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How Is Third Molar Status Associated With the Occurrence of Mandibular Angle and Condyle Fractures?
Accepted Manuscript How is third molar status associated with the occurrence of mandibular angle and condyle fractures? Shuai Xu, Ph.D, Resident, Jun-jie Huang, MS, Resident, Yu Xiong, Associate Professor, Ying-hui Tan, Professor PII:
S0278-2391(17)30339-7
DOI:
10.1016/j.joms.2017.03.021
Reference:
YJOMS 57711
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 24 November 2016 Revised Date:
14 March 2017
Accepted Date: 14 March 2017
Please cite this article as: Xu S, Huang J-j, Xiong Y, Tan Y-h, How is third molar status associated with the occurrence of mandibular angle and condyle fractures?, Journal of Oral and Maxillofacial Surgery (2017), doi: 10.1016/j.joms.2017.03.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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How is third molar status associated with the occurrence of mandibular angle and condyle fractures?
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Authors and Affiliations Shuai Xu, Resident, Ph.D1, Jun-jie Huang, Resident, MS2, Yu Xiong, Associate Professor3, and Ying-hui Tan, Professor4*.
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Medical University, Chongqing, China
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1. Resident, Department of Stomatology, Xinqiao Hospital, Third Military
2. Resident, Department of Stomatology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
3. Associate Professor, Department of Stomatology, Southwest Hospital,
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Third Military Medical University, Chongqing, 400038, China 4. Professor, Department of Stomatology, Xinqiao Hospital, Third Military
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Medical University, Chongqing, China *Correspondence Author: Ying-hui Tan
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Address: Department of Stomatology, Xinqiao Hospital, Third Military Medical University, 183 Xinqiaozhengjie St, Shapingba District, Chongqing 400037, China E-mail :[email protected]
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Abstract Purpose: The third molars (M3s) have been hypothesized to be associated with the risk of mandibular angle fracture and mandibular condylar fracture. We systematically
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estimated the relative risk of M3 status for the development of mandibular angle fracture and mandibular condylar fracture through a meta-analysis of cohort studies.
Methods: In this systematic review, PubMed, EMBASE, and the Cochrane Library
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were searched from inception to October 2016. The predictor of risk was the presence
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or absence of M3s. The primary outcome was the relative risk of mandibular angle or condylar fracture. Either a fixed or a random-effects model was applied to evaluate the pooled risk estimates. Sensitivity analysis was also performed to identify the potential sources of heterogeneity. Publication bias was assessed by the Begg’s and Egger’s
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tests.
Results: Overall, 13 retrospective cohort studies were included. Of these, 13 reported the association between M3s and mandibular angle fracture, while 5 reported the
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association with mandibular condylar fracture. Patients with M3s had an increased risk
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of mandibular angle fractures (RR = 2.63, 95% confidence interval [CI] 2.15–3.21) but a decreased risk of mandibular condylar fractures (RR = 0.47, 95% CI 0.25–0.86). Substantial heterogeneity in the risk estimates was revealed. No evidence of publication bias was found. Conclusion: The current meta-analysis provides further evidence that the presence of M3s is associated with an increased risk of mandibular angle fractures and a simultaneously decreased risk of mandibular condylar fracture. Due to the potentially
ACCEPTED MANUSCRIPT more serious complications associated with condylar fracture, clinicians should carefully consider the decision to remove M3s for the purpose of decreasing the risk of
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mandibular angle fracture.
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Introduction The mandible is the largest and the strongest bone in the facial skeleton. However, it is very frequently fractured because of its prominent and exposed location. According to
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previous biomechanical and epidemiologic studies, the incidence of mandibular fracture varies from 15.5 to 59% of all facial fractures, for patients between the age of 16 and 30 years1, 2. Ellis et al.1 also found that mandibular angle fracture is common and
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comprises approximately 30% of all mandibular fractures. The occurrence of
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mandibular angle fracture is usually related to many factors such as the direction and severity of the impact, presence of soft tissue bulk, and occlusal loading pattern, as well as biomechanical characteristics, such as the bone density, mass, and weak regions of anatomic structures3. As the mandibular angle forms the junction between the ramus
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and the body, it is commonly associated with the third molars (M3s). In other words, the status of the M3s affects the risk of mandibular angle fracture4. Various studies have reported that the presence of M3s is associated with an
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increased risk for angle fracture, especially when these M3s are partially erupted or
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unerupted5. Iida et al.6 showed that incompletely erupted M3s had a high risk for mandibular angle fracture. Antic et al.7 also observed that there was a 3.6-fold increased risk for mandibular angle fracture when M3s were present, compared with M3s being absent. Safdar et al8 reported that impacted M3s increased the likelihood of angle fractures by reducing the bone quality and bone mass in the mandibular angle region. Accordingly, some authors recommend the early extraction of asymptomatic M3s to decrease the risk of mandibular angle fracture.
ACCEPTED MANUSCRIPT However, more recent studies9 observed that patients without M3s were more likely to develop another type of mandibular fracture, mandibular condyle fracture, compared with those who had M3s. The treatment of condyle fracture is more
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challenging, with a higher risk of postoperative complications compared to angle fracture. Therefore, the decision to remove M3s as a means of preventing mandibular angle fracture might not be as straightforward as previously thought. These disputes
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mandibular angle and condylar fracture.
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require further systematic analysis on the relationship between M3 status and the risk of
Therefore, this systematic review aimed to pool data from individual studies, and a meta-analysis was performed to quantify the association between M3 status and the incidence of mandibular angle as well as condyle fracture. The investigators
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hypothesize that patients with M3s are at an increased risk of mandibular angle fracture, compared to those without, and that removal of M3s will decrease this risk,
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Methods
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while increasing the risk of condylar fracture.
Literature search and study selection We conducted a systematic literature search by using the PubMed, EMBASE, and Cochrane Library Database to identify relevant studies from the earliest available data to October 2016. To identify relevant studies, the search strategy combined MeSH terms and key words. The search was restricted to studies conducted on human subjects and published in English and Chinese. The following key words or MeSH terms were
ACCEPTED MANUSCRIPT used in our search strategies: (“mandibular fracture” OR “mandibular angle fracture” OR “mandibular condyle fracture”) AND (“third molar” OR “wisdom tooth”) (Supplementary Table 1). All reference lists from the main reports and relevant
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reviews were hand searched for additional eligible studies. The search strategy was conducted according to the recommendations of the Meta-analysis of Observational
Reviews and Meta-Analyses (PRISMA) statement11.
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Studies in Epidemiology (MOOSE)10 and the Preferred Reporting Items for Systematic
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The studies were considered eligible for analysis if they met the following criteria: 1. prospective or retrospective cohort study; 2. the association the between presence of M3s and the risk for mandibular angle or condyle fracture was mentioned, with sufficient data to estimate an effect size in the form of a relative risk (RR) or odds ratio
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(OR) with the corresponding 95% confidence interval (CI); 3. sample size over 100. In cases where separate publications reported on the same population, either the most recent or the one with the longest follow-up period was included.
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Two independent reviewers (S. Xu and J.J. Huang) screened the full text of each
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prospective article to determine if they met the inclusion criteria. Disagreement was settled by consensus.
Data collection and quality assessment The same two reviewers independently extracted the data from all included studies. Any discrepancies or uncertainties were resolved by consensus after rechecking the source and discussing with a third reviewer (Y.H. Tan). A standard electronic form was used to compile the extracted study information and included the following items: first
ACCEPTED MANUSCRIPT author’s surname, publication year, country, study design (prospective vs retrospective cohort study), sample size, age, years of data collected, number of mandibular fractures and third molars, status of third molar, mandibular angle fracture and mandibular
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condylar fracture parameters (number with M3s, number without M3s, total, adjusted OR/RR and their 95% CI, P values), data source, study quality, and main cause for mandibular fracture.
