Systematic Review: Is High-Energy Laser Therapy (HELT) With Flapless Corticotomy Effective in Accelerating Orthodontic Tooth Movement?

The objective of this review was to critically and systematically appraise the available evidence regarding the effectiveness of high-energy laser therapy (HELT) with flapless corticotomy in accelerating orthodontic tooth movement and the associated untoward effects. We searched eight databases electronically in August 2021: PubMed®, Medline®, Google Scholar, Cochrane Library, Scopus®, Web of Science™, Trip, and PQDT OPEN from ProQuest. Another search was done in the reference lists of the included studies. Randomized controlled trials (RCTs) were included in which patients had received fixed orthodontic treatment combined with HELT-assisted corticotomy in comparison with traditional orthodontic treatment. Cochrane’s risk of bias (RoB2) tool was used to assess the risk of bias. Five RCTs and one CCT were included in this review (155 patients). The HELT-based corticotomy around the upper canines led to a greater canine retraction at the first and second months (P < 0.001). In the third month, no statistically significant differences were noticed. In one RCT focusing on incisor intrusion, the irradiated upper incisors showed a greater intrusion speed than that of the control group (4.587 mm in 59 days vs. 3.78 mm in 95.8 days, respectively). No significant side effects associated with the application of HELT were reported. According to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, the quality of evidence supporting these findings was low to moderate. Although the acceleration of tooth movement appeared to be significant at least in the first two months, there was low to moderate evidence concerning the efficacy of HELT-based flapless corticotomy in the acceleration of orthodontic tooth movement. There is a need for more well-conducted high-quality RCTs.


Introduction And Background
Traditional orthodontic treatment for moderate to severe malocclusions usually takes several years when fixed appliances are used [1], and this can reduce patient compliance and cause multiple side effects [2]. A lot of subjects, particularly adults, refuse orthodontic treatment since it takes extended treatment time, especially if fixed appliances are used, which may have a negative impact on their daily life [3]. Thus, accelerating orthodontic treatment is a primary concern for both patients and clinicians.
In an attempt to accelerate orthodontic tooth movement, several approaches have been studied, including surgical approaches, such as corticotomy [4], distraction osteogenesis [5], and corticision and piezocision [6], and non-surgical approaches such as low-intensity laser irradiation, resonance vibration, pulsed electromagnetic fields, electrical currents, and biological approaches [7].
Dental lasers are generally divided into high-energy laser and low-level laser devices [8]. High-energy laser treatment (HELT) has a power output greater than 500 mW and can be used for cutting soft and hard tissues. Its energy ranges from hundreds to thousands of watts per square centimeter [8] such as neodymium-doped yttrium aluminum garnet (Nd: YAG) laser, argon laser, carbon dioxide (CO2) laser, erbium-doped yttrium aluminum garnet (Er: YAG) lasers, and the erbium-chromium yttrium scandium gallium garnet (Er, Cr: YSGG) lasers. High-energy laser therapy (HELT) is widely used in dentistry; it is used in caries removal, bacterial reduction during endodontic therapy, treatment of dentinal hypersensitivity, periodontal therapy, gingivectomy, and bone and soft tissue ablation [9]. In orthodontics, HELT has been shown to be effective in preventing enamel demineralization [10], preparation of surfaces for bracket bonding [11], debonding of ceramic brackets [12], and accelerating tooth movements [13].
Recently, HELT has been suggested to be used in performing alveolar corticotomy to induce the so-called 'regional acceleration phenomenon' (RAP) [13][14]. Erbium lasers can be used to perform flapless corticotomy due to their ability to ablate soft and hard tissues with minimal damage [15]. Therefore, they offer an alternative drilling modality to piezocision and conventional bur to drill holes, cut bone with minimal thermal damage, and have precise control of bone-cutting [16]. This causes transient demineralization and increases the activity of cells that accelerate tooth movement [17]. Therefore, it is considered one of the minimally invasive surgical methods of acceleration [13], whereas the low-level laser therapy (LLLT), which is considered one of the physical methods of acceleration, has been shown to affect bone remodeling by stimulating osteoclast, osteoblast, and fibroblast propagation, thereby accelerating orthodontic tooth movement [18].
Despite the importance of high-energy laser therapy and its widespread use in medical centers and teaching hospitals, few clinical trials have evaluated its efficacy as an adjunctive procedure for conducting corticotomies for accelerating tooth movement [13]. There are more than 10 systematic reviews and traditional reviews about the effectiveness of the LLLT in accelerating tooth movement [19][20], whereas, surprisingly, there is no single systematic review evaluating the effectiveness of high-energy laser therapy with flapless corticotomy in accelerating orthodontic tooth movement. Thus, the purpose of this systematic review was to critically and systematically appraise the existing evidence concerning the effectiveness of high-energy laser therapy in accelerating orthodontic tooth movement and the associated untoward effects with this procedure.

