White spot lesion remineralization by sugar-free chewing gum containing bio-available calcium and fluoride: A double-blind randomized controlled trial

Abstract

Objectives

To assess the effect of chewing gum containing phosphoryl oligosaccharides of calcium (POs-Ca) and fluoride on white spot lesion (WSL) remineralization in comparison with POs-Ca or placebo (control) chewing gums, in double- blind, randomized, controlled trial.

Methods

Thirty-seven healthy subjects, who had at least one WSL, with an ICDAS score of 2 or 1, were recruited for this study. The subjects were randomly divided into three groups (control, POs-Ca, POs-Ca + F) and chewed two slabs of each gum three times every day for 3 months. WSLs were assessed using ICDAS criteria and optical boundary depth (BD) by optical coherence tomography (OCT) system at a monthly recall. Data were analyzed by Wilcoxon rank-sum test and Wilcoxon signed rank test with Bonferroni corrections at 0.05 significance level.

Results

Visual score changes from ICDAS score 2 to score 1 over the course of the study were observed; control (30%), POs-Ca (48%) and POs-Ca + F (45%). Unlike the control gum, chewing POs-Ca and POs-Ca + F gums resulted in significant changes in the mean value of BD over the 3 months course of the study (p < 0.05). There was a significant difference in mean value of BD after first month between POs-Ca + F and control groups (p < 0.05).

Conclusions

This study highlighted the importance of calcium and fluoride ion bioavailability in the reinforcement of demineralized enamel lesions by chewing gums. Furthermore, adding fluoride to POs-Ca might speed up the remineralization progress on natural WSL.

Introduction

White spot lesion (WSL) is an initial non-cavitated enamel carious lesion that has reached the stage, where the subsurface mineral loss has produced changes in the optical properties of enamel such that these are visibly detectable as a loss of translucency, resulted in a white appearance of the enamel surface . According to the minimal intervention (MI) concept, non-cavitated lesions such as enamel WSL should be managed initially by remineralization techniques.

It has been reported that substances containing bioavailable calcium such as casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), which increases the concentration of calcium and phosphate ions, have potential for enhancement of the remineralization of subsurface lesions of enamel . Also phosphoryl oligosaccharides of calcium (POs-Ca), a highly soluble calcium material prepared from phosphoryl oligosaccharides (POs), were found to remineralize enamel lesions effectively in a previous in situ study . On the other hand, remineralization would also be accelerated or enhanced by the effect of fluoride . There is substantial evidence on the effectiveness of topical fluoride in the form of mouthwash, gel or varnish, as an agent for preventing caries and promoting remineralization of early lesions .

Sugar-free chewing gums may be an effective vehicle for bioavailable compounds such as calcium promoting enamel remineralization, while exerting an anticariogenic effect through the stimulation of saliva . Recently, manufacturers have been adding calcium and fluoride in various forms to enhance the potential anti-cariogenic and remineralization potential of gums .

It is well known that early diagnosis of the enamel caries lesions may allow the health care provider to implement non-invasive strategies to reverse the lesion. Visual inspection is one of the most common diagnostic methods in lesion assessment. The International Caries Detection and Assessment System (ICDAS), based on visual examination, has been introduced as a novel system to diagnose dental caries . Also, various optical methods have been explored to detect caries such as DIAGNODent and quantitative light induced fluorescence (QLF) since optical properties of enamel change during demineralization . Introduction of optical coherence tomography (OCT), which is a noninvasive and nondestructive, real-time high-resolution cross-sectional imaging system that can visualize the internal structures , has brought recent advancements in the field of diagnostic sciences . In dental literature, several in vitro and in vivo studies have utilized OCT to assess enamel demineralization and remineralization . Nevertheless, no single clinical evaluation provides adequate reliability for detection of demineralization and remineralization of enamel in WSL; therefore, it may be beneficial to combine at least two detection methods together for a clinical trial.

Until now, no randomized, controlled trial study has reported on the effect of chewing gum containing both bioavailable calcium and fluoride on enamel remineralization in vivo . The aim of this double-blind, randomized, controlled trial study was to assess the effect of chewing gum containing POs-Ca and fluoride on natural WSL remineralization in comparison with POs-Ca or placebo (control) chewing gums. The null hypothesis was that there were no differences in the degree of enamel remineralization of subsurface lesions between the three chewing gums.

