Ozone and caries: a review of the literature

A chronological perspective

The earliest publication identified which used ozone for treatment of caries was published in 2000.7 This examined the efficacy of ozone as an antibacterial agent on primary root caries lesions (PRCL) in 40 extracted teeth when exposed to ozonized water for 10s or 20s, and on saliva-coated glass beads covered with Streptococcus mutans and Streptococcus sobrinus with 10s exposure to ozone gas. Half of the PRCL was excavated using a sterile excavator, the remaining lesion being treated with the ozonized water. A significant reduction (p < 0.001) was observed in the ozone-treated groups. Similarly, the numbers of S. mutans and S. sobrinus were reduced. This publication raised hopes that a new form of quick, conservative and easy treatment for caries had arrived as it confirmed previously considered views that ozonated water and ozone gas were effective in killing micro-organisms.

This was reinforced by a paper, in 2003, from Julian Holmes,8 a UK general dental practitioner. In a double-blind trial of PRCLs in 89 subjects (aged between 60 and 82 years) for 18 months, patients were treated with ozone or air, followed by remineralizing solution. This was repeated at 6, 12 and 18 months. A good 98% recall was achieved, bearing in mind the age of the subjects since, in studies involving subjects of similar age, the recall rate could be expected to be reduced by deaths and serious illness. No details of the recall assessment and who carried it out were provided. The results indicated that 100% of the ozone-treated PRCLs had arrested at 18 months, while 37% of the control (not treated with ozone) lesions had gone from leathery to soft, a significant difference (p<0.01).8 The author concluded that the ozone treatment regime was an effective alternative to conventional ‘drilling and filling’.

In another study, ethical approval was obtained for treatment of 70 PRCLs in 26 patients.9 A ‘biopsy’ was taken from one half of the lesion using a sterile excavator, and this was sent for microbiological analysis: the other half of the lesion was treated with ozone, and again sent for microbiological analysis. A significant (p < 0.001) reduction in micro-organisms after ozone application was noted for either 10 or 20s applications, with the authors concluding that: ‘Ozone application for 10 or 20 seconds dramatically reduced most of the micro-organisms in PRCLs with no side-effects at recalls of up to 5.5 months and that the technique might be considered a potentially effective alternative to conventional ‘drilling and filling’.9

Another study, published in 2005 by a team from the University of Munich,10 investigated the effect of ozone on caries lesions in first permanent molar teeth in children in a randomized controlled clinical study. The results, albeit only at 3 months, and using Diagnodent to monitor the lesions, indicated that ozone-treated lesions successfully showed more caries reversal or reduced caries progression than the untreated lesions.10 On the other hand, results of a laboratory study by Muller and colleagues indicated that, when tested on the more realistic multispecies oral biofilm, ozone therapy was not successful.11 However, closer examination of the paper suggests that the researchers did not follow the manufacturer's directions in the use of the apparatus.

A review paper by Baysan and Lynch,12 in 2006, demonstrated the safety of the Healozone machine and concluded that the ‘use of ozone in the treatment of root caries looks very promising’. The authors added that ‘there is a need for further research’. However, these authors do not quote the results of the Holmes paper, which was published earlier (in 2003), despite it involving the use of ozone in the clinical treatment of root caries.

Further elucidation of the process by which ozone may affect the caries process was given by Baysan and Beighton in 2007.13 These workers carried out microbiological sampling of 104 freshly extracted (15 minutes following extraction) molar teeth which had non-cavitated, occlusal caries lesions, half of which were treated with ozone gas. The enamel was then removed to allow bacterial sampling, with the results indicating that there was no significant difference between the number of bacteria recovered from the dentine of ozone treated and non-treated groups. The authors discussed these findings in the light of previous work and considered that the concentration of ozone in the aqueous phase was insufficient to exert an antimicrobial effect.13 Lynch, however, in a reply to a review paper by Hodson and Dunne which quoted the above work, pointed out that the manufacturer's recommendations for the use of Healozone had not been carried out.14

Other in vivo and in vitro studies

A summary of the results from the review are presented in Tables 1 and 2. Four of the six in vivo papers indicate an effect of ozone on cervical caries. Five of the eight in vitro studies demonstrated a positive effect on cariogenic bacteria.

