Title

Accepted Article
Comparative efficacy of the bone-anchored maxillary protraction protocols for orthopedic treatment in

skeletal Class III malocclusion: A Bayesian network meta-analysis

Running title

BONE-ANCHORED MAXILLARY PROTRACTION

Author list

Shoushan Hu1, Ke An1, Yiran Peng1,2

Institutional affiliations and positions

1Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu,

610041, Sichuan, People’s Republic of China

2State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases,

Chengdu, 610041, Sichuan, People’s Republic of China

Corresponding author

Yiran Peng

Address

14 Renmin South Road Third Section, Chengdu, 610041, Sichuan, People’s Republic of China

Tel : +86-28-85503527

Fax : +86-28-85503527

Email : ortho_peng@hotmail.com

Acknowledgments

This work was financially supported by Project of Chengdu Science and Technology

(2019-YF05-00763-SN) and Experimental and Technical Project of Sichuan University (SCU203039).

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/OCR.12532
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Accepted Article
Conflict of Interest

The authors declare no conflict of interest.

Data Availability Statement

The data that supports the findings of this study are available in the supplementary material of this

article.

Author Contributions

Shoushan Hu: Conceptualization; Data curation; Formal analysis; Funding acquisition; Investigation;

Methodology; Resources; Software; Validation; Writing-original draft; Writing-review & editing. Ke An:

Data curation; Methodology; Software; Formal analysis. Writing-original draft; Writing-review & editing.

Yiran Peng ： Conceptualization; Funding acquisition; Investigation; Methodology; Resources;

Validation; Writing-review & editing.

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Accepted Article
DR SHOUSHAN HU (Orcid ID : 0000-0003-1853-2761)

DR KE AN (Orcid ID : 0000-0002-9933-1349)

DR YIRAN PENG (Orcid ID : 0000-0001-9982-9115)

Article type : Review Article

Title
Comparative efficacy of the bone-anchored maxillary protraction protocols for orthopedic

treatment in skeletal Class III malocclusion: A Bayesian network meta-analysis

Abstract
Objective To compare the treatment effects of five bone-anchored maxillary protraction protocols

(BAC3E, BAMP, BARME-FM, BARME-ME, SAFM) for skeletal Class III malocclusion.

Methods We conducted a systematic literature search through CENTRAL, EBSCO, PubMed and

Web of Science and, included the randomized controlled trials and clinical controlled trials, which

met the criteria. A Bayesian network meta-analysis (NMA) for SNA, SNB, ANB, SN-MP and Wits

appraisal was performed in R software using a random consistency model. The additional

analyses included node-splitting analysis, statistical heterogeneity analysis, sensitivity analysis

and ranking probability by SUCRA.

Results 598 articles were initially obtained; 13 articles involving 482 individuals were eventually

included. Among the five bone-anchored maxillary protraction protocols, the largest increment in

SNA and Wits appraisal was observed in the BAMP group and BAC3E group respectively; the

SAFM, BAC3E and BAMP groups showed similar capability in terms of changes of ANB; least

clockwise rotation of the mandible was found in the BARME-ME group, followed by the BAMP

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Accepted Article
group; dental compensation appears to be most pronounced in the BAC3E group; intermaxillary

traction seems to reduce the lingual inclination of lower incisors, even cause labial inclination.

Conclusions The SAFM, BAMP, BAC3E groups seem to be advantageous in the improvement of

the maxillo-mandibular relationship, followed by the BARME-FM and BARME-ME groups. The

findings of this study should be interpreted with caution since only short-term effects were

compared and the quality of evidence ranged from very low to moderate. More RCTs with

high-quality and long-term investigation are needed.

Keyword bone anchors; Class III malocclusion; orthopedic treatment; network meta-analysis

Main text
Introduction
Skeletal Class III malocclusion is characterized as either a retrognathic maxilla, a prognathic

mandible, or a combination of both.1 In clinical practice, maxillary protraction is a preferrable

choice for children and adolescents diagnosed as skeletal Class III malocclusion with the

retrognathic maxilla.2 With the increasing application of skeletal anchorages, bone-anchored

maxillary protraction protocols are gaining popularity in orthodontics in recent years. Regarding

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Accepted Article
classic bone-anchored maxillary protraction (BAMP), four miniplates were pairwise connected by

elastics, of which two were placed on the left and right infrazygomatic crest of the maxillary

buttress, with another two implanted between the mandibular left and right lateral incisors and

canine.3 As for bone-anchored Class III elastics (BAC3E), two titanium miniplates or miniscrews

were inserted at the labial vestibule of the mandible on both sides and connected to a bonded or

removable maxillary expander by elastics.4,5 Additionally, skeletally-anchored facemask (SAFM)

referred to a facemask in conjunction with two miniplates inserted in the lateral nasal walls of the

maxilla or two miniscrews fixed on both sides of zygomatic buttress areas.6,7 As regards

bone-anchored rapid maxillary expansion (BARME), two mini-implants were implanted into the

anterior palate to provide an absolute support system for the expansion device.8 BARME-FM and

BARME-ME respectively refer to the combination of BARME and facemask and the combination

of BARME and Mentoplate, which were miniplates inserted subapical to the lower incisors.8

Admittedly, Cubuk S et al.9 mentioned that bone-anchored appliances burdened additional

risks on patients such as instability of bone anchors, local inflammation, interference with the

eruption of teeth near bone anchors, etc. Compared with the traditional facemask, however,

maxillary protraction assisted by skeletal anchorage was more attractive to orthodontists for

minimizing undesirable dental effects and yielding greater skeletal effects.10 Whereas, among the

five bone-anchored maxillary protraction protocols (BAC3E, BAMP, BARME-ME, BARME-FM,

SAFM), the difference in dental and skeletal changes after treatment remained unknown to date.

Due to strictly limited publications providing a direct comparison between different

bone-anchored maxillary protraction protocols, it is difficult to manifest their differences in dental

and skeletal effects by traditional pairwise meta-analysis. Network meta-analysis (NMA) allowed

inferences into the comparative efficacy of interventions that were not evaluated directly against

each other, thus highlighting the relative advantages of each intervention.11 Therefore, the aim of

the present study was to compare the treatment effects of bone-anchored maxillary protraction

protocols for orthopedic treatment of skeletal Class III malocclusion by NMA.

Material and methods

Registration

The NMA was performed according to the PRISMA extension statement for reporting of

systematic reviews incorporating network meta-analyses of health care interventions.12 The

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Accepted Article
research protocol for this NMA was registered at PROSPERO (International prospective register

of systematic reviews): CRD42020180947.

Search strategy

From December 1, 2020, till January 1, 2021, a systematic literature search was performed to

identify potential research papers across four databases including Cochrane Central Register of

Controlled Trials (CENTRAL), EBSCO, PubMed, and Web of Science. There was no restriction

regarding paper language and publication date, and non-English articles were translated. Besides,

we did a manual search to widen the scope of the literature search. All references to previous

systematic reviews, meta-analyses, and selected full-text articles were manually screened for

potentially useful articles. The search strategies and results were provided in Appendix 1.

Eligibility criteria

The retrieved articles were initially screened independently by two authors (SH and KA)

based on title and abstract. Potentially eligible articles were then reviewed independently by two

authors (SH and KA) based on their full text. If a disagreement occurred, the relevant studies

would be discussed by all authors to determine whether they should be included.