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Mandibular angle fracture was defined as a fracture located posterior to the second
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molar and extending from any point on the curve formed by the junction of the body and ramus in the retromolar area to any point on the curve formed by the inferior border of the body and posterior border of the ramus of the mandible, given by Kelly and Harrigan6 in1975. Mandibular condyle fracture was defined as a fracture with the
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fracture line extending over the sigmoid notch9. The Newcastle-Ottawa Quality Assessment Scale (NOS)12 was used to evaluate the quality of the cohort studies, with
Data analysis
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scores as follows: low quality = 0–4; moderate quality = 5–7; high quality = 8–9.
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The relative risk (RR) and odds ratio (OR) are common means of measuring the association between M3s and the risk of mandibular angle and condyle fracture. In cohort studies, RR and OR can be considered to be equivalent. Therefore, the RR/OR from each study was converted to logRR to stabilize the variances and normalize the distributions. Then, the data were pooled together. The heterogeneity among studies was evaluated by Cochran’s Q statistic and quantified as I2 metric to establish whether it was reasonable to assume that the estimate
ACCEPTED MANUSCRIPT of relative risk across studies was consistent13. For the Q statistic, a P-value < 0.1 was considered statistically significant. For the I2 statistic, the following cutoff points were used: a value < 30% was considered little or no heterogeneity, 30–75% was moderate
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heterogeneity, and above 75% was high heterogeneity14. When there was high heterogeneity among studies, a random-effect model was used to calculate the pooled estimation. Otherwise, a fixed-effect model was applied.
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Potential publication bias was assessed by both Begg’s rank correlation test and
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Egger’s linear regression method. A sensitivity analysis was conducted by sequentially removing one study at a time with the metaninf algorithm in STATA (version 12.0; STATA Corporation, College Station, TX, USA).
All analyses were performed using the STATA statistical software. P values were
Results
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two-tailed and P < 0.05 was considered statistically significant.
Study selection process
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Overall, there were 515 articles identified from the PubMed (247 articles), EMBASE
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(266 articles), and Cochrane Library database (two articles) search. After evaluating the titles and abstracts, we excluded 445 records, while the remaining 70 studies were chosen for further review by reading the full text. Among them, 57 were excluded because 17 had no association with study outcomes; 32 had no OR/RR values; four had no original data; and four presented mechanical assays with computer simulation. Finally, 13 studies were included in the present meta-analysis3,6,7,15-24. The study selection process is shown in Fig. 1.
ACCEPTED MANUSCRIPT Study and patient characteristics The characteristics of the selected studies are presented in Table 1. The 13 selected articles consisted exclusively of retrospective cohort studies based on the review of
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hospital records and radiographic files. All 13 studies dealt with M3s and mandibular angle fracture, and five compared M3s with mandibular condyle fracture7,21-24. In the 13
studies
accepted
for
the
main
analysis,
seven
were
conducted
in
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America3,15,16,18,20,22,24, three in Asian countries19,21,23, two in African countries7,17, and
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1 in a European country6. All the studies were published between 1995 and 2016. The duration of follow-up ranged from 1 to 21 years. The average age of the participants ranged from 15 to 55 years. The most frequent cause was physical assault, followed by road traffic accidents. Studies on road traffic accidents originated in Asian and African
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countries, and those on physical assaults came from Western countries such as the USA, Germany, and Canada. The total number of patients was 6,066. There were 2,462 mandibular halves with mandibular angle fracture, 823 with condyle fracture, and
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6,312 with M3s. Regarding the NOS scores, one study20 had a score of 9, eight
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studies3,6,7,15,17,19,21,24 had a score of 7, and the remaining four studies16,18,22,23 had a score of 6 (Supplemental Table 2). M3s and risk of mandibular angle fracture The 13 retrospective cohort studies were pooled and analyzed as presented in Fig. 2. Overall, our analysis suggested that participants with M3s experienced a significantly increased risk for mandibular angle fracture (RR = 2.63, 95% CI, 2.15-3.21). A moderate statistical heterogeneity among studies was observed (P < 0.001, I2 = 73.7%).
ACCEPTED MANUSCRIPT By removing one study at a time, a sensitivity analysis was conducted to determine the influence of each study on the pooled RR; the pooled RR and 95% CI were not modified significantly, with a range from 2.15 (2.05–2.19) to 3.2 (2.80–3.40) (Fig. 3).
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This sensitivity analysis indicated that the results of this meta-analysis were stable and reliable. Additionally, no evidence of publication bias was observed, according to
M3s and risk of mandibular condyle fracture
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Begg’s test (P = 0.100) and Egger’s method (P = 0.307) (Fig. 4).
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The OR/RR from the five relevant retrospective cohort studies were pooled and analyzed as presented in Fig. 5. This analysis included 1,865 participants and 823 mandibular halves with condylar fractures. The findings suggested that participants with M3s experienced a significantly decreased risk for mandibular condyle fracture
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(RR = 0.47, 95% CI, 0.25–0.86). A severe statistical heterogeneity among studies was observed (P < 0.001, I2 = 93.8%). The sensitivity analysis found similar risk estimates, none of the studies modified the pooled RR significantly (Fig. 6). This sensitivity
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analysis indicated that the results of this meta-analysis were stable and reliable. The
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publication bias analysis was not carried out because the number of included studies was less than 10.
Discussion
This current meta-analysis confirmed an increased risk of mandibular angle fractures in the presence of M3s and a simultaneously decreased risk of mandibular condylar fractures, compared to patients without M3s. M3s and mandibular angle fracture
ACCEPTED MANUSCRIPT The association between M3s and mandibular angle fracture is believed to be because impacted M3s occupy more osseous space in the jaw that would otherwise be occupied by bone, thereby decreasing the quantity of bone and weakening the
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mandibular angle24. This hypothesis was supported by the study of Reitzik et al.25 They showed that vervet monkey mandible sides containing incompletely erupted M3s fractured at about 60% of the force required to fracture mandible sides containing
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normally erupted M3s. Rahimi-Nedjat et al.26 also showed that fractures of the
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mandibular angle were more likely to appear in patients with retained M3s, which might be due to the reduced bone mass. Iida et al.6 revealed that the highest incidence of angle fractures was observed in the group in which M3s decreased the amount of bone by more than 20%, especially in cases with a mesioangular M3. The present study
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showed that the relative risk of mandibular angle fracture was 2.63 times higher in patients with M3s, compared to those without. This is in accordance with a previous meta-analysis, which found that the presence of M3s results in a 2.4 times higher
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relative risk of mandibular angle fractures27.
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Furthermore, the presence of M3s significantly diminishes the tensile strength of the bone and encourages the propagation of the fracture along the least resistant path28. The external oblique ridge provides a pillar of strength for the mandible in that region of the jaw. When M3s are completely in occlusion, the external oblique ridge remains intact. However, when the M3s are partially impacted, the tension line may be disrupted, weakening the mandibular angle and making it more susceptible to fracture29.
ACCEPTED MANUSCRIPT In addition, the risk of mandibular angle fracture depends on the position of the M3s. Although the present study did not analyze this issue, many studies have found that M3 position or angulation is associated with a variable risk for angle fractures.
