Molar Distalization by Clear Aligners with Sequential Distalization Protocol: A Systematic Review and Meta-Analysis

Introduction: With the popularity of clear aligners, the sequential distalization protocol has been more commonly used for molar distalization. However, the amount of molar distalization that can be achieved, as well as the accompanying side effects on the sagittal dimension, are unclear. Methods: Registered with PROSPERO (CRD42023447211), relevant original studies were screened from seven databases (MEDLINE [PubMed], EBSCOhost, Web of Science, Elsevier [SCOPUS], Cochrane, LILACS [Latin American and Caribbean Health Sciences Literature], and Google Scholar) supplemented by a manual search of the references of the full-reading manuscripts by two investigators independently. A risk of bias assessment was conducted, relevant data were extracted, and meta-analysis was performed using RStudio. Results: After the screening, 13 articles (11 involving maxillary distalization, two involving mandibular distalization) met the inclusion criteria. All studies had a high or medium risk of bias. The meta-analysis revealed that the maxillary first molar (U6) mesiobuccal cusp was distalized 2.07 mm [1.38 mm, 2.77 mm] based on the post-distalization dental model superimposition, and the U6 crown was distalized 2.00 mm [0.77 mm, 3.24 mm] based on the post-treatment lateral cephalometric evaluation. However, the U6 mesiobuccal root showed less distalization of 1.13 mm [−1.34 mm, 3.60 mm], indicating crown distal tipping, which was validated by meta-analysis (U6-PP angle: 2.19° [1.06°, 3.33°]). In addition, intra-arch anchorage loss was observed at the post-distalization time point (U1 protrusion: 0.39 mm [0.27 mm, 0.51 mm]), which was corrected at the post-treatment time point (incisal edge-PTV distance: −1.50 mm [−2.61 mm, −0.39 mm]). Conclusion: About 2 mm maxillary molar distalization can be achieved with the sequential distalization protocol, accompanied by slight molar crown distal tipping. Additional studies on this topic are needed due to the high risk of bias in currently available studies.


Introduction
Achieving effective and efficient molar distalization to correct molar relationships and create space for crowding relief has been a long-lasting subject of debate in orthodontics.Historically, some of the most commonly used maxillary molar distalization strategies include inter-arch appliances such as class II elastics [1], Carriere 3D Motion appliance [2], Forsus fatigue resistant device [3], mandibular anterior repositioning appliance (MARA) [4], Herbst appliance [5], SAIF-springs [6], as well as intra-arch appliances such as the Pendulum [7], Jones jig [8], First Class Appliance [9], and Distal Jet [10].Other distalization strategies include extraoral appliances such as headgear [11].For many of the appliances mentioned above, there are concerns about patients' acceptance [12].For instance, several patients have reported difficulty in eating soon after delivery of these fixed appliances [13].Other side effects reported by patients include toothaches, limited maximum opening, aching jaws, difficulty in the upkeep of oral hygiene, and soreness on the lip/cheek due to abrasion from appliances [12,14].
In the past two decades, clear aligners have become popular as a more esthetic, less invasive, and more hygienic option for patients seeking orthodontic treatment [15].To achieve molar distalization with clear aligners, the sequential distalization protocol was introduced [16].The sequential distalization protocol is designed to start with moving the second molar distally.When the second molar reaches 50% of the total movement, the first molar starts moving distally, and so on up to the canine, and lastly, en masse incisor retraction is initiated.During the whole protocol, inter-arch elastics are often used to utilize the opposing arch as the anchorage.However, whether this protocol is a viable option for a significant amount of molar distalization is still questionable [17,18].When evaluated on the crown level on dental models, some articles reported up to 2.68 ± 0.50 mm distalization of the mesial buccal cusp of the maxillary first molar [19][20][21][22][23], while other articles reported unsatisfactory amounts of distalization were achieved [24,25].Patterson et al. found that anterior-posterior correction achieved at the end of clear aligner therapy for class II patients is only 6.8% of the predicted amount (0.23 mm achieved of the 3.29 mm predicted amount) [24], and both Patterson et al. [24] and Taffarel et al. [25] concluded that treatment of Class II malocclusions with clear aligners would not meet the standards of the American Board of Orthodontics (ABO) Model Grading System.
It is worth noting that while bodily distalization is a more desirable treatment outcome with molar distalization, several molar distalization strategies report crown distal tipping and mesial out-distal in rotation of molars [19,20], which are unwanted side effects that easily cause relapse [26].The previous literature indicates that pure crown tipping is the most predictable movement of clear aligners [17], and the movement involving any amount of root control has poor predictability, especially for the posterior teeth [17,27].Thus, whether the sequential distalization protocol in clear aligner therapy can achieve bodily distalization of the molars needs to be further evaluated.
In addition, with inter-arch elastic usage as an integral part of the sequential distalization protocol, anchorage loss in opposing arches has been reported in conjunction with molar distalization [28].Excessive incisor proclination or protrusion can result in undesirable side effects such as alveolar bone loss and gingival recession [29].These concerns suggest the need to evaluate the amount of anchorage loss created by molar distalization.
Considering all the clinical questions mentioned above, a systematic review was conducted in the current study to examine the current evidence on the amount of molar distalization achievable with the sequential distalization protocol of clear aligner therapy.Moreover, this review aims to assess the accompanying effects of rotation and tipping of molars as well as anterior anchorage loss, ultimately providing clinical insight into the effectiveness and limitations of clear aligner therapy.

