Adverse Effects of Surgically Accelerated Orthodontic Techniques: A Systematic Review

Evidence on the potential adverse effects of surgically accelerated orthodontic techniques is scarce. The aim of this review was to evaluate the available scientific evidence regarding the adverse effects on periodontium, tooth vitality, and root resorption, associated with these surgical procedures in children, adolescents, and adults. The reporting of this review was based on the PRISMA2020 guidelines. Seven databases and three registers were searched for randomized clinical trials (RCTs) and controlled clinical trials (CCTs) published up to 22 June 2022. Hand searching of the reference lists of the included studies was also performed. The quality of the evidence was assessed with the Cochrane risk of bias and ROBINS-I tools. A total of 887 records were initially screened. Finally, 33 RCTs (713 patients), six CCTs (103 patients), and six ongoing protocols were eligible for this systematic review. The current review indicated that there are no significant adverse effects of surgically accelerated orthodontic techniques on periodontium, root length, or tooth vitality. High-quality clinical trials with less risk of bias should be conducted to allow reliable conclusions regarding the adverse effects of the surgical procedures associated with the acceleration of orthodontic treatment on children, adolescents, and adults.


Rationale
Conventional orthodontic treatment on average requires less than 2 years to complete when fixed appliances are used to treat moderate to severe malocclusion [1]. Prolonged orthodontic treatment may result in several adverse effects, such as pain and discomfort, dental caries, gingival recession, and apical root resorption [2,3]. Shorter treatment time would benefit both children and adult patients, limiting discomfort, and would reduce the prevalence of iatrogenic adverse side effects [4][5][6][7]. Hence, orthodontists and patients alike are interested in techniques that can accelerate tooth movement and reduce treatment time [8].
Several methods to accelerate orthodontic tooth movement (OTM) have been proposed in order to shorten the orthodontic treatment, including specific bracket types [9], pharmacological approaches, such as the use of prostaglandins, interleukins, leukotrienes, vitamin D and platelet-rich plasma [10], photobiomodulation [11], and low-intensity laser irradiation [12]. According to research, surgical procedures have the best potential reduction in treatment time yet are limitedly applied due to their aggressiveness [13].
In 1959, corticotomy-assisted orthodontic treatment (CAOT) was introduced as an intervention to accelerate tooth movement [14]. The acceleratory impact of corticotomy was associated with a demineralization/remineralization process called the regional accelerated

Search Strategy
The systematic search was conducted by two examiners (I.P., A.X.) using appropriate medical subject headings (MeSH) and free text words. The search was restricted to articles written in the English language and published from January 2006-June 2022. Details of the complete electronic search strategy are provided in Supplementary Table S1. ScienceDirect was used as an adjunctive search database to identify additional eligible studies with the first 100 relevant results to be considered for inclusion. A partial grey literature search was conducted by using Google Scholar and was limited to the first 100 most relevant articles. Studies from grey literature, defined as theses, dissertations, and unpublished studies were retrieved through ClinicalTrials.gov, Open Grey, and the ISRCTN registry. The reference lists of selected articles and relevant reviews were screened for any possible related studies which may have not been discovered by the electronic search.

Study Selection
The studies retrieved from all databases and registers were cross-checked for duplicates. The study selection was accomplished in two phases. In the first phase, two reviewers (I.P., A.X.) independently screened the titles and abstracts which were identified by all electronic databases regarding accelerated orthodontic techniques and their side effects. In case of disagreement on which articles to screen with the full text, a consensus was reached by discussion. If necessary, the final decision was made after consultation with a third reviewer (A.M.). In the second phase, full-text articles were assessed independently by two reviewers (I.P., A.X.) for inclusion. Any disagreement concerning full text inclusion was resolved with discussion and, if necessary, with the consultation of the third reviewer (A.M.) until consensus was reached.

Data Collection and Data Items
The same two review authors (I.P., A.X.) collected the data independently in a customized and pre-defined data extraction table. Extracted data were compared, and in case of discrepancies, a consensus was reached through discussion and the re-examination of the studies. The data extraction form included the following items: general information (authors' names, publication year, and study setting); methods (study design, treatment comparison groups, and outcome assessment method); participants (sample size, gender, age, and malocclusion characteristics); intervention (type, site, and technical aspects of intervention); accelerated orthodontic aspects (details of surgical techniques, alveolar bone augmentation procedures and materials, type of movement, appliance characteristics and biomechanics and orthodontic adjustments' frequency, and follow-up time) and outcomes (outcomes stated, outcome measurements' methods).

