnish (no added calcium or fluoride). Two WSLs were prepared in enamel slabs and varnish applied to cover one of the two lesions. Each slab was immersed in artificial saliva for 14days at 37°C. Mineral content was determined using transverse microradiography and fluoride uptake using electron probe microanalysis. The data were statistically analysed using a linear mixed model. Both MI and Duraphat varnishes significantly remineralized the covered and uncovered WSLs when compared with the placebo varnish (P<0.001). The WSLs covered with varnish showed greater remineralization than those uncovered. MI varnish produced the highest level of remineralization and significantly greater fluoride uptake (0.44±0.08 wt%) compared with Duraphat (0.24±0.03 wt%) and the placebo varnish (0.06±0.05 wt%). Varnish containing fluoride and CPP-ACP was superior to varnish containing fluoride alone in promoting WSL remineralization and fluoride uptake.

Silver Diamine Fluoride Prevents Caries in Primary Teeth Superior to No Treatment, Placebo, or Fluoride Varnish

The effect of silver diamine fluoride in preventing caries in the primary dentition: a systematic review and meta-analysis. Oliveira BH, Rajendra A, Vietz-eenan A, Niederman R. Caries Res 2018;53(1):24-32. Government: National Institute on Minority Health and Health Disparities of the National Institutes of Health under award no. R01MD011526 and U24MD006964, and Patient-Centered Outcomes Research Institute (PCORI) Award (PCS-1609-36824). The Teacher Training Program of the University of the State of Rio de Janeiro (Programa de Capacitação Docente da Universidade do Estado do Rio de Janeiro-PROCAD UERJ) also supported this work. Systematic review with meta-analysis.

Protective Effect of 4% Titanium Tetrafluoride Varnish on Dentin Demineralization Using a Microcosm Biofilm Model

This study evaluated the effect of titanium tetrafluoride (TiF₄) varnish on the development of dentin carious lesions. Bovine root dentin samples were treated for 6 h with: (A) 4% TiF₄ varnish (2.45% F); (B) 5.42% sodium fluoride (NaF) varnish (2.45% F); (C) 2% chlorhexidine (CHX) gel – positive control; (D) placebo varnish; or (E) untreated – negative control (n = 4 × biological triplicate, n = 12). Treated dentin samples were exposed to human saliva mixed with McBain saliva (1:50) for the first 8 h in 24-well plates. Thereafter, the medium was removed, and McBain saliva containing 0.2% sucrose was applied for 16 h. From days 2 to 5, McBain saliva with sucrose was replaced daily (37°C, 5% CO₂). The demineralization was measured using transverse microradiography, while the effect on biofilm was analyzed using viability, extracellular polysaccharide (EPS), and lactic acid production assays. The data were statistically analyzed (p < 0.05). All treatments (fluorides and CHX) significantly reduced the biofilm viability compared to placebo varnish and negative control. However, none of them was able to reduce the colony-forming unit counting for total microorganism, total streptococci, and Streptococcus mutans. NaF significantly reduced the number of Lactobacillus sp. compared to negative control. No effect was seen on lactic acid production neither on EPS synthesis, except that CHX significantly reduced the amount of insoluble EPS. Both fluorides were able to reduce dentin demineralization compared to placebo varnish and negative control; TiF₄ had a better effect in reducing mineral loss and lesion depth than NaF. Therefore, TiF₄ varnish has the best protective effect on dentin carious lesion formation using this model.

Can TiF4 varnish or TiF4/NaF solution stain eroded and sound enamel?

