Timing matters: Dental development and outcomes on secondary alveolar bone grafting in cleft lip and palate patients

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Materials and Methods This retrospective single-center cohort study included 104 patients with unilateral or bilateral CLP (127 cleft sites). Orthopantomograms and clinical records were evaluated at three stages: pre-SABG, six months post-SABG, and post-orthodontic treatment. Canine root mineralization stage was classified as R = 0,25 − 1,0, corresponding to 25–100% root development respectively. Assessed parameters included the canine mineralization stage, axis-anglulation and vitality, limbus height, probing depths, and space closure strategy. Statistical analysis used the Student’s t-test. Results SABG performed at early stages of canine root development (R ≤ 0,5) was associated with higher success rates of orthodontic space closure (71,4% at R = 0,5 vs. 25% at R = 1,0; p < 0,05) and bone graft preservation. In patients with lateral incisor agenesis, early SABG facilitated mesial canine eruption but increased the incidence of canine impaction (18,6%). The mean axis-angle of cleft-side canines differed significantly between orthodontic and prosthodontic space closure (81,3° vs. 91,0°, t = 5,702). Limbus alveolaris height was reduced when SABG occurred after root completion (R = 1,0, t = 4,234). Periodontal probing depths remained < 3 mm, and canine vitality was preserved in all groups. Conclusions Early SABG, timed according to canine mineralization, supports alveolar bone preservation and space closure without compromising periodontal health. Clinical Relevance Tailoring SABG timing based on dental development can optimize orthodontic and prosthodontic outcomes in patients with CLP. Secondary alveolar bone grafting cleft lip and palate orthodontic space closure canine eruption Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Alveolar bone grafting (ABG) is a critical surgical procedure introduced in 1952 [ 1 ] for patients with cleft lip and palate. It primarily aims to reconstruct the alveolar cleft, maintaining arch continuity and stability. ABG supports tooth eruption [ 2 ], prevents alveolar segment collapse, and facilitates orthodontic tooth movement. Additionally, ABG improves facial symmetry [ 3 ], enhances aesthetics, restores function, and provides a foundation for future prosthodontic rehabilitation [ 4 , 5 ]. The timing of ABG plays a critical role in treatment outcomes. Primary ABG is typically performed until 2 years of age as part of comprehensive cleft care, promoting optimal bone regeneration and tooth support [ 6 ]. Secondary bone grafting (SABG) is generally recommended between 9 and 11 years of age, ideally before the permanent canine eruption, as later, the procedure has shown less favorable outcomes [ 7 , 8 ]. Some suggest that performing the procedure before or during the eruption of the lateral incisor can improve periodontal health and arch symmetry [ 6 , 9 ]. However, the optimal timing of SABG remains a subject of debate due to its impact on long-term dental and skeletal development. Early SABG, performed between 4 and 7,6 years, has largely been abandoned due to concerns associated with compromised maxillary growth [ 6 , 7 ]. Recent studies advocate that SABG performed around six years does not hinder midfacial growth [ 9 , 10 ]. While age ranges are commonly used, individualized approaches, such as assessing lateral incisor or canine root mineralization or the residual bone thickness over the adjacent crowns, offer a more tailored strategy for optimal grafting outcomes [ 6 ]. Beyond its impact on growth, SABG timing also influences dental eruption patterns, particularly regarding the risk of canine impaction. The initial position and angulation of the canine are critical factors, as a greater inclination and a higher initial position increased the risk of canine impaction, primarily when bone grafting was performed after significant root maturation [ 11 ]. The challenge in clinical decision-making lies in balancing the benefits of early intervention with potential effects on skeletal growth and dental development. Improper timing may lead to complications, including orthodontic instability or insufficient bone formation for future dental implants [ 4 ]. Notably, lateral incisor agenesis emerged as a critical factor, with canine impaction being more prevalent in cases with lateral incisor agenesis. This suggests that the lateral incisor plays a guiding role in directing the canine along its eruption path [ 12 ]. Conventional two-dimensional (2D) dental radiographs are widely used to assess secondary alveolar bone grafting outcomes. Nevertheless, they often systematically overestimate bone volume in the grafted alveolar clefts due to anatomical superimpositions and cannot capture bucco-palatal bone dimensions [ 13 – 15 ]. With advancements in imaging technology, computed tomography (CBCT) has become instrumental in treatment planning and outcome assessment in SABG [ 16 ]. The ability of CBCT to provide detailed three-dimensional information enhances clinical decision-making by allowing precise evaluation of graft volume, bone integration, and potential complications. No significant difference was found between the cleft and non-cleft sides. Despite the growing use of CBCT for post-surgical evaluation, clinical records in many institutions still rely on conventional 2D imaging due to existing patient documentation and accessibility. This study evaluates the timing of SABG based on canine root mineralization stages and its impact on alveolar bone preservation, eruption patterns, periodontal health and graft stability. Specific parameters assessed include alveolar bone height, periodontal probing depths and canine inclination adjacent to the clefts. By comparing treatment outcomes across different developmental stages and space closure strategies, this study identifies areas for improvement in interdisciplinary care protocols and decision-making in orthodontic and prosthodontic rehabilitation of cleft sites. Therefore, this study seeks to address gaps in the current understanding of optimal SABG timing in patients with CLP by investigating its influence on periodontal and dental outcomes and structural graft stability in orthodontic and prosthodontic reconstruction alternatives for the cleft region. 2. Participants and Methods 2.1 Participants This study retrospectively collected data from patients with unilateral or bilateral CLP (UCLP or BCLP) treated with SABG. The patients were born between 1976 and 1985, and their evaluation was performed between the ages of 8 to 14. All cleft-related interventions were conducted at the same center at Charité - Universitätsmedizin Berlin. A total of 104 patients with 127 cleft regions were included in the study. The mean patient’s age was 9,9 ± 1,6 years at the time of surgery. Eighty-two cleft regions showed agenesis of the lateral incisor. The inclusion criteria of this study were as follows: Patients with UCLP or BCLP with or without agenesis of the lateral incisor Treated from birth at Charité - Universtitätsmedizin Berlin Successful SABG was performed between 1984 and 1999 using autologous bone Caucasian ethnic background No associated congenital malformations, syndromes, or intellectual disabilities No multiple tooth agenesis Age at SABG ranged from 8 to 14 years 2.2 Treatment protocol The treatment of patients with CLP at the Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, followed a standardized treatment protocol, as summarized in Table 1 . If required, orthodontic expansion was performed before bone grafting. At Charité, autologous bone grafting is typically employed for SABG, with bone commonly harvested from the iliac crest and transplanted into the alveolar cleft. This study collected data before, after SABG, and after orthodontic treatment. 2.3 Data acquisition Data from patients with CLP who underwent SABG were retrospectively analyzed. Orthopantomograms taken before and after SABG, as well as following orthodontic treatment, were evaluated for the following parameters: Canine mineralization stage Inclination of the canine’s longitudinal axis Canine impaction incidence Canine eruption through the bone graft in both sagittal and transverse dimensions Bone graft and limbus alveolaris height of teeth adjacent to the cleft Clinical assessment included: Periodontal probing depth using a 6-point pocket chart Canine vitality test Table 1: Standardized surgical and orthodontic treatment protocol for patients with CLP treatment at the Charité - Universitätsmedizin Berlin, Campus Virchow age surgical treatment protocol orthodontic treatment protocol 4 - 6 months 2 - 4 years 4 - 6 years 6 - 11 years 11 - 16 years lip closure soft and hard palate closure secondary bone grafting (iliac crest bone) infant orthopedics correction of crossbite and/or collapsed arch segments and/or class III malocclusion treatment tooth eruption guidance (Hotz protocol), correction of rotated upper central incisors, and crossbite (removable and/or functional appliances) multibracket appliance 2.4 Methods The study adhered to the STROBE guidelines for observational studies. This retrospective cohort study was conducted in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The institutional ethics committee of Charité - Universitätsmedizin Berlin approved the study (EA2/240/17). The surgical intervention was considered successful if a continuous bone graft was radiographically discernable six months after secondary osteoplasty. 2.4.1 Radiographic analysis Orthopantomograms (OPTGs) were taken at the following time points: T0: preoperative assessment (mean age: 10,0 ± 1,8 years) T1: six months post-secondary osteoplasty (mean age: 12,5 ± 1,7 years) T2: after completion of orthodontic treatment (mean age: 16,6 ± 1,6 years) To minimize selection bias, only patients with complete and high-quality radiographic records were included in the analysis. Our retrospective study of all the eligible patients with cleft provided us a total of 127 OPTGs at T0 and T1. Moreover, 102 OPTGs or periapical radiograph regions from cleft areas were available at T2. The canine mineralization stage was determined using the Moorrees et al. method [ 17 ] as modified by Schopf [ 18 ]. An adapted scheme is presented in Fig. 1 . The limbus alveolaris height and bone graft were assessed using a modified version of the Long et al. method [ 19 ]. The axis angle of cleft-sided canines was measured following the method described by Dausch-Neumann [ 20 ]. 2.4.2 Measurement procedures To ensure standardized and reproducible data, the following measurements were applied: Insertion height: defined as the distance of the cementoenamel junction to the cervical bone margin. Bone graft height: measured as the distance to the most apical point of the bone graft, perpendicular to the cementoenamel junction of the central incisor and the canine on the cleft side. Relative height of the limbus alveolaris and the bone graft: expressed as a dimensionless ratio based on one-tenth of the canine crown length. Canine axis-angle: defined as the angle enclosed between the occlusal plane (connecting the distobuccal cusps of the first molars) and the longitudinal axis of the canine (in the coronal-apical direction) [Fig. 2]. 2.4.3 Orthodontic and clinical evaluation Three-dimensional plaster models (T2: 16,2 ± 1,7 years) of 64 cleft regions were used to measure the extent of orthodontic tooth movement during space closure via reflex microscopy. Clinical assessment of adjacent teeth at T3 (mean age: 17,7 ± 1,9 years) using the Parodontometer PCP 10 (Hu-Friedy©). Periodontal probing depth using a 6-point method on the teeth adjacent to the cleft was tested at a clinical follow-up on 58 cleft regions with a registration per tooth. Canine vitality was assessed using carbon dioxide snow testing. 2.5 Statistical analysis All data were recorded and analyzed using SPSS (Version 6.0; Chicago, III). The following variables were evaluated: The axis-angle of the teeth adjacent to the cleft (in degrees). Canine root mineralization was determined as a root-to-crown length ratio (dimensionless). Graft and limbus height of the alveolar ridge relative to the crown length (dimensionless). Model measurements for the distances (in millimeters). Data distribution was tested for normality using the Kolmogorov-Smirnov test. A normal distribution was confirmed at a 5% significance level, apart from a few isolated outliers. Statistical analysis was performed using Student’s t-test, with a significance level set at p < 0,05. Contingency tables reported the number of cleft sites, mean values, and 95% confidence intervals. For small sample sizes (n < 30), mean comparisons were performed using the Student’s t-test, applying the formula by Spiegel and Stephens [ 21 ]. 3. Results In total, 104 patients with 127 cleft sites and a mean age of 9,9 ± 1,6 years at the time of surgery were included in the study. Eighty-two cleft sites showed agenesis of the lateral incisor. To facilitate statistical evaluation and data interpretation, the patient population was stratified based on the presence or absence of the lateral incisors and the type of space closure (orthodontic vs. prosthodontic). All patients were successfully treated with secondary osteoplasty using autologous bone grafting. The four stages of canine root mineralization (R 0,25 − 1,0) were used to evaluate the optimal timing of SABG. Early and late SABG were used when bone grafting was performed at R ≤ 0,5 and R ≥ 0,5, respectively. Patient distribution according to cleft type and sex is presented in Fig. 3 . Of the 127 cleft sites, 81 (63,8%) were associated with unilateral cleft patients, while 46 (36,2%) involved bilateral clefts. The cohort included 91 males (71,6%) and 36 females (28,4%). The mineralization stage of canines adjacent to the cleft was age-dependent. The dental development of females was 0,2 − 0,5 years earlier than males. The sex distribution difference was statistically not significant. 3.1 Space closure and timing of SABG Among the 127 cleft sites, 77 (60,6%) underwent orthodontic space closure, while 44 (34,6%) received prosthodontic rehabilitation. In three cleft regions, severe canine impaction and lateral incisor agenesis required surgical removal of the canine. Additionally, three cleft sites exhibited lateral incisor transposition with the canine, which occurred exclusively in early SABG cases (R≤0,5) [Fig. 4 ]. The success rate of orthodontic space closure in lateral agenesis patients was highest when SABG was performed at R≤0,5, with 66,6% at the mineralization stage R = 0,25 and 71,4% at stage R = 0,5. However, when SABG was performed later, during stages R = 0,75 and R = 1,0, the success rate for orthodontic space closure declined to only 21,8% and 25%, respectively. However, the 82 cleft sites were nearly equally distributed between the two types of space closure: 43 (52,4%) received prosthodontic and 39 (47,6%) orthodontic space closure. The distribution of space closure type was equally balanced within these subgroups. 