The objective was to compare the efficiency of probiotic therapy (PT) vs antibiotic therapy (AT) as adjuvants to nonsurgical-mechanical debridement (NSMD) for the treatment of peri-implant mucositis (Pi-M). Volunteers with Pi-M were encompassed. Therapeutically, patients were randomly divided into 3 groups: (a) Group 1: NSMD + PT; (b) Group 2: NSMD + AT; and (c) Group 3: NSMD alone. Peri-implant plaque index (PI), bleeding on probing (BOP), probing depth (PD), and crestal bone loss (CBL) were recorded at baseline and at 3 and 6 months follow-up. P < .05 was selected as the indicator of statistical significance. Forty-two male individuals (14, 14, and 14 in Groups 1, 2, and 3, respectively) were included. At 3 and 6 months of follow-up, PI (P < .01), BOP (P < .01), and PD (P < .01) were higher in Group 2 than Group 1. At 3 months of follow-up, PI (P < .01), BOP (P < .01), and PD (P < .01) were higher in Group 3 than Group 2. At 6 months of follow-up, PI, BOP, and PD were comparable in Groups 2 and 3. In Group 3, PI, BOP, and PD were comparable with the respective baseline values at 6 months of follow-up. The CBL in all groups remained unchanged up to 6 months of follow-up. The NSMD with adjuvant PT is more effective than adjunct AT for the treatment of Pi-M for up to 3 months.

Peri-implant diseases are classified into 2 categories, namely peri-implant mucositis (Pi-M) and peri-implantitis.1  Peri-implant mucositis is clinically manifested as gingival inflammation (peri-implant bleeding on probing [BOP]), and pocket depth of ≥ 4 mm in the absence of crestal bone loss (CBL).2  It has been reported that 43% (range: 19%–55%) of the patients with dental implants develop Pi-M.3  Advancement of Pi-M leads to loss of supporting bone around dental implants (peri-implantitis) and ultimately implant failure.4  Conventionally, nonsurgical-mechanical debridement (NSMD) is done for the treatment of Pi-M.57  During NSMD, peri-implant sulci and implant surfaces is performed using hand-held instruments, such as plastic curettes. Although antibiotic therapy (AT) has been reported to be a useful adjuvant to NSMD for curing peri-implant diseases, its overall effectiveness remains debatable.810 

Probiotics are living micro-organisms, which offer health-related benefits to the host when dispensed in adequate doses and quantity.11,12  From the periodontal perspective, probiotic therapy (PT) using bacteria such as Lactobacillus reuteri has been reported to significantly reduce probing depth (PD) and gingival index (GI) in patients with chronic periodontitis (CP).13  Moreover, PT has also been shown to be useful for managing peri-implant diseases.5  In a study on self-reported nonsmokers with Pi-M, Alqahtani et al5  showed that in the short-term (up to 6 months of follow-up), NSMD with adjunct PT is more effective in the treatment of Pi-M than NSMD alone. Similar results were reported in a triple-blinded randomized controlled trial (RCT) by Galofré et al.14  It is however pertinent to note that in the studies by Alqahtani et al5  and Galofré et al,14  PT was not compared with any other form of adjuvant treatment (such as AT) in patients undergoing NSMD for the treatment of Pi-M. The authors of the present study hypothesize that PT as an adjunct to NSMD is more effective in the treatment of Pi-M than when NSMD is performed with adjuvant AT.

The objective was to compare the efficiency of PT vs AT as adjuvants to NSMD for the treatment of Pi-M.

Ethical approval

The trial was performed in Karachi, Pakistan and was registered by the Institutional Review Board of the Department of Dentistry at the Postgraduate Medical Center (OR/COD/01917-2B). An information sheet was given to all volunteering individuals before they signed the informed consent form. All volunteering individuals were also verbally informed about the objectives of the present study and were invited to ask questions. Individuals who agreed to participate in the present study were requested to sign an informed consent form. The consenting individuals reserved the right of withdrawal with no consequences. There were no monetary and/or other patient incentives for participating in this study.

Subjects

Participants were recruited from the Department of Dentistry of the Postgraduate Medical Center, Karachi, Pakistan. Participants were given contact numbers of the principal investigator to ask questions at any stage of the investigations. All participants were informed about the results of the present study.

