ORIGINAL ARTICLE

Treatment effects of mini-implants for

en-masse retraction of anterior teeth in
bialveolar dental protrusion patients:
A randomized controlled trial
Madhur Upadhyay,a Sumit Yadav,b K Nagaraj,c and Sameer Patild
Farmington, Conn, Indianapolis, Ind, and Belgaum, India
Introduction: The purpose of this randomized controlled trial was to quantify the treatment effects of
en-masse retraction of anterior teeth with mini-implants as anchor units in bialveolar dental protrusion
patients undergoing extraction of all 4 first premolars. Methods: A total of 40 patients (mean age, 17.5 years;
SD, 3.2 years) were randomly assigned either to group 1 (G1), anterior space closure with mini-implants as
anchor units, or group 2 (G2), anterior space closure with conventional methods of anchorage (without
mini-implants). Skeletal, dental, and soft-tissue changes were analyzed in both groups on lateral cephalograms taken before retraction and after space closure. Results: Student paired and unpaired t tests were
used to analyze the treatment changes in the 2 groups. For the skeletal parameters, a statistically significant
decrease in the facial vertical dimensions was seen in G1, but the variables in G2 showed no significant
differences (P 0.05). Anchorage loss, in both the horizontal and vertical directions, was noted in G2,
whereas G1 showed distalization (anchorage gain) and intrusion of molars. Although the soft-tissue response
was variable, facial convexity angle, nasolabial angle, and lower lip protrusion had greater changes in G1. No
differences were found in the amount of upper lip retraction between the groups (P 0.05). Conclusions:
Mini-implants provided absolute anchorage to allow greater skeletal, dental, and esthetic changes in patients
requiring maximum anterior retraction, when compared with other conventional methods of space closure.
The treatment changes were favorable. However, no differences in the mean retraction time were noted
between the 2 groups. (Am J Orthod Dentofacial Orthop 2008;134:18-29)

ialveolar dental protrusion is common in many

ethnic groups around the world.1-3 It is characterized by dentoalveolar flaring of both the
maxillary and mandibular anterior teeth with resultant
protrusion of the lips and convexity of the face.
Dentists often refer to this condition as just bimaxillary protrusion, a simpler term but a misnomer, since
a

Fellow, Division of Orthodontics, Department of Craniofacial Sciences,

School of Dental Medicine, University of Connecticut, Farmington, CT;
Assistant professor and researcher, Department of Orthodontics, KLES Academy of Higher Education and Research, Belgaum, India.
b
PhD student, Dental Sciences, Mineralized Tissue Histology and Research
Laboratory, Section of Orthodontics, Indiana School of Dentistry, Indiana
University-Purdue University, Indianapolis, Ind.
c
Assistant professor, Department of Orthodontics, KLES Institute of Dental
Sciences, Belgaum, India.
d
Professor, Department of Orthodontics, KLES Academy of Higher Education
and Research; consultant orthodontist, Cleft & Craniofacial Unit, KLES
Hospital & Medical Research Center, Belgaum, India; The Smile Train Project,
New York, NY.
Reprint requests to: Madhur Upadhyay, Division of Orthodontics, Department
of Craniofacial Sciences, School of Dental Medicine, University of Connecticut, Farmington, CT 06030; e-mail, madhurup@yahoo.com.
Submitted, December 2006; revised and accepted, March 2007.
0889-5406/$34.00
Copyright 2008 by the American Association of Orthodontists.
doi:10.1016/j.ajodo.2007.03.025

18

it is not the jaws but the teeth that protrude.4 The

present trend to treat bialveolar protrusion is extraction
of the 4 first premolars, followed by anterior tooth
retraction to obtain the desired dental and soft-tissue
profile changes.
Several authors have reported definite correlations
between incisor movements and changes in the overlying soft-tissue profile. Drobocky and Smith5 showed
that 95% of the patients with 4 premolars extracted had
decreased lip protrusion relative to the E-line, with
averages of 3.4 mm for the upper lip and 3.6 mm for the
lower lip. In another study, it was shown that a 1-mm
mandibular incisor tip retraction produced 0.4 mm of
retraction of the most anterior point on the upper lip and
0.6 mm of retraction of the lower lip.6 Furthermore, it
was reported that maxillary incisor retraction causes
upper lip retraction, increases lower lip length, and
increases the nasolabial angle,7 whereas mandibular
incisor position determines lower lip position and
shape.8
Although much research regarding soft-tissue response to anterior tooth retraction has been performed,

American Journal of Orthodontics and Dentofacial Orthopedics

Volume 134, Number 1

only a few studies have examined patients with minimal arch length deficiencies requiring maximum anterior retraction. Burstone9 suggested that how anchorage
is managed, not the mere extraction of teeth, determines
the magnitude of anterior dental reduction and the
resulting change in lip position. Williams and Hosila10
found that, in patients whose 4 first premolars were
extracted, only 66.5% of the available extraction space
was taken up by retraction of the anterior segment.
Creekmore11 stated that, as a rule of thumb, when first
premolars are extracted, one can expect the posterior
teeth to move forward approximately one third of the
space, leaving two thirds of the space for relief of
crowding and incisor retraction. In this scenario, maximum anchorage of the posterior teeth assumes importance in not only allowing the anterior teeth to be
retracted to their greatest extent but also increasing the
chances of straightening the profile by reducing the
convexity of the face.
With the introduction of dental implants,12 miniplates,13 and microscrews14-16 as anchorage units, it is
now possible to obtain absolute anchorage of the
posterior teeth and close the extraction spaces completely by anterior tooth retraction. However, there still
seems to be little accurate scientific evidence pertaining
to the treatment effects of skeletal anchorage in these
patients. Most treatment assessments were based on
either clinicians observations in their day-to-day practices (case reports14-16) or anecdotal clinical observations. It can be misleading to base future practice
decisions on such evidence.
Our purposes in this study were to investigate and
compare the dentoskeletal and soft-tissue treatment
effects with mini-implants as anchor units in bialveolar
dental protrusion patients requiring extraction of 4 first
premolars and maximum retraction of anterior teeth
with patients treated with conventional methods of
anchorage reinforcement. Additionally, the time taken
for space closure was compared.
MATERIAL AND METHODS

After obtaining formal approval from the local

ethical committee, the first 85 female subjects with
Class I bialveolar protrusion in the permanent dentition
applying for orthodontic treatment at the KLES Institute of Dental Sciences were screened for this study
over 18 months (Fig 1). Thirty-seven patients did not
meet the additional inclusion criteria: (1) minimum age
at the beginning of treatment of 14 years, to minimize
confounding results due to growth; (2) no congenitally
missing teeth (except for the third molars); (3) no
previous history of mouth breathing, thumb sucking,
tongue thrusting, or orthodontic treatment; (4) Class I

