Apical Periodontitis in Endodontically Treated Teeth: Cross-sectional Study of New Investigated Risk Factors

Background: The present study aimed at investigating risk factors associated to apical periodontitis in endodontically treated teeth and highlight the potential risk of some factors not assessed before in previous studies. Methods: A total of 358 endodontically treated teeth were evaluated after more than 1-year period in a Moroccan population according to predetermined criteria. Studied parameters were assessed clinically and radiographically. The association between coronal restoration quality, cavity design, periodontal status, root canal lling quality, coronal restoration related features, presence or absence of the opposing dentition and the periapical status was determined. Data were analyzed using chi-square test, odds ratio and logistic regression. Results: The present study revealed that gingival health, coronal restoration with CL II cavity design, and root canal lling quality inuenced periapical status of endodontically treated teeth. Multivariate analysis showed that this association was statistically signicant for gingival inammation (95% IC: 1.08-3.91, OR: 2.05, p=0.02), inadequate coronal restoration (95%IC: 1.16-4.04, OR: 2.16, p: 0.01), inadequate root canal lling length and homogeneity (95%IC: 1.24-3.01, OR: 1.93, P:0.004), (95%IC: 1.41-4.44, OR: 2.50, p:0.002) respectively. tooth and


Background
Apical periodontitis (AP) represents in ammation and destruction of the periradicular tissues occurring in response to the presence of microorganisms and their irritants within the root canal system [1] .
The ultimate goal of endodontic treatment is then to eliminate or at least reduce the microbial load within the root canal system through chemomechanical debridement followed by root lling [2]. Even though, post-treatment apical periodontitis is still raising despite technical developments of root canal treatment procedures and the evolution of the understanding of wound healing conditions [3,4]. Bacterial infection/reinfection has been con rmed as the most important etiologic factor related to endodontic treatment failure. Chàvez de Paz revealed in a study carried out on root canals persistent infections that oral microorganisms are able to survive in root canals by adhering to dentine walls. [5] Several factors can lead to endodontic treatment failure, technical quality of coronal restoration seems to have greater impact on periapical status than the quality of root canal lling as reported by many previous studies [6,7]. Nevertheless, contradictory results were revealed by other reports [8,9]. In fact, one of the recognized limitations of these studies that can explain the previous controversial ndings is the only radiographic assessment of coronal restoration quality and periapical status. A clinical and radiologic assessment should be adopted to identify apical periodontitis occurring or persisting after endodontic treatment to refrain from uncertainties that may lead to overdiagnosis or misdiagnosis [10].
It's also conceivable that scoring the quality of coronal restoration from a radiograph is not possible with certainty as it only provides a two dimensional image, and this is supported by previous ndings which stated a weak correlation between radiographic and clinical data related to coronal restoration quality [11][12][13].
Gingival in ammation was reported to be associated with progressing caries and bacterial bio lm activity on approximal surfaces of teeth . Mjör reported that the gingival wall in proximal restorations with overhangs is the most common site of plaque accumulation and the development of recurrent caries [14,15]. To the best of our knowledge, there is no study investigating risk of apical periodontitis in endodontically treated teeth (ETT) related to gingival in ammation and proximal restorations.
The aim of the present study was to assess both clinically and radiographically risk factors associated to apical periodontitis in ETT and to highlight the combined risk of AP assigned to proximal restorations and gingiva status in ETT not investigated previously.

Methods -study design
This cross-sectional study was carried out on patients attending the Department of Conservative dentistry and endodontics within the dental faculty hospital, Rabat (CCTD Rabat). The study was conducted in compliance with the ethical principles stated in the declaration of Helsinki and was approved by the Research Ethics Committee, Mohammed V University, Rabat (comité d'éthique pour la recherche biomédicale de Rabat [CERB]) under ID Number 08/18).

-Patient selection
The Study sample size was calculated considering error α at 0.05 and on the basis of a prevalence of apical periodontitis of (63,79%) in an urban Moroccan adult population seeking routine dental care at the faculty of dental medicine in Rabat . [16] -Inclusion criteria Subjects with no medical history who agreed to participate in the study.
Teeth endodontically treated for more than 1year.
Periapical radiographs with no processing artefacts allowing visualization of the investing bone beyond the radiographic apex at 2mm at least with good density and contrast.

