A randomised clinical in situstudy to evaluate the effects of novel low abrasivity anti-sensitivity dentifrices on dentine wear

Abstract

Objectives

To compare the abrasive wear on human dentine in an in situ model associated with use of an experimental low abrasivity anti-sensitivity dentifrice containing 1% alumina and 5% sodium tripolyphosphate (STP) with an experimental ultra-low abrasivity non-alumina 5% STP dentifrice, a higher abrasivity daily-use whitening dentifrice, and water as controls.

Methods

This was a single-centre, single-blind, randomised, split-mouth, four-treatment, two-period, crossover in situ study in 29 healthy subjects. Subjects wore bilateral lower buccal appliances, each fitted with four dentine specimens. Study treatments were applied ex vivo (three times daily). Dentine loss was measured by non-contact profilometry after 5, 10 and 15 days’ treatment.

Results

All 29 subjects were included in the efficacy analysis. Significantly less dentine loss was associated with brushing with the low and ultra-low abrasivity dentifrices than with the higher abrasivity dentifrice at all timepoints (p < 0.01). Brushing with ultra-low abrasivity dentifrice or water resulted in statistically significantly less dentine loss compared with brushing with the low abrasivity dentifrice at all timepoints (p < 0.05). Dentine loss after brushing with ultra-low abrasivity dentifrice was not significantly different from brushing with water.

Conclusions

The degree of dentine loss observed in this in situ model reflected the abrasivity of the study dentifrices. Brushing with low or ultra-low abrasivity STP-containing anti-sensitivity dentifrices resulted in significantly less dentine loss (equating to dentine wear) than with a higher abrasivity daily-use whitening dentifrice.

Introduction

Dentifrices – particularly daily-use whitening pastes – are typically formulated with dental abrasives, such as hydrated silica, chalk, dicalcium phosphate or alumina , or with a combination of abrasive and chemical cleaning agents, such as sodium tripolyphosphate (STP), to help control the build-up of stain on the surface of the teeth whilst helping to achieve good hygiene. Polyphosphates, such as STP, are often utilised in dentifrices to supplement the physical mode of action of stain removal offered by abrasives .

Particle hardness, shape, size, size distribution and concentration have all been reported to affect the stain-removal properties of dental-grade abrasives . These same parameters also influence the rate of abrasive wear, which increases as abrasive particle size increases up to a critical point, after which it becomes independent of size . Dentine is considerably softer than enamel , making it more vulnerable to abrasive wear from over-brushing or use of higher abrasivity dentifrices. The effect of abrasivity on dentine should be considered when formulating a dentifrice as most abrasives have a hardness similar to or greater than dentine . Abrasive wear is of particular concern in people with dentine hypersensitivity, where the dentine is exposed, notably at the cervical margin of the tooth . Use of a lower abrasivity dentifrice may be more appropriate for this population to help minimise wear of exposed dentine.

Relative dentine abrasivity (RDA) is a quantitative in vitro measure used to assess the abrasiveness of a dentifrice formulation on dentine . It is included in the International Organization for Standardization specification for a dentifrice and is the most widely accepted standardised measure of dentifrice abrasion . Dentifrices with an RDA value up to 250 are considered suitable for normal daily use . Effective extrinsic stain removal has long been associated with higher RDA formulations; indeed, a review of commercially available dentifrices noted that whitening dentifrices were generally more abrasive than other dentifrice products . However, dentifrice formulations containing a low calcined, small particle size alumina abrasive in combination with STP have also been reported to exhibit highly effective stain removal in vitro with low dentine abrasivity . More recently, the combination of a small particle size alumina and STP in a low abrasive anti-sensitivity dentifrice has also been shown to be clinically effective at removing extrinsic dental stain compared with a dentifrice containing abrasive dental silica alone .

Polyphosphates such as STP have been shown to strongly bind to the surface of the tooth, desorbing protein and chromogens from hydroxyapatite in vitro and desorbing the acquired enamel pellicle in vivo . It is understood that binding of polyphosphates to the surface of the tooth can cause changes to the surface charge that disrupt protein adsorption , thus enhancing the removal of protein-based stain offered from tooth brushing with a dentifrice containing dental-grade abrasive.

In vitro and in situ methodologies have been established to evaluate the long-term wear potential of abrasives and dentifrices on human dentine and enamel using a number of substrates and techniques . An in situ clinical study demonstrated significantly less dentine loss following use of an ultra-low abrasivity dentifrice (RDA ∼15) compared with brushing with moderate (RDA ∼70) or higher (RDA ∼240) abrasivity formulations, and no significant difference from brushing with water alone , i.e. it showed increased dentine loss (equating to wear) with increasing dentifrice abrasivity.

