Effects of micro-osteoperforations performed with Propel system on tooth movement, pain/quality of life, anchorage loss, and root resorption: a systematic review and meta-analysis

Background The aim of this systematic review was to evaluate the effect of micro-osteoperforations (MOPs) performed with Propel and other mini-screws on the rate of tooth movement, pain/discomfort, periodontal health, anchorage loss, and root resorption in patients undergoing orthodontic retraction compared to a control group. Materials and methods PubMed, Cochrane, Web of Science, LILACS, Google Scholar, Scopus, and OpenGrey were searched without restriction. A manual search was also carried out. Only randomized clinical trials (RCT) were included. The risk of bias (RoB) was assessed using RoB 2.0 and the certainty of evidence through the GRADE tool. Results Among the twelve RCTs reviewed, five used the Propel system. Overall, the RoB was classified as low (4), moderate (5), and high (3). Two RCTs with moderate and one with a low RoB using the Propel system reported mild increases on rate of tooth movement associated with MOPs. One RCT with a moderate and another with high RoB did not find a significant effect of Propel on orthodontic movement. Regarding tooth movement, a subgroup meta-analysis found no differences between control and Propel movement (95% CI = − 0.01 to 0.75) or other mini-screws (− 0.02 to 0.31) related to rate of tooth movement per month. There was no effect of MOPs on root resorption, periodontal health, anchorage loss, and a mild effect on pain and oral health related to quality of life regardless of mini-screw type. The level of certainty was graded as low for the rate of tooth movement and pain/discomfort, as moderate for anchorage loss, and high for root resorption. Conclusion A low certainty of evidence supports that MOPs performed with Propel seem to have no significant effect on the rate of tooth movement. Moreover, this intervention does not seem to cause an increase in root resorption, periodontal heath, pain/discomfort, or anchorage loss. Thus, the Propel system does not appear to produce different results from those observed for other mini-screws.


Introduction
With the aim of reducing orthodontic treatment time and side effects such as root resorption [1], pain [2], and impact on quality of life [3], several techniques used to accelerate tooth movement have excelled in orthodontics [4][5][6]. Some approaches cause cortical bone injuries and consequently increase the expression of inflammatory mediators, precursors of bone remodeling associated with orthodontic movement [7][8][9], such as corticotomies and micro-osteoperforations (MOPs).
Corticotomies are performed to reduce biological resistance to tooth movement and orthodontic treatment time [10]. A recent meta-analysis showed a reduction in total treatment time associated with corticotomies by approximately 2.8 months and a decline in rate of tooth movement after the first month of the procedure [7].
Less invasive than corticotomies, MOPs are performed using mini-screws without surgical flaps and with acceptable patient discomfort [4]. Some types of mini-screws have been used to produce MOPs. Propel (Propel Orthodontics, Ossining, NY) is a 1.4-mm surgical stainless steel mini-screw implant attached to a driver to create MOPs, which according to the company has a design to accelerate the rate of tooth movement [11]. Although, some studies have used this system to perform MOPs and reported a 2-3-fold increase in rate of movement [12,13]. Nevertheless, MOPs using conventional mini-screws following a methodology similar to the Propel system reported no impact on tooth movement [14,15].
Recent systematic reviews evaluated the influence of MOPs on the rate of tooth movement. However, to date, no comparative evaluation has been conducted to examine whether the Propel system could produce a different outcome than those observed when MOPs are performed with conventional mini-screws. These previous reviews have shown controversial findings and they have mixed Propel studies with others in the same meta-analysis, which is not appropriate considering the methodological heterogeneity [16,17]. One review pointed out an increase of 0.45 mm per month on the rate of canine retraction when compared to a no-intervention group [16]; however, four studies presented in the literature were not included [15,[18][19][20] in its analysis. In contrast, two other reviews stated that MOPs do not accelerate tooth movement [17,21]: one [21] with only two studies [14,15] and another [17] with three studies [12,14,18]. Therefore, the aim of this systematic review was to evaluate the effects of MOPs on the rate of tooth movement, considering the use of the Propel system and possible side effects inherent to the procedure.

Protocol and registration
This study was registered at PROSPERO database (https:// www.crd.york.ac.uk/prospero/display_record.php?RecordID = 113050) under registration code CRD42018113050 and was performed in accordance to the PRISMA [22] recommendations (Preferred Reporting Items for Systematic Review and Meta-Analysis).