3.2 Canine impaction and SABG timing Among the 127 canines adjacent to the cleft assessed, 13 required surgical exposure, followed by orthodontic extrusion, while three severely impacted canines were extracted. All extractions occurred solely in the lateral agenesis group. The impaction risk was increased when SABG was performed at early mineralization stages (R ≤ 0,5). In contrast, 96,6% of canines erupted spontaneously into the bone graft when SABG was performed late (R ≥ 0,75). 3.3 Canine axis-angle and eruption pattern Preoperative inclination The axis angle was assessed using preoperative orthopantomograms. Before SABG, the canine adjacent to the cleft with an existing lateral incisor exhibited a more upright position compared to those with lateral incisor agenesis, showing a statistically significant difference (Student’s t = 2,082) In cases where no SABG was performed, the canine tended to upright along the posterior cleft margin. Statistical comparison between mineralization stage subgroups was significant for both patient cohorts: Student’s t = 2,231 for regions with existing lateral incisors and Student’s t = 3,272 for those with lateral incisor agenesis. Post-eruption inclination SABG timing did not influence the canine axis-angle in patients with lateral incisors. However, in agenesis cases, a moderate but statistically significant correlation was found between SABG timing and the axis-angle of the canine on the cleft side. When SABG was carried out during early mineralization stages (R ≤ 0,5), canines erupted in a more tilted position into the bone graft - favoring orthodontic space closure. At a later stage (R ≥ 0,75), the canine tended to upright at the posterior cleft margin. The comparison between the two subgroups was statistically significant, with a Student’s t = 3,343. There was a mean canine inclination difference of 8,4 ° between the lateral incisor agenesis and non-agenesis patient cohorts. Overall, canines in non-agenesis cases exhibited higher axis angles and erupted more upright across all mineralization stages than in agenesis cases [Fig. 5 ]. After orthodontic treatment of patients with lateral incisor agenesis, the mean canine axis-angle was 91 ° following prosthodontic space closure and 81,3 ° following orthodontic space closure, resulting in a mean difference of 9,7 °, which was statistically significant (Student’s t = 5,702). In addition, surgical exposure and orthodontic traction of impacted canines did not negatively affect bone graft height. The results were even more favorable than those of spontaneously erupted canines. However, this difference was not statistically significant due to the small sample size of this cohort and should be interpreted with caution. Assessing the canine eruption pattern in a transverse dimension revealed that most (90,9%) canines erupt orthotopically in patients with lateral incisors. In agenesis cases, 24% were palatally, and 2% were buccally displaced. Hence, the timing of SABG plays an important role, as significantly higher displacement rates were observed when performed in early mineralization stages (R ≤ 0,5). A description of the transversal canine eruption pattern is shown in Fig. 6 . 3.4 Height of bone graft according to canine eruption and type of space closure The height of the bone graft adjacent to the cleft, measured after the canine eruption, showed a statistically significant correlation with the timing of secondary osteoplasty in the lateral incisor agenesis group. When the canine root mineralization was R>0,5 at the time of the surgery, the bone graft height was significantly reduced, compared to cases with SABG at R ≤ 0,5 (Student’s t = 4,234). No such correlation was observed in the patient cohort with lateral incisors. A similar trend was noted when evaluating bone graft height in relation to the presence of lateral incisors. However, in lateral incisor agenesis cases, the type of space closure significantly influenced bone graft preservation. Patients treated with orthodontic space closure experienced significantly less bone resorption compared to those who underwent prosthodontic space closure (Student’s t = 5,406). Taking arithmetic mean values into account, higher rates of bone resorption after prosthodontic space closure (M = 5,8) were observed compared to orthodontic space closure (M = 3,3). However, the difference was not statistically significant. This discrepancy was likely due to natural bone atrophy resulting from the lack of functional loading in prosthodontically treated sites. If orthodontic space closure was the treatment of choice, the bone graft height would remain stable regardless of the agenesis of the lateral incisors. However, bone graft height was lower when SABG was performed late (R ≥ 0,75), particularly in lateral incisor agenesis cases, as evident from the mean values (e.g., in R = 0,25: 1,8 vs. in R = 1: 5,8) as presented in Tables 2 and 3 . Table 2 Bone graft height (dimensionless value) with lateral incisors M: arithmetic mean value; CI: 95%-confidence interval; n: number of cleft regions type of space closure after canine eruption after orthodontic treatment M CI n M CI n prosthodontic 3,3 5,2 4 5,8 7,9 4 orthodontic 3,8 7,5 38 3,3 7,3 37 transposition 4,0 2,0 3 4,7 4,1 3 total 3,7 7,0 45 3,6 7,3 44 Table 3 Bone graft height (dimensionless value) with lateral incisor agenesis M: arithmetic mean value; CI: 95%-confidence interval; n: number of cleft regions type of space closure after canine eruption after orthodontic treatment M CI n M CI n prosthodontic 4,3 3,9 40 6,0 3,6 36 orthodontic 2,5 5,0 39 2,5 5,1 25 total 3,4 4,7 79 5,3 5,6 61 3.5 Height of the limbus alveolaris according to canine eruption and type of space closure The height of the limbus alveolaris was measured mesial to the canine adjacent to the cleft. Evaluating the height of the limbus alveolaris after canine eruption revealed a significantly (Student’s t = 4,221) lower bone level if SABG was performed late (R = 1) compared to surgical intervention in earlier root mineralization stages (R ≤ 0,75). In the earlier stages, limbus height differed only marginally and was independent of lateral incisor presence. The type of space closure had a strong influence on limbus alveolaris height. Before orthodontic treatment, the bone level was well preserved in all groups, with bone resorption rates below 2 mm. This stability persisted in cases treated with orthodontic space closure, where limbus alveolaris height remained stable during and after treatment. No statistical association was found between limbus height and SABG timing. However, prosthodontic space closure was linked to significantly higher bone resorption in both groups: patients with lateral incisors (Student’s t = 4,434) and those with lateral incisor agenesis (Student’s t = 3,762). 3.6 Periodontal evaluation As part of a clinical follow-up, probing depths were measured mesial to the canines and distal to the central incisors adjacent to the cleft. The clinical examination revealed a healthy periodontal situation with probing depths < 3 mm. Neither lateral incisor agenesis nor the type of space closure had a statistically significant impact on periodontal health. However, slightly higher probing scores were assessed in cases with orthodontic space closure. Here, it should be noted that the formation of an interdental papilla was not examined. No significant differences in probing scores were observed between the cleft and non-cleft sides in patients with UCLP. 3.7 Vitality of cleft-sided canines In this study, carbon dioxide snow (dry ice) was used for the pulp vitality testing. Only three canines showed no response to the test. One canine was endodontically treated and was in transposition with the lateral incisor. The other two non-responsive canines were part of a bridge construction used for prosthodontic space closure, resulting in unclear reactions during the vitality test. 4. Discussion The optimal timing of secondary alveolar bone grafting (SABG) remains a critical factor in successfully rehabilitating patients with cleft lip and palate (CLP), as it directly influences the bone graft integration, tooth eruption, and long-term orthodontic outcomes. Despite its widespread clinical application, the ideal timing for SABG remains a topic of debate. This single-center study aimed to assess the impact of SABG timing on key treatment outcomes, including bone graft height, limbus alveolaris integrity, canine eruption, inclination angle, and type of space closure, by using canine root mineralization stages as developmental reference instead of chronological age. Additionally, this study seeks to identify shortcomings in the interdisciplinary care approach during SABG and propose areas for improvement. The study considered the possibility of separately evaluating patients with UCLP and BCLP and accounting for gender differences. However, these stratifications were not applied to avoid compromising statistical power. Instead, the patients were grouped based on the canine root mineralization stage, which mitigates potential biases while maintaining the robustness of the findings. Root mineralization stages provide a more accurate reflection of dental developmental age than the chronological age, especially in patients with CLP, who often exhibit delayed and variable dental development [ 22 ]. The canine root mineralization stage can be assessed during routine preoperative radiological diagnostics without additional radiation exposure. Since canine eruption is closely linked to the root’s mineralization stage, it serves as a reliable developmental reference [ 23 ]. Additionally, the canine germ is located distal to the cleft and, unlike incisors, does not exhibit associated morphological aberrations that may interfere with root mineralization assessment [ 24 ]. The bone graft height and limbus alveolaris were evaluated relative to the canine crown. Orthopantomograms obtained at T0, T1, and T2 were assessed following the method described by Aurouze et al. [ 25 ] and Long et al. [ 19 ]. The canine angulation in the mesiodistal dimension was assessed using the method outlined by Dausch-Neumann [ 20 ]. Modern X-ray devices equipped with positioning aids and staff trained in their use ensure standardization and reproducibility of imaging. Positioning errors, such as deviations from the Frankfurter horizontal plane or dorsal- and ventral neck flexion during imaging, can affect occlusal plane alignment [ 18 ]. To minimize such errors, only orthopantomograms that strictly meet the criteria were analyzed. The occlusal plane was leveled, and the cranial angle was measured on 20 standardized images. Orthopantomograms deviating more than twice the standard error from the mean value were excluded to ensure accuracy. Numerous studies assessing SABG outcomes in CLP patients have reported good accuracy using intraoral radiographs [ 26 , 27 ]. A continuous and sufficient bone bridge is essential for successful tooth eruption into the graft and effective orthodontic movement. Bähr and Coulon recommended a minimum bone bridge width of 9 mm to accommodate the permanent canine [ 28 ]. These findings align with Mikoya et al., who advocated a buccopalatal width of 9,6 mm at the mid-level between the apical and coronal borders for positive treatment results [ 29 ]. To ensure these results and optimize SABG timing, precise radiologic examination of the target area around the erupting canine while considering the patient’s individual dental development is crucial. However, over the last years, alternative imaging methods such as computed tomography (CT) and cone-beam computed tomography (CBCT) have become increasingly crucial for the three-dimensional assessment of cleft regions and bone grafts. Studies have shown that conventional 2D orthopantomograms often underestimate bone resorption [ 30 ] because they evaluate only the vertical dimension. In this study, the quantity and quality of bone, or bucco-palatal resorption, could not be accurately assessed from orthopantomograms. Resorption may reach up to 49,5% within the first year after surgery [ 31 , 32 ]. This underlines the critical need to evaluate bucco-palatal bone thickness to ensure proper canine positioning. Our study is based on conventional radiographic measurements while acknowledging the limitations of volumetric assessment compared to CBCT. Although 3D imaging methods are superior to 2D methods, a consistent imaging protocol is necessary to ensure comparable diagnostic and follow-up results [ 33 ]. Furthermore, adherence to the ALARA (As Low As Reasonably Achievable) principle remains crucial for balancing diagnostic accuracy and radiation exposure, particularly in pediatric patients. Although Wriedt et al. found no significant differences between 2D and 3D imaging in predicting tooth alignment or orthodontic treatment planning, they acknowledge the surgical advantages of preoperative CBCT scans [ 34 ]. However, recent research indicated that volumetric CBCT assessment of the canine root formation offers no predictive advantage over conventional intraoral radiographs for assessing canine eruption following SABG [ 35 ]. These findings underscore the importance of carefully balancing the benefits of advanced imaging against its clinical utility and associated radiation risks. Introduced by Boyne and Sands in 1972 [ 36 ], SABG, during the late mixed dentition phase (8–12 years of age), has become the standard treatment for reconstructing bony defects in cleft lip and palate (CLP) patients [ 37 ]. After the age of eight, maxillary growth is primarily completed, minimizing the risk of growth impairment following SABG [ 38 – 40 ]. Bergland et al. [ 41 ] demonstrated optimal outcomes when SABG was performed before the canine eruption. In our study, only three out of 127 cleft areas were treated before the age of eight, making it unlikely that a significant impact on maxillary growth would be observed. Most patients (57%) underwent SABG between the ages 9 and 11 (mean age: 9 ± 1,6 years), which is consistent with the previous studies reporting an age range of 8,2 to 10,6 years for conventional SABG [ 31 , 36 – 39 ]. Impact of SABG timing on space closure SABG timing significantly influenced space closure outcomes in patients with lateral incisor agenesis. Early SABG (R ≤ 0,5) tripled the success rate of orthodontic space closures compared to late SABG (R ≥ 0,75). The measurements showed that the space between the cleft-sided central incisor and canine was significantly (Student’s t = 4,575) smaller in cases of early SABG (R ≤ 0,5) than in later stages (R = 0,75, R = 1). The mesial drift of the erupting canine (R ≤ 0,5) decreased the canine inclination angle, facilitating space closure with less orthodontic movement (Student’s t = 2,931). The required mesial movement for space closure ranged from only 1,7 mm (R = 0,25) to 6,2 mm (R = 1,0). Thus, early SABG (R ≤ 0,5) facilitates successful orthodontic space closure in CLP patients with lateral incisor agenesis. The absence or presence of lateral incisors and the mesio-distal space must be considered in decision-making on the type of space closure [ 42 ]. Although the aesthetic outcomes of both orthodontic and prosthodontic space closure are satisfactory and comparable in the long term, the risk of cranio-mandibular dysfunction increases after prosthodontic rehabilitation with resin-bonded bridges [ 41 ]. Despite conventional SABG being well documented and considered the gold standard, the current literature suggests a shift towards an earlier intervention before the eruption of the lateral incisors [ 43 , 44 ]. Early SABG may offer particular advantages for patients with CLP and existing lateral incisors, as performing the procedure before the age of 5–7 can provide adequate bone support for their eruption [ 45 ]. There is little but promising evidence that early SABG does not lead to impaired craniofacial growth [ 9 , 41 ]. The cephalometric evaluation of Brudnicki et al. directly compared the skeletal outcome of maxillary development of early versus late SABG and showed that both groups exhibited similar maxillary growth patterns [ 46 ]. Dissaux et al. focused on bone volume after 6 months as an indicator of grafting success and concluded that CLP patients undergoing surgery around the age of 5 years had better treatment outcomes than those with conventional SABG around the age of ten [ 36 ]. Additionally, the treatment proposed by Precious et al. [ 47 ] showed better periodontal health, crown length, and central incisor symmetry with early SABG. Regardless of the age at ABG, the eruption of a permanent tooth (lateral incisor or canine) into the graft has a positive and stabilizing effect on the bone height [ 36 ]. Bone graft and limbus alveolaris height This study highlights the impact of SABG on bone graft preservation in patients with lateral incisor agenesis. Bone graft resorption was 3,5 mm greater in the late SABG sites (R = 1) compared to early SABG (R = 0,25). These findings align with those of Bergland et al. [ 7 ], who reported that the standard interdental septum height was maintained in 64% of early SABG cases, compared to only 37% in late SABG cases performed before and after the canine eruption, respectively. Since septum height is crucial for future dental implants, early SABG may be preferable when orthodontic space closure is not indicated. These findings align with previous studies [ 7 , 48 ] that recommend SABG near the eruption of the tooth adjacent to the cleft, followed by early loading through orthodontic tooth movement or implant placement, to prevent bone atrophy due to functional loss. Zhang et al. supported this approach, showing a maximum bone graft reduction within three to six months post-SABG [ 39 ]. However, as CBCT was not yet standard, our assessments relied mainly on conventional 2D radiographs. Canine impaction and eruption Compared to non-cleft populations with a prevalence of 1–2% canine impaction [ 49 ], CLP patients are at a greater risk for impaction of cleft-sided canines. However, the data provided in the literature are not consistent and vary between 6%, 27%, and up to 56% [ 50 – 52 ]. This study’s overall impaction rate of cleft-sided canines was 10,2%, within the abovementioned range. The majority (89,8%) erupted spontaneously into the graft, revealing a positive effect of SABG on successful canine eruption. Thirteen of 127 evaluated cleft-sided canines were impacted. The three that required surgical removal were all from the agenesis cohort. Early SABG (R ≤ 0,5) was associated with an increasing impaction rate, supporting the findings of Hoang et al. [ 51 ], who reported a link between SABG performed at one-third of the canine root development and a higher impaction rate of cleft-sided canines. In our study, this trend was even more striking with lateral incisor agenesis, accounting for 76,9% of the impacted canines. This rate is over three times higher than in the cohort with existing lateral incisors. Additionally, lateral incisor agenesis is associated with palatinal displacement of the erupting canine, likely due to the absence of the lateral incisor root, which guides the canine’s eruption path [ 53 ]. Consequently, lateral incisor agenesis has been identified as a potential risk factor for canine displacement and impaction after early SABG. A systematic review by Lacerda et al. also identified a connection between canine impaction and lateral incisor agenesis, but there was low certainty of evidence [ 54 ]. Moreover, advanced root development, apical tooth position, sharper axial angulation, older age at the time of SABG and the need for regrafting are further predictive factors for canine impaction in cleft patients [ 11 , 55 – 57 ]. Nevertheless, in our cohort, impacted canines were successfully managed with surgical exposure and orthodontic traction without adverse effects on graft stability or periodontal health. These results support a risk-benefit approach: early SABG can be performed safely when radiographic and interdisciplinary planning are ensured. Clinical implications and interdisciplinary care Periodontal stability and inflammation-free tissues are crucial for long-term graft success. Existing literature indicates that SABG does not adversely affect the periodontal integrity of teeth adjacent to the cleft, with attachment levels comparable to those of non-cleft teeth [ 58 , 59 ]. According to our findings, the probing depths of all cleft-sided teeth remained within the healthy range (< 3 mm) and did not differ significantly from those of the contralateral side in patients with UCLP. Loss of vitality was seldom observed and was not associated with either the surgical intervention or subsequent orthodontic treatment. Neither periodontal health nor vitality was correlated with the timing of SABG, the presence of lateral incisors or the type of space closure. Poor oral hygiene is a known risk factor for surgical failure due to bone loss [ 60 ]. A 20-year follow-up study by Jabbari et al. demonstrated a positive correlation between gingival bleeding index and prosthetic restorations in cleft areas, leading to increased bone resorption [ 61 ]. Given the increased susceptibility of cleft patients to periodontitis, thorough oral hygiene instructions, regular professional dental care, and strong interdisciplinary collaboration with restorative dentists and periodontists are crucial to ensure the long-term health and stability of the cleft region and minimize the need for regrafting. Although this study provides important insight, some limitations should be acknowledged. The retrospective single-center study design may introduce selection bias and limit generalizability. Although strict inclusion criteria and a uniform treatment protocol were applied, the retrospective nature of the data prevented randomization and prospective control. Furthermore, the radiographic assessment relied exclusively on 2D-imaging procedures, which are limited to assessing bucco-palatal dimensions or volumetric changes at the grafted site. Although orthopantomograms were the clinical standard during the treatment period and offered longitudinal comparability, they may lead to under- or overestimation of actual bone graft volume due to anatomical superimpositions. The absence of CBCT limits the ability to evaluate three-dimensional graft morphology and spatial bone preservation. Future studies should incorporate CBCT-based volumetric analysis to validate and expand upon these findings, particularly by assessing long-term graft resorption and integration. While early SABG improved bone preservation and facilitated bone orthodontic space closure, it was also associated with a higher incidence of impaction, particularly in patients with lateral incisor agenesis. Although these impactions were successfully managed, the findings underscore the need for individualized treatment planning based on the developmental stage and eruption path, achieved through close monitoring. Although the imbalance between agenesis and non-agenesis cases may limit the power of subgroup comparison, stratified analysis and careful subgroup evaluation were used to minimize bias in interpretation. To strengthen the clinical evidence base, future trials should adopt a prospective, multicenter design with larger, demographically balanced cohorts. Incorporating three-dimensional imaging modalities such as CBCT will allow for accurate volumetric analysis. The use of standardized protocols for radiographic and periodontal examinations would enhance comparability across centers. Furthermore, stratification by cleft type and tooth agenesis status, combined with multivariate statistical models, may provide deeper insight into the complex interaction between SABG timing, dental development, and long-term outcomes. 5. Conclusions SABG timing is a critical factor in treatment outcomes in patients with CLP. The study identified the root mineralization stage of the tooth adjacent to the cleft as the key predictor for optimal SABG timing. Performing SABG during the early canine mineralization stages (R ≤ 0,5) promotes canine eruption success into the bone graft, facilitates space closure, especially in cases with lateral incisor agenesis, and preserves both the bone graft and the limbus alveolaris height. Furthermore, the study identified that bone resorption in the graft and adjacent to the limbus alveolaris was significantly lower following orthodontic space closure compared to prosthodontic treatment alternatives. Early SABG, at the R ≤ 0,5 stage, may slightly increase the risk of canine impaction or transposition with the lateral incisor. However, these complications can be effectively managed through surgical canine exposure and orthodontic extrusion without leading to higher bone resorption rates or periodontal damage. In conclusion, this study underscores the crucial role of precisely tailored and optimally timed SABG in optimizing functional and structural outcomes in cleft site management while minimizing potential complications. To refine treatment protocols and enhance outcomes for patients with CLP, further research should integrate CBCT-based volumetric assessment with additional clinical and biomechanical parameters. Declarations Ethics approval Ethical approval for this study was granted by the Ethics Committee of the Charité-Universitätsmedizin Berlin, Germany, ID: EA2/240/17. The trial was conducted in accordance with the ethical principles outlined in the 1964 Declaration of Helsinki. Competing interests The authors declare no competing interests. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author Contribution T.B. contributed to the study’s visualization, data interpretation, supervision, and review and editing of the manuscript. I.H. contributed to data interpretation visualization, drafted and critically revised the manuscript J.K. contributed to data interpretation, drafted and critically revised the manuscript F.J. contributed to data interpretation and drafted the initial version of the manuscript. M.S. contributed to the conception, design, data collection, interpretation and statistical analysis. C.O. contributed to the study’s conception, design, data interpretation and critically revised the manuscript. All authors read and approved and agree to accountability for integrity. References Axhausen (1952) Technik und Ergebnisse der Spaltplastiken (Technique and results of plastic operations on clefts). Carl Hanser, München Enemark H, Sindet-Pedersen S, Bundgaard M (1987) Long-term results after secondary bone grafting of alveolar clefts. J Oral Maxillofac Surg 45(11):913–919 Lemberger M et al (2024) Long-term radiographic and periodontal evaluations of the bone-grafted alveolar cleft region in young adults born with a UCLP. Eur J Orthod, 46(1) Kim J, Jeong W (2022) Secondary bone grafting for alveolar clefts: surgical timing, graft materials, and evaluation methods. Arch Craniofac Surg 23(2):53–58 Kyung H, Kang N (2015) Management of Alveolar Cleft. 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Übersetzung der 3.Auflage McGraw-Hill International (UK) Ltd.,pp. 242–244 Van Dyck J et al (2019) Dental development in cleft lip and palate patients: A systematic review. Forensic Sci Int 300:63–74 Demirjian A, Levesque GY (1980) Sexual differences in dental development and prediction of emergence. J Dent Res 59(7):1110–1122 Möller LH et al (2021) Prevalence of hypodontia and supernumerary teeth in a German cleft lip with/without palate population. BMC Oral Health 21(1):60 Aurouze C et al (2000) The presurgical status of the alveolar cleft and success of secondary bone grafting. Cleft Palate Craniofac J 37(2):179–184 Rawashdeh MA, Al KS, Nimri (2007) Outcome of secondary alveolar bone grafting before and after eruption of the canine in Jordanian patients with cleft lip and palate. J Craniofac Surg 18(6):1331–1337 Trindade IK et al (2005) Long-term radiographic assessment of secondary alveolar bone grafting outcomes in patients with alveolar clefts. 