|Year : 2019 | Volume
| Issue : 4 | Page : 506-511
|Efficacy of a mouthwash containing essential oils and curcumin as an adjunct to nonsurgical periodontal therapy among rheumatoid arthritis patients with chronic periodontitis: A randomized controlled trial
Divvi Anusha1, Preetha Elizabeth Chaly2, Mohammed Junaid2, JE Nijesh2, K Shivashankar1, Shyam Sivasamy2
1 Department of Public Health Dentistry, Indira Gandhi Institute of Dental Sciences, Pondicherry, Tamil Nadu, India
2 Department of Public Health Dentistry, Meenakshi Ammal Dental College and Hospital, Chennai, Tamil Nadu, India
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|Date of Submission||18-Nov-2017|
|Date of Decision||07-Mar-2018|
|Date of Acceptance||14-May-2018|
|Date of Web Publication||18-Nov-2019|
| Abstract|| |
Purpose: The purpose of this study was to assess the efficacy of mouthwash containing essential oils and curcumin (MEC) as an adjunct to nonsurgical periodontal therapy on the disease activity of rheumatoid arthritis (RA) among RA patients with chronic periodontitis (CP). Materials and Methods: A triple-blinded controlled trial was conducted among 45 female RA patients with CP randomized into three treatment groups as follows: Group A: scaling and root planing (SRP) with 0.2% chlorhexidine mouthwash as an adjunct (n = 15), Group B: SRP with MEC as an adjunct (n = 15), and Group C: SRP alone (n = 15). RA disease activity was assessed using erythrocyte sedimentation rate, serum C-reactive protein, serum anti-citrullinated protein antibody, and serum rheumatoid factor. Periodontal disease activity was assessed using plaque index, clinical attachment level (CAL), and pocket depth (PD). All parameters were recorded at baseline and 6 weeks thereafter. Data were assessed using one-way ANOVA and paired t-test. Results: A significant reduction in periodontal and RA disease activity parameters was observed from baseline to 6 weeks following intervention (P < 0.05). The highest percentage of mean reduction in plaque index and RA parameters from baseline to 6 weeks was observed in Group B followed by Groups A and C. The highest percentage of mean reduction in PD and CAL was observed in Group A followed by Groups B and C (P < 0.001). Conclusion: This study reveals that MEC as an adjunct to SRP is effective in reducing the disease activity of RA and CP, thereby warranting the use of the same.
Keywords: Anti-citrullinated protein antibody, chronic periodontitis, essential oil mouthwash with curcumin, rheumatoid arthritis
|How to cite this article:|
Anusha D, Chaly PE, Junaid M, Nijesh J E, Shivashankar K, Sivasamy S. Efficacy of a mouthwash containing essential oils and curcumin as an adjunct to nonsurgical periodontal therapy among rheumatoid arthritis patients with chronic periodontitis: A randomized controlled trial. Indian J Dent Res 2019;30:506-11
|How to cite this URL:|
Anusha D, Chaly PE, Junaid M, Nijesh J E, Shivashankar K, Sivasamy S. Efficacy of a mouthwash containing essential oils and curcumin as an adjunct to nonsurgical periodontal therapy among rheumatoid arthritis patients with chronic periodontitis: A randomized controlled trial. Indian J Dent Res [serial online] 2019 [cited 2020 Aug 10];30:506-11. Available from: http://www.ijdr.in/text.asp?2019/30/4/506/271070
| Introduction|| |
Periodontal disease (PD) is a chronic inflammatory disease where resident cells and preformed mediators induce leukocyte infiltration and progressive destruction of the tooth-supporting tissues as a result of interaction between bacterial products, cell populations, and mediators in disease-susceptible individuals. This is a complex disease with multifactorial etiology and influenced by genetic and environmental risk factors. Rheumatoid arthritis (RA) is a systemic, inflammatory disease that is chronic and progressive, which affects primarily the synovial membrane of the joints and may lead to the destruction of bone and cartilage. Global records indicate that the occurrence rate of this disease in the adult population is about 1% in all ethnic groups, predominantly in females where it is two to three times more prevalent when compared to males.
RA and periodontitis share some common pathogenic features; both are chronic inflammatory diseases with immune-regulatory imbalance, genetic and environmental influences leading to the destruction of conjunctive, and hard tissues. A previous study has reported that the frequency of RA is significantly higher in patients with periodontal disease than in patients without periodontitis (3.95% vs. 0.66%). In addition, other similar studies have reported a higher incidence of missing teeth, dental plaque, greater periodontal pocket depth (PD), or worse clinical attachment levels (CALs) in patients with RA.
