SYSTEMATIC REVIEW

Treatment effectiveness of Fr€ankel function

regulator on the Class III malocclusion:
A systematic review and meta-analysis
Xianrui Yang,a Chunjie Li,b Ding Bai,c Naichuan Su,d Tian Chen,a Yang Xu,a and Xianglong Hane
Chengdu, Sichuan, China

Introduction: The Fra €nkel function regulator III appliance (FR-3) has been used to correct Class III malocclu-
sions for many years; however, its treatment effectiveness is controversial. In this study, we aimed to assess
the effectiveness of the FR-3 in treating patients with Class III malocclusion in the growth and development
period. Methods: Medline (via PubMed), Cochrane Central Register of Controlled Trials, Embase, Chinese
Biomedical Literature Database, China National Knowledge Infrastructure, VIP Database for Chinese Technical
Periodicals, Scirus, Lilacs, Scopus, and World Health Organization International Clinical Trials Registry Platform
were searched electronically. Relevant journals and reference lists of included studies were manually searched.
The quality of the included studies was assessed with the Newcastle-Ottawa scale. The meta-analysis was
carried out using RevMan (version 5.2; Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen,
Denmark). Results: Seven high-quality cohort studies were included. The meta-analysis showed that SNA
changes did not differ in the short (mean difference, 0.43 ; 95% CI, 0.52 -1.39 ) and long (mean difference,
0.37 ; 95% CI, 0.29 -1.03 ) terms. However, SNB changes significantly differed in the short
(mean difference, 1.62 ; 95% CI, 2.62 to 0.62 ) and long (mean difference, 1.50 ; 95% CI, 2.12 to
0.88 ) terms. By contrast, MPA changes did not differ in the short term (mean difference, 0.55 ; 95%
CI, 0.74 -1.84 ). Conclusions: Clinical evidence suggests that the FR-3 might restrict mandibular growth
but not stimulate forward movement of the maxilla. Further high-quality studies are necessary to confirm the
effectiveness of the FR-3. (Am J Orthod Dentofacial Orthop 2014;146:143-54)