Eligibility criteria

Patients with the following characteristics were encompassed: (a) patients having undergone dental implant placement for partial and/or complete edentulism; (b) patients diagnosed with Pi-M (presence of peri-implant soft tissue redness, swelling, and BOP within 30 seconds of probing in the absence of additional CBL following initial healing15; (c) signing the consent form. Patients with the following characteristics were not sought: (a) tobacco smokers and individuals using smokeless tobacco products; (b) patients with self-reported systemic diseases including but not limited to diabetes mellitus, individuals with heart, liver, and kidney-related diseases, hepatic disorders, and renal diseases were excluded; (c) self-reported subjects infected with viruses such as herpes and HIV infection; (d) self-reported patients who had undergone any form of oral surgical and/or nonsurgical intervention such as scaling and root planing (SRP) within the past 6 months; (e) Patients who had consumed antibiotics, probiotics, nonsteroidal anti-inflammatory drugs, bisphosphonates, and chemotherapy/radiotherapy; (f) lactating and/or pregnant females were not sought; and (g) patients with a history or ongoing periodontal diseases (such as periodontitis).

Instrumentation

All patients underwent peri-implant NSMD (Implant Prophy Plastic Dental Instrument System Kit, Tess Corporation, Eau Claire, WI). Oral hygiene instructions related to toothbrushing and flossing were given to all participants. In Group 1, PT was performed as described elsewhere.5  In summary, PT started at the onset of NSMD. Probiotics (Gum PerioBalance; Sunstar, Etoy, Switzerland) were administered in the form of lozenges that contained active units of 2 L reuteri strains (1 × 108 C.F.U of A.T.C.C P.T.A 5289, and 1 × 108 colony forming units of DSM 17938).16,17  The patients were advised to use one lozenge 12 hourly for 21 days, after brushing their teeth.18  Individuals in Group 2 were prescribed amoxicillin 500 mg 3 times daily for 7 days.

Procedures

In the present study, a parallel arm trial design was utilized as described by Nair.19  The trained personnel (AM) established the patient's eligibility after evaluating the baseline and screening information. Randomization was done using a site-specific randomization assignment sequence generated prior to initiation of the present RCT; and allocation to the study groups was done via block randomization.20  Following the confirmation of patient eligibility, the personnel produced a randomization assignment electronically and notified the principal investigator. The principal investigator communicated with the participant with the assigned treatment group. The participants were divided into 3 groups as follows: (a) Group 1: NSMD with adjunct PT; (b) Group 2: NSMD with adjunct AT; and (c) Group 3: NSMD alone. Randomization was done using a computer program (www.random.org, Randomness and Integrity Services Ltd, Dublin, Ireland) (Figure 1).

Figure 1.

Randomization of study groups.

Figure 1.

Randomization of study groups.

Close modal

Questionnaire

Particulars about sex and age, quantity of placed implants, and duration of implants in function was collected. Volunteers were also asked if they had any allergies including penicillin allergy.

Assessment at baseline and at 3 and 6 months

In all groups, modified peri-implant plaque index (PI) and BOP were measured. The peri-implant PD21  was measured to the nearest millimeter using a plastic graded probe. The probe was inserted into the buccal and palatal/lingual sulci and gently moved down until resistance was felt and the corresponding PD was recorded. Plaque index and BOP were measured by a skilled and standardized examiner (κ 0.89). These measurements were performed on 6 surfaces per implant (midlingual/palatal, distolingual/palatal, mesiolingual/palatal, distobuccal, midbuccal, and mesiobuccal). These parameters were recorded at 6 sites (mesial, mid and distal surfaces on the buccal and lingual/palatal surfaces) per implant by a trained assessor (κ 0.94). A graded plastic probe (UNC15 periodontal-probe, Hu-Friedy, Chicago, IL) was used. In all groups, digital radiographs were taken at baseline to verify the extent of CBL.22 