The aim of this study was to compare the abrasive wear on human dentine of an experimental, low abrasivity anti-sensitivity dentifrice containing 1% w/w alumina abrasive and 5% w/w STP, developed to provide relief from dentinal hypersensitivity and stain removal benefits, with that of an experimental ultra-low abrasivity anti-sensitivity dentifrice containing no alumina and 5% w/w STP, a daily-use whitening dentifrice, and mineral water as reference controls. The null hypothesis was that there would be no significant difference in the abrasion of dentine from tooth brushing with the three toothpastes of different RDA values. Further, all three pastes would be significantly more abrasive to dentine than water.

Methods

Study design

This was a single-centre, single-blind (specimen analyst), randomised, split-mouth, four-treatment, two-period, crossover, exploratory in situ study in healthy subjects. The study was conducted in accordance with the Declaration of Helsinki at the Clinical Trials Unit of the Bristol Dental Hospital and School, with ethical review by an independent ethics committee (South West – Exeter, IRB number 14/SW/0044).

The in situ method used in the current study was based on a previously published in situ abrasion methodology . The model employs removable acrylic mandibular appliances that hold the dentine specimens buccally in the oral cavity. Subjects wear the intra-oral appliances for 5–7 h on a treatment day; they are removed for ex vivo treatment of the dentine specimens. Dentine loss is measured by surface profilometry at intervals over the treatment period.

Subjects

Subjects were recruited by the Clinical Trials Unit. The eligible study population comprised healthy adults aged ≥18 years with good general and oral health and the ability to accommodate lower bilateral buccal intra-oral appliances. Exclusion criteria included pregnancy; breastfeeding; current or recurrent disease or dental pathology that could have affected the study assessments; any oral appliance/restorations that could have interfered with study procedures; recurrent aphthous ulcers; susceptibility to acid regurgitation; severe gingivitis, carious lesions or periodontal disease; signs/history of dental erosion; and daily doses of medication that was causing xerostomia.

Preparation of dentine specimens and appliances

Dentine specimens were obtained from recently extracted caries-free human third molars. Slices of coronal root dentine with a surface area of 3 mm × 3 mm were sectioned from buccal and palatal areas of the teeth and set in composite (QuiXfil ® ; Dentsply IH Ltd, Weybridge, UK), polished with 1200 grit silica powder and 0.3 μm alumina powder to produce flat specimens (1 μm tolerance) with parallel sides, and ultrasonicated in deionised water after each polishing stage. Before use, a 3 mm × 1 mm area was scanned by non-contact profilometry (Proscan 2100; Scantron Industrial Products Ltd, Taunton, UK) to confirm that the specimens were flat and within the 1 μm tolerance. This included the area of the dentine to be exposed to study treatment and two outer (reference) areas from which changes from baseline were calculated. Polyvinyl chloride (PVC) tape was applied over the reference areas to protect them from abrasion, leaving an approximately 2 mm wide zone of exposed dentine along the length of the specimen for treatment.

During the study, subjects wore lower left and right buccal appliances, each fitted with four dentine specimens ( Fig. 1 ). At the start and end of each treatment day the buccal appliances including the dentine specimens were disinfected in chlorhexidine mouthwash (Corsodyl ® ; GSK Consumer Healthcare, Weybridge, UK) for approximately 3 min and rinsed with tap water before either placing in the mouth or storing overnight. At the end of each treatment day and during the profilometry analysis period, appliances were stored at the study site in moist conditions to ensure the dentine specimens remained hydrated. Before and after profilometry, the PVC tape was removed from the specimens and the appliances were disinfected for at least 20 min in a mixture of 0.5% chlorhexidine and 70% ethanol, then rinsed with tap water. After analysis, the PVC tape was re-applied and the specimen re-inserted into the appliance.

Fig. 1
Intra-oral lower buccal appliance showing four dentine specimens in situ.

Study products

Four study products were tested over two separate treatment periods: two during the first treatment period and two during the second.

  • Experimental low abrasive dentifrice: 5% w/w potassium nitrate (KNO 3 ), 1% w/w alumina, 5% w/w STP, 1150 ppm fluoride as sodium fluoride (NaF); RDA ∼40 (‘low abrasivity dentifrice’)

  • Experimental ultra-low abrasive dentifrice: 5% w/w KNO 3 , 5% w/w STP, 1100 ppm fluoride as NaF; RDA ∼13 (‘ultra-low abrasivity dentifrice’)

  • Daily-use whitening dentifrice: abrasive silica , 1450 ppm fluoride as NaF; RDA ∼142 (Colgate ® Total Advanced Whitening; Colgate-Palmolive Ltd, Guildford, UK) (‘higher abrasivity dentifrice’)

  • Water: RDA ∼8 (Volvic ® mineral water; Groupe Danone, London, UK).

