Authors: Nursezen Kavasoğlu, Emre Nai̇boğlu
Categories: Research, CT, Functional, Aligners
Source: BMC Oral Health
Authors: Nursezen Kavasoğlu, Emre Nai̇boğlu
The aim of this study was to evaluate the effects of the Mandibular Advancement Appliance (MAA) system on mandibular and maxillary volumes in growing individuals using three-dimensional cone-beam computed tomography (CBCT), and to compare the results with those obtained using a conventional functional appliance (Activator) and a control group.
This single-center, randomized, controlled study included 55 individuals with skeletal Class II malocclusion at cervical vertebral maturation stages 2 or 3. The MAA and Activator groups each comprised 20 participants, while the control group included 15 participants. Volumetric analyses were performed using CBCT data and Mimics 15.0^®^ software. Statistical analyses were conducted using SPSS version 21.
An increase in mandibular and maxillary volumes was observed in both the MAA and Activator groups during the treatment period. However, these increases were not statistically significant (p > 0.05). No significant differences were found between the treatment groups and the control group.
Within the scope of this short-term treatment protocol, the MAA and Activator systems demonstrated similar effects on maxillary and mandibular volumes. Considering the esthetic and comfort-related advantages of the MAA, this system may be an effective alternative for the treatment of Class II malocclusion.
ClinicalTrials.gov NCT07056829 (registered June 29, 2025; retrospectively registered).
Approximately 80% of skeletal Class II malocclusions are attributed to mandibular retrusion. This has led to an increased interest in the use of functional appliances to stimulate mandibular growth in growing patients, as well as studies evaluating their effectiveness [1]. Since the discovery that functional appliances can promote mandibular development, they have been widely used in the treatment of skeletal Class II malocclusions for over a century. Pioneering work by Robin and Andresen demonstrated the mandibular growth-promoting effects of these appliances [2].
In recent years, the use of aligners in orthodontic treatments has become increasingly widespread. Studies have shown that the Invisalign system (Align Technology, San Jose, Calif) is among the most commonly preferred worldwide [3–5]. In 2017, Align Technology introduced a mandibular advancement feature integrated into the Invisalign system to assist in the correction of Class II malocclusions in growing patients [6]. The Mandibular Advancement Appliance (MAA) utilizes buccally positioned precision wings integrated into the maxillary and mandibular aligners to posture the mandible forward [7].
Compared to traditional functional appliances, the MAA offers several advantages, including the simultaneous alignment of teeth during Class II correction, better control over lower incisor inclination and molar extrusion, enhanced patient comfort, and improved esthetics [6–9]. However, some limitations of the MAA have been reported, such as the need for high patient compliance, an initial adaptation period, and the requirement for effective interaction between the mandible and the precision Wings [6–8].
Moreover, the availability of initial and digitally planned models in the MAA system provides a significant advantage for academic research through the use of metrology software [10]. Although studies evaluating the clinical efficacy of MAA remain limited, current evidence suggests that treatment responses are comparable to those observed with traditional functional appliances and are predominantly manifested at the dentoalveolar level [6–9, 11–13]. However, the majority of existing research on MAA treatment has focused on the analysis of changes observed in two-dimensional lateral cephalometric radiographs [7, 12–14].
In a study investigating the reliability of landmark identification on three-dimensional cone-beam computed tomography (CBCT) images, the specified landmarks were found to be reliable [15]. Another study [16] demonstrated that landmark placement on CBCT images is more accurate than on conventional cephalometric radiographs. Therefore, it has been accepted that more anatomically appropriate reference planes can be established, allowing for more precise analyses. Three-dimensional imaging techniques have been increasingly adopted in orthodontic research to overcome the inherent limitations of two-dimensional cephalometric analyses, allowing more comprehensive assessment of craniofacial structures and growth-related skeletal changes, particularly in volumetric evaluations [17].
Global epidemiological studies have indicated a high prevalence of Class II malocclusion. With the increasing use of clear aligner therapy, evaluating the clinical efficacy of MAA has become a matter of significant interest for clinicians, patients, researchers, and aligner manufacturers alike.
With the increasing use of three-dimensional imaging in orthodontics, radiation safety—particularly in growing individuals—has become an important consideration. CBCT enables detailed three-dimensional and volumetric assessment of craniofacial structures; however, its use must be strictly justified and comply with radiation protection principles. Current guidelines recommend that CBCT should be prescribed only when clinically indicated, using a limited field of view and the lowest reasonably achievable dose (ALARA principle) [18, 19]. Accordingly, CBCT-based analyses in orthodontic research are considered acceptable when imaging is obtained as part of routine clinical care and retrospectively evaluated for scientific purposes, rather than acquired solely for research [20]. In the present study, CBCT imaging was not used as a screening or routine research tool, but as a clinically driven diagnostic modality whose existing data were analyzed to address a specific research question.
