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J Periodontal Implant Sci
J Periodontal Implant Sci
JPIS
Journal of Periodontal & Implant Science
2093-2278
2093-2286
Korean Academy of Periodontology

38014772
10.5051/jpis.2302400120
Research Article
Implant Science
Effects of adjacent periodontitis on osseointegrated dental implants
https://orcid.org/0000-0001-6979-7861
Ryoo Keun-Soo
https://orcid.org/0000-0001-5611-1242
Kim Kyoung-Hwa
https://orcid.org/0000-0002-4694-5988
Cho Young-Dan
https://orcid.org/0000-0002-2076-5452
Seol Yang-Jo
https://orcid.org/0000-0001-5682-0604
Ku Young
Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Seoul, Korea.
Correspondence: Young Ku. Department of Periodontology, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. guy@snu.ac.kr, Tel: +82-2-6256-3147
Correspondence: Young-Dan Cho. Department of Periodontology, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. cacodm1@snu.ac.kr, Tel: +82-2-6256-3153
8 2024
06 11 2023
54 4 280291
01 6 2023
25 9 2023
09 10 2023
Copyright © 2024. Korean Academy of Periodontology
2024
Korean Academy of Periodontology
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/).
Purpose

This study aimed to investigate whether new-onset periodontitis or apical periodontitis in the adjacent teeth affects osseointegrated dental implants in a beagle dog model.

Methods

One control group and 2 experimental groups (periodontitis and apical periodontitis groups) were defined based on the presence of experimental periodontitis or apical periodontitis, with 1 beagle dog randomly assigned to each group. The mandibular second and fourth premolars on both sides of the 3 beagles were extracted. Eight weeks after extraction, 4 bone-level implant fixtures, 2 on both sides of each mandible, were placed in each beagle. Six weeks after implant surgery, healing abutments were connected. After sufficient osseointegration, plaque control was performed in the control group, while periodontitis and apical periodontitis were induced in the experimental groups. The beagles were euthanized for histological analyses 20 weeks after induction of experimental periodontitis. Statistical analyses were performed using the Kruskal–Wallis test with the Bonferroni correction to compare the 3 groups.

Results

The implants in the control and apical periodontitis groups were well-maintained, while those in the periodontitis group showed clinical signs of inflammation with bone resorption. The bone-to-implant contact (BIC) and bone area values in the periodontitis group were lower than those in the other groups. The distance between the implant shoulder and the first BIC was significantly greater in the periodontitis group than in the control group (P<0.05).

Conclusions

The presence of periodontitis in adjacent teeth can pose a risk to dental implants, potentially resulting in peri-implantitis. However, this was not observed for apical periodontitis. Within the limitations of this study, periodontal care is necessary to reduce the impact of periodontitis in adjacent teeth on osseointegrated implants.

Graphical Abstract

Dental implants
Osseointegration
Periapical periodontitis
Periodontal diseases
Periodontitis
Seoul National University Dental Hospital https://doi.org/10.13039/501100016149 07-2021-0009 National Research Foundation of Korea https://doi.org/10.13039/501100003725 2020R1C1C1005830 2022M3A9F3082330 Ministry of Trade, Industry and Energy https://doi.org/10.13039/501100003052 20019259
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pmcINTRODUCTION

Osseointegration of dental implants results in stable anchorage with direct bone-to-implant contact (BIC) [1]. The concept of osseointegration was first proposed by Brånemark et al., [2] who observed firm anchorage of intra-osseous titanium implants in the rehabilitation of masticatory function in dogs. The long-term survival rate of implants has been reported to be over 95% [3], but several factors can cause implant failure. These failures are classified as early or late depending on whether they occur before or after the development of osseointegration [4]. Early implant failure occurs before or at abutment connection because of inadequate osseointegration due to interference with the healing process [5], which results in a predominance of fibrous tissue formation between the implant surface and the surrounding bone, potentially leading to implant mobility [6]. Among the various etiologic factors of early failure, microorganisms are a common cause of failure of osseointegration [78]. A prospective multicenter study on dental implants in partially edentulous patients reported that early failure was clustered in patients with high dental plaque and gingivitis indices [7]. Infections and inflammatory processes adjacent to an integrating implant may interfere with osseointegration [8]. In contrast, the most common etiologic factor for late implant failure is peri-implantitis [9]. Furthermore, implants with peri-implantitis have microbiota that includes pathogens associated with periodontitis, such as the red complex species (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) and orange complex species (Fusobacterium sp. and Prevotella intermedia) [10].