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J Craniomaxillofac Surg 44(1):21–216 Feichtinger M, Mossböck R, Kärcher H (2006) Evaluation of bone volume following bone grafting in patients with unilateral clefts of lip, alveolus and palate using a CT-guided three-dimensional navigation system. J Craniomaxillofac Surg 34(3):144–149 Ruppel JK et al (2016) The Americleft Project: A Comparison of Short- and Longer-Term Secondary Alveolar Bone Graft Outcomes in Two Centers Using the Standardized Way to Assess Grafts Scale. Cleft Palate Craniofac J 53(5):508–515 Zhang DZ et al (2015) Evaluation of Bone Height and Bone Mineral Density Using Cone Beam Computed Tomography After Secondary Bone Graft in Alveolar Cleft. J Craniofac Surg 26(5):1463–1466 Cabrera CT (2024) A Review of Orthodontic Considerations before and after Alveolar Bone Grafting in Patients with Cleft Lip and Palate. Acta Med Philipp 58(21):7–19 Doucet JC et al (2019) Facial Growth of Patients With Complete Unilateral Cleft Lip and Palate Treated With Alveolar Bone Grafting at 6 Years. Cleft Palate Craniofac J 56(5):619–627 A Review of Orthodontic Considerations before and after Alveolar Bone Grafting in Patients with Cleft Lip and Palate . Acta Medica Philippina, (2023) Lu X et al (2025) Comparing Three-dimensional Radiologic Outcomes Between Early Versus Late Secondary Alveolar Bone Grafting. J Craniofac Surg 36(1):78–83 Brudnicki A, Sawicka E, Fudalej PS (2021) Maxillofacial morphology in post-pubertal patients with unilateral cleft lip and palate following early vs. late secondary alveolar bone grafting. J Craniomaxillofac Surg 49(9):809–814 Cabrera C (2023) A Review of Orthodontic Considerations before and after Alveolar Bone Grafting in Patients with Cleft Lip and Palate. Acta Medica Philippina Brudnicki A et al (2017) Cephalometric comparison of early and late secondary bone grafting in the treatment of patients suffering from unilateral cleft lip and palate. J Craniomaxillofac Surg 45(4):479–484 Precious DS (2009) A New Reliable Method for Alveolar Bone Grafting at About 6 Years of Age. J Oral Maxillofac Surg 67(10):2045–2053 Horswell BB, Henderson JM (2003) Secondary osteoplasty of the alveolar cleft defect. J Oral Maxillofac Surg 61(9):1082–1090 Becker A, Chaushu S (2015) Etiology of maxillary canine impaction: A review. Am J Orthod Dentofac Orthop 148(4):557–567 da Silva Filho OG et al (2000) Secondary Bone Graft and Eruption of the Permanent Canine in Patients with Alveolar Clefts: Literature Review and Case Report. Angle Orthod 70(2):174–178 Hoang E et al (2023) Factors Contributing to Canine Impaction in Patients With Unilateral Cleft Lip and Palate Undergoing Alveolar Bone Grafts. J Oral Maxillofac Surg 81(10):1286–1294 El Deeb M et al (1982) Canine eruption into grafted bone in maxillary alveolar cleft defects. Cleft Palate J 19(1):9–16 Jacoby H (1983) The etiology of maxillary canine impactions. Am J Orthod 84(2):125–132 Lacerda-Santos R et al (2021) Effectiveness of Secondary Alveolar Bone Graft on Canine Eruption: Systematic Review. Eur J Dent 15(3):579–587 Caceres Manfio AS et al (2022) Eruption path of permanent maxillary canines after secondary alveolar bone graft in patients with nonsyndromic complete unilateral cleft lip and palate. Am J Orthod Dentofac Orthop 161(5):e416–e428 Simões Holz I et al (2018) Permanent canine eruption into the alveolar cleft region after secondary alveolar bone grafting: Are there prediction factors for impaction? Am J Orthod Dentofac Orthop 154(5):657–663 Westerlund A et al (2014) What factors are associated with impacted canines in cleft patients? J Oral Maxillofac Surg 72(11):2109–2114 Eldeeb ME et al (1986) Repair of alveolar cleft defects with autogenous bone grafting: periodontal evaluation. Cleft Palate J 23(2):126–136 Andlin-Sobocki A, Eliasson LA, Paulin G (1995) Periodontal evaluation of teeth in bone grafted regions in patients with unilateral cleft lip and cleft palate. Am J Orthod Dentofac Orthop 107(2):144–152 Lundberg J, Levring E, Jäghagen, Sjöström M (2021) Outcome after secondary alveolar bone grafting among patients with cleft lip and palate at 16 years of age: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol 132(3):281–287 Jabbari F et al (2018) Secondary Alveolar Bone Grafting in Patients Born With Unilateral Cleft Lip and Palate: A 20-Year Follow-up. Cleft Palate Craniofac J 55(2):173–179 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 30 Oct, 2025 Read the published version in Clinical Oral Investigations → Version 1 posted Editorial decision: Revision requested 07 Jul, 2025 Reviews received at journal 06 Jul, 2025 Reviews received at journal 23 Jun, 2025 Reviewers agreed at journal 14 Jun, 2025 Reviewers agreed at journal 12 Jun, 2025 Reviewers invited by journal 12 Jun, 2025 Editor assigned by journal 06 Jun, 2025 Submission checks completed at journal 06 Jun, 2025 First submitted to journal 02 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6804368","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471245365,"identity":"a0d4d700-5497-4a25-8a8a-faa5b6dd15cb","order_by":0,"name":"Theodosia Bartzela","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIie2QPUsDMRiAXzlIl7e5NaHl+hdyHBRKhf6VyMF1UdyKLmdAuEn3G/wRujinHHjL0bmd7C2dugnFbqYV8YNcdXTIQ7KEPDy8L4DD8R9h5uLH2UHB00eKeADabuB3RQIQIPJPCnxRUBxURp3r6XJ9kXZ91Z6+XL6mAWlVG55PhkBLZa90n+LwriqQaRrzSpKI4Nkjv5+NgVf2DLLTfqedaQSNgiuJJxkYpc4KEHPZoJxvjJJiT2O0VZJdZf569a48L5sqxCgeCo19UxGSmBf+sK80bGyeRPtZwoImA5XIMGOraJDPxmgmsyqtPK53GxsF5W2xUMdpz/fjenEzGQa0tI//ifez/8t/h8PhcBzgDVszWLw5eq/7AAAAAElFTkSuQmCC","orcid":"","institution":"University Hospital Carl Gustav Carus","correspondingAuthor":true,"prefix":"","firstName":"Theodosia","middleName":"","lastName":"Bartzela","suffix":""},{"id":471245366,"identity":"dfdeb013-1710-4f04-ba56-ffe12d8de06c","order_by":1,"name":"Isabel Hoffmann","email":"","orcid":"","institution":"University Hospital Carl Gustav Carus","correspondingAuthor":false,"prefix":"","firstName":"Isabel","middleName":"","lastName":"Hoffmann","suffix":""},{"id":471245367,"identity":"b985ff22-9723-4fc9-b4b7-18bbc2e31530","order_by":2,"name":"Jennifer Kluge","email":"","orcid":"","institution":"University Hospital Carl Gustav Carus","correspondingAuthor":false,"prefix":"","firstName":"Jennifer","middleName":"","lastName":"Kluge","suffix":""},{"id":471245368,"identity":"e5250175-84d9-4636-88bd-9c862b611a86","order_by":3,"name":"Fabian Jäger","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Fabian","middleName":"","lastName":"Jäger","suffix":""},{"id":471245369,"identity":"7e5862c6-f276-4821-a192-7b74a0d303f5","order_by":4,"name":"Michael Schmechel","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Schmechel","suffix":""},{"id":471245370,"identity":"b21ff257-cad0-470a-add2-ca8cbccaadbc","order_by":5,"name":"Charlotte Opitz","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Charlotte","middleName":"","lastName":"Opitz","suffix":""}],"badges":[],"createdAt":"2025-06-02 17:38:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6804368/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6804368/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00784-025-06594-w","type":"published","date":"2025-10-30T15:57:33+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84819217,"identity":"85ff2060-2d16-43bd-9484-45798cb291a3","added_by":"auto","created_at":"2025-06-17 15:58:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":10521,"visible":true,"origin":"","legend":"\u003cp\u003eCanine root mineralization stages (R)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6804368/v1/db7ad67e0f33d24bf931a7ec.png"},{"id":84819218,"identity":"d3178746-5fc1-4e8f-b81e-5455df5c733e","added_by":"auto","created_at":"2025-06-17 15:58:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":94900,"visible":true,"origin":"","legend":"\u003cp\u003eMeasurement of the canine axis angle. Method by Dausch-Neumann (1970) [20]\u003c/p\u003e\n\u003cp\u003eA: longitudinal canine axis, B: occlusal plane by Dausch-Neumann (1970) [20], connecting the distobuccal cusps of the first molars, a: canine axis-angle\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6804368/v1/288fb91437582ac18f54178a.png"},{"id":84820082,"identity":"f9c927a1-92c7-4c1f-b802-0dbfd0e58815","added_by":"auto","created_at":"2025-06-17 16:06:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":78594,"visible":true,"origin":"","legend":"\u003cp\u003ePatient distribution according to cleft type and sex and records available at the registration time points T0: preoperative assessment, T1: post-operative assessment, T2/T3: after orthodontic treatment, n: number of cleft regions, OPTG: Orthopantomogram\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6804368/v1/c4f2931972b3e6a037d69957.png"},{"id":84819222,"identity":"371d58ac-107b-469c-9476-72f6459a55a8","added_by":"auto","created_at":"2025-06-17 15:58:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":16079,"visible":true,"origin":"","legend":"\u003cp\u003eType of space closure (SC) depending on canine root mineralization (R) at the time of SABG\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6804368/v1/0db86f4f7a0a07cad6ff0d57.png"},{"id":84820083,"identity":"d44f4d42-d1b3-4cb4-b2f7-4653ea56d758","added_by":"auto","created_at":"2025-06-17 16:06:24","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":18598,"visible":true,"origin":"","legend":"\u003cp\u003eArithmetic mean values (M) of canine axis-angles (in degrees º) after canine eruption according to root mineralization (R) and SABG timing with 95% confidence intervals\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6804368/v1/e2684f28ad483a386f132cdb.png"},{"id":84819226,"identity":"c4473b23-49da-4253-a023-b40cebc140cd","added_by":"auto","created_at":"2025-06-17 15:58:24","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":9363,"visible":true,"origin":"","legend":"\u003cp\u003eCanine eruption pattern in transversal dimension according to the presence/absence of lateral incisors\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6804368/v1/0e133572ed16547f7ec870e1.png"},{"id":95040446,"identity":"382c135f-df59-4ba1-95ae-9501f0e11856","added_by":"auto","created_at":"2025-11-03 16:08:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1191127,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6804368/v1/fda33b41-aa92-46f9-b787-533e35f512ac.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Timing matters: Dental development and outcomes on secondary alveolar bone grafting in cleft lip and palate patients","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAlveolar bone grafting (ABG) is a critical surgical procedure introduced in 1952 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] for patients with cleft lip and palate. It primarily aims to reconstruct the alveolar cleft, maintaining arch continuity and stability. ABG supports tooth eruption [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], prevents alveolar segment collapse, and facilitates orthodontic tooth movement. Additionally, ABG improves facial symmetry [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], enhances aesthetics, restores function, and provides a foundation for future prosthodontic rehabilitation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The timing of ABG plays a critical role in treatment outcomes. Primary ABG is typically performed until 2 years of age as part of comprehensive cleft care, promoting optimal bone regeneration and tooth support [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Secondary bone grafting (SABG) is generally recommended between 9 and 11 years of age, ideally before the permanent canine eruption, as later, the procedure has shown less favorable outcomes [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Some suggest that performing the procedure before or during the eruption of the lateral incisor can improve periodontal health and arch symmetry [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, the optimal timing of SABG remains a subject of debate due to its impact on long-term dental and skeletal development. Early SABG, performed between 4 and 7,6 years, has largely been abandoned due to concerns associated with compromised maxillary growth [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Recent studies advocate that SABG performed around six years does not hinder midfacial growth [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. While age ranges are commonly used, individualized approaches, such as assessing lateral incisor or canine root mineralization or the residual bone thickness over the adjacent crowns, offer a more tailored strategy for optimal grafting outcomes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Beyond its impact on growth, SABG timing also influences dental eruption patterns, particularly regarding the risk of canine impaction. The initial position and angulation of the canine are critical factors, as a greater inclination and a higher initial position increased the risk of canine impaction, primarily when bone grafting was performed after significant root maturation [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The challenge in clinical decision-making lies in balancing the benefits of early intervention with potential effects on skeletal growth and dental development. Improper timing may lead to complications, including orthodontic instability or insufficient bone formation for future dental implants [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Notably, lateral incisor agenesis emerged as a critical factor, with canine impaction being more prevalent in cases with lateral incisor agenesis. This suggests that the lateral incisor plays a guiding role in directing the canine along its eruption path [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConventional two-dimensional (2D) dental radiographs are widely used to assess secondary alveolar bone grafting outcomes. Nevertheless, they often systematically overestimate bone volume in the grafted alveolar clefts due to anatomical superimpositions and cannot capture bucco-palatal bone dimensions [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. With advancements in imaging technology, computed tomography (CBCT) has become instrumental in treatment planning and outcome assessment in SABG [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The ability of CBCT to provide detailed three-dimensional information enhances clinical decision-making by allowing precise evaluation of graft volume, bone integration, and potential complications. No significant difference was found between the cleft and non-cleft sides. Despite the growing use of CBCT for post-surgical evaluation, clinical records in many institutions still rely on conventional 2D imaging due to existing patient documentation and accessibility.\u003c/p\u003e \u003cp\u003eThis study evaluates the timing of SABG based on canine root mineralization stages and its impact on alveolar bone preservation, eruption patterns, periodontal health and graft stability. Specific parameters assessed include alveolar bone height, periodontal probing depths and canine inclination adjacent to the clefts. By comparing treatment outcomes across different developmental stages and space closure strategies, this study identifies areas for improvement in interdisciplinary care protocols and decision-making in orthodontic and prosthodontic rehabilitation of cleft sites. Therefore, this study seeks to address gaps in the current understanding of optimal SABG timing in patients with CLP by investigating its influence on periodontal and dental outcomes and structural graft stability in orthodontic and prosthodontic reconstruction alternatives for the cleft region.\u003c/p\u003e"},{"header":"2. Participants and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Participants\u003c/h2\u003e \u003cp\u003eThis study retrospectively collected data from patients with unilateral or bilateral CLP (UCLP or BCLP) treated with SABG. The patients were born between 1976 and 1985, and their evaluation was performed between the ages of 8 to 14. All cleft-related interventions were conducted at the same center at Charit\u0026eacute; - Universit\u0026auml;tsmedizin Berlin. A total of 104 patients with 127 cleft regions were included in the study. The mean patient\u0026rsquo;s age was 9,9\u0026thinsp;\u0026plusmn;\u0026thinsp;1,6 years at the time of surgery. Eighty-two cleft regions showed agenesis of the lateral incisor.