Materials and methods

Study design and subject recruitment

Thirty-seven healthy subjects (median age: 26 year) were recruited following obtaining ethical approval for the study from the Ethics Committee of the Tokyo Medical and Dental University and signing the informed consent forms. Each of the volunteers completed the medical history forms and underwent intraoral examination for caries experience. For inclusion in the study, the subjects were required to have at least one WSL, with an ICDAS score of 2 or 1 as described below . Exclusion criteria included smoking, evidence of poor oral health including periodontal disease, recent professional fluoride therapy (<2 weeks), uptake of fluoridated water or any medication that could affect oral flora, and pregnancy. Each subject had between one and eleven WSL(s) with a total of 124 WSLs examined throughout the course of this study, as described in Fig. 1 .

Fig. 1
Participant disposition for the randomized control trial. Thirty-seven healthy subjects were recruited. After the intraoral examination, 10 subjects were excluded because of trismus or under orthodontic treatment or bleach treatment.

This clinical trial was based on a double-blind, randomized, controlled design with three sugar-free gums. One of the gums was a placebo sugar-free chewing gum without POs-Ca (Ezaki Glico, Osaka, Japan) and the other two contained 2.5 wt% POs-Ca or 2.5% POs-Ca and 1.2% fluoride-containing green tea extract, namely POs-Ca and POs-Ca + F (Ezaki Glico) ( Table 1 ). The placebo and intervention chewing gums were identical in appearance, taste and smell without any observable differences. The chewing gum slabs were received in code-labelled packages stored at room temperature. The codes were randomly assigned by a controller and remained unknown to the volunteers and operators until all remineralization data had been obtained. The subjects were randomly divided into three groups and chewed two slabs of each gum three times every day (at 8:00 a.m., 12:00 p.m. and 5:00 p.m.) for 20 min each time. Each subject followed this regimen for 3 months and attended a monthly review appointment. No alterations were made to the subjects’ diet for the duration of the study. Patients were supplied with each gum package at each visit after returning their previously used gum container which was evaluated to determine consumption compliance.

Table 1
Composition of the chewing gums used in the study (wt%).
Ingredients Gum
Placebo POs-Ca POs-Ca + F
POs-Ca 0 2.5 2.5
Green tea extract fluoride 0 0 1.2
Maltitol 41.0 41.0 41.0
Xylitol 27.5 25.0 23.8
Gum base 24.0 24.0 24.0
Flavour, etc. 7.5 7.5 7.5

ICDAS classification

WSL was assessed using ICDAS criteria by two calibrated examiners (YK, AS) with the aid of a three-in-one air syringe. First, the teeth were assessed moist and then were dried for 5 s. The visual examination was coded as follows: (code 0) sound tooth surfaces, no evidence of caries after prolonged air drying (5 s); (code 1) first visual change in enamel, opacity or discoloration (white or brown) is visible at the surface of WSL after prolonged air drying, which is not or hardly seen on a wet surface; (code 2) distinct visual change in enamel, opacity, or discoloration distinctly visible at the surface of WSL under dry condition, and lesion is still visible when wet. In the case of disagreement between the scores from the two examiners, the consensus was made through discussion. In this clinical study, complex WSLs suspected to be localized developmental defects of enamel, with some caries-related involvement (e.g. located at caries-susceptible areas in a high-risk subject) were also included and scored. Such lesions may appear as whitish horizontal bands that have matching defects on molars. Lesions with visible enamel surface defects were excluded. Intraoral digital photographs were also taken at baseline and at each recall appointment with a digital camera (D5000; Nikon, Tokyo, Japan).

OCT system

A swept-source OCT system (Prototype 2; Panasonic Health Care Co. Ltd., Shikoku, Japan) incorporating a high-speed, frequency-swept external cavity laser has been under development for dental applications . The system is equipped with a hand-held scanning probe designed for inter-oral imaging. The center wavelength is 1310 nm with a scan range of 110 nm at a 30-kHz sweep rate. Axial and lateral resolutions of the system are 12 μm in air and 20 μm, respectively. The probe is equipped with a complementary metal–oxide–semiconductor (CMOS) camera for photographic visualization of the outer surface being scanned in real-time. The focused light-source beam is projected onto the sample, backscattered light from the sample is coupled back to the system with the reference beam, digitized in time scale and then analyzed in the Fourier domain to reveal the depth-resolved reflectivity profile (A-scan) at each point along the scanned section. The combination of a series of A-scans along the section creates a raw data file (B-scan) that can be converted into a gray-scale image. The OCT images were obtained under hydrated conditions where moisture was gently wiped off from the lesion using a cotton pellet but the lesion was not excessively air-dried.