Although functional appliances have been extensively evaluated using two-dimensional cephalometric analyses, evidence regarding their short-term skeletal volumetric effects remains limited and inconsistent. In particular, comparative three-dimensional volumetric data between clear aligner–based mandibular advancement systems and conventional functional appliances during the pubertal growth phase are scarce. Therefore, the present study aimed to address this gap by evaluating and comparing short-term maxillary and mandibular volumetric changes using CBCT.
This study aimed to evaluate and compare the volumetric skeletal effects of two different mandibular advancement protocols—Invisalign MAA and conventional Activator therapy—using three-dimensional CBCT imaging. The primary hypothesis was that both functional appliances would induce favorable volumetric skeletal changes in Class II individuals during pubertal growth acceleration, but to varying extents. A secondary aim was to determine whether the novel Invisalign MAA system produced comparable or superior skeletal responses to those of the traditional Activator.
This study was designed as a single-center, controlled, and randomized parallel-group trial. This randomized controlled trial was conducted and reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines [21]. The study was registered at ClinicalTrials.gov (Identifier: NCT07056829).The trial was registered retrospectively due to delayed administrative processing; however, participant recruitment and data collection had already commenced prior to registration. No changes were made to the trial methodology after commencement.
The study protocol was approved by the Ethics Committee of the Faculty of Dentistry at Batman University (approval 2025/04–31). All procedures were conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants and their legal guardians.
CBCT examinations were not performed for research purposes. In accordance with internationally accepted radiation protection principles, justification preceded CBCT was prescribed only when a patient-specific clinical question could not be adequately answered using conventional two-dimensional imaging, such as the localization of impacted teeth, evaluation of temporomandibular joint conditions, or assessment of upper airway morphology. Importantly, the decision to obtain CBCT imaging was made independently of study participation and solely based on clinical need. Once clinically justified, exposure was optimized using a limited field of view and a standardized pediatric low-dose protocol (approximately 90–100 kVp, 3–5 mA, voxel size 0.3 mm) in line with the ALARA principle. The present study involved only the retrospective analysis of existing clinically indicated CBCT datasets, and no additional CBCT scans were requested or obtained to satisfy research objectives.
For the control group, CBCT images were retrieved retrospectively from existing clinical records obtained only when clinically indicated to address patient-specific diagnostic needs (e.g., impacted tooth localization, temporomandibular joint evaluation, or airway assessment). The decision to acquire CBCT imaging was made independently of study participation. No additional CBCT examinations were performed for research purposes, and no imaging was requested or repeated to satisfy study requirements.
The control group consisted of patients with skeletal Class II malocclusion for whom functional orthopedic treatment was deferred due to patient or parental preference, anticipated poor compliance, or clinical timing of growth modification. These individuals remained under routine orthodontic observation, and functional treatment was not withheld, delayed, or altered for research purposes.
Alternative imaging modalities without ionizing radiation were considered; however, they were deemed insufficient for accurate three-dimensional volumetric skeletal assessment. Therefore, CBCT examinations were strictly limited to clinically indicated cases only [22, 23].
CBCT images were obtained from individuals who presented to a private dental clinic for orthodontic treatment. The sample consisted of 55 individuals diagnosed with skeletal Class II anomalies. Inclusion criteria were as (1) Cervical vertebral maturation (CVM) stage 2 or 3; (2) Bilateral full or half cusp Class II molar relationship; (3) Skeletal Class II pattern with mandibular retrognathia (ANB > 4°, SNB < 78°); (4) Horizontal or average growth pattern (SN-GoGn ≤ 38°); (5) Overjet between + 4 mm and + 8 mm; and (6) Self-reported good compliance assessed during routine follow-up visits.
Exclusion criteria included CVM stage 5 or 6, prior orthodontic treatment, maxillary prognathism, high-angle growth pattern (SN-GoGn > 38°), transverse discrepancies or facial asymmetry, signs of TMJ dysfunction, craniofacial anomalies, poor oral hygiene, or imaging incompatibilities.
Compliance was assessed clinically and operationally rather than objectively at the recruitment stage. “Good compliance” was defined based on patient and parent self-reports, previous appointment attendance history, motivation for treatment, and clinician judgment during initial consultations. No objective wear-time monitoring system was used, and compliance was therefore not quantitatively measured. This limitation is acknowledged and discussed accordingly.
The MAA group included 10 females and 10 males (mean 12.5 years), the Activator group included 15 females and 5 males (mean 12.6 years), and the control group included 8 females and 7 males (mean 12.33 years). All had skeletal Class II malocclusion and similar overjet values.
