Comparative assessment of fluoride varnish and fluoride film for remineralization of postorthodontic white spot lesions in adolescents and adults over a 6-month period: A single-center, randomized controlled clinical trial

Introduction

The objective of this 3-arm parallel randomized trial was to evaluate the effects of a fluoride varnish and a fluoride film on the remineralization of white spot lesions around orthodontic brackets after orthodontic treatment.

Methods

Patients who had recently completed orthodontic treatment were randomly assigned to the varnish, film, and control groups. Eligibility criteria included age of 12 to 25 years, good general health, and at least 1 maxillary anterior tooth with a white spot lesion. The primary outcome was the decrease in the lesion volume of each patient after 6 months of treatment; fluorescence loss and area were the secondary outcome measures. Randomization was accomplished according to a computer-generated randomization schedule, and allocation concealment was achieved with nontransparent concealed envelopes. Blinding was applicable for the treatments only. The test groups received fluoride varnish or film treatment once a month for 6 months, and the control group received a placebo treatment. All patients received oral hygiene education and were required to use fluoride toothpaste daily. Quantitative light-induced fluorescence images were taken at baseline and at the 3-month and 6-month follow-ups. A mixed-effects linear model was used to analyze quantitative light-induced fluorescence parameters with confounders integrated into the model.

Result

Two hundred forty patients (mean age, 16.9 years; range, 12-25 years) with 597 teeth with a white spot lesion were randomized 1:1:1 to the varnish, film, and control groups. Baseline demographics were similar between groups, and 29 patients were lost to follow-up. The primary analysis was carried out on a per-protocol basis involving 72 patients in the control group, 69 patients in the varnish group, and 70 patients in the film group who completed the study. The product of fluorescence loss and lesion area values were statistically associated with time (estimate, −4.58; 95% confidence interval [CI], −5.84 to −3.31; P <0.0001), and a significant decrease in the product of fluorescence loss and lesion area was observed in all groups after 6 months with each treatment. The interaction between group and time in the statistical analysis indicated that the product of fluorescence loss and lesion area values of the 3 groups followed different trends over time. Further pair-wise comparisons showed that the decreases in the 2 test groups were significantly greater than those in the control group (varnish vs control: estimate, −11.83; 95% CI, −15.39 to −8.26; P <0.0001; film vs control, estimate: −7.72; 95% CI, −11.34 to 4.10; P <0.0001) in the analysis for 6 months. In addition, the decrease in the varnish group was significantly greater than that in the film group (estimate, 4.11; 95% CI, 0.48 to 7.73; P = 0.0266) in the analysis for 6 months. No serious adverse effects associated with the use of the tested varnish, film, or placebo occurred.

Conclusions

After removal of the orthodontic brackets, some natural remineralization of white spot lesions occurred, and daily use of fluoride toothpaste may be helpful for this process. However, not all patients experienced this remineralization, and treatment with fluoride varnish or fluoride film induced greater remineralization of white spot lesions. In addition, our results suggest that fluoride varnish may be slightly more effective than fluoride film. However, further similar clinical trials with more patients are needed to definitively determine which fluoride treatment is most effective.

Registration

This trial was registered on the Chinese Clinical Trial Register, number ChiCTR-TRC-13003764.

Protocol

The details of the trial protocol are posted online at: apps.who.int/trialsearch/Trial.aspx?TrialID=ChiCTR-TRC-13003764 .

Highlights

  • Patients with white spot lesions were randomized to varnish, film, and control groups.

  • Some natural remineralization occurs after bracket removal.

  • Daily brushing with fluoride toothpaste aids remineralization.

  • Fluoride varnish or film induces greater remineralization.

  • Fluoride varnish may be slightly more effective than fluoride film.

Although significant advances have been made in orthodontic materials and techniques, enamel demineralization around orthodontic brackets continues to negatively impact the health and esthetics of affected teeth. The prevalence of white spot lesions (WSLs) in patients undergoing orthodontic treatment has been reported to be between 2% and 96%. The banding and bonding of orthodontic appliances to teeth increases the number of sites conducive to plaque retention, and as a result, oral hygiene becomes more difficult. This encourages lower plaque pH adjacent to orthodontic brackets, which hinders remineralization and can lead to decalcification of enamel. Patients with poor dietary and oral hygiene practices can develop WSLs within 4 weeks after the start of orthodontic treatment. Some WSLs may remineralize and return to normal or at least to a visually acceptable appearance if patients practice good oral hygiene. However, WSLs also can persist despite these practices, resulting in an esthetically unacceptable result and even permanent damage such as cavitary caries in affected teeth. In severe cases, restorative treatment via destructive operations may be required.

