CRANIOMAXILLOFACIAL DEFORMITIES/COSMETIC SURGERY

Improved Apnea-Hypopnea Index

and Lowest Oxygen Saturation After
Maxillomandibular Advancement With
or Without Counterclockwise Rotation
in Patients With Obstructive Sleep Apnea:
A Meta-Analysis
Thorkild B. Knudsen, DDS,* Anne S. Laulund, BMSc,y Janne Ingerslev, DDS,z
Preben Homøe, MD, PhD, DrMedSc,x and Else M. Pinholt, DDS, MSc, DrOdontSck
Purpose: This study investigated whether patients with obstructive sleep apnea (OSA) who undergo
maxillomandibular advancement (MMA) with counterclockwise (CCW) rotation compared with those
who undergo MMA without CCW rotation have better outcomes.
Materials and Methods: This was a systematic review with meta-analysis. The Medline and Cochrane
databases were searched for randomized controlled trials using Medical Subject Headings. The predictor vari-
able was operative technique, namely MMA with or without CCW rotation of the maxillofacial complex. The
key outcome variables were changes in pre- and postsurgical values of pharyngeal volume measured on
computed tomogram or cone-beam computed tomogram and changes in Apnea-Hypopnea Index (AHI) and
lowest oxygen saturation (LSAT) values after surgery. Data were subjected to a meta-analysis based on odds ratios
(OR) with 95% confidence intervals (CIs) and P values lower than .05 by c2 test were considered significant.
Results: Twenty-one randomized controlled trials were identified and 4 were assessed for the variables of
interest. Postoperative AHI and LSAT measurements showed vast improvement. The sample was not large
enough to make a correlation between pharyngeal volume changes and surgical method used. Postopera-
tive parameters included an AHI lower than 5 (OR = 14.9; 95% CI, 2.7-83.5; P = .002), an AHI lower than 20
(OR = 114.8; 95% CI, 23.5-561.1; P <.00001), pooled results of a 50% decrease in the AHI (OR = 6.1; 95% CI,
2.2-17.0; P = .0006), and an increase greater than 90% in LSAT measurements during sleep (OR = 6.0; 95%
CI, 1.8-19.9; P = .003). The funnel plot showed no evidence of publication bias.
Conclusion: CCW-MMA or MMA in patients with OSA results in a statistically meaningful decrease in
postoperative AHI and a statistically meaningful increase in postoperative LSAT.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 73:719-726, 2015

*Consultant, Department of Otorhinolaryngology and
Maxillofacial Surgery, Køge University Hospital, Køge, Denmark.
yPhD Student, Department of Endocrinology and Metabolism,
Odense University Hospital, Odense, Denmark.
zConsultant, Department of Oral and Maxillofacial Surgery,
Hospital of South West Denmark, Esbjerg, Denmark.
xProfessor, Department of Otorhinolaryngology and Maxillofacial
Surgery, Køge University Hospital, Køge, Denmark.
kProfessor and Consultant, Department of Oral and Maxillofacial
Surgery, Hospital of South West Denmark, Esbjerg, Denmark.
This study was funded by the Regional Research Unit, Roskilde,
Denmark. The Regional Research Unit had no influence on the
contents in this study.
Address correspondence and reprint requests to Dr Knudsen:
Department of Otorhinolaryngology and Maxillofacial Surgery,
Køge University Hospital, Lykkebækvej 1, DK-4600 Køge, Denmark;
e-mail: thorkildk@hotmail.com
Received March 10 2014
Accepted August 3 2014
Ó 2015 American Association of Oral and Maxillofacial Surgeons
0278-2391/14/01312-3
http://dx.doi.org/10.1016/j.joms.2014.08.006

