Non-surgical treatment of peri-implantitis with and without erythritol air-polishing a 12-month randomized controlled trial

Peri-implantitis is characterized as a peri-implant mucosal inflammatory lesion coupled with progressive loss of supporting alveolar bone induced due to local accumulation of microbial biofilm [1, 2]. Early intervention appears critical to regain peri-implant mucosal health and arrest further implant bone loss [2, 3]. Hence, several non-surgical and surgical treatment protocols have been proposed, however, with limited clinical benefit [4, 5]. The primary objective of non-surgical treatment is to facilitate patient daily biofilm removal and professional decontamination of the implant disrupting biofilm formation and removing calculus. As surgical management of peri-implantitis is in general the advocated therapeutic intervention, peri-implantitis patients should be carefully monitored in a supportive care program including professionally administrated biofilm removal. Nevertheless, present non-surgical treatment appear unpredictable with time-limited benefit [6].

Several approaches for implant surface decontamination, including titanium curettes, air abrasive devices, ultrasonic devices, oscillating brushes, and lasers have been evaluated [7]. Air-polishing disrupts biofilm formation producing a fine jet of compressed air, water, and fine powder particles. Recent generations air-polishing devices have been equipped with low-abrasive glycine [8, 9], trehalose [10] or erythritol powders [11‐14], coupled with a nozzle for submucosal peri-implant delivery [10, 15‐18]. Erythritol is a non-toxic, chemically neutral, and completely water-soluble polyol produced by the reduction of erythrose [19]. The powder is non-caloric, has a high gastrointestinal tolerance, and does not increase blood glucose or insulin levels [20]. The Commercially available erythritol has a mean particle size of 14 µm with low abrasiveness [21]. Studies comparing conventional mechanical debridement with erythritol air-polishing in periodontitis patients, have reported similar results in supportive periodontal therapy (SPT) relative to clinical and microbiological outcomes [18, 22]. Such observations are also reflected in systematic reviews reporting that air-polishing systems as a monotherapy are comparable to conventional therapy in patients undergoing SPT in single- and multi-rooted teeth [23, 24].

In vitro studies may suggest that erythritol appears more effective than previous agents [21, 25]. In addition, the submucosal nozzle extends the application of air-polishing to reach deep submucosal implant sites to disrupt biofilm formation with minimal implant surface distortion [21]. Favorable clinical outcomes of air-polishing powder therapy of peri-implantitis have been observed [26, 27]. Compared with conventional treatment, higher patient satisfaction, improved time efficiency, without adverse events have been reported [28]. However, a recent 12-month randomized controlled trial (RCT), indicated that erythritol air-polishing as monotherapy had limited effect on subgingival decontamination of periodontal furcation defects compared with conventional mechanical debridement [29]. No prospective studies have reported on benefits of repeated submucosal decontamination of peri-implantitis lesions over 12 months using a low-abrasive erythritol air-polishing system as an adjunct to conventional mechanical instrumentation. We hypothesize that repeated submucosal instrumentation with a low abrasive erythritol air-polishing has an adjunctive decontamination effect compared with conventional non-surgical therapy.

Therefore, the primary objective of this RCT is to assess whether erythritol air-polishing produces an adjunctive effect to conventional non-surgical treatment of peri-implantitis in a cohort of maintenance patients, performed every third month over 12 months. A second objective is to evaluate if such adjunctive treatment influences patient comfort.

The study protocol and informed consent following the Helsinki Declaration of 1975 (version 2008) was approved by the Medical Research Ethics Committee (2019/30233), University of Bergen, Norway. The clinical trial was prospectively registered in ClinicalTrials.gov with registration NCT04152668 (05/11/2019). The study was conducted as a single-masked RCT. Prior to inclusion, participating patients read and signed the informed consent after the investigators had provided a thorough explanation of the study procedure and its associated risks and benefits. All methods were carried out in accordance with relevant guidelines and regulations. The CONSORT guidelines for reporting RCTs were followed.