Growing evidence suggests that pathogens such as Porphyromonas gingivalis which are associated with periodontal disease could play a role in RA propagation. P. gingivalis is the only known pathogen expressing peptidyl-arginine deiminase which is similar to its human counterpart. This enzyme catalyzes the citrullination of arginine-containing peptides and citrullinated antigens that are thought to drive adaptive immune responses which are exclusive to RA. Concentrations of circulating antibody to P. gingivalis have been revealed to be associated with the expression of anti-citrullinated peptide antibody (ACPA).
Curcumin has been consumed as a dietary supplement for centuries and is considered pharmacologically safe. In ayurvedic medicine, it has been widely used for its antioxidant, anti-inflammatory, analgesic, antiseptic, and antimalarial properties. Essential oils are volatile aroma compounds derived from the plants and are known for their anti-inflammatory, antimicrobial, and antioxidant properties. Research suggests that oxygenated terpenoids found in the essential oils diffuse within the bacterial cell membrane, irreversibly damaging it, and causing cell death.
Although previous studies have shown that periodontal treatment might induce a significant decrease in erythrocyte sedimentation rate (ESR) or disease activity scores in 28 joints in RA patients,, none as of date has been conducted to assess the effect of mouthwash containing essential oils and curcumin (MEC) as an adjunct to periodontal therapy among the patients with RA. Hence, a randomized controlled trial was conducted with the aim to assess RA disease activity after non-surgical periodontal therapy with MEC and chlorhexidine as adjunctive mouthwashes.
| Materials and Methods|| |
Subjects and study design
A triple-blinded randomized controlled trial with concurrent parallel design was carried out among 45 females randomly recruited from August 2016 to January 2017 from a private rheumatology clinic in Guntur city, Andhra Pradesh, India. All patients included in the trial were dentate with minimum 20 teeth and were diagnosed with both RA and moderate chronic periodontitis (CP). RA was diagnosed according to the revised criteria of the American College of Rheumatology, 2010. All selected patients had a joint involvement score of three (4–10 small joints, with or without involvement of large joints) and were under similar medication for RA for the past 1 month (Non-Steroidal anti-inflammatory drug included etodolac and disease-modifying antirheumatic drugs included methotrexate at a dosage determined by the treating rheumatologist based on patient's needs). The diagnostic criteria for moderate CP were the presence of at least two interproximal sites not on the same tooth with probing depth of ≥5 to <7 mm or clinical attachment loss of 3–4 mm or presence of 16%–30% radiographic bone loss with bleeding on probing. Patients with a history of previous antibiotic therapy or periodontal therapy in the past 6 months, systemic diseases other than RA, hypersensitivity to mouthwashes, pregnant women, and tobacco users were excluded from the study. Patients were instructed to continue their regular medications for RA and not to undergo any new treatment for RA during the trial period.
The present study was conducted by the guidelines for good clinical practice and with the Helsinki Declaration of 1975, as revised in 2000. The protocol was approved by the Institutional Ethical Committee of Meenakshi Ammal dental College and Hospital, Chennai, India (MADC/IEC/002/2016), and all the patients provided written informed consent to participate in this study. This trial has been registered in the Clinical Trial Registry of India (CTRI/2017/01/007713). The description of this clinical trial follows the recommendations made by CONSORT in 2010. No external funding was received for this study.
Sample size estimation
This pilot study was conducted among 15 patients (five patients in each group) who satisfied the inclusion criteria to assess the feasibility and sample size for the main study. Sample size estimation was made taking into account the mean difference in serum ACPA levels (since ACPA was considered as a major outcome measure of this study). Using a sampling software, (G power version 18.104.22.168, Heinrich–Heine–Universitat-Dusseldorf, Germany) minimum sample size was calculated to be 13 patients in each group (power 90% and α error at 5%). It was increased to 15 patients in each group based on anticipated dropout rate of 10% as estimated from the previous hospital records. A single examiner performed the clinical examination who was calibrated before the pilot study, and the intraexaminer reliability was assessed (Cronbach's α = 0.87).