Skeletal age was assessed using Grave and Brown’s hand–wrist criteria and the Greulich and Pyle atlas [24]. All individuals were in the pubertal growth acceleration phase but had not yet reached their peak pubertal growth. Cervical vertebral maturation (CVM) staging was used as the primary criterion for participant inclusion and group allocation, as it allows assessment of growth phase using routinely obtained lateral cephalograms. Hand–wrist radiographs were evaluated according to the Grave and Brown criteria and the Greulich and Pyle atlas as a supplementary method to confirm skeletal maturation status and ensure consistency of growth phase assessment.
Skeletal age assessment was performed using hand–wrist radiographs according to Grave and Brown’s criteria and the Greulich and Pyle atlas. Hand–wrist radiography is a routinely used, low-dose diagnostic method in orthodontic practice for evaluating growth status prior to functional orthopedic treatment. These radiographs were obtained only when clinically indicated as part of routine growth assessment and were not acquired specifically for research purposes. No additional hand–wrist radiographs were taken for the control group beyond standard clinical care.
Patients in the treatment groups received functional orthopedic therapy, whereas the control group was monitored without intervention for six months. Two records were at baseline and at the end of active treatment period.
In the MAA group, treatment was conducted using the Invisalign MA (Align Technology) system. The objective was to achieve Class I molar relationship or edge-to-edge overjet. Mandibular advancement was performed in 2 mm increments every 8 weeks, with follow-up visits scheduled every 5–6 weeks. The mean active treatment duration was 8.15 months.
In the Activator group, bite registration was standardized using the Projet Bite Wafer (Orthocare, UK). Appliances were prescribed for full-time wear (approximately 24 h per day), except during meals or physical activity. The average duration of active treatment was 7.15 months.
Compliance was assessed based on patient and parent reports during follow-up visits; however, no objective wear-time monitoring system was employed.
The primary outcome was the volumetric change in maxillary and mandibular skeletal structures assessed using three-dimensional CBCT imaging. Secondary outcomes included evaluation of skeletal age and overjet correction. No changes to outcome definitions or endpoints were made after trial commencement.
The sample size calculation was based on detecting a between-group difference in mandibular volumetric change, which was defined as the primary outcome of the study. A medium effect size (f = 0.25) was assumed, as volumetric skeletal changes following functional appliance therapy are generally reported to be modest in magnitude. With an alpha level of 0.05 and a statistical power of 80%, a minimum total sample size of 54 participants was required. Accordingly, 55 participants were included in the study.
No interim analyses were planned or conducted, and no stopping guidelines were specified for this study.
Participants were randomly allocated into three groups (MAA, Activator, and Control) using a computer-generated randomization list. Allocation concealment was ensured using sequentially numbered opaque sealed envelopes. The allocation process was implemented by an independent staff member who was not involved in the treatment or outcome assessment.
No stratification based on baseline mandibular volume or inter-scan interval was applied during randomization; therefore, adjusted statistical analyses were performed to minimize potential confounding effects.
Due to the nature of the orthodontic interventions, blinding of patients and treating clinicians was not feasible. However, volumetric analyses were performed by an investigator blinded to group allocations.
All CBCT scans were taken using the i-CAT 3D system (Imaging Sciences International, Hatfield, PA, USA). Data were saved in Digital Imaging and Communications in Medicine (DICOM) format and imported into Mimics 15.0^®^ software (Materialise, Leuven, Belgium).
Two-dimensional cross-sectional images were reconstructed into three-dimensional models for volumetric analysis. All scans were acquired using standardized pediatric acquisition settings according to manufacturer recommendations, and identical reconstruction parameters were applied for all analyses.
During segmentation, a HU threshold range of 226–3071 was applied in accordance with previous CBCT-based volumetric studies. It is acknowledged that CBCT-derived HU values are device-dependent and not absolute; therefore, consistent acquisition and reconstruction parameters were maintained throughout the study.
The segmentation workflow followed a standardized and reproducible protocol. DICOM datasets were imported into Mimics^®^ 15.0 software (Materialise, Leuven, Belgium). Bone structures were initially isolated using a predefined global threshold range (226–3071 HU), consistent with previously published CBCT-based volumetric studies. Region-growing tools were then applied to separate the maxilla and mandible from adjacent craniofacial structures.
Dental structures were removed to minimize beam-hardening artifacts using a combination of threshold-based masking and manual slice-by-slice refinement in axial, sagittal, and coronal planes. Following initial segmentation, manual corrections were applied to refine anatomical contours and ensure accurate delineation of skeletal boundaries [25–27].
Segmentation was performed first for the mandible and subsequently for the maxilla (Fig. 1). Mandibular segmentation included the condylar process, ramus, and mandibular body, while excluding dental crowns and roots. For maxillary segmentation, anatomical boundaries were defined superiorly at the nasal floor, posteriorly at the pterygomaxillary fissure, and inferiorly at the palatal plane passing through the anterior and posterior nasal spines (ANS–PNS) [28]. Laterally, segmentation followed the external cortical contours of the maxillary walls, excluding the zygomatic processes (Fig. 2).