Of 294 patient charts that were screened from October 2019 to May 2020, 48 met the inclusion criteria and were clinically examined (Fig. 1). Three patients were excluded during the clinical examination due to PD < 4 mm (i.e., a reduction in PD compared with previous records) and two patients declined to participate. Of the 43 patients included (62 implants), 23 were block randomized to the test group and 20 to the control group. In total, 40 patients (57 implants) completed the 12-month study and were included in the statistical analysis. Two patients (three implants) were excluded due to implant fracture and mobility by the 3-month examination. One patient with two implants declined to return to follow-up visits due to cost. No adverse events were reported. The mean age of the study group was 65.1 years, range 33–83 years. Details of age, gender, smoking habits, stage of periodontitis, implant location, brand, years in function, implant length, width of keratinized mucosa, and type of crown/bridge connection of the test and control groups respectively are specified in Table1. There were no intergroup differences at baseline for any of these variables.

The objective of this 12-month, examiner-masked, randomized, controlled clinical trial was to explore whether a low-abrasive erythritol air-polishing system offers adjunctive clinical effects to conventional non-surgical treatment of peri-implantitis, and secondly, to evaluate patient-centred outcomes using VAS. In short, the observations herein indicate that both treatment approaches support clinical improvements. For both groups, a significant reduction in PD was observed from baseline to 6 months, but at 12 months only for the control group. CBLs showed no change over time for either group. BoP was significantly reduced from baseline to 12 months for both treatments. Following instrumentation, less discomfort and pain was reported from the control group and significantly less by males.

At implant sites with peri-implantitis, PD is correlated with bone loss and therefore serves as a relevant surrogate for disease severity [32]. PD recordings around implants are influenced by probing errors [43], grade of inflammation [44], PD severity, and probing force [45]. Further, PD recordings around implants with peri-implantitis might be unprecise since the supracrestal collagen fibers are oriented parallel to the implant surface, allowing the probe to penetrate close to alveolar bone [45]. Despite potential confounding factors, increased PD compared with previous recordings comprise part of the World Workshop case definitions of peri-implantitis [32]. Therefore, we defined PD in addition to CBL loss beyond initial bone remodeling, as primary outcome variables.

Both test and control sites showed significant reduction in PD from baseline to 6 months, but at 12 months only for control sites with significant between-group differences. To date, no studies have reported on erythritol air-polishing as an adjunctive therapy to conventional non-surgical treatment of peri-implantitis in a cohort of maintenance patients. A recent RCT, comparing erythritol air-polishing as monotherapy with piezoelectric ultrasonic scaling in non-surgical treatment of peri-implantitis, reported no significant intergroup treatment differences for clinical peri-implant parameters as PD, suppuration on probing, and plaque score at a 3-month observation [26]. Fourteen patients, four in the airpolishing group and 10 in the ultrasonic group were followed over 12 months. Reported 3-month observations are partly congruent with our 6-month findings revealing no intergroup differences. The exact reason for observing a significant intergroup difference at 12 months and not at 6 month in the present study is hard to pinpoint possibly reflecting a pronounced inflammatory response in the test group expressed as a higher percentage BoP and SUP [46].

At baseline the proportions of sites with PDs ≥ 6 was within both groups above 40%. Over time a significant reduction was observed at 6 months followed by a slight relapse at 12 months particularly in the test group (from 35 to 38%). These findings together with rather high BoP at 12 months (test 37% and control 32%) underline the limitations of non-surgical interventions and that neither treatment approach effectively resolve peri-implantitis. Our observations are thus in support of retrospective [5] and prospective [26] analysis concluding that surgical treatment might be indicated for a significant number of peri-implantitis patients. CBL stability is essential for defining peri-implant health and predicting disease progression [32, 47]. The present study revealed that CBL was stable over time, thus demonstrating that conventional mechanical instrumentation with or without erythritol air-polishing may successfully preserve CBL during 12-month of supportive implant therapy. Similar findings are reported by others [48], indicating that none of the non-surgical decontamination approaches of peri-implantitis are preferred.