Materials and methods
A scoping PubMed search was performed to confirm the existence of similar systematic reviews and to investigate potentially relevant papers prior to writing the final systematic review protocol. No systematic review was found in the literature evaluating the effectiveness of high-energy laser therapy with flapless corticotomy in accelerating orthodontic tooth movement.

Eligibility Criteria
Exclusion and inclusion criteria were established according to the PICOS (Participants, Interventions, Comparisons, Outcomes, and Study design) framework: Study design: Randomized controlled trials (RCTs) of any design: parallel-group design, split-mouth design, or compound design (two or more parallel-group designs with a split-mouth design in each group) and nonrandomized controlled trials (CCTs) were included, without time-of-publication or language restrictions.
Participants: Healthy patients of all ages and malocclusions, both males and females, of all ethnic groups who received orthodontic treatment using a fixed orthodontic appliance were included.
Type of interventions: All types of treatment using fixed orthodontic appliances (with or without extraction) assisted by HELT-based corticotomies for accelerating orthodontic tooth movement were included.
Comparisons: Patients receiving traditional orthodontic treatment (without additional procedure to accelerate tooth movement) using fixed orthodontic appliances (with or without extraction).
Outcomes: The primary outcome was the rate of orthodontic tooth movement (RTM) or any measure indicating the effectiveness of high-energy lasers in accelerating teeth movements (i.e. treatment time, retraction time, the net of tooth movement, etc.). The secondary outcomes were patient-reported outcomes (pain, discomfort, alteration in mastication, other experiences, and satisfaction), loss of anchorage, and unwanted tooth movements. In addition, the other secondary outcomes were gingival and periodontal problems (gingival recession, loss of attachment, depth of probing, bone resorption), iatrogenic harm to teeth (vitality loss, root resorption), or stability of treatment in the long term.

Search Strategy
The following databases were electronically searched in August 2021: PubMed®, Medline®, Google Scholar, Cochrane Library databases, Scopus®, Web of Science™, Trip, and PQDT OPEN (to identify dissertations and theses).
The following terms and their derivatives were used: (Orthodontic) AND (Acceleration) AND (high-energy laser). Table 1 shows the details of the electronic search strategy. Another search in the reference lists of the included studies was done for any possible related paper that may have not been discovered by the electronic search.