Materials and Methods
This study was registered with PROSPERO (registration number: CRD42023447211) on 1 August 2023, and is compliant with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline [30].All original articles were accessed through a search from the following electronic databases: MEDLINE (PubMed), EBSCOhost, Web of Science, Elsevier (SCOPUS), Cochrane, LILACS (Latin American and Caribbean Health Sciences Literature), and Google Scholar, with an initial search finish date of 13 February 2024.

Study Selection Criteria
Based on the framework of population, interventions, comparison, and outcomes (PI-COs), we conducted a systematic literature review on the sequential distalization protocol of clear aligner therapy for molar distalization (Table 1).The inclusion criteria comprised (1) longitudinal studies (both prospective and retrospective) comparing pre-and postdistalization/treatment records, (2) participants with permanent dentition, and (3) molar distalization achieved by sequential distalization protocol.The exclusion criteria were (1) participants with congenital abnormalities or systemic pathologies, (2) case reports, (3) conference abstracts, (4) opinions, editorials, guidelines, or letters to the editors, (5) systematic reviews, (6) utilization of TADs or other auxiliaries during molar distalization, (7) molar distalization protocol not described, and (8) inconsistent data within the article and did not receive responses from the corresponding author(s).No language or date restrictions were imposed.The PRISMA flow diagram illustrating the process of obtaining the final included articles is presented in Figure 1.The control is pre-treatment models and radiographs

Outcome
The amount of molar distalization, molar rotation, molar tipping, and anterior anchorage loss achieved during molar distalization with clear aligners

Data Extraction and Analysis
For all the articles included for further data analysis, relevant information was extracted from each article, including study type, arch treated, sample size, gender, age, clear aligner brand, type of records, timing of treatment records, as well as parameters evaluating molar distalization, molar rotation, molar tipping, and maxillary and mandibular anterior anchorage loss reported by dental model superimposition or by radiographic analysis.

Risk of Bias/Quality Assessment
Due to the heterozygosity of the study types of the included studies, the risk of bias protocol was modeled after one established in a previous publication [31], which is similar in design to our study.A total of 17 biases were evaluated in four categories: study design, study measurements, statistical analysis, and others (Table 2), which were scored by two authors (C.S. and T.H.P.) individually.In cases of disagreement, a third author (C.L.) provided input.Each article's score was calculated by dividing the number of met criteria by the total number of criteria.The risk of bias-low, medium, or high-was determined based on randomization and reliability testing.A low risk of bias was assigned if both reliability and randomization criteria were met.A high risk of bias was indicated if interrater reliability was not assessed and if randomization was not conducted.All other studies were categorized as having a medium risk of bias (Table 2).