Upadhyay et al 19

molar relationship (1 mm), interincisal angle of 116 or

less, overbite of 0% to 50%, and overjet not exceeding 5
mm (measured on the study models with a digital caliper);
and (5) well-aligned maxillary and mandibular incisors
with minimal crowding (3.5 mm).
On the basis of the diagnosis of the malocclusion,
extraction of all 4 first premolars combined with
maximum anchorage of the posterior teeth was indicated in all subjects. Maximum anchorage was predicated on the need to restrict mesial movement of
posterior teeth until the bialveolar protrusion was resolved through complete retraction of the anterior teeth.
All patients and their parents were advised of the
purpose of this study, and the patient or a parent or
guardian signed a consent form. Seven patients did not
agree to participate in this study and were therefore not
included.
In the next step of division, the subjects were
randomly divided into 2 groups: the study group (G1)
and the control group (G2). A restricted randomization
method was used in blocks of 10 to ensure that equal
numbers of patients were allocated to each treatment
group. The principal investigator (M.U.) was blinded to
the allocation sequence, which was generated by the
statistician on this project using computer-generated
random numbers. In the G1 subjects (mean age, 17.6
years), mini-implants were used as anchorage units in
both arches for en-masse retraction of the anterior teeth.
In G2 (mean age, 17.3 years), conventional methods of
anchorage reinforcement were used according to the
need for space closure, such as headgears, transpalatal
arches, banding of the second molars, and application
of differential moments. The anterior teeth were retracted sequentially to maintain maximum anchorage.
The canines were retracted first and then the incisors.
All patients in both the groups were treated with the
preadjusted edgewise appliance system (Roth prescription, slot size 0.022 0.028 in).
After the initial leveling and aligning in G1, 0.017
0.025-in stainless steel archwires with crimpable hooks
distal to the lateral incisors were placed in both arches.
To ensure that the wires were passive, they were left in
place for at least 5 weeks before starting retraction.
Titanium mini-implants (1.3 mm in diameter, 8 mm in
length) were placed between the roots of the first molar
and the second premolar in all 4 quadrants. The surgical
procedure for implant placement involved incision of
the overlying mucosae, preparing a hole with a pilot
drill under constant irrigation with a coolant, and
placement of the mini-implants with a screwdriver. The
implants were immediately loaded with precalibirated
nickel-titanium closed-coil springs (150 g, GAC International, Bohemia, NY) extending from the implant

20 Upadhyay et al

American Journal of Orthodontics and Dentofacial Orthopedics

July 2008

Fig 1. Participant flow.

head to the crimpable hooks for en-masse retraction of

the maxillary and mandibular anterior teeth. The directions of the applied forces were upward and backward
for the maxillary arch, and downward and backward for
the mandibular arch (Figs 2 and 3).
To minimize the effects of any residual growth and
to estimate treatment changes primarily due to retraction of anterior teeth, radiographs were taken just
before retraction (T1) and after space closure (T2).
Lateral cephalometric radiographs for each subject
were taken with a Planmeca cephalometer (PM 2002
EC Proline, Helsinki, Finland). All subjects were positioned in the cephalostat with the sagittal plane at a
right angle to the path of the x-rays, the Frankfort plane
parallel to the horizontal, the teeth in centric occlusion,
and the lips completely relaxed. Radiographs obtained
were of good quality, with hard- and soft-tissue structures clearly discernible. The time between the 2

cephalograms was not more than 15 months for any

subject.
We carried out an intention-to-treat analysis so that
the data from all patients, regardless of treatment
outcome, were included in the analysis. This comprised
an analysis of all patients who entered the trial and for
whom baseline and final records were available.
One faculty member (K.N.) examined all 72 cephalograms. The same faculty member conducted the measurement analysis of the cephalograms and was unaware of
the objectives of the study. Both films from each patient
were placed side by side on the viewer to minimize errors
in locating cephalometric landmarks. The midpoint between the right and left traced images was used for
bilateral landmarks. The cephalograms were traced with a
0.5-mm lead pencil on 0.003-in matte acetate tracing
paper. Horizontal and vertical positional changes of certain landmarks were measured in relation to a Cartesian

Upadhyay et al 21

American Journal of Orthodontics and Dentofacial Orthopedics

Volume 134, Number 1

Fig 2. Schematic diagram illustrating the clinical setup

for en-masse retraction with mini-implants in both
arches. Closed-coil nickel-titanium springs extending
from crimpable hooks to the mini-implant head in both
arches, applying a constant force (F) of 150 g each.

coordinate system. The Frankfort horizontal plane was

constructed by subtracting 7 from the sella-nasion line.
This was the x-axis, and a line perpendicular to it through
sella was the y-axis. Measurements were recorded to the
nearest 0.5 mm. All data were entered into computer
databases by research assistants, who were also blinded to
the treatment group.
Landmarks, cephalometric planes, linear and angular parameters, and abbreviations used in this study are
shown in Figures 4 through 7.
Statistical analysis

All statistical analyses were performed with the

SPSS software package (SPSS for windows 98, version
10.0, SPSS, Chicago, Ill). The mean and standard
deviation for each cephalometric variable were determined. We used parametric statistical tests: 2-tailed
paired t tests (to determine the significance of changes
in the groups after the corresponding treatment) and
unpaired t tests (to determine the differences between
the 2 groups either before or after treatment). Power
analysis showed that a sample size of at least 16
subjects per group would give an 80% probability of
detecting a real difference between the groups at a
statistically significant level of 5%. A confidence level

Fig 3. Intraoral photographs with mini-implants at A, T1

and B, T2.

larger than 5% was considered statistically not significant. The statistical significance was determined at the
0.1%, 1%, and 5% levels of confidence.
All cephalometric measurements were repeated 5
weeks later by the same examiner. If there was a
difference between the 2 measurements, a third reading
was made, and the aberrant one was discarded. The
mean of the 2 closest was used in the calculations.
Additionally, the paired-samples t test was applied to
the 2 closest measurements of each variable. The
difference between the first and the second measurements of the 72 radiographs was insignificant (P
0.05). Correlation analysis applied to the same measurement showed the highest r value of 0.952 for the
SNB angle and lowest r value of 0.906 for inferior
sulcus to E-line.
RESULTS

The treatment changes for each measurement were

calculated by subtracting the pretreatment from the
posttreatment measurements. Linear measurements
with a negative sign mean distal or backward move-

22 Upadhyay et al

Fig 4. Cephalometric landmarks and planes used.