Articles were included when they met the following criteria:

(a) They were randomized clinical trials (RCTs) or non-randomized clinical controlled trials

(CCTs) on interceptive treatment for adolescents with skeletal Class III malocclusion;

(b) No other dento-maxillofacial deformities or systemic diseases, such as cleft lip and palate,

cleidocranial dysostosis, ectodermal dysplasia, or hypophosphatasia;

(c) No orthodontic treatment was performed simultaneously with orthopedic treatment;

(d) The trial included no less than two treatment groups (no less than ten subjects in each

group) and included at least one type among SAFM, BAMP, BAC3E, BARME-FM and

BARME-ME;

(e) If there was only one bone-anchored protocol included in the article, the matched group

had to be the TBFM group rather than the untreated control group.

(f) The effects of different interventions were compared by the changes (pre-treatment and

post-treatment) of lateral cephalometric measurements depicted in mean difference (MD) and

standard deviation (SD).

Additionally, systematic reviews, case reports, case series, personal opinion, qualitative

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Accepted Article
studies, and reviews were excluded.

Data extraction

The following specific information and variables were selected from included studies

independently by two authors (SH and KA):

(1) Study characteristics: first author, year of publication, type of study, sample group and

sample size;

(2) Patient characteristics: gender, mean age at pre-treatment, inclusion and exclusion

criteria;

(3) Intervention characteristics: treatment protocol, force magnitude each side, hours of

wearing elastic per day, treatment duration;

(4) Primary outcomes: MD and SD of changes of lateral cephalometric measurements:

SNA(°), SNB(°), ANB(°), Wits(mm), SN-MP(°) (the angle between SN and mandibular plane),

IMPA(°), U1-PP(°), U1-SN(°).

Risk of bias assessment

The risk of bias was assessed using the ROB 2.0 tool for randomized studies and the

ROBINS-I tool for non-randomized studies. Two authors (SH and KA) independently assessed the

risk of bias. Any disagreement was resolved through consultation with the third author (YP).

Strategy for data synthesis

A Bayesian framework was applied to Markov chain Monte Carlo methods in R software

(version 3.6.3) with the GeMTC and JAGS package to perform network meta-analyses of included

articles by using a random consistency model. Specifically, we used 4 chains with overdispersed

initial values, with Gibbs sampling based on 50,000 iterations after a burn-in phase of 100,000

iterations. We then ranked the different treatments in Stata software (version 14 StataCorp,

College Station, Tex) and defined the best strategy by surface under the cumulative ranking curve

(SUCRA), of which the larger value implied a higher hierarchy.13

Additional analysis

The network plot was utilized to graphically describe transitivity of different interventions. The

node-splitting analysis was conducted to assess inconsistency between indirect and direct

sources of evidence. Additionally, the global I² values was employed to quantify the degree of

heterogeneity.14 Meta-regression would be conducted if the global I² values were over 50%.

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Accepted Article
Sensitivity analysis was conducted to explore the reliability of the main outcome. The quality of

evidence for all studies was assessed by the GRADE approach.

Results
Study selection and characteristics

The initial search result in the four databases contained a total of 598 articles and no

additional articles were identified through manual research. A list of full-text studies excluded with

reasons was provided for transparency in Appendix 1. Eventually, 13 articles met the inclusion

criteria and were included in the network meta-analysis, which consisted of 3 RCTs and 10 CCTs,

involving a total of 482 individuals.4-8,15-22 In a recent publication, Cornelis et al.23 convincingly

identified some articles including identical samples, which were excluded in the present study.

Details about the search process and results were shown in Appendix 1. The characteristics of

included articles were summarized in Appendix 2. Network plots of different bone-anchored

maxillary protraction protocols included in the NMA were shown in Figure 1.

Risk of bias assessment

The results of risk of bias assessment were provided in Appendix 3. Among three RCTs, two

were assessed ‘some concerns’ and one was assessed at low level. Among ten CCTs, eight

studies were assessed at moderate level, while the level of risk of bias of two studies were low.

Network meta-analysis

The results of NMA were provided in Figure 2 and Appendix 4. Among the five

bone-anchored maxillary protraction protocols (BAC3E, BAMP, BARME-FM, BARME-ME, SAFM),

the BAMP group (versus TBFM: MD: 1.7; 95% Crl: 0.31, 3.1) showed a larger increment in SNA

with significance, while fewer changes in SNB with significance were observed in the BARME-ME

group (versus TBFM: MD: 2.1; 95% Crl: 0.43, 3.7). The SAFM, BAMP and BAC3E groups showed

similar increments in ANB, followed by the BARME-FM and BARME-ME groups. However, a

larger increment in Wits appraisal was observed the BAC3E group, compared with the other four

groups. The clockwise rotation of the mandible was most prominent in the BAC3E group (versus

TBFM: MD: 0.55; 95% Crl: -1.1 2.0), followed by the SAFM group.

The SUCRA values for SNA, SNB , ANB, SN-MP and Wits appraisal for different

bone-anchored maxillary protraction protocols were showed in Table 1. The higher value indicated

a higher possibility of obtaining desirable changes. For instance, the BAMP group showed the

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Accepted Article
highest probability of increase in SNA (90.1%), while the BARME-ME group was ranked first in

reduction of clockwise rotation of the mandible (98.1%).

Additional analyses

The node-splitting analysis showed that there was no inconsistency for SNA, SNB, ANB,

SN-MP and Wits appraisal (Appendix 5). The I2 values ranged from SN-MP (I2.pair = 0; I2.cons = 0)

to ANB (I2.pair = 16.63; I2.cons = 34.67), indicating that the level of heterogeneity ranged from low

to moderate, thus allowing data pooled together using a random consistency model. Transitivity

assumptions were be assessed by treatment protocol, treatment duration, patients’ mean age and

gender distribution (Appendix 2). Sensitivity analyses were conducted for SNA. Considering that

there were least patient samples in Lee et al.22 and Tripathi et al.16, they were excluded

respectively, followed by data synthesis. The results rarely changed after excluding the two

small-scale studies (Appendix 5). The considerable heterogeneity or incomplete network

transitivity did not allow the data synthesis for U1-PP, U1-SN and IMPA pooled into NMA and

therefore, they were listed in Table 2.

Discussion
Skeletal changes

ANB and Wits appraisal are crucial markers of skeletal changes. The SAFM, BAMP and

BAC3E groups were ranked top three in terms of increase in ANB and Wits appraisal. The BAMP

group showed ideal skeletal effects with the most increase in SNA and few changes in SN-MP,

indicating prominent advancement of the point A and mild clockwise rotation of the mandible.

Compared with the BAMP group, although fewer increments in SNA were observed in the SAFM

and BAC3E groups, they showed more clockwise rotation of the mandible, leading to their similar

capability of increasing ANB.

Compared with the SAFM and BAMP groups, a larger increment in Wits appraisal was

observed in the BAC3E group. It was reported that the undesired counter-clockwise rotation of the

maxilla was observed in the BAC3E group, which could be explained by the force vector passing

below the center of resistance of the maxilla.5 The combination of counter-clockwise rotation of

the maxilla and clockwise rotation of the mandible resulted in the counter-clockwise rotation of the

occlusal plane, which in part accounted for a significant increment in Wits appraisal.5

In comparison with the SAFM, BAMP and BAC3E groups, the BARME-ME and BARME-FM

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Accepted Article
groups showed a similar change in SNA but caused less clockwise rotation of the mandible, thus

resulting in fewer changes in ANB and Wits appraisal.