Overall management of WSLs involves methods to both prevent demineralization and encourage remineralization of existing lesions. Supplemental sources of fluoride such as fluoride varnish are often recommended. One study reported that application of a fluoride varnish can reduce enamel demineralization by 44.3% in orthodontic patients. For existing WSLs, fluorapatite formation resulting from either monthly administration of a high dose of fluoride or continually administered low doses of fluoride can be advantageous in reducing enamel decalcification during treatment involving fixed appliances.

Supplemental sources of fluoride may be recommended to orthodontic patients. However, based on the literature, there is a lack of reliable evidence to support the effectiveness of remineralizing agents for the treatment of postorthodontic WSLs.

Specific objectives

This randomized, examiner-blinded in-vivo study aimed to evaluate the effects of a fluoride varnish (Duraphat; Colgate-Palmolive, New York, NY; 5% sodium fluoride) and a fluoride film (Sheer; CAO Group, West Jordan, Utah; 5% acidulated sodium fluoride) on WSLs around orthodontic brackets.

Material and methods

Trial design and changes after trial commencement

This was a single-center, randomized, active-controlled, examiner-blinded parallel trial with a 1:1:1 allocation ratio.

Participants, eligibility criteria, and settings

At the beginning of the trial, written consent was provided by each patient who had recently finished orthodontic treatment. Then patients who had recently finished orthodontic treatment were screened at the West China Hospital of Stomatology at Sichuan University in Chengdu, China, and 240 eligible patients (597 teeth) were recruited by the first author (T.H.) from December 2011 to May 2012. Follow-up examinations were conducted from January 2012 to December 2012. Before the study, written approval was obtained from the ethics committee of the State Key Laboratory of Oral Diseases at Sichuan University. The following selection criteria were applied: age, 12 to 25 years; good general health; and at least 1 maxillary anterior tooth with a WSL on the buccal surface. Patients were excluded if they had an oral ulcer, ulcerous gingivitis, or acute bronchial asthma. Pregnant or nursing women were excluded. Patients with a history of allergic reactions or severe adverse effects after using fluoride varnish, fluoride film, or other dental products were excluded. No changes were made after trial commencement.

The trial was registered on the Chinese Clinical Trial Register, number ChiCTR-TRC-13003764, and the details of the protocol were posted online at: apps.who.int/trialsearch/Trial.aspx?TrialID=ChiCTR-TRC-13003764 .

Interventions

Eligible patients were given toothbrushing guidance and oral hygiene education by an author (D.H.). Patients were instructed to brush their teeth twice a day using the same commercial fluoride toothpaste and toothbrush during a 4-week pretest washout period. Then all teeth with a WSL of the eligible patients received fluoride varnish or film treatment, and the control patients received a placebo on the treatment day every month. All patients continued to use the same fluoride toothpaste and toothbrush twice a day on the nontreatment days and were required to return every month to receive treatment.

The fluoride varnish (Duraphat) contained 5% sodium fluoride as the active ingredient as well as adjuvant materials including alcohol, beeswax, gum-mastic, glucide, and flavoring agent. The fluoride film (Sheer) contained 5% acidulated sodium fluoride as the active ingredient. The placebos were fluoride-free deliquescent toothpastes prepared by the preventive department of West China Hospital of Stomatology and contained no active ingredients. The teeth of the patients in all groups received treatment once a month.

At baseline and after 3 and 6 months, quantitative light-induced fluorescence (QLF) images were taken of all maxillary anterior teeth with WSLs by an author (T.H.). Each tooth was dried for 5 seconds with compressed air before imaging. The images were acquired using a custom-built camera system. The equipment comprised a high-resolution 3 charge-coupled device camera (M91P; Jai, Copenhagen, Denmark) fitted with a 16-mm f/1.4 lens (Pentax, Slough, United Kingdom) and a long-pass yellow filter (495 nm; Schott, Stafford, United Kingdom). The light source was a 150-W fiber-optic unit with variable illumination (Fiber-Lite, PL-900; Dolan-Jenner, Boxborough, Mass) with a blue band-pass filter (370-nm peak; Dolan-Jenner). Illumination was passed through a fiber-optic cable to a ring illuminator (MA3172; Dolan-Jenner) attached to the camera. The whole assembly was mounted on a geometry-stabilizing unit that enabled accurate repositioning at each visit.