M
andibular prognathism and maxillary retru-
sion, which were first documented in the
artwork left by Egyptians and Greeks,1 are
categorized as Class III malocclusion and were clinically
characterized as anterior crossbite2 after the invention
and application of cephalometry.3 The treatment
strategies of Class III malocclusion for patients in the
growth and development period usually focus on growth
modification with various functional appliances.4 In
From the State Key Laboratory of Oral Diseases, West China Hospital of Stoma-
tology, Sichuan University, Chengdu, Sichuan, China.
a
Postgraduate student, Department of Orthodontics.
b
Attending doctor, Department of Oral and Maxillofacial Surgery.
c
Professor and director, Department of Orthodontics.
d
Postgraduate student, Department of Prosthodontics.
e
Associate professor, Department of Orthodontics.
All authors have completed and submitted the ICMJE Form for Disclosure of Po-
tential Conflicts of Interest, and none were reported.
Address correspondence to: Xianglong Han, Department of Orthodontics, State
Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan
University, Chengdu, Sichuan, China; e-mail, xhan@scu.edu.cn.
Submitted, November 2013; revised and accepted, April 2014.
0889-5406/$36.00
Copyright Ó 2014 by the American Association of Orthodontists.
http://dx.doi.org/10.1016/j.ajodo.2014.04.017
1970, Fr€ankel invented an appliance called the function
regulator type III (FR-3) to treat this type of malocclu-
sion.5 The appliance is composed of wire and acrylic,
with 4 acrylic parts. Two upper labial pads are positioned
in the labial vestibule above the maxillary incisors, which
are used to eliminate the restrictive pressure of the upper
lip on the underdeveloped maxilla. Two vestibular
shields extend from the depth of the mandibular
vestibule to the height of the maxillary vestibule; they
act to remove the restrictive forces created by the
buccinators and the associated facial muscles. These
pads can also stimulate labial alveolar bone apposition
by stretching the adjacent periosteum.6
Fr€ankel expected that the FR-3 could stimulate
forward growth of the maxilla and restrict mandibular
development by counteracting the forces of the
surrounding muscles.7 However, much controversy exists
on the treatment effectiveness of the FR-3.6,8,9 Some
studies have demonstrated that with the FR-3, the
mandible moved downward and backward,
thus correcting a Class III malocclusion.10-14 Some
researchers agreed that the malocclusion was corrected
by a substantial effect on the stimulation of maxilla
143
144
growth15; nevertheless, objections still exist.12,16 Most
published studies involve small sample sizes and do not
have sufficient power to confirm the effectiveness of the
FR-3.
To date, Class III patients treated with the FR-3 still
face concerns, such as whether the changes produced
are skeletal or dentoalveolar, whether an influence on
the maxilla or the mandible exists with respect to the
transverse and sagittal dimensions, and whether
treatment effects can be distinguished from normal
growth. The purpose of this article was to perform a
systematic review and a meta-analysis to evaluate
the effectiveness of the FR-3 in patients with Class III
malocclusion in the growth and development period
compared with untreated patients.
MATERIAL AND METHODS
A specified protocol was conducted in advance. Two
calibrated reviewers (X.Y. and C.L.) independently carried
out the study inclusion, data extraction, and risk of bias
processes. The kappa score, which measures the level of
agreement, was 0.92; this was a good score.17 Disagree-
ments between the 2 reviewers were discussed with a
third reviewer (D.B.) for consensus.
The inclusion criteria were the following. (1) Study
type: randomized controlled trials, clinical controlled
trials, and cohort studies. (2) Patients: all participants,
with ages from 5 to 15 years, who were diagnosed as
having an Angle Class III malocclusion in the growth
and development period, without limitations for sex
and race; the diagnostic criteria for Class III malocclusion
were mandibular prognathism, maxillary retrusion, or
anterior crossbite, including both skeletal and dental
deformities. (3) The intervention group wore FR-3
appliances according to the clinicians' instructions. (4)
The control group received no treatment. (5) Outcome
variables: changes in cephalometric measurements,
including overbite and overjet in both groups.
The exclusion criteria were the following. (1) Patients
had other diseases affecting growth and development.
(2) Repetitive publication (only well-described articles
were included).
The following electronic databases were searched for
any published or ongoing study without language
limitations: Medline (via PubMed), Cochrane Central
Register of Controlled Trials (issue 9, 2013), Embase
(www.embase.com), Scirus, Lilacs, Scopus, World Health
Organization International Clinical Trials Registry
Platform, Chinese BioMedical Literature Database, China
National Knowledge Infrastructure, and VIP Database
for Chinese Technical Periodicals. A total of 19 Chinese
dental journals were manually searched in the library
by scanning the titles and abstracts, and the MeSH words
August 2014  Vol 146  Issue 2 American Journal of Orthodontics and Dentofacial Orthopedics
Yang et al
were extracted by the librarians. The reference lists of all
included studies were also searched, and the “related
articles” tool was used in the PubMed search. The
updated search was performed in September 2013. The
search strategy combined MeSH heading words with
free-text words. The main search terms used were
“malocclusion, Angle Class III” and “Fr€ankel appliance.”
For example, the search strategy in PubMed used
“function regulator type III OR FR-3 OR Fr€ankel-III OR
Fr€ankel appliance and malocclusion, Angle Class III
(MeSH terms) OR Class III malocclusion.” The titles and
abstracts were first scanned to find any potentially
eligible studies, and their full texts were obtained for
final consideration. Any obscure or missing data were
obtained by contacting authors.
The Newcastle-Ottawa Scale18 was applied to assess
the quality of the studies. Using this “star system,” we
judged each included study on the basis of 3 broad
perspectives: the selection of the study groups (including
4 items and 1 star for each item), the comparability of the