Dental changes

Prominent proclination of maxillary incisors was observed in the BAC3E group (Table 1),

which resulted from the dental compensation caused by the maxillary expander.5 While, it was

found that maxillary incisors slightly retroclined in the SAFM and BARME-FM groups (Table 1),

which was in part due to the occlusal interference.24

Significant proclination of mandibular incisors was observed in the BAC3E group, followed by

the BAMP group, while the BARME-FM and SAFM groups showed the lingual inclination of

mandibular incisors (Table 1).The chin-cup effect of facemask was considered as a crucial factor

contributing to undesirable changes of the lower incisors.23,25 Additionally, it was reported that the

withdrawal of lip force and increased tongue pressure on the lower incisors after correction of

anterior crossbite might account for proclination of mandibular incisors.5,26

Strengths and limitations

In the present study, SAFM, BAMP, BAC3E, BARME-FM and BARME-ME were classified as

five separate bone-anchored maxillary protraction protocols for skeletal Class III malocclusion.

Publications with identical samples were carefully excluded to avoid magnifying the effects of

certain treatments, which was ignored in some previous studies.27,28 Besides, we included four

comparative studies6,15,16,29 on bone-anchored appliances, which were in absence in the previous

NMA.27 Our excessive work was likely not only to provide a reference for clinicians, but also to be

a reference for comparisons of multiple maxillary protraction protocols for future study.

Meanwhile, we have to admit some limitations. The long-term effects of bone-anchored

maxillary protraction protocols were rarely reported in included articles and, therefore treatment

comparison was limited in the short term. Besides, the findings of this study should be interpreted

with caution due to the fact that the statistical heterogeneity ranged from low to moderate.

Quality of evidence

As a result of the GRADE assessment, the level of quality of evidence ranged from very low

to moderate (Appendix 6). The downgraded grades resulted mainly from high risk of bias and

imprecision. Using the TBFM group as a common reference, most of the comparisons for BAMP,

SAFM, and BAC3E presented a low or moderate certainty in the evidence. However, both the

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Accepted Article
BARME-FM and BARME-ME comparisons presented very low certainty in the evidence,

suggesting that the clinical outcomes may be very different.

Implication for clinical application

BAMP, BARME-FM and BARME-ME showed a better control of the mandible, indicating that

they seemed to be alternatives for Class III malocclusion patients with high-angle vertical growth

pattern. More significantly, BARME-ME could be applied prior to full eruption of mandibular

canines, thus becoming an alternative for patients under nine years old.30 Besides, Elnagar et al.17

demonstrated that the same rate of maxillary protraction could be achieved by either BAMP or

SAFM, while BAMP could provide greater vertical closing of the mandibular plane than did SAFM.

Furthermore, Sar et al.5 suggested that SAFM was suitable for patients with severe maxillary

retrusion and a high-angle vertical pattern, while BAC3E was a preferable choice for patients with

a low- or normal-angle vertical pattern and retroclined mandibular incisors.

Implication for future research

Most comparative studies on bone-anchored maxillary protraction protocols adopted

2-dimensional cephalometric analysis, which provided limited information of overall facial changes.

For instance, it did not reflect changes in the glenoid fossa or asymmetric effects on both sides.31

Cone-beam computed tomography (CBCT) allowed a clear visualization of 3-dimensional (3D)

skeletal and dental changes before and after treatment as well as helped determine the ideal

position of the bone anchors.32,33 Heymann’s study34 illustrated the treatment changes induced by

BAMP in 3D-CBCT, which visually exhibited different individual responses to the maxillary

protraction in detail. Unfortunately, there is, to date, lack of articles comparing the treatment

effects of different bone-anchored maxillary protraction protocols by 3D-CBCT, possibly due to

time consumption and lack of a standardized comparison protocol. Therefore, 3D-CBCT is

expected to be applied to broaden our understanding of the differences in the efficacy of various

bone-anchored maxillary protraction protocols.

Conclusion

Compared with the BAC3E, BARME-FM, BARME-ME, SAFM groups, the BAMP group

showed ideal skeletal effects with a larger advancement of the point A and less clockwise rotation

of the mandible.

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Accepted Article The SAFM,BAMP, BAC3E groups seem to be advantageous in the improvement of the

maxillo-mandibular relationship, followed by the BARME-FM and BARME-ME groups.

The findings of this study should be interpreted with caution since only short-term effects

were compared and the quality of evidence ranged from very low to moderate. More RCTs with

high-quality and long-term investigation are needed.

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Accepted Article
Table 1. Dental effects of different bone-anchored maxillary protraction protocols

Changes of Changes of Changes of

Article Treatment N U1-PP U1-SN IMPA

(mean ± SD) (mean ± SD) (mean ± SD)

SAFM 17 -0.05 ± 4.72 - -6.08 ± 3.35

5
Sar et al.
BAC3E 17 4.5 ± 3.12 - 8.23 ± 2.81

Cevidanes et BAMP 21 0.6 ± 3.1 - 1.9 ± 1.6

21
al. TBFM 34 0.9 ± 10.6 - -4.3 ± 3.3

BARME-FM 17 -1.15 ± 6.45 - -3.84 ± 6.13

8
Willmann et al.
BARME-ME 17 0.57 ± 5.49 - -0.56 ± 3.83

Buyukcavus et SAFM 18 2.08 ± 0.46 - -2.37 ± 1.07

15
al. TBFM 18 5.18 ± 4.26 - -2.51 ± 1.39

SAFM 10 0.25 ± 0.37 - -2.56 ± 1.76

17
EInagar et al.
BAMP 10 0.14 ± 0.44 - 1.1 ± 0.18

BAC3E 10 4.4 ± 3.4 6.1 ± 3.8 0.7 ± 2.8

4
Jamilian et al.
TBFM 10 6.7 ± 10.5 6.7 ± 11.2 -6 ± 7.1

SAFM 20 - 1.88 ± 3.51 -5.57 ± 3.63

19
Ge et al.
TBFM 23 - 8.29 ± 3.27 -4.01 ± 2.23

SAFM 10 - 2.00 ± 1.154 -3.6 ± 1.82

16
Tripathi et al.
TBFM 10 - 6.40 ± 3.098 -6.81 ± 2.402

SAFM 19 - -1.116 ± 6.887 -2.863 ± 3.824

7
Koh et al.
TBFM 28 - 4.054 ± 5.243 -3.621 ± 3.47

SAFM 19 - 3.36 ± 6.79 -1.85 ± 5.19

6
Lee et al.
TBFM 27 - 7.36 ± 5.81 -2.09 ± 4.67

BARME-FM 20 - -4.42 ± 5.67 -2.23 ± 3.84

18
Ngan et al.
TBFM 20 - -0.19 ± 7.35 -4.33 ± 7.68

SAFM 10 - - -1.99 ± 5.49

22
Lee et al.
TBFM 10 - - -2.15 ± 3,87

20
Cha et al. SAFM 25 - - -0.37 ± 5.73

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Accepted Article TBFM 25 - - -1.53 ± 4.86

BAMP, bone-anchored maxillary protraction; SAFM, skeletal-anchored facemask; BAC3E,

bone-anchored Class III elastics; BARME-FM, bone-anchored rapid maxillary expander with

facemask; BARME-ME, bone-anchored rapid maxillary expander with mentoplate

Table 2. The SUCRA values for SNA, SNB , ANB, SN-MP and Wits for different bone-anchored

maxillary protraction protocols

Cephalometric measurement
Treatment
SNA SNB ANB SN-MP Wits

BAC3E 40.3 6.3 72.5 0.8 99.9

BAMP 90.1 70.6 73.7 76.4 78.3

BARME-FM 55.6 66.9 34.2 65.5 33.5

BARME-ME 54.2 98.8 2.7 98.1 9.7

SAFM 53.9 32.4 77.9 39.5 55.8

BAMP, bone-anchored maxillary protraction; SAFM, skeletal-anchored facemask; BAC3E,

bone-anchored Class III elastics; BARME-FM, bone-anchored rapid maxillary expander with

facemask; BARME-ME, bone-anchored rapid maxillary expander with mentoplate

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Accepted Article
Figure legends

Figure 1. Network plot of different bone-anchored maxillary protraction protocols included in the

network meta-analysis. (A) SNA, SNB, ANB, SN-MP; (B) Wits.