The images were acquired using the proprietary software QLF Patient, version 3.0.3.30 (Inspektor Research Systems, Amsterdam, The Netherlands), with video repositioning active and a grab level of 0.95 set for the 3-month and 6-month images. The acquired images were stored on the hard drive of a personal computer, and a unique subject identifier was allocated. The images were analyzed by an examiner (W.Y.) using the software QLF 2.00 g (Inspektor Research Systems). Data were exported as text files and imported into Excel (Microsoft, Redmond, Wash) using a custom macro.

Outcomes (primary and secondary) and any changes after trial commencement

QLF has 3 reportable metrics: ΔF (%), area (mm 2 ), and ΔQ (mm 2 × %). ΔF is the percentage of fluorescence loss comparing sound enamel with an identified lesion. ΔF is thresholded to 5%, indicating that fluorescence loss less than 5% was considered noise. Area is calculated as pixels considered by the analysis software to represent demineralized enamel (ie, those with fluorescence loss of 5% or more). ΔQ is the product of ΔF and area and indicates the volume of the lesion.

All maxillary anterior teeth with a WSL but no cavitary caries were included in the study. We took into account average QLF parameters for each patient. The primary outcome was the change in ΔQ for each patient at a 5% threshold after 6 months of product use. That was a site-level measurement, and treatment effects were estimated after 3 and 6 months. The secondary outcomes included ΔF and area measured on a site-level basis, and the treatment effects were estimated in the same way.

To minimize contamination, the unit of randomization and analysis was the whole patient unit, instead of the tooth unit. The unit was achieved by obtaining average QLF measurements for each tooth (eg, if 1 patient had 3 teeth with WSLs, we averaged the values for the 3 teeth). We also considered that the number of teeth with a WSL could affect the results; thus, we included the number of teeth with a WSL as a covariate.

Sample size calculation

The sample size was determined based on a sample size estimation formula for a case control study that assumed a 2-tailed test at α = 0.05, a general statistical power of β = 0.1, a difference between the test and control groups’ means of δ = 10, and a within-group standard deviation of σ = 15. These variables were obtained from a pilot QLF study. The result of the estimation formula showed that a minimum of 48 subjects was needed, and we recruited 80 patients for each group.

Interim analyses and stopping guidelines

Not applicable.

Randomization (random number generation, allocation concealment, implementation)

Randomization was accomplished using Excel (Microsoft) software for simple randomization. The schedule was prepared in Excel using first the key command “=RANDBETWEEN(1,3)” to make a schedule with 270 numbers. Then the command “=COUNTIF” was used to count how many ones, twos, and threes were in each list (eg, 85 “1’s,” 92 “2’s,” and 93 “3’s”). Finally, the last 5 “1’s,” the last 12 “2’s,” and the last 13 “3’s” were deleted. The final randomized schedule had 80 “1’s,” 80 “2’s,” and 80 “3’s.” After the schedule was made, group assignment information was written on cards and concealed in nontransparent envelopes with sequential numbers on the outside to achieve allocation concealment. The generation of a random allocation sequence and the preparation of the cards and envelopes were finished well before patient recruitment by an author (Y.Z.). Baseline QLF images were stored on an encrypted computer with only the randomized number but no group allocation. An author (X.L.) was responsible for opening each envelope in sequence and assigning the screened participants to the intervention groups.

Blinding

Both the doctor (Y.D.) in charge of product application and the patients at the time of treatment knew which treatment was applied. However, the patients did not know whether the product they received contained an active ingredient. Additionally, the examiners who conducted the imaging acquisition and the analysis of the images were blinded to the intervention allocation.

Statistical analysis

The data were analyzed by a statistician (N.Z.) from the statistical department of the School of Public Health at Sichuan University. The missing outcomes were excluded from analysis using a per-protocol analysis model. A mixed-effects linear model was used to analyze the QLF parameters (ΔQ, area, and ΔF), and restricted maximum likelihood was adopted for parameter estimation. The mixed model is a 2-level model for repeated measurable data. The second level is patient, and the first level is the time at which the data for each patient were measured. The random effects in the model were the differences among patients. Although the baseline ΔQ values of the 3 groups showed no significant difference ( P = 0.4675, analysis of variance), the baseline values of ΔQ and the number of teeth with a WSL in each patient appeared to be different ( P = 0.0509, analysis of variance). Thus, in our model, the average ΔQ value for each patient was the dependent variable, and the base value, group, time, interactions between group and time, and number of teeth with a WSL were the independent variables. In the model, we mainly wanted to determine whether each treatment would affect the ΔQ value and whether the ΔQ value would change as time passed. The unstructured type was selected as the variance-covariance structure for the random effects. The results were considered statistically different at P <0.05. ΔF and area were analyzed in the same way as ΔQ. Statistical analysis was performed using a software program (version 9.1; SAS, Cary, NC).