Statistical analysis and sample size calculation

The methodology was assessed by an independent statistician. Group comparisons were done using a computer-based statistical software package (SPSS, 21v, SPSS, Inc, Chicago, IL). Data normality was assessed using the Kolmogorov-Smirnov test. As study variables had normal distribution, analysis of variance and Bonferroni posthoc adjustment tests were done to compare significant differences in PI, BOP, and PD between the groups and 3 and 6 months of follow-up. A P value below 0.01 was considered as an indicator of statistical significance. Power analysis was done considering dental implants with mucositis and established that 14 patients per group showed a statistical power of 95% to detect a real difference in the mean BOP of 0.8 between treatment groups with a standard deviation of 1.7 and α value set at 5%.23 

Characteristics of the study groups

In total, 42 male individuals (14, 14, and 14 in Groups 1, 2 and 3, respectively) were included. The mean age of individuals in Groups 1, 2, and 3 were 45.2 ± 5.1, 45.3 ± 4.9, and 46.1 ±3.7 years, respectively. In Groups 1, 2, and 3, the implants were in function for 3.6 ± 0.5, 3.5 ± 0.3, and 3.5 ± 0.4 years, respectively. Tooth brushing once daily was reported by 85.7% (n = 12), 78.6% (n = 11), and 87.7% (n = 12) individuals in Groups 1, 2, and 3, respectively. Flossing and penicillin allergy were reported by none of the individuals in Groups 1, 2, and 3 (Table 1). All implants were placed at bone-level and had a platform-switched connection. All implants were loaded after approximately 3 months of placement and had moderately rough surfaces with diameters and lengths ranging between 4 and 4.1 mm and 11 and 12 mm. All patients had 1 cement-retained dental implant placed in the region of missing mandibular molars or premolars.

Table 1

Study groups, number of participants and demographics*

Study groups, number of participants and demographics*
Study groups, number of participants and demographics*

Peri-implant parameters at baseline and at 3 and 6 months

Baseline

There was no statistically significant difference in PI, BOP, PD, and CBL among patients in Groups 1, 2, and 3 (Table 2).

Table 2

Peri-implant inflammatory parameters at baseline*

Peri-implant inflammatory parameters at baseline*
Peri-implant inflammatory parameters at baseline*

Group Comparisons at Baseline and at 3 and 6 Months

In Groups 1 and 2, peri-implant PI (P < .01), BOP (P < .01), and PD (P < .01) were significantly higher at baseline compared with 3 and 6 months. In Group 3, peri-implant PI (P < .01), BOP (P < .01), and PD (P < .01) were significantly higher at baseline than at 3 months. In Group 3, peri-implant PI, BOP, and PD were comparable with the respective baseline values at 6 months of follow-up.

Group 1 vs Group 2 at 3 and 6 Months of Follow-up

At 3 and 6 months, PI (P < .01), BOP (P < .01), and PD (P < .01) were significantly higher among patients in Group 2 than Group 1. At 6 months of follow-up, peri-implant PI, BOP, and PD were comparable among patients in Groups 1 and 2 (Figures 2 and 3).

Figure 2.

Mean (± SD) of peri-implant plaque index (PI) (dark grey bars) and bleeding on probing (BOP) (light grey bars) at baseline and at 3 and 6 mo. *In contrast to PI at 3 (P < .01) and 6 mo (P < .01) in Group 1; †In contrast to BOP at 3 (P < .01) and 6 mo (P < .01) in Group 1; ‡In contrast to PI at 3 (P < .01) and 6 mo (P < .01) in Group 2; §In contrast to BOP at 3 (P < .01) and 6 mo (P < .01) in Group 2; ‖In contrast to PI at 3 mo in Group 3 (P < .01); ¶In contrast to BOP at 3 mo in Group 3 (P < .01); #In contrast to PI in Group 2 at 3 (P < .01) and 6 mo (P < .01); **In contrast to BOP in Group 2 at 3 (P < .01) and 6 mo (P < .01); ††In contrast to PI at 3 (P < .01) and 6 mo (P < .01) in Group 3; ‡‡In contrast to BOP at 3 (P < .01) and 6 mo (P < .01) in Group 3; §§In contrast to PI in Group 3 at 3 (P < .01) and 6 mo (P < .01); ‖‖In contrast to BOP in Group 3 at 3 (P < .01) and 6 mo (P < .01).

Figure 2.