groups (with only 1 item but 2 stars at most), and the
ascertainment of the outcome of interest (with 3 items
and 1 star for 1 item) (Table I).
A customized data extraction form was developed.
The following items were included: study identification,
including the first author's name and year of
publication; study type; number of participants and
their demographic data; setting; frequency of appliance
wear and duration in the intervention and control
groups; and cephalometric measurement results.
Statistical analysis
RevMan (version 5.2; Nordic Cochrane Centre,
Cochrane Collaboration, Copenhagen, Denmark) was
used in the data analysis. Statistical heterogeneity was
explored using a test for heterogeneity (I2 static) at
a 5 0.10. If I2 .50% and P #0.10, the causes of
the heterogeneity were analyzed, and subgroup
analysis was done. If heterogeneity was high
(I2 .50%), the random-effects model was chosen for
the meta-analysis; otherwise, the fixed-effects model
was adopted. The combined results for the dichotomous
data were expressed as relative risk and 95% confidence
intervals. For continuous data, the mean difference with
95% confidence intervals, as well as the standard error,
was calculated. The statistical significance of the
hypothesis test was set at P \0.05 (2-tailed z tests).
Sensitivity analyses were conducted, evaluating the
pooled effect estimates after omitting each study
individually, to determine the effect of individual studies
on the overall mean difference. If the data could not be
pooled, then they were described. Funnel plots and the
Begg's rank correlation test were chosen to detect
Yang et al
Table I. Items and criteria for quality assessment with the Newcastle–Ottawa scale
Items
Selection Representativeness of the exposed cohort
Selection of the nonexposed cohort
Ascertainment of exposure
Demonstration that outcome of interest was not
present at start of study
Comparability Comparability of cohorts on the basis of the design
or analysis
Outcome Assessment of outcome
Was follow-up long enough for outcomes to occur?
Adequacy of follow-up of cohorts
This table presents each item on the Newcastle–Ottawa scale and explains when stars should be given for each step. The assessment consists of 3
sections. The selection included 4 items, with 1 star for each item; comparability included 1 item, with at most 2 stars for this item; and outcome
included 3 items, with at most 1 star for each item. If the total number of stars was less than 5, the study was low quality; otherwise, it was high
quality.
publication bias if the number of included studies
exceeded 10.19,20
The clinical recommendation of meta-analysis was
assessed using GRADEprofiler, which is used to evaluate
the methodologic quality of studies, the directness of
evidence, the heterogeneity, the precision of effect
estimates, and the risk of publication bias. The GRADE qual-
ity was recorded as high, moderate, low, and very low. Clin-
ical recommendation was classified as strong or weak.21
RESULTS
A total of 151 citations were identified through
electronic and manual searching. Twenty studies were
considered eligible, and full texts were retrieved after
screening the titles and abstracts. Subsequently, 13
studies were excluded for specialized reasons. Finally,
7 studies9,12-14,22-24 were included in the qualitative
synthesis, 6 were included in the meta-analysis, and 1
study23 was described (Fig 1).
All 7 included studies were cohort studies, and all
participants in the treatment group wore the FR-3
appliance for at least a year during their growth and
development periods. Five studies reported short-term
effects, and 1 study reported long-term (8 years)
effects.9 One study reported both short-term (2-3 years)
and long-term (9 years) effects.15 However, 2 studies did
not report the frequency of wearing the appliance.22,23
For the control group without treatment of the Class
III malocclusion, 6 studies simultaneously compared
participants with the treatment group; however, the
authors of the other study chose a controlled sample
from a published study (Table II).14
American Journal of Orthodontics and Dentofacial Orthopedics
145
When to give stars
Truly representative of the average in the community
Somewhat representative of the average in the community
Drawn from the same community as the exposed cohort
Secure record
Structured interview
Yes
Study controls for the most important factor
Study controls for any additional factor
Independent blind assessment
Record linkage
Yes (select an adequate follow-up period for outcome of interest)
Complete follow-up
Subjects lost to follow-up unlikely to introduce bias; small
number lost follow-up, or description provided of those lost
The Newcastle-Ottawa scale, used for assessing the
quality of cohort studies, is shown in Table III. The scores
ranged from 6 to 8, indicating that these studies were
high quality.
Five studies reported the short-term effects of SNA
angle changes in 142 participants in the FR-3 groups
and in 92 participants in the control groups. Two studies
reported the long-term effects in 50 participants in the
FR-3 groups and in 46 participants in the control groups.
The meta-analysis showed that SNA changes did not
differ between the 2 groups in the short term (mean dif-
ference, 0.43 ; 95% CI, 0.52 -1.39 ) and long term
(mean difference, 0.37; 95% CI, 0.29 -1.03 ) (Fig 2).
Moreover, sensitivity analysis was carried out by
excluding 1 study with heterogeneity, showing that there
was no difference in either the short term (mean differ-
ence, 1.02 ; 95% CI, 0.53 -1.51 ) or long term (mean
difference, 0.37 ; 95% CI, 0.29 -1.03) (Fig 3).
SNB angle changes were reported in 5 studies with
142 participants in the FR-3 groups and 92 in the
control groups for the short-term effects, with
significant differences observed between the groups
(mean difference, 1.62 ; 95% CI, 2.62 to 0.62 ).
In terms of long-term effects, 2 studies with 52
participants in the FR-3 groups and 46 participants in
the control groups had significant differences (mean
difference, 1.50 ; 95% CI, 2.12 to 0.88 ) (Fig 4).
The mandibular plane angle (MPA) changes,
measured by the Frankfort MPA in all included studies
except one14 that mentioned only MPA, were reported
in 4 studies. The short-term effects among the 86
participants in the FR-3 groups and the 77 participants
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146 Yang et al