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Specifically, deeper impactions are associated with an increased risk of fractures. According to Fuselier et al.,18 angle fractures are more common in subjects with mesioangular M3s. In contrast, Ma ́aita et al.5 found that a higher risk was associated
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with the vertical and distoangular angulations. Choi et al.30 reported that the risk of
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mandibular angle fractures was the highest in Class II and position B. Gaddipati et al.23 reported that the risk of mandibular angle fractures was the highest in position A. Regarding the vertical position, these authors suggested that deeply impacted M3s were the main factor behind the higher risk of angle fractures. However, Tevepaugh’s15 study
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failed to confirm that more deeply impacted M3s led to an increased risk for angle fracture. They observed an association between a higher incidence of angle fractures and partially impacted M3s, specifically those of Class IIB and a mesioangular
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position. Halmos et al.20 confirmed this observation and added that superficial
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impactions (positions II-A and II-B of the Pell and Gregory system) may be more frequently associated with an increasing risk of these fractures. Lee et al.16 provided data showing an increase in the frequency of mandibular angle fractures associated with the position of the impacted third molar. The authors found that compared to the erupted M3s, all positions presented an increasing risk, except for completely impacted M3s. These findings are contrary to the conventional hypothesis that the deepest impactions should be associated with an increasing risk of mandibular angle fracture.
ACCEPTED MANUSCRIPT Iida et al.31 also found there was no significant difference between the position or angulation of the M3s and the risk of mandibular angle fractures. M3s and mandibular condylar fracture
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More recent studies have found that patients without M3s are more susceptible to mandibular condylar fracture, compared to those with impacted M3s9,21,32,33. This was confirmed by the present study, which found that the risk of sustaining a condylar
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fracture in patients with M3s was 0.47 times that in patients without M3s. Thangavelu
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et al.21 reported that in the absence of impacted mandibular M3s, the condyle was 2.5 times more prone to injury, compared with cases where impacted M3s were present. Zhu et al.9 postulated that the presence of impacted M3s reduced the incidence of condyle fractures. Gaddipati et al.23 demonstrated that patients are more likely to have
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both parasymphysis and angle fractures when unerupted M3s were present. In the absence of unerupted M3s, the patient’s injuries tended to be symphysis or mandibular condyle fractures. These findings suggest that, in the absence of unerupted M3s, much
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of the force may be transmitted to the condylar region, which might increase the
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incidence of associated fractures. Almost all condylar fractures are caused by indirect injury forces, because the condyle is usually protected by the zygomatic arch, muscles, and the structures of the temporomandibular joint(TMJ)28. The impact forces that cause the condylar fractures must transmit to the mandibular angle on the same side, which is biomechanically stronger than the condyle. Iida et al.31 also found that an incompletely erupted M3 decreased the risk of condylar fractures but increased the risk of mandibular angle fractures. Meanwhile, no relation appeared to exist between M3
ACCEPTED MANUSCRIPT position and condylar fracture pattern. Those findings support the hypothesis that the M3s help to prevent mandibular condylar fractures. Clinical significance
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Based on these findings, some investigators have advocated for the early removal of impacted M3s, particularly in young athletes involved in contact sports or other activities, as a prophylactic measure to prevent the possibility of mandibular angle
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fractures29. However, it is more difficult to treat mandibular condylar fractures than
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mandibular angle fractures, mainly because of difficulties in repositioning the condylar fragments, and performing accurate placement of the plates and screws34. In addition, there are many associated operative and postoperative complications, such as pain, restricted mandibular movement, muscle spasm, deviation of the mandible,
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malocclusion and pathological changes the in the TMJ, facial nerve injury, and ankylosis35. In contrast, excellent reduction and stable fixation in angle fractures are easily achieved because the access and visibility for plating are much better. Therefore,
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the prophylactic removal of symptom-free M3s may not be appropriate as a means of
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reducing the chances of angle fracture in patients at risk of maxillofacial trauma. Other factors
Other factors may influence the risk of angle fractures and condylar fractures, such as root of the M3s, the age of patients, occlusion, the character of the soft tissues adjacent to the mandible, and the state of the remaining dentition16.The single conical root of the M3s also showed a significant association with angle fractures. The reason is probably due to concentrated stress around the single root apex that overcomes the bone
ACCEPTED MANUSCRIPT strength.7 In the present study, the highest incidence of angular fracture and condylar fracture was found in patients aged 32 years, similar to previous findings15,20,29. This might be related to some specific behavior tendencies of young subjects, irrespective of
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M3 status. Similarly, Hasegawa et al.36 found that the presence of occlusal support was associated with mandibular angle and condylar fractures because of its buffering ability,
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and that this factor may be more important than the position of the M3s.
Strengths and limitations
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The present meta-analysis had strict inclusion criteria and well-defined variables of interest, which led to reliable and stable results. However, several limitations of this meta-analysis should be considered. First, only retrospective studies were included, because it is not ethically feasible to obtain prospective data regarding the impact of
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M3s on the prevalence of mandibular fractures. Second, we did not determine the effects of different individual conditions and different types of M3 position or
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angulation. Third, we found moderate heterogeneity regarding the data on mandibular angle fracture (I2 = 41.7%; P < 0.001) and high heterogeneity in the data on mandibular
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condyle fracture (I2 = 93.8%; P < 0.001). However, our sensitivity analysis did not find large changes to the pooled RR. Thus, the heterogeneity might be a result of variation between study populations, study design, follow-up, measurement methods, and statistical methods. A meta-regression or dose-response analysis might further explain the prognostic value and the source of heterogeneity. Finally, the underlying mechanisms of the relationship between the M3s and the risk of mandibular angle fracture and mandibular condylar fracture still need further investigation.
ACCEPTED MANUSCRIPT conclusion This current meta-analysis provides further evidence that the presence of M3s is associated with an increased risk of mandibular angle fracture and a simultaneously
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decreased risk of mandibular condylar fracture. As condylar fracture carries more potentially serious complications, the decision to extract M3s to decrease the risk of
Ellis E 3rd, Moos KF, el-Attar A: Ten years of mandibular fractures: an analysis
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Table 1 Characteristics of the retrospective cohort studies of the relationship between third molars (M3s) and mandibular angle fracture and
Country
Study design
Sample size (M/F)
Age (years)
Years of data collection
Mandibular fracture and third molars
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Author, year
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mandibular condylar fracture included in this meta-analysis.
110 (95/15)
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33.67 ± 14.94
18–55
2000– 2013
Canada
Retrospective cohort study
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Naghipur S et al.,24 2014
Retrospective cohort study
615 (527/88)
2011– 2013
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Gaddipati R et al.,23 India 2014
Retrospective cohort study
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Antic S et Serbia al.,7 2016
615 patients obtained 1035 mandibular fractures: Mandibular angle fractures (276), Mandibular condylar fracture (237), 403 mandibular halves without M3 and 827 with M3
446 (377/69) 29.3 ± 11.3
2007– 2012
110 patients with 125 mandible fractures, with 118 mandible fractures having M3s 446 patients with 731 mandibular fractures: Mandibular angle fractures (247), Mandibular condylar fracture (130), 394 mandible fracture sides had an impacted M3
Data source
Main cause for mandibular fracture
Assault (339), fall (145), Medical traffic accident (85), records and sport accident (24), work panoramic injury (16), iatrogenic radiographs injury (6)
Patient Traffic accident (98), records and assault (7), radiographs fall (5)
Hospital charts and panoramic radiographs
Assault (362), falls (31), sports injuries (20), other causes (20), traffic accident (13)
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460 (345/115)
NS
29.3 ± 10.8
2001– 2008
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Retrospective cohort study
234 (NS)
2010– 2012
460 patients with 870 mandibular fractures: Mandibular angle fractures (175), Mandibular condylar fracture (187), 442 fracture side had an unerupted M3 (260 patients)
Hospital charts and NS panoramic radiographs
Hospital case Road traffic accident records and (49%), assault (35%), fall panoramic (16%) radiographs
Retrospective cohort study
218 (169/48) 15–40
1997– 2001
218 mandibular fracture patients with 436 mandibular halves: Mandibular angle Panoramic Assault (85), fall (42), fractures (72), 282 radiographs bicycle accidents (30). mandibular fracture sides had M3 (161 patients)
Halmos D. R et al.,20 2004
USA
Retrospective cohort study
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Iida S et Germany al.,6 2005
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Thangave lu A et India al.,21 2010
Retrospective cohort study
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Luria J. S et al.,22 USA 2013
Mandibular angle fractures halves (123), Mandibular condylar fracture halves (81), 132 mandible fracture side had an impacted M3
1450 (1182/268)
30.6
1993– 2001
1,969 hemimandibles had M3d present (982 patients), Angle fractures were present in 733 of the hemimandibles (292 patients)
Clinical records and NS radiographs
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Lee J. T et al.,16 2000
Ugboko V. I et al.,17 2000
USA
Nigeria
Retrospective cohort study
Retrospective cohort study
Retrospective cohort study
1210 (981/229)
30.8 ± 10.4
367 (290/77) 31.7 ± 10
490 (369/121)
30 ± 9
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413 mandibular fractures in 214 patients, 127 angle fractures, Left M3 n=241, Right M3 n=229
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1995– 2000.