Randomization and blinding
Information on intervention allocation was placed in opaque envelopes and patients were asked to choose one envelope randomly. An independent investigator noted the group allocation of each patient, to which the chief investigator was blinded. Intervention allocation was revealed only after the data analysis was completed. The selected patients were randomly assigned into three groups, each group consisting of 15 patients as follows: Group A: scaling and root planning (SRP) with 0.2% chlorhexidine mouthwash as an adjunct, Group B: SRP with MEC as an adjunct, and Group C: SRP alone. The interventions were masked by dispensing them into identical cleaned, opaque amber plastic bottles with appropriate labeling done to avoid patient bias. The experimental mouthwash used in this study is commercially available and its constituents include curcumin (0.10%w/v), clove oil (0.15%v/v), mentha oil (0.15%v/v), eucalyptol (0.09% v/v), thymol (0.10%w/v), and tea tree oil (0.45%v/v).
The plaque index proposed by Silness and Loe in 1967 was used for the assessment of plaque accumulation. For measuring PD, William's periodontal probe was inserted between the tooth and the gingiva, and the distance from the gingival margin to the base of the pocket was noted against the measuring lines on the probe. The level of attachment was measured as the distance between the base of the pocket and a fixed point on the crown such as the cement-enamel junction. A tooth was probed in six sites, the mesiobuccal, midbuccal, distobuccal, and the corresponding sites on the lingual surface. Orthopantomograms of the patients were obtained and read by a periodontist for the confirmation of the diagnosis as moderate CP.
Patients in all three groups received nonsurgical periodontal therapy, which consisted of full mouth SRP using ultrasonic scaler in 1–2 sessions (with a time interval of 24 h between each session) by a single periodontist. Patients in Group A and B were advised to use 10 ml of respective mouthwash undiluted for 1 min twice a day 30 min after brushing (as per manufacturer instructions). All the patients received oral hygiene instructions along with an oral hygiene kit containing a soft-bristled toothbrush and fluoridated toothpaste during the study.
Venous blood samples were obtained by venepuncture under aseptic conditions from the antecubital fossa by a phlebotomist. After placement of a tourniquet, 5 ml of blood were collected using a 5-ml syringe from the median cubital vein in the antecubital region. The fasting blood samples were collected from the study patients between 6:30 and 9:30 AM, and were immediately transferred into K3 EDTA vacutainers. The vacutainers were then labeled and sent to the hematology laboratory of the affiliated hospital's pathology department, where a pathologist blinded to the clinical data performed the hematological investigations. The ESR (Wintrobe's method), C-reactive protein (CRP) (laser nephelometry), rheumatoid factor (RF) (enzyme-linked immunosorbent assay [ELISA]), and anticitrullinated protein antibody (ACPA) (ELISA) were measured.
Both hematological parameters of RA and clinical parameters of moderate CP were assessed at baseline and 6 weeks after intervention.
Statistical analysis was carried out using the statistical software SPSS version 16 (IBM. corp. Chicago., USA). Intergroup comparison of demographic data about the cultural identity, area of residence, and socioeconomic status was carried out using Pearson's Chi-square test. Quantitative data comprising clinical and hematological parameters were tested for normality using Shapiro–Wilks test and were found to be parametric in distribution. (P > 0.05).
Comparison of mean differences about clinical and hematological parameters between three treatment groups at individual time frames was carried out using one-way ANOVA and subsequent pair-wise comparison were done using Tukey's post hoc test. Intragroup mean differences for the above-mentioned parameters between baseline and 6 weeks were carried out using the paired sample t-test.
Percentage reduction in the values for both clinical and hematological parameters was estimated and compared between the three treatment groups using one-way ANOVA test followed by Tukey's post hoc test. A value of P < 0.05 was considered as statistically significant.
| Results|| |
Among the 45 patients who were initially enrolled in the study, 44 participated throughout the entire span of the study. One patient in Group C dropped out of the study due to a knee fracture [Figure 1]. No patients were excluded due to lack of compliance with or intolerance to either treatment regimen. Demographic distribution of patients in the three treatment groups has been revealed in [Table 1].