Eligibility criteria
The following selection criteria were adopted in accordance with the PICOS format: Population (P): orthodontic patients with permanent dentition who underwent premolar extraction, and canine retraction or total anterior retraction Intervention (I): MOPs during canine retraction or total anterior retraction Comparison (C): canine retraction or total anterior retraction without MOPs or other interventions Outcome (O): the primary outcome was the rate of tooth movement measured by the amount of canine retraction or total anterior retraction. Secondary outcomes were as follows: quality of life, impact on patient's daily routine, and adverse effects such as pain/discomfort, root resorption, periodontal health, and anchorage loss.

Study design (S): randomized clinical trials (RCTs)
Exclusion criteria included studies which evaluated other types of tooth movement acceleration therapy. Opinion articles, animal studies, laboratory studies, case reports, case-series, and literature reviews were also excluded.

Information sources
The following databases were searched: PubMed, Cochrane, Web of Science, LILACS, Google Scholar, Scopus, and OpenGrey. The searches were performed until May 2020. A hand search was also carried out of the reference lists of the selected articles. No language or date publication restriction has been applied.

Search strategy and study selection
Two independently reviewers (CS and PM) searched the databases. In cases of unresolved disagreements, a third author (DN) was consulted. The search strategy was created from a combination of MeSH, Entry terms, and Keywords related to the PICO strategy using Boolean operators (Appendix).
The reference manager software was used to save the citations (Mendeley Ltd., 2019, Elsevier). After the duplicates were removed, article titles and abstracts were read to select studies. Those relevant were analyzed by reading the full text and a final selection was done by two researchers (CS and PM). If discrepancies were unsolved, a third researcher (DN) was consulted.

Data collection process
Two authors (CS and DN) performed the data extraction independently. The following items were considered for data extraction: author, year, location, type of study; sample size, male/female, age; type of malocclusion, retraction model, MOP protocol, utilization of Propel system, follow-up period and losses, rate of tooth movement, outcomes evaluated (rate of tooth movement, periodontal health, pain/discomfort, root resorption, anchorage loss), outcome measurements, and conclusions.

Summary measures
The rate of tooth movement was considered the main outcome. Data was also collected on the system used to perforate, loss of anchorage, periodontal health, root resorption, pain and discomfort, and implications on the quality of life.

Risk of bias in individual studies
Cochrane risk of bias tool (RoB 2.0) was used [23]. This tool assesses possible bias in five domains: bias arising from the randomization process, bias due to deviations from the intended interventions, bias due to missing outcome data, bias in the measurement of the outcome, and bias in the selection of the reported results. The bias was judged for each domain and to an overall evaluation of low, some concerns or high. Each risk of bias (RoB) analysis was done by two reviewers (CS and PM) and in case of discordance a third reviewer (DN) was consulted.

Level of evidence
The certainty of scientific evidence of outcome was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) [24]. The outcomes assessed were rate of tooth movement, pain and discomfort, anchorage loss, and root resorption. The articles were evaluated considering their design, RoB, consistency, directness, and precision.

Study selection
The searches yielded 297 references: PubMed (n = 29), Scopus (n = 35), Cochrane (n = 88) Web of Science (n = 39), LILACS (n = 2), Google Scholar (n = 100), Open-Grey (n = 0), and four additional references were identified through the manual search. After removing duplicates, the title and abstract of 204 articles were read and at the end articles were evaluated by full text. Twelve were excluded after the full text was read. The reasons for exclusion are described in Table 1. Twelve RCTs were included for qualitative and quantitative synthesis. The process of identification, selection, and exclusion of studies are presented in a flowchart (Fig. 1).
Among eight studies which analyzed the pain associated with the interventions [12-15, 20, 25, 28, 29], one evaluated the impact on the daily routine of patients [14] and three studies evaluated the presence of root resorption [14,15,28]. None used the Propel system. One Propel study assessed the implications on quality of life [19]. Five studies, including one Propel [13], evaluated the occurrence of anchorage loss [13-15, 18, 28]. Two studies without Propel assessed the periodontal health associated to MOPs [14,28].
Ten studies measured the rate of tooth movement during the canine retraction [12-15, 18, 20, 26-29] and two studies during the total space closure of the extraction, corresponding to orthodontic movement of total anterior retraction [19,25].