Previous studies have reported that patients with a history of periodontitis may be more likely to experience implant loss due to greater marginal bone loss and peri-implantitis than patients without a history of periodontitis [1112]. Levin et al. [12] reported a prospective cohort study that revealed an 8-fold higher incidence of late implant failure in patients with severe periodontitis than in periodontally healthy patients. Furthermore, we have previously shown that untreated experimental periodontitis was correlated with early dental implant failure in a beagle dog model. Implant placement was planned in areas adjacent to teeth with induced experimental periodontitis, the presence of which was confirmed before extraction and implant placement. A higher rate of early implant failure was observed in the experimental groups with induced experimental periodontitis than in the control group receiving oral hygiene care [13].

Meanwhile, the occurrence of periodontitis in teeth adjacent to a dental implant, even after achieving osseointegration, may also impact implant survival, since periodontal status is a risk factor for late implant failures [12]; however, few experimental studies have been conducted on this topic.

Furthermore, the presence of periapical pathology and a history of endodontic infections may compromise the successful osseointegration of dental implants [14]. Several studies have reported impaired osseointegration in the periapical region of dental implants adjacent to teeth with periapical lesions [151617], and the term “retrograde peri-implantitis” is commonly used to refer to lesions in the periapical region of dental implants [1819]. Retrograde peri-implantitis is defined as a lesion presenting with progressive bone loss at the apex of an implant with intact peri-implant bone in the coronal portion, and it is considered as a distinct condition from peri-implantitis [18]. Retrograde peri-implantitis has been reported to be detected radiographically between 2 to 8 weeks and up to 4 years after implant placement [20]. Although multiple etiological factors have been proposed, such as excess heat during osteotomy [17] and residual lesions from extracted teeth [19], periapical lesions on neighboring teeth have been frequently discussed [15]. Endodontic infection in adjacent teeth is considered the most common potential cause of retrograde peri-implantitis [15], but our understanding of its etiology remains incomplete [16]. Additionally, there is a limited number of experimental studies addressing this topic.

Therefore, this study attempted to experimentally investigate whether newly induced periodontitis or apical periodontitis in the adjacent teeth affects osseointegrated dental implants, potentially leading to the development of peri-implantitis or retrograde peri-implantitis, in a beagle dog model.

MATERIALS AND METHODS

One control group and 2 experimental groups, namely, the periodontitis and apical periodontitis groups, were defined based on the presence of experimental periodontitis or apical periodontitis. One beagle dog was randomly assigned to each group.

Animals

This study was approved by the KNOTUS Institutional Animal Care and Use Committee of Incheon, Korea (KNOTUS IACUC 21-KE-1015). The animal experiments were performed in accordance with the principles of the 3 R’s (replacement, reduction, and refinement) and the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Three male beagles aged 1–2 years and weighing 11–12 kg were used for the study. The beagle dogs were fed appropriately under standard laboratory conditions with ad libitum access to water and housed individually at an ambient temperature of 23°C±3°C and relative humidity of 55%±15%. The entire surgical procedure was performed under general anesthesia induced using intravenous alfaxalone (3 mg/kg; Alfaxan; Jurox, Kansas City, MO, USA) and maintained with isoflurane (1%–3%; Terrell; Kyongbo Pharmaceutical, Ansan, Korea). Local anesthesia at the surgical sites was induced by injecting 2% lidocaine hydrochloride with 1:100,000 epinephrine.