Risk of Bias Assessment in Included Studies
The quality assessment of the included studies was carried out by two reviewers (I.P., A.X.) independently, using the revised Cochrane Risk of Bias (RoB 2.0) tool for randomized trials [32] and Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool for non-randomized trials [33]. In case of disagreement, the two authors thoroughly discussed until a consensus was reached. The overall judgment of the risk of bias (low, some concerns, high in RoB 2.0; low, moderate, serious, critical, no information in ROBINS-I) for each study was dictated by the highest RoB level in any of the domains that were assessed.

Effect Measures and Data Synthesis
The primary outcome of this systematic review was to investigate the effect of the surgical techniques used to accelerate orthodontic tooth movement on periodontal tissues, root length, and tooth vitality. Variables extracted from each article were the following: author and year of publication, study design, sample size, intervention type, treatment comparison, outcome assessment method, outcome of results, and follow-up time.
A detailed narrative description of the findings (qualitative data analysis) was preplanned to be employed if significant clinical and methodological heterogeneity of the included studies was detected.

Study Selection
In total, 887 records were retrieved from the seven databases and three registers. A total of 31 records were identified through citation searching. Duplicate references were removed, and a total of 448 articles were thoroughly screened. The titles and abstracts were assessed for eligibility, followed by the elimination of all papers not fulfilling the inclusion criteria. Seven records could not be retrieved for full-text evaluation and were removed. Therefore, 225 potentially related trials (205 articles and 20 registry entries for ongoing studies) remained for further examination. After reviewing the full-text articles and in line with the inclusion and exclusion criteria, 171 completed studies and 14 ongoing studies were excluded. More information about the studies that potentially could meet the inclusion criteria, but were excluded, can be found in Supplementary Table S2. Finally, 39 articles and 6 potentially eligible ongoing studies were included for qualitative analysis. A PRISMA2020 flow diagram is shown in Figure 1 [30]. 39 articles and 6 potentially eligible ongoing studies were included for qualitative analysis. A PRISMA2020 flow diagram is shown in Figure 1 [30].
From the six RCT protocols for ongoing studies, one tested lasercision, two investigated the effect of piezocision, one tested MOPs, one evaluated both corticotomy and piezocision, and one studied the effects of both MOP and lasercision. Further information concerning these ongoing research projects is presented in Appendix A Table A2.
From the six RCT protocols for ongoing studies, one tested lasercision, two investigated the effect of piezocision, one tested MOPs, one evaluated both corticotomy and piezocision, and one studied the effects of both MOP and lasercision. Further information concerning these ongoing research projects is presented in Appendix A Table A2.

Risk of Bias within Studies
Risk of bias assessments for the included studies are summarized in Appendix A  Tables A3 and A4 and Supplementary Tables S4 and S5.
Using the ROBINS-I tool, the overall risk of bias for the six CCTs [22,[67][68][69][70][71] was judged as being at serious risk. The most severely impacted domains were undetected confounding and classification of interventions, while the risk of systematic discrepancies in the measurement of outcomes also could not be overlooked.
Quantitative data synthesis (meta-analysis) was not conducted due to the heterogeneity of the studies. Therefore, qualitative data analysis was conducted in this review.

Description of Interventions
A corticotomy procedure includes full-thickness flaps elevation, the selective decortication of the buccal and lingual interdental bone to be moved, closure, and suturing the flaps. Only the cortical bone is penetrated or mechanically altered in a controlled surgical approach, and at the same time, the bone marrow is perforated minimally. A modification of this technique is periodontally accelerated osteogenic orthodontics (PAOO) utilizing bone grafts.
Minimally invasive alternatives that create interradicular cuts below each interdental papilla without flap elevation are the following: (a) corticision, where a surgical scalpel and mallet are used to create the cortical bone incision, (b) piezocision utilizing a piezosurgery knife, and (c) lasercision carried out with an Er,Cr:YSGG laser for soft tissue vertical incision in the buccal surface, and the hard tissue laser Er:YAG. for each alveolar perforation.
An additional minimally invasive technique included in the present review is microosteoperforations (MOPs), where surgical holes are drilled into the cortical bone using a Propel device, a surgical drill, or mini-implants.