Baseline characteristics did not differ significantly between the three groups. A significant reduction in ESR, RF, CRP, and ACPA was observed in all treatment groups individually between the two-time points (baseline vs. 6 weeks) (P < 0.001) [Table 2].
|Table 2: Mean values of rheumatoid arthritis and periodontitis parameters at baseline and 6 weeks following intervention|
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When the percentage mean reductions of the above-mentioned parameters were observed, patients in Group B showed the highest percentage mean reduction of inflammatory biomarkers of RA followed by Group A and Group C. A significant difference in percentage mean reduction of all the RA parameters was observed between Group A and Group B; between Group B and Group C; and between Group A and Group C (P = 0.001) [Table 3].
|Table 3: Comparison of mean reductions of inflammatory biomarkers of rheumatoid arthritis between the groups from baseline to 6 weeks after intervention|
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A significant reduction in plaque index scores, PD, and CAL was observed in all treatment groups individually between two time frames (baseline vs. 6 weeks). (P = 0.000) [Table 2] When the percentage mean reductions (from baseline to six weeks) of the above-mentioned parameters were observed, patients in Group B showed the highest percentage mean reduction of plaque index scores followed by Group A and Group C. A significant difference in percentage mean reduction of plaque index scores was observed between Group A and Group C and Group B and Group C, respectively (P = 0.001). However, the difference in percentage mean reduction of plaque index scores between Group A and Group B was not statistically significant (P = 0.243) [Table 3]. The highest percentage mean reduction of PD and CAL was observed in Group A followed by Group B and Group C. The difference was observed in the percentage mean reduction of PD and CAL between the three treatment groups was statistically significant (P = 0.001) [Table 4].
|Table 4: Comparison of mean reductions of clinical parameters of periodontitis between the groups from baseline to 6 weeks after intervention|
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| Discussion|| |
This is the first reported study to evaluate the effect of MEC when used as an adjunct to nonsurgical periodontal therapy on the disease activity of both RA and moderate CP. Heritable changes in gene expression that does not involve changes to the underlying DNA sequence are studied through epigenetics. Epigenetic modifications include chemical alterations of DNA and associated proteins leading to the remodeling of the chromatin and gene malfunctions which may be linked to both RA and periodontitis. These epigenetic alterations have been linked to the X chromosome which may, partly, explain the predominant female prevalence of RA. Hence, in the current trial the eligibility was restricted to female patients with RA.
Over many years, the fundamental treatment of periodontitis has been consistent with the removal of plaque/biofilm and calculus through SRP. Nevertheless, it has been noted that all the patients might not respond to mechanical debridement alone as this treatment aims at removing the whole dental plaque rather than target-specific periopathogens. Certain periopathogens including P. gingivalis may invade the gingival tissues and are thus spared from mechanical debridement providing the source for recolonization of periodontal pockets. Hence, chemical plaque control is advocated as an adjuvant treatment for such tissue invading periopathogens.
The current clinical trial showed that, after nonsurgical periodontal treatment, there was a reduction in inflammatory markers in RA patients with moderate CP, corroborating the impact of the periodontal condition on RA, and a finding similar to previous studies.,
ESR and CRP are the systemic inflammatory markers that can be used to determine the degree of activity of RA at a given point in time. In this regard, a significant decrease in ESR and CRP was observed following periodontal treatment. Two studies showed a significant decrease in ESR values in the RA patients following periodontal treatment., In this study, a statistically significant decrease in CRP levels was detected 6 weeks after nonsurgical periodontal therapy. This finding on the reduction in CRP values was by the results of a previous study, a reduction was observed in CRP levels 4 weeks after nonsurgical periodontal therapy.
Data have shown that ACPA in addition to the RF predate the onset of RA with ACPA levels having the highest predictive value. The results of the present study showed a significant reduction in ACPA levels in all the three groups. Thus, the improvement in RA condition after periodontal therapy might be attributed to a reduction in these markers. Another possible explanation is that elimination of periodontal pathogens by periodontal therapy might reduce exposure of the joints structures to bacteria and their toxins and subsequently lead to improved RA conditions.
The results of the current trial showed a significant improvement in all clinical parameters of the periodontitis in all groups. This can be explained by the fact that thorough SRP has an impact on the clinical findings, irrespective of the adjunctive treatment procedures. These results pertaining to the clinical parameters of periodontitis are consistent with the previous study.
In the present study, the intergroup comparison of periodontal PD and CALs showed a better result for chlorhexidine group compared to its study counterparts, which were by the previous study. The reduction observed in mean plaque scores observed in our study were consistent with the previous study, where turmeric was prescribed along with routine oral hygiene measures, however, not in RA patients. The probable explanation for the above observation lies in the antiplaque effect of curcumin as this was an ingredient of the mouthwash used in both studies. In a previous study, plaque reduction and gingivitis reduction were observed when a mouthwash containing essential oils was used twice daily for 6 weeks.