NS
240 mandibular fractures in 151 patients, 53 patients had mandibular angle fractures, 111 patients with M3
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USA
214 (NS)
1993– 2002.
1990 – 2000
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Fuselier J. C et al.,18 2002
Canada
Retrospective cohort study
151 (121/30) 29.9±14.9
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Meisami T et al.,3 2002
Retrospective cohort study
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Kasamats u A et Japan al.,19 2003
1993– 1998
1976– 1997
558 mandibular fractures in 1210 patients,326 patients had mandibular angle fractures,837patients with M3 196 mandibular fractures in 367 patients,99 patients had mandibular angle fractures,249patients with M3
490 patients sustained 572 fractures of the mandible 76 patients had mandibular angle fractures, 408 patients with M3
Medical records and panoramic X-rays
Fight (37), fall (41) sports(5), motor vehicle accident (62), others (6)
Physical assault (221), falls Hospital (98), sports (39), motor charts and vehicle accident (26), panoramic pathologic (7), radiographs other/unknown (22)
Panoramic NS radiographs
Altercation (212), motor Medical vehicle accident (38), fall records and (26), gunshot wound (21), radiographs occupation (1), others (11)
Case Road traffic accident (304), records and fight or assault (75), fall radiographs (57), sports (19), gunshot (22), others (13)
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Tevepaug h, D. B, USA et al.,15 1995
Retrospective cohort study
101 (80/21)
31.7 ± 9.2
1993– 1994
33 patients had mandibular angle fractures, 73 patients with M3
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NS: not stated
Medical records and Altercation (74), fall (12), panoramic others (13) radiographs
Iida S et al.,6 2005
<0.001
60
12
72
37.27 12.77-108.78
150
101
251
1.88 1.51-2.33
93
30
123
2.09 1.31-3.35
150
50
200
66
16
82
171
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Antic S et al.,7 2016 Gaddipati R et al.,23 2014 Naghipur S et al.,24 2014 Luria J. S et al.,22 2013 Thangavel u A et al.,21 2010
Number P value with M3s
2.51 2.10-3.00 2.16 1.23-3.78
Mandibular condyle fractures Number OR/RR without Total (95% CI) M3s 0.584 109 280 0.474-0.719
P value
Study quality
<0.05
7
10
43
53
0.027 0.009-0.078
<0.001
6
46
102
148
0.570 0.413-0.787
<0.001
7
NS
39
42
81
2.08 1.30-3.32
NS
6
<0.000 1
89
172
261
0.43333 0.336-0.5629
<0.0001
7
7
<0.001
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Author, year
Mandibular angle fractures Number Number OR/RR with without Total (95% CI) M3s M3s 3.55 228 59 287 2.73-4.59
<0.001
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fracture and mandibular condylar fracture included in this meta-analysis.
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Table 1 (continued) Characteristics of the retrospective cohort studies of the relationship between third molars (M3s) and mandibular angle
0.0025
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2.80 2.30-3.40
<0.000 1
9
48
5
53
3.50 1.70-6.90
0.0004
7
50
14
64 (left)
2.80 1.49-5.27 left)
<0.001
7
269
57
326
2.10 1.62-2.72
<0.001
6
79
20
99
1.90 1.20-2.90
0.03
6
65
11
76
1.98 1.30-4.40
0.002
7
30
3
33
3.80 1.30-11.60
0.04
7
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733
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Ugboko V. I et al.,17 2000 Tevepaug h, D. B, et al.,15 1995
128
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Lee J. T et al.,16 2000
605
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Halmos D. R et al.,20 2004 Kasamatsu A et al.,19 2003 Meisami T et al.,3 2002 Fuselier J. C et al.,18 2002
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Figure legends Figure 1. Flow chart of study selection
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Figure 2. Meta-analysis of cohort studies examining third molars (M3s) and relative risk (RR) of mandibular angle fracture
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Figure 4. Funnel plot of the included studies for publication bias assessment
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Figure 3. Sensitivity analysis of the meta-analysis of M3s and mandibular angle fracture, with estimated RR and corresponding 95% confidence intervals
Figure 5. Meta-analysis of cohort studies examining M3s and risk of mandibular condylar fracture
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Figure 6. Sensitivity analysis of the meta-analysis of M3s and mandibular condylar fracture, with estimated RR and corresponding 95% confidence intervals
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Supplemental Tables Supplemental Table 1. Search Strategy.
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Search Terms 1. “mandibular fracture [MeSH Terms]” OR “mandibular angle fracture [MeSH Terms]” OR “mandibular condyle fracture [MeSH
Terms]”
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2. “third molar [MeSH Terms]” OR “wisdom tooth [MeSH Terms]”
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3. 1 AND 2
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Supplemental Table 2. Methodological quality of studies included in the final analysis based on the Newcastle-Ottawa Scale for assessing the quality of retrospective cohort studies
1
1
1
1
1
1
1 1
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Halmos D. R et al.,20 2004 Kasamatsu A et al.,19 2003 Meisami T et al.,3 2002 Fuselier J. C et al.,18 2002
1
1
0
1
1
1
7
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Iida S et al.,6 2005
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SC
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Outcome Control Follow-up of for long Adequacy retrospective Representativeness Selection of interest Ascertainment important Assessment enough of cohort of the exposed non-exposed was not Total of exposure factor or of outcome for follow-up studies(n=13) cohorts cohort present additional outcomes of cohorts at start factor to occur of study Antic S et al.,7 1 1 1 1 0 1 1 1 7 2016 Gaddipati R et 1 1 1 0 0 1 1 1 6 al.,23 2014 Naghipur S et 1 1 1 1 0 1 1 1 7 al.,24 2014 Luria J. S et 1 1 1 0 0 1 1 1 6 al.,22 2013 Thangavelu A 1 1 1 1 0 1 1 1 7 et al.,21 2010
1
1
2
1
1
1
9
1
1
0
1
1
1
7
1
1
1
0
1
1
1
7
0
1
1
0
1
1
1
6
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1
0
1
0
1
1
1
6
1
1
1
1
0
1
1
1
7
1
1
1
1
0
1
1
1
7
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SC
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1
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Lee J. T et al.,16 2000 Ugboko V. I et al.,17 2000 Tevepaugh, D. B, et al.,15 1995
ACCEPTED MANUSCRIPT Figure 1. Flow chart of study selection Articles identified from PubMed, EMBASE and Cochrane Library search (n=515)
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Excluded by title and abstract (n = 445) - Duplicate records - Reviews or Meta-analysis or Case report or Letters - No relevant outcomes and exposure - Not cohort studies
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Full-text articles assessed for eligibility (n = 70)
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Excluded by full text screening (n = 57) - No association with study question (n = 17) - No odds ratio/relative risk reported (n = 32) - No original data (n = 4) - Mechanical assays with computer simulation (n = 4)
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Articles included for final meta-analysis (n = 13)
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SC
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relative risk (RR) of mandibular angle fracture
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(CI)
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Egger's publication bias plot
Begg's funnel plot with pseudo 95% confidence limits
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4
10
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2
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lo g r r
5
0
5 precision
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0
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1
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s ta n d a r d iz e d e ffe c t
3
10
0 0
.2
.4 s.e. of: logrr
.6
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condylar fracture
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Figure 6. Sensitivity analysis of the meta-analysis of M3s and mandibular condylar fracture, with estimated RR and corresponding 95% confidence
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intervals
Meta-analysis estimates, given named study is omitted Lower CI Limit Estimate Upper CI Limit
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Antic S et al., 2016
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Naghipur S et al., 2014
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Gaddipati R et al., 2014
Luria J. S et al., 2013
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Thangavelu A et al., 2010
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0.15 0.25
0.47
0.86
1.16
S0278-2391(17)30339-7
DOI:
10.1016/j.joms.2017.03.021
Reference:
YJOMS 57711
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 24 November 2016 Revised Date:
14 March 2017
Accepted Date: 14 March 2017
Please cite this article as: Xu S, Huang J-j, Xiong Y, Tan Y-h, How is third molar status associated with the occurrence of mandibular angle and condyle fractures?, Journal of Oral and Maxillofacial Surgery (2017), doi: 10.1016/j.joms.2017.03.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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How is third molar status associated with the occurrence of mandibular angle and condyle fractures?
