Loss of 908 Second Molars in Chinese adults: Consequences of the Presence of Their Neighboring Third Molars?

Background Many studies have reported that the presence of third molars (M3s) can increase the risk of pathology in neighboring second molars (M2s). However, whether the presence of M3s can effect the mortality of M2s remains unknown. The main aim of this study was to reveal the reasons for M2 loss and how the M2 loss were related to their neighboring M3s. Methods This was a retrospective cross-sectional study. A review of the medical records and radiographic imagines of patients who had their M2(s) removed was undertaken to analyze the reasons for tooth extraction and how those reasons were related to the presence of M3s situated adjacent to the removed M2s. Results Clinical material (from January to March 2019) of 800 patients met the inclusion criteria were involved into this study. M2s in 908 quadrants (i.e. 908 M2s) were removed from these enrolled patients, wherein 382 quadrants were with the absence of M3s and the other 526 quadrants were with the presence of M3s. The average age of patients whose missing M2s had or had no neighboring M3s was 52.4 ± 14.8 years and 56.7 ± 14.9 years respectively (Mann-Whitney U test, p < 0.001). When the reasons for the 908 extracted M2s were traced, it was found that 433 teeth (47.7%) were removed due to caries and sequelae, while 300 teeth (33.0%) were lost for periodontal diseases. In addition, substantial evidence conrmed that 14.4% of the M2s with adjacent M3s were removed due to diseases mainly in the distal surface which were closely related to their neighboring M3s, and it was much higher than that was identied from removed M2s without adjacent M3s (1.8%). Except for residual roots, 42.2% M3s were removed along with neighboring M2s simultaneously.


Background
Tooth loss is a global problem which not only impacts patients' daily life, but also be associated with various systemic diseases [1,2,3]. Clinical evidence suggests that, except for third molar (M3), second molar (M2) is one of the most frequently removed permanent teeth in adults [4,5]. Similar to other teeth, many factors may affect a M2's life span, such as oral hygiene, occlusal condition, trauma, smoking, etc. [6]. Among the various risk factors to M2 pathology, the presence of its neighboring M3s has attracted increasing attention [7,8,9]. In this context, studies have con rmed that the presence of impacted M3s (I-M3s) increases the risk of M2 pathology by 1.45-4.88 folds [8,9]. In recent years, investigations have found that erupted M3s (E-M3s) also negatively impact oral health and scientists have reported that the presence of E-M3s increases the risk of M2 pathology by 1.44-1.77 folds [8,9,10]. When M2s are too heavily damaged to be treated or controlled, they can only be removed.
To protect M2s from loss, on one hand we should try to identify early pathology (i.e. caries and periodontitis) before irreversible damage occurs in M2s, and on the other hand, minimizing the risk factors that cause M2 caries and periodontitis is of equal importance. With regard to the well-known risk factor --the presence of M3s, preventive extraction of M3s may be the most thoroughly solution. There is substantial evidence that the removal of M3s leads to a lower incidence rate of distal surface caries on M2s and improves the periodontal health of distal M2s [11,12,13,14]. However, the decision on preventive extraction of asymptomatic M3s is challenging for dentists as well as patients. In many clinical situations, asymptomatic M3s are indeed more likely retained until irreversible damages to their neighbors occur [15,16,17].
Unfortunately, researchers have found that, even the health status of M2s is actively monitored, there is still a signi cant rate of M2 mortality [18]. Till now, we still don't know whether there is a relationship between M2 loss and their adjacent M3s. If the M2s are removed due to the presence of M3s, maybe it is time to justify whether medical decision based on the high con dence to our patients' compliance is wise.
Tracing the reasons of M2 loss in clinics may help dentists better understand the relationship between M2 loss and their neighboring M3s and hence to do timely interventions to actively protect M2s from M3-related damage. In this study, 800 patients with their 908 M2s being removed were analyzed to identify (1) who's M2s were removed; (2) the reasons why M2s were extracted and to what degree those reasons were closely related to the presence of their neighboring M3s; (3) how these M3s were handled in clinic.