Cephalometric landmarks (hard tissue): 1, nasion (N);
2, sella (S); 3, pogonion (Pog); 4, gnathion (Gn); 5,
gonion (Go); 6, Point A; 7, Point B; 8, mesial cusp tip of
maxillary first molar (U6); 9, mesial cusp tip of mandibular first molar (L6); 10, incisal tip of the maxillary central
incisor (U1); 11, incisal tip of the mandibular central
incisor (L1). Cephalometric landmarks (soft tissue):
12, Nt: most anterior point on the sagittal contour of the
nose; 13, Sn (subnasale): point at the junction of the
columella and the upper lip; 14, Ss (sulcus superior):
point of greatest concavity in the midline between
labrale superior and subnasale; 15, Ls (labrale superior):
the most anterior point on the convexity of the upper lip;
16, Li (labrale inferior): the most anterior point on the
convexity of the lower lip; 17, Si (sulcus inferior): point of
greatest concavity in the midline between labrale inferior and soft-tissue pogonion; 18, Pg (soft-tissue Pog):
the most anterior point on the soft-tissue chin. Cephalometric planes: I, S-N plane; II, constructed Frankfort
horizontal plane (x-axis); III, palatal plane (anterior nasal
spine [ANS]-posterior nasal spine [PNS]); IV, mandibular
plane (Go-Gn); V, sella vertical (Sv or y-axis); VI, Ricketts E-plane (Nt-Pg).

ment to a relevant reference line, or shortening of the

vertical dimension; a positive value indicates forward
or mesial movement, or an increase in the vertical
dimension. A positive value for change in an angular
measurement indicates that the measurement became
more obtuse during treatment.
The patients ages were similar in both the groups;
no statistically significant differences were observed
between them (P 0.05) (Table I). Pretreatment differences in the variables for the groups are shown in Table II.

American Journal of Orthodontics and Dentofacial Orthopedics

July 2008

Fig 5. Skeletal angular measurements: 1, SNA angle;

2, SNB angle; 3, ANB angle; 4, SN-Go-Gn. Skeletal
linear measurements: 5, UFH (N-ANS); 6, LFH (ANSMe); 7, PFH (S-Go); 8, TAFH (N-Me); 9, Sv-Pog.

Although mean retraction time for G1 (8.61 2.2

months) was less than that for G2 (9.94 2.44
months), the differences were not significant (P 0.05)
(Table I). The descriptive statistics containing means
and standard deviations for the respective groups and
the treatment changes are given in Tables III through V.
Skeletal changes

In the anteroposterior changes, G1 had an overall

increase in the SNB angle (0.56 0.86) (P 0.05) and
a decrease in ANB angle (0.67 0.84) (P 0.01),
whereas G2 had a significant decrease in SNB angle
(0.78 1.44) (P 0.05). Forward displacement of the
chin (Sv-Pg) was noted for G1 (1.33 1.85 mm) (P 0.01).
In the vertical changes, G1 showed significant reductions in the lower facial height (LFH) (1.44 1.46 mm)
(P 0.001) and the SN-MP angle (1.11 1.78) (P
0.01), but an increase was noted for the other variables:
upper facial height (UFH)/LFH (2.22% 3.17%) (P
0.01), posterior facial height (PFH) (1.28 1.31 mm)
(P 0.01), and PFH/total anterior facial height (TAFH)
(1.48% 1.96%) (P 0.01). The differences were
statistically significant compared with G2. However, in
G2, only TAFH showed a significant increase (1.11
1.23 mm) (P 0.01).
Dental changes

In maxillary incisor movement, clinically significant

(P 0.001) levels of retraction were achieved in the 2

Upadhyay et al 23

American Journal of Orthodontics and Dentofacial Orthopedics

Volume 134, Number 1

Fig 6. Dental angular measurements: 1, U1-SN plane; 2,

IMPA; 3, U1-L1 (interincisal angle). Dental linear measurements: 4, U6-PP: vertical position of maxillary first molar;
5, U6-Sv: sagittal position of maxillary first molar; 6, L6-Sv:
sagittal position of mandibular first molar; 7, L6-MP:
vertical position of mandibular first molar; 8, U1-Sv: sagittal position of maxillary incisal edge; 9, L1-Sv: sagittal
position of mandibular incisal edge.

Fig 7. Soft-tissue angular measurements: 1, G-Sn-Pg:

facial convexity angle; 2, nasolabial angle: angle between
Sn tangent and Sn-Ls; 3, labiomental angle: angle between Li-Si and Si-Pg. Soft-tissue linear measurements: 4,
Sv-Nt: sagittal position of the most anterior point on the
nose; 5, E-lineSs: distance from sulcus superior to E-line;
6, E-lineLs: distance from labrale superior to E-line; 7,
E-lineLi: distance from labrale inferior to E-line; 8, E-line
Si: distance from sulcus inferior to Ricketts E-line.

groups for both angular (U1-SN) and linear (U1-Sv)

measurements. There were no significant differences
(P 0.05) between the groups.
In mandibular incisor changes, these teeth also
showed significant levels of uprighting in the 2 groups
(P 0.001), both for angular (IMPA) and linear (L1Sv) measurements. However, it was found that greater
levels of uprighting were achieved in G1 (IMPA
[14.22 3.75] [P 0.05], L1-Sv [6.06 1.76
mm] [P 0.01]), when compared with G2 (IMPA
[10.72 5.58], L1-Sv [4.56 1.46 mm]).
In maxillary first molar movements in G1, there were
net intrusion (U6-PP 0.22 0.65 mm) (P 0.05)
and distal movement of the molar (U6-Sv 0.78
1.35 mm) (P 0.05). The differences were significant
when compared with G2, which had extrusion (U6-PP
0.67 1.19 mm) (P 0.05) and mesial movement
(U6-Sv 3.22 1.06 mm) (P 0.001) for the same
measurements.
In the mandibular first molar movements, G1 had
net intrusion (L6-MP 0.75 0.84 mm) (P
0.001) and distal (0.89 1.23 mm) (P 0.01)
movement of the mandibular first molar. However, in
G2, significant amounts of anchor loss were noted in
both the vertical (L6-MP 1.22 1.59 mm) (P