Experimental dentifrices were supplied in plain white tubes, the marketed dentifrice was supplied in its commercial tubes, and the water was supplied in commercial bottles; all were identified by study labels.

Study visits

At screening, subjects provided written informed consent and a medical history was taken, followed by an oral soft tissue (OST) examination. Subjects were provided with a regular fluoride dentifrice (Crest ® Decay Prevention; Procter & Gamble, Weybridge, UK) and toothbrush (Aquafresh ® Clean Control; GSK Consumer Healthcare, Weybridge, UK) to use at home twice daily for the duration of the study. No other oral hygiene procedures were permitted, with the exception of dental floss if this was part of the subject’s normal routine.

At the start of the first treatment period, eligible subjects who satisfied all inclusion and exclusion criteria were randomised to receive two study products during each of the two treatment periods, according to a schedule generated by the Biostatistics Department of GSK Consumer Healthcare. Randomisation numbers were allocated in ascending numerical order by study site personnel. For each treatment period the randomisation schedule indicated which study product was to be applied to which side of the mouth for each subject.

Each subject completed 15 non-consecutive treatment days per treatment period (Monday–Friday only, with a 1 week break between treatment periods) to allow time for profilometry scanning after each treatment period. On treatment days, subjects brushed twice with the standard fluoride dentifrice, once before attending the study site and again in the evening after all study assessments had been completed. During each treatment day, subjects wore the intra-oral appliances (lower left and right) for approximately 6 h and attended the site three times for ex vivo application of study treatments (at 09:30 ± 30 min, 11:30 ± 30 min and 14:30 ± 30 min). Appliances were worn for at least 1 h before the first product application and for a minimum of 1 h following product application. Appliances were removed for up to 1 h and stored in a moist pot while the subjects had lunch.

On treatment days, subjects were not permitted to eat or drink (other than water) while the appliances were in situ , and were required to abstain from smoking and chewing gum. Subjects were not permitted to wear any mouth piercings or tongue jewellery during treatment periods, and were requested to delay having any non-emergency dental treatment until after completion of the study (including professional whitening treatments or prophylaxis).

Study treatment administration

For each treatment, 1.1 ± 0.1 g of the allocated study dentifrice was applied ex vivo by site personnel to the four dentine specimens, held in either the left or the right buccal appliance, using an electric toothbrush (Oral B ® Vitality Precision Clean power toothbrush with EB 20 Precision Clean Oral B brush head; Procter & Gamble, Weybridge, UK). Study treatments were dispensed by study staff directly onto a wetted brush then applied to the study samples. All four dentine samples in a particular appliance were brushed for a total of 60 s (15 s per sample) then rinsed with bottled mineral water. For the water control, dentine specimens were brushed ex vivo for 60 s using the electric toothbrush while immersed in 50 mL of the bottled mineral water, then rinsed as above. The same member of staff administered the study products for a particular subject for the duration of the study. The staff member was trained prior to the start of the study to brush with a force of 200 g. Appliances were returned to the mouth immediately after rinsing.

Assessments

A non-contact profilometry scan was taken of each dentine specimen before treatment and after 5, 10 and 15 days’ treatment, for measurement of dentine loss. A Proscan 2100 non-contact profilometer (Scantron Industrial Products Ltd, Taunton, Somerset, UK) was used to capture topographical images of each dentine specimen. A 3 mm × 1 mm area was scanned and Proscan software used to apply a three-point level to the image by placing the three points on the outer edges of the two control (reference) areas. Any erroneous peaks or troughs were removed and a three-point height measurement was taken by highlighting the two control areas, followed by the exposed channel. The software calculated any difference in height between the control (reference) and exposed areas. A maximum of 9 days (starting from the Friday on which the specimens were removed) was required to complete the non-contact profilometry analysis before the next 5 days of treatment could commence.

Safety

OST examinations were completed at screening, on the first day of each treatment period, on completion of each treatment period and within 7 days of the final treatment day. Adverse events (AEs) were recorded from the first use of standard fluoride dentifrice until 5 days after the last use of study product. Safety was assessed from treatment-emergent AEs and OST findings. However, as this was an in situ study with ex vivo treatment application, it was not feasible to evaluate clinically meaningful tolerability of the study products. The safety population was defined as those subjects who were randomised and received at least one dose of study product.