Ethics
This was a retrospective cross-sectional study based on the medical records and radiographic imagines of patients who had their M2(s) removed in the Dental Hospital of Fourth Military Medical University (FMMU), Xi'an, China. The research process was strictly followed the requirements of the Helsinki declaration and was approved by the ethics committee of this hospital.

Inclusion and exclusion criteria
Clinical material of patients who had visited the Department of Oral and Maxillofacial Surgery from January 2019 to March 2019 were continuously screened. The inclusion criteria were: (i) patients with age ≥ 18 years old; (ii) patients who have at least one M2 extracted; (iii) patients with complete and explicit medical records and radiographic imagines of their extracted M2s (prior to extraction) and their neighboring M3s (if any).
Patients with incomplete medical records or inadequate quality of radiographic imagines on either the extracted M2 or their neighboring M3 had incomplete medical records or inadequate quality of radiographic imagines were excluded from this study. Besides, patients with discrepant medical records and radiographic imagines also excluded from analysis.

Reasons for M2 extraction
The reasons for M2 extraction were mainly classi ed into the following three categories: (i) Severe caries and sequelae -whenever the primary indication for extraction was caries or its sequelae, e.g., untreatable caries, residual roots, diseases of pulp and periapical tissue; (ii) Irreversible periodontitis -when M2 was extracted for periodontal breakdown; (iii) Others -Orthodontic needs, cysts or tumors, non-carious defect (e.g., tooth fracture or root resorption), and other ambiguous reasons for M2 extraction. When periodontal disease and caries (or its sequelae) presented in a M2 at the same time, only the predominant reason for M2 extraction was recorded. In this case, if it is not possible to identify which disease was more likely the main reason for M2 loss, it was recorded as comorbidities and assigned to the category of "others".

Data collection
Demographic information of patients (age, gender, systematic diseases, smoking status, etc.) and details about the extracted M2s (prior to extraction) and their neighboring M3s (disease and clinical situation of the M2s before extraction, the status of M3s, etc.) were continuously extracted from the electronic medical system (doctors) of the Hospital. To minimize errors, the radiographic images were observed in a digital viewer (Hi Net, Hwatech, Xi'an, China) to judge whether ndings from the radiographic images were consistent with the data in medical records (especially the reasons of M2 extraction).

Groups
Based on the absence/presence and status of M3s, quadrants with M2s being extracted were divided into M3 (-) group (quadrants with M2s being extracted with the absence of M3s) and M3 (+) (quadrants with M2s being extracted with the presence of M3s). In this context, quadrants in M3 (+) group were further divided into E-M3 group (quadrants with M2s being extracted with erupted M3s) and I-M3 group (quadrants with M2s being extracted with impacted M3s), wherein quadrants with M2s being extracted with neighboring M3s that were residual roots or microdontia were excluded for analysis.

Statistical methods
EpiData (version 3.0, the EpiData Association, Denmark) was used to collect data, and SPSS (version 20, IBM, Chicago, USA) was used to analysis data. Missing or abnormal data were replenished according to patients' medical records and radiographic images. The normality of qualitative data (age) was tested by Shapiro-Wilk test. Results showed that the age of all groups was non-normally distributed. Therefore, the differences of age between two groups were tested by Mann-Whitney U tests. The differences of quantitative data (gender, jaw, right/left and indications) between two groups were tested by Chi-Square tests. The two-sided signi cant level was set at p < 0.05.

Clinical material for analysis
According to the electronic medical records system, approximately twenty thousand person-time visited the Department of Oral and Maxillofacial Surgery from January to March in 2019. Among them, there were 854 patients who had at least one M2 removed. Clinical material of 54 patients was excluded to this study due to either incomplete medical records or poor quality of radiographic images or both reasons. Finally, Clinical material of 800 patients was applied for analysis in this study.

