A systematic review and meta-analysis of the prevalence and global distribution of middle mesial canals in mandibular molars identified by CBCT

The inability to identify and debride all infected root canals can contribute to failure in root canal treatment [1, 2]. The complexities of anatomy can limit the ability of clinicians to see or find root canals and hence reduce their ability to disinfect and adequately obturate the canals [2].

Mandibular 1^st and 2^nd molars have been commonly described as having two roots, one mesial and one distal [3, 4], with the mesial root having a mesiobuccal (MB) and a mesiolingual canal (ML), while the distal root has a single canal [5]. A variation is an additional canal originating between the MB and the ML canal, referred to as the middle mesial canal (MMC) [6]. Due to the poor accessibility of the MMC, this canal might act as a reservoir for residual infected pulp tissue and bacteria, leading to persistent apical periodontitis [2, 7].

A systematic review assessed MMC’s prevalence, finding that MMCs ranged between 0.26-53.8% [8]. This wide range was related to the included studies that varied in methodology. The methods of the studies included the clearing technique, conventional radiography, scanning electron microscope, dental operating microscope (DOM), cone-beam computed tomography (CBCT), and micro-CT. Moreover, their search keywords were somehow limited and were not comprehensive.

Micro-CT studies are accurate and can reveal details of the root canal anatomy. However, the sample size of such studies is often limited due to the expenses of such studies [9]. Moreover, they can only be performed on extracted teeth that are not representative of healthy teeth because extracted teeth may have been associated with endodontic or periodontal disease [10]. Furthermore, these studies are primarily performed on a pool of extracted teeth; therefore, they cannot differentiate between the extracted 1^st, 2^nd, and 3^rd molars.

Clinical in vivo studies with an operating microscope can explore negotiable MMCs in non-extracted teeth [11, 12]. However, it may be difficult to distinguish a true MMC from an isthmus [11]; therefore, a higher incidence of MMC may be found in such studies.

CBCT is as accurate as micro-CT for identifying canals and is clinically realistic for what can be identified when treating patients [9]. CBCT has the advantages of being in vivo and non-invasive and allows for expanding the sample size compared to microscopic analysis or other laboratory studies using extracted teeth. CBCT is an appropriate in vivo tool for evaluating anatomic variations and has been widely used to study large populations [13, 14]. In addition, detailed epidemiological data such as gender, race, and ethnicity can also be obtained from CBCT studies.

Recently, a meta-analysis was performed on the global prevalence of MMC, focusing primarily on CBCT studies [15]. They reported the pooled prevalence rates on 4 continents (Asia, Europe, America, and Africa). However, categorizing into only 4 continents and reporting the prevalence based on such vast continents seems biased. For example, there are different races in East Asia compared to West Asia or North America compared to South America. Moreover, after their study, some new articles in new regions with considerable sample sizes were published; the most prominent one is a very well-designed multinational study with a sample size of 12,608 teeth [16].

Thus, this study aimed to perform a systematic review of the literature and meta-analysis to evaluate the prevalence of MMC in permanent mandibular molars of different populations based on CBCT studies.

This systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) [17]. The protocol of this review was registered in PROSPERO under the code number CRD42022375405.

A total of 1165 articles were obtained from the electronic database search, gray literature, and hand searching. After applying the eligibility criteria and eliminating duplicates, 88 articles were selected for full-text assessment. Following the reading of the full-texts, 54 studies were excluded. Thus, 34 studies that fulfilled the eligibility criteria were included for quality assessment and quantitative synthesis (Fig. 1 & Supplementary Table S2).

In the present study, the worldwide prevalence of MMC in the mandibular 1^st molar was 4.15%. However, the presence of MMC varies in different geographical regions and ranges from 0 to 29.7%. Except for the prevalence of MMC in the United States of America, which was based on only a single study (26%), the highest prevalence of MMC in the mandibular 1^st molar was found in South Asia (11.24%), followed by Africa (6.61%).

According to the results of the present study, a cumulative prevalence of 1.2% was found for the occurrence of MMC in the mandibular 2^nd molars. The highest prevalence of MMC in the mandibular 2^nd molar was found in the South Asia (3.97%) and the West Asia (3.56%).