719
720
Obstructive sleep apnea (OSA) is defined as a pause
in breathing during sleep. The patient stops breathing
for 10 to 20 seconds, or even up to 40 seconds, with
subsequent arousal or oxygen desaturation.1-5
The incidence of OSA is 2 to 4% in men, 1 to 2% in
women,1,5 and 5 to 25% in adults.2,6,7 OSA is classified
according to the Apnea-Hypopnea Index (AHI) as the
number of apnea or hypopnea episodes per hour. The
number of episodes per hour is 5 to 20 in the mild
form, 20 to 35 in the moderate form, and more than
35 in the severe form. The normal form is fewer than
5 episodes per hour.1
Another unit of measurement is the Respiratory
Disturbances Index (RDI). The RDI is defined as the
average number of respiratory disturbances (obstruc-
tive apneas, hypopneas, and respiratory event-related
arousals) per hour.8
The common and effective treatment of OSA is contin-
uous positive airway pressure (CPAP),3,9 but patients
often require lifelong treatment.9,10 CPAP treatment is
indicated when the AHI is higher than 15 and with
severe clinical symptoms, such as a disabling active
somnolence not attributable to other causes plus an
impairment in daytime performance or when an AHI
higher than 30 is combined with mild to moderate
clinical symptoms.9 However, 25 to 50% of patients
have difficulties in accepting this treatment.1-3
The pathogenesis of OSA may be a smaller upper
airway volume or a smaller cross-sectional pharyngeal
area at the narrowest point9 owing to local abnormal-
ities, such as retrognathic development of the maxilla
or mandible, hypertrophy of the adenoid tonsillar tis-
sues, or other abnormalities in the anatomy of the phar-
ynx.9 General medical causative conditions include
adipositas owing to excessive submucosal fat deposits
of the pharynx.1,10 Different nonsurgical treatments,
such as the mandibular advancement device (MAD),
have been investigated, with different outcomes.11,12
OSA may be decreased by surgical forward movements
of the maxilla and mandible, with subsequent improve-
ment of airway volumes, thereby eliminating the need
for CPAP.9,13 OSA may be treated by counterclockwise
(CCW) rotation combined with maxillomandibular
advancement (MMA) or by conventional MMA of the
jaws as a first choice.14-17
The authors hypothesized that CCW-MMA and MMA
would have no effect on airway volume, minimum
cross-sectional pharyngeal area, AHI, or lowest oxygen
saturation (LSAT) in patients with OSA. Therefore, this
study investigated whether patients with OSA who un-
dergo MMA with CCW rotation compared with those
who undergo MMA without CCW rotation would
have better outcomes.
Another goal was to perform a systematic review
and meta-analysis of pre- and postoperative measure-
ments of pharyngeal volume (by computed tomogra-
MAXILLOMANDIBULAR ADVANCEMENT FOR SLEEP APNEA
phy [CT] or cone-beam CT [CBCT]), including the
minimum cross-sectional pharyngeal area, AHI, and
LSAT, of patients with OSA who underwent CCW-
MMA or MMA. Another objective was, if possible, to
calculate a difference in the effect of the binary predic-
tor variable (CCW-MMA vs MMA).
Materials and Methods
STUDY DESIGN AND DATA COLLECTION
The authors designed and implemented a systematic
review and meta-analysis. A literature search was carried
out in the PubMed database (http://www.pubmed.org)
and the Cochrane database (http://www.cochrane.org)
using the search terms sleep apnea, obstructive/
snoring/cpap/continuous positive airway pressure +
maxillary/mandible + advancement/mandibular
advancement/maxillomandibular advancement/
orthognathic surgical procedures/maxilla/surgery.
The search was carried out for January 2000 until
February 2014. Medical Subject Headings and keywords
were used in different combinations, as presented in
Table 1. Articles were included if patients had been
diagnosed with OSA, the patients were adults, the pa-
tients did not have a syndrome, CBCT or CT had been
performed before and after surgery, and patients were
treated using CCW-MMA or MMA of the jaws. Articles
were excluded if the treatment was mandibular setback,
patients were treated with a snorkeler’s hanger or a
MAD or similar device, the article was published before
2000, and there was an insufficient number of patients
for statistical analysis.
VARIABLES
The predictor variable was binary and defined as
MMA and combined maxillary Le Fort I and bilateral
mandibular sagittal split osteotomy procedures with
CCW rotation of the jaws18 (CCW-MMA) or without
rotation (MMA).
The outcome variables were changes in pre- versus
postoperative measurements of pharyngeal volume
(by CT or CBCT), AHI, and LSAT. If the outcome vari-
able was not defined using the AHI, the RDI was used.
STATISTICAL ANALYSIS
Statistical analyses of the outcome variables were in-
serted in 2  2 tables (Table 2). Odds ratios (ORs) with
matching 95% confidence intervals (CIs) were selected
for the effect size and calculated with the method of
Bland and Altman19 using a contingency 2  2 table.
P values were calculated using c2 tests and a signifi-
cance level of .05 was chosen. Pooled estimates were
reported when an excess of 2 original cohorts contrib-
uted data. Standard errors and ORs were plotted in fun-
nel plots using the Egger test to visually aid in detecting
KNUDSEN ET AL 721