Characteristics of the patients
Characteristics of the patients whose clinical material was applied for investigation were shown in Table 1.
Most of the subjects (87.6%) had only one M2 removed. The age of these enrolled patients ranged from 19 years to 91 years and the mean age was 54.1 (SD: 15.0) years. Of all the subjects, 95.3% were nonsmokers. The proportion of males (54.6%) was higher than that of females (45.4%). In addition, the prevalence of systematic disease(s) in these patients was 36.0%, and among them, 36.1% suffered a combination of several systematic diseases.  Reasons for M2 extraction When the reasons for M2 extraction was traced (Fig. 1), nearly half of M2s (47.7%) were extracted due to caries and indeed the consequences of M2 caries; among them 61.7% M2s were residual roots. Other 33.0% M2s were removed due to local advanced periodontitis and the remaining 19.3% extractions were for other reasons including tooth fracture, comorbidities, cysts, tumors and so on. It was interesting that in the category of "others", non-carious tooth fracture was the most common reason and about 1/10 of the 908 M2s were extracted for this reason.
The main reasons for extraction of the 908 M2s were caries and its sequelae (47.7%) and periodontal diseases (33.0%) (Fig. 1). But the distribution of them (caries and sequelae, periodontal diseases and others) were not the same between M2s with/without neighboring M3s. Table 3 showed the reasons for M2 removal in these groups. Similar to the entire samples, the most common reason of M2 extraction in the M3 (+) group and the M3 (-) group was still the caries and its sequelae. However, the distribution of indications for M2 removal between the two groups was different (p = 0.003). The percentage of M2 loss due to periodontal diseases was higher in the M3 (+) group than that of the M3 (-) group. Besides, the prevalence of extracted M2s ascribe to periodontal diseases was higher in the E-M3 group (42.3%) than that of the I-M3 group (29.7%, p = 0.009).
In order to study whether the M2 loss was related to their adjacent M3s, the M2s were divided into three categories according to the location of diseases in M2s: mainly occurred in the distal surface of M2s, mainly occurred in other surfaces except for the distal surface, and the diseases which were unable to con rm whether they mainly occurred in the distal surface or not (Table 3). On the whole, in the M3 (-) group, only 1.8% M2s were extracted for diseases mainly occurred in the distal surface, however, it was much higher in the M3 (+) group (14.4%). In the I-M3 group, 64 M2s (44.1%) were extracted due to distal diseases, including 29 extractions caused by periodontal diseases, 24 extracted M2s due to caries and its sequelae, and 11 M2s loss of root resorption, cyst or other diseases. In the E-M3 group, although the rate of M2 extraction due to distal diseases (3.5%) was lower than that of the I-M3 group, it was still higher than that of M2s without neighboring M3s.  The reasons of M3 removal along with adjacent M2 extraction were further analyzed in Fig. 2; indications for extraction were generally classi ed into four categories: prophylactic extraction, caries and sequelae, periodontal diseases and others. Except for the 33 residual roots, 92 I-M3s and 112 E-M3s (Table 4) were enrolled in this analysis. Results showed that the distribution of M3 removal were greatly different between I-M3s and E-M3s group (p < 0.001). Most I-M3s (81.5%) were disease-free or in the early stages of diseases and they were proactively removed during the neighboring M2 extraction surgeries; only 7.6% I-M3s were removed due to caries and sequelae and 3.3% I-M3s were extracted because of periodontitis (Fig. 2a). However, across the extracted E-M3s, 4/5 were removed due to irreversible diseases (Fig. 2b) Tooth loss can not only affects the daily quality of life of patients, but is also associated with a variety of systemic diseases, even with patients' longevity [1,2]. Therefore, clarifying the patterns of tooth loss may help dentists protect teeth more e ciently. Caries and periodontal diseases are the two major causes of tooth loss reported in previous studies [21,22], and they were consistent with the main reasons for M2 loss in this study ( Fig. 1). Meanwhile, what makes the M2 different from other teeth is the presence of neighboring M3s, which is the most frequently impacted tooth [23]. M3 related diseases includes pericoronitis, caries, cysts, tumors, as well as the destruction of adjacent M2s, etc. [24,25,26]. The in uence of M3s on adjacent M2s is widely concerned. Studies have con rmed that the presence of M3s is a risk factor for adjacent M2s [8,9,10]. Thus, it's not rigorous to separate M2s with neighboring M3s when tracing the pattern of M2 loss.