0.01) and horizontal (L6-Sv 2.67 2.11 mm) (P

0.001) directions.
Soft-tissue changes

In the profile changes, a significant decrease in the

facial convexity angle (G-Sn-Pg) was noted in both G1
(2.33 1.37) (P 0.001) and G2 (1.17
1.91) (P 0.05). However, the reduction was significantly greater in G1 (P 0.05). Similarly, although the
nasolabial angle was increased for both the groups, the
increase was significantly greater for G1 (11.67
5.94) (P 0.001).
For the upper lip changes, statistically significant
levels of lip retraction were seen for both groups
(P 0.001), but the intergroup differences were not
statistically significant (2.89 1.3 mm) (P 0.05),
although G1 had a greater reduction in lip prominence.
For the lower lip changes, significant levels of
retraction were seen for both groups (P 0.001), but
G1 showed a statistically greater level of lower lip
retraction than did G2 (4.78 1.33 mm) (P 0.001).
DISCUSSION

This was a prospective, randomized controlled trial

performed under the strict treatment guidelines of our

24 Upadhyay et al

Table I.

American Journal of Orthodontics and Dentofacial Orthopedics

July 2008

Details of the study sample (n 36)

G1 (n 18)

G2 (n 18)

Measurement

Mean

SD

Mean

SD

P value

Significance

Age at T1 (y)
Duration of retraction (mo) (T2-T1)

17.61
8.61

3.56
2.2

17.38
9.94

2.89
2.44

0.838
0.094

NS
NS

NS, Not significant.

Table II.

Comparison of morphologic characteristics of the patients treated with mini-implants (G1) and without (G2)

at T1
G1 (n 18)

Skeletal measurements
SNA ()
SNB ()
ANB ()
Go-Gn-SN ()
UFH (N-ANS) (mm)
LFH (ANS-Me) (mm)
UFH/LFH (%) (mm)
PFH (S-Go) (mm)
TAFH (N-Me) (mm)
PFH/TAFH (%)
Pog-Sv (mm)
Dental measurements
U1-SN ()
IMPA ()
U1-L1 ()
U6-PP (mm)
U6-Sv (mm)
L6-MP (mm)
L6-Sv (mm)
U1-Sv (mm)
L1-Sv (mm)
Soft-tissue measurements
G-Sn-Pg ()
Nasolabial angle ()
Labiomental angle ()
Sv-Nt (mm)
E-lineLs (mm)
E-lineLi (mm)
E-lineSs (mm)
E-lineSi (mm)

G2 (n 18)

Mean

SD

Mean

SD

P value

Significance

82.67
78
4.67
30.78
48.94
67.44
72.94
75.44
116.11
65.47
64

2.57
3.82
2.38
6.92
2.5
4
6.38
7.01
4.1
5.04
8.03

80.45
76.67
4.67
31.28
51.56
64.78
80.1
75.94
116.44
65.23
59

3.6
2.22
1.68
7.09
1.89
4.17
7.03
4.68
3.63
5.38
5.71

0.3243
0.3512
1
0.8318
0.0013
0.0585
0.003
0.8031
0.7979
0.8939
0.0393

NS
NS
NS
NS

113
98.56
112.67
21.78
50.56
32
50.78
80.22
75.44

7.19
6.81
9.13
1.06
5.88
2.66
6.94
6.86
6.91

115.83
104.72
103.22
21.44
44.44
31
44.78
76.44
71.44

4.16
9.52
7.26
1.89
4.42
3.46
5.08
3.73
4.68

0.1595
0.0327
0.0016
0.5189
0.0013
0.3385
0.0059
0.0501
0.051

NS
*

18.67
92.11
114.33
98.67
1.39
5.83
9.39
3

6.53
10.69
19.31
6.63
1.84
2.47
0.76
2.54

19.33
103.44
109.78
97.11
0.11
4
9.38
3.44

3.94
16
21.31
2.93
1.57
1.46
1.45
1.2

0.7134
0.0182
0.5062
0.372
0.0129
0.0114
0.973
0.5197

NS
*
NS
NS
*
*
NS
NS

NS

NS
NS
NS
*

NS

NS

NS
NS

NS, Not significant; *P 0.05; P 0.01.

institute and monitored by 1 operator (M.U.). The selected

patients were randomly assigned to either group, thus
eliminating operator bias. Moreover, because the measurement analysis of the cephalogram was performed
blindly, the risk of the examiner affecting the measurements was low.
Meticulous selection of patients led to a substantial
reduction in many variables that might have affected
the results. To reduce the effects of growth, selection

was limited to only adolescent girls above 14 years of

age. The assumption was that, by the onset of menstruation, the growth spurt is all but complete.4 Additionally, only T1 and T2 cephalograms (rather than
pretreatment and posttreatment cephalograms) were
included in the study for a minimal time difference
between the 2 sets of records.
When the x-rays were taken, each patient was asked
to maintain a relaxed lip position to reduce variability

Upadhyay et al 25

American Journal of Orthodontics and Dentofacial Orthopedics

Volume 134, Number 1

Table III.

Comparison of the treatment changes (T2-T1) in the G1 patients

T1

Skeletal measurements
SNA ()
SNB ()
ANB ()
Go-Gn-SN ()
UFH (N-ANS) (mm)
LFH (ANS-Me) (mm)
UFH/LFH (%)
PFH (S-Go) (mm)
TAFH (N-Me) (mm)
PFH/TAFH (%)
Pog-Sv (mm)
Dental measurements
U1-SN ()
IMPA ()
U1-L1 ()
U6-PP (mm)
U6-Sv (mm)
L6-MP (mm)
L6-Sv (mm)
U1-Sv (mm)
L1-Sv (mm)
Soft-tissue measurements
G-Sn-Pg ()
Nasolabial angle ()
Labiomental angle ()
Sv-Nt (mm)
E-lineLs (mm)
E-lineLi (mm)
E-lineSs (mm)
ElineSi (mm)

