Is there a place for Tooth Mousse® in the prevention and treatment of early dental caries? A systematic review

A broad search of the literature was carried out in December 2013 that identified 7576 articles of which the majority were duplicates. Once these duplicates were removed and the remainder limited to those where CPP-ACP was the primary focus and published in English, 172 articles were identified for closer inspection. The PREMEDLINE search identified one additional paper. Of the 173 articles, the inclusion and exclusion criteria in Table 1 were applied which led to 28 articles being excluded immediately as they were review articles, case reports or letters to the editor.

All of the 145 articles remaining were studied by title and abstract as an initial filter. As the current systematic review is focussed entirely on the CPP-ACP formulations of Tooth Mousse® (MI Paste®) and Tooth Mousse Plus® (MI Paste Plus®) – all studies employing any other formulations of CPP-ACP including solutions, chewing gum and dentifrice were excluded. This filter decreased the number of articles to 29. These 29 articles were studied in full text, nine of which were excluded as they were either in vitro studies or in situ studies utilising bovine enamel, giving 20 studies dating from 2007 to 2013 for final review (Fig. 1). Eight of the twenty studies were excluded – the titles and reasons for exclusion are summarised in Table 2. Andersson et al. [22] did not use Tooth Mousse® (MI Paste®) or Tooth Mousse Plus® (MI Paste Plus®) but instead utilised a proprietary CPP–ACP dental crème which is either no longer readily available or has been discontinued. Robertson et al. [23] delivered the MI Paste Plus® in preformed trays, which does not follow the manufacturer’s directions for use. The remaining six [24‐29] studies were found on closer examination to have used outcome measures not recognised as clinical care measures or employed artificially demineralised tooth substance in an ‘in situ’ model which were exclusion criteria (See Table 1). Both authors (SR and AB) reviewed the final 20 studies independently and reached consensus on which papers were included in the final review. Of the 12 studies available for this systematic review, three studies reported on prevention [30‐32] (Table 3) and nine reported on the treatment or regression of caries [33‐41] (Table 4).

Two of the three prevention studies were double-blind randomized controlled trials in populations of pre-school children [31, 32]. These studies found no significant benefits in the use of Tooth Mousse® (MI Paste®) over standard brushing with either 1000 ppm [31] or 400 ppm [32] fluoride toothpaste. The authors concluded that there was insufficient evidence to justify the daily use of Tooth Mousse® (MI Paste®) to control dental caries in these populations. The other prevention study published by Uysal et al. [30] was the in vivo study comparing the use of Tooth Mousse® or a 5 % sodium fluoride gel with a control group to prevent white spot lesions. The results of the in vitro study described in this article were not considered or included in this systematic review. In the in vivo study, patients used a non-fluoride toothpaste and did not receive any oral hygiene instruction. This study showed a statistically significant difference in the enamel microhardness of premolar teeth extracted after the 60 day test period in both the Tooth Mousse® and fluoride gel groups, compared to the control group, but no significant difference between the test groups.

Nine studies [33‐41] reported on the treatment or regression of dental caries (Table 4). In the majority of studies fluoride toothpaste was used by participants in all the study groups. However, one study [39] did not specify whether fluoride toothpaste was used, a second study did not fully specify the use of fluoride toothpaste in all groups [38] and in another [37] a non-fluoride toothpaste was used in the test group but fluoride toothpaste was used in the control group.

All except two [34, 39] of the nine studies reported on the regression of white spot lesions in orthodontic patients. This body of evidence, containing seven clinical studies [33, 35‐38, 40, 41] of variable strength of evidence utilised either visual scoring or fluorescence techniques for the assessment of dental caries. Some were compared with placebo pastes and others with different preventive products and/or control groups. Of these seven studies, four showed a significant advantage from the use of Tooth Mousse® in the regression of white spot lesions in orthodontic patients over 12 weeks to 6 months [33, 37, 38, 40].

The remaining three studies reported no significant difference between the Tooth Mousse® (MI Paste®) or Tooth Mousse Plus® (MI Paste Plus®) group and control/placebo group over periods of four weeks to three months [35, 36, 41].

Altenburger et al. [34] reported the remineralization of demineralized enamel fissures in 32 young adults using Tooth Mousse® using both laser fluorescence and visual classification. The Tooth Mousse® group showed significant improvements in laser fluorescence but no difference was noted by the visual scoring at 2 and 3-weeks when compared to the control group.

Krithikadatta et al. [39] carried out a pilot study on 45 adolescent dental students with occlusal white spot lesions, comparing Tooth Mousse® and Tooth Mousse Plus® to a 0.5 % fluoride mouthrinse. All three groups showed highly significant remineralising potential over the 30 day test period, but Tooth Mousse® and Tooth Mousse Plus® were significantly more effective than the fluoride mouthrinse.

Of the twelve studies included in this systematic review, three studies were direct comparisons of Tooth Mousse® versus a control group [34, 36, 40] and two studies versus a placebo crème [31, 33]. The remaining six studies compared the efficacy of Tooth Mousse® (MI Paste®) and/or Tooth Mousse Plus® (MI Paste Plus®) to other products and techniques with or without a control group - including fluoride toothpaste [37], fluoride mouthrinse [38, 39], fluoride gel [30], fluoride varnish [41], chlorhexidine gel [32] and microabrasion [38]. The studies by Beerens et al. [35], Krithidkadatta et al. [39], and Huang et al. [41] involved comparisons with Tooth Mousse Plus® (MI Paste Plus®) - containing 900 ppm Fluoride, all other studies utilised only the non-fluoride containing Tooth Mousse® (MI Paste®).

With regard to safety, no serious side effects or adverse events were reported in any of the studies included in the final review. However, five studies [35, 37, 39‐41] did not report side effects or adverse events in their papers. One study [33] recorded one participant with non-serious gastro-intestinal symptoms that were possibly related to the use of Tooth Mousse® and another [38] made the statement “although CPP-ACP had side effects” but did not make any reference to what the side effects were.

Figure 2 indicates that the prevention studies included in our review were classified as having a low risk of bias, although questions are raised on the Uysal et al. [30] research on possible selection and performance bias and Plonka et al. [32] has a question mark over outcome assessment. The regression studies do not show such good results (Fig. 3) with over half having questionable scores for selection bias and the majority having high risk of performance bias.

The strength of evidence of the group of studies included in this systematic review are further weakened by short observation periods (five studies with duration shorter than 3 months [30, 34, 36, 38, 41]), varying outcome measures (clinical indices [31‐34, 39, 40], enamel microhardness [30], laser and light-induced fluorescence [34‐36, 39, 40] and visual scoring of photographs [36‐38, 41]) and small number of total participants (939 participants for the three prevention studies [30‐32] and 542 participants for the nine regression studies [33‐41]).