Fig. 1Three-dimensional volumetric images of the Mandible
Fig. 2Three-dimensional volumetric images of the Maxilla
Maxillary segmentation was performed as a functional skeletal unit rather than an isolated anatomical bone. Due to anatomical continuity, the zygomatic buttress and adjacent cortical structures may appear partially included in three-dimensional renderings; however, volumetric calculations were strictly limited to the predefined maxillary boundaries. The nasal septum was separated along the mid-sagittal plane at the level of the nasal floor, and the maxilla was isolated inferiorly by the palatal plane passing through the anterior and posterior nasal spines (ANS–PNS). Figure 2 represents a three-dimensional visualization of the segmented region and is provided for illustrative purposes. Structures such as the zygomatic bone and orbital floor visible in the three-dimensional renderings represent adjacent anatomical surfaces for orientation purposes and were not included in the volumetric calculations.
All three-dimensional surface models and volumetric measurements were generated using the “Segmentation” and “Simulation” modules of Mimics^®^ software with identical reconstruction parameters for all subjects. All segmentations were performed by a single experienced orthodontist following the same protocol. To assess intra-operator consistency, each segmentation and volumetric measurement was repeated three times at two-week intervals, and the mean values were used for statistical analysis.
The statistical analysis of the data was conducted using the licensed IBM SPSS version 21 software package. The normality of data distribution was assessed using the Shapiro–Wilk and/or Kolmogorov–Smirnov tests, depending on the sample size. A significance level of 0.05 was adopted; p-values less than 0.05 indicated a deviation from normal distribution, whereas p-values greater than 0.05 suggested normal distribution.
To evaluate differences between groups, the Kruskal–Wallis H test was used when the variables were not normally distributed. If the Kruskal–Wallis test revealed a statistically significant difference, a post hoc multiple comparison test was performed to identify which groups differed.
To account for baseline differences in mandibular volume and heterogeneity in inter-scan intervals, adjusted analyses were additionally performed. Analysis of covariance (ANCOVA) models were constructed with post-treatment volumetric values as dependent variables, treatment group as the fixed factor, and baseline volume and inter-scan interval as covariates. Adjusted mean differences with 95% confidence intervals were calculated.
For the comparison of two related variables, the Wilcoxon signed-rank test was employed due to non-normal distribution. A significance level of 0.05 was used in interpreting the results; p-values less than 0.05 indicated statistically significant differences, whereas* p*-values greater than 0.05 indicated no significant difference.
When baseline volume values and inter-scan intervals differed significantly between groups, analysis of covariance (ANCOVA) was additionally performed to adjust for these variables.
A total of 55 children aged between 10 and 15 years participated in this study, comprising 22 boys and 33 girls. All participants completed the study, and no early discontinuations or dropouts were recorded during the study period. The allocation of individuals into groups and the flow of participants throughout the study are summarized in Table 1 (gender and age distribution).
Table 1Baseline characteristics of the groupsVariableActivator (n = 20)MAA(n = 20)Control(n = 15)Total(n = 55)Sex (F/M)15/510/108/733/22Age (Mean ± SD)12.6 ± 0.8812.5 ± 1.0512.33 ± 1.1812.49 ± 1.02
Intra-operator reliability was assessed using the intraclass correlation coefficient (ICC), which demonstrated excellent reproducibility (ICC > 0.90).
The mean ages were 12.6 years in the Activator group, 12.5 years in the MAA group, and 12.3 years in the control group, indicating a balanced distribution in terms of age and gender across all groups. These baseline characteristics suggest that the randomization process resulted in comparable groups at the outset of the study.
Despite randomization, baseline mandibular volume values differed significantly between groups (p = 0.001), and mean inter-scan intervals also differed (p = 0.001). Therefore, subsequent analyses were interpreted with adjustment for these baseline imbalances.
CBCT images were obtained at two time before treatment initiation and after completion of the active treatment phase. The average interval between CBCT acquisitions was approximately 7 months for the Activator group, 8 months for the MAA group, and 6 months for the control group (Table 2). All participants were included in the final analysis, and no interim analyses or data exclusions occurred. Subgroup analyses were not conducted.