Cochrane
Library) #1 orthodontic* OR "Tooth movement" OR "orthodontic tooth movement" OR "Tooth displacement " OR "orthodontic Treatment" OR "orthodontic Therapy" #2 accelerat* OR rapid* OR short* OR speed* OR fast OR velocity OR duration OR rate OR time OR "regional accelerated phenomenon" OR RAP. #3 laser OR high intensity laser therapy OR HELT OR hard laser OR high-energy laser OR Erbium lasers OR Er: YAG laser OR Er,Cr:YSGG laser OR CO2 laser OR Nd:YAG laser. #4 laser-assisted corticotomy OR lasersicion OR laserassisted* OR laser induced* OR laser decortication. #5 #3 OR #4 #6 #1 AND #2 AND #5 PubMed #1 orthodontic* OR "Tooth movement" OR "orthodontic tooth movement" OR "Tooth displacement " OR "orthodontic Treatment" OR "orthodontic Therapy" #2 accelerat* OR rapid* OR short* OR speed* OR fast OR velocity OR duration OR rate OR time OR "regional accelerated phenomenon" OR RAP. #3 laser OR high intensity laser therapy OR HELT OR hard laser OR high-energy laser OR Erbium lasers OR Er: YAG laser OR Er,Cr:YSGG laser OR CO2 laser OR Nd:YAG laser. #4 laser-assisted corticotomy OR lasersicion OR laserassisted* OR laser induced* OR laser decortication. #5 #3 OR #4 #6 #1 AND #2 AND #5 Google Scholar #1(orthodontic OR "Tooth movement") AND (accelerate OR acceleration OR accelerating OR duration OR rate) AND (laser OR high intensity laser therapy OR HELT OR hard laser OR high-energy laser OR Erbium lasers OR Er: YAG laser OR Er,Cr:YSGG laser OR CO2 laser OR Nd:YAG laser) #2 (orthodontic OR "Tooth movement") AND (accelerate OR acceleration OR accelerating OR duration OR rate) AND (laser-assisted corticotomy OR lasersicion OR laser-assisted* OR laser induced* OR laser decortication) Scopus #1TITLE-ABS-KEY (orthodontic* OR "Tooth movement" OR "orthodontic tooth movement" OR "Tooth displacement "OR "orthodontic Treatment" OR "orthodontic Therapy"). #2 TITLE-ABS-KEY (accelerat* OR rapid* OR short* OR speed* OR fast OR velocity OR duration OR rate OR time OR "regional accelerated phenomenon" OR RAP) #3TITLE-ABS-KEY (laser OR high intensity laser therapy OR HELT OR hard laser OR high-energy laser OR Erbium lasers OR Er: YAG laser OR Er,Cr:YSGG laser OR CO2 laser OR Nd:YAG laser). #4 TITLE-ABS-KEY (laser-assisted corticotomy OR lasersicion OR laser-assisted* OR laser induced* OR laser decortication). #5 #3 OR #4 #6 #1 AND #2 AND #5 Web of Science #1TS= (orthodontic OR "Tooth movement" OR "orthodontic tooth movement" OR "Tooth displacement "OR "orthodontic Treatment" OR "orthodontic Therapy"). #2TS= (accelerat* OR rapid* OR short* OR speed* OR fast OR velocity OR duration OR rate OR time OR "regional accelerated phenomenon" OR RAP). #3TS= (laser OR high intensity laser therapy OR HELT OR hard laser OR high-energy laser OR Erbium lasers OR Er: YAG laser OR Er,Cr:YSGG laser OR CO2 laser OR Nd:YAG laser). #4 TS= (laser-assisted corticotomy OR lasersicion OR laser-assisted* OR laser induced* OR laser decortication). #5 #3 OR #4 #6 #1 AND #2 AND #6 PQDT OPEN #1(orthodontic OR "Tooth movement") AND (accelerate OR acceleration OR accelerating OR accelerated OR rapid OR speed OR fast OR quick OR velocity OR duration OR rate OR time OR "regional accelerated phenomenon" OR RAP) AND (laser OR high-intensity laser therapy OR HELT OR hard laser OR high-energy OR laser OR Erbium lasers OR Er: YAG laser OR Er,Cr:YSGG laser OR CO2 laser OR Nd:YAG laser) #2 (orthodontic OR "Tooth movement") AND (accelerate OR acceleration OR accelerating OR accelerated OR rapid OR speed OR fast OR quick OR velocity OR duration OR rate OR time OR "regional accelerated phenomenon" OR RAP) AND (laserassisted corticotomy OR lasersicion OR laser-assisted* OR laser induced* OR laser decortication) Trip (orthodontic OR "Tooth movement") AND (accelerate OR acceleration OR accelerating OR accelerated OR rapid OR speed OR fast OR quick OR velocity OR duration OR rate OR time OR "regional accelerated phenomenon" OR RAP) AND (laser OR high-intensity laser therapy OR HELT OR hard laser OR high-energy OR laser OR Erbium lasers OR Er: YAG laser OR Er,Cr:YSGG laser OR CO2 laser OR Nd:YAG laser OR laser-assisted corticotomy OR lasersicion OR laser-assisted* OR laser induced* OR laser decortication)

Study Selection and Data Extraction
Two reviewers (RIS and MYH) independently assessed the articles for suitability according to the selection criteria; a third reviewer (GM) was asked to decide in case of disagreement. Initially, the titles and abstracts of articles were checked by the two reviewers during the search by using the eligibility criteria. Then, the same two reviewers evaluated the full text of all articles that might be included in the review or if the title or summary was ambiguous to reach a clear judgment. If any article did not fulfill one or more of the eligibility criteria, it was discarded from the review. Finally, the same two authors (RIS and MYH) conducted data extraction in the piloted and predefined data extraction tables. The data extraction sheet contained the following elements: general information (author's name, publication year, and place of study); method (study design, comparison group); participants (sample size (Male/Female), mean age, malocclusion); interventions (type of laser, type, and site of intervention); outcomes (primary and secondary outcomes); and results (the main finding). Other information about orthodontic aspects (appliance characteristics and biomechanics, anchorage tools, frequency of orthodontic adjustments, follow-up time, methods of outcome measurements) was also included.