Statistical Analysis
The outcomes of this study were as follows: (1) the amount of molar distalization achieved during distalization with clear aligners, as well as the amount of concurrent (2) molar rotation, (3) molar tipping, and (4) anterior anchorage loss.A meta-analysis utilizing the data extracted from the included articles was conducted using RStudio (version 2023.09.1+494,Posit Software, PBC) [40,41].In cases where articles only provided the mean difference along with upper and lower 95% confidence intervals, the standard deviation was computed using the conventional definition SD = √ N × (upper limit − lower limit)/3.92,regardless of the normal distribution within the sample population [42].The meta-analysis was carried out employing a random effects model, and heterogeneity was evaluated for variance among studies using the Tau2 method (τ²).The results were presented as mean and 95% confidence interval [CI].Sensitivity analysis and selective reporting within studies were not evaluated due to the limited number of studies included per analyzed variable.

Risk of Bias
The strength of evidence was evaluated by conducting a methodological risk of bias assessment on the 13 studies included (Table 2).Among these, only one study [32] reported both random sampling and random allocation of treatment.The remaining studies did not provide information on randomization.Four studies [32,33,35,39] mentioned blinding conducted by the examiner, but only one [32] of them extended blinding to the statistician.Other studies did not incorporate blinding measures.Intra-rater reliability was addressed in 7 of the 13 studies [19,21,22,32,33,35,37], while one article's reporting on intra-rater reliability was unclear [23].Three articles reported inter-rater reliability [19,22,33].Based on criteria on randomization and reliability testing, none of the studies scored low for risk of bias.Five studies were categorized as having a medium risk of bias [19,20,22,32,33], while the remaining eight were deemed to have a high overall risk of bias [21,23,[34][35][36][37][38][39].

Maxillary Molar Distalization
The amount of maxillary molar distalization was evaluated on post-treatment and postdistalization dental models (Table 4) and post-treatment radiographs (Table 5).Distalization was measured based on varying parameters.Meta-analyses were also performed on the amount of maxillary first (U6, Figure 3) and second molar (U7, Figure 4) distalization evaluated on radiographic images.A random effects model was used for meta-analysis for the parameters U6 and U7 PtV-CC (distance between the pterygoid vertical plane and the center of the crown of the maxillary molar), PtV-MC (distance between the pterygoid vertical plane and the mesial cusp of maxillary molar), PtV-PRA (distance between the pterygoid vertical plane and the palatal root apex of the maxillary molar), and PtV-VMRA (distance between the pterygoid vertical plane and the vestibulomesial root apex of maxillary molar).Of the four parameters analyzed for the U6 distalization evaluated on radiographic images, both parameters at the crown level showed a significant amount of distalization, while both parameters at the root level showed non-significant distalization (Figure 3).Of the four parameters analyzed for U7 distalization evaluated on radiographic images, parameters at the crown level as well as at the palatal root apex showed a significant amount of distalization, while the mesial buccal root apex did not (Figure 4).[33] 1.67 [1.03, 2.31] 1 U6: maxillary first molar; 2 U7: maxillary second molar; 3 PtV-CC: distance between the pterygoid vertical plane and the center of the crown of the maxillary molar; 4 PtV-MC: distance between the pterygoid vertical plane and the mesial cusp of the maxillary molar; 5 PtV-PRA: distance between the pterygoid vertical plane and the palatal root apex of the maxillary molar; 6 PtV-VMRA: distance between the pterygoid vertical plane and the vestibulomesial root apex of the maxillary molar; 7 UMD: upper molar distalization; *: data from lateral cephalometric radiograph extracted from CBCT.