Table 2Statistical analysis of group differences in measurement outcomesGroupKruskal-Wallis H Test n MeanMedianMinMaxSDMean RankH p Inter-radiograph IntervalActivator207.1576101,1826.7815.017 0.001 MAA208.1586101,1437.58Control156.264112,0416.87Total557.2574111,623 − 2AgeActivator2012.61311140,8829.680.3930.822MAA2012.51211151,0527.33Control1512.331310141,1826.67Total5512.491310151,02Pre-treatment Mandibular VolumeActivator2038011.7238201.8927710.2947002.804837.8119.7025.695 0.001 MAA2039763.9139113.4930412.6052135.994764.4823.00Control1549103.7747967.8941792.0764780.655705.1945.73Total5541673.9841092.1227710.2964780.656805.381–3 2–3Post-treatment Mandibular VolumeActivator2038430.9538645.7430100.8747271.494608.5919.9023.351 0.001 MAA2040027.3939651.0830173.4554146.455234.3123.45Control1549978.2747641.4841427.9967702.717387.2944.87Total5542160.7441085.9930100.8767702.717421.281–3 2–3Pre-treatment Maxillary VolumeActivator2027729.3627880.5918038.9237213.105749.1625.353.1050.212MAA2028306.9728712.0020088.3543367.975091.2426.00Control1531448.6129556.3624192.1947526.855801.1634.20Total5528953.7429096.8118038.9247526.855649.26Post-treatment Maxillary VolumeActivator2028538.8528265.3519411.4144936.346566.7623.804.9250.085MAA2029303.5628287.8621163.9145530.335318.7626.50Control1531837.5332410.3423857.5744601.554632.7535.60Total5529716.5728953.1919411.4145530.335702.37Mean Rank represents the average rank of observations in the Kruskal–Wallis H testMin minimum values, Max maximum values, SD standard deviationBold values indicate statistically significant results (p < 0.05)
Analysis of pre- and post-treatment changes in mandibular volume values is presented in Table 3. Although there was an increase in mandibular volume in both the Activator and MAA groups, the difference was not statistically significant.
Table 3Within-Group comparison of mandibular volume values before and after treatmentWilcoxon Test n MeanMedianMinMaxSDMean Rankz p ActivatorPre-treatment Mandibular Volume2038011.7238201.8927710.2947002.804837.8110.83-1.4930.135Post-treatment Mandibular Volume2038430.9538645.7430100.8747271.494608.5910.36MAAPre-treatment Mandibular Volume2039763.9139113.4930412.6052135.994764.4811.86-0.8210.411Post-treatment Mandibular Volume2040027.3939651.0830173.4554146.455234.319.77ControlPre-treatment Mandibular Volume1549103.7747967.8941792.0764780.655705.197.67-0.7950.427Post-treatment Mandibular Volume1549978.2747641.4841427.9967702.717387.298.22In the Wilcoxon signed-rank test, positive ranks indicate post-treatment increases, negative ranks indicate decreases, and Mean Rank represents the average rank of the absolute paired differencesMin minimum values, Max maximum values, SD standard deviation
Changes in maxillary volume before and after treatment are shown in Table 4. Similarly, although there was an increase in maxillary volume in the Activator and MAA groups during the treatment period, this change was not statistically significant. Although a statistically significant increase in maxillary volume was observed within the MAA group in the intragroup (pre–post) analysis (Table 4), intergroup comparisons revealed no statistically significant differences between the MAA, Activator, and control groups.
Table 4Within-Group comparison of maxillary volume values before and after treatmentWilcoxon Test n MeanMedianMinMaxSDMean Rankz p ActivatorPre-treatment Maxillary Volume2027729.3627880.5918038.9237213.105749.1610.25-0.8590.391Post-treatment Maxillary Volume2028538.8528265.3519411.4144936.346566.7610.67MAAPre-treatment Maxillary Volume2028306.9728712.0020088.3543367.975091.247.00-2.613 0.009 Post-treatment Maxillary Volume2029303.5628287.8621163.9145530.335318.7611.67ControlPre-treatment Maxillary Volume1531448.6129556.3624192.1947526.855801.168.83-0.3980.691Post-treatment Maxillary Volume1531837.5332410.3423857.5744601.554632.757.44In the Wilcoxon signed-rank test, positive ranks indicate post-treatment increases, negative ranks indicate decreases, and Mean Rank represents the average rank of the absolute paired differencesMin minimum values, Max maximum values, SD standard deviationBold values indicate statistically significant results (p < 0.05)
Adjusted analyses controlling for baseline volume and inter-scan interval confirmed that no statistically significant differences were observed between treatment groups and the control group.
Given the observed variability in volumetric measurements, the possibility of a type II error cannot be excluded.
Changes in overjet and skeletal age were evaluated as secondary outcomes. All participants were in the pubertal growth acceleration phase (CVM stages 2–3) at baseline, and no statistically significant differences were observed between groups with respect to skeletal maturation during the observation period (p > 0.05).
Overjet reduction was observed in both the MAA and Activator groups following treatment; however, intergroup comparisons revealed no statistically significant differences between the treatment groups. As expected, no meaningful overjet change was observed in the control group during the follow-up period.