T2

Mean

SD

Mean

SD

P value

Significance

84.67
80
4.67
30.78
48.94
67.44
72.94
75.44
116.11
65.47
64

2.57
3.82
2.38
6.92
2.5
4
6.38
7.01
4.1
5.04
8.03

84.44
80.56
4
29.67
49.56
66
75.17
76.72
115.44
66.94
65.33

2.96
4.29
1.94
6.6
2.79
4.31
6.59
7.09
4.31
5.46
8.56

0.4299
0.0135
0.0037
0.0168
0.0063
0.0006
0.0086
0.0007
0.0967
0.0053
0.007

NS
*

113
98.56
112.67
21.78
50.56
32
50.78
80.22
75.44

7.19
6.81
9.13
1.06
5.88
2.66
6.94
6.86
6.91

97.89
84.33
141.11
21.56
49.78
31.25
49.89
73
69.39

7.22
6.89
6.76
1.1
6.11
2.17
7.12
7.01
6.87

0
0
0
0.1631
0.026
0.0151
0.007
0
0

18.67
92.11
114.33
98.67
1.39
5.83
9.39
3

6.53
10.69
19.31
6.63
1.84
2.47
0.76
2.54

16.33
103.78
118
99.56
1.5
1.06
9.89
5.06

6.08
11.67
19.7
6.88
1.85
2.18
0.58
2.48

0
0
0.2362
0.0456
0
0
0.0066
0

NS

NS
*

NS
*

NS, Not significant; *P 0.05; P 0.01; P 0.001.

in lip posture and increase the reproducibility of the

soft-tissue measurements.17 However, as noted by Zierhut et al,18 lip tension can vary between subjects and
even from time to time in 1 subject. The inability to
quantify or control this variable was a shortcoming of
this study. Cephalograms showing excessive lip strain
were eliminated.
Mini-implants proved to be a stable source of
anchorage for en-masse retraction of maxillary and
mandibular anterior teeth. Of the 72 implants used,
67 showed complete stability throughout the retraction phase; 5 mini-implants came loose within several weeks after placement. They were subsequently
replaced. The overall success rate was 93%. In 2
patients, retraction was discontinued for 3 and 5
weeks, respectively, because of persistent inflammation around the implant sites. Retraction was resumed when the inflammation was brought under
control by improving oral hygiene. The mini-implants used in this study were custom made at our

institute by modifying surgical micro-screws routinely used to stabilize plates in the facial bones and
fracture reduction surgeries. To adapt these screws to
our needs (ie, for attachment of nickel-titanium coil
springs), we modified the shape of the head and made
the neck slightly longer.
Contrary to previous reports, we found no significant shortening of treatment time in patients treated
with mini-implants (P 0.05) (Table I).14 A possible
explanation could be that, in the G1 patients, closure of
extraction space was completely done by distalization
of anterior teeth; in the G2 patients, due to anchorage
loss, there was simultaneous movement of anterior and
posterior teeth into the extraction space. However,
treatment time depends not only on the rate of tooth
movement but also on other variables, such as mechanics, patient cooperation, and parent or patient motivation. These variables were not controlled in this study,
and it was assumed that patient cooperation and motivation in both groups were the same.

26 Upadhyay et al

Table IV.

American Journal of Orthodontics and Dentofacial Orthopedics

July 2008

Comparison of the treatment changes (T2-T1) in the G2 patients

T1

Skeletal measurements
SNA ()
SNB ()
ANB ()
Go-Gn-SN ()
UFH (N-ANS) (mm)
LFH (ANS-Me) (mm)
UFH/LFH (%)
PFH (S-Go) (mm)
TAFH (N- Me) (mm)
PFH/TAFH (%)
Pog-Sv (mm)
Dental measurements
U1-SN ()
IMPA ()
U1-L1 ()
U6-PP (mm)
U6-Sv (mm)
L6-MP (mm)
L6-Sv (mm)
U1-Sv (mm)
L1-Sv (mm)
Soft-tissue measurements
G-Sn-Pg ()
Nasolabial angle ()
Labiomental angle ()
Sv-Nt (mm)
E-lineLs (mm)
E-lineLi (mm)
E-lineSs (mm)
E-lineSi (mm)

T2

Mean

SD

Mean

SD

P value

Significance

81.33
76.67
4.67
31.28
51.56
64.78
80.1
75.94
116.44
65.23
59

3.6
2.22
1.68
7.09
1.89
4.17
7.03
4.68
3.63
5.38
5.71

80.89
77.23
4.67
31.56
51.67
65.33
79.71
76.22
117.56
64.93
58.33

3.74
2.14
1.68
6.82
2.9
5.11
8.86
4.11
4.34
4.97
5.64

0.1037
0.0347
1
0.5457
0.8061
0.1806
0.6811
0.3958
0.0013
0.2947
0.1209

NS
*
NS
NS
NS
NS
NS
NS

115.83
104.72
103.22
21.44
44.44
31
44.78
76.44
71.44

4.16
9.52
7.26
1.89
4.42
3.46
5.08
3.73
4.68

99
94
128
22.11
47.67
32.22
47.44
70.11
66.89

7.62
7.64
9.57
1.97
4.5
3.78
4.15
4.1
4.48

0
0
0
0.0293
0
0.0046
0.0001
0
0

19.33
103.44
109.78
97.11
0.11
4
9.38
3.44

3.94
16
21.31
2.93
1.57
1.46
1.45
1.2

18.17
108.44
114.67
97.22
2.67
0.89
10.29
5.29

3.29
14.1
12.2
2.73
0.49
2.08
1.54
1.54

0.019
0
0.1686
0.4299
0
0
0
0.0002

NS
NS

NS
NS

NS, Not significant; *P 0.05; P 0.01; P 0.001.

Dentoskeletal effects

The 2 primary reasons for removal of permanent

teeth are to correct a discrepancy between tooth size
and arch length, and to reduce bimaxillary protrusion.
In addition, the desire to control the vertical dimension
can also be a reason to extract permanent teeth.19,20
This rationale for extraction is sometimes referred to as
the wedge hypothesis, which essentially suggests that
orthodontic forward movement of posterior teeth after
mandibular and maxillary premolar extraction leads to
reduction in the vertical dimension. Schudy21 recommended an extraction approach to close the bite in
hyperdivergent facial types. Sassouni and Nanda22
concurred with this treatment philosophy. An analysis
of the variables in Tables III, IV, and V suggests that,
in G1, there was an overall decrease in the vertical
dimension, but, in G2, no change in the vertical
dimension was recorded (except for the TAFH) in spite
of significant mesial molar movement. Most orthodon-

tic force applications tend to cause extrusion of the

molars.23,24 According to Staggers,23 even though the
molar moves forward in premolar extraction patients,
the vertical dimension of the face is maintained by
extrusion of the posterior teeth. A similar concept was
stated by Cusimano et al,25 that occlusal movement of
the posterior teeth tends to keep pace with the increase
in anterior facial height, thus maintaining the mandibular plane angle and nullifying the bite-closing effect of
posterior protraction. This perhaps explains the constancy of facial dimensions in G2, in which both
extrusion and protraction of molars were recorded
(Table IV).
In G1, decreases in LFH and MPA, and increases in
chin prominence and SNB angle were noted, suggesting anticlockwise rotation of the mandible (Tables III
and V). This was perhaps related to intrusion of the
molars in both arches, causing a decrease in the facial
vertical dimension. Small vertical changes at the pos-

Upadhyay et al 27

American Journal of Orthodontics and Dentofacial Orthopedics

Volume 134, Number 1

Table V.

