The denouement of ozone therapy vying to chlorhexidine in non surgical periodontal therapy

1 Introduction

Nonsurgical periodontal therapy, which includes scaling and root planing and considered as Gold standard of Periodontal Therapy aims at removal of soft and hardened microbial deposits, disruption of the biofilm which is regarded as a trigger in etiopathogenesis of Periodontitis [1] and decontaminating the root surface from microbial by products thereby arresting the disease progression and establishing healthy, stable, maintainable periodontal conditions [2]. As inaccessible areas restricts its efficacy nonsurgical periodontal therapy do not warrant its remission thus necessitating the use of antimicrobial agents both systemically and locally as an adjunct [3]. To abrogate the limitations of systemic antimicrobials like drug toxicity, bacterial resistance, drug interaction and patient’s compliance local delivery of antimicrobial agents have been adapted [4]. Local drug delivery warrants antimicrobial therapy to be placed directly in periodontal pockets and attain elevated concentrations that are sustained for prolonged periods [5].

Chlorhexidine (CHX), a bis-biguanide molecule is a potent anti-infective and antibacterial agent used for prophylactic and therapeutic measure against periodontal disease. CHX mouth rinses have been effective in reducing plaque formation and restraining gingivitis. Topical usage of Chlorhexidine has demonstrated toxicity to gingival fibroblasts thereby delaying periodontal healing, and also elevated number of immediate type of allergies like asthma, urticaria and anaphylactic shock have been reported thus restricting its topical usage [6]. Umpteen mechanisms have been modelled apropos to toxicity which comprises cytotoxicity related to increased electrostatic forces, inhibition of membrane-bound Na+-K+- ATPase, Release of lysosomal enzymes, increase in permeability to Ca2+ accompanied by leakage of Lactate de Hydrogenase, negatively influencing cell proliferation, protein synthesis and the activities of two types of matrix metalloproteinases (gelatinases A and B) via a cation-chelating mechanism [7].

In contrast, Ozone a naturally occurring gas with three oxygen atoms is a potent oxidant exhibiting low toxicity and broad spectrum of activity, an host immunomodulator displaying biocompatibility with oral epithelial cells, periodontal cells and gingival fibroblasts justifying its use as a local therapeutic agent [8]. Ozone with its anti-hypoxic, bioenergetic, biosynthetic effect improves metabolism of inflamed tissues by activating protein synthesis, increasing number of ribosomes and mitochondria in cells thus explaining the elevation of functional activity as the basis for tissue regeneration [9].

Ozonated water, ozonated olive oil and gaseous ozone happen to be the different modes of delivery of which ozonated olive oil is the ideal delivery system as it entraps and releases ozone in a sustained manner. Ozonated olive oil is pure olive oil that has undergone ozonization using a steady flow of ozone- oxygen mixture in the ratio of 5:95% until olive oil transforms from the greenish-coloured liquid status to the whitish gel status [10].

The evolution of new delivery systems of local drug delivery and with only restricted data available comparing the clinical effectiveness of ozone olive oil in comparison to Chlorhexidine this study was conducted with an aim to evaluate and compare the effects of subgingival application of ozonated olive oil and 0.2% CHX as an adjunct to SRP in patients with chronic periodontitis.

2 Materials and methods

This double-blind non randomized clinical trial, was carried out at the Department of Periodontics, Rural Dental College, Loni. This was a 3months follow up study and the recordings were done at start and at 3 months. After obtaining ethical approval (Pravara Institute of Medical Sciences, PIMS/IEC-DR/2019/14) all participants were verbally informed, and written assent was collected for participation in the study.

3 Statistical analysis

Analysis of statistics was done by descriptive statistics as mean, SD, percentage, proportions. To attain a 90% power and determine mean differences of clinical parameters among groups, 25 sites for every group was required. Comparison of plaque index, gingival index, pocket depth, clinical attachment level from baseline to 3 months in two groups was done by applying student’s paired ‘t’ test at 5% (p < 0.05) level of significance. Statistical analysis software namely SYSTAT version 12 (made by Crane’s software, Bangalore) a licensed copy was used to analyse the data.

4 Results

A total of 50 sites from 25 patients finished the study. Group I consisted of 25 sites, treated by chlorhexidine gel along with SRP (control group); group II comprised of 25 sites, treated with ozonated oil (test group). All treated sites healed without impediment. Baseline analysis exhibited no substantial variation amongst groups for the assessed variables allowing post-treatment results to be compared. The demographic variables are described in Table 1. Demographic data showed that 44% of the sample group were males and 56% were females aged 25–40 (M = 35.84 years, SD = 4.03 years).

Both the groups demonstrated significant intragroup reduction in PI, GI, PD, CAL from baseline to 3 months follow-up. However, on intergroup comparison, no statistically significant differences were found between the CHX and ozonated olive oil groups regarding any of the clinical parameters at the follow-up visit (Tables 2–5).