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Authors and Affiliations Shuai Xu, Resident, Ph.D1, Jun-jie Huang, Resident, MS2, Yu Xiong, Associate Professor3, and Ying-hui Tan, Professor4*.
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Medical University, Chongqing, China
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1. Resident, Department of Stomatology, Xinqiao Hospital, Third Military
2. Resident, Department of Stomatology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
3. Associate Professor, Department of Stomatology, Southwest Hospital,
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Third Military Medical University, Chongqing, 400038, China 4. Professor, Department of Stomatology, Xinqiao Hospital, Third Military
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Medical University, Chongqing, China *Correspondence Author: Ying-hui Tan
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Address: Department of Stomatology, Xinqiao Hospital, Third Military Medical University, 183 Xinqiaozhengjie St, Shapingba District, Chongqing 400037, China E-mail :[email protected]
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Abstract Purpose: The third molars (M3s) have been hypothesized to be associated with the risk of mandibular angle fracture and mandibular condylar fracture. We systematically
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estimated the relative risk of M3 status for the development of mandibular angle fracture and mandibular condylar fracture through a meta-analysis of cohort studies.
Methods: In this systematic review, PubMed, EMBASE, and the Cochrane Library
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were searched from inception to October 2016. The predictor of risk was the presence
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or absence of M3s. The primary outcome was the relative risk of mandibular angle or condylar fracture. Either a fixed or a random-effects model was applied to evaluate the pooled risk estimates. Sensitivity analysis was also performed to identify the potential sources of heterogeneity. Publication bias was assessed by the Begg’s and Egger’s
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tests.
Results: Overall, 13 retrospective cohort studies were included. Of these, 13 reported the association between M3s and mandibular angle fracture, while 5 reported the
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association with mandibular condylar fracture. Patients with M3s had an increased risk
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of mandibular angle fractures (RR = 2.63, 95% confidence interval [CI] 2.15–3.21) but a decreased risk of mandibular condylar fractures (RR = 0.47, 95% CI 0.25–0.86). Substantial heterogeneity in the risk estimates was revealed. No evidence of publication bias was found. Conclusion: The current meta-analysis provides further evidence that the presence of M3s is associated with an increased risk of mandibular angle fractures and a simultaneously decreased risk of mandibular condylar fracture. Due to the potentially
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mandibular angle fracture.
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Introduction The mandible is the largest and the strongest bone in the facial skeleton. However, it is very frequently fractured because of its prominent and exposed location. According to
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previous biomechanical and epidemiologic studies, the incidence of mandibular fracture varies from 15.5 to 59% of all facial fractures, for patients between the age of 16 and 30 years1, 2. Ellis et al.1 also found that mandibular angle fracture is common and
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comprises approximately 30% of all mandibular fractures. The occurrence of
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mandibular angle fracture is usually related to many factors such as the direction and severity of the impact, presence of soft tissue bulk, and occlusal loading pattern, as well as biomechanical characteristics, such as the bone density, mass, and weak regions of anatomic structures3. As the mandibular angle forms the junction between the ramus
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and the body, it is commonly associated with the third molars (M3s). In other words, the status of the M3s affects the risk of mandibular angle fracture4. Various studies have reported that the presence of M3s is associated with an
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increased risk for angle fracture, especially when these M3s are partially erupted or
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unerupted5. Iida et al.6 showed that incompletely erupted M3s had a high risk for mandibular angle fracture. Antic et al.7 also observed that there was a 3.6-fold increased risk for mandibular angle fracture when M3s were present, compared with M3s being absent. Safdar et al8 reported that impacted M3s increased the likelihood of angle fractures by reducing the bone quality and bone mass in the mandibular angle region. Accordingly, some authors recommend the early extraction of asymptomatic M3s to decrease the risk of mandibular angle fracture.
ACCEPTED MANUSCRIPT However, more recent studies9 observed that patients without M3s were more likely to develop another type of mandibular fracture, mandibular condyle fracture, compared with those who had M3s. The treatment of condyle fracture is more
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challenging, with a higher risk of postoperative complications compared to angle fracture. Therefore, the decision to remove M3s as a means of preventing mandibular angle fracture might not be as straightforward as previously thought. These disputes
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mandibular angle and condylar fracture.
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require further systematic analysis on the relationship between M3 status and the risk of
Therefore, this systematic review aimed to pool data from individual studies, and a meta-analysis was performed to quantify the association between M3 status and the incidence of mandibular angle as well as condyle fracture. The investigators
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hypothesize that patients with M3s are at an increased risk of mandibular angle fracture, compared to those without, and that removal of M3s will decrease this risk,
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Methods
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while increasing the risk of condylar fracture.
Literature search and study selection We conducted a systematic literature search by using the PubMed, EMBASE, and Cochrane Library Database to identify relevant studies from the earliest available data to October 2016. To identify relevant studies, the search strategy combined MeSH terms and key words. The search was restricted to studies conducted on human subjects and published in English and Chinese. The following key words or MeSH terms were
ACCEPTED MANUSCRIPT used in our search strategies: (“mandibular fracture” OR “mandibular angle fracture” OR “mandibular condyle fracture”) AND (“third molar” OR “wisdom tooth”) (Supplementary Table 1). All reference lists from the main reports and relevant
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reviews were hand searched for additional eligible studies. The search strategy was conducted according to the recommendations of the Meta-analysis of Observational
Reviews and Meta-Analyses (PRISMA) statement11.
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Studies in Epidemiology (MOOSE)10 and the Preferred Reporting Items for Systematic
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The studies were considered eligible for analysis if they met the following criteria: 1. prospective or retrospective cohort study; 2. the association the between presence of M3s and the risk for mandibular angle or condyle fracture was mentioned, with sufficient data to estimate an effect size in the form of a relative risk (RR) or odds ratio
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(OR) with the corresponding 95% confidence interval (CI); 3. sample size over 100. In cases where separate publications reported on the same population, either the most recent or the one with the longest follow-up period was included.
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Two independent reviewers (S. Xu and J.J. Huang) screened the full text of each
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prospective article to determine if they met the inclusion criteria. Disagreement was settled by consensus.
Data collection and quality assessment The same two reviewers independently extracted the data from all included studies. Any discrepancies or uncertainties were resolved by consensus after rechecking the source and discussing with a third reviewer (Y.H. Tan). A standard electronic form was used to compile the extracted study information and included the following items: first
ACCEPTED MANUSCRIPT author’s surname, publication year, country, study design (prospective vs retrospective cohort study), sample size, age, years of data collected, number of mandibular fractures and third molars, status of third molar, mandibular angle fracture and mandibular
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condylar fracture parameters (number with M3s, number without M3s, total, adjusted OR/RR and their 95% CI, P values), data source, study quality, and main cause for mandibular fracture.