Results of Individual Studies Periodontal Evaluation
The periodontal parameters that were examined throughout the included studies were indices (probing depth, gingival index, plaque index, papillary bleeding index, periodontal index), attachment loss, gingival recession, gingival bleeding, the width of attached gingiva, bone density, alveolar bone height/level, bone width, dehiscence, fenestration, furcation defect, mobility scores, and gingival scar formation. Most of the studies [22,34,35,38,40,41,43,[48][49][50]53,54,[57][58][59]61,62,66,67,71] that assessed the adverse effects on the periodontium concluded that there were statistically insignificant differences between the experimental and control groups or even within the groups pre-and postoperatively. No significant differences in the probing depth were found between the study groups in a trial by Bahammam et al.; nonetheless, there was a slight improvement in the probing depth values [42]. Sirri et al. reported an increase in the probing depth, the gingival index, the plaque index, and the width of the attached gingiva. However, these changes were not statistically significant between the corticision and control groups [43].
A clinical trial by Khlef et al. compared corticotomy and flapless corticotomy using piezotome (piezocision) and found significant differences between both groups in gingival, papilla bleeding, and plaque indices, before and after orthodontic treatment [48]. Singh and Jayan demonstrated a statistically significant difference in the probing depth, plaque, and gingival indices between the experimental and control groups, with better results shown in the first group following PAOO [39].
Both studies by Charavet et al. observed scar formations in over 50% of the patients in the piezocision group. Significant increases in dehiscence or fenestration in the piezocision and control groups were not recorded [49,50]. On the other hand, according to Agrawal et al., root dehiscence was present at 40% and 30% of the sample after corticotomy and MOP procedures, respectively [65].
Interestingly, Shoreibah et al., while performing PAOO, observed a net increase of approximately 25% in bone density in the group where bone grafting was applied [36]. Bahammam et al. reported a greater increase in bone density in both experimental groups utilizing different bone grafts in comparison with the control group [42]. Singh and Jayan observed that after bone graft placement, the PAOO group presented better results in the probing depth and the gingival and plaque index [39]. However, one trial suggested a significant increase in bone thickness after performing MOPs and corticotomy even without the use of bone grafting [65].
As far as the alveolar bone level is concerned, Raj et al. compared piezocision and conventional orthodontics and reported a greater increase in buccal and mesial bone on the experimental side [51]. However, a statistically significant decrease in the alveolar bone level on the distal surface of the MOPs group was found by Thomas et al. while comparing MOPs and conventional orthodontics. In the same study, a statistically significant increase in probing depth was noted by the end of the trial in both groups [64].
The study of Abdelqader evaluated the effect of corticotomy and corticision on the root length and concluded at significant canine root resorption in both groups [44]. However, the difference between both interventions was non-significant.
Two trials compared the root resorption after the first premolar extraction between the conventional treatment and piezocision [51,52]. The study of Raj reported significant canine root resorption on the control and experimental sides after an observation period of 6 months [51]. Hartom et al. showed statistically significant root resorption after the completion of en masse retraction in both groups. Only the right and left central incisors and right canine presented statistically significantly (p < 0.05) more root resorption in the control group compared to the Piezo group (0.09 ± 0.39, 1.00 ± 0.53, and 1.03 ± 0.63, respectively) [52].
One split-mouth trial that calculated the root length before and after canine retraction using CBCT scans did not report any differences between MOPs or conventional orthodontic treatment (p > 0.05) [56]. In the same study, a second comparison was conducted between piezocision and conventional orthodontic treatment. Overall, this study drew the conclusion that piezocision resulted in a significant decrease in canine root length in comparison with both the MOP and control sides after canine retraction (p < 0.05). Among the six non-randomized trials, only two of them evaluated root resorption following surgically accelerated orthodontic techniques [69,70]. Chan et al. concluded greater root resorption of 42% on the MOP side compared with traditional orthodontic treatment (MOP: Mean ± SD = 0.576 ± 0.219 mm 3 , Control: Mean ± SD = 0.406 ± 0.168 mm 3 , p < 0.001) [69]. The second study [70] tested piezocision against the control and concluded that the piezocision sides presented significantly greater root resorption (p < 0.05). In the included studies, there was no reported evidence of the effects of lasercision on the root length.