Fig 1. Flow chart showing the process of study inclusion. A total of 146 studies were identified through
the databases, and 5 studies were identified through other sources, including manual searches and
reference lists. After removal of 14 duplicated studies, 137 studies were screened for their titles and
abstracts, and only 20 studies became eligible for inclusion. However, after the full texts of the 20
studies were read, only 7 studies were included in the qualitative synthesis, and 6 studies were included
in the quantitative synthesis.

in the control groups showed no difference (mean
difference, 0.55 ; 95% CI, 0.74 -1.84 ) (Fig 5).
Five studies reported ANB angle changes for the
short-term effects among 142 participants in the FR-3
group and among 92 participants in the control groups.
Two studies reported long-term effects among 52 par-
ticipants in the FR-3 groups and among 46 participants
in the control groups. The meta-analysis showed
statistical differences in both the short term (mean
difference, 1.84 ; 95% CI, 0.96 -2.71 ) and long term
(mean difference, 0.07 ; 95% CI, 3.17 -3.30 ) (Fig 6).
Only 2 studies reported changes in the Wits appraisal
in the short term among 62 participants in the FR-3
groups and 52 participants in the control groups; these
had significant differences (mean difference, 2.70 mm;
95% CI, 1.88-3.52 mm) (Fig 7).
Four studies with 86 participants in the FR-3 groups
and 77 participants in the control groups reported
changes of overjet and overbite for the short-term
effects. Two studies with 52 participants in the FR-3
groups and 46 participants in the control groups
reported the long-term effects. The meta-analysis showed
significant differences in overjet between the short term
(mean difference, 3.47 mm; 95% CI, 2.93-4.01 mm)
and long term (mean difference, 4.56 mm; 95% CI,
3.78-5.35 mm) (Fig 8). However, no difference existed
in overbite in the short term (mean difference,
0.06 mm; 95% CI, 0.53-0.65 mm) and long term (mean
difference, 1.07 mm; 95% CI, 3.71-1.58 mm) (Fig 9).
One study reported statistically significant increases in
the maxillary intermolar, interpremolar, and intercanine
widths, as well as increases in the mandibular intermolar

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 American Journal of Orthodontics and Dentofacial Orthopedics