Figure 2. Network meta-analysis of different bone-anchored maxillary protraction protocols

compared with the TBFM group.

Appendices (provided in a separate file)

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Accepted Article
Comparative efficacy of the bone-anchored maxillary protraction protocols for

orthopedic treatment in skeletal Class III malocclusion: A Bayesian network

meta-analysis

Appendix 1 Search strategy and result

Appendix 2 Summary of the included articles

Appendix 3 Risk of bias assessment

Appendix 4 Mixed treatment comparison for every cephalometric measurement

Appendix 5 Node-splitting analysis, analysis of heterogeneity, sensitivity analysis

Appendix 6 Quality of evidence (GRADE)

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Accepted Article
Appendix 1
Table 1. Search strategy and result

Database Terms Results

#1 Class III malocclusion[Title/Abstract] OR Habsburg 4901

Jaw[Title/Abstract] OR mandibular prognathism[Title/Abstract] OR

underbite[Title/Abstract] OR retrognathia[Title/Abstract] OR skeletal

class III[Title/Abstract] OR angle class III[Title/Abstract] OR

mandibular hyperplasia[Title/Abstract] OR maxillary

retrusion[Title/Abstract] OR maxillary hypoplasia[Title/Abstract] OR

mandibular protrusion[Title/Abstract]

#2 skeletal anchorage[Title/Abstract] OR skeletally 5802

anchored[Title/Abstract] OR bone anchorage[Title/Abstract] OR bone

anchored[Title/Abstract] OR bone screw[Title/Abstract] OR bone

PubMed plate[Title/Abstract] OR miniscrew[Title/Abstract] OR

miniplate[Title/Abstract] OR mini-implant[Title/Abstract] OR

mentoplate[Title/Abstract] OR miniscrew appliance[Title/Abstract] OR

orthodontic miniscrew[Title/Abstract]

#3 maxillary protraction[Title/Abstract] OR removable orthodontic 919

appliances[Title/Abstract] OR functional orthodontic

appliances[Title/Abstract] OR activator appliance[Title/Abstract] OR

activator orthodontic appliance[Title/Abstract] OR function

activator[Title/Abstract] OR bionator[Title/Abstract] OR extraoral

traction appliances[Title/Abstract]

#4 #1 AND #2 AND #3 58

#1 TS=(Class III malocclusion OR Habsburg Jaw OR mandibular 16,024

prognathism OR underbite OR retrognathia OR skeletal class III OR

Web of
angle class III OR mandibular hyperplasia OR maxillary retrusion OR
Science
maxillary hypoplasia OR mandibular protrusion)

#2 TS=(skeletal anchorage OR skeletally anchored OR bone anchorage 159,309

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Accepted Article OR bone anchored OR bone screw OR bone plate OR miniscrew OR

miniplate OR mini-implant OR mentoplate OR miniscrew appliance

OR orthodontic miniscrew)

#3 TS=(maxillary protraction OR removable orthodontic appliances OR 77,714

functional orthodontic appliances OR activator appliance OR

activator orthodontic appliance OR function activator OR bionator OR

extraoral traction appliances)

#4 #1 AND #2 AND #3 268

S1 TX=(Class III malocclusion OR Habsburg Jaw OR mandibular 15,559

prognathism OR underbite OR retrognathia OR skeletal class III OR

angle class III OR mandibular hyperplasia OR maxillary retrusion OR

maxillary hypoplasia OR mandibular protrusion)

S2 TX=(skeletal anchorage OR skeletally anchored OR bone anchorage 79,977

OR bone anchored OR bone screw OR bone plate OR miniscrew OR

EBSCO miniplate OR mini-implant OR mentoplate OR miniscrew appliance

OR orthodontic miniscrew)

S3 TX=(maxillary protraction OR removable orthodontic appliances OR 23,844

functional orthodontic appliances OR activator appliance OR

activator orthodontic appliance OR function activator OR bionator OR

extraoral traction appliances)

S4 S1 AND S2 AND S3 238

#1 Title Abstract Keyword=(Class III malocclusion OR Habsburg Jaw 690

Cochrane OR mandibular prognathism OR underbite OR retrognathia OR

Central skeletal class III OR angle class III OR mandibular hyperplasia OR

Register of maxillary retrusion OR maxillary hypoplasia OR mandibular

Controlled protrusion)

Trials #2 Title Abstract Keyword=(skeletal anchorage OR skeletally anchored 3,800

(CENTRAL) OR bone anchorage OR bone anchored OR bone screw OR bone

plate OR miniscrew OR miniplate OR mini-implant OR mentoplate

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Accepted Article #3
OR miniscrew appliance OR orthodontic miniscrew)

Title Abstract Keyword=(maxillary protraction OR removable 72,756

Fr

om

orthodontic appliances OR functional orthodontic appliances OR Decem

activator appliance OR activator orthodontic appliance OR function ber 1,

activator OR bionator OR extraoral traction appliances) 2020

#4 #1 AND #2 AND #3 34 till

Januar

y 1, 2021, we performed a systematic literature search across four databases including Cochrane Central Register

of Controlled Trials (CENTRAL), EBSCO , PubMed and Web of Science. There was no restriction regarding paper

language and publication date, and non-English articles were translated. The search terms and results were

showed in Table 1.

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Accepted Article
Fig 1. PRISMA flow diagram showing results and process of literature search and selection

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Accepted Article
Table 1. Full text studies excluded with reasons.