Ravera et al. (2016)
Meta-analyses (Figure 2) were performed on the amount of maxillary first and second molar mesiobuccal cusp distalization evaluated on post-distalization dental models.The maxillary first and second molars showed significant distalization of 2.07 mm [1.38 mm, 2.77 mm] and 2.38 mm [1.19 mm, 3.57 mm], respectively.Meta-analyses were also performed on the amount of maxillary first (U6, Figure 3) and second molar (U7, Figure 4) distalization evaluated on radiographic images.A random effects model was used for meta-analysis for the parameters U6 and U7 PtV-CC (distance between the pterygoid vertical plane and the center of the crown of the maxillary molar), PtV-MC (distance between the pterygoid vertical plane and the mesial cusp of maxillary molar), PtV-PRA (distance between the pterygoid vertical plane and the palatal root apex of the maxillary molar), and PtV-VMRA (distance between the pterygoid vertical plane and the vestibulomesial root apex of maxillary molar).Of the four parameters analyzed for the U6 distalization evaluated on radiographic images, both parameters at the crown level showed a significant amount of distalization, while both parameters at the root level showed non-significant distalization (Figure 3).Of the four parameters analyzed for U7 distalization evaluated on radiographic images, parameters at the crown level as  1 U6: maxillary first molar; 2 U7: maxillary second molar; 3 PtV-CC: distance between the pterygoid vertical plane and the center of the crown of the maxillary molar; 4 PtV-MC: distance between the pterygoid vertical plane and the mesial cusp of the maxillary molar; 5 PtV-PRA: distance between the pterygoid vertical plane and the palatal root apex of the maxillary molar; 6 PtV-VMRA: distance between the pterygoid vertical plane and the vestibulomesial root apex of the maxillary molar; 7 UMD: upper molar distalization; *: data from lateral cephalometric radiograph extracted from CBCT.
J. Funct.Biomater.2024, 15, x FOR PEER REVIEW 10 of 22 well as at the palatal root apex showed a significant amount of distalization, while the mesial buccal root apex did not (Figure 4).

Maxillary Molar Rotation and Tipping
Maxillary molar rotation accompanying maxillary molar distalization was only evaluated on post-distalization and post-treatment dental models (Table 6).Maxillary molar

Maxillary Molar Rotation and Tipping
Maxillary molar rotation accompanying maxillary molar distalization was only evaluated on post-distalization and post-treatment dental models (Table 6).Maxillary molar tipping accompanying maxillary molar distalization was evaluated on post-treatment radiograph images and dental models (Table 7).Due to the high heterogeneity of the parameters reported in the included studies, a meta-analysis could only be performed on the amount of maxillary first and second molar distal tipping in reference to the palatal plane on post-treatment radiographic images (Figure 5).The analysis revealed 2.19

Anterior Anchorage Loss after Maxillary Molar Distalization
The amount of anchorage loss on both upper and lower arches during maxillary molar distalization was evaluated on both dental models (Table 8) and radiographic images (Table 9).2017) Right [23] 0.25 ± 0.85 *
Meta-analyses were conducted on the amount of maxillary central incisor protrusion based on the evaluation of pre-treatment and post-distalization dental models (Figure 6) as well as on the amount of maxillary central incisor protrusion and proclination based on the evaluation of pre-and post-treatment radiographic analysis (Figure 7).At the post-distalization time point, 0.39 mm [0.27 mm, 0.51 mm] of maxillary central incisor protrusion was observed (Figure 6).At the post-treatment time point, 1.50 mm [0.39 mm, 2.61 mm] of central incisor retraction at the incisal edge level (IE-PTV) was observed, while no significant amount of retraction was observed of the central incisor at the crown level  7).Meta-analyses could not be performed on the opposing arch evaluations due to insufficient data.
Meta-analyses were conducted on the amount of maxillary central incisor protrusion based on the evaluation of pre-treatment and post-distalization dental models (Figure 6) as well as on the amount of maxillary central incisor protrusion and proclination based on the evaluation of pre-and post-treatment radiographic analysis (Figure 7).At the postdistalization time point, 0.39 mm [0.27 mm, 0.51 mm] of maxillary central incisor protrusion was observed (Figure 6).At the post-treatment time point, 1.50 mm [0.39 mm, 2.61 mm] of central incisor retraction at the incisal edge level (IE-PTV) was observed, while no significant amount of retraction was observed of the central incisor at the crown level (CC-PTV, −0.78 mm [−3.95 mm, 2.39 mm]) or at the root apex level (RA-PTV, −0.20 mm [−4.28 mm, 3.89 mm]).Slight incisal retroclination was observed based on the U1-PP angle (−3.40° [−5.61°, −0.47°]), but not based on the U1-SN angle (−2.66° [−58.31°,52.99°]) (Figure 7).Meta-analyses could not be performed on the opposing arch evaluations due to insufficient data.