Risk of bias within studies
Overall, four RCTs were classified with a low RoB, including two that used Propel, [14,15,25,29], five were classified as some concerns, including two which used Propel [12,13,19,27,28], and three showed a high RoB, including one that used Propel [18,20,26]. The main causes of RoB were due to confounding factors in the randomization process [12, 13, 18-20, 26, 27], deviations from intended interventions [12,18], missing outcome data [20,27], measurement of the outcome [20,28], and selection of the reported result [13]. No article was able to maintain double-blind analysis due to the nature of the study. Figure 2 shows the RoB evaluations of the included studies.

Results of individual studies
Among five studies that used the Propel system, three [12,13,25] reported an increase in the rate of tooth movement, one with a low RoB [25], and two with a moderate RoB [12,13]. Another study [20] with a high and another [19] with a moderate RoB reported no difference between groups. Seven studies used conventional mini-screws to perform the MOPs. Four of these [18,26,27,29] reported an increase in the rate of orthodontic movement, while three [14,15,28] found no difference between groups, two with a low RoB [14,15], and one with a moderate RoB [28]. The summary of the included studies characteristics is described in Table 2.
Regarding root resorption, three studies that used conventional mini-screws [14,15,28] revealed no differences between the control and experimental groups. Eight studies analyzed the pain associated with the    MOPs were effective in accelerating tooth movement over a period of 3 months, but not clinically significant. There was no increase in the level of pain and discomfort due to MOPs.
NA not available, MOPs micro-osteoperforations, MBT McLaughlin-Bennet-Trevisi, SS stainless steel, NiTi niquel-titanium, OHIP oral health impact profile, SD standard deviation, GCF gingival crevicular fluid, TAD temporary anchorage device, CBCT cone beam computed tomography, VAS visual analogue scale interventions [12-15, 20, 25, 28, 29], only three reported a mild discomfort associated to MOPs after the perforation [13,15,20], two with the Propel system [13,20], and one with other mini-screws [15]; also, five studies, including two with Propel, did not report pain associated to the MOP procedure [12,14,25,28,29]. The impact on quality of life was evaluated for one study with the Propel system [19] that reported more impact on OHR-QoL immediately following the MOP procedure and for 3 days after. Another study [14] evaluated the MOPs impact on daily routine and reported that MOPs had no effect on the patients' daily life except for a feeling of swelling on the first day. The anchorage loss was evaluated in one study with Propel [13] and in four with conventional mini-screws [14,15,18,28], and did not find differences between the control and experimental groups.

Synthesis of results
A random-effect meta-analysis with subgroups was performed using the RevMan 5.3 software; the subgroups were selected according to the perforation system: Propel or conventional mini-screw. The subgroup Propel system included five studies [12,13,19,20,25] and the another with conventional mini-screws included seven studies [14,15,18,[26][27][28][29]. Both revealed no statistically significant differences in the monthly rate of tooth movement between the control and MOP groups. The mean difference between the control and MOPs' group using the Propel system was 0.37 mm (95% CI − 0.01 to 0.75, Fig. 3), and for the group with mini-screws, it was 0.15 mm (95% CI − 0.02 to 0.31, Fig. 4).

Assessment of the certainty of evidence
The evaluation of the evidence according to GRADE was described in Table 3. The quality of evidence was rated as low for orthodontic tooth movement [12-15, 18-20, 25, 26, 28, 29] and pain or discomfort [12-15, 20, 25, 28] due to inconsistency and imprecision of the studies, as well as the RoB. The outcome related to anchorage loss [13][14][15]18] presented a moderate level of certainty, justified by the RoB of the evaluated studies.
The GRADE tool rated the outcome root resorption as high [14,15,28]. Outcomes investigated by only one study [19] were not evaluated according to GRADE, since this tool aims to analyze the certainty of evidence generated by different studies. Evaluating only one study can lead to an incorrect result. Therefore, quality of life and periodontal outcomes were not analyzed.