Table 1. KEYWORDS USED IN SYSTEMATIC SEARCH, INCLUDING NUMBER OF HITS DEALING WITH
MAXILLOMANDIBULAR SURGERY FOR OBSTRUCTIVE SLEEP APNEA, USING THE SEARCH ENGINES PUBMED
(HTTP://WWW.PUBMED.ORG) AND THE COCHRANE DATABASE (HTTP://WWW.COCHRANE.ORG)

Search MeSH Term MeSH Term Results Included

#1 sleep apnea, obstructive — 18,342

#2 sleep apnea, obstructive OR snoring 20,794
#3 sleep apnea, obstructive OR snoring OR cpap 23,353
#4 sleep apnea, obstructive OR snoring OR cpap OR continuous positive 25,624
airway pressure
#5 sleep apnea, obstructive OR snoring OR cpap AND maxillary OR 845
OR continuous positive airway pressure mandible
#6 sleep apnea, obstructive OR snoring OR cpap OR AND advancement 86
continuous positive airway pressure))
AND ((((((maxillary OR mandible[Title]))
#7 ((((sleep apnea, obstructive OR snoring OR mandibular advancement 762
cpap OR continuous positive airway OR maxillomandibular
pressure)) AND ((((((maxillary OR advancement
mandible[Title])) AND advancement[Title]))
#8 ((((sleep apnea, obstructive OR snoring OR cpap OR ((orthognathic 819
OR continuous positive airway pressure)) AND surgical procedures OR
((((((maxillary OR mandible[Title])) AND maxilla/surgery)))))
advancement[Title])) OR ((mandibular
advancement) OR maxillomandibular
advancement))
Total ((((sleep apnea, obstructive OR snoring OR cpap AND imaging, three 21 8 articles, but only 4
OR continuous positive airway pressure)) AND dimensional had enough patients
((((((maxillary OR mandible[Title])) AND for statistical analysis
advancement[Title])) OR ((mandibular
advancement) OR maxillomandibular
advancement)) OR ((orthognathic surgical
procedures OR maxilla/surgery)))))

Abbreviations: cpap, continuous positive airway pressure; MeSH, Medical Subject Heading.
Knudsen et al. Maxillomandibular Advancement for Sleep Apnea. J Oral Maxillofac Surg 2015.

systematic heterogeneity and publication bias.20 Only Results

funnel plots with a sufficient interpretation value
from an adequate number of included studies are
reported. I2 statistics described the inconsistency
between studies not caused by a random error. An I2
statistic greater than 50% was used as a threshold, indi-
cating high heterogeneity. Studies were pooled using a
random-effects model when the I2 statistic was greater
than 50% and a fixed-effects model when the I2 statistic
was less than 50%.
Wide CIs are indicative of less confidence in the
data. When the CI does not cross the ‘‘line of no effect’’
(OR = 1), the association between x and y is consid-
ered statistically important (x = AHI <5; y = operation).
The Preferred Reporting Items for Systematic
Reviews and Meta-Analyses guidelines for reporting
systematic reviews and meta-analyses were fol-
lowed.21 Data were analyzed with Excel (Microsoft,
Redmond, WA) and RevMan (Nordic Cochrane Centre,
Copenhagen, Denmark).
REVIEW
For the meta-analysis, 21 articles were extracted
(Table 1), 8 articles were selected, and only 4 of the
included studies met the criterion of a sufficient num-
ber of patients for inclusion in a meta-analysis
(Table 2).22-25 The funnel plot showed no presence
of publication bias (not shown) in the results.
EFFECT OF OPERATION ON AHI, WITH THE AIM OF
ACHIEVING A NORMAL AHI LEVEL (AHI #5)
Three studies were included in the analysis of the
association between an AHI no higher than 5 and
surgery (49 patients; Fig 1).
The results showed a low level of heterogeneity
(I2 = 0); hence, the fixed-effects model was used.
The range of ORs was large, from 5.5 (95% CI,
.25-123.1) in the study by Fairburn et al22 to 25.0
722 MAXILLOMANDIBULAR ADVANCEMENT FOR SLEEP APNEA

