A critical evaluation of the use of ozone and its derivatives in dentistry


Objective: The therapeutic application of ozone and its derivatives in the dental field has been used for many purposes. However, there has yet to be a consistent evaluation of the outcomes, due to the lack of standardization of the treatment operating procedures.

Materials and methods: The keywords “ozone”, “ozonated”, “ozonation” “ozonized”, “ozonization”, “dentistry”, “periodontology”, “oral surgery”, “oxygen-ozone therapy” were used to perform a literature review using PubMed, Cochrane, Google Scholar, Zotero databases with the temporal restriction for manuscripts published between 2010 and 2020. Clinical trials and case reports of good, neutral, as well as negative results related to ozone treatment specifications were evaluated.

Discussion: A better understanding of the mechanisms of action of this bio-oxidative therapy could open new horizons related to the personalization of treatments and the quality of dental care. The critical condition to achieve these goals is an improved knowledge of the qualitative/quantitative characteristics of ozone and its derivatives.



The positive therapeutic effects of ozone and its derivatives have been studied in multiple fields of medicine. However, there is no limited agree-ment in the medical community on its use and benefits. This may be due to the fact that, unlike other drugs, ozone does not act directly through traditional drug-receptor interactions. When ad-ministered in the gaseous form, it is a gaseous mixture where ozone represents at most 5% of the total, while the remaining part is generally made up of oxygen, acting as a gas transmitter. On the other hand, ozone, due to its extreme reactivity, cannot be used for the transmission of chemical signals to induce physiological or biochemical changes. Moreover, ozone cannot be considered a pro-drug in the common sense of the term. A pro-drug is a biologically inactive molecule that, once introduced into the body, requires chemical transformations, generally of enzymatic nature, for its activation. Ultimately, ozone can be classified as an effector molecule generator. Depending on method of administration, admin-istration site, dosage and derivative formulations, different hydrophilic (mainly hydrogen peroxide) and lipophilic (mainly alkenals) small molecules will be produced. These molecules selectively interact with protein moieties, regulating their biological activity epigenetically. Therefore, ef-fector molecules acting as ligands can increase or decrease enzyme activity, gene expression or cellular signals. In general, oxygen-ozone therapy is classified as regenerative medicine, provided that the cor-rect conditions of the use of these substances are respected1,2. In this sense, it is possible to foresee the use of ozone in personalized therapy based on the patients’ clinical history3.Oxygen-ozone therapy has multiple methods of application in dental practice4 -18. Given the increased attention to this subject, further stud-ies and reviews are expected to be published19. However, analytical evaluation of the published clinical results has not been performed. The pres-ent study addresses knowledge gaps related to research protocols and resulting outcomes related to the use of ozone and its derivatives in dentistry, using the following classification (Table I).The present study will also address the operative protocols (in terms of ozone generators, ozone concentrations, ozone derivatives and so on) adopted by practicing dentists.

Four databases (PubMed, Cochrane, Goo-gle Scholar, Zotero) were consulted, using the keywords “ozone”, “ozonated”, “ozonation” “ozonized”, “ozonization”, “dentistry”, “periodon-tology”, “oral surgery”, “oxygen-ozone therapy”. For homogeneity’s sake, the terms “ozonation” and “ozonated” were used in the present manuscript.The aim of this review is to analyze clinical trials and case reports, confronting good and negative results with respect to ozone treatment specifications. In the “Presentation of the papers” section, summaries of both usual Materials and Methods, as well as Results units, are reported. In order to make reading easier, the specific part relating to the characteristics of use of ozone, where present, is specifically indicated at the end of each summary. The clinical results obtained from the various works are grouped by similarity of treatment in the Discussion section . …


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