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Mandibular angle fracture was defined as a fracture located posterior to the second
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molar and extending from any point on the curve formed by the junction of the body and ramus in the retromolar area to any point on the curve formed by the inferior border of the body and posterior border of the ramus of the mandible, given by Kelly and Harrigan6 in1975. Mandibular condyle fracture was defined as a fracture with the
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fracture line extending over the sigmoid notch9. The Newcastle-Ottawa Quality Assessment Scale (NOS)12 was used to evaluate the quality of the cohort studies, with
Data analysis
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scores as follows: low quality = 0–4; moderate quality = 5–7; high quality = 8–9.
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The relative risk (RR) and odds ratio (OR) are common means of measuring the association between M3s and the risk of mandibular angle and condyle fracture. In cohort studies, RR and OR can be considered to be equivalent. Therefore, the RR/OR from each study was converted to logRR to stabilize the variances and normalize the distributions. Then, the data were pooled together. The heterogeneity among studies was evaluated by Cochran’s Q statistic and quantified as I2 metric to establish whether it was reasonable to assume that the estimate
ACCEPTED MANUSCRIPT of relative risk across studies was consistent13. For the Q statistic, a P-value < 0.1 was considered statistically significant. For the I2 statistic, the following cutoff points were used: a value < 30% was considered little or no heterogeneity, 30–75% was moderate
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heterogeneity, and above 75% was high heterogeneity14. When there was high heterogeneity among studies, a random-effect model was used to calculate the pooled estimation. Otherwise, a fixed-effect model was applied.
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Potential publication bias was assessed by both Begg’s rank correlation test and
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Egger’s linear regression method. A sensitivity analysis was conducted by sequentially removing one study at a time with the metaninf algorithm in STATA (version 12.0; STATA Corporation, College Station, TX, USA).
All analyses were performed using the STATA statistical software. P values were
Results
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two-tailed and P < 0.05 was considered statistically significant.
Study selection process
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Overall, there were 515 articles identified from the PubMed (247 articles), EMBASE
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(266 articles), and Cochrane Library database (two articles) search. After evaluating the titles and abstracts, we excluded 445 records, while the remaining 70 studies were chosen for further review by reading the full text. Among them, 57 were excluded because 17 had no association with study outcomes; 32 had no OR/RR values; four had no original data; and four presented mechanical assays with computer simulation. Finally, 13 studies were included in the present meta-analysis3,6,7,15-24. The study selection process is shown in Fig. 1.
ACCEPTED MANUSCRIPT Study and patient characteristics The characteristics of the selected studies are presented in Table 1. The 13 selected articles consisted exclusively of retrospective cohort studies based on the review of
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hospital records and radiographic files. All 13 studies dealt with M3s and mandibular angle fracture, and five compared M3s with mandibular condyle fracture7,21-24. In the 13
studies
accepted
for
the
main
analysis,
seven
were
conducted
in
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America3,15,16,18,20,22,24, three in Asian countries19,21,23, two in African countries7,17, and
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1 in a European country6. All the studies were published between 1995 and 2016. The duration of follow-up ranged from 1 to 21 years. The average age of the participants ranged from 15 to 55 years. The most frequent cause was physical assault, followed by road traffic accidents. Studies on road traffic accidents originated in Asian and African
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countries, and those on physical assaults came from Western countries such as the USA, Germany, and Canada. The total number of patients was 6,066. There were 2,462 mandibular halves with mandibular angle fracture, 823 with condyle fracture, and
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6,312 with M3s. Regarding the NOS scores, one study20 had a score of 9, eight
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studies3,6,7,15,17,19,21,24 had a score of 7, and the remaining four studies16,18,22,23 had a score of 6 (Supplemental Table 2). M3s and risk of mandibular angle fracture The 13 retrospective cohort studies were pooled and analyzed as presented in Fig. 2. Overall, our analysis suggested that participants with M3s experienced a significantly increased risk for mandibular angle fracture (RR = 2.63, 95% CI, 2.15-3.21). A moderate statistical heterogeneity among studies was observed (P < 0.001, I2 = 73.7%).
ACCEPTED MANUSCRIPT By removing one study at a time, a sensitivity analysis was conducted to determine the influence of each study on the pooled RR; the pooled RR and 95% CI were not modified significantly, with a range from 2.15 (2.05–2.19) to 3.2 (2.80–3.40) (Fig. 3).
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This sensitivity analysis indicated that the results of this meta-analysis were stable and reliable. Additionally, no evidence of publication bias was observed, according to
M3s and risk of mandibular condyle fracture
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Begg’s test (P = 0.100) and Egger’s method (P = 0.307) (Fig. 4).
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The OR/RR from the five relevant retrospective cohort studies were pooled and analyzed as presented in Fig. 5. This analysis included 1,865 participants and 823 mandibular halves with condylar fractures. The findings suggested that participants with M3s experienced a significantly decreased risk for mandibular condyle fracture
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(RR = 0.47, 95% CI, 0.25–0.86). A severe statistical heterogeneity among studies was observed (P < 0.001, I2 = 93.8%). The sensitivity analysis found similar risk estimates, none of the studies modified the pooled RR significantly (Fig. 6). This sensitivity
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analysis indicated that the results of this meta-analysis were stable and reliable. The
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publication bias analysis was not carried out because the number of included studies was less than 10.
Discussion
This current meta-analysis confirmed an increased risk of mandibular angle fractures in the presence of M3s and a simultaneously decreased risk of mandibular condylar fractures, compared to patients without M3s. M3s and mandibular angle fracture
ACCEPTED MANUSCRIPT The association between M3s and mandibular angle fracture is believed to be because impacted M3s occupy more osseous space in the jaw that would otherwise be occupied by bone, thereby decreasing the quantity of bone and weakening the
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mandibular angle24. This hypothesis was supported by the study of Reitzik et al.25 They showed that vervet monkey mandible sides containing incompletely erupted M3s fractured at about 60% of the force required to fracture mandible sides containing
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normally erupted M3s. Rahimi-Nedjat et al.26 also showed that fractures of the
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mandibular angle were more likely to appear in patients with retained M3s, which might be due to the reduced bone mass. Iida et al.6 revealed that the highest incidence of angle fractures was observed in the group in which M3s decreased the amount of bone by more than 20%, especially in cases with a mesioangular M3. The present study
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showed that the relative risk of mandibular angle fracture was 2.63 times higher in patients with M3s, compared to those without. This is in accordance with a previous meta-analysis, which found that the presence of M3s results in a 2.4 times higher
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relative risk of mandibular angle fractures27.
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Furthermore, the presence of M3s significantly diminishes the tensile strength of the bone and encourages the propagation of the fracture along the least resistant path28. The external oblique ridge provides a pillar of strength for the mandible in that region of the jaw. When M3s are completely in occlusion, the external oblique ridge remains intact. However, when the M3s are partially impacted, the tension line may be disrupted, weakening the mandibular angle and making it more susceptible to fracture29.
ACCEPTED MANUSCRIPT In addition, the risk of mandibular angle fracture depends on the position of the M3s. Although the present study did not analyze this issue, many studies have found that M3 position or angulation is associated with a variable risk for angle fractures.
