SYSTEMATIC REVIEW

Effectiveness of orthodontic treatment with

functional appliances on mandibular growth in
the short term
Elvira Marsico,a Elda Gatto,b Maryalba Burrascano,a Giovanni Matarese,c and Giancarlo Cordascod
Messina, Italy

Introduction: The aim of this study was to analyze the current literature for the best evidence (randomized clin-
ical trials) about the efficacy of functional appliances on mandibular growth in the short term. Methods: A survey
of articles published up to September 2009 was performed by using the following electronic databases:
PubMed, Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, Web of Science, LILACS,
and Google Scholar. The reference lists of the retrieved articles were hand-searched for possible missing arti-
cles. No language restriction was applied during the identification of the published studies. A methodologic scor-
ing process was developed to identify which randomized clinical trials were stronger methodologically. The
selection process and the quality assessment were undertaken independently and in duplicate by 2 authors.
A meta-analysis was attempted by using random-effects models. Clinical and statistical heterogeneity was
examined, and a sensitivity analysis was performed. Results: Electronic searches identified the following items:
146 articles were retrieved from PubMed, 45 from Cochrane Central Register of Controlled Trials, 29 from Ovid,
42 from LILACS, 628 from Web of Science, and 1000 from Google Scholar. Thirty-two articles fulfilled the
specific inclusion criteria and were identified as potentially appropriate randomized clinical trials to be
included in this meta-analysis. Only 4 articles, based on data from 338 patients (168 treated vs 170 controls)
with Class II malocclusion in the mixed dentition, were selected for the final analysis. The quality analysis of
these studies showed that the statistical methods were at the medium-high level. The outcome
measurements chosen to evaluate the efficacy of the various functional appliances were Co-Pg, Pg/Olp 1
Co/Olp, and Co-Gn and the values were annualized and standardized to a uniform scale with the
standardized mean differences (SMD). The results of the meta-analysis from the random-effects model
showed a statistically significant difference of 1.79 mm in annual mandibular growth of the treatment group
compared with the control group (SMD 5 0.61, 95% CI, 0.30 to –0.93; chi-square test, 5.34; 3 df; P 5 0.15;
I2 5 43.9%; test for overall effect, Z 5 3.83 and P 5 0.0001). The sensitivity analysis showed a substantially
similar outcome of 1.91 mm (SMD 5 0.65, 95% CI, 0.25 to 1.25; chi-square test, 4.96; 2 df; P 5 0.08; I2 5
59.7%; test for overall effect, Z 5 3.19 and P 5 0.001). Conclusions: The analysis of the effect of treatment
with functional appliances vs an untreated control group showed that skeletal changes were statistically signif-
icant, but unlikely to be clinically significant. (Am J Orthod Dentofacial Orthop 2011;139:24-36)

O
ne of the most controversial topics in orthodon- II malocclusion, mandibular retrusion seems to be a ma-
tics relates to the effectiveness of functional ap- jor contributing factor; it occurs in about one third of
pliances on mandibular growth. In skeletal Class the population.1 Functional appliances encompass
a
a range of removable and fixed devices that are designed
Private practice, Messina, Italy.
b
Research fellow, Department of Orthodontics, School of Dentistry, University of
to alter the position of the mandible, both sagittally and
Messina, Messina, Italy. vertically, to induce supplementary lengthening of the
c
Assistant professor, Department of Orthodontics, School of Dentistry, University mandible by stimulating increased growth at the condy-
of Messina, Messina, Italy.
d
Professor, head, and chairman, Department of Orthodontics, School of Den-
lar cartilage.2-5
tistry, University of Messina, Messina, Italy. Experiments have demonstrated that appliances that
The authors report no commercial, proprietary, or financial interest in the prod- position the mandible anteriorly stimulate significant man-
ucts or companies described in this article.
Reprint requests to: Elvira Marsico, Vle Boccetta, 14, 98122 Messina, Italy;
dibular growth by condyle remodeling in animal models,
e-mail, elvira.marsico@alice.it. but the effects produced in humans are not the same.6-9
Submitted, December 2009; revised and accepted, April 2010. Evidence shows that favorable growth responses are not
0889-5406/$36.00
Copyright Ó 2011 by the American Association of Orthodontists.
always achieved with functional therapy; some authors
doi:10.1016/j.ajodo.2010.04.028 reported increases in overall mandibular length10-14 and
24
Marsico et al 25