In the present study, for the first time, the cumulative prevalence of MMC is reported by different countries (Fig. 5). Moreover, the prevalence of MMC is reported separately in different regions and continents of the world. Before our study, a systematic review assessed the prevalence of MMC [8]. However, their study had some limitations; for instance, the studies varied in methodology, and voxel sizes of more than 200 μm were included, which is unsuitable for detecting root canal anatomy [55]. Moreover, there was no mention of whether the studies excluded endodontically treated teeth [8]. These differences might depict why the prevalence range of MMCs varied in their study (0.26-53.8%) compared to ours (0-29.7%). Recently, Al-Maswary et al. published a meta-analysis on the global prevalence of MMC focused primarily on CBCT studies [15]. They reported the global prevalence of MMC to be 4.4% in the 1^st molar and 1.3% in the 2^nd molar, which was in accordance with the results of our study. However, they reported the pooled prevalence rates based on only 4 continents (Asia, Europe, America, and Africa). The racial discrepancy cannot be applied in such a classification based on the vast extent of the continents. For instance, there are different races in East Asia compared to West Asia or North America compared to South America. Therefore, in our study, the regions were classified more precisely including more number of regions but with less extent, including South Asia, West Asia, East Asia, Africa, Europe, North America, and South America. By doing this, the racial bias can be controlled. Compared to the study of Al-Maswary et al., we reported the pooled prevalence rates based on countries wherever possible; therefore, clinicians can find the prevalence of MMC in their country (Fig. 5). More importantly, based on the studies that were published after the study of Al-Maswary, we were able to include another 11,820 samples from new countries, including Saudi Arabia, Egypt, Germany, Croatia, Jordan, Kazakhstan, Libya, Malaysia, Poland, and Turkey.

A well-designed multinational cross-sectional study on the prevalence of MMC with a sample size of 12,608 reported a range of 1-23% [16]. In their study, the prevalence of MMC was 7% for the mandibular 1^st molar, which is more than the results of our study. The greater prevalence can be because their study does not include countries from East Asia, North America, and South America [16].

One of the limitations of our study is that regional prevalence cannot necessarily imply ethnic diversities [4]. A geographic region can have multiple ethnic origins, as many countries are a mix of ethnicities. For example, in the study by Pan et al. performed in Malaysia, the majority were Chinese (92.3%), followed by Indians (4.3%), Malays (2.4%), and other races (1.0%) [56]. Furthermore, the root canal anatomy of teeth may vary with sex and age [4]. In our study, the gender and age of the studied population could not be analyzed due to variations in measurements and frequently missed data. However, in general, the studies that focused only on the prevalence of the MMC canal did not find any difference in gender [10, 16, 30, 57].

As mentioned above, no meta-analysis was performed on age and its relation with the prevalence of MMC because of the insufficient data and heterogeneity of the most included studies regarding age. However, some studies reported that the prevalence of identifiable MMC decreases as age increases [8, 46]. Therefore, the prevalence of identifiable MMC could be related to secondary dentin deposition [58]. In contrast, Tahmasbi et al. [10] found the highest prevalence of MMC in the 41-60 age group, and Srivastava et al. [57] found the highest prevalence of MMC in the 31-50 age group. The contrast in findings could also be due to the formation of dentin within the isthmus between the MB and the ML canal, where a previously joined canal becomes separated by dentin and thus creates another canal.

It is also essential to differentiate and clarify the meaning of the isthmus and MMC. Bansal et al. defined an isthmus as a narrow connection between two root canals containing pulp tissue [8]. Pomeranz et al. described MMC as a fin, confluent, or independent canal between the MB and ML canals [6]. However, this definition cannot distinguish between an isthmus and an actual canal [10]. Some have defined a “true MMC” as a clear, round cross-section in the radiographic image between the MB and ML canals, which can be with an isthmus [10, 45]. A systematic review discussed that the inconsistent definition of MMC might be a reason for the wide range of MMC occurrences [8].

Another reason for the diversity of the data in the literature might be the different detection methods to identify MMC. For example, clinical in vivo studies with a DOM can explore negotiable MMCs in non-extracted teeth [11, 12]; however, differentiating a true MMC from an isthmus may not be possible [11], which may account for a higher incidence of MMC in the study of Azim et al. (46%) [11] compared with our study (4.15%).