Study Exclusion reason

1
Wilmes 2010 No matched group

2
Nienkemper 2013 No matched group

3
Meng 2012 No matched group

4
Maino 2018 No matched group

5
Kircelli and Pektas 2008 No matched group

6
Kaya 2011 No matched group

7
Kale and Buyukcavus 2020 No matched group

8
Coscia 2012 No matched group

9
Al-Mozany 2017 No matched group

10
Nienkemper 2015 Using untreated patients as control

11
Eissa 2018 Using untreated patients as control

12
Eid 2016 Using untreated patients as control

13
De Clerck 2010 Using untreated patients as control

14
Bozkaya 2017 Using untreated patients as control

15
Baccetti 2011 Using untreated patients as control

16
Kim 2014 Aim to modify therapeutic protocol

17
Lee 2013 Aim to study how to improve the stability of anchorage

18
Van Hevele 2018 Aim to study the factors influencing anchorage success

19
De Clerck and Swennen 2011 Aim to improve the success rate of miniplate anchorage

20
Vachiramon 2009 Participants as cleft lip and palate patients

21
Showkatbakhsh 2011 Participants as cleft lip and palate patients

22
Lucchese 2014 Participants as cleft lip and palate patients

23
Seiryu 2020 Irrelevant interventions

24
Algarci 2016 Irrelevant interventions

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 25
Accepted Article
Esenlik 2019

Majanni and Hajeer 2016

26
Irrelevant interventions

Irrelevant interventions

27
Nakamura 2017 Irrelevant interventions

28
Meyns 2018 A review

29
Koh and Chung 2014 A review

30
Wilmes 2014 Case report

31
Muthukumar 2016 Case report

32
Miranda 2020 Case report

33
Kuen 2007 Case report

34
Kook 2015 Case report

35
Gera 2021 Case report

36
Favero 2012 Case report

37
Esenlik 2015 Case report

38
Degala 2015 Case report

39
De Menezes 2016 Case report

40
Cha 2021 Case report

41
Cantarella 2020 Case report

42
Alhalabi 2017 Case report

43
Ding 2007 Samples in each group less than 10

44
De Souza 2019 Inappropriate outcomes

45
Sar 2011 Duplicate data

46
Tung 2014 Three-dimensional data

47
Elnagar 2017 Three-dimensional data

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Accepted Article
Appendix 2
Table 1. Summary of the included articles
Type First Inclusion criteria or exclusion criteria End of Included Intervention of Sample size Treatment Extracted
of author maxillary group treatment/ force (female/male)/ duration variables
study /year of protraction magnitude on mean age at
publication each side/ hours T0
of wearing
elastic per day
RCT Jamilian (1) SNA ≤ 80°, SNB ≤ 80°, ANB ≤ 0° at the initial lateral NR Group 1 TBFM 10 (7f 3m) 13±2 mo SNA, SNB,
2011 cephalograms ---/--- 10.5±1.5 y ANB, IMPA,
(2) No syndromic or medically compromised patients or Group 2 BAC3E 10 (5f 5m) 11±3 mo U1-PP,U1-SN,
previous surgical intervention or skeletal asymmetry 350 g/24 h 11.3±0.8 y SN-MP
(3) No use of other appliances before or during the
period of functional treatment
(4) A normal mandibular growth pattern; neither
horizontal nor vertical growers; Class III molar
relationship with concave profile
RCT Elnagar (1) Growing Class III patients with a prepubertal stage of 3 to Group 1 SAFM 10 (4f 6m) 8±1.33 mo SNA, SNB,
2016 skeletal maturity according to the cervical vertebral 4 mm of 400-500 g/14-16 11.9±1.3 y ANB, Wits,
maturation method positive h IMPA, U1-PP,
(2) Skeletal Class III malocclusion with maxillary anterior Group 2 BAMP 10 (3f 7m) 8.9±2.33 SN-MP
deficiency (ANB, <0°; Nperp-A, <0°) with or without overjet. 250 g/24 h 12.24±1 y mo
mandibular prognathism
(3) Late mixed or early permanent dentition at the start of
treatment characterized by a Wits appraisal of -1 mm
or less and an Angle Class III molar relationship or
anterior crossbite
(4) Vertically normal growth pattern

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Accepted Article
(5) No cleft and other craniofacial anomaly or previous
orthodontic treatment

RCT Ge 2012 (1) Prepubertal stage of skeletal maturity according to Positive Group 1 SAFM 20 (11f 9m) 11 mo SNA, SNB,
the cervical vertebral maturation method (CS1‐ dental 200-250 g/14 h 10.3 y ANB, Wits,
CS3); Skeletal and dental Class III malocclusion with overjet Group 2 TBFM 23 (12f 11m) 13 mo IMPA, U1-SN,
maxillary deficiency (ANB < 0; Wits appraisal < 2 400-500 g/--- 10.5 y SN-MP
mm)
(2) No significant skeletal asymmetry and no systemic
diseases or congenital deformities
CCT Cha 2011 (1) Class III malocclusions in growing patients overjet of Group 1 SAFM 25 (15f 10m) 9.2 ± 2.4 SNA, SNB,
(2) No previous orthodontic treatment 2-3 mm. 300-400 g/--- 11.0±1.4 y mo ANB, IMPA
Group 2 TBFM 25 (16f 9m) 8.5 ± 2.4
400 g/14-16 h 10.8±0.9 y mo
CCT Cevidanes (1) Anterior crossbite or incisor end-to-end relationship in correction Group 1 BAMP 21 (11f 10m) 12 mo Wits, IMPA,
2010 the mixed or permanent dentitions of the 250 g/24 h 11.8±1.83 y U1-PP
(2) Wits appraisal of −1 mm or less, and Class III molar anterior Group 2 TBFM 34 (20f 14m) 10 mo
relationship crossbite 500 g/14 h 8.25±1.83 y
(3) Prepubertal stage of skeletal maturity according to
the (CS1‐CS3)
CCT Koh 2014 (1) Overjet greater than -2 mm NR Group 1 SAFM 19 (11f 8m) --- SNA, SNB,
(2) No craniofacial deformity, cervical vertebra 400-500 g/16 h 11.21 y ANB, IMPA,
maturation stage of 3 and no previous orthodontic Group 2 TBFM 28 (21f 7m) --- U1-SN
treatment or Surgery ---/12-14 h 10.09 y
CCT Lee 2012 (1) Skeletal and dental Class III malocclusion with NR Group 1 SAFM 10 (5f 5m) 1.0±0.1 y SNA, SNB,
maxillary hypoplasia in the mixed or early permanent 400 g/12-14 h 11.2±1.2 y ANB, Wits,
dentition (SNA<80°;ANB<-1°; A-Nperp<0 mm) Group 2 TBFM 10 (6f 4m) 1.1±0.1 y IMPA
(2) Anterior crossbite and positive overbite 400 g/12-14 h 10.7±1.3 y
(3) No cleft and other craniofacial syndromes and

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Accepted Article
significant skeletal asymmetry (less than 2 mm
chin-point deviation)
CCT Lee 2019 (1) Negative overjet or edge-to-edge bite at first; ANB < 2 mm of Group 1 SAFM 19 (11f 8m) 1.38±0.5 y SNA, SNB,
0° and/or Wits appraisal<-4mm at first; CVM stage 3 incisor 400-500 g/16 h 11.19±1.1 y ANB, Wits,
or 4 at T0 overjet Group 2 TBFM 27 (12f 15m) 1.35±0.5 y IMPA, U1-SN,
(2) Maxillary protraction without bonded acrylic-splint 400-500 g/12-14 11.21±1.2 y SN-MP
maxillary expander h
(3) No congenital craniofacial deformities, previous
orthopaedic or orthodontic treatment or congenital
missing or extraction of permanent teeth during
treatment
CCT Ngan 2015 (1) Anterior crossbite or edge-to-edge incisal relationship NR Group 1 TBFM 20 (12f 8m) 0.8 y SNA, SNB,
(2) Accentuated mesial step or class III permanent molar 380 g /12–14 h 9.7±1.6 y ANB, Wits,
relationship Group 2 BARME-FM 20 (12f 8m) 0.6 y IMPA, U1-SN,
(3) A Wits appraisal smaller than -3 mm or an ANB 380 g /12–14 h 9.8±1.2 y SN-MP
smaller than -2°
(4) No prior orthopedic or orthodontic treatment and no
craniofacial syndromes
CCT Sar 2014 (1) Skeletal and dental Class III malocclusion with NR Group 1 SAFM 17 7.4 mo SNA, SNB,
maxillary deficiency (ANB＜0°; Nperp-A<1 mm;Wits 400 g/16 h 11.23±1.48 y ANB, Wits,
appraisal<–2 mm) and retrusive nasomaxillary IMPA, U1-PP,
Group 2 BAC3E 17 7.6 mo
complex with or without mandibular prognathia SN-MP
500 g/24 h 11.25±1.52 y
(2) Vertically normal growth pattern (SN-GoGn<40°)
(3) Anterior crossbite and Angle Class III molar
relationship
(4) Normal or increased overbite
CCT Tripathi (1) Essential features of skeletal III malocclusion with Positive Group 1 SAFM 10 5.8 mo SNA, SNB,
2016 maxillary deficiency (point A, nasion and point B <0); overjet of 4 400 g/12-14 h 10.10±1.1 y ANB, Wits,