Elimination of entire subgingival plaque and calculus being the main stay of scaling and root planing, culminates in decline of gingival inflammation and probing pocket depth [11]. However finite access to furcation areas, deep pockets, and irregular surfaces obscure the removal of bacterial deposits, and the procedure is enormously dependent on the skills of the clinician thus necessitating the adjunctive use of antimicrobial agents either as locally delivered or as systemically delivered agents [12]. Adjunctive use of chemotherapeutic agents like ozone and chlorhexidine are therapeutic choices in patients with chronic periodontitis intended for nonsurgical periodontal therapy.

The intent of the present study was to get the measure of the effectiveness of subgingival applications of ozone gel in addition to SRP, with respect to SRP plus a conventional chlorhexidine gel. Intergroup and intragroup differences at the various intervals have been conducted with a view to assess which chemical compound could be more beneficial for the treatment of periodontitis in addition to SRP. The current study noted that clinical parameters such as plaque index, Gingival Index, periodontal pocket depth, and total clinical attachment level were found to favour both the techniques analogously with no intergroup differences and displayed excellent clinical improvements when compared from baseline to 3 months.

Ozone (O₃) gas comprising of three oxygen molecules, has broadened beyond the concept of just another gas of aerosphere. It being a highly water-soluble and inherently unstable inorganic molecule, has showcased substantial benefits in treating a myriad of pathologies [13]. The use of ozone in periodontal therapy is based on its antimicrobial, immune-stimulating, anti-hypoxic, and biosynthetic properties [14].

Ozone’s antibacterial activity against putative periodontopathic microorganisms [15] elucidated by the characteristic peroxidation of the phospholipids leading to the disruption of the bacterial cell envelope integrity [16] consequently attributing to the improvement in the clinical plaque indices following its subgingival application. The reduction of plaque by ozone along with its antioxidant and anti-inflammatory properties furthermore acumens the diminution in inflammation thereupon abating gingival inflammation following therapy. The antioxidant and anti-inflammatory effects of ozone involve activation of nuclear factor erythroid 2-related factor 2 Nrf2, which is considered as a key factor for the efficacy of ozone treatments [17]. Nrf modulates inflammation by conglomeration of the regulation of redox homeostasis and the suppression of pro-inflammatory genes, either directly or through the interaction with NF-κB nuclear transcription factor. NF-κB, coordinates the expression of a spectrum of genes involved in the inflammatory response [18].

The intricate reaction between the immune inflammatory response and periodontopathogenic bacteria usually culminates in chronic periodontitis (CP) symbolized by periodontal pockets, gingival inflammation, and loss of attachment to and in the alveolar bone, eventually leading to tooth loss [19]. Notable improvement in probing pocket depth, clinical attachment level by ozone can be attributed to diverse biological effects like the enhancement of phagocytic activity of defending cells, accelerated migration of epithelial cells, angiogenesis, activation of fibroblasts which are crucial for collagen synthesis [20, 21] along with higher expression of cytokines that are important for wound healing, especially TGF-β1, an important substance for regulation and coordination in the initial wound healing phase [22].

The fundament of successful wound healing dwells on angiogenesis coupled with the interaction of cellular reactions in connective tissue orchestrated by the interaction of blood cells such as neutrophils, platelets, macrophages, and lymphocytes, with cells of the connective tissue including fibroblasts as well as feedback mechanism mediating the rearrangement of extracellular matrix [23].

Angiogenesis, a vital part of the repair process is swayed by both systemic signals from blood compartments and locally from the extracellular matrix. Activin receptor-like kinases (ALK)-1 and 5 are TGF- receptors expressed on endothelial cells and pericytes. Alk-1 promotes proliferation and migration of mesenchymal cells, whereas Alk-5 is known to induce differentiation [24].

The outcome of great deal of earlier studies comparing the efficacy of the application of ozone therapy to chlorhexidine in chronic periodontitis therapy comply with our study exhibiting analogy amidst the two antiseptics [25–29]. Contrasting the remainder of studies displayed no supplementary gain defying the utilization of ozone in nonsurgical periodontal therapy [30–32].

Heinging on the results of our present study ozone can be suggested as a pragmatic approach in the nonsurgical treatment of chronic periodontitis though not surpassing the results of standard SRP and chlorhexidine. Ozone with its antibacterial activity contributes to the reduction of bacterial load along with low fatalness to fibroblasts and osteoblasts as compared to chlorhexidine [29] justifying its preferential use to chlorhexidine.

6 Conclusion

In consideration with the limitations of this study, the promising aspect of ozone therapy to activate several defence mechanisms that cooperate to regain a normal redox system, antimicrobial action and less cytotoxicity can be intended to treat periodontal disease non-surgically and can serve as a good tool during supportive periodontal therapy. Addedly ozone can be regarded as a valid substitute to chlorhexidine, particularly in light of the shortcomings accompanied with the latter. The authors have no acknowledgments.