In the present study, both interventions induced a significant reduction in the inflammatory surrogates. Improvement in secondary outcomes BoP and PCF have been reported previously comparing air-abrasives devices and conventional mechanical debridement [9, 49, 50]. Whereas present study showed a significant reduction in BoP for both groups, they found a significantly greater reduction in BoP in the air-abrasive group at 3 and 6 months concluding that neither control (ultrasonic) nor test (air-abrasive device) may effectively resolve peri-implantitis [26]. PCF provides an early indication of patients at risk for peri-implantitis and implant loss [51, 52]. Inflammatory exudate leaking out into PCF reflects the nature of the inflammatory lesion [53, 54]. In the present study, PCF was significantly reduced for both groups, between baseline and 6 months and between baseline and 12 months. At both observation intervals, the reductions were increased in the test group compared with the control. However, there were no changes in PCF for either group between 6 and 12 months, corroborating the notion that non-surgical treatment of peri-implantitis is unpredictable [6]. A retrospective study of 304 implants with peri-implantitis reported the prevalence of SUP to be 28% at implant level, and that grades of SUP were associated with peri-implant bone loss and increased PD [46]. Increased tissue inflammation may influence healing response, and implants diagnosed with SUP are more frequently associated with a distinct microbiome compared with implants without [55].

Non-surgical dental implant biofilm disruption appears insufficient intervention in patients with less than optimal oral hygiene [56]. In the present study, at 12 months, plaque scores averaged 35% and 45% for the test and control, respectively. All patients had a previous history of regular maintenance and the implants had been exposed to numerous instrumentations. Less than ideal compliance may thus be explained by loss of motivation after years of comprehensive periodontal and implant therapy. Also, it appears more challenging to obtain clinical resolution in residual than in previously untreated lesions [22, 29]. Further, nine patients (22,5%) were smokers with long-term negative effect on mucosal, periodontal, and peri-implant soft-tissue inflammation and loss of CBL [57].

Previous reports showing enhanced effects of air-abrasive treatment have been limited to teeth [12, 18]. One in vitro study showed that erythritol may alter the microstructure and metabolomic profile of the biofilm composed of Streptococcus gordonii and Porphyromonas gingivalis [58]. Moreover, a more effective biofilm reduction in addition to bactericidal effects of erythritol on pathogenic bacteria have also been observed [59‐61]. Due to the complexity of the dental implant micro/macro structure, the disruption of the biofilm over the exposed threads might be insufficient for clinical resolution and demands further study to optimize clinical protocol, delivery system, as well as agents for submucosal delivery. The same challenge applies also for non-surgical instrumentation with titanium curettes. In agreement with a systematic review and meta-analysis [62], despite clinical improvements, a complete resolution of inflammation was not achieved by any of the treatment approaches.

For both groups, minor pain/discomfort (VAS2) was reported, with significantly less pain/discomfort experienced in control group at baseline, 3, 6, and 9 months. The difference vanished at 12 months, as after 6 months the VAS scores for the test group decreased whereas continued to increase in the control. In the test group the percentage of implants diagnosed with SUP at baseline was 32.3, whereas the corresponding percentage in the control group was 16.7. Thus, a higher proportion of SUP at baseline in the test group, possibly reflecting a higher degree of peri-implant mucosal inflammation, may partly explain the increased pain/discomfort reported up to 9 months in this group. A previous RCT also reported on pain/discomfort following air polishing and ultrasonic scaling [26], however, a closer between studies comparison is prohibited due to that in this RCT local anesthesia was used as needed during interventions. In the present study, females perceived more pain and discomfort than males also reported by Seymour et al. finding females experiencing more post-operative pain than males [63].

The observations reported indicate that ultrasonic/curette subgingival instrumentation with and without erythritol air-polishing support clinical improvements. Over a 12-month period, both treatments prevented further bone loss, but did not adequately arrest inflammation. Thus, neither treatment approach effectively resolves peri-implantitis. A significant inter-treatment difference in PD was observed in favor of ultrasonic/curette instrumentation over 12 months. Following instrumentation, less discomfort and pain were reported in the control group. Future RCTs based on more powerful datasets and with longer follow-up periods are needed to draw clear conclusion about the efficiency of erythritol air-polishing alone or in combination with other non-surgical therapies. Moreover, in advance identification of potential patients characteristics increasing the probability of successful non-surgical peri-implantitis therapy, would be of immense importance. Overall, the results highlight a demand for effective non-surgical protocols for decontamination of dental implants diagnosed with peri-implantitis and that surgical management might be indicated for a significant number of peri-implantitis patients.