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Accepted Article
edge to edge bite or reverse incisor relationship and mm Group 2 TBFM 10 10 mo U1-SN, SN-MP
normal or increased overbite 400 g/12-14 h 9.90±1.1 y
(2) No systemic diseases or congenital deformities
CCT Willmann (1) Moderate/severe class III: Wits ≤–2 mm NR Group 1 BARME-FM 17 (9f 8m) 0.79±0.26 SNA, SNB,
2018 (2) Anterior crossbite or incisor edge-to-edge 400 g/14-16 h 8.74±1.20 y y ANB, Wits,
relationship, class III molar relationship Group 2 BARME-ME 17 (10f 7m) 0.87±0.25 IMPA, U1-PP,
(3) No craniofacial anomalies, systemic diseases and 200 g/24 h 9.43±0.95 y y SN-MP
forced or functional bite
CCT Buyukcavus (1) An absence of any craniofacial anomaly or systemic 2 mm Group 1 SAFM 18 0.7 ± 0.21 SNA, SNB,
MH 2020 disorder and the presence of a negative overjet, a positive 400–500 g/20 h 11.96±0.92 y y ANB, Wits,
maxillary deficiency and a concave profile, and a overjet Group 2 TBFM 18 0.94 ± IMPA, U1-PP,
decreased SNA angle and negative ANB angle 400–500 g/20 h 10.59±1.03 y 0.42 y SN-MP
identified in the cephalometric analysis
(2) No functional Class III anomaly, and patients treated
with different RME appliances (banded hyrax
appliance, full coverage appliance, fan-type
expanders, etc.) and different Alt-RAMEC protocols
BAMP, bone-anchored maxillary protraction; SAFM, skeletal-anchored facemask; BAC3E, bone-anchored Class III elastics; BARME-FM, bone-anchored rapid maxillary expander with facemask;
BARME-ME, bone-anchored rapid maxillary expander with mentoplate; TBFM, tooth-borne facemask; NR, not reported

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 Appendix 3
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Table 1. Assessment of risk of bias of the randomized studies (RCTs) by ROB 2.0 tool

Deviations from Missing Measureme Selection of

Randomization
Study intended outcome nt of the the reported Overall Bias
process
interventions data outcome result

Jamilian Some
Some concerns Low Low Low Low
2011 concerns
Ge Some
Some concerns Low Low Low Low
2012 concerns
Elnagar
Low Low Low Low Low Low
2016

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Accepted Article
Table 2. Assessment of risk of bias of the non-randomized studies (CCTs) by ROBINS-I
Deviations
Selection Classification Missing Measuring Reporting Overall
Studies Confounding from Comments
bias in intervention data outcomes bias bias
interventions
Buyukcavus Moderate Low Low Low Low Moderate Low Moderate No comparison of pre-treatment
2020 measurement baselines; no blinding
for measuring.
Cevidanes Moderate Low Low Moderate Low Moderate Low Moderate Significant differences in pre-treatment
2010 age and measurements at baseline;
no assessment of differential patient
compliance effects; no blinding for
measuring.
Cha 2011 Moderate Moderate Low Low Low Moderate Low Moderate Significant differences in pre-treatment
age and a few measurement; no
specific inclusion criteria; replacement
of a patient’s miniplate; no blinding for
measuring.
Koh 2014 Low Low Low Low Low Moderate Low Moderate No significant differences in
measurements at baseline; subgroup
analysis based on age; no blinding for
measuring.
Lee 2012 Low Low Low Low Low Moderate Low Moderate No significant differences in baseline
measurements and age before and
after treatment; no blinding for
measuring; small sample size.
Lee 2019 Low Low Low Low Low Low Low Low No significant differences in age,
gender, skeletal maturity, treatment
duration and measurements at

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Accepted Article
baseline; information blinded in the
cephalometric analysis.
Ngan 2015 Moderate Low Low Low Low Low Low Moderate No comparison on the baseline
situation; information blinded in the
cephalometric analysis.
Sar 2014 Low Low Low Moderate Low Moderate Low Moderate No significant differences in baseline
situation; replacement of miniplates in
2 patients per group; no blinding for
measuring.
Tripathi Moderate Low Low Low Low Moderate Low Moderate No comparison on the baseline
2016 situation; no blinding for measuring.
Willmann Low Low Low Low Low Low Low Low No significant differences in age,
2018 gender, treatment duration and
measurements at baseline; no
replacement of implants required;
information blinded in the
pre-treatment cephalometric analysis.

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 Appendix 4
Accepted Article
Table 1-5. Mixed treatment comparison of mean difference (MD) and their respective 95% CrI for SNA, SNB, ANB,
Wits and SN-MP for different intervention of skeletal Class III malocclusions

Table 1
SNA
BAC3E

-1.08 BAMP
(-2.36,0.21)
-0.27 0.81 BARME-FM
(-1.81,1.27) (-0.90,2.52)
-0.27 0.81 0.00 BARME-ME
(-2.14,1.61) (-1.21,2.83) (-1.06,1.06)
-0.21 0.87 0.06 0.06 SAFM
(-0.98,0.57) (-0.16,1.90) (-1.31,1.43) (-1.68,1.80)
0.63 1.71 0.90 0.90 0.84 TBFM
(-0.17,1.43) (0.62,2.80) (-0.42,2.22) (-0.80,2.60) (0.47,1.21)

Table 2
SNB
BAC3E

-1.18 BAMP
(-2.04,-0.32)
-1.17 0.01 BARME-FM
(-2.43,0.09) (-1.29,1.31)
-2.38 -1.20 -1.21 BARME-ME
(-3.83,-0.93) (-2.69,0.28) (-1.92,-0.50)
-0.36 0.82 0.81 2.02 SAFM
(-0.94,0.22) (0.18,1.46) (-0.32,1.95) (0.68,3.36)
-0.30 0.88 0.87 2.08 0.06 TBFM
(-0.93,0.33) (0.17,1.59) (-0.23,1.96) (0.77,3.38) (-0.24,0.36)

Table 3
ANB
BAC3E

-0.11 BAMP
(-1.78,1.57)

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 0.96 1.07 BARME-FM
Accepted Article
(-0.79,2.72)
2.17
(-1.08,3.22)
2.28 1.21 BARME-ME
(0.08,4.27) (-0.16,4.72) (0.06,2.36)
-0.06 0.05 -1.02 -2.23 SAFM
(-0.92,0.81) (-1.38,1.48) (-2.63,0.59) (-4.21,-0.25)
0.56 0.66 -0.41 -1.62 0.61 TBFM
(-0.29,1.40) (-0.85,2.17) (-1.94,1.13) (-3.54,0.30) (0.13,1.09)