Assessing the Risk of Bias of the Included Studies
The two reviewers (RIS and MYH) independently assessed the risk of bias of all included studies using Cochrane's risk of bias tool for randomized trials (RoB2) and the risk of bias in non-randomized studies of interventions (ROBINS-I) tool for non-randomized controlled trials [21][22]. Then, the judgments of both reviewers were compared, a third reviewer (GM) was asked to decide in case of disagreement and could not reach a consensus by discussing. For randomized trials, the following fields were judged as having a high, low, or unclear risk of bias: Randomization process, Deviations from intended interventions, missing outcome data, Measurement of the outcome, Selection of the reported result. Then, the overall risk of bias for each trial was reported according to the following criteria: low risk of bias was reported if all fields were assessed as having a low risk of bias; moderate risk of bias was reported if one or more fields were assessed as having an unclear risk of bias; high risk of bias was reported if one or more fields were assessed as being at high risk of bias.

Literature Search Flow and the Retrieved Studies
A total of 2780 references were found in the electronic search. Five hundred ninety-seven citations were carefully checked after duplicate references were removed. The titles and abstracts were checked for eligibility and all papers that did not meet the selection criteria were discarded. As a result, six studies were left for full-text assessment. No studies were excluded. Finally, six studies were included in the systematic review [13,16,18,[23][24][25]. Figure 1 shows the Preferred Reporting Items for Systematic Reviews (PRISMA) flow diagram.

Characteristics of the Included Studies
An overview of the characteristics of the six included studies is given in Table 2. Out of the six included trials, five were RCTs. However, the designs of these studies were not similar. One RCT was a parallel-group design with a control group of non-accelerated tooth movement [18], two RCTs were compound trials (twoarm parallel-group design with a split-mouth design for each arm [13,23], and the last two RCTs had a splitmouth design [24][25]. In addition, the only CCT in this systematic review also had a split-mouth design [16]. All of these studies were written in English. All of the studies included males and females without any gender preference. Patient ages ranged between 16.9±2.5 and 21.7 years, noting that the study of Al-Jundi et al. did not mention the mean age of its patients [18].  Extraction treatment (maxillary first-premolar extraction followed by a canine retraction) was performed in five studies [13,16,[23][24][25], and only one study evaluated the effect of HELT-based flapless corticotomy on upper incisors' intrusion; it was a non-extraction-based study [18].
A pre-adjusted orthodontic appliance (MBT 0.022 × 0.028-inch slots) was used in the five trials to investigate the effects of HELT on tooth movement [13,18,[23][24][25]. The sixth study by Salman and Ali did not report any information about the type and prescription of brackets [16]. The canine retraction was done using a nickeltitanium closed-coil spring, which applied 150 g force, in three studies [13,23,25]. Jaber et al. used elastic chains that extended from canine brackets to the first molars bands, with 150 g force to retract canines [24]. The upper incisors intrusion was commenced using 0.016 × 0.022-inch stainless steel archwire with T-loops, which applied a constant force of 50 grams on each side in the Al-Jundi et al. trial [18]. Of note, the study by Salman and Ali was lacking this information [16].
The primary outcome was the rate of canine movement in three studies [13,[24][25], the net canine movement in one study [16], and the time of teeth movement in one study [18]. However, the primary outcome in the sixth study of Alfawal et al. [23] was a secondary outcome in the current review (i.e., patient-centered outcomes associated with upper canine retraction). The secondary outcome, such as pain, was evaluated in four studies [18,[23][24][25]. Anchorage loss and undesirable tooth movements were evaluated in two studies [13,25], and periodontal problems were evaluated in two studies [16,25].
The follow-up lasted until the completion of the intended tooth movement in four studies and ranged from two to four months [13,18,[23][24], whereas Mohmoudzadeh M et al. followed up the patients for one month only [25]. Finally, the trial of Salman and Ali followed the recruited patients for only six weeks [16]. The included studies were published from 2014 to 2021.