Yang et al
Table II. Characteristics of included studies
Waheed-Ul-
Study Levin9 (2008) Falck9 (2007) Kalavritinos14 (2005) Baik13 (2004) Hameed22 (2002) Sonmez23 (1996) Mustafa24 (1994)
FR-3 group (n) 32 (15 M, 17 F) 56 (20 M, 36 F) 14 (7 M, 7 F) 30 (13 M, 17 F) 10 (5 M, 5 F) 20 (10 M, 10 F) 20 (10 M, 10 F)
Location of selection Heinrich Braun Heinrich Braun Department of Yonsei University Orthodontic clinic, Department of Faculty of Dentistry,
of Fr€ankel patients Regional Hospital, Hospital, Zwickau, Orthodontics, Dental Hospital, Lahore, Pakistan Orthodontics, University of
Zwickau, Germany Germany School of Dentistry, Seoul, Korea University of Istanbul, Turkey
Thessaloniki, Greece Istanbul, Turkey
Initial mean age (y) 7 7.6 9.7 8 8.7 9.5 9.5
Inclusion criteria Anterior crossbite or Angle Class III molar Angle Class III molar Mild or pseudo Class III with maxillary Only anterior crossbite Could move the
edge-to-edge relationship and relationship, overjet (functional) Class III deficiency, mandible backward
incisor relationship, overjet of \0 mm of #0 mm for all malocclusion; good functional anterior and bite the anterior
with a Wits for all incisors incisors cooperation crossbite, no teeth in an edge-to-
appraisal of 2 mm anterior open bite edge position
or more
Frequency of Only daytime until the Full-time for 14-16 hours per day At least 14 hours per Not specified Not specified Full time
appliance wear third month, then 1-2 years, then day
full-time for 2-3 while sleeping and
years 4-5 h during the day
for another
2-3 years
Mean period of Short term: 2-3 8.2 2.4 1.3 1 1.9 1.9
treatment (y) Long-term: 9
Numbers in untreated Short term: 32 15 (7 M, 8 F) 15 (8 M, 7 F) 20 (10 M, 10 F) 10 (5 M, 5 F) 19 (9 M, 10 F) 20 (10 M, 10 F)
control group (15 M,17 F)
Long term: 26
(13 M, 13 F)
Location of selection University of Florence, Department of Department of Not specified Orthodontic clinic, Department of Not specified
August 2014  Vol 146  Issue 2

of untreated Italy, and University Orthodontics, Orthodontics, Lahore, Pakistan Orthodontics,

controls of Michigan, Heinrich Braun School of Dentistry, University of
Ann Arbor Hospital, Zwickau, Thessaloniki, Greece Istanbul, Turkey
Germany
Initial mean age (y) 6.1 8 8.1 8.2 8.74 9.4 9.3
Mean observation Short term: 2-3 8 6 1.5 1 1.8 1.8
period (y) Long term: 9
This table shows the characteristics of the 7 included studies. The study identification, including the first author's name and year of publication, the number of participants and their demographic data,
the setting, the frequency of appliance wear and duration in the intervention group, and the control group of each study were described.
M, Male; F, female.

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Table III. Quality assessment of nonrandomized studies

Study
22 14
Waheed-Ul-Hameed Kalavritinos Levin15 Sonmez23 Baik13 Falck9 Mustafa24
Quality evaluation (2002) (2005) (2008) (1996) (2004) (2007) (1994)
Representativeness of the FR-3 group * * * * * * *
Selection of the control group * * *
Ascertainment of FR-3 treatment group * * * * * * *
Demonstration that outcome of interest * * * * * * *
was not present at start of study
Comparability of participants in FR-3 and ** * ** ** * * **
control groups
Assessment of outcome with independent
blinding
Adequacy of follow-up * * * * * * *
Lost to follow-up acceptable * * * * * * *
(\10% and reported)
Total quality (score) High (8) High (6) High (7) High (8) High (6) High (6) High (8)

This table shows the quality assessment of each study. Each item received 1 star (*), except for comparability, which can receive 2 stars. The total
number of stars represents the score, which demonstrates the quality of the study. All included studies were of high quality according to this
assessment.

Fig 2. Meta-analysis of SNA changes comparing the FR-3 groups with the untreated groups. Forest
plot for the mean differences of the SNA changes between the FR-3 and untreated groups, including
the number of source studies, effect sizes with 95% confidence intervals, assessments of heterogene-
ity, and statistical significance. Subgroup analysis consisted of the results in the short and long terms.