Table 4
Wits
BAC3E

2.47 BAMP
(0.68,4.26)
4.32 1.85 BARME-FM
(2.00,6.63) (-0.15,3.85)
4.99 2.52 0.67 BARME-ME
(2.47,7.51) (0.28,4.76) (-0.34,1.67)
3.44 0.97 -0.88 -1.55 SAFM
(2.04,4.83) (-0.16,2.09) (-2.73,0.97) (-3.66,0.55)
4.44 1.97 0.12 -0.55 1.01 TBFM
(2.83,6.05) (0.86,3.08) (-1.54,1.79) (-2.49,1.40) (0.20,1.81)

Table 5
SN-MP
BAC3E

4.12 BAMP
(3.32,4.92)
3.64 -0.48 BARME-FM
(2.06,5.21) (-2.07,1.11)
5.35 1.24 1.72 BARME-ME
(3.55,7.16) (-0.58,3.06) (0.85,2.59)
1.11 -3.01 -2.53 -4.25 SAFM
(0.54,1.67) (-3.58,-2.44) (-4.02,-1.04) (-5.97,-2.52)
0.63 -3.49 -3.01 -4.73 -0.48 TBFM
(-0.09,1.34) (-4.23,-2.75) (-4.42,-1.60) (-6.39,-3.07) (-0.96,0.00)

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Accepted Article

Appendix 5
1. Node-splitting analysis
Table 1. Node-splitting analysis of inconsistency for SNA
comparison p.value 95% CrI
BAC3E vs SAFM 0.548225
direct -0.00044 (-1.3, 1.3)
indirect 0.57 (-1.0, 2.2)
network 0.22 (-0.73, 1.2)
BAC3E vs TBFM 0.53825
direct -0.30 (-1.8, 1.2)
indirect -0.88 (-2.3, 0.56)
network -0.63 (-1.6, 0.38)
SAFM vs TBFM 0.5289
direct -0.87 (-1.4, -0.33)
indirect -0.28 (-2.3, 1.7)
network -0.84 (-1.3, -0.36)

Table 2. Node-splitting analysis of inconsistency for SNB

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 comparison p.value 95% CrI
Accepted Article
BAC3E vs SAFM
direct
0.428625
0.49 (-0.52, 1.5)
indirect -0.28 (-2.0, 1.4)
network 0.33 (-0.54, 1.1)
BAC3E vs TBFM 0.455725
direct -0.27 (-1.9, 1.4)
indirect 0.43 (-0.67, 1.5)
network 0.26 (-0.69, 1.0)
SAFM vs TBFM 0.427525
direct -0.047 (-0.52, 0.39)
indirect -0.80 (-2.7, 1.1)
network -0.076 (-0.52, 0.32)

Table 3. Node-splitting analysis of inconsistency for ANB

comparison p.value 95% CrI
BAC3E vs SAFM 0.21725
direct -0.53 (-2.0, 0.88)
indirect 0.64 (-0.86, 2.0)
network 0.060 (-1.0, 1.1)
BAC3E vs TBFM 0.22895
direct -0.11 (-1.4, 1.2)
indirect -1.2 (-2.7, 0.33)
network -0.55 (-1.6, 0.47)
SAFM vs TBFM 0.226675
direct -0.71 (-1.2, -0.100)
indirect 0.44 (-1.6, 2.4)
network -0.61 (-1.1, -0.018)

Table 4. Node-splitting analysis of inconsistency for Wits

comparison p.value 95% CrI
BAC3E vs SAFM 0.5265
direct -0.33 (-3.9, 3.2)
indirect -1.5 (-5.7, 2.3)
network -0.93 (-3.2, 1.4)
BAC3E vs TBFM 0.517075
direct -2.3 (-5.7, 1.1)
indirect -1.1 (-5.1, 3.1)
network -1.9 (-4.0, 0.50)
SAFM vs TBFM 0.529425
direct -0.78 (-2.7, 1.4)
indirect -2.0 (-6.9, 3.0)
network -0.95 (-2.5, 0.78)

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Accepted Article
Table 5. Node-splitting analysis of inconsistency for SN-MP
comparison p.value 95% CrI
BAC3E vs SAFM 0.755625
direct -1.2 (-3.6, 1.3)
indirect -0.68 (-3.9, 2.5)
network -1.1 (-2.5, 0.46)
BAC3E vs TBFM 0.758625
direct -0.23 (-3.0, 2.6)
indirect -0.68 (-3.3, 2.1)
network -0.55 (-2.0, 1.1)
SAFM vs TBFM 0.734950
direct 0.47 (-0.87, 1.9)
indirect 0.95 (-2.7, 4.6)
network 0.50 (-0.45, 1.6)

2. Analysis of heterogeneity
Table 1. Analysis of heterogeneity for SNA
Per-comparison I-squared:
2 2
t1 t2 I .pair I .cons incons.p
1 BAC3E SAFM NA 0.00000 0.6307457
2 BAC3E TBFM NA 0.00000 0.5790210
3 BAMP SAFM NA NA NA
4 BARME-FM BARME-ME NA NA NA
5 BARME-FM TBFM NA NA NA
6 SAFM TBFM 33.62622 24.15414 0.7305391
Global I-squared:
2 2
I .pair I .cons
1 33.63325 28.10912
2 2
t1: treatment 1; t2: treatment 2; I .pair: I-square of pair-wise meta-analysis; I .cons: I-square of network
meta-analysis; Incons.p: inconsistency p-values for pair-wise and network meta-analysis; NA: not applicable

Table 2. Analysis of heterogeneity for SNB

Per-comparison I-squared:
2 2
t1 t2 I .pair I .cons incons.p
1 BAC3E SAFM NA 0.00000 0.6262622
2 BAC3E TBFM NA 0.00000 0.4419029
3 BAMP SAFM NA NA NA
4 BARME-FM BARME-ME NA NA NA
5 BARME-FM TBFM NA NA NA
6 SAFM TBFM 0.00000 0.00000 0.6387828
Global I-squared:
2 2
I .pair I .cons

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 1 0 0
Accepted Article 2 2
t1: treatment 1; t2: treatment 2; I .pair: I-square of pair-wise meta-analysis; I .cons: I-square of network
meta-analysis; Incons.p: inconsistency p-values for pair-wise and network meta-analysis; NA: not applicable

Table 3. Analysis of heterogeneity for ANB

Per-comparison I-squared:
2 2
t1 t2 I .pair I .cons incons.p
1 BAC3E SAFM NA 5.536056 0.2179813
2 BAC3E TBFM NA 52.14721 0.2850996
3 BAMP SAFM NA NA NA
4 BARME-FM BARME-ME NA NA NA
5 BARME-FM TBFM NA NA NA
6 SAFM TBFM 16.60176 23.65759 NA
Global I-squared:
2 2
I .pair I .cons
1 16.63357 34.67431
2 2
t1: treatment 1; t2: treatment 2; I .pair: I-square of pair-wise meta-analysis; I .cons: I-square of network
meta-analysis; Incons.p: inconsistency p-values for pair-wise and network meta-analysis; NA: not applicable