\u003c/p\u003e \u003cp\u003eThe inclusion criteria of this study were as follows:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePatients with UCLP or BCLP with or without agenesis of the lateral incisor\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eTreated from birth at Charit\u0026eacute; - Universtit\u0026auml;tsmedizin Berlin\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSuccessful SABG was performed between 1984 and 1999 using autologous bone\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCaucasian ethnic background\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNo associated congenital malformations, syndromes, or intellectual disabilities\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNo multiple tooth agenesis\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAge at SABG ranged from 8 to 14 years\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e2.2 Treatment protocol\u003c/h3\u003e\n \u003cp\u003eThe treatment of patients with CLP at the Charit\u0026eacute; - Universit\u0026auml;tsmedizin Berlin, Campus Virchow Klinikum, followed a standardized treatment protocol, as summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. If required, orthodontic expansion was performed before bone grafting. At Charit\u0026eacute;, autologous bone grafting is typically employed for SABG, with bone commonly harvested from the iliac crest and transplanted into the alveolar cleft. This study collected data before, after SABG, and after orthodontic treatment.\u003c/p\u003e\n\u003ch3\u003e2.3 Data acquisition\u003c/h3\u003e\n\u003cp\u003eData from patients with CLP who underwent SABG were retrospectively analyzed. Orthopantomograms taken before and after SABG, as well as following orthodontic treatment, were evaluated for the following parameters:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eCanine mineralization stage\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eInclination of the canine\u0026rsquo;s longitudinal axis\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCanine impaction incidence\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCanine eruption through the bone graft in both sagittal and transverse dimensions\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eBone graft and limbus alveolaris height of teeth adjacent to the cleft\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eClinical assessment included:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePeriodontal probing depth using a 6-point pocket chart\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCanine vitality test\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1:\u003c/strong\u003e Standardized surgical and orthodontic treatment protocol for patients with CLP treatment at the Charit\u0026eacute; - Universit\u0026auml;tsmedizin Berlin, Campus Virchow\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\" style=\"margin-right: calc(1%); width: 99%;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.619%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38.2582%;\"\u003e\n \u003cp\u003e\u003cstrong\u003esurgical treatment protocol\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47.1229%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eorthodontic treatment protocol\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.619%;\"\u003e\n \u003cp\u003e4 - 6 months\u003c/p\u003e\n \u003cp\u003e2 - 4 years\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 - 6 years\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 - 11 years\u003c/p\u003e\n \u003cp\u003e11 - 16 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 38.2582%;\"\u003e\n \u003cp\u003elip closure\u003c/p\u003e\n \u003cp\u003esoft and hard palate closure \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003esecondary bone grafting (iliac crest bone)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47.1229%;\"\u003e\n \u003cp\u003einfant orthopedics\u003c/p\u003e\n \u003cp\u003ecorrection of crossbite and/or collapsed arch segments and/or class III malocclusion treatment\u0026nbsp;\u003c/p\u003e\n \u003cp\u003etooth eruption guidance (Hotz protocol), correction of rotated upper central incisors, and crossbite (removable and/or functional appliances)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003emultibracket appliance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cbr\u003e\n\u003ch3\u003e2.4 Methods\u003c/h3\u003e\n\u003cp\u003e The study adhered to the STROBE guidelines for observational studies. This retrospective cohort study was conducted in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The institutional ethics committee of Charit\u0026eacute; - Universit\u0026auml;tsmedizin Berlin approved the study (EA2/240/17).\u003c/p\u003e \u003cp\u003eThe surgical intervention was considered successful if a continuous bone graft was radiographically discernable six months after secondary osteoplasty.\u003c/p\u003e \u003cp\u003e2.4.1 Radiographic analysis\u003c/p\u003e \u003cp\u003eOrthopantomograms (OPTGs) were taken at the following time points:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eT0: preoperative assessment (mean age: 10,0\u0026thinsp;\u0026plusmn;\u0026thinsp;1,8 years)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eT1: six months post-secondary osteoplasty (mean age: 12,5\u0026thinsp;\u0026plusmn;\u0026thinsp;1,7 years)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eT2: after completion of orthodontic treatment (mean age: 16,6\u0026thinsp;\u0026plusmn;\u0026thinsp;1,6 years)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eTo minimize selection bias, only patients with complete and high-quality radiographic records were included in the analysis. Our retrospective study of all the eligible patients with cleft provided us a total of 127 OPTGs at T0 and T1. Moreover, 102 OPTGs or periapical radiograph regions from cleft areas were available at T2. The canine mineralization stage was determined using the Moorrees et al. method [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] as modified by Schopf [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. An adapted scheme is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The limbus alveolaris height and bone graft were assessed using a modified version of the Long et al. method [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The axis angle of cleft-sided canines was measured following the method described by Dausch-Neumann [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e2.4.2 Measurement procedures\u003c/p\u003e \u003cp\u003eTo ensure standardized and reproducible data, the following measurements were applied:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eInsertion height: defined as the distance of the cementoenamel junction to the cervical bone margin.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eBone graft height: measured as the distance to the most apical point of the bone graft, perpendicular to the cementoenamel junction of the central incisor and the canine on the cleft side.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eRelative height of the limbus alveolaris and the bone graft: expressed as a dimensionless ratio based on one-tenth of the canine crown length.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCanine axis-angle: defined as the angle enclosed between the occlusal plane (connecting the distobuccal cusps of the first molars) and the longitudinal axis of the canine (in the coronal-apical direction) [Fig.\u0026nbsp;2].\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e2.4.3 Orthodontic and clinical evaluation\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eThree-dimensional plaster models (T2: 16,2\u0026thinsp;\u0026plusmn;\u0026thinsp;1,7 years) of 64 cleft regions were used to measure the extent of orthodontic tooth movement during space closure via reflex microscopy.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eClinical assessment of adjacent teeth at T3 (mean age: 17,7\u0026thinsp;\u0026plusmn;\u0026thinsp;1,9 years) using the Parodontometer PCP 10 (Hu-Friedy\u0026copy;).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePeriodontal probing depth using a 6-point method on the teeth adjacent to the cleft was tested at a clinical follow-up on 58 cleft regions with a registration per tooth.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCanine vitality was assessed using carbon dioxide snow testing.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e\n\u003ch3\u003e2.5 Statistical analysis\u003c/h3\u003e\n\u003cp\u003eAll data were recorded and analyzed using SPSS (Version 6.0; Chicago, III). The following variables were evaluated:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eThe axis-angle of the teeth adjacent to the cleft (in degrees).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eCanine root mineralization was determined as a root-to-crown length ratio (dimensionless).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eGraft and limbus height of the alveolar ridge relative to the crown length (dimensionless).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eModel measurements for the distances (in millimeters).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eData distribution was tested for normality using the Kolmogorov-Smirnov test. A normal distribution was confirmed at a 5% significance level, apart from a few isolated outliers. Statistical analysis was performed using Student\u0026rsquo;s t-test, with a significance level set at p\u0026thinsp;\u0026lt;\u0026thinsp;0,05. Contingency tables reported the number of cleft sites, mean values, and 95% confidence intervals. For small sample sizes (n\u0026thinsp;\u0026lt;\u0026thinsp;30), mean comparisons were performed using the Student\u0026rsquo;s t-test, applying the formula by Spiegel and Stephens [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eIn total, 104 patients with 127 cleft sites and a mean age of 9,9\u0026thinsp;\u0026plusmn;\u0026thinsp;1,6 years at the time of surgery were included in the study. Eighty-two cleft sites showed agenesis of the lateral incisor. To facilitate statistical evaluation and data interpretation, the patient population was stratified based on the presence or absence of the lateral incisors and the type of space closure (orthodontic vs. prosthodontic). All patients were successfully treated with secondary osteoplasty using autologous bone grafting. The four stages of canine root mineralization (R 0,25\u0026thinsp;\u0026minus;\u0026thinsp;1,0) were used to evaluate the optimal timing of SABG. Early and late SABG were used when bone grafting was performed at R\u0026thinsp;\u0026le;\u0026thinsp;0,5 and R\u0026thinsp;\u0026ge;\u0026thinsp;0,5, respectively. Patient distribution according to cleft type and sex is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOf the 127 cleft sites, 81 (63,8%) were associated with unilateral cleft patients, while 46 (36,2%) involved bilateral clefts. The cohort included 91 males (71,6%) and 36 females (28,4%). The mineralization stage of canines adjacent to the cleft was age-dependent. The dental development of females was 0,2\u0026thinsp;\u0026minus;\u0026thinsp;0,5 years earlier than males. The sex distribution difference was statistically not significant.\u003c/p\u003e\n\u003ch3\u003e3.1 Space closure and timing of SABG\u003c/h3\u003e\n\u003cp\u003eAmong the 127 cleft sites, 77 (60,6%) underwent orthodontic space closure, while 44 (34,6%) received prosthodontic rehabilitation. In three cleft regions, severe canine impaction and lateral incisor agenesis required surgical removal of the canine. Additionally, three cleft sites exhibited lateral incisor transposition with the canine, which occurred exclusively in early SABG cases (R\u0026le;0,5) [Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe success rate of orthodontic space closure in lateral agenesis patients was highest when SABG was performed at R\u0026le;0,5, with 66,6% at the mineralization stage R\u0026thinsp;=\u0026thinsp;0,25 and 71,4% at stage R\u0026thinsp;=\u0026thinsp;0,5. However, when SABG was performed later, during stages R\u0026thinsp;=\u0026thinsp;0,75 and R\u0026thinsp;=\u0026thinsp;1,0, the success rate for orthodontic space closure declined to only 21,8% and 25%, respectively.\u003c/p\u003e \u003cp\u003eHowever, the 82 cleft sites were nearly equally distributed between the two types of space closure: 43 (52,4%) received prosthodontic and 39 (47,6%) orthodontic space closure. The distribution of space closure type was equally balanced within these subgroups.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003e3.2 Canine impaction and SABG timing\u003c/h3\u003e\n\u003cp\u003eAmong the 127 canines adjacent to the cleft assessed, 13 required surgical exposure, followed by orthodontic extrusion, while three severely impacted canines were extracted. All extractions occurred solely in the lateral agenesis group. The impaction risk was increased when SABG was performed at early mineralization stages (R\u0026thinsp;\u0026le;\u0026thinsp;0,5). In contrast, 96,6% of canines erupted spontaneously into the bone graft when SABG was performed late (R\u0026thinsp;\u0026ge;\u0026thinsp;0,75).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Canine axis-angle and eruption pattern\u003c/h2\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003ePreoperative inclination\u003c/h2\u003e \u003cp\u003eThe axis angle was assessed using preoperative orthopantomograms.\u003c/p\u003e \u003cp\u003eBefore SABG, the canine adjacent to the cleft with an existing lateral incisor exhibited a more upright position compared to those with lateral incisor agenesis, showing a statistically significant difference (Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;2,082)\u003c/p\u003e \u003cp\u003eIn cases where no SABG was performed, the canine tended to upright along the posterior cleft margin.\u003c/p\u003e \u003cp\u003eStatistical comparison between mineralization stage subgroups was significant for both patient cohorts: Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;2,231 for regions with existing lateral incisors and Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;3,272 for those with lateral incisor agenesis.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePost-eruption inclination\u003c/h2\u003e \u003cp\u003eSABG timing did not influence the canine axis-angle in patients with lateral incisors. However, in agenesis cases, a moderate but statistically significant correlation was found between SABG timing and the axis-angle of the canine on the cleft side. When SABG was carried out during early mineralization stages (R\u0026thinsp;\u0026le;\u0026thinsp;0,5), canines erupted in a more tilted position into the bone graft - favoring orthodontic space closure. At a later stage (R\u0026thinsp;\u0026ge;\u0026thinsp;0,75), the canine tended to upright at the posterior cleft margin. The comparison between the two subgroups was statistically significant, with a Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;3,343. There was a mean canine inclination difference of 8,4 \u0026deg; between the lateral incisor agenesis and non-agenesis patient cohorts. Overall, canines in non-agenesis cases exhibited higher axis angles and erupted more upright across all mineralization stages than in agenesis cases [Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAfter orthodontic treatment of patients with lateral incisor agenesis, the mean canine axis-angle was 91 \u0026deg; following prosthodontic space closure and 81,3 \u0026deg; following orthodontic space closure, resulting in a mean difference of 9,7 \u0026deg;, which was statistically significant (Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;5,702). In addition, surgical exposure and orthodontic traction of impacted canines did not negatively affect bone graft height. The results were even more favorable than those of spontaneously erupted canines. However, this difference was not statistically significant due to the small sample size of this cohort and should be interpreted with caution.