Tooth Vitality
Three randomized [40,47,54] and three non-randomized trials [22,67,71] analyzed the influence of surgically accelerated orthodontic techniques on tooth vitality. Three of them compared corticotomy with conventional orthodontic treatment [47,67,71], two studies investigated piezocision, and one study performed lasercision. All these studies revealed no loss of tooth vitality in any of the examined groups.
According to the present results, evidence of significant adverse effects on periodontium, root resorption, and pulp vitality is scarce. A meta-analysis of the combined data was not feasible due to the dissimilarities of the retrieved trials. Further research with a sufficiently low risk of bias is required.

Summary of Evidence
Recent evidence suggests that surgically accelerated orthodontic techniques may provide an effective option for shorter orthodontic treatment duration [7,13,24,28]. The orthodontic community has shown great interest in these techniques, which can be inferred from the increasing number of clinical trials in this domain. In the current systematic review, strict eligibility criteria were established to evaluate the effects of surgically accelerated orthodontic techniques on periodontium, root length, and pulp vitality. We investigated 39 randomized and controlled clinical trials that were eligible, with a total of 816 participants.
Most of the studies that assessed periodontal parameters post-surgically did not report deleterious effects [22,34,35,38,40,41,43,44,[48][49][50]53,54,[57][58][59]61,62,66,67,71]. This is in agreement with the findings of several systematic reviews that concluded that the surgically accelerated procedures do not impose a serious risk of harm on periodontal tissues, tooth vitality, and root resorption [24][25][26]28]. The surgical techniques implemented in these reviews were only corticotomy, piezocision, and MOPs. However, a Cochrane review concluded that the data regarding the impact of corticotomy and corticision on periodontal parameters were not clearly reported [7]. In contrast with the already existing systematic reviews, our review evaluates all types of surgically accelerated techniques and their adverse effects, leading to comprehensive results.
Aboul-Ela et al. observed significantly greater gingival index scores on the corticotomy side in comparison with the non-operated side after 4 months [34]. Similar results are reported in two systematic reviews on corticotomy for accelerated orthodontic treatment. They found not only increased gingival index scores at the surgical side 4 months post-operatively but also various complications, such as pain, swelling, subcutaneous hematomas of the face and neck, and dentinal hypersensitivity [24,26].
Piezocision appears to be a promising treatment alternative for accelerated orthodontic tooth movement with no significant periodontal problems [40,[47][48][49][50]53,54,59]. In line with our study, a review by Nimeri et al. also did not report evidence of statistically significant periodontal damage after piezocision, and they concluded that it is the least invasive surgical procedure with excellent clinical and aesthetic outcomes [13].
Three of the studies included in the present review compared changes in bone density following corticotomy with and without the application of bone grafts [35,36,42]. Their findings appear to be consistent with the results of Wilcko et al. showing that corticotomy surgery and alveolar augmentation is a safe method and contributes to enhancing the pre-treatment alveolar bone [15]. Even though some studies assessed bone density before and after corticotomy procedures, the number of participants in each study was limited, and their assessment methods varied significantly since different software was used [35,36,42]. Furthermore, these observations were not confirmed by any form of histological examination, and there was no long-term follow-up.
The greater percentage of root dehiscence described in both groups in the study of Agrawal et al. might be attributed to thin buccal bone, implying that this anatomical variation should be considered prior to surgery [65]. The scar formation after piezocision was described in two studies [49,50]. Additional care, namely, sutures, should be provided to patients with high smile lines when this procedure is implemented. However, piezocision may be contraindicated in these patients due to aesthetic issues [50].
Studies implementing piezocision and MOPs reported a high risk of root resorption [51,52,56,69,70]. Furthermore, mild root resorption was demonstrated by Shoreibah et al. [35] in the corticotomy group compared to the control group between the pre-surgical and the 6-month post-surgical values. Nevertheless, the study employed periapical radiographs to measure root resorption, which leads to questionable conclusions, due to the two-dimensional limitations and low accuracy of this assessment method.
Two trials used microtomography to detect root resorption. They reported significantly greater root resorption in areas that underwent MOP [69] and piezocision [70]. However, serious limitations were identified in these experiments regarding the design, due to allocation bias. Moreover, these results should be verified in patients under comprehensive orthodontic treatment since the follow-up period in these trials was only 4 weeks.
Root resorption is a three-dimensional phenomenon, and its extent can be accurately measured with CT and CBCT imaging, which have shown high sensitivity and excellent specificity. Using CBCT to measure external apical root resorption provides reliable results and eliminates the errors produced when two-dimensional radiographs are used [56]. Three studies [41,49,50] investigated root resorption with CT or CBCT and detected no significant difference between the groups. However, another CBCT study reported significantly greater root resorption in both the corticotomy and corticision groups at 5 months [45].
One study [70] reported that piezocision may lead to iatrogenic root damage during surgery when applied in proximity to neighboring roots. Hence, caution should be taken when piezocision is implemented to accelerate tooth movement.
Tooth vitality was briefly assessed in a few studies [22,40,47,54,67,71] and they did not report any case of loss of tooth vitality. However, comparisons between the studies were not achievable due to the different assessment methods that were implemented.