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Specifically, deeper impactions are associated with an increased risk of fractures. According to Fuselier et al.,18 angle fractures are more common in subjects with mesioangular M3s. In contrast, Ma ́aita et al.5 found that a higher risk was associated
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with the vertical and distoangular angulations. Choi et al.30 reported that the risk of
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mandibular angle fractures was the highest in Class II and position B. Gaddipati et al.23 reported that the risk of mandibular angle fractures was the highest in position A. Regarding the vertical position, these authors suggested that deeply impacted M3s were the main factor behind the higher risk of angle fractures. However, Tevepaugh’s15 study
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failed to confirm that more deeply impacted M3s led to an increased risk for angle fracture. They observed an association between a higher incidence of angle fractures and partially impacted M3s, specifically those of Class IIB and a mesioangular
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position. Halmos et al.20 confirmed this observation and added that superficial
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impactions (positions II-A and II-B of the Pell and Gregory system) may be more frequently associated with an increasing risk of these fractures. Lee et al.16 provided data showing an increase in the frequency of mandibular angle fractures associated with the position of the impacted third molar. The authors found that compared to the erupted M3s, all positions presented an increasing risk, except for completely impacted M3s. These findings are contrary to the conventional hypothesis that the deepest impactions should be associated with an increasing risk of mandibular angle fracture.
ACCEPTED MANUSCRIPT Iida et al.31 also found there was no significant difference between the position or angulation of the M3s and the risk of mandibular angle fractures. M3s and mandibular condylar fracture
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More recent studies have found that patients without M3s are more susceptible to mandibular condylar fracture, compared to those with impacted M3s9,21,32,33. This was confirmed by the present study, which found that the risk of sustaining a condylar
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fracture in patients with M3s was 0.47 times that in patients without M3s. Thangavelu
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et al.21 reported that in the absence of impacted mandibular M3s, the condyle was 2.5 times more prone to injury, compared with cases where impacted M3s were present. Zhu et al.9 postulated that the presence of impacted M3s reduced the incidence of condyle fractures. Gaddipati et al.23 demonstrated that patients are more likely to have
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both parasymphysis and angle fractures when unerupted M3s were present. In the absence of unerupted M3s, the patient’s injuries tended to be symphysis or mandibular condyle fractures. These findings suggest that, in the absence of unerupted M3s, much
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of the force may be transmitted to the condylar region, which might increase the
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incidence of associated fractures. Almost all condylar fractures are caused by indirect injury forces, because the condyle is usually protected by the zygomatic arch, muscles, and the structures of the temporomandibular joint(TMJ)28. The impact forces that cause the condylar fractures must transmit to the mandibular angle on the same side, which is biomechanically stronger than the condyle. Iida et al.31 also found that an incompletely erupted M3 decreased the risk of condylar fractures but increased the risk of mandibular angle fractures. Meanwhile, no relation appeared to exist between M3
ACCEPTED MANUSCRIPT position and condylar fracture pattern. Those findings support the hypothesis that the M3s help to prevent mandibular condylar fractures. Clinical significance
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Based on these findings, some investigators have advocated for the early removal of impacted M3s, particularly in young athletes involved in contact sports or other activities, as a prophylactic measure to prevent the possibility of mandibular angle
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fractures29. However, it is more difficult to treat mandibular condylar fractures than
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mandibular angle fractures, mainly because of difficulties in repositioning the condylar fragments, and performing accurate placement of the plates and screws34. In addition, there are many associated operative and postoperative complications, such as pain, restricted mandibular movement, muscle spasm, deviation of the mandible,
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malocclusion and pathological changes the in the TMJ, facial nerve injury, and ankylosis35. In contrast, excellent reduction and stable fixation in angle fractures are easily achieved because the access and visibility for plating are much better. Therefore,
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the prophylactic removal of symptom-free M3s may not be appropriate as a means of
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reducing the chances of angle fracture in patients at risk of maxillofacial trauma. Other factors
Other factors may influence the risk of angle fractures and condylar fractures, such as root of the M3s, the age of patients, occlusion, the character of the soft tissues adjacent to the mandible, and the state of the remaining dentition16.The single conical root of the M3s also showed a significant association with angle fractures. The reason is probably due to concentrated stress around the single root apex that overcomes the bone
ACCEPTED MANUSCRIPT strength.7 In the present study, the highest incidence of angular fracture and condylar fracture was found in patients aged 32 years, similar to previous findings15,20,29. This might be related to some specific behavior tendencies of young subjects, irrespective of
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M3 status. Similarly, Hasegawa et al.36 found that the presence of occlusal support was associated with mandibular angle and condylar fractures because of its buffering ability,
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and that this factor may be more important than the position of the M3s.
Strengths and limitations
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The present meta-analysis had strict inclusion criteria and well-defined variables of interest, which led to reliable and stable results. However, several limitations of this meta-analysis should be considered. First, only retrospective studies were included, because it is not ethically feasible to obtain prospective data regarding the impact of
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M3s on the prevalence of mandibular fractures. Second, we did not determine the effects of different individual conditions and different types of M3 position or
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angulation. Third, we found moderate heterogeneity regarding the data on mandibular angle fracture (I2 = 41.7%; P < 0.001) and high heterogeneity in the data on mandibular
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condyle fracture (I2 = 93.8%; P < 0.001). However, our sensitivity analysis did not find large changes to the pooled RR. Thus, the heterogeneity might be a result of variation between study populations, study design, follow-up, measurement methods, and statistical methods. A meta-regression or dose-response analysis might further explain the prognostic value and the source of heterogeneity. Finally, the underlying mechanisms of the relationship between the M3s and the risk of mandibular angle fracture and mandibular condylar fracture still need further investigation.
ACCEPTED MANUSCRIPT conclusion This current meta-analysis provides further evidence that the presence of M3s is associated with an increased risk of mandibular angle fracture and a simultaneously
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decreased risk of mandibular condylar fracture. As condylar fracture carries more potentially serious complications, the decision to extract M3s to decrease the risk of
Ellis E 3rd, Moos KF, el-Attar A: Ten years of mandibular fractures: an analysis
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Table 1 Characteristics of the retrospective cohort studies of the relationship between third molars (M3s) and mandibular angle fracture and
Country
Study design
Sample size (M/F)
Age (years)
Years of data collection
Mandibular fracture and third molars
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Author, year
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mandibular condylar fracture included in this meta-analysis.
110 (95/15)
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33.67 ± 14.94
18–55
2000– 2013
Canada
Retrospective cohort study
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Naghipur S et al.,24 2014
Retrospective cohort study
615 (527/88)
2011– 2013
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Gaddipati R et al.,23 India 2014
Retrospective cohort study
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Antic S et Serbia al.,7 2016
615 patients obtained 1035 mandibular fractures: Mandibular angle fractures (276), Mandibular condylar fracture (237), 403 mandibular halves without M3 and 827 with M3
446 (377/69) 29.3 ± 11.3
2007– 2012
110 patients with 125 mandible fractures, with 118 mandible fractures having M3s 446 patients with 731 mandibular fractures: Mandibular angle fractures (247), Mandibular condylar fracture (130), 394 mandible fracture sides had an impacted M3
Data source
Main cause for mandibular fracture
Assault (339), fall (145), Medical traffic accident (85), records and sport accident (24), work panoramic injury (16), iatrogenic radiographs injury (6)
Patient Traffic accident (98), records and assault (7), radiographs fall (5)
Hospital charts and panoramic radiographs
Assault (362), falls (31), sports injuries (20), other causes (20), traffic accident (13)
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460 (345/115)
NS
29.3 ± 10.8
2001– 2008
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Retrospective cohort study
234 (NS)
2010– 2012
460 patients with 870 mandibular fractures: Mandibular angle fractures (175), Mandibular condylar fracture (187), 442 fracture side had an unerupted M3 (260 patients)
Hospital charts and NS panoramic radiographs
Hospital case Road traffic accident records and (49%), assault (35%), fall panoramic (16%) radiographs
Retrospective cohort study
218 (169/48) 15–40
1997– 2001
218 mandibular fracture patients with 436 mandibular halves: Mandibular angle Panoramic Assault (85), fall (42), fractures (72), 282 radiographs bicycle accidents (30). mandibular fracture sides had M3 (161 patients)
Halmos D. R et al.,20 2004
USA
Retrospective cohort study
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Iida S et Germany al.,6 2005
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Thangave lu A et India al.,21 2010
Retrospective cohort study
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Luria J. S et al.,22 USA 2013
Mandibular angle fractures halves (123), Mandibular condylar fracture halves (81), 132 mandible fracture side had an impacted M3
1450 (1182/268)
30.6
1993– 2001
1,969 hemimandibles had M3d present (982 patients), Angle fractures were present in 733 of the hemimandibles (292 patients)
Clinical records and NS radiographs
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Lee J. T et al.,16 2000
Ugboko V. I et al.,17 2000
USA
Nigeria
Retrospective cohort study
Retrospective cohort study
Retrospective cohort study
1210 (981/229)
30.8 ± 10.4
367 (290/77) 31.7 ± 10
490 (369/121)
30 ± 9
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413 mandibular fractures in 214 patients, 127 angle fractures, Left M3 n=241, Right M3 n=229
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1995– 2000.