Guntur city has only two hospitals exclusively for treating RA, and one of it was selected for this study. The patients were selected randomly from this hospital, and hence, the study results can be generalized to a wider population. Shorter duration follow-up and inability to conduct microbiological analysis of plaque samples could be listed as few limitations of our study.
| Conclusion|| |
In summary, we have provided quality evidence to suggest that the commercially available mouthwash containing essential oils with curcumin when used as an adjunct to SRP showed a significant reduction in the disease activity of RA and CP among the study patients compared to other two treatments. The findings of this study may have influence on clinical practice and potentially contribute to further development of new research directions for both dentists and rheumatologists.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005;366:1809-20.
Monsarrat P, Vergnes JN, Cantagrel A, Algans N, Cousty S, Kémoun P, et al
. Effect of periodontal treatment on the clinical parameters of patients with rheumatoid arthritis: Study protocol of the randomized, controlled ESPERA trial. Trials 2013;14:253.
van Vollenhoven RF. Sex differences in rheumatoid arthritis: More than meets the eye. BMC Med 2009;7:12.
Mercado F, Marshall RI, Klestov AC, Bartold PM. Is there a relationship between rheumatoid arthritis and periodontal disease? J Clin Periodontol 2000;27:267-72.
Pischon N, Pischon T, Kröger J, Gülmez E, Kleber BM, Bernimoulin JP, et al
. Association among rheumatoid arthritis, oral hygiene, and periodontitis. J Periodontol 2008;79:979-86.
Ishi Ede P, Bertolo MB, Rossa C Jr., Kirkwood KL, Onofre MA. Periodontal condition in patients with rheumatoid arthritis. Braz Oral Res 2008;22:72-7.
Mikuls TR, Payne JB, Reinhardt RA, Thiele GM, Maziarz E, Cannella AC, et al
. Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis. Int Immunopharmacol 2009;9:38-42.
Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: The Indian solid gold. Adv Exp Med Biol 2007;595:1-75.
Bhatti HN, Khan SS, Khan A, Rani M, Ahmad VU, Choudhary MI, et al
. Biotransformation of monoterpenoids and their antimicrobial activities. Phytomedicine 2014;21:1597-626.
Al-Katma MK, Bissada NF, Bordeaux JM, Sue J, Askari AD. Control of periodontal infection reduces the severity of active rheumatoid arthritis. J Clin Rheumatol 2007;13:134-7.
Ortiz P, Bissada NF, Palomo L, Han YW, Al-Zahrani MS, Panneerselvam A, et al
. Periodontal therapy reduces the severity of active rheumatoid arthritis in patients treated with or without tumor necrosis factor inhibitors. J Periodontol 2009;80:535-40.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd
, et al
. 2010 rheumatoid arthritis classification criteria: An American college of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-81.
American Academy of Periodontology Task Force Report on the update to the 1999 classification of periodontal diseases and conditions. J Periodontol 2015;86:835-8.
Löe H. The gingival index, the plaque index and the retention index systems. J Periodontol 1967;38 Suppl 6:610-6.
Ospelt C, Reedquist KA, Gay S, Tak PP. Inflammatory memories: Is epigenetics the missing link to persistent stromal cell activation in rheumatoid arthritis? Autoimmun Rev 2011;10:519-24.
Amano A. Disruption of epithelial barrier and impairment of cellular function by porphyromonas gingivalis. Front Biosci 2007;12:3965-74.
D'Aiuto F, Nibali L, Parkar M, Suvan J, Tonetti MS. Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol. J Dent Res 2005;84:269-73.
Rantapää-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, et al
. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 2003;48:2741-9.
Gottumukkala SN, Koneru S, Mannem S, Mandalapu N. Effectiveness of sub gingival irrigation of an indigenous 1% curcumin solution on clinical and microbiological parameters in chronic periodontitis patients: A pilot randomized clinical trial. Contemp Clin Dent 2013;4:186-91.
] [Full text]
Nandini N, Vidya D, Komal A. Comparative evaluation of 1% curcumin solution and 0.2% chlorhexidine irrigation as an adjunct to scaling and root planning in management of chronic periodontitis: A clinico-microbiological study. J Pharm Biomed Sci 2012;14:1-7.
Waghmare PF, Chaudhari AU, Karhadkar VM, Jamkhande AS. Comparative evaluation of turmeric and chlorhexidine gluconate mouthwash in prevention of plaque formation and gingivitis: A clinical and microbiological study. J Contemp Dent Pract 2011;12:221-4.
Dr. Divvi Anusha
Department of Public Health Dentistry, Indira Gandhi Institute of Dental Sciences, Pondicherry - 607 402
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4]
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