Mandibular Molar Distalization
The amount of mandibular molar distalization (Table 10), mandibular molar tipping (Table 11), and anterior anchorage loss after mandibular molar distalization (Table 12) was evaluated on post-distalization and post-treatment radiographic images with one study available from each time point.Further analysis of mandibular molar distalization with a clear aligner sequential distalization protocol was not possible due to insufficient data.

Summary of Evidence
Molar distalization has been a topic of ongoing debate in orthodontics.With the increase in popularity of clear aligners in the past two decades, whether clear aligners can effectively achieve a significant amount of molar distalization with the sequential distalization protocol has become a hot topic of discussion.Due to the varying evidence supporting the efficiency of molar distalization with clear aligners, this study further elucidates currently available data on clear aligner molar distalization and the accompanying side effects.
Our literature search showed high variability in study characteristics, limiting the data that could be utilized for each meta-analysis.Overall, about 2 mm of maxillary molar crown distalization was observed, accompanied by molar crown distal tipping and intra-arch anterior anchorage loss.There was not enough evidence on inter-arch anchorage loss, as well as on mandibular molar distalization with clear aligners.In addition, large variations in the amount of achieved molar distalization and anterior teeth movement were noticed among the reported studies.
Discrepancies between the distalization of the maxillary molars achieved by each study can be attributed to several factors.Primarily, differences in the time points may not be comparable due to changes in molar position during orthodontic treatment between the post-distalization and post-treatment stages.Additionally, studies contained data that varied greatly in the types of records, parameters, and time points, making the available data difficult to compare.Even within the same studies, variations were found in the amount of distalization achieved when different structures and measurement parameters were used (Figures 2-4).Tracing errors due to distortion, differences in magnification, and overlapping structures on radiographic image superimpositions were also important contributing factors in the variations in molar distalization determined in this study.
The varying attachment designs of each study may also have affected the amount of distalization achieved.Garino et al. [32] noted a significant difference in the distalization achieved with the three-attachment protocol compared to the five-attachment protocol, with approximately 1.54 mm and 2.3 mm of maxillary first molar distalization achieved, respectively.Though the attachment protocol could potentially influence the efficiency of molar distalization, most studies did not include specific information regarding the attachment design.This lack of crucial information may have contributed to the variance in reported molar distalization from the included studies, further challenging the analysis of the available literature.
It is worth noting that none of the included studies compared clear aligner therapy to other well-studied molar distalization strategies.Thus, to obtain a better sense of the efficiency of molar distalization with clear aligners in comparison with fixed appliances, we can only compare the meta-analysis results with articles that report molar distalization with fixed appliances in adult patients.With a sample population of 33 adult patients that underwent molar distalization therapy using different types of intraoral distalizing appliances, including Pendulum, Distal Jet, and Fast Back appliances, 2.9 ± 0.6 mm maxillary first molar distalization was observed on post-treatment lateral cephalometric radiographs without significant molar crown distal tipping (U6-SN angle: −0.2 • ± 1.8 • ) [69].In another study evaluating 46 non-growing patients treated with different types of distalizing appliances (Cetlin distalizing appliance, compressed Niti coil springs, Loca system wire, intraoral palatal distalizing appliances, and "Zig-Zag loops" in conjunction with intermaxillary elastics), 2.16 ± 0.84 mm maxillary first molar distalization was observed on post-treatment lateral cephalometric radiographs accompanied with 1.45 • (range 2.22 • to −6.45 • ) of molar crown distal tipping [70].Thus, the sequential distalization protocol of clear aligners appears to provide a slightly reduced amount of maxillary molar distalization (2.07 mm [1.38 mm, 2.77 mm]) with more prominent molar crown distal tipping (2.19 • [1.06 • , 3.33 • ]) in adult patients when compared to non-TAD-supported fixed appliances.However, additional studies directly comparing different treatment strategies are needed to provide clear evidence on this aspect.
Regarding the anterior anchorage loss during molar distalization, our study found significant maxillary incisor protrusion at the post-distalization time point, but incisor retraction and retroclination at the end of treatment.However, it is unclear if the space achieved for retraction was due purely to whole arch distalization or if the retraction space was from interproximal reduction or arch expansion.Future studies should provide more details on the specific protocols for a more accurate comparison of retraction achieved following molar distalization.In addition, although there was insufficient data to run a meta-analysis on the mandibular incisor sagittal position changes, the available data consistently show proclination and protrusion of lower incisors at post-distalization and post-treatment time points (Tables 8 and 9), indicating significant mandibular anchorage loss during maxillary molar distalization with clear aligners.