Discussion
Although three studies with the Propel system have associated the acceleration in rate of tooth movement to MOPs [12,13,25], one with low RoB [25] and two with moderate [12,13], the subgroup meta-analysis did not show statistically significant increases in the monthly rate of tooth movement when MOPs were performed with Propel compared to a control group. Also, the subgroup analysis with mini-screw perforations revealed no differences between the control and MOP groups, as the mean is 0.15 (95% CI − 0.02 to 0.31).
A previous systematic review [16] concluded that the rate of tooth movement increased after performing MOPs in 0.45 mm (95% CI 0.17 to 0.74), in contrast with another review [21] that reported no differences between the mean difference of MOP and control group equal to − 0.01 (95% CI − 0.13 to 0.11). It is important to highlight that a previous review [16] reported an inaccurate sample size [14,15] and follow-up period [15] of some included studies. Furthermore, this previous review [16] included three studies which used the Propel system [12,13,25] and three which used other types of mini-screw [14,26,27] in the same meta-analysis.
In this present review, five studies [12,13,19,20,25] investigated the Propel and seven [14,15,18,[26][27][28][29] used conventional mini-screws. To see if the use of the Propel system influences the rate of tooth movement, we performed a meta-analysis with subgroups only with studies that evaluated this system. No differences between the control and Propel MOP groups were found. The mean difference was 0.37 mm (95% CI − 0.01 to 0.75, Fig. 3). These findings are not different from those obtained from studies that used other types of miniscrews (mean difference 0.15 mm; 95% CI − 0.02 to Fig. 3 Forest plot for the mean difference of the monthly rate of tooth movement comparing studies that used Propel system 0.31). These results showed that the use of the Propel system, as well as other mini-screws, do not affect orthodontic movement significantly.
Regarding the five studies included in our metaanalysis that used Propel, four [12,19,20,25] measured the outcomes near the date of the perforations. One study [13] performed the MOP once and measured the rate of tooth movement until the space closed, which according to the study seemed to correspond to 4 months and found a higher rate of tooth movement associated to the MOP group. To minimize the effect of time on the quantification of results, we divided the amount of rate of movement in millimeters by the follow-up period. Evaluating the monthly rate of tooth movement during all the follow-up period is done because the acceleration of tooth movement tends to be greater during the first month after the MOP procedure and decreases after that [14,15].
The evaluated studies have different follow-up periods, orthodontic movement regarding canine retraction and total anterior retraction, frequency of performing MOPs, mechanics used for canine retraction, and measurement methods of tooth movement. Two [12,27] studies demonstrated accelerated tooth movement in the MOPs' group and have a shorter investigation time of 28 days. One study [25] followed the movement throughout the total space closure, however expressed an increase in monthly rate of tooth movement of 0.2 mm. The study with the longer follow-up [19] and moderate RoB corresponding to 9 months did not find differences in the monthly rates of tooth movement between the control and MOP groups, even when performing MOPs monthly. Studies with three [14,28,29] and four [14] months of follow-up and low RoB reported no acceleration on tooth movement related to MOPs. After the procedure, MOPs might increase the rate of tooth movement, but this effect seems to be clinically insignificant and it is not maintained along the treatment.
Regarding orthodontic movement, ten studies measured the rate of tooth movement associated to canine retraction [12-15, 18, 20, 26-29], which included one with a low and one with a moderate RoB, and using the Propel system evaluated the rate of tooth movement during the anterior retraction [19,25]. It is important to assess the rate of tooth movement not only during canine retraction, but mainly during anterior retraction, as cases with premolar extraction will require anterior retraction in addition to canine retraction. The data from these two studies [19,25] report results with greater clinical relevance for determining the choice for performing MOPs during orthodontic treatment. However, one study reported no difference between the control and MOP groups related to the monthly rate of tooth movement [19] and the other reported a mean difference of 0.3 mm between the control and MOP groups. This appears to be a clinically insignificant value to justify the MOPs' procedure.
Considering the frequency of performing MOPs, one study with a moderate and one with a low RoB performed MOPs with the Propel system once a month [19,25]. One study with a 4-month follow-up reported acceleration of tooth movement [25]; however, this was clinical insignificant (0.2 mm/month). One study [19] with a 9-month follow-up and a moderate RoB did not find any effects on the monthly rate of tooth movement. Thus, better designed studies that perform MOPs with Propel system every month could be conducted to clarify whether this approach could increase, in a clinically significant way, the rate of tooth movement.
