Relationship between Craniovertebral Abnormalities and Maxillary Lateral Incisors Agenesis: A Case-Control Study

Objectives This study aimed to investigate whether the sella turcica bridging (STB) and ponticulus posticous (PP) are associated with the congenital missing maxillary lateral incisor (CMMLI), based on lateral cephalograms of patients who needed orthodontic treatment. Materials and Methods This case-control study examined 160 panoramic images and lateral cephalograms of 2000 patients seeking orthodontic treatment. The case group included 80 patients with CMMLI (40 with unilateral and 40 with bilateral CMMLI) and the control group included 80 patients without CMMLI. Panoramic images were used to diagnose CMMLI and lateral cephalograms showed STB and PP extension. The researchers used statistical analyses to examine the relationship among STB, PP, and CMMLI (P < 0.05). Results The prevalence of STB type I, II, and III was 47.5%, 35%, and 17.5% in the case group and 72.5%, 22.5%, and 5% in the control group, respectively, determining a positive relationship between CMMLI and STB and a significant relationship between bilateral CMMLI and STB (P < 0.05 for both). The prevalence of normal, incomplete, and complete PP extension was 80%, 5%, and 15% in the case group and 82.5%, 5%, and 12.5% in the control group, respectively. There was no significant relationship between CMMLI and PP extension (P > 0.05) and between the STB and the PP extension (P > 0.05). Conclusion CMMLI was significantly related to STB but not to PP extension. Investigating the relationship between unilateral/bilateral CMMLI, STB, and PP has shown only a significant relationship between bilateral CMMLI and STB. There was no significant relationship between STB and PP extension.


Introduction
e sella turcica is located on the sphenoid's intracranial surface. Its anterior and posterior borders are represented by the tuberculum sella (TS) and the dorsum sellae (DS), forming a U-shaped structure that surrounds the pituitary gland. e distance between TS and DS is known as the sella length or interclinoid distance. e maximum distance between the head of TS and the furthest point on the inner surface of the posterior sella contour is called sella diameter [1,2]. e "sella turcica bridging" (STB) morphologic variation (1.1% to 22%) is the consequence of the dura mater ossifying excessively between the anterior and posterior clinoid processes of the sphenoid, or a product of the sphenoid's improper embryologic development. Multiple craniofacial deformities and local dental anomalies, such as tooth transposition and congenitally missing teeth are thought to be associated with STB [3][4][5]. Ponticulus posticous (PP) or atlas arcuate foramen is defined as an abnormal bony protrusion arising from the superior articulating process of the atlas, partially or entirely surrounding the vertebral arteries and reaching the posterior arch of the atlas [6]. is anomaly can cause a variety of clinical issues such as headaches, dizziness, double vision, and soreness in the shoulder and neck are some of the clinical signs of PP [7].
Tooth agenesis is the most common congenital and developmental dental and craniofacial anomaly, usually resulting from disturbance at the early stages of odontogenesis [8][9][10]. Congenitally missing teeth are those caused by a germ lacking sufficient development to induce dental tissue differentiation, resulting in the missing of one or more teeth [11]. e etiology of tooth agenesis is unclear. However, a variety of probable explanations have been hypothesized, including inherited factors, trauma, localized inflammation, radiation, systemic diseases, and idiopathic diseases [12,13]. After the third molars, the maxillary lateral incisors are the second most common case for agenesis. A number of findings have demonstrated the link between congenital missing maxillary lateral incisors (CMMLIs), displaced teeth, and premolar rotations. Patients with missing permanent teeth may experience various complications such as malocclusion, periodontal disease, lack of alveolar bone development, impaired chewing capacity, pronunciation issues, and alterations in skeletal relationships. e CMMLI depicts a clinical condition in which individuals have functional and aesthetic issues from an early age. erefore, many patients with this anomaly frequently require orthodontic treatment or prosthetic tooth replacement [13,14].
In orthodontics, the lateral cephalogram is the most commonly utilized diagnostic radiograph [3]. Although the cervical vertebrae maturation index is often employed to assess skeletal maturation and clarify the growth potential of young patients, not enough attention is devoted to the pathological aspect of the radiological anatomy of this region. A regular lateral cephalogram can detect significant diseases in the cranium and cervical spine, including the abnormal morphology of the sella turcica and the fusion of the cervical vertebrae, which is associated with craniofacial and dental anomalies [4,15,16].
Since STB is considered a developmental and genetic anomaly, the difference in the genetic composition of the populations may lead to different results [17]. In addition, the research conducted so far on the prevalence of STB in different patients in terms of age, race, skeletal classification, and anomalies has had contradictory results [18]. Moreover, few studies have been performed regarding the relationship between PP and dental anomalies. erefore, this study aimed to identify a link between CMMLI, STB, and the development of PP, examining the lateral cephalograms of patients referred to an oral and maxillofacial radiology center in Iran.