and intercanine widths, without comparisons with a
control group.14 Only 1 study with a control group
focused on transversal dimension changes.23 This study
indicated that the FR-3 appliance caused significant
increases in the intermolar and interpremolar distances
in the maxilla in both the dental and alveolar areas;
however, these increases were not apparent in the width
of the nasal cavity or the maxillary base.
According to the GRADE quality analysis, the quality
of the evidence for overjet outcomes in both the short
and long terms was high; therefore, it is suggested
that these outcomes can be adopted in the clinic. The
quality of the evidence for overbite in the long term
was very low, and for ANB in the long term was low.
The quality of the evidence for all other results was mod-
erate, and further research is needed for a definite
confirmation (Table IV).
DISCUSSION
This systematic review was performed to provide data
on the effectiveness of the FR-3 appliance for Class III
malocclusion patients in their growth and development
period. After our comprehensive search and evaluation,
only 7 articles were included. All were cohort studies

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Yang et al 149

Fig 3. Sensitive analysis of SNA changes comparing the FR-3 groups with the untreated groups.
Forest plot for the mean difference of the SNA changes between the FR-3 and untreated groups
excluding 1 study with opposite results, including the number of source studies, effect sizes with
95% confidence intervals, assessment of heterogeneity, and statistical significance. Subgroup
analysis consisted of the results in the short and long terms.

Fig 4. Meta-analysis of SNB changes comparing the FR-3 groups with the untreated groups. Forest
plot for the mean difference of the SNB changes between the FR-3 and untreated groups, including
the number of source studies, effect sizes with 95% confidence intervals, assessment of heterogeneity,
and statistical significance. Subgroup analysis consisted of the results in the short and long terms.

without blinding of participants and personnel because
the appliance is evident in the participants. The
meta-analysis results demonstrated that SNA changes
have a statistical difference in the short term between
the FR-3 group and the untreated group but did not differ
in the long term. The SNB changes differed significantly
in both short and long terms, indicating that the FR-3
possibly restricted mandibular growth. MPA changes in
the short term showed no difference, and data for the
long-term effects of the FR-3 were unavailable. The
ANB changes showed a significant difference in the short
term but not in the long term. The Wits appraisal changes
were significant; however, only 2 studies were included,
possibly decreasing reliability. With respect to overjet
and overbite, all included studies reported a significant
difference for overjet in both the short and long terms;
the results for overbite varied and did not differ after
meta-analysis in the short and long terms.
Cephalometric analysis was used in most of the
studies, but with different methods. Some used
landmarks to locate the position changes. However,
identification was difficult, and the changes were not

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Fig 5. Meta-analysis of MPA changes comparing the FR-3 groups with the untreated groups. Forest
plot for the mean difference of the MPA changes between the FR-3 and untreated groups, including
the number of source studies, effect sizes with 95% confidence intervals, assessment of heterogeneity,
and statistical significance.

Fig 6. Meta-analysis of ANB changes comparing the FR-3 groups with the untreated groups. Forest
plot for the mean difference of the ANB changes between the FR-3 and untreated groups, including
the number of source studies, effect sizes with 95% confidence intervals, assessment of heterogeneity,
and statistical significance. Subgroup analysis consisted of the results in the short and long terms.

Fig 7. Meta-analysis of changes in the Wits appraisal comparing the FR-3 groups with the untreated
groups. Forest plot for mean difference of the Wits appraisal changes between the FR-3 and untreated
groups, including the number of source studies, effect sizes with 95% confidence intervals, assess-
ment of heterogeneity, and statistical significance.

typically represented; some varied downward or such as overjet and overbite, whereas others used
backward, as denoted by minus signs with a highly un- angular values (eg, SNA and SNB) for indicators.
detected bias. Some authors used linear measurements, Soft-tissue changes were also adopted in some studies

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Yang et al 151

Fig 8. Meta-analysis of overjet changes comparing the FR-3 groups with the untreated groups. Forest
plot for the mean difference of the overjet changes between the FR-3 and untreated groups, including
the number of source studies, effect sizes with 95% confidence intervals, assessment of heterogeneity,
and statistical significance. Subgroup analysis consisted of the results in the short and long terms.