Surgical procedures

The experimental schedule and the surgical procedure are presented in Figures 1 and 2, respectively. Four implants were assigned to each of the 3 groups (control group, n=4; periodontitis group, n=4; apical periodontitis group, n=4).

Figure 1 Experimental procedure. Implants were placed 8 weeks after tooth extraction in all groups. Healing abutments were connected at 8 weeks after implant placement in all groups. After 2 weeks of healing, abutment connection, scaling, and plaque control were performed in the control group, and experimental periodontitis and apical periodontitis were induced in groups 2 and 3, respectively. All beagles were euthanized 20 weeks after the induction of periodontitis.

Figure 2 Clinical photos of the experimental procedure. (A) At 8 weeks after tooth extraction, the ridge had healed well. (B) The first implant operation to place the fixtures was performed in the healed ridge. (C) At 6 weeks after implant placement, the second implant operation to connect healing abutments was performed. (D-F) At 2 weeks after healing abutment connection, scaling and plaque control were performed in the control group, and experimental periodontitis and apical periodontitis were induced in the experimental groups. At 20 weeks after induction of the experimental conditions, the control (D) and apical periodontitis (F) groups showed a favorable gingival condition, but the periodontitis group showed gingival inflammation (E).

The bilateral mandibular second (2P2) and fourth premolars (4P4) were extracted (Figure 2A). The teeth were separated into mesial and distal parts by hemisecting at the furcation region using a high-speed handpiece with a diamond point bur. The roots were extracted individually to minimize damage to the alveolar bone. Eight weeks after extraction, an incision was made in the midcrestal area in the edentulous sites on both the left and right sides, and full-thickness flaps were raised. Four implants, with two fixtures on each side, were placed in the edentulous area of each beagle dog, specifically in the middle between the mandibular first premolar (1P1) and the mandibular third premolar (3P3), and in the middle between the mandibular third premolar (3P3) and the mandibular first molar (1M1) (Figure 2B). The implants used for this study were internal-type bone-level implants (TSIII; Osstem Implant, Seoul, Korea) with a diameter of 3.5 mm and a length of 8.5 mm. The surface of the implants was sandblasted with large grit and acid-etched, with an average surface roughness (Ra) of 2.0–3.0 µm. The screws were connected to the fixtures and the flaps were sutured with 5-0 nylon (Ethilon; Ethicon, Cornelia, GA, USA). After 8 weeks of healing, full-thickness flaps were raised, and the cover screws were disconnected. Healing abutments with a diameter of 4.0 mm and a length of 3.0 mm were connected to the fixtures (Figure 2C). All implants in the 3 groups exhibited successful osseointegration, and no early implant failure was observed.

Induction of experimental periodontitis and apical periodontitis

Ten weeks after implant placement, experimental periodontitis and apical periodontitis were induced in the experimental groups and oral hygiene care was provided to the control group. In the control group, oral hygiene care with scaling and plaque control procedures was performed monthly, and healthy periodontal conditions were confirmed clinically (Figure 2D) and radiographically (Figure 3A). Experimental periodontitis was induced using gingival retraction cords to allow plaque accumulation on teeth. An experimental study conducted by Lindhe et al. [21] observed that periodontitis could gradually develop from a healthy periodontium simply by allowing plaque to accumulate on the teeth of beagle dogs. In addition, gingival retraction cords were soaked in a suspension of Porphyromonas gingivalis (ATCC 33277) [22]. P. gingivalis produces virulence factors, including lipopolysaccharide, fimbriae, outer membrane proteins, and metabolic end products, which contribute to its pathogenicity and disease progression in chronic periodontitis [23]. Gingival retraction cords were ligatured at the cervical area of the mandibular first premolar (1P1), third premolar (3P3), and first molar (1M1), and packed into the gingival pocket. The condition of the retraction cords was routinely checked, and P. gingivalis was applied monthly. After approximately 20 weeks, experimental periodontitis was confirmed on the basis of clinical signs of gingival inflammation (Figure 2E) and radiographs showing alveolar bone loss (Figure 3B).