Material and methods

Trial design and changes after trial commencement

This was a single-center, randomized, active-controlled, examiner-blinded parallel trial with a 1:1:1 allocation ratio.

Participants, eligibility criteria, and settings

At the beginning of the trial, written consent was provided by each patient who had recently finished orthodontic treatment. Then patients who had recently finished orthodontic treatment were screened at the West China Hospital of Stomatology at Sichuan University in Chengdu, China, and 240 eligible patients (597 teeth) were recruited by the first author (T.H.) from December 2011 to May 2012. Follow-up examinations were conducted from January 2012 to December 2012. Before the study, written approval was obtained from the ethics committee of the State Key Laboratory of Oral Diseases at Sichuan University. The following selection criteria were applied: age, 12 to 25 years; good general health; and at least 1 maxillary anterior tooth with a WSL on the buccal surface. Patients were excluded if they had an oral ulcer, ulcerous gingivitis, or acute bronchial asthma. Pregnant or nursing women were excluded. Patients with a history of allergic reactions or severe adverse effects after using fluoride varnish, fluoride film, or other dental products were excluded. No changes were made after trial commencement.

The trial was registered on the Chinese Clinical Trial Register, number ChiCTR-TRC-13003764, and the details of the protocol were posted online at: apps.who.int/trialsearch/Trial.aspx?TrialID=ChiCTR-TRC-13003764 .

Interventions

Eligible patients were given toothbrushing guidance and oral hygiene education by an author (D.H.). Patients were instructed to brush their teeth twice a day using the same commercial fluoride toothpaste and toothbrush during a 4-week pretest washout period. Then all teeth with a WSL of the eligible patients received fluoride varnish or film treatment, and the control patients received a placebo on the treatment day every month. All patients continued to use the same fluoride toothpaste and toothbrush twice a day on the nontreatment days and were required to return every month to receive treatment.

The fluoride varnish (Duraphat) contained 5% sodium fluoride as the active ingredient as well as adjuvant materials including alcohol, beeswax, gum-mastic, glucide, and flavoring agent. The fluoride film (Sheer) contained 5% acidulated sodium fluoride as the active ingredient. The placebos were fluoride-free deliquescent toothpastes prepared by the preventive department of West China Hospital of Stomatology and contained no active ingredients. The teeth of the patients in all groups received treatment once a month.

At baseline and after 3 and 6 months, quantitative light-induced fluorescence (QLF) images were taken of all maxillary anterior teeth with WSLs by an author (T.H.). Each tooth was dried for 5 seconds with compressed air before imaging. The images were acquired using a custom-built camera system. The equipment comprised a high-resolution 3 charge-coupled device camera (M91P; Jai, Copenhagen, Denmark) fitted with a 16-mm f/1.4 lens (Pentax, Slough, United Kingdom) and a long-pass yellow filter (495 nm; Schott, Stafford, United Kingdom). The light source was a 150-W fiber-optic unit with variable illumination (Fiber-Lite, PL-900; Dolan-Jenner, Boxborough, Mass) with a blue band-pass filter (370-nm peak; Dolan-Jenner). Illumination was passed through a fiber-optic cable to a ring illuminator (MA3172; Dolan-Jenner) attached to the camera. The whole assembly was mounted on a geometry-stabilizing unit that enabled accurate repositioning at each visit.

The images were acquired using the proprietary software QLF Patient, version 3.0.3.30 (Inspektor Research Systems, Amsterdam, The Netherlands), with video repositioning active and a grab level of 0.95 set for the 3-month and 6-month images. The acquired images were stored on the hard drive of a personal computer, and a unique subject identifier was allocated. The images were analyzed by an examiner (W.Y.) using the software QLF 2.00 g (Inspektor Research Systems). Data were exported as text files and imported into Excel (Microsoft, Redmond, Wash) using a custom macro.