ObjectivesThis study evaluated the staining potential of TiF4 varnish and TiF4/NaF solution on both sound and previously eroded enamel in vitro. MethodsOne hundred and eighty bovine enamel samples were polished; half of them remained sound and the other half was eroded (4 × 90 s each, using a 0.1% citric acid). Thereafter, the baseline color reading was performed (T0). The samples were then subdivided into the following treatments: TiF4 varnish (24,500 ppm F, 1 × 6 h), NaF varnish (24,500 ppm F, 1 × 6 h), placebo varnish (1 × 6 h), TiF4/NaF solution (500 ppm F, 6 × 1 min), Erosion Protection-Elmex® (500 ppm F, 6 × 1 min) and control (water, 6 × 1 min). Between the applications, the samples were exposed to artificial saliva for 30 min. The color changes were measured immediately after the applications (T1-T6) and after the exposure to artificial saliva (S1-S6) by using a spectrophotometer (Vita EasyShade®). The ΔE00, L*, a* and b* data were compared using 2-way ANOVA/Tukey (p < 0.05). ResultsTiF4 varnish induced significantly higher color change (ΔE00) compared to NaF and placebo varnishes on sound enamel immediately after application, but not after saliva exposure. TiF4/NaF solution induced lower ΔE00 values compared to control on sound enamel; however, no differences were found between TiF4/NaF and Elmex®. For eroded, no differences were seen between the tested varnishes and solutions. Both types of fluoride solutions increased the yellow appearance of enamel, while the varnishes did not. ConclusionsThe color changes induced by the experimental TiF4 products are similar to the commercial ones. Clinical significanceBoth TiF4 varnish and TiF4/NaF solution have shown staining potential similar to commercially available varnish (NaF) and solution (Elmex®) on sound and eroded enamel. These findings support the conduction of clinical trials, which, in the future, may lead to the commercialization of these products.

Randomized Trial of Silver Nitrate with Sodium Fluoride for Caries Arrest.

The aim of this noninferiority double-blind randomized clinical trial was to compare the effectiveness of the topical semiannual application of a 25% silver nitrate (AgNO3) solution followed by a 5% sodium fluoride (NaF) varnish with that of a 38% silver diamine fluoride (SDF) solution in arresting caries among preschool children. Healthy 3-y-old children with active dentine carious lesions were randomly allocated to 2 groups via computer-generated random numbers. Lesions in group A received applications of a 25% AgNO3 solution followed by a 5% NaF varnish semiannually (every 6 mo). Lesions in group B received semiannual applications of a 38% SDF solution followed by a placebo varnish. A trained examiner recorded the status of caries and oral hygiene at baseline and during follow-up examinations. The examiner, children, and their caretakers were blinded to the intervention allocation. This study adopted an intention-to-treat analysis. A noninferiority test was conducted for the data analysis. Group A's noninferiority was accepted if the lower limit of the 95% CI for the difference in the mean number of arrested surfaces was >-0.5. A total of 1,070 children were recruited at baseline, with 535 children in each group. After 18 mo, the mean ± SD number of arrested surfaces was 3.3 ± 3.4 in group A (n = 484) and 3.2 ± 3.5 in group B (n = 476; P = 0.664). The difference in the mean number of arrested surfaces between the groups was 0.092 (95% CI, -0.322 to 0.505). Apart from black staining on the arrested lesions, no other significant side effect was observed. A semiannual application of 25% AgNO3 followed by 5% NaF is no worse than a 38% SDF in arresting dentine caries among preschool children over 18 mo. The Hong Kong Research Grants Council (GRF 17107315) funded this trial, which was registered at ClinicalTrials.gov (NCT02019160). This randomized clinical trial found that silver nitrate solution followed by sodium fluoride varnish is effective in arresting dentine caries among preschool children. As silver nitrate followed by sodium fluoride is a noninvasive and simple protocol, it can be an alternative strategy to manage dental caries among young children, especially in countries where silver diamine fluoride is not available.