-Exclusion criteria
Patients with medical conditions that may affect the healing process or the immune system conditions included: Diabetes, chemotherapy, Jaw bones radiotherapy, autoimmune disease and patients taking any medication known to alter metabolism such as : immunosuppressive drugs, corticosteroids, Biphosphonates.

Immature teeth
Teeth that have undergone endodontic surgery and apical resection.
Missing information or incomplete record.
-Clinical and radiographic examination Patients participating in the study and seeking routine dental care (no emergency care) were examined clinically and radiographically. All radiographs had been examined using an x-ray viewer under good illumination and 5 × magni cation , optimal conditions were adopted for the best possible radiographic contrast.
A clinical examination was carried out including periodontal probing, palpation of the adjacent mucosa and vertical percussion of the endodontically treated teeth. The coronal restorations were clinically assessed using explorary probe 6 (Dentsply Maillefer, Ballaigues, Switzerland).

-Data collection
For each subject, the following informations were recorded: -Patient's age and Sex.
-Existence of opposing tooth: opposing tooth present or absent.
-Date of root canal treatment completion.
-Type of coronal restoration of the endodontically treated teeth: * full coverage crown: restoration of the coronal part of the tooth which appeared to be a cast restoration or a porcelain crown.
* coronal lling inserted during plastic phase: restoration of the coronal part of the tooth which appeared radiopaque on the radiographs.
-The coronal lling material was speci ed: a composite resin or amalgam restoration.
-cavity design: the cavities were matched according to cavity type (Black's classi cation) -Periodontal health status was classi ed as follows: Presence of dental plaque, bleeding, calculus during probing, gingival recession, loss of periodontal attachment, pocket depth, bone loss in the alveolar crest or in the furcation area and tooth mobility were considered in the assessment of periodontal health. All the periodontal pockets deeper than 4mm were considered pathologic accordingly with the criteria established by the American Academy of Periodontology (2015). [17] *Healthy: no visible bio lm, no gingival bleeding on periodontal probing, physiologic tooth mobility, no probing depth recorded on buccal, lingual, mesial and distal surfaces. *Periodontal disease: presence of gingival bleeding on periodontal probing, pocket depth 4mm, bone loss visible on radiographs, pathologic tooth mobility due to insertion loss.
-Periapical status was classi ed as follows: *Healthy: No clinical symptoms, no rarefaction of bone visible on the radiograph, periodontal ligament of normal width or slightly widened. *Apical periodontitis: clinical signs and symptoms of periapical in ammation, infection or both, widened periodontal ligament, presence of any discernible periapical radiolucency.
The periapical status of endodontically treated teeth was evaluated clinically and radiographically, radiographic criteria used by De Moor et al (2000) and Song et al (2014) were retained [18,19]. The worst periapical status of all canals was taken to represent the periapical status in multi-rooted teeth.
-Coronal restoration quality was assessed as follows: *Adequate: any permanent restoration that appeared clinically and radiographically intact.
*Inadequate: any permanent restoration with detectable clinical and radiographic signs of open margins, overhangs or caries, or no restoration at all.
Coronal restoration was clinically and radiographically determined to have well-sealed margins, to restore tooth anatomy and to be without any recurrent caries. Modi ed and simpli ed Ryge's Criteria were used [20]. (Table1) -The root canal lling quality was classi ed as follows: *Adequate: when all root canals were obturated with dense llings, no visible space between the material and the walls of the canal or within the body of the obturating material, the root canal lling ending within 0-2mm short of the radiographic apex with a consistent taper from the ori ce to the apex. *Inadequate: when the root canal llings were poorly condensed, the canal space visible laterally and apically with no consistent taper and when the root canal llings were over lled or ended 2mm shorter than the radiographic apex or in the presence of un lled canals.
In Multi-rooted teeth, the worst root canal lling quality was considered.
The root canal llings were evaluated according to the European Society of Endodontology (ESE 2006) [21]. Root canal conicity was evaluated on periapical radiographs of endodontically treated teeth according to Shilder's design objectives for root canal shaping and lling as a continuously tapering funneled preparation from the canal ori ce to the apex [22].
A well performed endodontic treatment was assessed according to the previous recommendations as dense with radiopaque appearance of the lled canals and no voids seen between canal lling and canal walls, and the root canal lling ending at 0-2mm from the radiographic apex. Table 1 shows criteria used to assess the quality of coronal restorations and root canal llings.