Outcomes (primary and secondary) and any changes after trial commencement

QLF has 3 reportable metrics: ΔF (%), area (mm 2 ), and ΔQ (mm 2 × %). ΔF is the percentage of fluorescence loss comparing sound enamel with an identified lesion. ΔF is thresholded to 5%, indicating that fluorescence loss less than 5% was considered noise. Area is calculated as pixels considered by the analysis software to represent demineralized enamel (ie, those with fluorescence loss of 5% or more). ΔQ is the product of ΔF and area and indicates the volume of the lesion.

All maxillary anterior teeth with a WSL but no cavitary caries were included in the study. We took into account average QLF parameters for each patient. The primary outcome was the change in ΔQ for each patient at a 5% threshold after 6 months of product use. That was a site-level measurement, and treatment effects were estimated after 3 and 6 months. The secondary outcomes included ΔF and area measured on a site-level basis, and the treatment effects were estimated in the same way.

To minimize contamination, the unit of randomization and analysis was the whole patient unit, instead of the tooth unit. The unit was achieved by obtaining average QLF measurements for each tooth (eg, if 1 patient had 3 teeth with WSLs, we averaged the values for the 3 teeth). We also considered that the number of teeth with a WSL could affect the results; thus, we included the number of teeth with a WSL as a covariate.

Sample size calculation

The sample size was determined based on a sample size estimation formula for a case control study that assumed a 2-tailed test at α = 0.05, a general statistical power of β = 0.1, a difference between the test and control groups’ means of δ = 10, and a within-group standard deviation of σ = 15. These variables were obtained from a pilot QLF study. The result of the estimation formula showed that a minimum of 48 subjects was needed, and we recruited 80 patients for each group.

Interim analyses and stopping guidelines

Not applicable.

Randomization (random number generation, allocation concealment, implementation)

Randomization was accomplished using Excel (Microsoft) software for simple randomization. The schedule was prepared in Excel using first the key command “=RANDBETWEEN(1,3)” to make a schedule with 270 numbers. Then the command “=COUNTIF” was used to count how many ones, twos, and threes were in each list (eg, 85 “1’s,” 92 “2’s,” and 93 “3’s”). Finally, the last 5 “1’s,” the last 12 “2’s,” and the last 13 “3’s” were deleted. The final randomized schedule had 80 “1’s,” 80 “2’s,” and 80 “3’s.” After the schedule was made, group assignment information was written on cards and concealed in nontransparent envelopes with sequential numbers on the outside to achieve allocation concealment. The generation of a random allocation sequence and the preparation of the cards and envelopes were finished well before patient recruitment by an author (Y.Z.). Baseline QLF images were stored on an encrypted computer with only the randomized number but no group allocation. An author (X.L.) was responsible for opening each envelope in sequence and assigning the screened participants to the intervention groups.

Blinding

Both the doctor (Y.D.) in charge of product application and the patients at the time of treatment knew which treatment was applied. However, the patients did not know whether the product they received contained an active ingredient. Additionally, the examiners who conducted the imaging acquisition and the analysis of the images were blinded to the intervention allocation.

Statistical analysis

The data were analyzed by a statistician (N.Z.) from the statistical department of the School of Public Health at Sichuan University. The missing outcomes were excluded from analysis using a per-protocol analysis model. A mixed-effects linear model was used to analyze the QLF parameters (ΔQ, area, and ΔF), and restricted maximum likelihood was adopted for parameter estimation. The mixed model is a 2-level model for repeated measurable data. The second level is patient, and the first level is the time at which the data for each patient were measured. The random effects in the model were the differences among patients. Although the baseline ΔQ values of the 3 groups showed no significant difference ( P = 0.4675, analysis of variance), the baseline values of ΔQ and the number of teeth with a WSL in each patient appeared to be different ( P = 0.0509, analysis of variance). Thus, in our model, the average ΔQ value for each patient was the dependent variable, and the base value, group, time, interactions between group and time, and number of teeth with a WSL were the independent variables. In the model, we mainly wanted to determine whether each treatment would affect the ΔQ value and whether the ΔQ value would change as time passed. The unstructured type was selected as the variance-covariance structure for the random effects. The results were considered statistically different at P <0.05. ΔF and area were analyzed in the same way as ΔQ. Statistical analysis was performed using a software program (version 9.1; SAS, Cary, NC).

Only gold members can continue reading. Log In or Register to continue

Apr 4, 2017 | Posted by in Orthodontics | Comments Off on Comparative assessment of fluoride varnish and fluoride film for remineralization of postorthodontic white spot lesions in adolescents and adults over a 6-month period: A single-center, randomized controlled clinical trial
Premium Wordpress Themes by UFO Themes