In this study, the main reason for M2 extraction was caries and its sequelae and the next was the periodontal diseases, however, the distribution of the indications were different in different groups. In the I-M3 group, approximately 1/2 M2s were extracted for caries and its sequelae, and 1/3 M2s were removed due to periodontal diseases (Table 3). However, when M3s were erupted, the percentage of periodontal diseases were much higher and it almost caught up with the percentage of caries and its sequelae. In recent years, several studies have explored the negative effect of erupted M3s and found that the risk of periodontal destruction of M2s may increase 1.44-6.79 folds when erupted M3 present [8,9,20,27]. In this study, the high percentage of periodontal diseases in the E-M3 group also remained clinicians to focus not only on the caries but also on the periodontal diseases.
There are too many factors affect a M2's life span [6,19], that's why to date there is no direct evidence revealing the relationship of M2 loss with their neighboring M3s. It's generally believed that the negative effect of M3s mainly occurred in the distal M2s [9,13,20], thus the prevalence of M2 loss due to diseases in the distal surface may re ect the in uence of M3s on the adjacent M2s. On the basis of this assumption, we compared the incidence of distal diseases in extracted M2s adjacent to different status of M3s. In this study, when M2s were divided into different groups according to the status of neighboring M3s, the ndings were interesting. Results (Table 3) showed that the prevalence of M2 loss due to diseases in the distal surface was higher in M2s with presence of adjacent M3s (14.4%) than those without M3s (1.8%), especially when M3s were impacted (44.1%). Although the rate of M2 extraction due to distal diseases (3.5%) was lower than that of the I-M3 group, the passive effect of erupted M3s on their neighboring M2s still needs attention. In a 25- year corhort study, scientists reported that during the follow-up, 14.6-39.1% M2s adjacent to impacted M3s and 3.8% M2s neighbored with erupted M3s were removed, while none of the M2s with the absence of M3s were extracted [18]. Combined the two studies, the authors concluded that the presence of M3s may lead to the loss of M2s. Besides, in this study, the diseases in 4/5 M2s were too severe to con rm where they mainly occurred (Table 3), which means diseases in some of these M2s may originated from the distal surface.
What's more, most of caries or periodontal diseases that occurred only in distal M2s can be treated, thus our study may underestimated the negative effect of M3s.
Although the presence of M3s is generally believed to increase the residual periodontal pockets and caries risks of M2s [24,26,28], the decision on preventive extraction of asymptomatic M3s is hard for dentists and patients [17,29]. Even in most studies, the preventive extraction of M3s can be bene t for the health of neighboring M2s [11,13,14], in many clinical situations, asymptomatic M3s are indeed more likely retained until irreversible damages happen [15,16]. Such evidence were also found in this study (Table 4) Preventive extraction of M3s may be the most thoroughly way to protect M2s. However, M3 extraction is neither risk-free nor cost-free, especially for some of E-M3s whom still have occlusal function in mouth.
Therefore, the prophylactic removal of all asymptomatic M3s is unreasonable, and it is important to screen out high-risk patients and M2s. Studies have found that men, old age and other factors can increase the risk of M2 destruction [10,27,30]. Although the characteristics of the population included in this study could not verify the risk factors of M2s, the mean age of patients were old, the percentage of males were higher than that of females (Table 1).
Many studies have con rmed that age is signi cantly associated with tooth loss [3,4]. In our study, patients' mean age was 54.1 years and it was similar to that of the studies of all types of permanent tooth loss [5,31].
Compared with M2s without adjacent M3s, the mean age of M2 extraction was younger when M3 present (

Declarations
Ethics approval and consent to participate The research process was strictly followed the requirements of the Helsinki declaration and was approved by the ethics committee of the Dental Hospital of Fourth Military Medical University (IRB-REV-2017034).

Consent for publication
Not applicable.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests. Reasons for extraction of I-M3 (a) and E-M3 (b) along with adjacent M2 extraction