Protocol and registration

This systematic review was conducted following the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. After searching for previously registered similar studies, the review protocol of this systematic review was submitted in December, 2018 and registered on January 17, 2019 with the National Institute of Health Research database ( https://www.crd.york.ac.uk/prospero/ ; trial registration number: PROSPERO CDR42019118642).

Eligibility criteria

The selection criteria applied for this review are as presented in Table I .

Information sources, search strategy, and study selection

Comprehensive Electronic database search was conducted from January to March 2019, with no limitation on the year of study publication. Relevant databases such as Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, PubMed, and Web of Science were included in this review. Unpublished literature was searched electronically through ClinicalTrials.gov ( www.clinicaltrials.gov ) and OpenGrey ( www.opengrey.eu ) databases. In addition, relevant journals and reference lists of included studies were hand-screened for additional searches. Corresponding authors were contacted for obtaining clarifications or for additional data extraction. An e-mail alert was set for the PubMed search that allowed updates of results during the process of developing the review. Alerts were checked regularly until June 2019.

The search strategy used a combination of Medical Subject Headings and free-text words for PubMed and was optimized for each database respectively. The details of the search strategies are summarized in Table II . The literature search, study inclusion, methodology quality assessment, and data extraction were performed independently and in duplicate by 2 reviewers (S.S. and L.P.R.) who were not blinded to the authors. The results of the search were revised by the third and fourth authors (M.F. and W.M.C.).

Eligible articles were assessed in 2 phases. In the first phase, only titles and abstracts were screened. Assessment of full text was then conducted in the second phase for final eligibility. Articles were excluded when they did not meet 1 or more of the inclusion criteria. Any disagreements were resolved by discussion and consultation with the third and fourth authors for consensus (M.F. and W.M.C.).

Data items and collection

Data extraction was performed by 2 reviewers independently and in duplicate (S.S. and L.P.R.) using standardized data extraction sheets. This included the following items: general information (the name of authors, the year of publication, and study setting), methods (study design, duration, and treatment comparison), participants (sample size, age, and gender), intervention (type of interventions, intervention site, and technical aspects of interventions), orthodontic aspects (malocclusion characteristics, type of movement, appliance characteristics and biomechanics, frequency of orthodontic adjustments, and follow-up duration), and outcomes (primary and secondary outcomes, data of interest, methods of outcome measurements, and statistical significance of reported differences).

Risk of bias (ROB) and quality assessment in individual studies

Cochrane Collaboration’s tool was used for assessing the ROB of RCT studies. Seven components of bias were evaluated: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective reporting, and (7) other bias. An overall assessment of bias (high, unclear, low) was made for each included study. Any study that was evaluated with at least 1 component as high risk was regarded as having an overall high ROB and excluded from the meta-analysis.

Quality of the evidence

The quality of evidence was evaluated according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The GRADE approach appraises the quality of a body of evidence based on the extent to which one can be confident that an estimate of effect or association. The GRADE profiler was used to summarize the quality of evidence. This assessment was based on certain considerations, including study design, ROB, consistency, directness, heterogeneity, precision, publication bias, and other aspects reported by studies included in the systematic review. Depending on the seriousness, the quality of the evidence could be downgraded by 1 or 2 levels for each aspect.

ROB across studies

Standard funnel plots and contoured enhanced funnel plots would be drawn if more than 10 studies were included in the meta-analysis.

Summary measures and synthesis of results

When there is sufficient homogeneity in the methodology and original data of primary studies, the data were combined using RevMan (version 5.3; Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark) for quantitative analysis. Otherwise, the results were summarized qualitatively. Statistical heterogeneity was explored using chi-square–based Q statistic methods and the I ² index, with values of 25%, 50%, and 75% corresponding to low, moderate, and high heterogeneity, respectively. According to the I ² test, the fixed-effects model and the random-effects model were applied to studies with < 50% heterogeneity and > 50% heterogeneity, respectively.

Additional analyses

No subgroup analysis or sensitivity was undertaken because specific eligibility criteria were set and strictly followed during the search.

Study selection and characteristics

Details on the search and the study selection are shown in Figure 1 . The total number of identified records was 1889, with 36 duplicates. After screening a total of 1853 articles by title and abstract, 17 trials fulfilled the inclusion and exclusion criteria. Based on full article search, 2 articles and 7 ongoing studies were excluded as 1 study was an uncontrolled prospective study that investigated the bacteremia after MOPs, and another study was a nonrandomized study that reported on physical properties of root cementum. Finally, 8 articles ^, were selected for the qualitative evaluation, and only 2 ^, were deemed suitable for inclusion in the meta-analysis.

PRISMA diagram of article retrieval.

Study characteristics and ROB within studies

This systematic review included 8 randomized controlled trials ^, for the qualitative analysis. Only 2 studies were included in the quantitative synthesis. ^, Five of the studies included in the quantitative synthesis were of split-mouth design, ^, and 3 were parallel-group RCT ^{, ,} ( Table III ).