Materials and Methods
e Research Ethics Committee of the Mazandaran University of Medical Sciences approved the study protocol (code: IR.MAZUMS.REC.1400.10433).

Subjects' Characteristics and Sample Size Determination.
is case-control study was performed with 160 pretreatment lateral cephalograms and panoramic radiographs of two groups. e case group consisted of 80 radiographs of patients (40 patients with unilateral and 40 patients with bilateral CMMLI). e control group consisted of 80 radiographs of individuals who needed orthodontic treatment but did not have CMMLI. According to research conducted by Alqahtani [19], the sample size was determined to be 80 samples per group (case and control) (p1 � 46.9%, p2 � 69.4%, α � 0.05, and β � 0.2). e radiographs recorded between 2018 and 2021, belonged to patients seeking orthodontic treatment. e images were selected from among 2000 radiographs in the archive of a private oral and maxillofacial radiology clinic in Sari, Iran, under the supervision of an oral and maxillofacial radiologist.
e inclusion criteria encompassed were as follows: (1) Candidates for orthodontic treatment (2) Patients with unilateral or bilateral CMMLI for the case group (3) Patients with panoramic and cephalometric radiographs of high quality Patients with the following conditions were excluded: (1) Systemic or syndromic disease (2) A history of chemotherapy or radiotherapy (3) A history of previous trauma (4) A history of orthodontic treatment or surgery Panoramic radiographs were used to diagnose the CMMLI ( Figure 1). Lateral cephalograms were traced to assess the calcification of sella turcica. All panoramic radiographs and lateral cephalograms were obtained by an experienced technician using a Planmeca ProOne ® panoramic device (PLANMECA OY©, Helsinki, Finland) and a Vatech lateral cephalometric device (PaX-i Insight model, Vatech Inc., NJ, USA) with a fixed magnification of 1.1. e lateral cephalograms were traced using the CephX (ORCA Dental AI, Las Vegas, NV) by a senior dental student under the guidance of an orthodontist [20].

Determining the STB and PP Extension. According to
Leonardi's conventional categorization [21], there are three varieties of STB based on the length and diameter of the sella ( Figure 2): (i) Type I or normal sella: the sella length is equal to or greater than ¾ of the sella diameter (ii) Type II or partial (incomplete) calcification: the sella length is equal to or less than ¾ of the sella diameter (iii) Type III or complete calcification: only the diaphragm of the sella is visible on the radiograph Complete (full bony bridge), incomplete (partial bony emergence), and normal (no bone emerging) were the three levels of PP development [6] (Figure 3).

Statistical Analysis.
To describe the data, mean and standard deviation were used for quantitative variables and frequency percentages for qualitative variables. Chi-square and independent-sample t-test were used to compare the results of these groups. SPSS 25 software (IBM, Armonk, NY, USA) was used and the significance level was considered P < 0.05.

Results
Based on inclusion and exclusion criteria, 160 out of 2000 lateral cephalometric radiographs were selected and divided into case and control groups. e case group consisted of 80 patients with CMMLI, 40 with unilateral, and 40 with bilateral CMMLI. e control group included 80 patients with both maxillary lateral incisors present. e demographic features of the patients are presented in Table 1.