Mean (± SD) of peri-implant plaque index (PI) (dark grey bars) and bleeding on probing (BOP) (light grey bars) at baseline and at 3 and 6 mo. *In contrast to PI at 3 (P < .01) and 6 mo (P < .01) in Group 1; †In contrast to BOP at 3 (P < .01) and 6 mo (P < .01) in Group 1; ‡In contrast to PI at 3 (P < .01) and 6 mo (P < .01) in Group 2; §In contrast to BOP at 3 (P < .01) and 6 mo (P < .01) in Group 2; ‖In contrast to PI at 3 mo in Group 3 (P < .01); ¶In contrast to BOP at 3 mo in Group 3 (P < .01); #In contrast to PI in Group 2 at 3 (P < .01) and 6 mo (P < .01); **In contrast to BOP in Group 2 at 3 (P < .01) and 6 mo (P < .01); ††In contrast to PI at 3 (P < .01) and 6 mo (P < .01) in Group 3; ‡‡In contrast to BOP at 3 (P < .01) and 6 mo (P < .01) in Group 3; §§In contrast to PI in Group 3 at 3 (P < .01) and 6 mo (P < .01); ‖‖In contrast to BOP in Group 3 at 3 (P < .01) and 6 mo (P < .01).

Close modal
Figure 3.

Mean (± SD) of peri-implant probing depth index (PD) (dark grey bars) and mesiodistal crestal-bone-loss (light grey and dotted bars, respectively) at baseline and at 3 and 6 mo. *In contrast to PD at 3 (P < .01) and 6 mo (P < .01) in Group 1; †In contrast to PD at 6 mo in Group 1 (P < .01); ‡In contrast to PD at 3 (P < .01) and 6 mo (P < .01) in Group 2; §In contrast to PD at 6 mo in Group 2 (P < .01); ‖In contrast to PD at 3 mo in Group 3 (P < .01); ¶In contrast to PD at 3 and 6 mo in Groups 2 (P < .01) and 3 (P < .01).

Figure 3.

Mean (± SD) of peri-implant probing depth index (PD) (dark grey bars) and mesiodistal crestal-bone-loss (light grey and dotted bars, respectively) at baseline and at 3 and 6 mo. *In contrast to PD at 3 (P < .01) and 6 mo (P < .01) in Group 1; †In contrast to PD at 6 mo in Group 1 (P < .01); ‡In contrast to PD at 3 (P < .01) and 6 mo (P < .01) in Group 2; §In contrast to PD at 6 mo in Group 2 (P < .01); ‖In contrast to PD at 3 mo in Group 3 (P < .01); ¶In contrast to PD at 3 and 6 mo in Groups 2 (P < .01) and 3 (P < .01).

Close modal

Group 1 vs Group 3 at 3 and 6 months

At both time intervals (3 and 6 months), peri-implant PI (P < .01), BOP (P < .01), and PD (P < .01) were significantly higher among patients in Group 3 than Group 1 (Figures 2 and 3).

Group 2 vs Group 3 at 3 and 6 months

At 3 months, PI (P < .01), BOP (P < .01), and PD (P < .01) were significantly higher among patients in Group 3 than Group 2. At 6 months of follow-up, peri-implant PI, BOP, and PD were comparable among patients in Groups 2 and 3 (Figures 2 and 3).

There was no significant difference in mesial and distal CBL in all groups up to 6 months of follow-up (Figures 2 and 3).

Traditionally, antibiotics are used as adjuncts to NSMD for managing periodontal and peri-implant inflammatory conditions, such as CP and Pi-M, respectively.24  However, a limited number of studies5,23,25  have shown that PT is a potentially useful form of adjunct therapy for the management of peri-implant diseases. The precise mode of action of probiotics remains poorly understood; however, one hypothetical justification for this is that NSMD disengages the oral-biofilm thereby augmenting the anti-inflammatory effect of L reuteri. This in turn may reduce the counts of pathogenic microbes such as Prevotella intermedia, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans in the oral biofilm.2628  In a recent systematic review on 9 RCTs, Vives-Soler and Chimenos-Küstner29  concluded that NSMD with adjunct PT is more beneficial than NSMD alone in the treatment of periodontitis. Because the pathogenic microbes associated with the etiopathogenesis of periodontal inflammatory disorders and dental implant-related diseases are similar, NSMD with adjuvant PT seems to be a promising therapeutic protocol for the treatment of peri-implant diseases, including Pi-M.