Limitations
A major limitation of this study was the variation in the evaluation time points, the type of data collected, and the measurement parameters, which significantly affected the number of studies that could be incorporated into the meta-analysis.While both maxillary and mandibular molar distalization are pertinent in orthodontic treatment, only two of the 13 included studies included information regarding mandibular molar distalization [38,39].Despite the inclusion of these two studies, mandibular molar measurements could not be analyzed via meta-analysis.
Secondly, none of the included studies provided details regarding the ClinCheck ® set-ups.Studies may have had differing amounts of molar distalization programmed into the digital set-up, which could affect the amount of molar distalization achieved clinically.
Thirdly, this study did not explore the vertical control and transverse expansion aspects of molar distalization.Further studies exploring all aspects of molar distalization with clear aligners are necessary to better support the clinical use of clear aligners in molar distalization.
Nevertheless, the current study points to the glaring gaps in the available data on molar distalization with clear aligners.More comprehensive studies in molar distalization by clear aligners and the accompanying effects are recommended.

Conclusions
This study demonstrates that approximately 2 mm maxillary molar distalization is achievable with the sequential distalization protocol of clear aligners with a certain amount of crown distal tipping.However, the high risk of bias among current available studies and the high variations in the time points assessed, type of data collected, and parameters measured among the available studies point to the insufficient data currently available on molar distalization with clear aligners.Additional studies are needed to determine if a sequential distalization protocol with clear aligners alone is a viable option for molar distalization.

Figure 1 .
Figure 1.The PRISMA flow diagram demonstrating the study identification and screening.

Figure 1 .
Figure 1.The PRISMA flow diagram demonstrating the study identification and screening.

Figure 3 .
Figure 3. Forest plots for the amount of maxillary first molar distalization evaluated on the radiographic images.U6: maxillary first molar; PtV-CC: distance between the pterygoid vertical plane and the center of the crown of the maxillary molar; PtV-MC: distance between the pterygoid vertical plane and the mesial cusp of the maxillary molar; PtV-PRA: distance between the pterygoid vertical plane and the palatal root apex of the maxillary molar; PtV-VMRA: distance between the pterygoid vertical plane and the vestibulomesial root apex of the maxillary molar; SD: standard deviation; CI: confidence interval[32,33,36].

Figure 3 .
Figure 3. Forest plots for the amount of maxillary first molar distalization evaluated on the radiographic images.U6: maxillary first molar; PtV-CC: distance between the pterygoid vertical plane and the center of the crown of the maxillary molar; PtV-MC: distance between the pterygoid vertical plane and the mesial cusp of the maxillary molar; PtV-PRA: distance between the pterygoid vertical plane and the palatal root apex of the maxillary molar; PtV-VMRA: distance between the pterygoid vertical plane and the vestibulomesial root apex of the maxillary molar; SD: standard deviation; CI: confidence interval[32,33,36].

Figure 4 .
Figure 4. Forest plots for the amount of maxillary second molar distalization evaluated on the radiographic images.U7: maxillary second molar; PtV-CC: distance between the pterygoid vertical plane and the center of the crown of the maxillary molar; PtV-MC: distance between the pterygoid vertical plane and the mesial cusp of the maxillary molar; PtV-PRA: distance between the pterygoid vertical plane and the palatal root apex of the maxillary molar; PtV-VMRA: distance between the pterygoid vertical plane and the vestibulomesial root apex of the maxillary molar; SD: standard deviation; CI: confidence interval[32,33,36].

Figure 4 .
Figure 4. Forest plots for the amount of maxillary second molar distalization evaluated on the radiographic images.U7: maxillary second molar; PtV-CC: distance between the pterygoid vertical plane and the center of the crown of the maxillary molar; PtV-MC: distance between the pterygoid vertical plane and the mesial cusp of the maxillary molar; PtV-PRA: distance between the pterygoid vertical plane and the palatal root apex of the maxillary molar; PtV-VMRA: distance between the pterygoid vertical plane and the vestibulomesial root apex of the maxillary molar; SD: standard deviation; CI: confidence interval[32,33,36].