Figure 3 Radiographs obtained before and after the induction of experimental periodontitis and apical periodontitis. The left column shows the radiographs obtained before the induction of periodontitis, and the right column shows the radiographs obtained 20 weeks after induction. (A) Control, (B) periodontitis, and (C) apical periodontitis.

Using the methods of previous studies on periapical lesion models [2425], experimental apical periodontitis was induced at 1P1, 3P3, and 1M1 on both sides of the mandible. Balto et al. [24] reported periapical bone resorption in a mouse model through surgical pulp exposure, followed by bacterial infection with a combination of 4 pulpal pathogens: Fusobacterium nucleatum, P. intermedia, Peptostreptococcus micros, and Streptococcus intermedius. Using a similar method, Oseko et al. [25] examined the formation of periapical lesions by infecting surgically exposed pulp with P. gingivalis and P. intermedia. For this study, the pulp was exposed using a carbide round bur, and a suspension of P. gingivalis was injected into the pulp and sealed with a temporary restorative material (Caviton; GC, Tokyo, Japan) (Figure 2F). The procedure was performed monthly until the periapical lesion could be clearly verified on periapical radiographs (Figure 3C). The beagles were euthanized 20 weeks after the induction of experimental and apical periodontitis.

Histologic examination and histometric analysis

The mandibles of the beagles were retrieved and placed in 10% neutral buffered formalin. Tissue blocks, each containing the implant and surrounding soft and hard tissues, were prepared using a diamond saw (Exakt; Kulzer, Germany). Ground sectioning was performed according to previously described methods [26]. The specimens were dehydrated in increasing concentrations of ethanol and embedded in acrylic resin (Technovit 7200 VLC resin; Kulzer, Germany). Each block was sectioned mesiodistally parallel to the implant axis. Two sections were obtained near the center of the implant, and each section was reduced to approximately 50 µm by microgrinding. One was stained with Masson–Goldner trichrome and the other with hematoxylin and eosin. Digital images of the sections were obtained using a digital slide scanner (Panoramic 250 Flash III; 3DHistech, Hungary). Histological and histomorphometric analyses were performed using image analysis software (CaseViewer; 3DHistech, Budapest, Hungary and Image-Pro Plus; Media Cybernetics, Rockville, MD, USA). The following data were obtained from the mesial and distal sides of each implant: 1) the percentage of BIC from the first BIC (fBIC) at the coronal part of the implant to the bottom (Figure 4A); 2) the percentage of bone area (BA) in the areas of interest between the threads [27] in the region of the coronal 3.0 mm (Figure 4B); and 3) the distance between the implant shoulder (IS) and fBIC (IS-fBIC) (Figure 4C).

Figure 4 Methods for histometric analysis. (A) The length of the BIC was measured from the mesial and distal sides of the implant surface, and the percentage of BIC was calculated from these lengths. (B) The area within the implant threads and the reproduced mirror area were chosen as the area of interest for analyzing the bone area. (C) IS and fBIC measurements were used to evaluate marginal bone loss.

BIC: bone-to-implant contact, IS: implant shoulder, fBIC: first BIC.

Statistical analysis

Medians and interquartile ranges (IQRs) were calculated for each group. A normal distribution could not be assumed because of the sample size. The Kruskal–Wallis test, a nonparametric method, was performed to compare the 3 groups, with Bonferroni correction for multiple comparisons. The significance level was set at a P value of less than 0.05. Statistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA).

RESULTS

Clinical and radiographic findings

In the control and the apical periodontitis groups, all implant sites showed uneventful healing without significant inflammation (Figure 2D and F). No marked bone loss was detected on the radiographs in either the crestal or apical area of the implant for the control and the apical periodontitis groups during the experiment (Figure 3A and C). Twenty weeks after implant placement, however, in the periodontitis group, the implants showed signs of inflammation with gingival swelling, redness, and pus discharge on the peri-implant mucosa (Figure 2E). The periodontal group showed marked bone loss on the radiographs in the crestal area of the implant (Figure 3B). At the time of euthanasia, 1 implant in the periodontitis group showed complete loss of the surrounding bone and had spontaneously fallen out.