changes in the amount of condylar growth,15-18 but others

Table I. PubMed search history
believe that mandibular length cannot be altered by such
therapy.19-21 It has been claimed that most of the Keywords Results
correction of the malocclusion is due to dentoalveolar (1) Randomized controlled trial 335,072
changes with a small but statistically significant amount (2) Randomized controlled trials 338,843
(3) Random allocation 66,497
of skeletal effects.3,22,23
(4) Double blind 123,934
There are also controversies concerning the effects of (5) Double blind method 103,271
functional appliances on the maxilla. Many studies indi- (6) Single blind 29,535
cate that forward growth of the maxilla might be in- (7) Single blind method 24,124
hibited,21,24 but other authors stated that there is no (8) #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 427,734
(9) Class II malocclusion 4387
appreciable effect on the position of the maxilla.3,25-27
(10) Orthodontic functional appliances 1599
All of these conflicting claims could be attributable to (11) #9 OR #10 5386
retrospective study designs or methodologic limitations (12) #8 AND #11 169
such as small samples, inadequate or no control group, (13) #8 AND #11, limit: humans 146
dishomogeneity of the groups for sex and age at the start
of therapy, and different lengths of treatment.28 therapy of Class II malocclusion; (4) had a comparable
In addition, there is a lack of long-term studies on the untreated control group; (5) analyzed treatment effects
effect of functional appliances to evaluate the stability not confounded by additional and concomitant treat-
of skeletal changes because of the great difficulties in re- ments (headgear, extractions, or fixed appliances);
cruiting patients after treatment.12 (6) used cephalometric analysis at the start of treatment
The aim of this study was to analyze results from ran- and just after removal of the functional appliances; and
domized controlled trials (RCTs) in the literature con- (7) concerned with mandibular anteroposterior changes
cerning Class II functional therapy to evaluate the measured by using the anatomic condylion.
efficacy of functional appliances on mandibular growth. Articles were not selected if they did not meet the in-
clusion criteria, if they did not relate to this topic, or if
MATERIAL AND METHODS
they related but had a different aim. Abstracts, labora-
A survey of articles published up to September 2009 tory studies, descriptive studies, individual case reports,
about the effects of functional appliances on mandibular series of cases, reviews, studies of adult patients, con-
growth was performed by using several electronic trolled clinical trials, retrospective longitudinal studies,
databases: PubMed, Ovid (Ovid Medline and Embase), and meta-analyses were excluded. Articles reporting in-
Cochrane Central Register of Controlled Trials, Web of terim outcomes or updates were considered only once
Science, LILACS, and Google Scholar. All electronic because they related to the same samples of subjects.
searches were conducted on September 30, 2009. The RCTs including patients who had received previous or
search strategy for PubMed was conducted according to concomitant treatment for their Class II malocclusion
Cochrane Collaboration guidelines (Table I).29 The key- were also excluded.
words used to identify the corresponding studies in the
other databases were Class II malocclusion and ortho- Data abstraction
dontic functional applianc*. A more selective search strat-
The selection process was done by 2 independent re-
egy for Google Scholar was performed with the following
viewers (E.M. and M.B.) using separate printed forms.
terms: Class II malocclusion, orthodontic functional
The data extracted from each article were compared
appliances, and randomized clinical trial. Electronic
and discussed to resolve any discrepancies and to reach
search results are given in detail in Table II. The reference
unanimous consensus. Cohen’s kappa score was calcu-
lists of the retrieved articles were also hand-searched to
lated to determine interrater reliability.
identify any articles to be included in this evaluation
that might have been missed in the electronic biblio-
graphic databases. No language restriction was applied Validity assessment
during the identification process of published studies. Because high-quality methodologic studies can pro-
vide more reliable conclusions, the current Cochrane
Selection criteria guidelines for assessing quality were adopted to evaluate
To be included in our study, each article had to fulfil the risk of bias of the trials included.30 The quality assess-
the following requirements: (1) related human clinical ment was undertaken independently and in duplicate by
trials; (2) included a randomized selection of the sam- using separate printed forms by the 2 reviewers, and
ples; (3) concerned with functional appliances in the agreement was assessed with the kappa statistic.