Risk of Bias in the Included Studies
The summary of the overall risk of bias of the included RCTs is shown in Figures 2-3. The five RCTs were at unclear risk of bias, whereas the only CCT was also at moderate risk of bias. The five included RCTs adequately addressed sequence generation (randomization). For blinding, only the outcome assessor's blinding was possible in these studies because the included patients and the investigators could not be blinded regarding the surgical intervention performed. For missing data and selective reporting bias, all studies were at low risk of bias. More information about the risk of bias assessment, along with the reasons supporting each assessment can be found in Appendices 1 and 2.

Effects of Interventions
Primary outcome: Rate of tooth movement. Out of the six included trials, four trials assessed the effect of erbium lasers on canine retraction speed after premolar extraction [13,16,[24][25], the fifth trial evaluated the effect of Er: YAG laser on the incisors intrusion rate in a non-extraction treatment [18]; Table 3 and Appendix 3.  The effect of erbium lasers in accelerating upper canine retraction: three split-mouth trials [16,[24][25] and one compound trial [13] assessed the efficacy of erbium lasers in accelerating upper canine retraction. Noteworthy, the results could not pool in a meta-analysis because of the differences in the way of orthodontic force delivery, types and parameters of lasers, and laser application protocol.   [13,[24][25]) and one level for indirectness* b Decline one level for risk of bias (unclear risk of bias of deviations from intended intervention in [13,24]), one level for indirectness*, and one level for imprecision** c Decline one level for risk of bias (unclear risk of bias of deviations from intended intervention in [18]), one level for indirectness*, and one level for imprecision**.

Study
d Decline one level for risk of bias (unclear risk of bias of deviations from intended intervention in [18,[23][24][25]), one level for indirectness*, and one level for imprecision**.
e Decline one level for risk of bias (unclear risk of bias of deviations from intended intervention in [13,25]), one level for indirectness*, and one level for imprecision**.
f Decline two levels for risk of bias (moderate risk of bias in classification of interventions [16], unclear risk of bias of deviations from intended intervention [25]), one level for imprecision**, and one level for indirectness*.
*Outcome is not directly related; the included trials involved only adult patients, so the efficacy of Er: YAG radiation could not be confirmed on adolescent patients. Also, patient-centered outcomes were very limited. The study by Salman and Ali also found that the canine in the laser side moved twice the amount of that in the control side after six weeks of observation [16]. Two trials assessed the cumulative maxillary canine movement following the first-premolar extraction with two months observation period [13,24], comprising 70 left and right canines. There was a greater canine retraction (1.25±0.30, 0.40±0.18 mm, respectively) in the laser-assisted flapless corticotomy group (p< 0.001). According to GRADE, the quality of evidence supporting this outcome was low ( Table 4).
The degree of retraction at the third month was assessed by two trials [13,24], comprising 70 canines. The retraction rate on the experimental side was almost equal to its rate on the control side (p=0.220, p=0.427, respectively). According to GRADE recommendations, the strength of evidence supporting this outcome was low ( Table 4).
Effect of Er: YAG laser in accelerating upper incisors intrusion. One trial conducted by Al-Jundi et al. evaluated the acceleratory effect of using the Er: YAG laser in flapless corticotomy at the anterior regions of the maxilla for incisor intrusion [18]. This study was performed on 30 adult patients with a deep overbite. An intrusion arch with T loops of 0.016*0.022 stainless steel wire and attached to mini-implants of self-drilling type inserted between the upper central and lateral incisors by an elastic chain was used to accomplish incisor intrusion in patients. The Er: YAG laser was started on the same day as the placement of the intrusion arch. This study reported a significant difference in treatment time between the conventional and experimental groups (3.78 mm in 95.8 days vs. 4.587 mm in 59 days, respectively). The time for the treatment in the experimental group was 38.4% less compared with the control group.