\u003c/p\u003e \u003cp\u003eAssessing the canine eruption pattern in a transverse dimension revealed that most (90,9%) canines erupt orthotopically in patients with lateral incisors. In agenesis cases, 24% were palatally, and 2% were buccally displaced. Hence, the timing of SABG plays an important role, as significantly higher displacement rates were observed when performed in early mineralization stages (R\u0026thinsp;\u0026le;\u0026thinsp;0,5). A description of the transversal canine eruption pattern is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Height of bone graft according to canine eruption and type of space closure\u003c/h2\u003e \u003cp\u003eThe height of the bone graft adjacent to the cleft, measured after the canine eruption, showed a statistically significant correlation with the timing of secondary osteoplasty in the lateral incisor agenesis group. When the canine root mineralization was R\u0026gt;0,5 at the time of the surgery, the bone graft height was significantly reduced, compared to cases with SABG at R\u0026thinsp;\u0026le;\u0026thinsp;0,5 (Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;4,234). No such correlation was observed in the patient cohort with lateral incisors. A similar trend was noted when evaluating bone graft height in relation to the presence of lateral incisors. However, in lateral incisor agenesis cases, the type of space closure significantly influenced bone graft preservation. Patients treated with orthodontic space closure experienced significantly less bone resorption compared to those who underwent prosthodontic space closure (Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;5,406). Taking arithmetic mean values into account, higher rates of bone resorption after prosthodontic space closure (M\u0026thinsp;=\u0026thinsp;5,8) were observed compared to orthodontic space closure (M\u0026thinsp;=\u0026thinsp;3,3). However, the difference was not statistically significant. This discrepancy was likely due to natural bone atrophy resulting from the lack of functional loading in prosthodontically treated sites.\u003c/p\u003e \u003cp\u003eIf orthodontic space closure was the treatment of choice, the bone graft height would remain stable regardless of the agenesis of the lateral incisors. However, bone graft height was lower when SABG was performed late (R\u0026thinsp;\u0026ge;\u0026thinsp;0,75), particularly in lateral incisor agenesis cases, as evident from the mean values (e.g., in R\u0026thinsp;=\u0026thinsp;0,25: 1,8 vs. in R\u0026thinsp;=\u0026thinsp;1: 5,8) as presented in Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBone graft height (dimensionless value) with lateral incisors M: arithmetic mean value; CI: 95%-confidence interval; n: number of cleft regions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003etype of space closure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eafter canine eruption\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eafter orthodontic treatment\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eCI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eCI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eprosthodontic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eorthodontic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etransposition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBone graft height (dimensionless value) with lateral incisor agenesis M: arithmetic mean value; CI: 95%-confidence interval; n: number of cleft regions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003etype of space closure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eafter canine eruption\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eafter orthodontic treatment\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eCI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eCI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eprosthodontic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eorthodontic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5,6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Height of the limbus alveolaris according to canine eruption and type of space closure\u003c/h2\u003e \u003cp\u003eThe height of the limbus alveolaris was measured mesial to the canine adjacent to the cleft.\u003c/p\u003e \u003cp\u003eEvaluating the height of the limbus alveolaris after canine eruption revealed a significantly (Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;4,221) lower bone level if SABG was performed late (R\u0026thinsp;=\u0026thinsp;1) compared to surgical intervention in earlier root mineralization stages (R\u0026thinsp;\u0026le;\u0026thinsp;0,75). In the earlier stages, limbus height differed only marginally and was independent of lateral incisor presence.\u003c/p\u003e \u003cp\u003eThe type of space closure had a strong influence on limbus alveolaris height. Before orthodontic treatment, the bone level was well preserved in all groups, with bone resorption rates below 2 mm. This stability persisted in cases treated with orthodontic space closure, where limbus alveolaris height remained stable during and after treatment. No statistical association was found between limbus height and SABG timing. However, prosthodontic space closure was linked to significantly higher bone resorption in both groups:\u003c/p\u003e \u003cp\u003epatients with lateral incisors (Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;4,434) and those with lateral incisor agenesis (Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;3,762).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.6 Periodontal evaluation\u003c/h2\u003e \u003cp\u003eAs part of a clinical follow-up, probing depths were measured mesial to the canines and distal to the central incisors adjacent to the cleft. The clinical examination revealed a healthy periodontal situation with probing depths\u0026thinsp;\u0026lt;\u0026thinsp;3 mm. Neither lateral incisor agenesis nor the type of space closure had a statistically significant impact on periodontal health. However, slightly higher probing scores were assessed in cases with orthodontic space closure. Here, it should be noted that the formation of an interdental papilla was not examined. No significant differences in probing scores were observed between the cleft and non-cleft sides in patients with UCLP.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.7 Vitality of cleft-sided canines\u003c/h2\u003e \u003cp\u003eIn this study, carbon dioxide snow (dry ice) was used for the pulp vitality testing. Only three canines showed no response to the test. One canine was endodontically treated and was in transposition with the lateral incisor. The other two non-responsive canines were part of a bridge construction used for prosthodontic space closure, resulting in unclear reactions during the vitality test.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe optimal timing of secondary alveolar bone grafting (SABG) remains a critical factor in successfully rehabilitating patients with cleft lip and palate (CLP), as it directly influences the bone graft integration, tooth eruption, and long-term orthodontic outcomes. Despite its widespread clinical application, the ideal timing for SABG remains a topic of debate.\u003c/p\u003e \u003cp\u003eThis single-center study aimed to assess the impact of SABG timing on key treatment outcomes, including bone graft height, limbus alveolaris integrity, canine eruption, inclination angle, and type of space closure, by using canine root mineralization stages as developmental reference instead of chronological age. Additionally, this study seeks to identify shortcomings in the interdisciplinary care approach during SABG and propose areas for improvement.\u003c/p\u003e \u003cp\u003eThe study considered the possibility of separately evaluating patients with UCLP and BCLP and accounting for gender differences. However, these stratifications were not applied to avoid compromising statistical power. Instead, the patients were grouped based on the canine root mineralization stage, which mitigates potential biases while maintaining the robustness of the findings. Root mineralization stages provide a more accurate reflection of dental developmental age than the chronological age, especially in patients with CLP, who often exhibit delayed and variable dental development [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The canine root mineralization stage can be assessed during routine preoperative radiological diagnostics without additional radiation exposure. Since canine eruption is closely linked to the root\u0026rsquo;s mineralization stage, it serves as a reliable developmental reference [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, the canine germ is located distal to the cleft and, unlike incisors, does not exhibit associated morphological aberrations that may interfere with root mineralization assessment [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The bone graft height and limbus alveolaris were evaluated relative to the canine crown. Orthopantomograms obtained at T0, T1, and T2 were assessed following the method described by Aurouze et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] and Long et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The canine angulation in the mesiodistal dimension was assessed using the method outlined by Dausch-Neumann [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Modern X-ray devices equipped with positioning aids and staff trained in their use ensure standardization and reproducibility of imaging. Positioning errors, such as deviations from the Frankfurter horizontal plane or dorsal- and ventral neck flexion during imaging, can affect occlusal plane alignment [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. To minimize such errors, only orthopantomograms that strictly meet the criteria were analyzed. The occlusal plane was leveled, and the cranial angle was measured on 20 standardized images. Orthopantomograms deviating more than twice the standard error from the mean value were excluded to ensure accuracy. Numerous studies assessing SABG outcomes in CLP patients have reported good accuracy using intraoral radiographs [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. A continuous and sufficient bone bridge is essential for successful tooth eruption into the graft and effective orthodontic movement. B\u0026auml;hr and Coulon recommended a minimum bone bridge width of 9 mm to accommodate the permanent canine [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. These findings align with Mikoya et al., who advocated a buccopalatal width of 9,6 mm at the mid-level between the apical and coronal borders for positive treatment results [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. To ensure these results and optimize SABG timing, precise radiologic examination of the target area around the erupting canine while considering the patient\u0026rsquo;s individual dental development is crucial.\u003c/p\u003e \u003cp\u003eHowever, over the last years, alternative imaging methods such as computed tomography (CT) and cone-beam computed tomography (CBCT) have become increasingly crucial for the three-dimensional assessment of cleft regions and bone grafts. Studies have shown that conventional 2D orthopantomograms often underestimate bone resorption [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] because they evaluate only the vertical dimension. In this study, the quantity and quality of bone, or bucco-palatal resorption, could not be accurately assessed from orthopantomograms. Resorption may reach up to 49,5% within the first year after surgery [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. This underlines the critical need to evaluate bucco-palatal bone thickness to ensure proper canine positioning. Our study is based on conventional radiographic measurements while acknowledging the limitations of volumetric assessment compared to CBCT.\u003c/p\u003e \u003cp\u003eAlthough 3D imaging methods are superior to 2D methods, a consistent imaging protocol is necessary to ensure comparable diagnostic and follow-up results [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFurthermore, adherence to the ALARA (As Low As Reasonably Achievable) principle remains crucial for balancing diagnostic accuracy and radiation exposure, particularly in pediatric patients. Although Wriedt et al. found no significant differences between 2D and 3D imaging in predicting tooth alignment or orthodontic treatment planning, they acknowledge the surgical advantages of preoperative CBCT scans [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. However, recent research indicated that volumetric CBCT assessment of the canine root formation offers no predictive advantage over conventional intraoral radiographs for assessing canine eruption following SABG [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. These findings underscore the importance of carefully balancing the benefits of advanced imaging against its clinical utility and associated radiation risks.\u003c/p\u003e \u003cp\u003eIntroduced by Boyne and Sands in 1972 [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], SABG, during the late mixed dentition phase (8\u0026ndash;12 years of age), has become the standard treatment for reconstructing bony defects in cleft lip and palate (CLP) patients [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. After the age of eight, maxillary growth is primarily completed, minimizing the risk of growth impairment following SABG [\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Bergland et al. [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] demonstrated optimal outcomes when SABG was performed before the canine eruption. In our study, only three out of 127 cleft areas were treated before the age of eight, making it unlikely that a significant impact on maxillary growth would be observed. Most patients (57%) underwent SABG between the ages 9 and 11 (mean age: 9\u0026thinsp;\u0026plusmn;\u0026thinsp;1,6 years), which is consistent with the previous studies reporting an age range of 8,2 to 10,6 years for conventional SABG [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan additionalcitationids=\"CR37 CR38\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eImpact of SABG timing on space closure\u003c/h2\u003e \u003cp\u003eSABG timing significantly influenced space closure outcomes in patients with lateral incisor agenesis.