Limitations
Overall, the majority of the included RCTs studies presented a risk of bias of some concerns with inadequate sample size, missing information about randomization, alloca-tion concealment, and the blinding of the outcome assessors. All the included CCTs were considered as being at serious risk of bias due to confounding, intervention assignment affected by knowledge of the outcome, limited information on the blinding of the outcome assessors, and selective outcome reporting. In addition, a long-term follow-up of the response of periodontal tissue, root resorption, and pulp vitality to these surgically accelerated orthodontic procedures was lacking. More than half of the included studies had a split-mouth design that is likely to give biased results if the effect is carried across to the other side of the arch. Bone grafts may also act as a confounding factor. Language restrictions might be an additional limitation. Hence, the results of this systematic review should be taken into careful consideration.
The heterogeneity of the studies mainly concerning the type of outcome assessed and the applied surgically accelerated intervention did not allow a balanced comparison between the results of the included studies, and, therefore, conducting a meta-analysis was not possible.

Conclusions
Although no major adverse effects following surgically assisted accelerated orthodontic techniques were reported in the available body of literature, currently, there is no scientific evidence to support the presence or absence of clinically meaningful post-operative periodontal side effects, root resorption, and loss of tooth vitality. The results of the present systematic review should be interpreted with caution due to the inadequate sample of participants, short-term follow-up, and unclear safety.
Before these techniques can be proposed in daily clinical practice, reliable conclusions should be provided from further research on their safety. Thus, there is a need for high-quality studies conducted with additional attention paid to increased sample size, improvements in the randomization of participants, the allocation concealment and blinding of the outcome assessments, the follow-up period, the adopted surgical protocol, the type of surgically accelerated orthodontic techniques, the type of examined adverse effects, and the outcome measurement methods.

Supplementary Materials:
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/children9121835/s1, Table S1: Electronic Search Strategy. Table S2: Excluded studies and the reasons beyond exclusion. Table S3: Extracted data of included studies in the systematic review. Table S4: Detailed assessment of included randomized studies with the RoB 2.0 tool. Table S5: Detailed assessment of included non-randomized studies with the ROBINS-I tool.

Conflicts of Interest:
The authors declare no conflict of interest.

Abbreviations
RCTs: randomized clinical trials, CCTs: controlled clinical trials, OTM: orthodontic tooth movement, CAOT: corticotomy assisted orthodontic treatment, RAP: regional accelerated phenomenon, MOPs: micro-osteoperforations, PRISMA: preferred reporting items for systematic reviews and meta-analyses, PAOO: periodontally accelerated osteogenic orthodontics, SD: standard deviation, CT: computed tomography, CBCT: cone beam CT.       Six months post-treatment, both groups showed a decrease in PD, which was non-significant. No statistically significant difference in BD between the two groups from baseline to six months post-treatment.