The GRADE analysis classified the certainty of the outcome rate of tooth movement as low due to the presence of bias in the included studies, and due to inconsistency. In fact, the certainty of the evidence would already be compromised no matter how low the RoB was, as several studies have shown divergence in the direction of effect size found. The statistical heterogeneity may reflect the methodological heterogeneity found in Fig. 4 Forest plot for the mean difference of the monthly rate of tooth movement comparing studies that used conventional mini-screws the included studies. When comparing the results of this review with others [17,21], we realize that when a statistically significant effect is found, it has no clinical relevance. Apparently, the system specially developed for performing MOPs, the Propel system, has no impact on the rate of tooth movement.
Great methodological diversity was found concerning the mechanics used for canine retraction. Three RCTs which utilized the Propel system [12,19,20] used mini-screws for absolute anchorage and two [13,25] used conventional anchorage. Of the three studies that used the Propel system and found an increase on the rate of tooth movement, one used mini-screws as anchorage and NiTi springs [12], another used conventional anchorage and NiTi springs [13], and the third used conventional anchorage and Haliloglu-Ozkan et al. [18] and Sivarajan et al. [26] presented bias in randomization process; Fattori et al. [19] presented deviations from intended interventions; Puetter et al. [20] showed tie-backs for canine retraction [25]. These variations in methodologies may have reflected the high heterogeneity found among the results of the included studies. Complementing the methodological difference, nine studies used scanned models [13-15, 18-20, 25, 27, 28] to perform the measurements, one study evaluated tooth movement through clinical examination [26], and two RCTs took digital caliper measurements on plaster models [12,29]. Linear measurements made on digital models have similar reliability and accuracy as measurements made on plaster models [30].
The pain reported by patients during the performance of MOPs was investigated by eight studies [12-15, 20, 25, 28, 29]. Three studies with Propel system [12,20,25] and two with mini-screw [14,28] found no difference between pain reported by patients in the control and experimental groups. Three studies with mini-screw perforations [15,28,29] and one with Propel system [13] reported pain after performing MOPs, decreasing posteriorly. Pain does not seem to be critically associated to the MOPs' procedure. Considering the heterogeneity assessment and bias of the studies, the GRADE classified the quality of this evidence as low.
The periodontal condition was evaluated for two studies without the Propel system [14,28] and both reported no difference between the control and MOP group related to gingival and periodontal index. MOPs had no adverse effect on periodontal health. The assessment of anchorage loss associated with canine retraction was performed by five studies [13-15, 18, 28], which only one used Propel system [13] and no study reported statistically significant differences between control and MOPs' groups. Two studies with a low RoB [14,15] and one with a high RoB [18] used skeletal anchorage, which may have influenced the result found. The level of certainty of the anchorage loss was rated by GRADE as moderate. Three studies [14,15,28] which performed MOPs with mini-screw, two with low RoB [14,15], and one with a moderate RoB [28] evaluated the incidence of root resorption and found no significant difference intergroup, confirming the findings in the literature [1,31]. The level of evidence generated for this outcome is high.
The impact of MOPs on the patients' daily routine and quality of life was assessed by two studies [14,19]. One study [19] which used the Propel system and with a moderate RoB showed MOPs produced a greater impact on oral health-related quality of life immediately following the MOP procedure and for 3 days after, affecting mostly "psychological discomfort" and "psychological disability" domains. This variable is influenced by several factors, such as social, economic, and cultural, not addressed by the study, which may lead to an inconclusive outcome. The other study with low a RoB [14] has no statistical difference between the control and the MOP group. These suggest that MOPs have a discrete effect on the patient's daily routine, limited to the moments after their completion.

Limitations
The studies sample sizes have great variability which may have influenced the differences between the experimental and MOPs' groups. Most studies did not follow patients throughout the entire closure of the extraction space; moreover, the procedure was performed only at the beginning of orthodontic retraction in some studies [12-15, 20, 26, 27, 29]. New studies using the Propel system with appropriate sample sizes that evaluate the effects of MOPs throughout the total anterior retraction may generate a higher level of evidence.
Furthermore, it is particularly important to highlight the clinical and methodological heterogeneity observed among the included studies. The differences between the frequencies of MOPs, follow-up periods, perforation systems, and types of retraction reflected a great statistical heterogeneity when performing the meta-analysis. Previously published systematic reviews also present the same limitations [16,17] or have included only two studies in the meta-analysis [21]. Therefore, it is important to report that a meta-analysis is unfeasible in the presence of high clinical and methodological heterogeneity.
In our systematic review, we tried to control this issue, performing meta-analyses of subgroups, one for the Propel system and one for conventional mini-implants. Furthermore, a monthly average of orthodontic movement due to the different follow-up times was evaluated. After these adjustments, MOPs appear to have no significant clinical effect on the orthodontic movement.