American Journal of Orthodontics and Dentofacial Orthopedics January 2011  Vol 139  Issue 1
26 Marsico et al

Table II. Search results from various electronic databases

Not related to the topic or
Database Keywords Results related with different aim No RCTs Selected
PubMed Search history as described by 146 102 16 28
Table I
Cochrane Central Register of (1) Orthodontic functional 45 12 32 1
Controlled Trials appliances; (2) Class II
malocclusion; #1 AND #2;
Ovid (1) Orthodontic functional 29 11 17 1
appliances; (2) Class II
malocclusion; #1 AND #2;
Web of Science (1) Orthodontic functional 628 412 198 18
applianc*; (2) Class II
malocclusion; #1 AND #2;
Google Scholar (1) Orthodontic functional 1000 883 95 22
applianc*; (2) Class II
malocclusion; (3)
randomized clinical trials;
#1 AND #2 AND #3;
LILACS (1) Orthodontic functional 42 10 32 0
applianc*; (2) Class II
malocclusion; #1 AND #2;
Hand search Bibliographies of RCTs, RCTs 1 1
known to the authors
before this study, and RCTs
encountered during
searches for other projects

Study characteristics deviations of the continuous outcomes were used to

All selected RCTs related to orthodontic functional
therapy in children during the transitional dentition
stage of development with Class II malocclusion.31-34
From the selected articles, the following study
characteristics were recorded: sample size, type of
functional appliance, sex and age, time of treatment or
observation, time of daily appliance wear, cephalometric
measurements of outcomes, and follow-up. Clinical
heterogeneity was assessed by examining the types of
participants and the interventions for the outcome in
each study.
Quantitative data synthesis
The effective increase of total mandibular length was
the outcome chosen to evaluate the efficacy of the various
functional appliances. Cephalometric reference points
and linear measurements of overall mandibular length
recorded from each selected study were condylion-
pogonion (Co-Pg), condylion-gnathion (Co-Gn), and
pogonion-occlusal line perpendiculare 1 condylion-
occlusal line perpendiculare (Pg/Olp 1 Co/OLp).
Studies that used articulare were excluded because
this end-point landmark does not measure the real man-
dibular increase.32 We did not consider angular mea-
surements because they do not evaluate effective
mandibular growth. The mean differences and standard
summarize the data for each group.
The outcome values were standardized to a uniform
scale with standardized mean differences (SMD) and
were combined by using random-effects models. When
studies use different measurements to evaluate the
same outcome, SMD (difference in mean outcome be-
tween groups or standard deviations of outcomes
among participants) can be used in a meta-analysis for
combining continuous data.
The significance of any discrepancies in the esti-
mates of the treatment effects from the RCTs was as-
sessed with the Cochrane test for heterogeneity and
the I2 statistic. We performed a sensitivity analysis to
examine the effect of the study quality assessment on
the overall estimates of effect.
RESULTS
Electronic searches identified the following items:
146 articles from PubMed, 45 from Cochrane Central
Register of Controlled Trials, 29 from Ovid, 42 from LI-
LACS, 628 from Web of Science, and 1000 from Google
Scholar. Articles that did not relate to our topic or related
with a different aim, and those that were not RCTs, were
excluded, as shown in Table II.
Of the remaining potentially appropriate RCTs, 38 were
duplicates, so 32 were identified as eligible RCTs to be

January 2011  Vol 139  Issue 1 American Journal of Orthodontics and Dentofacial Orthopedics
Marsico et al 27

Manual search Electronic search

Potentially relevant articles identified and

RCTs retrieved by manual
screened for retrieval (PM=146,
search to be included in the
CCRCT=45, Ov=29, WS=628, GS=1000,
meta-analysis (n=1)
LI=42)

Articles excluded, not relate to the

present topic or relate with different aim
(PM=102, CCRCT=12, Ov=11,
WS=412, GS=883, LI=10)

Articles retrieved for more detailed

evaluation (PM=44, CCRCT=33, Ov=18,
WS=216, GS=117, LI=32)

Articles excluded, not randomized

clinical trials (PM=16, CCRCT=32,
Ov=17, WS=198, GS=95, LI=32)

Potentially appropriate RCTs to be

included in the meta-analysis (PM=28,
CCRCT=1, Ov=1, WS=18, GS=22, LI=0)

RCTs excluded, the same references

retrieved in several databases (n=38)

RCTs to be included in the meta-analysis

(n=32)

RCTs withdrawn as reported by Table III

(n=29)

RCTs with usable information, by

outcome (n=3)

PM=PubMed, CCRCT=Cochrane Central Register of Controlled Trials, Ov=Ovid, WS=Web of Science, GS=Google Scholar, LI=LILACS.