NS
240 mandibular fractures in 151 patients, 53 patients had mandibular angle fractures, 111 patients with M3
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USA
214 (NS)
1993– 2002.
1990 – 2000
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Fuselier J. C et al.,18 2002
Canada
Retrospective cohort study
151 (121/30) 29.9±14.9
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Meisami T et al.,3 2002
Retrospective cohort study
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Kasamats u A et Japan al.,19 2003
1993– 1998
1976– 1997
558 mandibular fractures in 1210 patients,326 patients had mandibular angle fractures,837patients with M3 196 mandibular fractures in 367 patients,99 patients had mandibular angle fractures,249patients with M3
490 patients sustained 572 fractures of the mandible 76 patients had mandibular angle fractures, 408 patients with M3
Medical records and panoramic X-rays
Fight (37), fall (41) sports(5), motor vehicle accident (62), others (6)
Physical assault (221), falls Hospital (98), sports (39), motor charts and vehicle accident (26), panoramic pathologic (7), radiographs other/unknown (22)
Panoramic NS radiographs
Altercation (212), motor Medical vehicle accident (38), fall records and (26), gunshot wound (21), radiographs occupation (1), others (11)
Case Road traffic accident (304), records and fight or assault (75), fall radiographs (57), sports (19), gunshot (22), others (13)
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Tevepaug h, D. B, USA et al.,15 1995
Retrospective cohort study
101 (80/21)
31.7 ± 9.2
1993– 1994
33 patients had mandibular angle fractures, 73 patients with M3
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NS: not stated
Medical records and Altercation (74), fall (12), panoramic others (13) radiographs
Iida S et al.,6 2005
<0.001
60
12
72
37.27 12.77-108.78
150
101
251
1.88 1.51-2.33
93
30
123
2.09 1.31-3.35
150
50
200
66
16
82
171
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Number P value with M3s
2.51 2.10-3.00 2.16 1.23-3.78
Mandibular condyle fractures Number OR/RR without Total (95% CI) M3s 0.584 109 280 0.474-0.719
P value
Study quality
<0.05
7
10
43
53
0.027 0.009-0.078
<0.001
6
46
102
148
0.570 0.413-0.787
<0.001
7
NS
39
42
81
2.08 1.30-3.32
NS
6
<0.000 1
89
172
261
0.43333 0.336-0.5629
<0.0001
7
7
<0.001
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Author, year
Mandibular angle fractures Number Number OR/RR with without Total (95% CI) M3s M3s 3.55 228 59 287 2.73-4.59
<0.001
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fracture and mandibular condylar fracture included in this meta-analysis.
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Table 1 (continued) Characteristics of the retrospective cohort studies of the relationship between third molars (M3s) and mandibular angle
0.0025
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2.80 2.30-3.40
<0.000 1
9
48
5
53
3.50 1.70-6.90
0.0004
7
50
14
64 (left)
2.80 1.49-5.27 left)
<0.001
7
269
57
326
2.10 1.62-2.72
<0.001
6
79
20
99
1.90 1.20-2.90
0.03
6
65
11
76
1.98 1.30-4.40
0.002
7
30
3
33
3.80 1.30-11.60
0.04
7
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Ugboko V. I et al.,17 2000 Tevepaug h, D. B, et al.,15 1995
128
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Lee J. T et al.,16 2000
605
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Halmos D. R et al.,20 2004 Kasamatsu A et al.,19 2003 Meisami T et al.,3 2002 Fuselier J. C et al.,18 2002
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Figure legends Figure 1. Flow chart of study selection
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Figure 2. Meta-analysis of cohort studies examining third molars (M3s) and relative risk (RR) of mandibular angle fracture
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Figure 4. Funnel plot of the included studies for publication bias assessment
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Figure 3. Sensitivity analysis of the meta-analysis of M3s and mandibular angle fracture, with estimated RR and corresponding 95% confidence intervals
Figure 5. Meta-analysis of cohort studies examining M3s and risk of mandibular condylar fracture
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Figure 6. Sensitivity analysis of the meta-analysis of M3s and mandibular condylar fracture, with estimated RR and corresponding 95% confidence intervals
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Supplemental Tables Supplemental Table 1. Search Strategy.
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Search Terms 1. “mandibular fracture [MeSH Terms]” OR “mandibular angle fracture [MeSH Terms]” OR “mandibular condyle fracture [MeSH
Terms]”
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2. “third molar [MeSH Terms]” OR “wisdom tooth [MeSH Terms]”
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Supplemental Table 2. Methodological quality of studies included in the final analysis based on the Newcastle-Ottawa Scale for assessing the quality of retrospective cohort studies
1
1
1
1
1
1
1 1
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Halmos D. R et al.,20 2004 Kasamatsu A et al.,19 2003 Meisami T et al.,3 2002 Fuselier J. C et al.,18 2002
1
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0
1
1
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7
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Outcome Control Follow-up of for long Adequacy retrospective Representativeness Selection of interest Ascertainment important Assessment enough of cohort of the exposed non-exposed was not Total of exposure factor or of outcome for follow-up studies(n=13) cohorts cohort present additional outcomes of cohorts at start factor to occur of study Antic S et al.,7 1 1 1 1 0 1 1 1 7 2016 Gaddipati R et 1 1 1 0 0 1 1 1 6 al.,23 2014 Naghipur S et 1 1 1 1 0 1 1 1 7 al.,24 2014 Luria J. S et 1 1 1 0 0 1 1 1 6 al.,22 2013 Thangavelu A 1 1 1 1 0 1 1 1 7 et al.,21 2010
1
1
2
1
1
1
9
1
1
0
1
1
1
7
1
1
1
0
1
1
1
7
0
1
1
0
1
1
1
6
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0
1
0
1
1
1
6
1
1
1
1
0
1
1
1
7
1
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1
1
0
1
1
1
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Lee J. T et al.,16 2000 Ugboko V. I et al.,17 2000 Tevepaugh, D. B, et al.,15 1995
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Excluded by title and abstract (n = 445) - Duplicate records - Reviews or Meta-analysis or Case report or Letters - No relevant outcomes and exposure - Not cohort studies
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relative risk (RR) of mandibular angle fracture
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(CI)
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Egger's publication bias plot
Begg's funnel plot with pseudo 95% confidence limits
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Figure 6. Sensitivity analysis of the meta-analysis of M3s and mandibular condylar fracture, with estimated RR and corresponding 95% confidence
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intervals
Meta-analysis estimates, given named study is omitted Lower CI Limit Estimate Upper CI Limit
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Antic S et al., 2016
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Naghipur S et al., 2014
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Gaddipati R et al., 2014
Luria J. S et al., 2013
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Thangavelu A et al., 2010
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0.15 0.25
0.47
0.86
1.16