The analysis of intergroup differences in mandibular and maxillary volume changes is presented in Table 5. According to the findings, there was no statistically significant difference in mandibular and maxillary volume changes between the treatment groups and the control group (p > 0.05). These results suggest that although volumetric increases were observed within the treatment groups, these increases did not differ significantly from the natural changes seen in untreated controls.
Table 5Intergroup comparison of mandibular and maxillary change valuesGroupKruskal-Wallis H Test n MeanMedianMinMaxSDMean RankH p Change in Mandibular VolumeActivator20419.23604.08-5431.113025.002025.8729.000.1280.938MAA20263.48510.02-4068.483374.871961.6927.25Control15874.50492.85-2447.4810866.313174.8727.67Total55486.76541.70-5431.1110866.312339.50Change in Maxillary VolumeActivator20809.49685.26-4060.979663.023173.6727.601.1760.556MAA20996.591070.35-1829.644735.821633.1630.75Control15388.92323.66-4794.308284.123399.6624.87Total55762.82640.93-4794.309663.022745.67Mean Rank represents the average rank of observations in the Kruskal–Wallis H testMin minimum values, Max maximum values, SD standard deviation
Because baseline volume values and inter-scan intervals differed significantly between groups, an ANCOVA analysis was performed to control for these potential confounders (Table 6). After adjustment, no statistically significant intergroup differences were observed for mandibular (p = 0.877) or maxillary (p = 0.952) volumetric changes.
Table 6ANCOVA-adjusted intergroup comparison of volumetric changes n Adjusted MeanSD95% Confidence IntervalANCOVALower BoundUpper BoundF p Change in Mandibular VolumeActivator2042027.23771.91740476.78843577.6690.1310.877MAA2041916.45594.45540722.45143110.446Control1542664.481237.18440179.52145149.434Change in Maxillary VolumeActivator2029583.28858.1927859.55631307.0060.0490.952MAA2029859.83673.36628507.3331212.322Control1529703.271343.54927004.67732401.871ANCOVA was performed to adjust for baseline volume and inter-scan interval. Adjusted means (estimated marginal means) and 95% confidence intervals are presented. Statistical significance was set at p < 0.05SD: standard deviation
Throughout the course of the study, no adverse effects or harms were reported in any of the groups. Patients tolerated both appliances well, and no complications such as temporomandibular joint pain, masticatory muscle tenderness, or imaging-related discomfort were observed. Compliance remained high across both treatment groups, and no protocol violations or unexpected events occurred during the study period.
The development of clear aligner systems capable of supporting mandibular advancement during the growth period has gained increasing popularity among patients, primarily due to their favorable esthetic appearance, improved comfort compared with conventional functional appliances, enhanced oral hygiene, and reduced incidence of appliance-related emergencies [8, 30]. In this study, the effects of the MAA appliance, used in growing individuals with Class II Division 1 anomalies due to mandibular retrusion, on the volumes of the maxilla and mandible were evaluated through CBCT and compared with traditional functional appliances and a control group.
Although previous studies suggest that functional appliances primarily induce positional rather than volumetric skeletal changes, high-quality three-dimensional controlled data directly comparing clear aligner–based mandibular advancement with conventional functional appliances and untreated controls remain limited. Volumetric assessment was intentionally selected to explore whether mandibular advancement induces true skeletal volumetric growth beyond positional adaptation. The absence of statistically significant differences in maxillary and mandibular volumes between the treatment groups and the control group suggests that correction of Class II malocclusion during the pubertal growth phase is achieved predominantly through positional adaptation rather than true volumetric skeletal growth, particularly over a short observation period. These findings are consistent with previous reports indicating that functional appliances primarily produce dentoalveolar and positional skeletal changes, while clinically meaningful skeletal remodeling may require longer treatment durations and extended follow-up. Therefore, the lack of significant volumetric changes in the present study should be interpreted within the context of short-term evaluation and high inter-individual growth variability, rather than as evidence of treatment inefficacy.
Three-dimensional CBCT superimposition techniques are widely used to evaluate craniofacial growth and treatment effects by assessing positional and surface-based changes relative to stable reference structures. This approach is particularly useful for identifying directional growth patterns and rotational adaptations. However, superimposition methods primarily capture displacement and remodeling patterns rather than absolute changes in skeletal tissue quantity. In contrast, volumetric analysis provides a quantitative assessment of total skeletal volume, allowing investigation of whether functional appliances induce true skeletal volumetric growth beyond positional adaptation. While volumetric comparison may not fully characterize regional remodeling or rotational changes, it represents a complementary method that addresses a distinct biological question. Therefore, volumetric analysis should not be considered a replacement for superimposition techniques, but rather an adjunctive approach that contributes additional insight into the nature of skeletal response to functional treatment [31].