The present results showed that PT is a more effective adjuvant to NSMD for the treatment of Pi-M than adjunct AT. Nevertheless, it is worth mentioning that in the present study, PT was administered in the form of lozenges (Group 1), whereas antibiotics were administered in the form of tables that the patients swallowed. Moreover, probiotics were prescribed for 21 days as recommended in a previous study18 ; whereas AT was performed for 7 days (based upon the traditional pharmacological instructions).30  The authors speculate that because the probiotics were used as lozenges in the present RCT, the localized intraoral anti-inflammatory effect of L reuteri particularly in the region of the inflamed peri-implant soft tissues was more pronounced as compared with patients in Group 2, in which, the penicillin-based antibiotic induced its effect by reaching the blood-stream through the orogastric route. In a recent RCT, Trajano et al24  assessed the efficacy of SRP with and without the application of a 10% doxycycline (DOX)-based gel in the treatment of periodontitis. In this study, the DOX-based gel was locally applied to the periodontal tissues at baseline and 30 and 60 days after SRP.24  The results showed that local application of 10% DOX-based gel significant reduced periodontal soft tissue inflammatory parameters (BOP, PD, and clinical attachment loss) and improved the alveolar bone density.24  In the present study, PT and AT were performed at one point in time, that is, at the onset of NSMD. This is one explanation for the 3 months of follow-up beneficial effects observed in Group 1 compared with Groups 2 and 3. The authors speculate that the overall anti-inflammatory effect of NSMD are comparable in Groups 1 and 2 when adjuvant AT is performed locally preferably in gel-form). Moreover, pre- and post-NSMD PT and AT are more effective in reducing the severity of Pi-M compared with a single session of these antimicrobial agents. The authors hypothesize that local delivery and repeated sessions of probiotics and antibiotics significantly reduces the severity of Pi-M and the overall anti-inflammatory effects can be sustained in the long-term (for at least 6 months after treatment). Further power-adjusted and well-designed RCTs are needed to these hypotheses.

One limitation of the present RCT is that 1 probiotic strain (L reuteri) was used. A variety of probiotic bacteria such as Lactobacillus salivarius, Lactobacillus brevis, Lactobacillus ratus, and Lactobacillus plantarum have been assessed for the treatment of oral inflammatory conditions such as periodontitis.30  However, the probiotic strain that is most suitable for the treatment of peri-implant diseases remains to be determined. Moreover, in the present study, patients with Pi-M were assessed exclusively. It remains to be determined whether or not NSMD with adjuvant PT helps new bone formation around implants in patients with peri-implantitis. Furthermore, stringent inclusion and exclusion criteria were imposed in the methodology of the present study. Alqahtani et al5  in a RCT showed that tobacco-smoking negatively influences the outcomes of NSMD and this relation is independent of adjuvant treatments including PT. Similarly, systemic diseases such as poorly controlled diabetes mellitus augment oral inflammation compromise the outcomes of oral surgical and nonsurgical interventions.31,32  It is hypothesized that tobacco smoking and a state of immunosuppression negatively affect the efficacy of NSMD with and without adjunct PT and AT in patients with Pi-M. Further studies are needed to test this hypothesis.

The NSMD with adjuvant PT is more effective than adjunct AT in the treatment of Pi-M for up to 3 months.

Abbreviations

Abbreviations
AT:

antibiotic therapy

BOP:

bleeding on probing

CBL:

crestal bone loss

CP:

chronic periodontitis

DOX:

doxycycline

GI:

gingival index

NSMD:

non-surgical-mechanical debridement

PD:

probing depth

PI:

plaque index

Pi-M:

peri-implant mucositis

PT:

probiotic therapy

RCT:

randomized controlled trial

SRP:

scaling and root planing

The authors thank the Statistician Mr Shafqat Saleem for performing the statistical analysis.

FAlq designed and supervised the study and wrote the manuscript; MA, NA, and FA performed the methodology and wrote the results; AB performed the statistical analysis and wrote the results takes responsibility for the integrity of the work as a whole, from inception to published article. AA, FA, NA, and FAlq wrote the discussion. All authors also read and revised the manuscript prior to submission.

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Note The authors declare that they have no conflict of interest and there was no external source of funding for the present study.