Secondary Outcomes
Pain and discomfort: Four trials evaluated the levels of pain and discomfort associated with erbium laser radiation [18,[23][24][25]. However, the results could not be pooled to quantitative synthesis due to the use of different scales for pain assessment.
Alfawal et al. [23] evaluated pain and discomfort levels associated with laser-assisted flapless corticotomy during canine retraction using self-reported questionnaires. The levels of pain and discomfort were significantly higher in the experimental group on the first day compared to the control group (mean NRS difference was 4 and 5.5 with P-values of 0.005 and <0.001 for pain and discomfort, respectively). Then, the levels of experienced pain and discomfort dramatically decreased in the experimental group at three days (T2); seven days (T3); and 14 days (T4), and insignificant differences were reported between the two sides.
A five-item questionnaire was used by Jaber et al. [24] to assess the levels of pain and discomfort during canine retraction. They found that 11.1% and 44% of the patients experienced severe and mild pain during the first day, respectively. On the third day, 72.2% of the patients were free of pain, and this percentage rose to 83.3% on the seventh day. Of the 12 patients examined by Mahmoudzadeh et al. [25], only one patient reported mild pain in the laser side after the wire insertion (visual analog score (VAS) score: 2), and it lasted for less than one day. Al-Jundi et al. assessed pain during acceleration of tooth intrusion [18]. There was no significant increase in pain scores. On Day 3 as on Day 7, the pain score in the experimental group was significantly lower as compared with the control group. According to GRADE recommendations, the strength of the evidence supporting this outcome was low ( Table 4).
Anchorage loss and undesirable tooth movements: Only two trials evaluated these variables [13,25]. Alfawal et al. and Mahmoudzadeh et al. investigated molar anchorage loss and upper canines' rotation during their retraction ( Table 3).
For molar anchorage loss, the differences between the experimental and control sides were not significant during the observation time (p>0.05 and p= 0.680, respectively). The observation time in the study of Mahmoudzadeh et al. [25] was only one month. According to GRADE, the evidence supporting this outcome is very low ( Table 4).
The rates of canines' rotation were greater in the experimental sides compared to the control sides in both trials. However, these differences were insignificant (p>0.05) after four months of observation in the Alfawal et al. trial [13]. There was very low evidence supporting this outcome according to GRADE (Table 4).
Periodontal problems: These problems were evaluated in two studies [16,25]. Salman and Ali compared mean gingival sulcus depth values of retracted canines pre and post-surgery and found clinically insignificant differences (i.e. less than 4 mm) [16]. The width of the attached gingiva and gingival index were evaluated by Mahmoudzadeh et al. who did not find any significant difference between the laser and control sides in these measures [25].