The relatively short duration of treatment and follow-up represents an important limitation of the present study, as functional growth modification effects are known to become more evident over longer observation periods. Accordingly, the absence of significant volumetric skeletal changes should be interpreted cautiously within the context of short-term evaluation. The six-month observation period was deliberately selected to assess early adaptive and positional skeletal responses during the pubertal growth acceleration phase rather than definitive long-term growth modification. Previous studies have demonstrated that the initial effects of functional appliances are predominantly positional, whereas cumulative skeletal remodeling generally requires longer treatment and follow-up durations [32]. Therefore, the present study was designed to capture short-term volumetric trends rather than long-term skeletal growth outcomes.
Although the MAA protocol is widely used in clinical practice, literature investigating its effects on craniofacial volumetric changes remains limited. Therefore, this study emphasized a comparative evaluation of the effectiveness of MAA and conventional functional treatment approaches, rather than focusing solely on volumetric measurements. In orthodontic treatments, patient-reported outcomes such as quality of life, satisfaction, and comfort have become increasingly important [33, 34].
Recent evidence also suggests that social media platforms play a significant role in shaping patient perceptions and expectations regarding clear aligner therapy, emphasizing the growing importance of patient-centered outcomes in contemporary orthodontic practice [35].
Glaser et al. reported that aligners cause minimal pain and rarely discomfort patients due to their limited contact with soft tissues [6]. In a study comparing clear aligners and Twin-Block appliances, Zybutz et al. highlighted advantages of aligners such as being less noticeable, easier to use, and physically less perceptible to patients [8].
According to a meta-analysis by Ghorbani et al. aligners were associated with slightly higher levels of dental pain compared to Twin-Block appliances, although no significant difference was found between the two in terms of lip discomfort. Additionally, aligners were reported to require fewer additional clinic visits due to reduced breakage and fitting issues—22% for aligners compared to 50% for Twin-Block appliances [36]. This difference may be attributed to the replacement of aligners every 7–17 days, whereas Twin-Block appliances remain in the mouth for longer durations.
However, the effectiveness of aligners in achieving skeletal and dental correction comparable to traditional functional appliances remains controversial. While some studies report favorable skeletal outcomes such as mandibular advancement accompanied by overjet reduction, increased SNB angle, and stable SNA angle [12, 37], others emphasize limitations in achieving significant mandibular advancement with aligners [5]. A meta-analysis comparing functional appliances and MAA reported that both treatment approaches were similarly effective in reducing the ANB angle. In the same study, evaluation of incisor positions revealed better maintenance of incisor angulation in patients treated with MAA, which may be attributed to the more precise control of tooth movement provided by aligners. In contrast, patients treated with functional appliances exhibited torque loss in the upper incisors and increased buccal inclination in the lower incisors [36].
Regarding temporomandibular joint (TMJ) effects, studies by Zhang and Wu demonstrated that both Twin-Block appliances and aligners promoted adaptive remodeling of condylar morphology [37, 38]. Zhang et al. reported that aligners were more effective in supporting vertical condylar growth, while Twin-Block appliances were superior in promoting sagittal growth and mandibular ramus development. Yue et al. [39] reported significant improvements in upper airway morphology and reduced airway resistance during mandibular advancement with aligners. Both aligners and functional appliances showed positive effects on airway parameters; however, aligners were found to be more successful in expanding the narrow hypopharyngeal region. These findings suggest that aligners may be a clinically meaningful option in cases with specific airway concerns [40]. It should be noted, however, that condylar adaptations, mandibular rotation patterns, and airway-related outcomes were not directly evaluated in the present study, as the analysis was limited to short-term volumetric skeletal changes.
In our study, MIMICS 15.0^®^ (Materialise, Leuven, Belgium) modeling software was used for volumetric measurements. Moerenhout et al. demonstrated that measurements performed with MIMICS are reliable by comparing them with actual distances on 3D digital models [41]. The absence of a significant difference between CT-based volumetric calculations and actual organ volumes supports the accuracy of this method [42, 43].
Volumetric analysis was selected as an objective method to assess global skeletal changes of the mandible and maxilla without relying on landmark-based superimposition, which may be influenced by growth-related morphological variability. While three-dimensional superimposition techniques are widely used to evaluate craniofacial growth, they depend heavily on the stability of reference structures and landmark reproducibility, which may be challenging during the pubertal growth period. Volumetric assessment, in contrast, allows quantification of overall skeletal size changes and provides complementary information regarding structural adaptation. Previous studies have demonstrated that CBCT-based volumetric measurements of craniofacial structures are reliable and reproducible, supporting their validity as an alternative tool for evaluating skeletal changes in growing patients [17, 44–46]. However, it should be emphasized that volumetric analysis does not replace traditional growth assessment methods but rather serves as an adjunct approach to better understand short-term skeletal adaptations.