Table 2. NUMBERS OF PATIENTS COUNTED AND INSERTED INTO 2  2 CHARTS

Study CCW-MMA vs MMA

Fairburn et al22 MMA

Data extracted as
indicated in Table 1
AHI >5 AHI #5 Total

Before surgery 20 0 20*

After surgery 18 2 20*
Total 38* 2* 40*
AHI >20 AHI #20 Total

Before surgery 20 0 20*

After surgery 7 13 20*
Total 27* 13* 40*
AHI reduction >50% after surgery AHI pre-op Total

Before surgery 8 12 20
After surgery 16 4 20
Total 24 16 40

LSAT $90% LSAT <90% Total

Before surgery 1 19 20*

After surgery 6 14 20*
Total 7* 33* 40*

Lin et al23 CCW-MMA

Data extracted as
indicated in Table 1

AHI >5 AHI #5 Total

Before surgery 12 0 12*

After surgery 6 6 12*
Total 18* 6* 24*

AHI >20 AHI #20 Total

Before surgery 10 2 12*

After surgery 0 12 12*
Total 10* 14* 24*
AHI decrease >50% after surgery AHI decrease <50% after surgery Total

Before surgery 0 0 0
After surgery 12 0 12
Total 12* 0* 12*
LSAT $90% LSAT <90% Total

Before surgery 2 10 12*

After surgery 6 6 12*
Total 8* 16* 24*

Abramson et al24 MMA

Data extracted as
indicated in Table 1
KNUDSEN ET AL 723

Table 2. Cont’d

Study CCW-MMA vs MMA

RDI >5 RDI #5 Total

Before surgery 10 0 10*

After surgery 7 0 7*
Total 17* 0* 17*
RDI >20 RDI #20 Total

Before surgery 9 1 10*

After surgeryy 1 6 7*
Total 10* 7* 17*
RHI reduction >50% after surgery RHI pre-op Total

Before surgery 5 2 7
After surgery 5 2 7
Total 10 4 14

LSAT $90 LSAT <90 Total

Before surgery 3 8 11*

After surgery 4 2 6*
Total 7* 10* 17*

Zinser et al25 CCW-MMA

Data extracted as
indicated in Table 1

AHI >5 AHI # 5 Total

Before surgery 17 0 17
After surgery 11 6 17
Total 28 6 34

AHI >20 AHI #20 Total

Before surgery 17 0 17*

After surgery 0 17 17*
Total 17* 17* 34*
AHI reduction >50% after surgery AHI pre-op Total

Before surgery 7 8 15
After surgery 17 0 17
Total 24 8 32
LSAT $90% LSAT <90% Total

Before surgery — — —*
After surgery — — —*
Total —* —* —*
Abbreviations: AHI, Apnea-Hypopnea Index; CCW-MMA, maxillomandibular advancement with counterclockwise rotation;
LSAT, lowest oxygen saturation; MMA, maxillomandibular advancement without counterclockwise rotation; RDI, Respiratory
Disturbances Index.
* Total patients with obstructive sleep apnea before and after surgery using CCW-MMA or MMA.
y After surgery there were 5 patients who did not follow the controls, so these 5 patients were omitted from this row.
Knudsen et al. Maxillomandibular Advancement for Sleep Apnea. J Oral Maxillofac Surg 2015.
724 MAXILLOMANDIBULAR ADVANCEMENT FOR SLEEP APNEA

FIGURE 1. Statistical analysis of the postoperative effect of surgery at an AHI lower than 5. The pooled result is statistically significant, but the
study by Fairburn et al22 showed no important association between maxillomandibular advancement without counterclockwise rotation and
maxillomandibular advancement with counterclockwise rotation. AHI, Apnea-Hypopnea Index; CI, confidence interval; M-H, Mantel-
Haenszel test; RDI, Respiratory Disturbances Index.
Knudsen et al. Maxillomandibular Advancement for Sleep Apnea. J Oral Maxillofac Surg 2015.