Fig 9. Meta-analysis of overbite changes comparing the FR-3 groups with the untreated groups. Forest
plot for the mean difference of the overbite changes between the FR-3 and untreated groups, including
the number of source studies, effect sizes with 95% confidence intervals, assessment of heterogeneity,
and statistical significance. Subgroup analysis consisted of the results in the short and long terms.

to evaluate the upper and lower lips in relation to the
E-plane. Kalavritinos et al14 pointed out that the
thicknesses in the upper and lower lips increased, and
significant increases in facial convexity and nose prom-
inence were observed upon assessment of the soft-tissue
profile. However, the soft-tissue changes were reported
only in 1 study, which did not have enough reliability
because of its small sample size.14 Thus, further
evidence is required for confirmation. Moreover, dental
cast evaluations were carried out in only a few studies.
Sonmez and Mustafa23 declared that the FR-3 could
cause increases in the intermolar and interpremolar
distances in the maxilla. Lacking large sample support,
the results were not reliable enough to be clinically
applied, and more relevant studies with high quality
are needed. By contrast, the IMPA changes did not differ
in the reported studies, whereas the changes in the angle
between the maxillary and mandibular central incisors
were significantly different.21 This finding lacks
reliability because of the small sample size. Lateral
crossbite was pointed out in some studies. Sonmez
and Mustafa reported that the unilateral crossbite
tendency disappeared in 3 of the 4 patients. However,
in 1 patient, the tendency was enhanced to a complete

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Table IV. Results of GRADE quality analysis of the studies and their outcomes
Number of participants Expected absolute effects
Outcomes followed Quality of the evidence (GRADE) Risk difference with FR-3 (95% CI)
ANB, short term 234 (5 studies) 444. Mean ANB, short term, in the
Moderate1,2,3 intervention groups was 1.84
due to inconsistency, large effect, possible higher (0.96 -2.71 higher)
confounding would change the effect
ANB, long term 98 (2 studies) 44.. Mean ANB, long term, in the
Low1,2,3,4 intervention groups was 0.07
due to inconsistency, imprecision, large higher (3.17 lower-3.3 higher)
effect, possible confounding would
change the effect
SNA, short term 234 (5 studies) 444. Mean SNA, short term, in the
Moderate1,2,3 intervention groups was 0.43
due to inconsistency, large effect, possible higher (–0.52 lower-1.39 higher)
confounding would change the effect
SNA, long term 96 (2 studies) 444. Mean SNA, long term, in the
Moderate2,3,4 intervention groups was 0.37
due to imprecision, large effect, possible higher (0.29 lower-1.03 higher)
confounding would change the effect
SNB, short term 234 (5 studies) 444. Mean SNB, short term, in the
Moderate1,2,3 intervention groups was1.62
due to inconsistency, large effect, possible lower (2.62 - 0.62 lower)
confounding would change the effect
SNB, long term 98 (2 studies) 444. Mean SNB, long term, in the
Moderate2,3,4 intervention groups was 1.5
due to imprecision, large effect, possible lower (2.12 -0.88 lower)
confounding would change the effect
MPA, short term 163 (4 studies) 444. Mean MPA, short term, in the
Moderate2,3,4 intervention groups was 0.55
due to imprecision, large effect, possible higher (0.74 lower-1.84 higher)
confounding would change the effect
Overjet, short term 163 (4 studies) 4444 Mean overjet, short term, in the
High1,2,3 intervention groups was 3.47 mm
due to large effect, possible confounding higher (2.93-4.01 mm higher)
would change the effect
Overjet, long term 98 (2 studies) 4444 Mean overjet, long term, in the
High1,2,3,4 intervention groups was 4.56 mm
due to imprecision, large effect, possible higher (3.78-5.35 mm higher)
confounding would change the effect
Overbite, short term 163 (4 studies) 4444 Mean overbite, short term, in the
High2,3 intervention groups was 0.06 mm
due to large effect, possible confounding lower (0.53 mm lower-0.65 mm higher)
would change the effect
Overbite, long term 98 (2 studies) 4... Mean overbite, long term, in the
Very low1,2,3,4 intervention groups was 1.07 mm
due to inconsistency, imprecision, possible lower (3.71 mm lower-1.58 mm higher)
confounding would change the effect
Wits appraisal 114 (2 studies) 444. Mean Wits appraisal in the
Moderate2,3,4 intervention groups was 2.7 mm
due to imprecision, large effect, possible higher (1.88-3.52 mm higher)
confounding would change the effect
The table shows the results of the GRADE quality analysis of the studies and their outcomes. The quality of evidence was classified as “High,”
“Moderate,” “Low,” and “Very low.” High quality, further research is unlikely to change our confidence in the effect estimation. Moderate quality,
further research is likely to have an important effect on our confidence in the effect estimation and might change the estimate. Low quality, further
research is likely to have an important effect on our confidence in the effect estimation and to change the estimate. Very low quality, we are
uncertain about the estimate. The classification was according to the assumed risk: 1, the meta-analysis showed that heterogeneity was high;
2, the mean difference was apparent; 3, all participants were schoolchildren, who might not have worn the appliance all the time; 4, the sample
was small, and the results had a wide confidence interval.
4indicates the number of items increasing the evidence quality; .indicates the number of items decreasing the evidence quality.