Fig 1. Flow chart.

included in this study (Fig 1).32-63 In detail, 6 studies were
retrieved from PubMed; 4 from Google Scholar; 4 from
both PubMed and Google Scholar; 4 from PubMed and
Web of Science; 12 from PubMed, Google Scholar, and
Web of Science; 1 from PubMed, Google Scholar, Web
of Science, and Ovid; and 1 from PubMed, Google
Scholar, Web of Science, and Cochrane Central Register
of Controlled Trials (Table III).
Twenty-nine of the 32 RCTs were withdrawn accord-
ing to the following exclusion reasons: (1) lack of an
untreated control group40,46,47,50,53,56,57,59,63; (2) lack
of random allocation of the untreated control

American Journal of Orthodontics and Dentofacial Orthopedics January 2011  Vol 139  Issue 1
28 Marsico et al

Table III. Studies excluded from the meta-analysis and reasons of exclusion
Reference Databases Study Reason for exclusion
35 Web of Science, PubMed Webster T et al. Associations between Reported interim outcomes or
changes in selected facial updates32
dimensions and the outcome of
orthodontic treatment. Am J
Orthod Dentofacial Orthop
1996;110:46-53.
36 PubMed Cura N, Saraç M. The effect of Concomitant use of headgear with
treatment with the Bass appliance Bass appliance; cephalometric
on skeletal Class II malocclusions: analysis that did not use condylion
a cephalometric investigation. Eur J
Orthod 1997;19:691-702.
37 PubMed Mao J, Zhao H. The correction of Class Concomitant use of headgear with
II, division 1 malocclusion with bionator appliance
bionator headgear combination
appliance. J Tongji Med Univ
1997;17:254-6.
38 Web of Science, PubMed Tulloch JFC et al. Influences on the Related to the present topic but
outcome of early treatment for different aim
Class II malocclusion. Am J Orthod
Dentofacial Orthop 1997;111:
533-42.
39 Google Scholar, PubMed Keeling SD et al. Anteroposterior Patients received previous treatment
skeletal and dental changes after
early Class II treatment with
bionators and headgear. Am J
Orthod Dentofacial Orthop
1998;113:40-50.
40 Google Scholar, Web of Science, Ghafari J et al. Headgear versus No untreated control group
PubMed function regulator in the early
treatment of Class II division 1
malocclusion: a randomized clinical
trial. Am J Orthod Dentofacial
Orthop 1998;113:51-61.
41 Google Scholar, Web of Science, Tulloch JFC et al. Benefit of early Class Reported interim outcomes or
PubMed II treatment: progress report of updates33
a two-phase randomized clinical
trial. Am J Orthod Dentofacial
Orthop 1998;113:62-72.
42 Google scholar, Web of Science, Illing HM et al. A prospective Lack of control group’s randomization
PubMed evaluation of Bass, bionator and
twin block appliances. Part I—the
hard tissues. Eur J Orthod
1998;20:501-16.
43 Google scholar, Web of Science, Ehmer U et al. An international Lack of control group’s
PubMed, Cochrane comparison of early treatment of randomization: the control sample
angle Class-II/1 cases. Skeletal is the same as in Tulloch et al33
effects of the first phase of
a prospective clinical trial. J Orofac
Orthop 1999;60:392-408.
44 PubMed Wheeler TT et al. Effectiveness of early Reported interim outcomes or
treatment of Class II malocclusion. updates39
Am J Orthod Dentofacial Orthop
2002;121:9-17.
45 Web of Science, PubMed Cevidanes LH et al. Clinical outcomes Cephalometric analysis did not use
of Fr€ankel appliance therapy condylion
assessed with a counterpart
analysis.Am J Orthod Dentofacial
Orthop 2003;123:379-87.

