Subjects and study design
This study followed a retrospective, longitudinal, single-blind design. An initial sample of 128 subjects seeking orthodontic treatment, who had never been treated before and presenting at the Section of Orthodontics of the Department of Oral Sciences, Second University of Naples, was screened. As a routine procedure, a signed informed consent to release diagnostic records for scientific purposes was obtained from the parents of the subjects prior to entry into the treatment. Other inclusion criteria were as follows: (1) skeletal class II malocclusion by mandibular retrusion, (2) good general health with no growth or nutritional problems, (3) European (white) ancestry, (4) absence of major craniofacial or dental anomalies and (5) availability of pre-treatment and post-treatment records all during the pre-pubertal growth phase.
Class II division 1 malocclusion was strictly diagnosed at baseline according to the following signs [10, 16, 17]: full- or half-cusp class II molar relationship, excessive overjet (>4 mm), skeletal sagittal relationship of class II (ANB angle > 4°), mandibular retrusion (SNB angle < 78°) and no maxillary protrusion (SNA angle > 84°). Subjects who refused to be treated at the initial visit but re-presented later were included in the control group whenever a second set of diagnostic recording was available. After this selection, 34 subjects (18 females and 16 males, mean age 8.8 ± 1.5 years), 17 treated and 17 untreated controls, were included in the study.
Observational term and treatment
Lateral cephalograms were taken at two time periods referred to as T0 (baseline) and T1 (end of observational term). At T0, the mean ages were 8.9 ± 1.1 years for the treated group and 8.9 ± 1.8 years for the untreated control group. At T1, the mean ages were 10.4 ± 1.1 years for the treated group and 10.5 ± 2.0 years for the untreated control group. The treatment/observational period was 1.6 ± 0.8 years for both groups.
The FR-2 appliances were constructed according to the design recommended by Fränkel and Fränkel [6] with an initial mandibular advancement that did not exceed about 3 mm, followed by subsequent step-by-step advancement of the same entities. After FR-2 treatment, care was taken to ensure that the mandible could not be retruded clinically, e.g. dual bite. Treatment was interrupted when a class I molar relationship was achieved.
To discriminate between the lack of effect due to the treatment protocol and poor patients' compliance, only those who declared to have worn the appliance for at least 18 h a day during the first 12 months of the treatment were selected herein [10]. This judgment was based on routine reports from parents of the patients. The initial lateral cephalogram was obtained not earlier than 4 months before the onset of the FR-2 treatment, and the final one was obtained not later than 2 months after the end of treatment.
Assessment of the pre-pubertal growth phase
Pre-pubertal growth phase was assessed through the third middle phalanx maturation (MPM) method [18]. The MPM method as proposed herein comprises five stages (MPS), of which stages 1 and 2 are present in the pre-pubertal subjects and were briefly defined as follows:
MPS1 is when the epiphysis is narrower than the metaphysis or when the epiphysis is as wide as the metaphysis but with both tapered and rounded lateral borders. The epiphysis and metaphysis are not fused. This stage was described to be attained more than 1 year before the onset of the pubertal growth spurt [13].
MPS2 is when the epiphysis is at least as wide as the metaphysis with sides of increasing thickness and showing a clear line of demarcation at right angle. In case of asymmetry between the two sides, e.g. one typical of MPS2 and the other less mature, the former is used to assign the stage. This stage was described to be attained 1 year before the onset of the pubertal growth phase [13, 19].
All the included subjects had to show an MPS1 or MPS2 at T1.
Cephalometric analysis
A customised digitization regimen and analysis with cephalometric software (Viewbox, version 3.0, dHAL Software, Kifissia, Greece) was used for all cephalograms examined in this study. The cephalometric analysis required the digitization of 17 landmarks. The customised cephalometric analysis included measurements from the analyses of Steiner [20], Jacobson [21] and McNamara [22], generating 17 variables, eight angular and nine linear, for each tracing (Figure 1). Lateral cephalograms of both treated and untreated subjects at T0 and T1 were standardised as to magnification factor (8%).
All sets of cephalograms were traced at the same time by a blind operator. A preliminary tracing was made for each film in the series, with particular attention to tracing the outlines of the maxilla and the mandible, including the mandibular condyle. A second blind investigator checked each tracing for accuracy. Individual changes were expressed as total, i.e. not annualised.
Sample size calculation and method error analysis
A sample size of at least 17 subjects per group was necessary to detect an effect size (ES) coefficient [23] of 1.0 for each cephalometric parameter in the comparison between the groups at T1, with an alpha set at 0.05 and a power of 0.8 [24]. The ES coefficient is the ratio of the difference between the recordings of the two groups, divided by the within-subject standard deviation (SD). In particular, the ES coefficient has been defined as the ratio of the difference between the mean changes of the two groups divided by the corresponding weighted SDs. A threshold of 0.8 [23] or 1.0 [25] has been reported to be indicative of a clinically relevant effect.
With the aim of quantifying the full method error of the recordings for each cephalometric parameter, the method of moments variance estimator was used [26, 27]. This variance estimator has the advantages of not being affected by any unknown bias, i.e. systematic errors, between pairs of measurements [27]. This analysis was performed on 20 pairs of recordings randomly selected.
Statistical analysis
The SPSS software, version 13.0 (SPSS® Inc., Chicago, IL, USA) and Comprehensive Meta-Analysis, version 2 (BiostatTM, Englewood, NJ, USA) were used to perform the statistical analyses. After having tested the normality of the data with the Shapiro-Wilk test and the equality of variance among the datasets using a Levene test, non-parametric methods were used for data analysis. Nevertheless, data were summarised as mean ± SD. For each of the cephalometric parameters, a Wilcoxon test and a Mann–Whitney U test were used to test the significance of the differences between the time points within each group and between the two groups within either time point, respectively.
For both treated and untreated control groups, the total changes for all cephalometric variables between T1 and T0 were computed. The significance of the differences in these changes between the groups was also evaluated by the Mann–Whitney U test. Finally, the changes seen in the treated group subtracted by the corresponding ones seen in the untreated control group were referred to as the ‘treatment effect’, and for these, the ES coefficients along with the 95% confidence intervals (CIs) were calculated, as previously described [28].
Briefly, the ES coefficients have been calculated to assess the results in terms of statistically and/or clinically significant differences. In particular, the ES coefficient has been defined as the ratio of the difference between the mean changes of the two groups divided by the corresponding weighted SDs. Even though a threshold of 0.2 [23] has been reported to be indicative of the minimal value to assess the existence of a ‘small effect’, herein the null hypothesis for the ES coefficient was to be equal to zero, i.e. when the 95% CI includes the zero value, then ‘no treatment effect’ was assessed. A p <0.05 was used to reject the null hypothesis.