Histologic findings

Direct contact of the bone with the implants was observed in all groups (Figure 5). Typical trabecular bone patterns surrounding the implants were observed in all groups, and osteocytes were embedded in the lacunae. No marked inflammatory cells were detected in the control (Figure 5A) and apical periodontitis (Figure 5C) groups. Furthermore, the marginal bone was intact for most of the implants in the control (Figure 5A) and apical periodontitis (Figure 5C) groups. However, the periodontitis group showed prominent marginal bone loss and infiltrated connective tissue (Figure 5B) as well as complete loss of the surrounding bone near the failed implant.

Figure 5 Histologic images of all groups. (A) Control, (B) periodontitis, (C) apical periodontitis. Scale bar = 2.0 mm.

Histometric analyses

The BIC values in the periodontitis group (mesial, 54.40% [IQR, 36.72%–60.14%]; distal, 57.66% [IQR, 34.08%–70.14%]) were lower than those in the control group (mesial, 63.34% [IQR, 59.76%–69.06%]; distal, 74.68% [IQR, 68.17%–81.33%]) and apical periodontitis group (mesial, 70.64% [IQR, 64.31%–74.30%)] distal, 76.74% [IQR, 70.06%–81.94%]), although the differences were not statistically significant (Table 1). Likewise, the BA values in the periodontitis group (mesial, 23.85% [IQR, 17.23%–36.39%]; distal, 1.87% [IQR, 0%–19.70%]) were lower than those in the control group (mesial, 65.66% [IQR, 44.78%–86.77%]; distal, 67.62% [IQR, 64.93%–69.64%]) and the apical periodontitis group (mesial, 68.89% [IQR, 61.13%–75.07%]; distal, 74.17% [IQR, 65.70%–77.67%]); however, the differences were not statistically significant. The distal IS-fBIC value in the periodontitis group (distal, 3.44 mm [IQR, 2.52–5.05 mm]) was significantly higher than that in the control group (distal, 0 mm [IQR, 0–0.06 mm]) (P<0.05). The BIC and BA of the failed implant were both considered 0%, while its IS-fBIC was counted as 8.5 mm for the statistical analyses.

Table 1 Median and interquartile range of BIC, BA, and IS-fBIC values

Variables	BIC (%)	BA (%)	IS-fBIC (mm)	
Control (n=4)				
	Mesial	63.34 (59.76–69.06)	65.66 (44.78–86.77)	0.05 (0.03–0.10)	
	Distal	74.68 (68.17–81.33)	67.62 (64.93–69.64)	0 (0–0.06)a)	
Periodontitis (n=4)				
	Mesial	54.40 (36.72–60.14)	23.85 (17.23–36.39)	2.69 (1.75–4.44)	
	Distal	57.66 (34.08–70.14)	1.87 (0–19.70)	3.44 (2.52–5.05)a)	
Apical periodontitis (n=4)				
	Mesial	70.64 (64.31–74.30)	68.89 (61.13–75.07)	0.20 (0.13–0.28)	
	Distal	76.74 (70.06–81.94)	74.17 (65.70–77.67)	0.14 (0.09–0.23)	
Values are presented as median (interquartile range).

BIC: bone-to-implant contact from the fBIC at coronal part of implant to bottom, BA: bone area surrounding implant in the region of the coronal 3.0 mm, IS-fBIC: distance between IS to the fBIC, fBIC: first BIC, IS: implant shoulder.

a)P value less than 0.05 by post hoc comparison using Kruskal-Wallis test with Bonferroni correction.