(95% CI, 1.2-516.7) in the study by Lin et al.23 The result was found to be significant (OR = 6.09; 95% CI,
pooled OR was 14.9 (95% CI, 2.7-83.5; P = .002). 2.18-16.96; P = .0006).

EFFECT OF SURGERY ON AHI WITH THE AIM OF
ACHIEVING A MILD AHI LEVEL (AHI #20)
When investigating the association between surgery
and mild OSA (Fig 2), 4 original studies met the inclusion
criteria (59 patients).22-25 Each included study was found
to be statistically meaningful, with no CIs crossing the
vertical line (OR = 1) and with ORs ranging from 54.0
(95% CI, 2.8-1040.1) to 1225.0 (95% CI, 23.0-65266.1).
The pooled analysis showed an I2 statistic of 0%.
Therefore, a fixed-effects analysis was chosen and the
pooled effect was found to be statistically significant
(OR = 114.8; 95% CI, 23.5-561.1; P <.00001).
The OR for CCW-MMA ranged from 105.00 (95% CI,
4.52-2,438.70) to 1225.0 (95% CI, 23.0-65266.1). The
OR for MMA ranged from 54.0 (95% CI, 2.8-1040.1)
to 73.8 (95% CI, 3.89-1,401.56).
EFFECT OF SURGERY ON AHI WITH THE AIM OF
ACHIEVING AN AHI DECREASE GREATER THAN 50%
Three studies were included in the analysis of the as-
sociation between an AHI decrease greater than 50% and
surgery (36 patients; Fig 3).22,24,25 The analysis showed
an I2 statistic of 48, which is borderline, but still
accepted as a low level of statistical heterogeneity;
hence, the fixed-effects model was used. The pooled
EFFECT OF SURGERY ON LSAT DURING SLEEP
($90%)
Three studies were included in the analysis of the as-
sociation between surgery and postoperative LSAT
measured during sleep (35 patients; Fig 4).22-24 The
results showed no statistical heterogeneity (I2 = 0).
The pooled result was found to be statistically
significant (OR = 6.01; 95% CI, 1.82-19.86; P = .003).
Discussion
In patients with OSA, the pharyngeal volume may
be increased as an effect of CCW-MMA or MMA. The
authors investigated whether the AHI and LSAT would
be affected in these patients. Their hypothesis was that
CCW-MMA and MMA would have no effect on airway
volume, minimum cross-sectional pharyngeal area,
AHI, or LSAT in patients with OSA.
An aim of this study was to perform a systematic
review and meta-analysis on changes of pre- versus
postoperative measurements of pharyngeal volume
(by CT or CBCT), including the minimum cross-
sectional pharyngeal area, AHI, and LSAT of patients
with OSA who underwent CCW-MMA or MMA. Another
aim was, if possible, to calculate a difference in effect of
the binary predictor variable (CCW-MMA vs MMA).

FIGURE 2. Statistical analysis of the postoperative effect of surgery at an AHI lower than 20. Each of these 4 studies showed a positive
correlation between RDI below 20 and surgery. AHI, Apnea-Hypopnea Index; CI, confidence interval; M-H, Mantel-Haenszel test; RDI,
Respiratory Disturbances Index.
Knudsen et al. Maxillomandibular Advancement for Sleep Apnea. J Oral Maxillofac Surg 2015.
KNUDSEN ET AL 725

FIGURE 3. Statistical analysis of a decrease of at least 50% of the postoperative AHI. The pooled result is statistically meaningful, but the study
by Abramson et al24 was not found to be statistically important. AHI, Apnea-Hypopnea Index; CI, confidence interval; M-H, Mantel-Haenszel
test; RDI, Respiratory Disturbances Index.
Knudsen et al. Maxillomandibular Advancement for Sleep Apnea. J Oral Maxillofac Surg 2015.