Comparison of the treatment changes (T2-T1) between G1 and G2

G1 (n 18)

Skeletal measurements
SNA ()
SNB ()
ANB ()
Go-Gn-SN ()
UFH (N-ANS) (mm)
LFH (ANS-Me) (mm)
UFH/LFH (%)
PFH (S-Go) (mm)
TAFH (N-Me) (mm)
PFH/TAFH (%)
Pog-Sv (mm)
Dental measurements
U1-SN ()
IMPA ()
U1-L1 ()
U6-PP (mm)
U6-Sv (mm)
L6-MP (mm)
L6-Sv (mm)
U1-Sv (mm)
L1-Sv (mm)
Soft-tissue measurements
G-Sn-Pg ()
Nasolabial angle ()
Labiomental angle ()
Sv-Nt (mm)
E-lineLs (mm)
E-lineLi (mm)
E-lineSs (mm)
E-lineSi (mm)

G2 (n 18)

Mean

SD

Mean

SD

P value

Significance

0.22
0.56
0.67
1.11
0.61
1.44
2.22
1.28
0.67
1.48
1.33

1.17
0.86
0.84
1.78
0.83
1.46
3.17
1.31
1.61
1.96
1.85

0.44
0.78
0
0.28
0.11
0.56
0.39
0.28
1.11
0.3
0.67

1.1
1.44
0.49
1.91
1.89
1.69
3.95
1.35
1.23
1.18
1.73

0.5598
0.0022
0.007
0.0306
0.315
0.0006
0.036
0.0308
0.0008
0.0027
0.002

NS

13.11
14.22
28.44
0.22
0.78
0.75
0.89
7.22
6.06

6.57
3.75
7.34
0.65
1.35
0.84
1.23
2.07
1.76

16.83
10.72
24.78
0.67
3.22
1.22
2.67
6.33
4.56

9.2
5.58
10.4
1.19
1.06
1.59
2.11
2.57
1.46

0.1724
0.035
0.2311
0.0097
0
0
0
0.2608
0.0088

NS
*
NS

2.33
11.67
3.67
0.89
2.89
4.78
0.5
2.06

1.37
5.94
12.67
0.9
1.3
1.33
0.69
1.34

1.17
5
4.89
0.11
2.56
3.11
0.33
1.06

1.91
3.36
14.43
0.58
1.29
1.02
3.18
2.31

0.0435
0.0003
0.7887
0.0045
0.4461
0.0002
0.2911
0.1231

*
NS

*
*

NS

NS

NS

NS
NS

NS, Not significant; *P 0.05; P 0.01; P 0.001.

terior teeth can produce profound changes in the

anterior dimension. Only 1 mm of intrusion of the
posterior teeth can produce 3 to 4 mm of upward and
forward movement of the chin.26 In G1, the chin was
displaced forward by 1.3 mm (P 0.01), but the TAFH
remained unchanged through the retraction phase. This
might have been because of some residual growth,
causing downward and forward mandibular growth,
although it was very limited at this age. Similarly in G2,
there was a statistically significant increase in TAFH
(P 0.01) and a decrease in the SNB angle (P 0.05)
but no change in the other vertical parameters (Table
IV). Similar findings were reported in other studies.23,27,28 However, because there was no significant
difference between the mean ages of the groups (P
0.05) (Table I), the effect of any residual growth was
expected to be the same, and thus the effect of age on the
treatment results can be eliminated.
Anchorage preservation is a key factor in treating
bialveolar dental protrusion patients. Anchorage loss

was observed in G2, whereas, in G1, small amounts of

molar distalization (anchorage gain) were noted; this
was statistically significant. After complete space closure in G1, the contacts between the canine and the
second premolar were established. At this point, any
further continuation of the retraction force resulted in
its transmission to the posterior segment through the
interdental contacts. The coil springs in most patients
were left in place for at least several months after space
closure. This might have caused some distalization of
the molars as observed cephalometrically (Tables III
and V).
In previous reports, 1.6 to 4 mm of mesial molar
movement was reported while retracting canines with
traditional mechanics.29,30 With adjuncts for anchor
preservation, up to 2.4 mm of anchorage loss was
observed.31,32 Additionally, in G2, the incisors were
more protruded (Table I) compared with G1 (P 0.01).
This might have also contributed to the anchorage loss
observed in the G2 patients. The results could have

28 Upadhyay et al

been more accurate if the pretreatment axial inclinations of the incisors in both the groups had been
identical. Although 1 to 2 mm of anchorage loss is
clinically acceptable, higher amounts can be detrimental to the overall efficiency of the treatment, especially
when anchorage demand is critical. We believe that
mini-implants are better suited for patients who require
high or maximum anchorage, especially for vertical
growth patterns.
Soft-tissue changes

Facial appearance after treatment is obviously of

paramount importance to contemporary orthodontists.33 Whether viewed dynamically or statically, facial
harmony and profile balance are determined by the
interaction of the inherent morphology of the soft
tissues, the characteristics of the underlying skeletal
foundation, and the positions and angulations of the
teeth. All these factors combine to provide the visual
impact of each face.34-36 Much previous research about
the response of soft tissues to tooth retraction has been
done, but few authors have examined patients requiring
minimal arch length deficiency correction and maximum anterior retraction. Even fewer have focused on
patients who might benefit from skeletal anchorage but
were treated conventionally.
Overall, there was a greater change in the softtissue profile in G1, with statistically significant results
obtained for facial convexity angle, nasolabial angle,
and lower lip projection (Tables III and V). A mean
increase in the nasolabial angle of 11.67 was observed
in G1; this is perhaps much greater than reported in
previous studies. The change we observed is most
likely because of the strict retraction requirements of
the patient sample and the larger mean maxillary
incisor retraction than in previous studies.
Similarly, greater changes were observed for facial
convexity angle and lower lip projection in G1. Relative to the E-line, the upper lip was retracted by
averages of 2.89 mm in G1 and 2.56 mm in G2; the
lower lip showed values of 4.78 and 3.11 mm in the
groups, respectively. Greater retraction of the lower lip
was perhaps expected.37 In bialveolar dental protrusion,
the lower lip often contacts both maxillary and mandibular incisors and would therefore be influenced by
not only retraction of the mandibular incisors but also
retraction of the maxillary incisors. In spite of the
extensive retractions, no evidence of a dished-in profile
was observed in any patient. This was perhaps because
most patients in our sample had severe dentoalveolar
protrusion and required maximum anterior tooth retraction. Only 1 patient in G1 ended up with the upper and
lower lips behind the prescribed norm for the E-line. In