DISCUSSION

In the present study, the osseointegrated implants adjacent to teeth with experimentally induced periodontitis showed progressive bone loss along with inflammation on the peri-implant mucosa, while apical periodontitis did not have any notable effect on the peri-implant supporting bone during the experimental period. The average IS-fBIC values were highest in the periodontitis group, and the distal IS-fBIC values in the periodontitis group were significantly higher than those in the control group. In the histological assessments, 1 of the osseointegrated implants in the periodontitis group failed due to progressive loss of the supporting bone. These results indicate that periodontitis induced in adjacent teeth can further affect the implant, resulting in peri-implantitis.

One possible explanation for these findings could be the transmission of periodontopathic microbiota from the teeth adjacent to implants. Quirynen and Listgarten [28] proposed that the gingival crevices surrounding the remaining teeth in partially edentulous patients serve as “reservoirs” for the colonization of newly placed abutments on implants. This conclusion was supported by the lack of significant differences in the distribution of bacterial morphotypes around natural teeth and titanium implants observed in their intra-subject comparison. In another study investigating the correlation between periodontopathic bacteria in periodontal pockets and the implant sulcus within individuals using polymerase chain reaction for detection, the authors reported a statistically significant correlation in the colonization of P. gingivalis and Aggregatibacter actinomycetemcomitans between the periodontal pockets and the implant sulcus [29]. Another study reported that the colonization of periodontopathic bacteria such as A. actinomycetemcomitans, F. nucleatum, P. intermedia, P. gingivalis, and T. denticola at the implant sulcus was associated with the microbiota in the gingival crevice of the adjacent teeth instead of the contralateral and occluding teeth [30]. Our results showing that peri-implantitis was induced at implants adjacent to the teeth with periodontitis, but not in those in the control group, are in line with the findings of previous studies regarding the transmission of microorganisms.

This experiment showed that implants adjacent to teeth with newly developed periodontitis exhibited peri-implantitis, while implants adjacent to periodontally healthy teeth showed no signs of peri-implantitis. These findings offer a potential explanation for the increased risk of peri-implantitis in patients with periodontal disease compared to those with healthy periodontal conditions. Stacchi et al. [31] conducted a systematic review, to evaluate whether the history of periodontitis increases the risk of peri-implantitis. The study included 3 prospective studies with more than 3 years of follow-up, comparing patients with periodontal disease to periodontally healthy individuals [113233]. Both implant-based and patient-based meta-analyses showed a significantly higher risk in patients with periodontitis, but more long-term prospective studies with large subjects were needed due to limited evidence [31].

This study aimed to investigate whether the presence of periodontal or endodontic infection in adjacent teeth can affect osseointegrated dental implants, and the results from the periodontitis groups supported the hypothesis. Additionally, prior findings from our research group, as reported by Lee et al., [13] provided evidence of a significant correlation between untreated experimental periodontitis and compromised osseointegration of dental implants in a beagle dog model. Among the 12 implants in the experimental group with induced periodontitis, 4 implants (3 from the immediate implant placement group and 1 from the delayed implant placement group) failed to achieve osseointegration after placement, while no failures were observed in the control group where plaque control procedures were implemented. Derks et al. [34] conducted a multilevel analysis involving 2,765 patients (with 11,311 implants) and found a significantly higher odds ratio (3.29) for early implant loss in patients diagnosed with periodontitis, as opposed to periodontally healthy patients. Moreover, a retrospective study by Olmedo-Gaya et al., [35] involving 142 patients who received a total of 276 implants, observed a significant association between early implant failure and severe periodontal disease. These findings suggest that the presence of periodontal infection can pose a risk to dental implants both before and after osseointegration.

