Comparison of Ozonated Olive Oil and Chlorhexidine Gel as an Adjunct to Nonsurgical Periodontal Therapy for the Treatment of Chronic Periodontitis: A Randomized Controlled Clinical Trial.

Objectives: Complete elimination of the pathogenic microorganisms from the gingival sulcus area is the ultimate goal of any periodontal therapy. Certain factors such as anatomical variation of teeth, deep periodontal pocket, and tissue-invading ability of some bacteria decrease the effectiveness of conventional nonsurgical periodontal therapy, i.e., scaling and root planing (SRP). Hence, antimicrobial agents could be used as an adjunct to SRP, in order to increase the efficacy of it. Although Chlorhexidine (CHX) is the gold standard as an antiplaque agent, it has several drawbacks. Recently, ozone therapy is being tried for the treatment of several diseases in the field of dentistry. Therefore, the purpose of this study was to evaluate and compare the efficacy of local application of CHX and ozonated olive oil as adjunctive to SRP for the treatment of chronic periodontitis. Materials and
Methods: Thirty individuals who fulfilled the eligibility criteria were selected for this split-mouth randomized controlled trial. The treatment sites from each individual were randomly allocated into two groups. Along with SRP, the local application of CHX and ozonated olive oil was done for the control and test sites, respectively. Pocket probing depth, relative attachment loss, and sulcus bleeding index were measured before and 3 months after the treatment. Intragroup and intergroup differences in the clinical parameters were analyzed by Wilcoxon signed-rank test and Mann-Whitney U test, respectively.
Results: Three months' posttreatment, all the parameters showed significant improvement in both the groups. However, the intergroup comparison failed to be significant statistically.
Conclusion: Ozonated olive oil could enhance the outcomes of SRP for the treatment of periodontal diseases. Copyright:

INTRODUCTION

Chronic periodontitis (CP) is defined as an inflammatory disease of tooth-supporting tissues. If left untreated, CP leads to progressive destruction of the tissues, which clinically features through gingival bleeding, progressively increasing pocket depth, clinical attachment loss and alveolar bone loss, ultimately results in loss of teeth.[1] The primary etiology for periodontal diseases is the complex of dysbiotic microbiota present in dental plaque biofilm.[2] Therefore, elimination of the pathogenic microorganisms is the ultimate goal of any periodontal therapy. This is done by disrupting and removing the dental plaque biofilms from the tooth surface. There are nonsurgical and surgical methods to accomplish the debridement which aims to effective removal of the dental plaque.[3] Although mechanical debridement through scaling and root planing (SRP) is considered as the gold standard for nonsurgical periodontal therapy, certain factors such as anatomical variation of teeth, deep periodontal pocket, and tissue-invading ability of some bacteria decrease the effectiveness of it.[4]

Thus, complete elimination of the microorganisms is hardly achieved, and the bacterial reservoirs survive in those areas, which allows the microbial activity to continue.[5] These factors have led us to the use of various antimicrobial agents, systemically prescribed or locally applied, as adjunctive to the mechanical debridement.[6] Local application of antimicrobial agents has several advantages over systemic use, such as achievement and maintenance of higher concentration of drug for a longer period of time at the diseased site, reduced systemic absorption of the drug, and most importantly, reduced production of the drug-resistant bacterial strains.[7] Over the years, various antimicrobial agents have been tried for subgingival application for the treatment of periodontal diseases and have shown considerable results.[89]

Chlorhexidine (CHX) is a highly effective widely used broad-spectrum antimicrobial agent considered as the gold standard for chemical plaque control. Broad-spectrum antimicrobial activity, substantivity, and lack of toxicity are some of its properties.[10] However, prolonged use of CHX may cause tooth staining, altered taste sensation, impaired wound healing, mucosal erosion, and reduced attachment of fibroblast to tooth surface.[11] These drawbacks of CHX motivate us to seek for a novel antimicrobial therapy, with lesser adverse effects.

Recently, ozone therapy is being successfully used for the treatment of several oral diseases. Ozone is the allotropic form of oxygen. An ozone molecule consists of three oxygen atoms instead of two. This extra atom makes it highly potent for oxidation. High oxidation is necessary for killing microorganisms, especially anaerobic ones.[12] Thus, ozone therapy can be highly effective when used as an antimicrobial agent for the treatment of periodontal diseases, since majority of the potent periodontopathogens are anaerobic in nature.[13]

Ozone can be used in either gaseous or aqueous form. The gaseous form of ozone is very unstable in nature. Therefore, the aqueous form is preferred when using it for the local application. Ozonated olive oil could be a good option for this.[14] The reaction between ozone and the monosaturated fatty acids present in the olive oil occurs, which produces various compounds such as ozonides, aldehydes, peroxides, hydroxyperoxides, etc., these compounds add to the effects of ozone, which is responsible for the wide antimicrobial activity of ozonated olive oil. The wide availability of olive oil makes ozonated olive oil an inexpensive antimicrobial agent.[15] In a recent clinical trial, has concluded that ozonated oil can effectively be used for the improvement of gingival health.[16171819] Although several in vitro studies have shown higher antimicrobial efficacy of ozone compared to CHX, very limited literature are available to prove it clinically. Therefore, this clinical trial was conducted to evaluate and compare the efficacy of ozonated olive oil and CHX when used as a local drug therapy, adjunctive to SRP in patients with CP.