Discussion
To our knowledge, this is the first systematic review in the literature evaluating the effectiveness of highenergy lasers therapy (HELT) with flapless corticotomy in accelerating orthodontic tooth movement. The present review performed an overall qualitative assessment of the currently available studies, which comprised 155 patients from six trials. In order to minimize bias and possible confounders, only randomized and non-randomized controlled trials were included. The six trials that evaluated HELT were judged to be at unclear risk of bias; Participant blinding was the most problematic field. So this has affected the level of certainty of the achieved results.
Four trials investigated the efficacy of erbium lasers irradiation in accelerating canine retraction after premolar extraction [13,[24][25]. They reported greater tooth movement with the erbium laser as compared to the conventional method by 2-and 1.5-fold in the first and second months, respectively. However, the retraction rate on the experimental side was almost equal to its rate on the control side at the third month of intervention. This acceleration can be explained by the RAP phenomenon that was induced by laser-assisted corticotomy and decreased resistance of the alveolar bone to tooth movement [17,26]. In addition, the increased expression of inflammatory markers and cytokine levels stimulated by the selective removal of alveolar bone may have led to an increase in osteoclast activity, which, in turn, may have enhanced bone remodeling and accelerated tooth movement [27][28]. The temporary nature of the RAP could also explain why the acceleration occurred in the first two months only and then the canine retraction speed decreased gradually.
With erbium lasers, the peak of the RAP was after a month and decreased at the end of the second month. However, Wilcko et al. reported that the RAP phenomenon starts within a few days following injury, reaches its peak after four to eight weeks, and lasts for two to four months [26,29]. This difference with laser-assisted flapless corticotomy could be attributed to the less aggressive nature of this intervention compared to that of Wilcko. On the other hand, the present findings corroborate the results of Alfawal et al. who reported a significant reduction in treatment time when using minimally invasive flapless techniques for corticotomy like micro-osteoperforations or piezocision during teeth movement [6]. They showed that the tooth movement increased in the first two months, which is similar to what was found in this systematic review.
Al-Jundi et al. evaluated the effectiveness of flapless corticotomy with Er: YAG laser in accelerating incisors intrusion (non-extraction treatment) and reported a significant difference in the overall treatment time; the mean increase in the rate of tooth movement was 38.4% (95.8 and 59 days, respectively) [18]. When comparing the findings of this non-extraction-based trial (the tooth movement was approximately 2.5 times faster in the experimental group) [18] with the three previous extraction-based trials (the tooth movement was approximately two times faster in the experimental group) [13,[24][25], it seems that the types of movements did not influence the accelerating rate by the erbium laser.
One hundred fifty-five participants were included in the six studies. The six trials included only adult patients. The previously included trials evaluated a variety of flapless corticotomy protocols with variations in the design and size of the cortical bone cuts. Therefore, future studies must test the effect of these differences on the amount of acceleration and the adverse side effects of each individual intervention.
The levels of pain and discomfort associated with HELT were higher at the experimental sides than those at the control sides on the first day only [23][24]. The trauma of the alveolar bone and gingiva after surgery and the associated increase in inflammatory markers and cytokine levels can explain these slightly greater levels of perceived pain during the application of laser. When comparing the levels of pain and discomfort associated with laser-assisted flapless corticotomy with conventional corticotomy [4], no significant levels of pain and discomfort associated with erbium laser radiation were reported. This can be explained by the conservative and less invasive nature of this irradiation. Also, no flap reflection or sutures were required.
Another assumption is related to the sensory nerve endings that may have been blocked by the protein coagulation caused by laser cutting and thus relieving the sensation of pain [30]. Furthermore, the noncontact mode used with laser-assisted flapless corticotomy was accompanied by no mechanical pressure on the gingival tissue as opposed to the traditional corticotomy, which resulted in less discomfort.
Although no important levels of pain and discomfort associated with laser-assisted flapless corticotomy were reported in the evaluated trials, the evidence is weak. Therefore, further trials should investigate this outcome as well as other patient-reported measures.
Only two included trials investigated the undesirable tooth movements (canine rotation, molar anchorage loss) associated with laser-assisted flapless corticotomy [13,25]. Insignificant differences between the experimental and control groups were reported about the loss of anchorage. The anchorage loss rate ranged from 0.11 to 0.61 mm/month. However, these mean values are considered clinically insignificant and can be attributed to the conservative and less invasive nature of laser-assisted flapless corticotomy. Minimal weakening of the alveolar cortical bone may have allowed the upper canines to retract without exerting enough forces to allow mesial drifting of the posterior anchoring teeth.
Higher canines' rotation rate was reported on the surgical side compared to the control side [13,25]. However, this increase was not significant and could be negligible. This may be attributed to the high retraction rate and least alveolar bone density on the surgical site so that the movement of the teeth became easier and the surrounding structures were less resistant.
The included trials did not report any adverse effects of laser-assisted flapless corticotomy on the periodontal tissue [25]. Salman and Ali evaluated only the gingival sulcus depth to assess periodontal changes following the acceleratory intervention [16], whereas the width of the attached gingiva and the gingival index were evaluated by Mahmoudzadeh et al. [25]. However, they did not assess other important variables such as plaque index, bleeding index, and gingival recession. Therefore, future research work should place more emphasis on the possible side effects of laser-assisted flapless corticotomy on periodontal tissues.

Limitations
A lack of large, high-quality studies investigating HELT-based flapless corticotomy in the acceleration of tooth movement is evident. Altogether, most of the included studies were at unclear risk of bias and had small sample sizes. Most studies evaluated part of the provided orthodontic treatment and not the entire treatment duration. Adverse effects are investigated in a limited number of studies, and there have been no attempts to assess the interventions in terms of cost-benefit analysis. Long-term follow-up of the response to these interventions was also lacking among the included studies.

Conclusions
The efficacy of HELT with flapless corticotomy in accelerating tooth movement appeared to be significant at least in the first two months according to this review. However, the evidence has been found low to moderate according to the GRADE approach. More well-conducted studies are needed, with more attention paid to the size of the sample, the overall follow-up period, the surgical protocol (site, size, and design of surgical procedure, and the number of surgical interventions), the type of orthodontic treatment (extraction vs. non-extraction), side effects, and cost-benefit ratios.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.