The voxel size is crucial for detecting root canal system anatomy in CBCT studies. Mirmohammadi et al. has shown that a voxel size of 125 μm has an accuracy of 96% for detecting the second MB canal in maxillary molars [59]. Zhang et al. came to the same conclusion for choosing a voxel size of 125 μm when detecting root canal anatomy of mandibular premolars [60]. Vizzotto et al. reported that a CBCT voxel size of 200 μm had a higher sensibility than larger voxel sizes to detect the second MB canal [55]. Therefore, voxel sizes of more than 200 μm might miss some root canal anatomy. Thus, we excluded the studies that had advocated voxel sizes of more than 200 μm from the present study (Supplementary Figure S1). However, the analysis of the effect of different voxel sizes <200 μm on MMC detection has shown no significant differences [16]. In the study of Hatipoglu et al., the prevalence of MMC was equal (7%) for either voxel sizes ≤150 μm or 150–200 μm [16].

Field of view (FOV) is an important criterion in CBCT imaging. In endodontics, particularly for detecting root canals, a limited FOV CBCT is preferred over medium or large FOV CBCT [61]. This preference is due to the lower radiation dose to the patient, higher spatial resolution, and fewer volumes to interpret. As the FOV size increases, the spatial resolution and image quality decrease, resulting in a higher probability of missing a canal [61]. It should be noted that in morphological studies, CBCT images were not prescribed for endodontic reasons but for general aims such as surgical interventions or evaluation of the surrounding anatomies. Therefore, a medium to high field of view is commonly used, which can lead to underestimation of root canals, such as MMCs. The larger field of view is an inevitable limitation of studies included in the present meta-analysis.

Based on the recommendation of the joint position statement of the American Association of Endodontists and the American Academy of Oral and Maxillofacial Radiology, a limited FOV CBCT should be considered the imaging modality of choice for initial treatment of teeth with the potential for extra canals and suspected complex morphology [61]. As mentioned before, along with a limited FOV, voxel sizes ≤200 μm should be set for endodontic evaluations [55], such as detecting MMCs.

DOM is another essential aid in nonsurgical and surgical endodontics for locating additional canals [62]. In particular, performing a standardized troughing under high magnification between MB and ML canals is suggested to search for a MMC [11]. To manage the MMC canal during apical surgery of mandibular molars, Pomeranz et al. suggested that after resecting the apex and retro-preparation of the MB and ML canals, to deeply connect the canals to satisfactorily debride and to allow for good retention and sealing of the retrograde filling material [6]. Although the prevalence of MMC was rare in all geographic populations included in this study, the authors suggest always looking for MMC when doing an endodontic treatment on mandibular molars.

A limitation of the present study is that most of the included studies did not include C-shaped and single-rooted teeth in their sample size for estimating the prevalence of MMC; therefore, in only one study [34], to calculate the total number of included teeth, we excluded C-shaped and single-rooted teeth from the original sample size in that study. This procedure was performed to match and adjust their methodology to the other included studies. Although C-shaped and single-rooted molars are rare, excluding such teeth from the study may result in an over-representation of the remaining teeth, leading to an overestimation of the prevalence of MMC. Based on the topic of the present review, only cross-sectional studies could be inserted that, in the hierarchy of evidence, were considered as low level of evidence. However, 94.1% of the included studies had low bias levels.

When interpreting the results of the present study, it is important to consider the limited number of studies available in certain regions. For example, only a single study was conducted on the vast continent of North America [10]. Similarly, countries like Libya and Germany, which are larger than their neighbors, had only one study that met the inclusion criteria for our meta-analysis [16]. The scarcity of studies in these regions may explain the higher prevalence of MMCs compared to their neighboring countries. Among the included studies, only a few countries had two or more studies on the prevalence of MMCs. These countries included China, India, Iran, Pakistan, Yemen, Saudi Arabia, Portugal, and Brazil. Furthermore, there are still many countries for which we were unable to find any data regarding the prevalence of MMCs. Therefore, caution should be employed when generalizing the results of this meta-analysis to each region. It seems that further studies are needed on the prevalence of MMCs in different regions of the world.

For future studies, it is suggested that 1) studies must define their precise definition of a MMC versus isthmus so that it is easier to interpret the data, 2) perform studies on patients over multiple decades of age to determine how age may affect the detectability of MMC, and 3) consider a voxel size equal to or lower than 200 μm.

The prevalence of MMC varies among regions. The MMC prevalence in mandibular 1^st molars is 4.15% globally. The mandibular 2^nd molar rarely has the MMC (1.2%). Understanding the incidence of MMC can guide clinicians as to whether troughing under high magnification or further investigation with CBCT is indicated when performing endodontic treatment of mandibular molars.