Figure 6 .
Figure 6.Forest plot for the amount of maxillary central incisor protrusion after maxillary molar distalization based on the evaluation of pre-treatment and post-distalization dental models.SD: standard deviation; CI: confidence interval [20,22,23].

Figure 6 .
Figure 6.Forest plot for the amount of maxillary central incisor protrusion after maxillary molar distalization based on the evaluation of pre-treatment and post-distalization dental models.SD: standard deviation; CI: confidence interval [20,22,23].

Table 1 .
(1) PICO questions of this study.The exclusion criteria were(1)participants with congenital abnormalities or systemic pathologies, (2) case reports, (3) conference abstracts, (4) opinions, editorials, guidelines, or letters to the editors, (5) systematic reviews, (6) utilization of TADs or other auxiliaries during molar distalization, (7) molar distalization protocol not described, and (8) inconsistent data within the article and did not receive responses from the corresponding author(s).No language or date restrictions were imposed.The PRISMA flow diagram illustrating the process of obtaining the final included articles is presented in Figure1.
PopulationPatients undergoing orthodontic treatment with clear aligners requiring molar distalization Intervention Molar distalization with sequential distalization protocol of clear aligner therapy ComparisonsThe control is pre-treatment models and radiographsOutcomeThe amount of molar distalization, molar rotation, molar tipping, and anterior anchorage loss achieved during molar distalization with clear aligners J. Funct.Biomater.2024, 15, x FOR PEER REVIEW 3 of 22 distalization/treatment records, (2) participants with permanent dentition, and (3) molar distalization achieved by sequential distalization protocol.

Table 1 .
The PICO questions of this study.

Table 2 .
Risk of bias assessment of the thirteen included studies.⊕: Low risk of bias; ?: medium risk of bias; ⊖: high risk of bias.

Table 4 .
The amount of maxillary molar distalization in millimeters (mm) evaluated on the dental model.The data are reported as mean ± standard deviation.

Table 5 .
The amount of maxillary molar distalization in millimeters (mm) was evaluated on the radiographic images.The data are reported as either mean ± standard deviation or mean [95% confidence interval].

Table 6 .
The amount of maxillary molar rotation in degrees ( • ) during maxillary molar distalization was evaluated on the dental model.The data are reported as mean ± standard deviation.

Table 7 .
The amount of maxillary molar tipping in degrees ( • ) during maxillary molar distalization.The data are reported as either mean ± standard deviation or mean [95% confidence interval].

Table 8 .
The amount of anchorage loss during maxillary molar distalization was evaluated on the dental model.A positive value indicates the protrusion and proclination of the anterior teeth.The data are reported as mean ± standard deviation.

Table 8 .
The amount of anchorage loss during maxillary molar distalization was evaluated on the dental model.A positive value indicates the protrusion and proclination of the anterior teeth.The data are reported as mean ± standard deviation.U1: maxillary central incisor; 2 U2: maxillary lateral incisor; 3 U3: maxillary canine; 4 L1s: mandibular central incisors; *: average and standard deviation calculated based on the individual data of seven patients; & : data from the model integrated into CBCT. 1

Table 9 .
The amount of anterior anchorage loss during maxillary molar distalization was evaluated on the radiographic images.A positive value indicates the protrusion and proclination of the anterior teeth.

Table 10 .
The amount of mandibular molar distalization in millimeters (mm) was evaluated on the radiographic images.The data are reported as either mean ± standard deviation or mean ± standard error (SE).

Table 11 .
The amount of mandibular molar tipping in degrees ( • ) during mandibular molar distalization.The data are reported as either mean ± standard deviation or mean ± standard error (SE).

Table 12 .
The amount of anterior anchorage loss during mandibular molar distalization.A positive value indicates the protrusion and proclination of the incisor; a negative value indicates the retrusion and retroclination of the incisor.The data are reported as either mean ± standard deviation or mean ± standard error (SE).