January 2011  Vol 139  Issue 1 American Journal of Orthodontics and Dentofacial Orthopedics
Marsico et al 29

Table III. Continued

Reference Databases Study Reason for exclusion

46 PubMed King GJ et al. Comparison of peer No untreated control group
assessment ratings (PAR) from
1-phase and 2-phase treatment
protocols for Class II malocclusions.
Am J Orthod Dentofacial Orthop
2003;123:489-96.
47 Google Scholar, Web of Science, O’Brien K et al. Effectiveness of No untreated control group
PubMed treatment for Class II malocclusion
with the Herbst or twin-block
appliances: a randomized,
controlled trial. Am J Orthod
Dentofacial Orthop 2003;124:
128-37.
48 Google Scholar, PubMed Araujo AM et al. Adaptive condylar Cephalometric analysis did not use
growth and mandibular condylion
remodelling changes with bionator
therapy—an implant study. Eur J
Orthod 2004;26:515-22.
49 Google Scholar Huang G. Twin-block appliance is Summary trial of O’Brien et al34
effective for the correction of Class
II Division I malocclusion during
mixed dentition. J Evid Based Dent
Pract 2004;4:222-3.
50 PubMed Banks P et al. Incremental versus No untreated control group
maximum bite advancement during
twin-block therapy: a randomized
controlled clinical trial. Am J
Orthod Dentofacial Orthop
2004;126:583-8.
51 Google Scholar, Web of Science, Tulloch JF et al. Outcomes in a Reported interim outcomes or
PubMed 2-phase randomized clinical trial of updates33
early Class II treatment. Am J
Orthod Dentofacial Orthop
2004;125:657-67.
52 Google Scholar Kalha A. Early treatment with the Summary trial of O’ Brien et al34
twin-block appliance is effective in
reducing overjet and severity of
malocclusion. Is the twin-block
orthodontic appliance effective in
early treatment of developing class
II division 1 malocclusion? Evid
Based Dent 2004;5:102-3.
53 Web of Science, PubMed Gill DS et al. Prospective clinical trial No untreated control group
comparing the effects of
conventional Twin-block and
mini-block appliances: part
1. Hard-tissue changes. Am J
Orthod Dentofacial Orthop
2005;127:465-72.
54 Google scholar, Web of Science, Cevidanes LH et al. Assessment of Magnetic resonance imaging study,
PubMed. mandibular growth and response to no cephalometric analysis
orthopedic treatment with
3-dimensional magnetic resonance
images. Am J Orthod Dentofacial
Orthop 2005;128:16-26.

American Journal of Orthodontics and Dentofacial Orthopedics January 2011  Vol 139  Issue 1
30 Marsico et al

Table III. Continued

Reference Databases Study Reason for exclusion

55 Google Scholar, Web of Science, Cevidanes LH et al. Comparison of Magnetic resonance imaging study,
PubMed relative mandibular growth vectors no cephalometric analysis
with high-resolution 3-dimensional
imaging. Am J Orthod Dentofacial
Orthop 2005;128:27-34.
56 Google Scholar, Web of Science, Efstratiadis S et al. Evaluation of Class No untreated control group
PubMed II treatment by cephalometric
regional superpositions versus
conventional measurements. Am J
Orthod Dentofacial Orthop
2005;128:607-18.
57 Google Scholar Liu Ji-hui. A comparative study of No untreated control group
clinical effects of Twin-Block and
strigth wire appliance combined
with cervical headgear and class II
elastic on the treatment of class II,
division I malocclusion. Chinese
Journal of Traditional & Western
Medicine 2006;7:1925-9.
58 PubMed Karacay S et al. Forsus nitinol flat Concomitant use of fixed edgwise
spring and Jasper jumper appliances
corrections of Class II division 1
malocclusions. Angle Orthod.
2006;76:666-72.
59 Google Scholar, PubMed Lee RT et al. A controlled clinical trial No untreated control group
of the effects of the Twin Block and
Dynamax appliances on the hard
and soft tissues. Eur J Orthod
2007;29:272-82.
60 Google scholar, Web of Science, Dolce C et al. Timing of Class II Reported interim outcomes or
PubMed, Ovid Medline treatment: skeletal changes updates39
comparing 1-phase and 2-phase
treatment. Am J Orthod Dentofacial
Orthop 2007;132:481-9; erratum
in Am J Orthod Dentofacial Orthop
2007;132:727.
61 Google Scholar Ren Y. Very few indications justify Summary trial of Tulloch et al51
early treatment for severe Class II
malocclusions. Evid Based Dent
2004;5:100-1.
62 Google scholar, Web of Science, O’Brien K et al. Early treatment for Reported interim outcomes or
PubMed Class II Division 1 malocclusion updates34
with the Twin-block appliance:
a multi-center, randomized,
controlled trial. Am J Orthod
Dentofacial Orthop 2009;135:
573-9.
63 Google Scholar, PubMed Baccetti T et al. Comparison of 2 No untreated control group
comprehensive Class II treatment
protocols including the bonded
Herbst and headgear appliances:
a double-blind study of
consecutively treated patients at
puberty. Am J Orthod Dentofacial
Orthop 2009;135:698.e1-10.