MATERIALS AND METHODS

The protocol for this double-blinded randomized, controlled, clinical trial was reviewed and approved by Dr. NTR University of Health Sciences, Vijaywada and the Institutional Ethical Committee (IEC RC No. NDC/PG/2014-15/EC/2014). The study period was from January 2016 to January 2017. Participants were selected from the outpatient department of Periodontology, Narayana Dental College and Hospital, Nellore, India. The inclusion criteria of the participants were as follows: (1) Age between 30 and 50 years, (2) diagnosed with CP, as defined by American Association of Periodontology,[20] (3) presence of pocket probing depth (PPD) of ≥5 mm and relative attachment level[21] (RAL) of ≥3 mm in two contralateral quadrants of mouth, and (4) presence of minimum of 20 teeth in oral cavity. The participants with a history of any antimicrobial therapy in the last 6 months, systemic disease, pregnancy, lactation, and smoking were excluded from the study.

Thirty participants who fulfilled the eligibility criteria and willing to participate in the study were selected. Informed written consent was obtained from all the participants before starting the study.First, the patients received full-mouth supragingival scaling using the ultrasonic device (EMS Piezon ultrasonic system, EMS Electro Medical Systems, Switzerland) along with proper oral hygiene instructions. A week later, on the baseline day, patients were recalled to undergo the proposed treatment for the study. Each individual was then treated with two treatment protocols. Following a split-mouth design, two sites with PPD ≥5 mm and RAL ≥3 mm were chosen from two contralateral quadrants. Randomization of the treatment sites was done using a coin-toss method and they were divided into two treatment groups. Sites of the test group were treated with SRP along with ozonated olive oil application, and the control sites were subjected to SRP with CHX gel. The SRP was performed with both hand instruments (Supragingival scaler, Hu-Friedy, Chicago, USA) and ultrasonic device.

Preparation of stent and application of drugs

Impressions were made with alginate and casts were poured with dental stone. The casts were used to prepare occlusal stents for the selected sites using self-cure clear acrylic. These stents served as a guide for the measurement of RAL.[21]

Ozonated olive oil gel (purO3 LLC, Fayetteville, Arizona, USA) and CHX gel (Hexigel, ICPA Health Products Ltd., Mumbai, India) were used as local dugs in this study. These drugs were introduced into the selected periodontal pockets with blunt cannula until the drugs overflow.

Outcome variables

All the clinical parameters were recorded by an examiner using a calibrated periodontal probe (UNC-15 graduated periodontal probe, Hu-Friedy, Chicago, United States). The outcome variables of the study were as follows: (1) PPD, (2) RAL, and (3) sulcus bleeding index.[22]

Statistical analysis

All the clinical parameters were subjected to the statistical analysis using the SPSS software version 20.0 (IBM LLC, Chicago, Illinois, USA). Intragroup and intergroup differences in clinical parameters were analyzed by Wilcoxon signed-rank test and Mann–Whitney U test, respectively. P < 0.05 was considered statistically significant.

RESULTS

Three of the participants were lost to follow-up. Therefore, 27 participants were analyzed 3 months' posttreatment. Tissue healing was satisfactory, and no adverse effects due to ozonated olive oil as well as CHX were reported by any of the subjects. The mean age of the patients was 38.2 years. Baseline values of all the parameters were comparable [Table 1]. After 3 months, there was a significant reduction in all the clinical parameters in both the groups [Tables 2 and 3]. However, the difference between the groups in all the parameters was statistically nonsignificant [Table 4].

Table 1

Comparison of mean differences of clinical parameters between the groups at baseline

Clinical parameters	Test site	Control site	Mean difference	P
Probing pocket depths	5.48±0.58	5.67±0.55	0.185±o. 74	0.197 (NS)
Relative attachment level	7.78±0.70	8.04±0.90	0.26±1.10	0.251 (NS)
Sulcus bleeding index	1.50±0.51	1.50±0.51	0.00±0.48	1.0 (NS)

NS: Nonsignificant

Table 2

Comparison of clinical parameters for control group (n=27)

Clinical parameters	Baseline	3 months	Mean difference	P
Probing pocket depths	5.67±0.55	4.56±0.57	1.11±0.32	<0.0001 (HS)
Relative attachment level	8.04±0.89	6.89±0.75	1.15±0.60	<0.0001 (HS)
Sulcus bleeding index	1.52±0.50	0.00±0.000	1.52±0.51	<0.0001 (HS)

