# Ozonized Water Administration in Peri-Implant Mucositis Sites: A Randomized Clinical Trial
## 4 Discussion
In fact, PPD, like the other indexes considered, results in being a surrogate endpoint whose improvement might not coincide with more \"patient-centered\" ones (e.g., the long-term survival rate of the implant in the mouth) which should be evaluated in future studies. Taking a glance at the literature, we can observe that little research has been conducted to date on the treatment of peri-implant mucositis using ozone therapy. [PERSON] et al. [29] conducted a randomized controlled trial to test the effect of subgingival applications of ozone and/or hydrogen peroxide on peri-implant mucositis. The following treatments were randomly applied for 60 s (as in our study) to the implant sites on days 0, 7 and 14: (1), O\({}_{2}\) and 0.9% NaCl (control group), (2) O\({}_{2}\) and H\({}_{2}\)O\({}_{2}\) (3%), (3) O\({}_{3}\) and 0.9% NaCl, and (4) O\({}_{3}\) and H\({}_{2}\)O\({}_{2}\) (3%). On days 0, 7, 14 and 21, both plaque, gingival, and bleeding indices were registered. The authors found that both treatments including ozone produced optimal gingival health scores and equally controlled bleeding more effectively than the other experimental treatment. The use of ozone has been mostly evaluated as an adjunct to the surgical treatment of peri-implantitis, the irreversible form of inflammation occurring on implant sites. In the study by [PERSON] et al., [30] 41 patients were randomly allocated to an implant surface decontamination by means of sterile saline with additional ozone gas or the control group with sterile saline alone. According to the authors, the additional use of ozone for Scaling and Root Planing (SRP) showed both clinical and radiographic significant improvements. Despite our results disagreeing with these conclusions, no direct comparison can be carried out because of the different methodologies considered. For instance, the latter study considered peri-implantitis, instead of peri-implant mucositis, and additionally, a different formulation of ozone was used, like in the previous trial mentioned (gaseous ozone instead of the ozonized water used in our current research). The results obtained by our group show a certain efficacy of ozonized water if considered alone, but the absence of significant differences if compared to the control treatment allow us to draw no firm conclusions, especially because of the presence of some limitations in the study. For example, the type of implant, the time since its insertion, and the eventual intake of anti-inflammatory/antibiotics among participants were not considered, thus affecting the homogeneity of the two random groups at baseline. Additionally, the absence of intra-rater reliability (measured by the [PERSON]'s kappa coefficient) might hide a measurement bias, especially for PPD considering the highly variability between operators when using a probe (e.g., different session used, etc. ), thus affecting the reliability of clinical measurements, resulting in underestimated or overestimated values. Moreover,the use of PPD as a clinical parameter to perform sample size calculation might lead to a wider trial with more conclusive results. Therefore, future research deserves to be conducted with the aim to clearly define the efficacy of ozonized water for the management of peri-implant mucositis, along with other devices for the domiciliary treatment of this condition [31]. In particular, subsequent randomized clinical trials should compare its action with that of treatments considered as positive controls (such as chlorheximide and glycine or bicarbonate powder) [25]. A longer follow up should be considered in order to evaluate the long-term benefit of ozone. Finally, microbiological tests should also be addressed to fully understand which oral hygiene protocol guarantees the major efficacy towards peri-implant mucositis.