STB Measurements.
e prevalence of STB was evaluated in the case and control groups. Table 2 shows the frequency of each type of STB. According to this table, the calcification of interclinoid ligament (type II and III STB) was more prevalent in the patients with CMMLI compared to the control group (52.5% vs. 27.5%). e analysis performed using the Chi-square test has shown a significant difference (P � 0.01), indicating a significant relationship between the occurrence of CMMLI and STB. Furthermore, the frequency of STB in patients with unilateral and bilateral CMMLI is shown separately in Table 2. As the data suggests, it is established that the prevalence of STB in bilateral CMMLI is more than in unilateral CMMLI. According to the performed analyses and comparisons, there was a statistically significant relationship between STB and the bilateral CMMLI (P � 0.01) but no significant relationship was found between STB and the unilateral CMMLI (P � 0.06) (Figure 4).

PP Measurements.
e frequency of PP was also measured in the case and control groups ( Table 2). In the case group, 80% of patients were without and 20% with the PP extension (incomplete and complete). In the control group, 82.5% of patients were without and 17.5% with the PP extension.
e Chi-square analysis found no statistically significant relationship between the PP extension and the CMMLI occurrence (P � 0.12). e frequency of PP extension was also compared between unilateral/bilateral CMMLI groups and the control groups. e prevalence of PP extension was similar in unilateral and bilateral CMMLI groups. e analysis has shown no significant relationship between the occurrence of CMMLI (whether unilaterally or bilaterally) and the PP extension (P � 0.12 for both) ( Figure 5).

e Relationship between STB and PP.
e relationship between the STB and the PP extension was studied as an additional hypothesis in this study but no statistically significant correlation was identified (P � 0.14) ( Table 3).

Discussion
is research studied the frequency of each form of STB and PP among orthodontic patients with and without CMMLI. STB and PP were present in 40% and 18.75% of the total study population, respectively. In both case and control groups, the frequency of the incomplete STB was higher than the complete type. Research has recently looked into the link between dentoskeletal anomalies and craniofacial and cervicovertebral anomalies [18,[22][23][24][25][26]. Consistent with the descriptive results of our study, several studies have reported that the prevalence of incomplete STB was higher than the complete form [19, 22, 27 to 29]. On the other hand, other studies have found that the incomplete form of PP was more prevalent than the complete type [22 and 28].

STB and CMMLI.
According to the results of this study, the prevalence of STB was significantly greater in the patients with CMMLI than in the control group (52.5% vs. 27.5%), a finding similar to that of the previous studies [19, 28, and 29]. Although the prevalence of STB was higher in the patients with CMMLI than in the control group in the study of Ozturk et al., no significant relationship was found between STB and CMMLI. is finding was most likely due to the unbalanced distribution of males and females [22]. Other studies have found a significant relationship between STB with other dental abnormalities such as tooth displacement and aplasia [3,21,[30][31][32]. According to the findings of many investigations, STB has been linked to a variety of disorders, including cleft lip and palate, Williams syndrome, severe craniofacial deviations, craniofacial classification, and palatal canine impactions [4, 18, 31, 33, and 34]. is could suggest the presence and role of neural crest cells and homeobox, or HOX genes during tooth formation and development [35].

PP and CMMLI.
ere is scant research studying the link between PP extension and dental abnormalities. e results of this study revealed a slightly greater prevalence of PP extension in patients with CMMLI compared to the control group (20% vs. 17.5%), although it was not statistically significant. In a study by Kaya et al. the prevalence of PP was found to be 26.6% and 16.9% among 75 patients with and 145 individuals without CMMLI, respectively. In contrast to the findings of the present study, the relationship between CMMLI and PP was significant, similar to the International Journal of Dentistry 3 findings of Ozturk et al. [22 and 28]. Studies have demonstrated a significant relationship between PP and other dental anomalies, such as palatal impaction of maxillary canine, hypodontia, and hyperdontia [3, 4, 23, 35 to 37]. e importance of the neural crest as an embryonic source for cervical skeletal and dental development could explain this observation [3,35].