American Journal of Orthodontics and Dentofacial Orthopedics

July 2008

a study of 160 orthodontic patients treated with 4

first-premolar extractions, Drobocky and Smith5 reported that the frequency of excessively flattened profile was only about 4%.
Compared with skeletal and dental parameters, few
soft-tissue parameters showed statistically significant
differences between the groups in spite of obtaining
absolute anchorage in G1 and using the complete
extraction space for incisor retraction. This contrasts
with the findings of Lo and Hunter,38 who suggested
that the soft-tissue profile followed closely the underlying skeletal framework. Oliver37 found that patients
with thin lips or high lip strain had a significant
correlation between incisor retraction and lip retraction,
but patients with thick lips or low lip strain had no such
correlation. It was also reported that lip response, as a
proportion of incisor retraction, decreases as the
amount of incisor retraction increases, indicating that
the lips have some inherent support.39 The mobile and
flexible lip texture can also produce large variations of
lip position on the lateral cephalogram, even when
patients are asked to keep their lips relaxed and their
teeth in occlusion.40 The more regional effect of incisor
retraction should be expected because, even with orthognathic surgery, soft-tissue changes decrease as the
distance from the surgical site increases.
CONCLUSIONS

The purpose of this study was to compare the treatment effects of mini-implants as anchorage units in
bialveolar dental protrusion patients requiring maximum
retraction of anterior teeth to similar patients treated
conventionally. Favorable and greater levels of skeletal
and dental changes were observed in the bialveolar dental
protrusion patients treated with mini-implants as anchor
units than with conventional methods. However, the
soft-tissue response, although greater in G1, was variable.
The following conclusions can be drawn from this
study.
1. Mini-implants placed in maxillary and mandibular
interradicular bone provided absolute anchorage for
en-masse retraction of anterior teeth.
2. The success rate of the mini-implants was 93%. Of
the 72 implants used, only 5 came loose.
3. The time taken for retraction might be less for
patients treated with mini-implants, but, in this
study, the results were not statistically or clinically
significant.
4. The molars were distalized and intruded in G1; in
G2, there were significant levels of anchorage loss
in both the horizontal and vertical directions.

American Journal of Orthodontics and Dentofacial Orthopedics

Volume 134, Number 1

5. The facial vertical dimension (FVD) showed no

change in G2, whereas, in G1, forward rotation of
the mandible was recorded, causing reduction in the
FVD. However, it would be of interest to study the
long-term effects of mini-implants on the FVD in
treated patients.
6. Although the soft-tissue response was variable,
facial convexity angle, nasolabial angle, and lower
lip protrusion showed greater changes in G1. The
strict retraction requirements of the anterior teeth
did not result in adverse facial changes for any
patient. With more crowding, soft-tissue changes
are expected to be smaller.
REFERENCES
1. Farrow AL, Zarrinnia K, Azizi K. Bimaxillary protrusion in black
Americansan esthetic evaluation and the treatment considerations. Am J Orthod Dentofacial Orthop 1993;104:240-50.
2. Dandajena TC, Nanda RS. Bialveolar protrusion in a Zimbabwean sample. Am J Orthod Dentofacial Orthop 2003;123:
133-7.
3. Carter NE, Slattery DA. Bimaxillary proclination in patients of
Afro-Caribbean origin. Br J Orthod 1988;15:175-84.
4. Proffit WR, Fields HW. Contemporary orthodontics. 3rd ed. St
Louis: Mosby; 2000.
5. Drobocky OB, Smith RJ. Changes in facial profile during
orthodontic treatment with extraction of four first premolars.
Am J Orthod Dentofacial Orthop 1989;95:220-30.
6. Kusnoto J, Kusnoto H. The effect of anterior tooth retraction on
lip position of orthodontically treated adult Indonesians. Am J
Orthod Dentofacial Orthop 2001;120:304-7.
7. Talass MF, Talass L, Baker RC. Soft-tissue profile changes
resulting from retraction of maxillary incisors. Am J Orthod
Dentofacial Orthop 1987;91:385-94.
8. Roos N. Soft-tissue profile changes in Class II treatment. Am J
Orthod 1977;72:165-75.
9. Burstone CJ. The segmented arch approach to space closure.
Am J Orthod 1982;82:361-78.
10. Williams R, Hosila FJ. The effect of different extraction sites
upon incisor retraction. Am J Orthod 1976;69:388-410.
11. Creekmore TD. Where teeth should be positioned in the face and
jaws and how to get them there. J Clin Orthod 1997;31:586-608.
12. Roberts WE, Nelson CL, Goodacre CJ. Rigid implant anchorage
to close a mandibular first molar extraction site. J Clin Orthod
1994;28:693-704.
13. Choi BH, Zhu SJ, Kim YH. A clinical evaluation of titanium
miniplates as anchors for orthodontic treatment. Am J Orthod
Dentofacial Orthop 2005;128:382-4.
14. Park HS, Kwon TG. Sliding mechanics with microscrew implant
anchorage. Angle Orthod 2004;74:703-10.
15. Park HS, Bae SM, Kyung HM, Sung JH. Micro-implant anchorage for treatment of skeletal Class I bialveolar protrusion. J Clin
Orthod 2001;35:417-22.
16. Park YC, Chu JH, Choi YJ, Choi NC. Extraction space closure
with vacuum-formed splints and miniscrew anchorage. J Clin
Orthod 2005;39:76-9.
17. Burstone CJ. Lip posture and its significance in treatment
planning. Am J Orthod 1967;53:262-84.