TiF4 and NaF varnishes induce low levels of apoptosis in murine and human fibroblasts through mitochondrial Bcl-2 family and death receptor signalling

ObjectivesThis study evaluated the level and mechanism of apoptosis in human gingival fibroblasts (HGF) and murine fibroblasts (NIH/3T3) treated with a titanium tetrafluoride (TiF4) varnish compared those treated with a sodium fluoride (NaF) varnish. MethodsCells were treated with a TiF4, NaF (both 2.45%F) or placebo varnish for 6 h and were then examined using the TUNEL method. The activities of caspase-3, -8 and -9 were assessed. cDNA for Bax, Bad, Bcl-2 and Fas-L was amplified by quantitative PCR. Bax, Bcl-2 and Fas-L were further detected by western blot analysis. ResultsBoth fluorides similarly increased the percentage of apoptosis, while they failed to activate caspases. The Bax/Bcl-2 gene expression ratio was not altered by either fluoride treatment regardless of the type of cell. NaF varnish increased the amplification of the Fas-L gene in NIH/3T3 and HGF cells, while treatment with the TiF4 varnish resulted in a lower Bad/Bcl-2 expression ratio compared to that of the control for NIH/3T3 cells, but not for HGF cells. No effect of the fluorides was detected in the protein analysis. ConclusionsNaF and TiF4, at the studied conditions, similarly induce a low level of apoptosis, with consequent modest activation of the Bcl-2 and Fas-l-dependent signalling pathways. Generally, HGF cells are more susceptible to the fluoride effect than NIH/3T3 cells.

Effect of TiF4 varnish on microbiological changes and caries prevention: in situ and in vivo models.

The aim of this study was to evaluate microbiological changes, oral soft tissue toxicity, and caries-preventive effect of an experimental titanium tetrafluoride (TiF4) varnish compared with a commercially available fluoride varnish (NaF), using in situ and in vivo models. The treatment groups were the following: TiF4 varnish (experimental varnish), Duraphat® (fluoride positive control), placebo varnish (no fluoride), and no treatment (negative control). The varnishes were applied once over the enamel surface using a microbrush. For the in vivo study, 48 Wistar rats were infected with Streptococcus sobrinus 6715, received a treatment, and were submitted to a cariogenic challenge. After 4weeks, S. sobrinus, oral soft tissue toxicity, presence, and severity of caries were evaluated. For the in situ study, 12 volunteers took part in this randomized crossover, double-blind study performed in four phases of 14days each. They used intraoral appliances containing four enamel specimens that received the varnish according treatment group. After 24h, the varnish was removed and plaque accumulation was allowed. A 20% sucrose solution was dripped over the enamel blocks (10×/day for 5min each). Total streptococci, S. mutans, Lactobacillus, Candida spp. counts, and presence of white spot lesions were evaluated. Lesion depth was also quantified by micro-CT. For the in vivo study, the fluoride (F-varnishes) showed a statistically significant reduction in the percentage of S. sobrinus compared to the negative control (p < 0.05). Toxicological analysis revealed no abnormalities in oral tissues of rats from all groups, and both F-varnishes reduced the number and severity of caries lesions, without significant differences (p < 0.05). No statistical differences in microbiological counts were seen for the in situ experiment (p > 0.05). However, the specimens treated with TiF4 exhibited lower percentage of white spot lesions and the lesion depth was significantly reduced by F-varnishes (p < 0.05). F-varnishes showed reduction in the percentage of S. sobrinus in vivo, no oral soft tissue toxicity, and a caries-preventive effect in vivo and in situ. NaF varnish is largely used due its capacity to form CaF2-like layer on enamel. Therefore, development of studies focused on other fluoride compounds such as a TiF4 varnish, which may have greater efficacy than NaF against tooth demineralization, is important.

