Minimally invasive micro-osteoperforations (MOPs) look promising for a routine acceleration of orthodontic tooth movement (OTM). The objective of this research was to systematically evaluate evidence regarding the effects of MOPs on the OTM rate, treatment duration, and associated complications.
Electronic database and hand search of English literature in PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, and clinical trial.gov, with author clarification were performed. The selection criteria were randomized controlled trial (RCT) comparing MOPs with conventional treatment involving both extraction and nonextraction. Cochrane’s risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation approach were used for quality assessment. Studies were analyzed with chi-square–based Q statistic methods, I 2 index, fixed-effects, and random-effects model. Quantitative analysis was done on homogenous studies using Review Manager.
Eight RCTs were included for the qualitative analysis. Meta-analysis of 2 homogenous studies indicated insignificant effect with MOPs (0.01 mm less OTM; 95% CI, 0.13-0.11; P = 0.83). No difference ( P >0.05) was found in anchorage loss, root resorption, gingival recession, and pain.
Meta-analysis of 2 low–risk of bias studies showed no effect with single application MOPs over a short observation period; however, the overall evidence was low. The quality of evidence for MOP side effects ranged from high to low. Future studies are suggested to investigate repeated MOPs effect over the entire treatment duration for different models of OTM and its related biological changes. Trial registration number: PROSPERO CDR42019118642.
Eight randomized controlled trials were assessed in this systematic review.
Risk of bias were low in 3 studies, unclear in 2 studies and high in 3 studies.
Meta-analysis of two low risk of bias studies showed no effect with single application MOPs over a short observation period
High-quality evidence showed that MOPs do not have any effects on pain, gingival recession and root resorption
Lengthy treatment time has remained one of the main challenges in orthodontic treatment. Comprehensive orthodontic treatment with fixed appliances could take an average of 19.9 months, which can be prolonged because of the severity of malocclusion, complexity of treatment, or clinician’s and patient’s factors. , Prolonged treatment time can be unfavorable to both orthodontists and patients, as this could not only expose the patient to risk of caries, root resorption, and periodontal diseases, but also adversely affect patient’s compliance and satisfaction of the treatment outcome. Thus, shortening treatment duration has become a prime interest for both orthodontists and patients. Accordingly, the development of different modalities to reduce orthodontic treatment duration has emerged, among which is the surgical modality.
Micro-osteoperforation (MOP) is a recent innovative method to accelerate orthodontic tooth movement (OTM), and with the distinction of being minimally invasive, MOPs might prove to be a more favorable modality for routine clinical application than other surgically assisted modalities. MOPs involve minimal perforation of cortical bone using tools such as the PROPEL device , or a miniscrew, , without the need to raise a flap. The first study of MOPs in a human trial reported a promising 2.3-fold increase in the rate of canine retraction, with significant elevation in chemokines and cytokine levels compared with control group. Several clinical human trials have also shown significant acceleration of OTM with the use of MOP, some claiming that MOPs could reduce approximately 30% to 62% of orthodontic treatment time , and with minimal patient-perceived discomfort.
However, recent findings by Alkebsi et al and Aboalnaga et al reported contradicting results in which no significant differences were found in the rate of tooth movement between MOPs and control groups, and it was postulated that MOPs may not be sufficient to trigger inflammatory responses and activate the regional acceleratory phenomena. Therefore, a critical systematic review to better understand the effect of MOPs in accelerating OTM would be beneficial to the clinician. The present review thus aims to systematically assess and summarize available evidence related to the effect of MOPs on the rate of OTM, orthodontic treatment duration, and any reported adverse effects.
The objective of the systematic review and meta-analysis was to systematically evaluate available evidence related to the effect of MOPs on the rate of OTM, orthodontic treatment duration, and any reported posttreatment adverse effects of MOPs such as gingival recession, formation of black triangles, root resorption, anchorage loss, presence of bacteremia, and pain, in comparison with control groups.
Material and methods
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 ( www.crd.york.ac.uk/prospero/ ; trial registration number: PROSPERO CDR42019118642).