Statistical analysis

No formal power-related calculations were carried out for this study. The outcome variable was mean dentine loss (μm), measured by non-contact profilometry on Days 5, 10 and 15. Based on previous studies (GSK Consumer Healthcare, data on file), the within-subject standard deviation at Day 10 was assumed to be 0.86 μm and it was estimated that it would increase by up to 30% (to 1.12 μm) at Day 15. Using a two-sided 5% significance test, 22 evaluable subjects were required to detect a minimum difference between the treatments of approximately 1.0 μm, with 80% power. Allowing for dropouts and protocol violations, sufficient subjects were screened to randomise a maximum of 30 subjects, to ensure that at least 24 evaluable subjects completed the study.

The primary population for evaluation of study outcomes was the per-protocol (PP) population, defined as those subjects in the intent-to-treat (ITT) population with at least one assessment of efficacy considered unaffected by protocol violation. If more than 10% of data were excluded from the PP analyses, the same analyses were planned to be conducted in the ITT population, defined as those subjects who were randomised, received at least one dose of study product, and had at least one post-treatment efficacy measurement.

Mean dentine loss (μm) per treatment was calculated as the mean of the four specimens in each appliance taken at each timepoint, and was analysed using analysis of variance based on a mixed model with treatment period, location of sample in mouth (left/right) and study product as fixed effects, and subject as a random effect. Pairwise comparisons were conducted at the two-sided 5% significance level. No adjustment for multiplicity was planned.

Methods

Study design

This was a single-centre, single-blind (specimen analyst), randomised, split-mouth, four-treatment, two-period, crossover, exploratory in situ study in healthy subjects. The study was conducted in accordance with the Declaration of Helsinki at the Clinical Trials Unit of the Bristol Dental Hospital and School, with ethical review by an independent ethics committee (South West – Exeter, IRB number 14/SW/0044).

The in situ method used in the current study was based on a previously published in situ abrasion methodology . The model employs removable acrylic mandibular appliances that hold the dentine specimens buccally in the oral cavity. Subjects wear the intra-oral appliances for 5–7 h on a treatment day; they are removed for ex vivo treatment of the dentine specimens. Dentine loss is measured by surface profilometry at intervals over the treatment period.

Subjects

Subjects were recruited by the Clinical Trials Unit. The eligible study population comprised healthy adults aged ≥18 years with good general and oral health and the ability to accommodate lower bilateral buccal intra-oral appliances. Exclusion criteria included pregnancy; breastfeeding; current or recurrent disease or dental pathology that could have affected the study assessments; any oral appliance/restorations that could have interfered with study procedures; recurrent aphthous ulcers; susceptibility to acid regurgitation; severe gingivitis, carious lesions or periodontal disease; signs/history of dental erosion; and daily doses of medication that was causing xerostomia.

Preparation of dentine specimens and appliances

Dentine specimens were obtained from recently extracted caries-free human third molars. Slices of coronal root dentine with a surface area of 3 mm × 3 mm were sectioned from buccal and palatal areas of the teeth and set in composite (QuiXfil ® ; Dentsply IH Ltd, Weybridge, UK), polished with 1200 grit silica powder and 0.3 μm alumina powder to produce flat specimens (1 μm tolerance) with parallel sides, and ultrasonicated in deionised water after each polishing stage. Before use, a 3 mm × 1 mm area was scanned by non-contact profilometry (Proscan 2100; Scantron Industrial Products Ltd, Taunton, UK) to confirm that the specimens were flat and within the 1 μm tolerance. This included the area of the dentine to be exposed to study treatment and two outer (reference) areas from which changes from baseline were calculated. Polyvinyl chloride (PVC) tape was applied over the reference areas to protect them from abrasion, leaving an approximately 2 mm wide zone of exposed dentine along the length of the specimen for treatment.

During the study, subjects wore lower left and right buccal appliances, each fitted with four dentine specimens ( Fig. 1 ). At the start and end of each treatment day the buccal appliances including the dentine specimens were disinfected in chlorhexidine mouthwash (Corsodyl ® ; GSK Consumer Healthcare, Weybridge, UK) for approximately 3 min and rinsed with tap water before either placing in the mouth or storing overnight. At the end of each treatment day and during the profilometry analysis period, appliances were stored at the study site in moist conditions to ensure the dentine specimens remained hydrated. Before and after profilometry, the PVC tape was removed from the specimens and the appliances were disinfected for at least 20 min in a mixture of 0.5% chlorhexidine and 70% ethanol, then rinsed with tap water. After analysis, the PVC tape was re-applied and the specimen re-inserted into the appliance.

Jun 19, 2018 | Posted by in General Dentistry | Comments Off on A randomised clinical in situstudy to evaluate the effects of novel low abrasivity anti-sensitivity dentifrices on dentine wear
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