Upadhyay et al 29

18. Zierhut EC, Joondeph DR, rtun J, Little RM. Long-term profile
changes associated with successfully treated extraction and
nonextraction Class II Division 1 malocclusions. Angle Orthod
2000;70:208-19.
19. Isaacson JR, Isaacson RJ, Speidel TM, Worms FW. Extreme
variation in vertical facial growth and associated variation in
skeletal and dental relations. Angle Orthod 1971;41:219-29.
20. Aras A. Vertical changes following orthodontic extraction treatment
in skeletal open bite subjects. Eur J Orthod 2002;24:407-16.
21. Schudy FF. The control of vertical overbite in clinical orthodontics. Angle Orthod 1968;38:19-39.
22. Sassouni V, Nanda S. Analysis of dentofacial vertical proportions. Am J Orthod 1964;50:801-23.
23. Staggers JA. A comparison of results of second molar and first
premolar extraction treatment. Am J Orthod Dentofacial Orthop
1990;98:430-6.
24. Hans MG, Groisser G, Damon C, Amberman D, Nelson S,
Paloma JM. Cephalometric changes in overbite and vertical
facial height after removal of 4 first molars or first premolars.
Am J Orthod Dentofacial Orthop 2006;130:183-8.
25. Cusimano C, McLaughlin RP, Zernik JH. Effects of first bicuspid
extractions on facial height in high-angle cases. J Clin Orthod
1993;27:594-8.
26. Kuhn RJ. Control of anterior vertical dimension and proper
selection of extraoral anchorage. Angle Orthod 1968;38:
340-9.
27. Kocadereli I. The effect of first premolar extraction on vertical
dimension. Am J Orthod Dentofacial Orthop 1999;116:41-5.
28. Kim TK, Kim JT, Mah J, Yaung WS, Baek SH. First or second
premolar extraction effects on facial vertical dimensions. Angle
Orthod 2005;75:177-82.
29. Ziegler P, Ingervall B. A clinical study of maxillary canine
retraction with a retraction spring and with sliding mechanics.
Am J Orthod Dentofacial Orthop 1989;95:99-106.
30. Thiruvenkatachari B, Pavithranand A, Rajasigamani K, Kyung
HM. Comparison and measurement of the amount of anchorage
loss of the molars with and without the use of implant anchorage
during canine retraction. Am J Orthod Dentofacial Orthop
2006;129:551-4.
31. Baker RW, Guay AH, Peterson HW. Current concepts of
anchorage management. Angle Orthod 1972;42:129-38.
32. Gjessing P. Biomechanical design and clinical evaluation of new
canine-retraction spring. Am J Orthod 1985;87:353-62.
33. Peck S, Peck L, Kataja M. Skeletal asymmetry in esthetically
pleasing faces. Angle Orthod 1991;61:43-8.
34. Bowman SJ. More than lip service: facial esthetics in orthodontics. J Am Dent Assoc 1999;130:1173-81.
35. Prahl-Andersen B, Ligthelm-Bakker AS, Wattel E, Nanda R.
Adolescent growth changes in soft tissue profile. Am J Orthod
Dentofacial Orthop 1995;107:476-83.
36. Zylinski CG, Nanda RS, Kapila S. Analysis of soft tissue facial
profile in white males. Am J Orthod Dentofacial Orthop 1992;
101:514-8.
37. Oliver BM. The influence of lip thickness and strain on upper lip
response to incisor retraction. Am J Orthod 1982;82:141-9.
38. Lo FD, Hunter WS. Changes in nasolabial angle related to
maxillary incisor retraction. Am J Orthod 1982;82:384-91.
39. Wisth J. Soft tissue response to upper incisor retraction in boys.
Br J Orthod 1974;1:199-204.
40. Hillesund E, Fjeld D, Zachrisson BU. Reliability of soft-tissue
profile in cephalometrics. Am J Orthod 1978;74:537-50.

29.e1 Upadhyay et al

American Journal of Orthodontics and Dentofacial Orthopedics

July 2008

APPENDIX

CONSORT checklist of items to include when reporting a randomized trial

Article section and topic

Item

Description

Title and abstract

Introduction, background
Methods, participants

2
3

Interventions

Objectives
Outcomes

5
6

Sample size

Randomizationsequence
generation
Randomizationallocation
concealment

How participants were allocated to interventions (eg, random

allocation, randomized, or randomly assigned).
Scientific background and explanation of rationale.
Eligibility criteria for participants and the settings and locations
where the data were collected.
Precise details of the interventions intended for each group and how
and when they were actually administered.
Specific objectives and hypotheses.
Clearly defined primary and secondary outcome measures and, when
applicable, any methods used to enhance the quality of
measurements (eg, multiple observations, training of assessors).
How sample size was determined and, when applicable, explanation
of any interim analyses and stopping rules.
Method used to generate the random allocation sequence, including
details of any restrictions (eg, blocking, stratification).
Method used to implement the random allocation sequence (eg,
numbered containers or central telephone), clarifying whether the
sequence was concealed until interventions were assigned.
Who generated the allocation sequence, who enrolled participants,
and who assigned participants to their groups.
Whether participants, those administering the interventions, and those
assessing the outcomes were blinded to group assignment. When
relevant, how the success of blinding was evaluated.
Statistical methods used to compare groups for primary outcomes;
methods for additional analyses, such as subgroup analyses and
adjusted analyses.
Flow of participants through each stage (a diagram is strongly
recommended). Specifically, for each group report, the numbers of
participants randomly assigned, receiving intended treatment,
completing the study protocol, and analyzed for the primary
outcome. Describe protocol deviations from study as planned,
together with reasons.
Dates defining the periods of recruitment and follow-up.
Baseline demographic and clinical characteristics of each group.
Number of participants (denominator) in each group included in each
analysis and whether the analysis was by intention-to-treat. State
the results in absolute numbers when feasible (eg, 10 of 20, not
50%).
For each primary and secondary outcome, a summary of results for
each group, and the estimated effect size and its precision (eg,
95% confidence interval).
Address multiplicity by reporting any other analyses performed,
including subgroup analyses and adjusted analyses, indicating
those prespecified and those exploratory.
All important adverse events or side effects in each intervention
group.
Interpretation of the results, taking into account study hypotheses,
sources of potential bias or imprecision and the dangers associated
with multiplicity of analyses and outcomes.
Generalizability (external validity) of the trial findings.
General interpretation of the results in the context of current
evidence.

Randomizationimplementation

10

Blinding (masking)

11

Statistical methods

12

Results, participant flow

13

Recruitment
Baseline data
Numbers analyzed

14
15
16

Outcomes and estimation

17

Ancillary analyses

18

Adverse events

19

Interpretation

20

Generalizability
Overall evidence

21
22

Reported on page
18
18, 19
19
19, 20
19
19-21

19, 20
19
19

19
19

21

20, flow chart (Fig 1)

19, 20
19,24 (Tables I and II)
19, 20, flow chart (Fig 1)

21-23, 25-27 (Tables III-V)

21

20, Flow chart (dropouts), 25

23-28

28
25-28