Table 4. Analysis of heterogeneity for Wits

Per-comparison I-squared:
2 2
t1 t2 I .pair I .cons incons.p
1 BAC3E SAFM NA NA NA
2 BAMP SAFM NA 0.000000 0.6588276
3 BAMP TBFM NA 0.000000 0.7871255
4 BARME-FM BARME-ME NA NA NA
5 BARME-FM TBFM NA NA NA
6 SAFM TBFM 39.04984 8.948117 0.7778958
Global I-squared:
2 2
I .pair I .cons
1 39.09319 29.7784
2 2
t1: treatment 1; t2: treatment 2; I .pair: I-square of pair-wise meta-analysis; I .cons: I-square of network
meta-analysis; Incons.p: inconsistency p-values for pair-wise and network meta-analysis; NA: not applicable

Table 5. Analysis of heterogeneity for SN-MP

Per-comparison I-squared:
2 2
t1 t2 I .pair I .cons incons.p
1 BAC3E SAFM NA 0.000000 0.9445019
2 BAC3E SAFM NA 0.000000 0 0.7697487
3 BAMP SAFM NA NA NA
4 BARME-FM BARME-ME NA NA NA
5 BARME-FM TBFM NA NA NA
6 SAFM TBFM NA 0.000000 0 0.9463387

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 Global I-squared:
Accepted Article
1 0
2
I .pair
2
I .cons
0
2 2
t1: treatment 1; t2: treatment 2; I .pair: I-square of pair-wise meta-analysis; I .cons: I-square of network
meta-analysis; Incons.p: inconsistency p-values for pair-wise and network meta-analysis; NA: not applicable

3. Sensitivity analysis
Table 1. Analysis of heterogeneity for SNA (including Tripathi 2016 and Lee 2012)
Per-comparison I-squared:
2 2
t1 t2 I .pair I .cons incons.p
1 BAC3E SAFM NA 0.00000 0.6307457
2 BAC3E TBFM NA 0.00000 0.5790210
3 BAMP SAFM NA NA NA
4 BARME-FM BARME-ME NA NA NA
5 BARME-FM TBFM NA NA NA
6 SAFM TBFM 33.62622 24.15414 0.7305391
Global I-squared:
2 2
I .pair I .cons
1 33.63325 28.10912
2 2
t1: treatment 1; t2: treatment 2; I .pair: I-square of pair-wise meta-analysis; I .cons: I-square of network
meta-analysis; Incons.p: inconsistency p-values for pair-wise and network meta-analysis; NA: not applicable

Table 2. Analysis of heterogeneity for SNA (excluding Tripathi 2016)

Per-comparison I-squared:
2 2
t1 t2 I .pair I .cons incons.p
1 BAC3E SAFM NA 0.00000 0.6327127
2 BAC3E TBFM NA 0.00000 0.5488818
3 BAMP SAFM NA NA NA
4 BARME-FM BARME-ME NA NA NA
5 BARME-FM TBFM NA NA NA
6 SAFM TBFM 32.36907 20.8949 0.7556387
Global I-squared:
2 2
I .pair I .cons
1 32.38447 27.53749
2 2
t1: treatment 1; t2: treatment 2; I .pair: I-square of pair-wise meta-analysis; I .cons: I-square of network
meta-analysis; Incons.p: inconsistency p-values for pair-wise and network meta-analysis; NA: not applicable

Table 3. Analysis of heterogeneity for SNA (excluding Lee 2012)

Per-comparison I-squared:
2 2
t1 t2 I .pair I .cons incons.p
1 BAC3E SAFM NA 0.00000 0.6974215
2 BAC3E TBFM NA 0.00000 0.6056120
3 BAMP SAFM NA NA NA

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 4 BARME-FM BARME-ME NA NA NA
Accepted Article
5
6
BARME-FM
SAFM
TBFM
TBFM
NA
37.05113
NA
26.00955
NA
0.8027579
Global I-squared:
2 2
I .pair I .cons
1 37.06284 29.70519
2 2
t1: treatment 1; t2: treatment 2; I .pair: I-square of pair-wise meta-analysis; I .cons: I-square of network
meta-analysis; Incons.p: inconsistency p-values for pair-wise and network meta-analysis; NA: not applicable

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Accepted Article
Appendix 6
Table 1. Quality of evidence (GRADE)

Number Number of
Outcome Intervention Mean Difference* (95% CI) Quality of evidence
of studies participants

SNA changes BAMP 1 10 1.71 higher (0.62,2.80) ⊕⊕OO Low c

SAFM 9 148 0.84 higher (0.47,1.21) ⊕⊕⊕O Moderate a

BAC3E 2 27 0.63 higher (-0.17,1.43) ⊕⊕OO Low c

BARME-FM 2 37 0.90 higher (-0.42,2.22) ⊕OOO Very low ac

BARME-ME 1 17 0.90 higher (-0.80,2.60) ⊕OOO Very low ac

SNB changes BAMP 1 10 0.88 higher (0.17,1.59) ⊕OOO Very low ac

SAFM 8 138 0.06 higher (-0.24,0.36) ⊕⊕OO Low c

BAC3E 2 27 0.30 lower (-0.93,0.33) ⊕⊕OO Low c

BARME-FM 2 37 0.87 higher (-0.23,1.96) ⊕OOO Very low ac

BARME-ME 1 17 2.08 higher (0.77,3.38) ⊕OOO Very low ac

ANB changes BAMP 1 10 0.66 higher (-0.85,2.17) ⊕⊕OO Low c

SAFM 9 148 0.61 higher (0.13,1.09) ⊕⊕OO Low ab

BAC3E 2 27 0.56 higher (-0.29,1.40) ⊕⊕OO Low c

BARME-FM 2 37 0.41 lower (-1.94,1.13) ⊕OOO Very low ac

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Accepted Article
BARME-ME 1 17 1.62 lower (-3.54,0.30) ⊕OOO Very low ac

Wits changes BAMP 2 31 1.97 higher (0.86,3.08) ⊕⊕⊕O Moderate a

SAFM 5 57 1.01 higher (0.20,1.81) ⊕⊕⊕O Moderate a

BAC3E 1 17 4.44 higher (2.83,6.05) ⊕⊕⊕O Moderate a

BARME-FM 2 37 0.12 higher (-1.54,1.79) ⊕OOO Very low ac

BARME-ME 1 17 0.55 lower (-2.49,1.40) ⊕OOO Very low ac

SN-MP changes BAMP 1 10 3.49 lower (-4.23,-2.75) ⊕⊕⊕O Moderate a

SAFM 5 57 0.48 lower(-0.96,0.00) ⊕⊕⊕O Moderate a

BAC3E 2 27 0.63 higher (-0.09,1.34) ⊕⊕⊕O Moderate a

BARME-FM 2 37 3.01lower (-4.42,-1.60) ⊕⊕⊕O Moderate a

BARME-ME 1 17 4.73 lower(-6.39,-3.07) ⊕⊕⊕O Moderate a

*Mean Difference: differences between the changes in outcomes of the bone-anchored intervention groups (BAMP, SAFM, BAC3E, BARME-FM and

BARME-ME) and TBFM group.

No significant intransitivity was found in the indirect estimates and no significant incoherence was found in the NMA estimates.

a. Downgraded one level for serious risk of bias

b. Downgraded one level for serious imprecision

c. Downgraded two levels for very serious imprecision

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Accepted Article

ocr_12532_f1.tif

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ocr_12532_f2.tif

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