Cervicovertebral Anomalies and Uni/Bilateral CMMLI.
In addition to the preceding information, this study looked into the relationship between the STB and PP with the unilateral or bilateral occurrence of CMMLI. Except for the correlation between STB and bilateral CMMLI, the findings of this analysis revealed no significant relationship in any of the comparisons. To the best of authors' knowledge, only one   other study looked into the relationship between bilateral CMMLI and Cervicovertebral anomalies [22]. Contrary to the results of this study, Ozturk et al. did not detect a significant relationship between bilateral CMMLI and STB, whereas they found a significant relationship between bilateral CMMLI and PP [22], which was in contrast to the current study's findings.

e Relationship between the STB and PP.
Similar to the study by Leonardi et al. [35], there was no statistically significant association between STB and PP extension in this study. On the other hand, Tassoker et al. [38] discovered a significant relationship between STB and the prevalence of PP, which could be attributed to differences in the number of samples investigated. Another issue that might cause contradictory results is the quality of radiographs, leading to not identifying the anomalies, influenced by the proper selection of kVp and mA and the proper film processing method. Furthermore, heredity and external mechanical elements, such as carrying heavy objects on one's head and bone development due to aging can influence the study results.

STB and PP, Age and Gender.
e investigations on the relationship between age/gender and STB/PP have yielded conflicting results. is study did not investigate the effects of age and gender on STB and PP. Research claim that there is no significant difference in STB and PP between men and women [4, 16, 39, and 40]. Alqahtani, on the other hand, found a significant association in CMMLI, indicating that males had more STB than females [19]. In addition, some studies have discovered a significant relationship between the dimensions of sella turcica in both men and women. e dimensions of sella turcica were also strongly related to the subjects' age [34,41]. However, contrary to those findings, some research found no link between age and STB or PP [4,27].

Clinical Significance.
e relationship between STB and dental anomalies has been discussed in the literature and this study. e literature reported an increased frequency of PP development in individuals with dental anomalies such as CMMLI and palatally impacted canines [3, 19, 28, 29, and 35]. Moreover, some studies investigated the relationship between STB and skeletal malocclusions and found a higher frequency of STB in patients with skeletal Class II and III malocclusions compared to skeletal Class I malocclusion [1,18,42,43]. As many cervicovertebral abnormalities such as STB and PP appear in early childhood, orthodontists must diagnose them on time. is can help predict dental and skeletal anomalies, leading clinicians to take preventative interventions. Orthodontists should be familiar with these types of malformations in the craniofacial area and not just focus on the maxillomandibular complex to have a comprehensive and broad overview contributing to a proper diagnosis and treatment plan.      e use of two-dimensional lateral cephalometric films to examine a three-dimensional anatomical structure was a limitation of this work. Cone-beam computed tomography, which gives three-dimensional imaging, may be more accurate for this purpose. However, such imaging modalities are not recommended for routine usage in orthodontic patients due to high-dose radiation exposure [44]. Moreover, skeletal classification was not taken into account for participants with dental anomalies and equal sex distribution was overlooked in all groups. erefore, future research should include people of similar ages and skeletal malocclusions, as well as an equal number of female and male participants (Table 4).

Conclusion
(i) Both STB and PP were found in individuals with CMMLI. e STB was positively correlated with CMMLI. Although the extension of PP was slightly more frequent in patients with CMMLI, no significant relationship was determined. (ii) e STB was significantly related to the occurrence of bilateral CMMLI but not to the occurrence of unilateral CMMLI. ere was no significant difference between the PP extension and the occurrence of CMMLI (whether unilaterally or bilaterally). (iii) No significant relationship existed between the STB and the PP extension.
Data Availability e datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Conflicts of Interest
e authors declare that they have no conflicts of interest.

Authors' Contributions
FS, MA, and SD conceived the idea, designed and performed experiments, supervised the project, and revised the initial manuscript of the article. SMG collected the data and wrote the initial manuscript. KM analyzed the data and wrote the initial manuscript. All of the authors have approved the final manuscript.