The Effect of Silver Diamine Fluoride in Preventing Caries in the Primary Dentition: A Systematic Review and Meta-Analysis

Objectives: To investigate whether silver diamine fluoride (SDF) is effective in preventing new caries lesions in primary teeth when compared to placebo or active treatments. Methods: Systematic review (CRD42016036963) of controlled clinical trials. Searches were performed in 9 electronic databases, 5 registers of ongoing trials, and reference lists of identified review articles. Two researchers carried out data extraction and quality appraisal independently. The primary outcome was the difference in caries increment (decayed, missing, and filled surfaces or teeth – dmfs or dmft) between SDF and control groups. These differences were pooled as weighted mean differences (WMD) and prevented fractions (PF). Results: Searches yielded 2,366 unique records; 6 reports of 4 trials that randomized 1,118 and analyzed 915 participants were included. Two trials compared SDF to no treatment, 1 compared SDF to placebo and sodium fluoride varnish (FV), and 1 compared SDF to high-viscosity glass ionomer cement (GIC). All studies had at least 1 domain with unclear or high risk of bias. After 24 months of follow-up, in comparison to placebo, no treatment, and FV, SDF applications significantly reduced the development of new dentin caries lesions (placebo or no treatment: WMD = –1.15, PF = 77.5%; FV: WMD = –0.43, PF = 54.0%). GIC was more effective than SDF after 12 months of follow-up but the difference between them was not statistically significant (WMD, dmft: 0.34, PF: –6.09%). Conclusion: When applied to caries lesions in primary teeth, SDF compared to no treatment, placebo or FV appears to effectively prevent dental caries in the entire dentition. However, trials specifically designed to assess this outcome are needed.

Effect of a Titanium Tetrafluoride Varnish in the Prevention and Treatment of Carious Lesions in the Permanent Teeth of Children Living in a Fluoridated Region: Protocol for a Randomized Controlled Trial.

BackgroundTitanium tetrafluoride (TiF4) has regained interest due to new formulations that have been shown to be more effective against tooth demineralization than sodium fluoride (NaF) formulations in vitro and in situ.ObjectiveThe aim of this study is to evaluate the effect of two types of varnishes (4% TiF4 and a commercial 5% NaF) on the prevention of carious lesions and the treatment of noncavitated enamel carious lesions in the permanent teeth of children living in a fluoridated area.MethodsThis randomized, controlled, parallel and single-blind clinical trial involves 63 children, 6-7 years old, living in Bauru, São Paulo, Brazil. Children were selected according to their caries activity (ie, presence of at least 1 tooth with a Nyvad score of 1) and randomly divided into the following treatment categories: 4% TiF4 varnish (2.45 % F-, pH 1, FGM); 5% NaF varnish (2.26% F-, pH 5, Duraphat, Colgate) and control (placebo varnish, pH 5, FGM). The varnishes will be applied on all permanent teeth, once a week for 4 weeks and they will be reapplied only once 6 and 12 months after the study begins. Two calibrated examiners will carry out the clinical examination (International Caries Detection and Assessment System [ICDAS] and Nyvad indexes, kappa>.8) at baseline, before the first application, after the 1st, 6th, 12th, and 18th month of the study begins. Furthermore, quantitative fluorescence changes will be measured using Quantitative Light-Induced Fluorescence (QLF). The degree of patient satisfaction with the treatment will also be computed. The data will undergo statistical analysis (P<.05).ResultsThis ongoing study is funded by funding agencies from Brazil (São Paulo Research Foundation, FAPESP-015/14149-1, and National Council for Scientific and Technological Development, CNPq-401313/2016-6). We expect to confirm the efficacy of TiF4 on the prevention and treatment of carious lesions by comparing it to NaF varnish. The subjects are under 1 month evaluation and the dropout was about 8%. No differences between the treatments have been detected at the first month so far (P>.05).ConclusionsIf our hypothesis is confirmed, TiF4 varnish can be marketed and applied at the individual level and used in community programs to control dental caries.Trial RegistrationBrazilian Clinical Trials Registry: RBR-5VWJ4Y; http://www.ensaiosclinicos.gov.br/rg/?q=RBR-5VWJ4Y (Archived by WebCite at http://www.webcitation.org/6wUurEnm7)