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Marsico et al 31

Table IV. Study charateristics of the selected RCTs

Selected Sample and Treatment or Time of daily Methods
references appliances Sex Age (y) Setting observation time appliance wear of meassurement Follow-up
Jakobsson31 17 act NA 8.5 Karolinska 18 mo 11.5 h/d Co-Pg No
Institutet
1967 18 contr 8.5 (Sweden) 18 mo
Nelson 12 HA 7 M, 10-12.9 University of 18 mo Minimum Cephalometric No
et al32 5F Otago of 14 h analysis,
1993 13 FR-2 7 M, Mean, (New Zealand) 18 mo Co-Go, Go-Pg,
6F 11.6 Co-Pg
17 contr 11 M, 18 mo
6F
Tulloch 53 bio 30 M, 9.4 University of 15 mo Not Cephalometric No
et al33 23 F analysis,
1997 61 contr 35 M, 9.4 North Carolina 15 mo declared Co-Gn, hand-wrist
26 F radiographs
O’ Brien 73 TB NA Mean, National Health 15 mo 24 h/d Cephalometric No
et al34 9.7 Service analysis,
2003 74 contr Mean, (United 15 mo excluding Pg/Olp 1 Co/OLp,
9.8 Kingdom) contact stage of maturation
sports and of cervical
swimming spine analysis

Act, Activator; HA, Harvold activator; FR-2, Fr€ankel function regulator; bio, bionator; TB, Twin-block appliance; contr, controls; M, male;
F, female; NA, not available.

group42,43; (3) lack of cephalometric analysis54,55; (4)
cephalometric analysis that did not use anatomic
condylion45,48; (5) simultaneous use of additional
treatments36,37,39,58; (6) progress reports35,41,44,51,60,62;
(7) summary trials49,52,61; or (8) related to this topic
but with a different aim.38 The reasons for excluding
these studies are given in detail in Table III. Only 3 arti-
cles met all eligibility criteria and were selected for the
final analysis.32-34 One more RCT with available
outcomes, identified by hand-searching, was included.31
Study characteristics
We collected data from 338 patients (168 treated vs
170 controls) with Class II malocclusion in the mixed
dentition. Two trials included only subjects with severe
Class II malocclusion and without clinically obvious fa-
cial asymmetry.33,34 The samples were heterogeneous
for the numbers and the ages of participants.
The numbers of treated subjects and controls ranged
from 17 to 73 and from 17 to 74, respectively; the mean
ages of 2 studies was homogeneous at 9.57 years,33,34
whereas the others reported mean ages of 8.531 and
11.632 years. Only O’Brien et al34 and Tulloch et al33 de-
tected an effective level of skeletal maturity through the
evaluation of cervical spine and hand-wrist radiographs,
respectively.
It was not possible to assess clinical sex heterogeneity
because, in 2 trials, data were not available about the
sexes of the samples.31,34 Strong heterogeneity was
found in time of daily appliance wear, probably due to
the different functional appliances tested. Every selected
RCT analyzed a different type of functional appliance
(activator, bionator, Twin-block, Frankel 2, Harvold acti-
vator), but they had similar mechanisms of action. Treat-
ment or observation times ranged from 15 months33,34 to
18 months.31,32 No article reported long-term results.
Considerable variability in the outcome measure-
ments (Co-Pg,31,32 Co-Gn,33 and Pg/Olp 1 Co/OLp34)
was seen because of the many different types of cepha-
lometric analyses adopted by the investigators. The data
of the selected articles are summarized in Table IV.
Validity assessment
Because studies with high methodologic quality
might provide more reliable conclusions,64 a quality
evaluation of the selected articles was performed accord-
ing to the current Cochrane guidelines for assessment of
risk of bias.30
The following quality criteria of each article were ex-
amined: sequence generation; allocation concealment;
blinding of participants, personnel, and outcome asses-
sors; incomplete outcome data; selective outcome report-
ing; and other sources of bias. Allocation concealment
was adequate for all trials, but 2 failed to generate an ad-
equate allocation sequence; the outcome assessor was
appropriately blinded in only 1 study, and incomplete
outcome data were adequately addressed in 3 reports.
All studies apparently seemed free of other problems