The meta-analysis showed meaningful improve-
ments in the AHI and LSAT after CCW-MMA or MMA
owing to positive changes of an AHI lower than 5, an
AHI lower than 20, a 50% decrease in the AHI, and
increased LSAT (measured during sleep). For the first
time, a meta-analysis of measurements obtained after
treatment with CCW-MMA or MMA in patients with
OSA has been performed. However, no statistical data
were obtainable to distinguish which treatment,
CCW-MMA or MMA, was the most beneficial. Hence,
the authors’ hypothesis can by rejected because the
AHI and LSAT showed improvement. Airway volumes
were not measurable.
The systematic review showed that only 2 of 8
published studies, by Lin et al23 and Zinser et al,25
described results after CCW-MMA treatment, whereas
the remaining 6 studies reported results after only
MMA. Four of the 8 studies had too few patients evalu-
ated and were subsequently omitted from the meta-
analysis. This review also showed that it was not
possible to perform or evaluate a meta-analysis on
postoperative results on pharyngeal volume or cross-
sectional pharyngeal area changes after CCW-MMA or
MMA, because comparable measurements of the phar-
ynx were obtained in only 3 patients,26-28 although all
patients in the included studies underwent CBCT or
CT. Furthermore, it was not possible to investigate
how much the extent advancement and degree of
rotation of the maxilla and mandible influenced the
change in the pharyngeal airway space (PAS) because
relevant data in the articles were absent. It remains
unexamined and this issue needs to be investigated in
future research projects.
Furthermore, there is a lack of standardized methods
for head and tongue positioning when performing
CBCT or CT on a patient. A CBCT scan implies a patient
who is sitting upright with a neutral position of the
head, tongue, and peripharyngeal soft tissues. A con-
ventional CT scan and some CBCT scans imply a patient
who is lying supine with subsequent changes from
neutral anatomic positioning of head, tongue, and pe-
ripharyngeal soft tissues. The head and tongue posi-
tions are expected to have an important influence on
the pharyngeal soft tissue positions and, hence, the
pharyngeal volume.29 Reproducible head and tongue
positions remain to be defined and ought to be included
in future studies.
Because these parameters are crucial in patients
with OSA and CPAP treatment is costly, the effects of
different treatment modalities on these patients
require controlled clinical trials in search of evidence
of best treatment for these patients.
In a study by Raffaini and Pisani,30 a noteworthy
3-dimensional improvement in the PAS was found after
CCW-MMA, leading the patient to notice a subjective
improvement in breathing function, but none of
the patients were tested for OSA.30 However, one
can assume that the positive effect noted in this study
also might be observed in patients with OSA.
The criteria for successful treatment of OSA are diffi-
cult to define. Some researchers have set criteria for
successful treatment of OSA and those parameters

FIGURE 4. Statistical analysis of the postoperative effect of surgery on LSAT under sleep. The pooled result is meaningful, but none of the
included studies were statistically important. CI, confidence interval; LSAT, lowest oxygen saturation; M-H, Mantel-Haenszel test.
Knudsen et al. Maxillomandibular Advancement for Sleep Apnea. J Oral Maxillofac Surg 2015.
726
were chosen for the meta-analysis of this review.14,31
However, it may represent a weakness and ought to
be considered in future studies.
In this review, the different parameters (AHI #5, AHI
#20, or AHI decrease to $50% compared with preoper-
ative measurement and LSAT increase $90% during
sleep) were tested. These values were obtained when
treating patients with MMA. Neither a definition of the
values nor knowledge concerning the best treatment
modality is known. The present systematic review and
meta-analysis did not indicate which surgical approach
was the most effective owing to insufficient data.
Orthognathic procedures such as CCW-MMA and
MMA result in a statistically meaningful decrease in
the postoperative AHI and a statistically meaningful
increase in the postoperative LSAT in patients with
OSA. It was not possible to distinguish which procedure
was the most beneficial or to perform a meta-analysis of
pharyngeal volumes and narrowest cross-sectional
pharyngeal area in the reviewed material owing to insuf-
ficient data.
Future prospective clinical trials should evaluate the
magnitude of forward movement and degree of rota-
tion necessary to obtain effective treatment of OSA,
with the objective to free these patients from
CPAP treatment.
Standardized head and tongue positions during
scanning ought to be defined to obtain optimal repro-
ducible data.
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