On the other hand, implants immediately placed after teeth extraction with periodontal or endodontic infections demonstrate a high survival rate when appropriate clinical procedures, such as meticulous cleaning and socket debridement, are implemented [14]. In a retrospective study by Bell et al. [36] involving 922 implants, dental implants placed immediately into extraction sites with chronic periapical infections after curettage and irrigation of the periapical lesions had a success rate of 97.5%, while implants placed in sockets without signs of periapical infections exhibited a success rate of 98.7%, but the difference in success rates between the two groups was not statistically significant. Crespi et al. [37] conducted a prospective 4-year study to compare the outcomes of immediate loading of dental implants placed immediately in teeth extraction sites, with and without chronic periodontal lesions. Prior to dental implantation, antibiotic administration, meticulous cleaning, and alveolar debridement procedures were performed. At the 48-month follow-up, the survival rates of 197 implants placed in periodontally infected sites and 78 implants placed in non-infected sites were 98.9% and 100%, respectively, with no statistically significant difference observed between the 2 groups. Similarly, the results of the current study highlight the importance of addressing periodontal infection, as they revealed that 1 out of 4 implants in the periodontitis group failed, while no failures were observed in the control group.

The lack of a significant difference between the periapical periodontitis group and the control group contradicts the findings of several studies that have proposed periapical lesions on adjacent teeth of retrograde peri-implantitis as a potential etiological factor. Sarmast et al. [15] reviewed 20 case reports, which involved a total of 95 dental implants affected by retrograde peri-implantitis. According to the authors, the most frequently suggested possible etiology was an endodontic infection in the adjacent tooth. In a retrospective analysis reported by Lefever et al., [38] the prevalence of retrograde peri-implantitis in implants without endodontic pathology in adjacent teeth was found to be 1%. However, when endodontic pathology was present in adjacent teeth, the percentage increased to 25%, with an odds ratio of 8.0. Another retrospective study reported a prevalence of 7.8% with implants placed adjacent to endodontically treated teeth and a higher incidence of retrograde peri-implantitis in cases where the distances between implants and adjacent teeth were shorter (<2 mm), suggesting that the presence of pre-existing inflammation in the adjacent teeth could potentially lead to retrograde peri-implantitis In other words, that study suggested maintaining a minimum space of 2 mm between the implant and adjacent tooth to reduce the occurrence of retrograde peri-implantitis [39]. However, in the present experiment, the distance between periapical periodontitis and the neighboring implant was not taken into consideration, and this could be a possible reason why the results of the study showed no correlation between periapical lesions and retrograde peri-implantitis. Regrettably, the underlying mechanisms were not investigated in this study, and we hope to address this topic in future studies.

Additionally, a small sample size was allocated for each group, with only 4 implants per beagle in each group. Low statistical power resulting from insufficient sample sizes can compromise the reliability of statistical analysis, making it difficult to interpret the results accurately [40]. Therefore, it is important to consider the limitations imposed by the sample size and approach the interpretation of results with caution.

Within the limitations of this study, proper periodontal care is necessary due to the effects of periodontitis in adjacent teeth on osseointegrated implants. Experimentally induced periodontitis in adjacent teeth significantly affected osseointegrated implants, resulting in progressive bone loss along with inflammation of the peri-implant mucosa. In contrast, experimentally induced apical periodontitis in the adjacent teeth had no effect on osseointegrated implants during the experimental period.

Funding: This study was supported by SNUDH Research Fund (No. 07-2021-0009) and National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1C1C1005830), and Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2022M3A9F3082330), and Technology Innovation Program (or Industrial Strategic Technology Development Program-2022 Industrial Technology Alchymist Project) (20019259, Development of Tissue Rejuvenation technology based on targeted delivery of dental booster) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).

Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Author Contributions: Conceptualization: Keun-Soo Ryoo, Young-Dan Cho, Young Ku.

Formal analysis: Keun-Soo Ryoo, Kyoung-Hwa Kim.

Investigation: Keun-Soo Ryoo.

Methodology: Keun-Soo Ryoo, Kyoung-Hwa Kim, Young-Dan Cho, Young Ku.

Project administration: Yang-Jo Seol, Young-Dan Cho, Young Ku.

Writing - original draft: Keun-Soo Ryoo.

Writing - review & editing: Yang-Jo Seol, Young-Dan Cho, Young Ku.
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