Data Analysis
Data analysis was performed by using the SPSS Software (Statistical Package for the Social Sciences, version 13.0, IBM, Chicago , IL), continuous variables were presented as means and Standards deviation, or as medians and interquartile range, as appropriate. Categorical variables were presented as numbers and percentages. Association between risk factors and AP was identi ed by a chi-square test or Fisher's exact test, as appropriate. Odds ratio (OR) and 95% con dence interval (CI) were also calculated for each association. Signi cance level was set at p<0.05.
The main outcome measure was the absence versus the presence of apical periodontitis. Apical periodontitis (AP) was the dependent variable , explanatory variables (covariates) were coronal restoration quality, cavity design, coronal lling type and material, root canal lling quality, periodontal health, tooth location, existing of opposing tooth, age and gender.
Univariate and multivariate logistic regressions were used to relate patient and treatment variables with the AP prevalence. Explanatory variables to be included on multivariate analysis were identi ed in multivariate analysis.

Results
AP was detected on 258(72.1%) of the studied endodontically treated teeth. Coronal restoration with open margins and recurrent decay were recorded in 68(19%) and 45 (12.6%) of endodontically treated teeth respectively. 160 (65%) of the restored teeth matched CL II cavity design. (Table 3) shows descriptive data of coronal restoration and root canal lling quality.
( Table 2) gives an overview of the study sample.
Univariate regression analysis showed that inadequate coronal restoration, inadequate root canal lling quality, gingival in ammation and coronal restorations with CL II cavity design were identi ed as risk factors associated with higher rate of apical periodontitis. The results of unadjusted (univariable model) are shown in (table 4).