Although a priori power analysis was performed assuming a medium effect size, the relatively small sample size and high inter-individual growth variability may have limited the ability to detect subtle volumetric differences. Therefore, the possibility of a type II error cannot be excluded, particularly for small skeletal effects.
In our study, DICOM-format data were transferred into MIMICS software before and after treatment, and changes in maxillary and mandibular volumes were evaluated using three-dimensional analyses. Our findings revealed no statistically significant intergroup differences in maxillary or mandibular volumes between the MAA, Activator, and control groups. While intragroup analysis demonstrated a statistically significant increase in maxillary volume in the MAA group, this finding did not translate into a significant intergroup difference when compared with the Activator or untreated control group. This suggests that the observed volumetric change reflects short-term adaptive or growth-related variation rather than a treatment-specific skeletal effect. This result supports the notion that, at least in the short term, mandibular correction in Class II cases due to mandibular retrognathia is achieved primarily through anterior repositioning rather than true skeletal growth. It is known that aligner-guided maxillary expansion aims to create space for the forward positioning of the mandible, which may lead to buccal tipping of the posterior teeth and could explain why the increase in maxillary volume did not result in a significant intergroup difference [47–49].
Despite these insights, the study has several limitations that should be acknowledged. First, the relatively small sample size limits the statistical power and generalizability of the findings. Additionally, the short duration of treatment and follow-up may not fully reflect long-term skeletal or dental changes. Another limitation is the lack of direct monitoring of patients’ appliance wear time, which could significantly affect treatment outcomes. The absence of objective wear-time monitoring represents a major confounding factor, as treatment effectiveness in both appliance groups is highly dependent on patient compliance. Furthermore, although the volumetric analysis was conducted using validated and reliable methods, operator variability and segmentation thresholds could introduce minimal measurement bias. The lack of complementary traditional skeletal measurements (e.g., condylar growth, mandibular length, SNB/ANB changes) limits direct comparison with conventional functional appliance studies and represents a methodological limitation.
The present analysis was limited to group-based comparisons, and multivariable predictive modeling (e.g., regression analysis) was not performed. Future studies with larger samples are warranted to explore the influence of demographic and treatment-related variables on volumetric changes. Additionally, volumetric assessment alone may not fully capture regional skeletal adaptations or positional changes. The absence of complementary traditional skeletal measurements (e.g., condylar growth, mandibular length, angular changes) represents a methodological limitation.
It is well established that children are more radiosensitive than adults and have a longer lifetime during which radiation-induced stochastic effects may manifest. As emphasized by Aps (2013) in the widely cited ‘To beam or not to beam’ commentary, the use of CBCT in growing patients represents a particularly sensitive ethical issue and should be avoided unless clearly justified by clinical need [49]. Accordingly, CBCT use in the present study was restricted to retrospectively analyzed, clinically indicated cases only, and imaging was not obtained for research purposes. This ethical consideration constitutes an important limitation and underscores the need for cautious interpretation of the findings.
Within the limitations of this short-term randomized controlled trial, no statistically significant skeletal volumetric differences were detected between Invisalign Mandibular Advancement and conventional Activator therapy. Therefore, conclusions regarding skeletal effectiveness should be interpreted with caution, and further long-term studies with larger sample sizes and adjusted analytical models are required. Longer observation periods (12–24 months), as used in classical functional appliance studies, may be necessary to capture cumulative skeletal remodeling effects. Given the relatively small sample size and high inter-individual growth variability, the study may have been underpowered to detect small but potentially clinically relevant volumetric differences, and a type II error cannot be excluded.
Given these limitations, caution is advised when generalizing the results to broader populations. The homogeneity of the sample in terms of skeletal pattern and age enhances internal validity but restricts external applicability to more diverse clinical cases. Nevertheless, the inclusion of a control group and the comparison of two distinct treatment modalities provide valuable insights for clinical orthodontic practice. Future studies incorporating more heterogeneous populations, longer follow-up periods, and patient-reported outcome measures are warranted to better define the long-term clinical relevance of MAA therapy. Within the limitations of this short-term study, MAA demonstrated volumetric skeletal effects comparable to those of the Activator, without evidence of significant volumetric growth modification.
Within the limitations of this short-term randomized controlled trial, no statistically significant differences were detected in maxillary or mandibular volumetric changes between Invisalign Mandibular Advancement therapy, conventional Activator treatment, and untreated controls. The observed volumetric increases in the treatment groups did not differ from changes associated with normal growth over the observation period. These findings suggest that short-term functional correction in Class II malocclusion is predominantly related to positional adaptation rather than true skeletal volumetric growth. Given the relatively small sample size, short follow-up duration, and inherent growth variability, the results should be interpreted with caution. Future studies with larger cohorts, longer observation periods, and complementary skeletal and patient-reported outcome measures are warranted to further clarify the long-term effects of clear aligner–based mandibular advancement therapy.