Systematic reviews

Systematic reviews may be considered the highest form of ‘evidence’, with the exception of meta-analyses, so their results, in synthesizing the data on a given topic, must be held in the highest regard.

The first systematic review on ozone in the treatment of caries, a Cochrane Review, was carried out by Rickard and colleagues and published in 2004.22 Inclusion criteria were:

Two published studies, a large number of conference abstracts, two PhD theses and a submitted manuscript were located during the search or provided by authors known to be researching the subject. The authors excluded 42 conference papers, abstracts and posters (from an unknown number of studies) and included three trials with a total of 432 randomized lesions. The review concluded that: ‘Given the high risk of bias in the available studies and the lack of consistency between different outcome measures, there is no reliable evidence that application of ozone gas to the surface of decayed teeth stops or reverses the decay process. There is a fundamental need for more evidence of appropriate rigour and quality before the use of ozone can be accepted into mainstream primary dental care’. In addition, the authors added that ‘Dental care providers should not advocate the use of ozone on the sole basis of high patient acceptability as compared with less attractive drilling and filling’.

The second systematic review was carried out by the UK's National Institute for Health and Clinical Excellence (NICE),23 concluding as follows: ‘NICE has concluded that there is not enough reliable evidence to show that Healozone is more effective than existing treatments for decay of the biting surfaces and roots of the teeth. The authors added that they ‘will consider a review of the guidance in 2008 when we hope there will be further good quality evidence available at that time’.

At the time of writing this paper, no such review has been published.

The third review was published by Brazzelli and colleagues.5 Inclusion criteria were:

Five full text reports on the use of Healozone in management of occlusal caries and five studies published as abstracts (four on occlusal caries one on root caries) met the inclusion criteria. In the discussion in the paper, the authors stated that: ‘Nearly all the research to date comes from the same group who developed and pioneered the procedure… and that there is a need for trials to be carried out by independent research teams: they should be properly randomized, apply appropriate statistical methods, use validated and reproducible criteria for the assessment of caries, mask participants and outcome assessors, should measure caries incidence for at least two years, but realistically much longer.’ They concluded that ‘any treatment that preserves teeth and avoids fillings is welcome. However, the current evidence base for Healozone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries’.

The most recent systematic review, published in 2008,6 was carried out by Azarpazooh and Limeback. It concluded, on in vitro results, that there was good evidence of ozone biocompatibility with human oral epithelial cells but conflicting evidence of the antimicrobial efficacy of ozone. On the in vivo data, the authors concluded that ‘despite the promising in vitro evidence, the clinical application of ozone in management of dental and root caries has not achieved a strong level of efficacy and cost-effectiveness’, concluding that ‘the promising potential of ozone has not been realized in clinical studies to date’. Lynch24 criticized the review by Azarpazooh and Limeback for having criticized subjective tactile hardness for the clinical severity score as being a methodological concern. He stated that hardness was the most reliable clinical measure of lesion severity but did not reference this statement. Azarpazooh and Limeback25 were given the last word in this discussion, stating: ‘We are happy that Dr Lynch, as one of the experts in the field, has found many useful parts in the paper’. However, they stated that:

In summary, Table 3 demonstrates that four systematic reviews failed to ascertain the cariostatic effect of ozone.

Safety

Millar and Hodson26 tested the safety of ozone devices using a phantom head clinical simulation while ozone levels were monitored in the pharyngeal and nasal regions of the ‘patient’. The results indicated that Healozone was safe to use, but that the Ozi-cure device should not be used without adequate suction, as inadequate suction allowed the ozone levels to reach a concentration above permitted levels. The Ozi-cure device has now been superseded by Ozo-top (Tip Top Tips Sarl, Rolle, Switzerland).

Finally, the author has received a variety of reports, from UK-based general dental practitioners, of clinical reversal of caries lesions, with one such report being presented as Figures 4 (a–d). While reports such as this are helpful, it could be considered appropriate that a long-term, randomized, clinical controlled trial should be carried out to demonstrate, once and for all, whether the exponents of ozone treatment of caries are correct in their beliefs, or whether the procedure should be confined to the annals of history.