\u003c/p\u003e \u003cp\u003eEarly SABG (R\u0026thinsp;\u0026le;\u0026thinsp;0,5) tripled the success rate of orthodontic space closures compared to late SABG (R\u0026thinsp;\u0026ge;\u0026thinsp;0,75). The measurements showed that the space between the cleft-sided central incisor and canine was significantly (Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;4,575) smaller in cases of early SABG (R\u0026thinsp;\u0026le;\u0026thinsp;0,5) than in later stages (R\u0026thinsp;=\u0026thinsp;0,75, R\u0026thinsp;=\u0026thinsp;1). The mesial drift of the erupting canine (R\u0026thinsp;\u0026le;\u0026thinsp;0,5) decreased the canine inclination angle, facilitating space closure with less orthodontic movement (Student\u0026rsquo;s t\u0026thinsp;=\u0026thinsp;2,931). The required mesial movement for space closure ranged from only 1,7 mm (R\u0026thinsp;=\u0026thinsp;0,25) to 6,2 mm (R\u0026thinsp;=\u0026thinsp;1,0). Thus, early SABG (R\u0026thinsp;\u0026le;\u0026thinsp;0,5) facilitates successful orthodontic space closure in CLP patients with lateral incisor agenesis. The absence or presence of lateral incisors and the mesio-distal space must be considered in decision-making on the type of space closure [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Although the aesthetic outcomes of both orthodontic and prosthodontic space closure are satisfactory and comparable in the long term, the risk of cranio-mandibular dysfunction increases after prosthodontic rehabilitation with resin-bonded bridges [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Despite conventional SABG being well documented and considered the gold standard, the current literature suggests a shift towards an earlier intervention before the eruption of the lateral incisors [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Early SABG may offer particular advantages for patients with CLP and existing lateral incisors, as performing the procedure before the age of 5\u0026ndash;7 can provide adequate bone support for their eruption [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. There is little but promising evidence that early SABG does not lead to impaired craniofacial growth [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The cephalometric evaluation of Brudnicki et al. directly compared the skeletal outcome of maxillary development of early versus late SABG and showed that both groups exhibited similar maxillary growth patterns [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Dissaux et al. focused on bone volume after 6 months as an indicator of grafting success and concluded that CLP patients undergoing surgery around the age of 5 years had better treatment outcomes than those with conventional SABG around the age of ten [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Additionally, the treatment proposed by Precious et al. [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e] showed better periodontal health, crown length, and central incisor symmetry with early SABG. Regardless of the age at ABG, the eruption of a permanent tooth (lateral incisor or canine) into the graft has a positive and stabilizing effect on the bone height [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eBone graft and limbus alveolaris height\u003c/h2\u003e \u003cp\u003eThis study highlights the impact of SABG on bone graft preservation in patients with lateral incisor agenesis. Bone graft resorption was 3,5 mm greater in the late SABG sites (R\u0026thinsp;=\u0026thinsp;1) compared to early SABG (R\u0026thinsp;=\u0026thinsp;0,25). These findings align with those of Bergland et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], who reported that the standard interdental septum height was maintained in 64% of early SABG cases, compared to only 37% in late SABG cases performed before and after the canine eruption, respectively. Since septum height is crucial for future dental implants, early SABG may be preferable when orthodontic space closure is not indicated.\u003c/p\u003e \u003cp\u003eThese findings align with previous studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] that recommend SABG near the eruption of the tooth adjacent to the cleft, followed by early loading through orthodontic tooth movement or implant placement, to prevent bone atrophy due to functional loss. Zhang et al. supported this approach, showing a maximum bone graft reduction within three to six months post-SABG [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. However, as CBCT was not yet standard, our assessments relied mainly on conventional 2D radiographs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eCanine impaction and eruption\u003c/h2\u003e \u003cp\u003eCompared to non-cleft populations with a prevalence of 1\u0026ndash;2% canine impaction [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e], CLP patients are at a greater risk for impaction of cleft-sided canines. However, the data provided in the literature are not consistent and vary between 6%, 27%, and up to 56% [\u003cspan additionalcitationids=\"CR51\" citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. This study\u0026rsquo;s overall impaction rate of cleft-sided canines was 10,2%, within the abovementioned range. The majority (89,8%) erupted spontaneously into the graft, revealing a positive effect of SABG on successful canine eruption. Thirteen of 127 evaluated cleft-sided canines were impacted. The three that required surgical removal were all from the agenesis cohort. Early SABG (R\u0026thinsp;\u0026le;\u0026thinsp;0,5) was associated with an increasing impaction rate, supporting the findings of Hoang et al. [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e], who reported a link between SABG performed at one-third of the canine root development and a higher impaction rate of cleft-sided canines. In our study, this trend was even more striking with lateral incisor agenesis, accounting for 76,9% of the impacted canines. This rate is over three times higher than in the cohort with existing lateral incisors.\u003c/p\u003e \u003cp\u003eAdditionally, lateral incisor agenesis is associated with palatinal displacement of the erupting canine, likely due to the absence of the lateral incisor root, which guides the canine\u0026rsquo;s eruption path [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Consequently, lateral incisor agenesis has been identified as a potential risk factor for canine displacement and impaction after early SABG. A systematic review by Lacerda et al. also identified a connection between canine impaction and lateral incisor agenesis, but there was low certainty of evidence [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Moreover, advanced root development, apical tooth position, sharper axial angulation, older age at the time of SABG and the need for regrafting are further predictive factors for canine impaction in cleft patients [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR56\" citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNevertheless, in our cohort, impacted canines were successfully managed with surgical exposure and orthodontic traction without adverse effects on graft stability or periodontal health. These results support a risk-benefit approach: early SABG can be performed safely when radiographic and interdisciplinary planning are ensured.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eClinical implications and interdisciplinary care\u003c/h2\u003e \u003cp\u003ePeriodontal stability and inflammation-free tissues are crucial for long-term graft success. Existing literature indicates that SABG does not adversely affect the periodontal integrity of teeth adjacent to the cleft, with attachment levels comparable to those of non-cleft teeth [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. According to our findings, the probing depths of all cleft-sided teeth remained within the healthy range (\u0026lt;\u0026thinsp;3 mm) and did not differ significantly from those of the contralateral side in patients with UCLP. Loss of vitality was seldom observed and was not associated with either the surgical intervention or subsequent orthodontic treatment. Neither periodontal health nor vitality was correlated with the timing of SABG, the presence of lateral incisors or the type of space closure. Poor oral hygiene is a known risk factor for surgical failure due to bone loss [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. A 20-year follow-up study by Jabbari et al. demonstrated a positive correlation between gingival bleeding index and prosthetic restorations in cleft areas, leading to increased bone resorption [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]. Given the increased susceptibility of cleft patients to periodontitis, thorough oral hygiene instructions, regular professional dental care, and strong interdisciplinary collaboration with restorative dentists and periodontists are crucial to ensure the long-term health and stability of the cleft region and minimize the need for regrafting.\u003c/p\u003e \u003cp\u003eAlthough this study provides important insight, some limitations should be acknowledged. The retrospective single-center study design may introduce selection bias and limit generalizability. Although strict inclusion criteria and a uniform treatment protocol were applied, the retrospective nature of the data prevented randomization and prospective control. Furthermore, the radiographic assessment relied exclusively on 2D-imaging procedures, which are limited to assessing bucco-palatal dimensions or volumetric changes at the grafted site. Although orthopantomograms were the clinical standard during the treatment period and offered longitudinal comparability, they may lead to under- or overestimation of actual bone graft volume due to anatomical superimpositions. The absence of CBCT limits the ability to evaluate three-dimensional graft morphology and spatial bone preservation. Future studies should incorporate CBCT-based volumetric analysis to validate and expand upon these findings, particularly by assessing long-term graft resorption and integration.\u003c/p\u003e \u003cp\u003eWhile early SABG improved bone preservation and facilitated bone orthodontic space closure, it was also associated with a higher incidence of impaction, particularly in patients with lateral incisor agenesis. Although these impactions were successfully managed, the findings underscore the need for individualized treatment planning based on the developmental stage and eruption path, achieved through close monitoring.\u003c/p\u003e \u003cp\u003eAlthough the imbalance between agenesis and non-agenesis cases may limit the power of subgroup comparison, stratified analysis and careful subgroup evaluation were used to minimize bias in interpretation.\u003c/p\u003e \u003cp\u003eTo strengthen the clinical evidence base, future trials should adopt a prospective, multicenter design with larger, demographically balanced cohorts. Incorporating three-dimensional imaging modalities such as CBCT will allow for accurate volumetric analysis. The use of standardized protocols for radiographic and periodontal examinations would enhance comparability across centers. Furthermore, stratification by cleft type and tooth agenesis status, combined with multivariate statistical models, may provide deeper insight into the complex interaction between SABG timing, dental development, and long-term outcomes.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eSABG timing is a critical factor in treatment outcomes in patients with CLP. The study identified the root mineralization stage of the tooth adjacent to the cleft as the key predictor for optimal SABG timing. Performing SABG during the early canine mineralization stages (R\u0026thinsp;\u0026le;\u0026thinsp;0,5) promotes canine eruption success into the bone graft, facilitates space closure, especially in cases with lateral incisor agenesis, and preserves both the bone graft and the limbus alveolaris height. Furthermore, the study identified that bone resorption in the graft and adjacent to the limbus alveolaris was significantly lower following orthodontic space closure compared to prosthodontic treatment alternatives.\u003c/p\u003e \u003cp\u003eEarly SABG, at the R\u0026thinsp;\u0026le;\u0026thinsp;0,5 stage, may slightly increase the risk of canine impaction or transposition with the lateral incisor. However, these complications can be effectively managed through surgical canine exposure and orthodontic extrusion without leading to higher bone resorption rates or periodontal damage.\u003c/p\u003e \u003cp\u003eIn conclusion, this study underscores the crucial role of precisely tailored and optimally timed SABG in optimizing functional and structural outcomes in cleft site management while minimizing potential complications.\u003c/p\u003e \u003cp\u003eTo refine treatment protocols and enhance outcomes for patients with CLP, further research should integrate CBCT-based volumetric assessment with additional clinical and biomechanical parameters.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for this study was granted by the Ethics Committee of the Charit\u0026eacute;-Universit\u0026auml;tsmedizin Berlin, Germany, ID: EA2/240/17. The trial was conducted in accordance with the ethical principles outlined in the 1964 Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eT.B. contributed to the study\u0026rsquo;s visualization, data interpretation, supervision, and review and editing of the manuscript. I.H. contributed to data interpretation visualization, drafted and critically revised the manuscript J.K. contributed to data interpretation, drafted and critically revised the manuscript F.J. contributed to data interpretation and drafted the initial version of the manuscript. M.S. contributed to the conception, design, data collection, interpretation and statistical analysis. C.O. contributed to the study\u0026rsquo;s conception, design, data interpretation and critically revised the manuscript. All authors read and approved and agree to accountability for integrity.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAxhausen (1952) Technik und Ergebnisse der Spaltplastiken (Technique and results of plastic operations on clefts). Carl Hanser, M\u0026uuml;nchen\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEnemark H, Sindet-Pedersen S, Bundgaard M (1987) Long-term results after secondary bone grafting of alveolar clefts. J Oral Maxillofac Surg 45(11):913\u0026ndash;919\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLemberger M et al (2024) Long-term radiographic and periodontal evaluations of the bone-grafted alveolar cleft region in young adults born with a UCLP. 