American Journal of Orthodontics and Dentofacial Orthopedics January 2011  Vol 139  Issue 1
32 Marsico et al

Table V. Summary assessment of risk of bias

Blinding of
participants, Incomplete Selective
Sequence Allocation personnel outcome outcome Other
generation: concealment: and outcome data: reporting: sources Risk of bias
yes, no, yes, no, assessors: yes, no, yes, no, of bias: yes, (low, unclear,
Articles unclear unclear yes, no, unclear unclear unclear no, unclear high)
Jakobsson31 No Yes No Yes Yes Yes Unclear
Nelson et al32 No Yes No No Yes Yes High
Tulloch et al33 Yes Yes No Yes Yes Yes Low
O’ Brien et al34 Yes Yes Yes Yes Yes Yes Low
Low, Unlikely to seriously alter the results, all criteria met; unclear, some doubt raised about results, at least 1 criterion partially met; high, seriously
weakens the confidence in the result, at least 1 criterion not met.

Fig 2. Forest plot representing the effect of functional appliances with the random-effects model.

that could cause a high risk of bias. Only 2 RCTs were as-
sessed with a low risk of bias33,34; 1 was at high risk of
bias,34 and the last 1 was unclear31 (Table V).
The quality assessment was undertaken indepen-
dently and in duplicate by using separate printed forms
by the reviewers, and agreement was assessed by using
the kappa statistic. Substantial agreement was reached
between the reviewers, with a kappa score of 0.75.
Quantitative data synthesis
The selected RCTs assessed the same outcome (in-
crease in mandibular length) but measured it in a variety
of ways (Co-Pg,31,32 Co-Gn,33 and Pg/Olp 1 Co/OLp34),
so it was necessary to standardize the values to a uniform
scale (SMD) to combine them in a meta-analysis.29
All the values were annualized to compare different
treatment time. Finally the dimensionless value of
SMD obtained from the random effects model was mul-
tiplied by the standard deviation to find the actual dif-
ference in mandibular length.30 The results of the
meta-analysis showed a statistically significant differ-
ence of 1.79 mm in the annual mandibular growth of
the treatment groups compared with the control groups
(SMD 5 0.61, 95% CI, 0.30 to –0.93; chi-square test,
5.34; 3 df; P 5 0.15; I2 5 43.9%; test for overall effect,
Z 5 3.83 and P 5 0.0001) (Fig 2).
To test how robust the results of this meta-analysis
were, a sensitivity analysis was performed. A new meta-
analysis was carried out without the study with the
highest risk of bias,32 with a substantially similar out-
come of 1.91 mm (SMD 5 0.65, 95% CI, 0.25-1.25;
chi-square test, 4.96; 2 df; P 5 0.08; I2 5 59.7%; test
for overall effect, Z 5 3.19 and P 5 0.001) as shown
in Figure 3.
DISCUSSION
In this meta-analysis, we investigated the current lit-
erature with best evidence (RCTs) about the efficacy of
functional appliances on mandibular growth. Evidence
is lacking in this field because of the difficulties