Four of the studies investigated the rate of canine retraction with MOPs in the maxillary arch only, ^, while 4 studies reported the rate of canine retraction both in the maxillary and mandibular arches. ^{, , ,} Gender was equally distributed in all the studies except for one study which had female participants only. The observation period in all the studies varied from the shortest observation period of 28 days, ^{, ,} 8 weeks, 12 weeks, 16 weeks, ^, to the entire period of space closure ( Table III ). The MOP was done only once in 6 studies. ^, Meanwhile, repeated MOPs were performed in 3 studies ^{, ,} ( Table IV ). One study repeated MOP every 28 days until space closure was completed, another repeated MOP every 4, 8, and 12 weeks for different intervention groups over an observation period of 16 weeks, and 1 more study repeated MOP once only at 4 weeks after the first MOP.

Table IV

Design, observation period, interventions, and outcome measures of the studies included in the qualitative synthesis (outcome data)

Study	Appliances used and biomechanical characteristics	Details on MOP intervention	Primary outcome	Secondary outcome
Attri et al, 2018	MBT with second molar banding & transpalatal arch as anchorage. En-masse retraction done with force 150 g NiTi coil spring immediately following the intervention	Location: 3 MOPs done at maxillary and mandibular first premolar extraction site, during space closure Device: Propel device with 1.5-mm width and 2-3-mm depth. MOPs repeated after every 28 d until space closure completed	Rate of space closure (mm/mo) using 3D digital models (study models scanned using White Light Scanner) between CG vs EG; Maxilla vs mandible	Pain perception VAS
Sivarajan et al, 2019	MBT with TADs to reinforce anchorage. Canine retraction done with power chain force 140-200 g, from canine bracket to TADs	Location: 3 MOPs (randomly assigned left/right) done on buccal mucosa of the extraction site Device: Orlus screw with 1.6-mm width and 3-mm depth MOPs repeated at 4, 8, and 12 weekly according to the assigned group	Rate of canine retraction in mm using a digital caliper	The difference in the rate of tooth movement between maxilla & mandible; Rate of tooth movement at 3 intervals of MOP (4,8,12 wk intervals); Pain intensity questionnaire
Alkebsi et al, 2018	MBT with mini screw as anchorage between 6s and 5s. Canine retraction done with 150 g NiTi closing coil from canine power arm extension to TADs immediately following the intervention	Location: 3 MOPs (randomly assigned left/right) at first premolar extraction site, during space closure Device: Aarhus mini-implant system with 1.5-mm width and 3-4-mm depth	Rate of canine tooth movement (mm/mo) using indirectly using 3D digital models (study models scanned with Ceramil Map 400 scanner) superimposed at the rugae and directly intraorally with a digital caliper	Anchorage loss; Canine tipping; Canine rotation; Root resorption; Plaque and gingival index; Pain level and pain interference; Level of satisfaction; Willingness to repeat the procedure
Alikhani et al, 2013	MBT with an auxiliary vertical slot in the maxillary canine. Canine retraction with 100 g NiTi closing coil from canine power arm extension to TADs	Location: 3 MOPs (randomly assigned left/right)done at first premolar extraction site, during space closure Device: PROPEL with 1.5 mm wide and 2 to 3-mm depth	Rate of canine tooth movement (mm/mo) using a digital caliper	Cytokines level; Pain score using a numeric scale
Aboalnaga et al, 2019	Roth prescription with TADs between the upper first molar and second premolar as anchorage. Canine retraction done with NiTi Coil spring force 150 g, from canine bracket hook to the first molar	Location: 3 MOPs (randomly assigned left/right) done on the buccal mucosa of extraction site, Device: TAD Unitek with 1.8-mm width and 8-mm depth, 3 months after first premolar extraction	Rate of canine retraction (mm/mo) and the total distance of canine movement by superimposing digital models (study models scanned using 3 Shape R900 scanner) with the pretreatment CBCT images	Anchorage loss; Canine root resorption; Pain level
Feizbakhsh et al, 2018	Roth prescription with the second molar as anchorage. Canine retraction done with NiTi Coil spring force 200 g, from canine bracket hook to auxiliary hook on the second molar	Location: 2 MOPs (randomly assigned left/right) done on at first premolar extraction site Device: Jeil Medical Corporation screwdriver (1.6-mm diameter and 3-mm length)	Rate of tooth movement (mm/mo) using 3D imaging scanning on study model	None
Haliloglu et al, 2018	MBT with TADs (between upper 6s and 5s) and transpalatal arch as anchorage. Canine retraction done with NiTi coil spring force 150 g, from canine bracket hook to TADs	Location: 3 MOPs done at the buccal site of upper and lower distal canine Device: mini screw MNT-2 (1.6-mm diameter and 5-mm depth)	Rate of tooth movement (mm/mo) using 3D imaging scanning on study model	Anchorage loss (Molar mesialization) Canine rotation; Canine tipping
Kundi et al, 2018	Canine retraction done with NiTi closing coil 100 g force	Location: 3 MOPs done distal to upper Device: PROPEL with 1.5 mm wide	Canine movement in mm using a digital caliper	None

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