Discussion
The current study aimed to investigate risk factors associated to apical periodontitis and to highlight the combined risk of AP assigned to proximal restorations and gingival status in endodontically treated teeth not investigated previously. Epidemiological studies in different populations often reveal a high rate of AP associated with root lled teeth [23][24][25]. The results of the present study indicate that (72.1%) of the root lled teeth had AP, this gure is in the range of those found in previous studies [26][27][28][29], and higher than other reports [30].
The interpretation of radiographs is the most common method used to evaluate AP in epidemiological studies [31,32], clinical symptoms such as pain, swelling, sinus tract formation and tenderness are moderately speci c. In the current study AP was diagnosed clinically and radiographically for a better accuracy. In this study periapical radiography was preferred to panoramic examination because not only the presence of AP but also endodontic treatment and coronal restoration quality were assessed.
The present study revealed that both quality of root lling and coronal restoration are equally important for periapical health in endodontically treated teeth and this is in accordance with Hommez et al ndings [11]. On the other hand, according to the present study, when the root canal lling was inadequate, the good coronal seal did not prevent AP in endodontically treated teeth. (Figure A) The present study revealed that inadequate coronal restorations especially those with large proximal margins (CL II cavity design), and gingival in ammation increased the risk of AP in endodontically treated teeth. Only few studies have linked gingival disease to periapical status, Costa et al (2017) reported that gingival bleeding on probing was signi cantly associated to periapical status, however periodontal bone loss didn't in uence periapical health [33]. This is in agreement with the present study results. In similar context, Skupien et al and Khalighinejad et al con rmed in two recent studies the high predictable survival rate of endodontically treated teeth after root canal treatment in cases with a healthy periodontium [34,35].
We can suggest that in endodontically treated teeth several factors can interact with each other, absence of immune defense mechanisms related to vital pulp tissue, coronal restoration with inadequate proximal margins, gingival disease, and inadequate root canal lling if concurrent can potentiate diffusion of micro-organisms in relation to gingival in ammation into root canal space. Gingivitis and apical periodontitis are both a bacterial bio lm-induced diseases, bacteria exert their pathogenicity through direct and/or indirect mechanisms, they can damage host cells and/or the intercellular matrix of connective tissue; host cells can also be stimulated by bacterial components and release chemical mediators involved in the induction of bone resorption [5,36].
In the same context, it was stated that Bio lm formation in root canals is probably initiated after the rst invasion of the pulp chamber by planktonic oral organisms after some tissue breakdown [36]. The invading planktonic organisms can multiply and continue attaching to the root canals, an in ammatory lesion frontage moves successively toward the apex, and bacteria can detach from inner root canal surfaces and mass in the in ammatory lesion [37]. These in ammatory changes occurring in the periapical periodontium are responsible for the disease. The host defenses can eliminate bacteria egressing from the canal, but are unable to eradicate bacteria con ned in the canal because of the absence of an active microcirculation , therefore bacterial infection stays beyond the reaches of body defenses [38]. According to the present study ndings, we can suggest that coronal restorations with inadequate proximal margins especially when gingival in ammation is concurrent and the root canal lling is inadequate are the most affected by bacterial leakage, therefore endodontic treatment failure. Thus the importance of a well sealing coronal restorations for lasting success of endodontic treatment that was stressed by several reports was evident in this study as well [39,40].
Recontamination of the root canal system by coronal leakage has been emphasized. Root canal lling leakage studies reported root canal system reinfection due to micro-organisms and their products after root canal lling exposure [41,42]. Although there is a need to establish the relationship between bacterial leakage and periapical in ammation, thereby the combination of our results and those of other studies [43,44] provide a clinical signi cance to the in vitro ndings.
Frisk reported that association between type of restoration and AP in endodontically treated teeth has signi cance for recurrent caries [45]. However, contrarily to previous studies ndings, the type of coronal restoration in the present study was not associated with AP [46]. This may be explained by the fact that the current study was not statistically powered to demonstrate such differences.
Root canal lling >2mm short from the radiographic apex and root canal llings with inadequate homogeneity were associated with AP in the current study, these results agree with the ndings of previous studies [2] supporting the necessity of instrumentation closer to the radiographic apex and adequate lling of the root canal system . Histopathologic observation studies reported in cases of under-llings, bacterial proliferation in unsealed spaces of the root canal system, over-llings are also associated with extrusion of infected debris toward periapical tissues [1,47]. Eventhough, residual bacteria can not always maintain an infectious process, this is supported by apical periodontitis healing even when bacteria are found in the canal at the lling stage [29], and this could be explained by the fact that a tridimensional and homogenous root canal lling can entomb bacteria in the canal denying them access to periradicular tissues [48].
In the literature, a few reports have been published on the in uence of root canal lling conicity on periapical health [28,49], controversial results were reported in this respect. In the present study, inadequate root canal lling conicity was associated to apical periodontitis when studied as a separate variable, in combination with the above ndings we could suggest that root canal lling conicity can affect periapical health when root canal lling length and homogeneity are inadequate.

Conclusions
Within the limitations of this retrospective study, we can assume that periapical health is a multifactorial disease. Root canal lling and coronal restoration adequacy, gingival in ammation are the most risk factors of apical periodontitis in endodontically treated teeth according to the present study. In addition to the reportings of many surveys, the present study gives an overview of the high prevalence of apical periodontitis still recorded despite restorative and endodontic advances. High prevalence of apical periodontitis within endodontically treated teeth in the current study, should make practitioners aware of the multifactorial aspect of the disease, therefore key features in relation to restorative and endodontic procedures must be well managed to improve periapical health conditions. -Consent for publication: Not applicable -Availability of data and materials: all data generated or analyzed during this study are included in this published article.
-Competing interests: the authors declare that they have no competing interests.
-Funding: the present study didn't receive any funding. All authors read and approved the manuscript.