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Marsico et al
Fig 3. Sensitivity analysis: forest plot representing the effect of functional appliances without the
lower-quality study (Nelson et al32).
associated with conducting high-quality studies.65 De-
spite an accurate and wide bibliographic search strategy,
we found only 4 eligible trials.31-34
The literature showed great variability in the mea-
surements of the effective increase of total mandibular
length with functional therapy; different variables and
reference points were used because of the several types
of cephalometric analysis adopted by the investigators.
In this meta-analysis, we included only articles that
reported the anatomic condylion. Studies that used ar-
ticulare were excluded because its location is determi-
nated by mandibular position: the forward and
downward posture of the condyles after functional ap-
pliance therapy can alter any measurement taken from
this point, and it could be interpreted as an increase in
mandibular length.66-68
Because the selected studies reported 3 types of mea-
surements (Co-Pg,31,32 Co-Gn,33 and Pg/Olp 1 Co/
OLp34), it was necessary to standardize the values to a uni-
form scale (SMD) to combine them in a meta-analysis.29
The results obtained from the random-effects model
analysis showed a statistically significant difference of
1.79 mm annual mandibular growth of the treatment
groups compared with the control groups (SMD 5
0.61, 95% CI, 0.30 to –0.93; chi-square test, 5.34; 3 df;
P 5 0.15; I2 5 43.9%; test for overall effect, Z 5 3.83
and P 5 0.0001) (Fig 2). The I2 value described a consis-
tent percentage (43.9%) of total variation across the
studies that was due to heterogeneity rather than chance.
This statistical heterogeneity can be explained with
the different dimensions of the samples and with the dif-
ferent sizes of treatment effects observed in the selected
trials. The sensitivity analysis showed a substantially
similar outcome of 1.91 mm (SMD = 0.65, 95%
American Journal of Orthodontics and Dentofacial Orthopedics
33
CI, 0.25 to 1.25; chi-square test, 4.96; 2 df; P 5 0.08;
I2 5 59.7%; test for overall effect, Z 5 3.19 and P 5
0.001) as shown in Figure 3. This implies that differences
in mandibular growth observed between groups of pa-
tients allocated to different interventions (controls vs
treated) can, apart of random error, be attributed to
the therapy under investigation. Because the selected
trials were of high to moderate quality (Table V), with
wide clinical heterogeneity (use of different functional
appliances on children in different phases of mixed den-
tition, and subjects from 4 countries), the results of this
meta-analysis are most likely generalizable.
Implications for practice
This meta-analysis showed that the treatment resulted
in a change of skeletal pattern; however, these effectively
small increases of the mandibular length, even if statisti-
cally significant, appear unlikely to be very clinically
significant. These data seem to support recent reports
that 2-phase treatment has no advantages over 1-phase
treatment.51,62,69 However, several benefits must be
attributed to the early treatment of Class II malocclusion
with functional appliances: prevention of trauma to
maxillary incisors associated with a large overjet,
interception of the development of dysfunction,
psychosocial advantages for the child during an
important formative period of life, stable dentoalveolar
correction, and improved prognosis and shorter duration
of treatment with fixed appliances.3,67,70,71
Implications for research
The RCT results, as suggested by O’Brien,72 “only
show the average effect of an intervention on an average
patient with a condition. This is a useful information to
January 2011  Vol 139  Issue 1
34
most clinicians who are interested in treating the average
patient.” But the dramatic changes that occasionally
occur within the samples should not be ignored.
In deciding whether these appliances are useful,
indeed, it is important to note that the blending of Class
II divergencies might have affected the outcome of the
study. Class II studies should separate patients into at
least the hypodivergent, neutral, and hyperdivergent
phenotypes. Obviously, it would be harder to obtain an
appropriate sample size, but different rotation patterns
are associated with different phenotypes and require
different treatments.73
The results of the literature search showed great
variability in the cephalometric measurements of the ef-
fective increase of total mandibular length; the investi-
gators adopted different cephalometric analyses and
different variables and reference points. It would be use-
ful to form a consensus on the types of measurements
used in orthodontic studies, so that direct comparisons
between trials can be achieved.
Finally, RCTs should be carried out and reported
according to the Consolidated Standards of Reporting
Trials (CONSORT) guidelines.
CONCLUSIONS
In this systematic review, we analyzed results from
RCTs in the literature concerning Class II functional ther-
apy to evaluate the efficacy of functional appliances on
mandibular growth in the short term.
This meta-analysis showed that, when functional ap-
pliance treatment is provided in early adolescence, there
are small beneficial changes in skeletal patterns, but
these are probably not very clinically significant.
We thank Rita Aveni for her assistance with the data-
base search.
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