The selection criteria applied for this review are as presented in Table I .
|Category||Inclusion criteria||Exclusion criteria|
|Study design||RCT with split-mouth or parallel-group designs||Nonrandomized prospective clinical trials, retrospective studies, and case reports|
|Participants||Healthy male and female patients, aged 13 years and above, treated with fixed orthodontic treatment involving either
||Nonhuman studies (animal or laboratory studies)|
|Intervention||MOPs in the intervention group or side|
|Control||Patients or sides treated with conventional orthodontic mechanics without the aid of any tooth acceleration modalities||Patients or sides treated with any other techniques or drugs for tooth movement acceleration as a comparator|
|Others||English articles||Non-English articles|
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.).
|Search engines||Keywords||Results||Internal duplicates||External duplicates||Exclusion by title||Exclusion by abstract||Exclusion by full text||Final|
|CENTRAL (The Cochrane Library)||(Orthodontic* OR “Tooth movement” OR “Orthodontic tooth movement” OR “Tooth displacement” OR “Orthodontic treatment” OR “Orthodontic therapy”) and (accelerate* OR rapid* OR short* OR speed* OR fast OR velocity OR duration OR rate OR time OR “regional accelerated phenomenon” OR RAP) and (“minimally invasive” OR “micro-osteoperforations” OR “microperforations” OR osteoperforations)||16||0||5||6||5||0||0|
|Scopus||Same as above||1422||0||6||1407||1||1||7|
|PubMed||Same as above||103||0||8||89||5||1||0|
|Web of Science||Same as above||70||0||8||60||2||0||0|
|ClinicalTrial.gov||Orthodontic AND acceleration, Orthodontic AND accelerating, Orthodontic AND accelerate, Tooth movement AND accelerated, micro-osteoperforations, Minimally invasive AND accelerated, minimally invasive AND acceleration, Minimally invasive AND accelerating, Minimally invasive AND orthodontics, Rapid orthodontics, Rate orthodontics||153||0||9||136||0||7||1|
|OpenGrey||Acceleration AND tooth movement, orthodontic AND acceleration, minimally invasive OR micro-osteoperforations||125||0||0||125||0||0||0|
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.
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.
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 ).
|Study||Study design||Observation period||Participants||Mean age||Gender||Malocclusion||Type of tooth movement|
|Attri et al, 2018||Parallel-group RCT||Over period of space closure||60 subjects;
CG: 30; EG: 30
|17.83 ± 2.08||M: 27; F: 23||NIL||Maxillary and mandibular en-masse retraction|
|Sivarajan et al, 2019||Split-mouth RCT||16 wk||30 subjects;
CG: 30; EG: 30
|22.2 ± 4.00||M: 7; F: 23||Class I molar, less than half unit Class II and Class III molar||Maxillary and mandibular canine retraction|
|Alkebsi et al, 2018||Split-mouth RCT||12 wk||32 subjects;
CG: 32; EG: 32
|19.26 ± 2.48||M: 8; F: 24||Class II/Division 1||Maxillary canine retraction|
|Alikhani et al, 2013||Split-mouth RCT||28 d||20 subjects;
CG: 10; EG: 10
|19.5 ± 33.1;
CG: 24.7; EG: 26.8
|M: 8; F: 12||Class II/Division 1||Maxillary canine retraction|
|Aboalnaga et al, 2019||Split-mouth RCT||16 wk||18 subjects;
CG: 18; EG: 18
|20.5 ± 3.85||M: 0; F: 18||Class II/Division 1 and Bimax||Maxillary canine retraction|
|Feizbakhsh et al, 2018||Split-mouth RCT||28 d||20 subjects;
CG: 20; EG: 20
|28 ± 3.1||M: 12; F: 8||Class I||Maxillary and mandibular canine retraction|
|Haliloglu et al, 2018||Parallel-group RCT||8 wk||32 subjects;
CG: 15; EG: 17
|—||M: 19; F: 13||NIL||Maxillary and mandibular canine retraction|
|Kundi et al, 2018||Parallel-group RCT||28 d||28 subjects;
CG: 28; EG: 28
|28.4 ± 4.2
CG: 26.4 ± 4.1; EG: 28.4 ± 4.2
|M: 12; F: 16||Class II/Division 1||Maxillary canine retraction|
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.
|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;
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;
|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)
|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|