HS: Highly significant

Table 3

Comparison of clinical parameters for test group (n=27)

Clinical parameters	Baseline	3 months	Mean difference	P
Probing pocket depths	5.48±0.58	4.19±0.78	1.30±0.47	<0.0001 (HS)
Relative attachment level	7.78±0.69	6.33±0.92	1.44±0.64	<0.0001 (HS)
Sulcus bleeding index	1.52±0.50	0.00±0.00	1.52±0.51	<0.0001 (HS)

HS: Highly significant

Table 4

3 months’ posttreatment comparison of mean differences of clinical parameters between the groups

Clinical parameters	Test site	Control site	P
Probing pocket depth	1.30±0.47	1.11±0.32	0.09 (NS)
Relative attachment level	1.44±0.64	1.15±0.60	0.08 (NS)
Sulcus bleeding index	1.52±0.51	1.52±0.51	1.00 (NS)

NS: Nonsignificant

DISCUSSION

The aim of the present study was to evaluate and compare the efficacy of two different drugs, i.e., ozonated olive oil and CHX gel, when delivered locally as an adjunctive to SRP for the treatment of CP. Split-mouth design was preferred for this study since inter-individual variabilities can be virtually eliminated with this type of study design.[23]

CP is a multifactorial inflammatory disease of the tooth-supporting tissues and dysbiotic microbiota present in dental plaque biofilm being its primary etiology. The tissue destruction in CP results from the interaction between these pathogenic microorganisms and host immune system.[24] The microbiota responsible for periodontal tissue destruction is predominantly anaerobic in nature and located in the gingival sulcus area. Therefore, the main aim of any periodontal treatment is to eradicate or significantly reduce the number of pathogenic microorganisms.[25] SRP, done either by manual instrumentation or by ultrasonics, is usually sufficient to remove the bacterial load to a level where further tissue destruction can be prevented and the periodontal health can be achieved.[25] However, SRP is not adequate in situations such as deep periodontal pocket, presence of anatomical variations, and areas which are inaccessible for the instruments.[4] Therefore, complete removal of the microorganisms is hardly achieved, which demands for the use of an antimicrobial agent in addition to SRP. Adjunctive antimicrobials can be given systemically or locally. Systemic antimicrobials have major drawbacks such as development of antimicrobial resistance and production of drug-resistant bacterial strains.[26] Antimicrobials when delivered locally have lesser adverse effects compared to systemic therapy, with an added advantage that the desired concentration of drug can be maintained at the diseased site for longer duration.[27] Till date, there are various antimicrobials in the form of local drug have been tried successfully for the treatment of periodontal diseases.[9] In our study, subgingival application of CHX showed a significant improvement in the clinical outcomes for the control sites. CHX is a broad-spectrum antimicrobial agent. It has wide range of advantages such as substantivity and antibacterial-antifungal-antiviral activity.[28] CHX is also shown to inhibit dental plaque biofilm significantly.[29] These properties make CHX gold-standard agent for the treatment of gingival and periodontal diseases. However, long-term use of CHX is reported to cause mucosal ulceration, loss of taste sensation, and staining of teeth.[30] These drawbacks of CHX motivate us to search for an alternative antimicrobial agent, with lesser adverse effects.

Ozone molecule, having an extra oxygen atom in it, could be highly effective when used as an antimicrobial agent. It is also capable of stimulating immune response and blood circulation in tissue. Ozone shows the highest level of biocompatibility compared to the other commercially available antiseptic agents. Ozone could be efficacious against both Gram-positive and Gram-negative oral microorganisms.[31] In a study, Nagayoshi et al. confirmed the time-dependant inactivation of cariogenic and periodontopathogenic bacteria by ozone.[17] Another study by Patel et al. had done a study using ozonated olive oil and demonstrated a significant decrease in the count of the potent periodontopathogens without any adverse effects.[32] A number of other clinical studies had also shown the antimicrobial efficacy against microorganisms such as Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythus.[33] Several systematic reviews have concluded that ozone can be successfully used as an antimicrobial agent for periodontal diseases.[343536] In our study, all the clinical parameters showed significant improvements after 3 months of the treatment with subgingival application of ozonated olive oil adjunctive to SRP. Similar results were found in several recent studies where ozone therapy and CHX were compared.[3738] However, contradictory results were also reported.[394041] The factors such as heterogeneity of the studies, presence of confounding factors, and short follow-up period might have played a role for the inconsistencies seen in the results of these studies.[36] Nevertheless, unique properties such as immune modulation, antihypoxia, angiogenesis with no adverse effects makes ozone therapy promising for the treatment of CP.

CONCLUSION

For the treatment of CP, ozonated olive oil could be successfully used as an adjunct to nonsurgical periodontal therapy without any harmful effects. However, clinical trials are further required to confirm its long-term efficacy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.