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Cleft Palate J 23(3):175\u0026ndash;205\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoyne PJ, Sands NR (1976) Combined orthodontic-surgical management of residual palato-alveolar cleft defects. Am J Orthod 70(1):20\u0026ndash;37\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDoucet JC et al (2023) Early Secondary Alveolar Bone Grafting and Facial Growth of Patients with Complete Unilateral Cleft Lip and Palate. Cleft Palate Craniofac J 60(6):734\u0026ndash;741\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu AC et al (2022) Early Alveolar Bone Grafting Is Associated with Lower Regraft Rates and Improvements in Long-Term Psychosocial Outcomes. Plast Reconstr Surg 149(1):60e\u0026ndash;67e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRizell S et al (2021) Predictive factors for canine position in patients with unilateral cleft lip and palate. 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Cleft Palate Craniofac J 33(3):225\u0026ndash;230\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDausch-Neumann D (1970) [The eruption path of permanent cuspids]. Fortschr Kieferorthop 31(1):9\u0026ndash;16\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpiegel MR, Stephens LJ (1999) \u003cem\u003eStatistik\u003c/em\u003e. \u0026Uuml;bersetzung der 3.Auflage McGraw-Hill International (UK) Ltd.,pp. 242\u0026ndash;244\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Dyck J et al (2019) Dental development in cleft lip and palate patients: A systematic review. Forensic Sci Int 300:63\u0026ndash;74\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDemirjian A, Levesque GY (1980) Sexual differences in dental development and prediction of emergence. 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Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100(3):271\u0026ndash;277\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026auml;hr W, Coulon JP (1996) Limits of the mandibular symphysis as a donor site for bone grafts in early secondary cleft palate osteoplasty. Int J Oral Maxillofac Surg 25(5):389\u0026ndash;393\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMikoya T et al (2010) Monocortical mandibular bone grafting for reconstruction of alveolar cleft. Cleft Palate Craniofac J 47(5):454\u0026ndash;468\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu X, Guo R, Li W (2020) Comparison of 2- and 3-dimensional radiologic evaluation of secondary alveolar bone grafting of clefts: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol 130(4):455\u0026ndash;463\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeichtinger M, Mossb\u0026ouml;ck R, K\u0026auml;rcher H (2007) Assessment of bone resorption after secondary alveolar bone grafting using three-dimensional computed tomography: a three-year study. Cleft Palate Craniofac J 44(2):142\u0026ndash;148\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan der Meij AJ et al (2001) Bone volume after secondary bone grafting in unilateral and bilateral clefts determined by computed tomography scans. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92(2):136\u0026ndash;141\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Mulder D et al (2019) Three-dimensional radiological evaluation of secondary alveolar bone grafting in cleft lip and palate patients: a systematic review. Dentomaxillofac Radiol 48(1):20180047\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWriedt S et al (2017) Analyzing the teeth next to the alveolar cleft: Examination and treatment proposal prior to bone grafting based on three-dimensional versus two-dimensional diagnosis-A diagnostic study. J Craniomaxillofac Surg 45(8):1272\u0026ndash;1277\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerguson MA et al (2023) Evaluation of Dental Root Development Regarding Maxillary Canine Eruption Status after Secondary Alveolar Bone Grafting in Patients with Cleft Lip and Palate. Diagnostics (Basel). 13(9)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDissaux C et al (2016) Evaluation of success of alveolar cleft bone graft performed at 5 years versus 10 years of age. J Craniomaxillofac Surg 44(1):21\u0026ndash;216\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeichtinger M, Mossb\u0026ouml;ck R, K\u0026auml;rcher H (2006) Evaluation of bone volume following bone grafting in patients with unilateral clefts of lip, alveolus and palate using a CT-guided three-dimensional navigation system. J Craniomaxillofac Surg 34(3):144\u0026ndash;149\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuppel JK et al (2016) The Americleft Project: A Comparison of Short- and Longer-Term Secondary Alveolar Bone Graft Outcomes in Two Centers Using the Standardized Way to Assess Grafts Scale. Cleft Palate Craniofac J 53(5):508\u0026ndash;515\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang DZ et al (2015) Evaluation of Bone Height and Bone Mineral Density Using Cone Beam Computed Tomography After Secondary Bone Graft in Alveolar Cleft. J Craniofac Surg 26(5):1463\u0026ndash;1466\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCabrera CT (2024) A Review of Orthodontic Considerations before and after Alveolar Bone Grafting in Patients with Cleft Lip and Palate. Acta Med Philipp 58(21):7\u0026ndash;19\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDoucet JC et al (2019) Facial Growth of Patients With Complete Unilateral Cleft Lip and Palate Treated With Alveolar Bone Grafting at 6 Years. Cleft Palate Craniofac J 56(5):619\u0026ndash;627\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cem\u003eA Review of Orthodontic Considerations before and after Alveolar Bone Grafting in Patients with Cleft Lip and Palate\u003c/em\u003e. Acta Medica Philippina, (2023)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu X et al (2025) Comparing Three-dimensional Radiologic Outcomes Between Early Versus Late Secondary Alveolar Bone Grafting. J Craniofac Surg 36(1):78\u0026ndash;83\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrudnicki A, Sawicka E, Fudalej PS (2021) Maxillofacial morphology in post-pubertal patients with unilateral cleft lip and palate following early vs. late secondary alveolar bone grafting. J Craniomaxillofac Surg 49(9):809\u0026ndash;814\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCabrera C (2023) A Review of Orthodontic Considerations before and after Alveolar Bone Grafting in Patients with Cleft Lip and Palate. Acta Medica Philippina\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrudnicki A et al (2017) Cephalometric comparison of early and late secondary bone grafting in the treatment of patients suffering from unilateral cleft lip and palate. J Craniomaxillofac Surg 45(4):479\u0026ndash;484\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrecious DS (2009) A New Reliable Method for Alveolar Bone Grafting at About 6 Years of Age. J Oral Maxillofac Surg 67(10):2045\u0026ndash;2053\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHorswell BB, Henderson JM (2003) Secondary osteoplasty of the alveolar cleft defect. J Oral Maxillofac Surg 61(9):1082\u0026ndash;1090\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBecker A, Chaushu S (2015) Etiology of maxillary canine impaction: A review. Am J Orthod Dentofac Orthop 148(4):557\u0026ndash;567\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eda Silva Filho OG et al (2000) Secondary Bone Graft and Eruption of the Permanent Canine in Patients with Alveolar Clefts: Literature Review and Case Report. Angle Orthod 70(2):174\u0026ndash;178\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoang E et al (2023) Factors Contributing to Canine Impaction in Patients With Unilateral Cleft Lip and Palate Undergoing Alveolar Bone Grafts. J Oral Maxillofac Surg 81(10):1286\u0026ndash;1294\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl Deeb M et al (1982) Canine eruption into grafted bone in maxillary alveolar cleft defects. Cleft Palate J 19(1):9\u0026ndash;16\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJacoby H (1983) The etiology of maxillary canine impactions. Am J Orthod 84(2):125\u0026ndash;132\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLacerda-Santos R et al (2021) Effectiveness of Secondary Alveolar Bone Graft on Canine Eruption: Systematic Review. Eur J Dent 15(3):579\u0026ndash;587\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCaceres Manfio AS et al (2022) Eruption path of permanent maxillary canines after secondary alveolar bone graft in patients with nonsyndromic complete unilateral cleft lip and palate. Am J Orthod Dentofac Orthop 161(5):e416\u0026ndash;e428\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSim\u0026otilde;es Holz I et al (2018) Permanent canine eruption into the alveolar cleft region after secondary alveolar bone grafting: Are there prediction factors for impaction? Am J Orthod Dentofac Orthop 154(5):657\u0026ndash;663\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWesterlund A et al (2014) What factors are associated with impacted canines in cleft patients? J Oral Maxillofac Surg 72(11):2109\u0026ndash;2114\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEldeeb ME et al (1986) Repair of alveolar cleft defects with autogenous bone grafting: periodontal evaluation. Cleft Palate J 23(2):126\u0026ndash;136\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndlin-Sobocki A, Eliasson LA, Paulin G (1995) Periodontal evaluation of teeth in bone grafted regions in patients with unilateral cleft lip and cleft palate. Am J Orthod Dentofac Orthop 107(2):144\u0026ndash;152\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLundberg J, Levring E, J\u0026auml;ghagen, Sj\u0026ouml;str\u0026ouml;m M (2021) Outcome after secondary alveolar bone grafting among patients with cleft lip and palate at 16 years of age: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol 132(3):281\u0026ndash;287\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJabbari F et al (2018) Secondary Alveolar Bone Grafting in Patients Born With Unilateral Cleft Lip and Palate: A 20-Year Follow-up. Cleft Palate Craniofac J 55(2):173\u0026ndash;179\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"clinical-oral-investigations","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cloi","sideBox":"Learn more about [Clinical Oral Investigations](http://link.springer.com/journal/784)","snPcode":"784","submissionUrl":"https://submission.nature.com/new-submission/784/3","title":"Clinical Oral Investigations","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Secondary alveolar bone grafting, cleft lip and palate, orthodontic space closure, canine eruption","lastPublishedDoi":"10.21203/rs.3.rs-6804368/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6804368/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate the impact of secondary alveolar bone grafting (SABG) timing, based on canine root mineralization stages, on bone graft preservation, canine eruption, and space closure in patients with cleft lip and palate (CLP).\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eThis retrospective single-center cohort study included 104 patients with unilateral or bilateral CLP (127 cleft sites). Orthopantomograms and clinical records were evaluated at three stages: pre-SABG, six months post-SABG, and post-orthodontic treatment. Canine root mineralization stage was classified as R\u0026thinsp;=\u0026thinsp;0,25\u0026thinsp;\u0026minus;\u0026thinsp;1,0, corresponding to 25\u0026ndash;100% root development respectively. Assessed parameters included the canine mineralization stage, axis-anglulation and vitality, limbus height, probing depths, and space closure strategy. Statistical analysis used the Student\u0026rsquo;s t-test.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSABG performed at early stages of canine root development (R\u0026thinsp;\u0026le;\u0026thinsp;0,5) was associated with higher success rates of orthodontic space closure (71,4% at R\u0026thinsp;=\u0026thinsp;0,5 vs. 25% at R\u0026thinsp;=\u0026thinsp;1,0; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0,05) and bone graft preservation. In patients with lateral incisor agenesis, early SABG facilitated mesial canine eruption but increased the incidence of canine impaction (18,6%). The mean axis-angle of cleft-side canines differed significantly between orthodontic and prosthodontic space closure (81,3\u0026deg; vs. 91,0\u0026deg;, t\u0026thinsp;=\u0026thinsp;5,702). Limbus alveolaris height was reduced when SABG occurred after root completion (R\u0026thinsp;=\u0026thinsp;1,0, t\u0026thinsp;=\u0026thinsp;4,234). Periodontal probing depths remained\u0026thinsp;\u0026lt;\u0026thinsp;3 mm, and canine vitality was preserved in all groups.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eEarly SABG, timed according to canine mineralization, supports alveolar bone preservation and space closure without compromising periodontal health.\u003c/p\u003e\u003ch2\u003eClinical Relevance\u003c/h2\u003e \u003cp\u003eTailoring SABG timing based on dental development can optimize orthodontic and prosthodontic outcomes in patients with CLP.\u003c/p\u003e","manuscriptTitle":"Timing matters: Dental development and outcomes on secondary alveolar bone grafting in cleft lip and palate patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 15:58:19","doi":"10.21203/rs.3.rs-6804368/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-07T08:14:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-06T12:04:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-23T16:09:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"92119475523942136163699643560757906684","date":"2025-06-14T11:30:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"107978616544090263452256646355368404452","date":"2025-06-12T11:08:20+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-12T11:00:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-06T13:34:15+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-06T13:30:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"Clinical Oral Investigations","date":"2025-06-02T17:23:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"clinical-oral-investigations","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cloi","sideBox":"Learn more about [Clinical Oral Investigations](http://link.springer.com/journal/784)","snPcode":"784","submissionUrl":"https://submission.nature.com/new-submission/784/3","title":"Clinical Oral Investigations","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"578aa700-3791-49a6-8e43-688666542ae6","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T16:04:29+00:00","versionOfRecord":{"articleIdentity":"rs-6804368","link":"https://doi.org/10.1007/s00784-025-06594-w","journal":{"identity":"clinical-oral-investigations","isVorOnly":false,"title":"Clinical Oral Investigations"},"publishedOn":"2025-10-30 15:57:33","publishedOnDateReadable":"October 30th, 2025"},"versionCreatedAt":"2025-06-17 15:58:19","video":"","vorDoi":"10.1007/s00784-025-06594-w","vorDoiUrl":"https://doi.org/10.1007/s00784-025-06594-w","workflowStages":[]},"version":"v1","identity":"rs-6804368","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6804368","identity":"rs-6804368","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}