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Yang et al
unilateral crossbite by the end of the treatment period.
The bilateral crossbite tendency was completely treated
in 2 patients, and 2 of the 3 patients with unilateral
crossbite were successfully treated. Nevertheless, 1
patient still had a crossbite at the end of treatment.
The premolar region was successfully treated in 2 of
the 3 patients with bilateral crossbite, whereas the first
molars continued in crossbite. Bilateral crossbite did
not disappear in 1 patient. However, these results,
which were also based on a small sample size, need
more relevant high-quality studies to confirm the
conclusions.
The quality of these studies was assessed with the
Newcastle-Ottawa scale, and all had a high level.
However, the cohort study had a low level of evidence
when compared with the randomized clinical trials.19
Therefore, the GRADE evaluating system was used to
comprehensively assess the level of evidence. On the
basis of this review and meta-analysis, the maxillary
position, measured by SNA, did not significantly change,
with moderate GRADE quality in both the short and
long terms. Mandibular position, measured by SNB,
significantly changed, with moderate GRADE quality in
the short term with high heterogeneity, and in the
long term without heterogeneity. ANB change had
moderate quality in the short term and low quality in
the long term. Both the MPA and the Wits appraisal
changes had moderate quality. The overjet changes
were reported to be significant in all studies, and the
meta-analysis of these studies showed high levels of
evidence in the GRADE assessment.
Although the normalized process of systematic
review and meta-analysis was carefully carried out,
some bias still persisted. First, selection bias could not
be completely avoided; this is a problem that all system-
atic reviews face. We searched both electronic databases
and ongoing trials and also performed a manual search,
which could restrict this bias to some extent. Second, the
sample size in each study was small. Therefore, statistical
power was lacking. The nonconformity of the cephalo-
metric measurement results also made data synthesis
unsatisfactory. Third, clinical heterogeneity among the
studies could not be avoided; this can be explained by
many influencing factors, such as the various growth
speeds among patients and the sex data.25,26 The sex
data were combined in all studies because there were
no statistically significant differences between males
and females in either the treatment or the control
group.13,23 Fourth, only 7 studies were included, and
funnel plots and the Begg's rank correlation test were
not conducted. Therefore, some publication bias might
exist, such as funding support for published studies.
Although Levin et al15 emphasized the importance of
American Journal of Orthodontics and Dentofacial Orthopedics
153
considering long-term (.5 years) treatment outcomes
of wearing the FR-3 appliance, few studies reported
the long-term effectiveness of the appliance, and those
that did lacked follow-up data. Furthermore, the unex-
plained statistical heterogeneity and lack of randomized
controlled trial studies limited the overall conclusions,
which call for future high-quality studies to obtain
more stable conclusions.
CONCLUSIONS
This systematic review and meta-analysis shows that
the evidence supporting the forward movement of the
maxilla caused by the FR-3 appliance is not strong
enough. Conversely, the theory that the FR-3 appliance
restricts mandibular development seems reasonable;
however, further high-quality studies are needed to
arrive at a stable conclusion on the effectiveness of
the FR-3 appliance on Angle Class III malocclusions.
Moreover, a global normalized cephalometric measure-
ment method should be developed so that clinicians
can easily communicate, and research data from
different institutions can be pooled to enlarge the
sample size, thus reinforcing inferences and conclusions.
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