Outcomes of permanent canines on the cleft side after secondary alveolar grafting using different materials in complete unilateral cleft lip and palate

Abstract The prevalence of impaction of the permanent canine on the cleft side (PCCS) ranges from 12-35% after alveolar bone grafting (ABG). PCCSs usually develop above other permanent teeth in the alveolar process, gradually becoming vertical until they reach the occlusal plane. The type of cleft, hypodontia of lateral incisor on the cleft side, slower PCCS root development, and genetic factors are predictors of impaction and/or its ectopic eruption. Objective: To compare the behavior of PCCS in individuals with complete unilateral cleft lip and palate (UCLP) subjected to secondary alveolar grafting (SAG) with different materials. Methodology: This retrospective longitudinal study analyzed 120 individuals undergoing SAG with iliac crest bone, rhBMP-2, and mandibular symphysis. The individuals were selected at a single center and equally divided into three groups. Panoramic radiographs were analyzed by the Dolphin Imaging 11.95 software to measure PCCS angulation and PCCS height from the occlusal plane at two different timepoints. Results: No statistical significance was found between grafting materials (P=0.416). At T1, the PCCS height from the occlusal plane was greater for rhBMP-2 and mandibular symphysis compared to iliac crest bone. The lateral incisor on the cleft side was not related to success or lack of eruption of PCCS (P=0.870). Conclusion: Impaction rates of PCCS were similar for the materials studied. Absence of the lateral incisor on the cleft side did not prevent spontaneous eruption of PCCSs.


Introduction
The prevalence of permanent canine impaction on the cleft side ranges from 12-35% after secondary alveolar bone grafting (ABG) 1,2 compared to 1.7-3% in the general population. 3,4 Maxillary canines usually develop above other permanent teeth in the alveolar process. During spontaneous eruption, the canine moves toward the occlusal plane and gradually becomes vertical. Permanent canine on the cleft side (PCCS) erupts more slowly, with delayed root development compared to the contralateral side.
This long-lasting eruption makes it more susceptible to ectopia and increases the risk of impaction. 5,6 Furthermore, a relationship between tooth agenesis, clefts, and genetic disorders has been suggested. 5,7 Studies have shown that an increased mesiodistal angulation and a more apical position of PCCS are associated with its impaction. 2,5,[8][9][10] Some authors have associated impacted canines with the lack of bone in alveolar defects, which reduces the space available for eruption. 9 Also, timing of ABG surgery can also interfere with PCCS eruption. 5,11 Secondary alveolar bone grafting (SABG) is performed at mixed dentition, preferably before PCCS eruption, due to its contribution to maintenance of the grafted site and neighboring supporting periodontium. 12-14 Besides favoring spontaneous eruption of PCCS, the main advantage of SABG is to allow orthodontic movement into the grafted alveolar cleft without harming periodontal tissues. S A B G s u s i n g r e c o m b i n a n t h u m a n b o n e morphogenetic protein

Results
Intra-examiner reliability for PCCS angulation and PCCS height measurements was excellent, with ICCs=0.996 and 0.994, respectively. ICCs for interexaminer reliability were also excellent (0.963 and 0.992), as shown in Table 2. Intra-examiner and inter-examiner random error for PCCS angulation ranged from 1.17-3.55º, respectively. For PCCS height, intra-examiner and inter-examiner random error ranged from 0.63-0.74 mm, respectively. Only PCCS angulation showed a significant inter-examiner systematic error (P=0.007) ( Table 2).

Discussion
The null hypothesis that the SAG material does not influence PCCS outcome was confirmed (P=0.416) and agrees with previous studies that showed similar rates of canine eruption into the cleft site grafted by iliac crest, rhBMP-2, or mandibular symphysis. 5,17 The panoramic radiograph is used to determine the angulation and height of canines 4,18,20,21,23 and has *statistical significance. PCCSs, permanent canines on the cleft side; BMP, rhBMP-2 group; IC, iliac crest group; MS, mandibular symphysis group.  shown reproducibility and reliability of the technique in previous studies. 18,20,23 Similarly, in this study, intraexaminer and inter-examiner reliabilities for angulation and height ranged from 0.96-0.99 ICC. Intra-examiner and inter-examiner random error for PCCS angulation was less than 4º. Intra-examiner and inter-examiner random error for PCCS height was less than 1.00 mm ( Table 2). Although PCCS angulation showed a significant systematic error (P=0.007, Table 2), the quality of some older panoramic radiographs impaired the identification of condyles. A previous study also reported difficulty in identifying the condyle landmark on some panoramic radiographs, 25 which encourages the use of radiographs with better quality and does not make the method unfeasible.
Despite the attempt to pair groups in starting forms to eliminate biases, differences between groups were found for PCCS height, root formation stage, and mean age at T1. Although patients in the ICG were chronologically older than those in the BMPG, with no statistically significant difference between the chronological ages of ICG and MSG, tooth development was more delayed in both ICG and BMPG compared to MSG (Figure 3). This probably occurred because bone harvesting from the mandibular symphysis is safer when mandibular permanent canines have more developed roots. 18, [26][27][28] The similarity of the three graft materials compared in this study concerning the ability to fill the cleft was previously shown. 18,19,29,30 MS was an attractive donor site with low morbidity compared to IC. Its advantages include restriction to intraoral operative sites, minimal pain or discomfort, and an invisible scar in the lower labial sulcus. 1,26 The restriction to the intraoral operative site was also a disadvantage since it does not allow two teams to operate simultaneously, leading to longer operations. Other disadvantages of the donor site include limited supply, making it not suitable for large or bilateral clefts, 18,31 impairment of neighboring teeth and mental nerve, and an increased rate of impacted canines. 1,26,27 In this study, the ratio of impacted canines at grafted sites that required surgical exposure for orthodontic traction was similar to the previous literature (27.5% against 12-35%). 5,8 Of 33 unerupted canines, 28 underwent surgical exposure and orthodontic traction.
Five canines are being followed and will likely require surgical exposure for orthodontic traction. Of 28 orthodontically tractioned canines, 12 were in the ICG, eight in the BMPG, and eight in the SMG.
In agreement with previous studies that showed that late alveolar bone grafting may be associated with an increased canine angulation and a higher canine position in the horizontal and vertical sectors, 5,11 a time interaction was found in intergroup and intragroup comparisons for PCCS angulation, PCCS height, and root formation stage in this study. An increased mesiodistal angulation and greater height were also observed as predictors of canine impaction, confirming a previous study. 20 In our study, impacted canines showed mean differences of approximately 11º and 8mm in angulation and height before and after AG, respectively. Although AGs were performed before PCCS eruption, starting differences in root development may have influenced PCCS behavior.
Future studies should compare PCCS outcomes after AG performed at the same root formation stage. Also, a study mentioning more details about the final position of PCCS after AG should be carried out. Panoramic radiographs analyzed varied in timing standardization.
Possible explanations would be that the institution is a teaching hospital and serves patients with socioeconomic difficulties, making protocol follow-ups unfeasible.

Conclusion
Impaction rates of permanent canines on the cleft side were similar between ABG performed with iliac crest, rhBMP-2, and mandibular symphysis. The absence of the lateral incisor on the cleft side did not prevent spontaneous eruption of PCCS.