The OCT scans were obtained along the longer axis of the lesion (i.e. either inciso-cervical or mesio-distal). OCT imaging was repeated at exactly the same location at each patient recall. The CMOS camera photographic image registered with the OCT data served as a guide to accurately reposition the imaging plane. Several OCT scans were obtained and saved at each appointment for subsequent selection of the “best matching shots”, which involved digital superimposition of the CMOS photographic images to ensure repeatability.

OCT image analysis

2D OCT scans of the lesions were compared according to optical boundary depth (BD) derived from the images using specially developed code in ImageJ (ImageJ version 1.45S; Wayne Rasband, NIH, Bethesda, Maryland) software. BD was calculated over a fixed region of interest (ROI, width 250 μm × optical depth 1000 μm) at the center of each lesion at the baseline, as described in Fig. 2 .

Fig. 2
OCT image analysis of optical boundary depth (BD). BD was calculated as average depth of the visual boundary in the region of interest (ROI; width 250 μm × optical depth 1000 μm), according to a signal intensity cutoff threshold determined by the operator using the image analysis software.

BD is the depth of the boundary that is observable between bright, highly scattering area of the lesion and the darker region beneath the lesion, and is reported to be strongly correlated with lesion depth . All the image analyses were performed by the same operator (YS) who was blinded to the visual assessment results, case history and sequence of the scans, and the OCT system was calibrated and validated every time the image analyses were performed.

Statistical analysis

Analysis of normality was performed on the data and non-parametric test was selected. The results of OCT image analysis of the all lesions were subjected to Wilcoxon rank-sum test to determine significant changes in BD over time, followed by multiple comparisons with Bonferroni correction. To avoid an accumulation of errors due to multiple comparisons, the Bonferroni correction modified the significance level by dividing it (p < 0.05) over the number of comparisons made.

Materials and methods

Study design and subject recruitment

Thirty-seven healthy subjects (median age: 26 year) were recruited following obtaining ethical approval for the study from the Ethics Committee of the Tokyo Medical and Dental University and signing the informed consent forms. Each of the volunteers completed the medical history forms and underwent intraoral examination for caries experience. For inclusion in the study, the subjects were required to have at least one WSL, with an ICDAS score of 2 or 1 as described below . Exclusion criteria included smoking, evidence of poor oral health including periodontal disease, recent professional fluoride therapy (<2 weeks), uptake of fluoridated water or any medication that could affect oral flora, and pregnancy. Each subject had between one and eleven WSL(s) with a total of 124 WSLs examined throughout the course of this study, as described in Fig. 1 .

Fig. 1
Participant disposition for the randomized control trial. Thirty-seven healthy subjects were recruited. After the intraoral examination, 10 subjects were excluded because of trismus or under orthodontic treatment or bleach treatment.

This clinical trial was based on a double-blind, randomized, controlled design with three sugar-free gums. One of the gums was a placebo sugar-free chewing gum without POs-Ca (Ezaki Glico, Osaka, Japan) and the other two contained 2.5 wt% POs-Ca or 2.5% POs-Ca and 1.2% fluoride-containing green tea extract, namely POs-Ca and POs-Ca + F (Ezaki Glico) ( Table 1 ). The placebo and intervention chewing gums were identical in appearance, taste and smell without any observable differences. The chewing gum slabs were received in code-labelled packages stored at room temperature. The codes were randomly assigned by a controller and remained unknown to the volunteers and operators until all remineralization data had been obtained. The subjects were randomly divided into three groups and chewed two slabs of each gum three times every day (at 8:00 a.m., 12:00 p.m. and 5:00 p.m.) for 20 min each time. Each subject followed this regimen for 3 months and attended a monthly review appointment. No alterations were made to the subjects’ diet for the duration of the study. Patients were supplied with each gum package at each visit after returning their previously used gum container which was evaluated to determine consumption compliance.

Jun 19, 2018 | Posted by in General Dentistry | Comments Off on White spot lesion remineralization by sugar-free chewing gum containing bio-available calcium and fluoride: A double-blind randomized controlled trial
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