Yonago Acta medica 2013;56:21–27

Original Article

Morphological and Volumetric Analysis of the Development of Atlantoaxial Vertical
Subluxation in Rheumatoid Arthritis
Toshiyuki Dokai,* Hideki Nagashima,* Toru Okano,* Yoshiro Nanjo,* Yuji Kishimoto,* Atsushi Tanida,* Suguru
Kakite† and Hiroshi Hagino‡*Division of Orthopedic Surgery, Department of Medicine of Sensory and Motor Organs, School of Medicine, Tottori University Facultyof Medicine, Yonago 683-8504, Japan, †Division of Radiology, Department of Pathophysiological and Therapeutic Science, Schoolof Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan and ‡Department of Fundamental Nursing, School of
Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan

ABSTRACT
Background Cervical disorders in rheumatoid arthritis (RA) patients have been an important problem for along time. Although the recent progression of the treatment strategies for RA might change the progression ofatlantoaxial vertical subluxation (VS) in RA patients,
to reveal the risk factors for VS progression should be
important at present. Osteoporosis (OP) and RA sharethe same risk factors. The purposes of this study were to
identify the progression of VS in RA, and to evaluate therelationship between the VS development and OP.
Methods Eighty female patients with RA and 18 female patients with OP were retrospectively analyzed.
The RA patients were divided into VS (10 patients) and
non-VS groups (70 patients). Morphological parameters
on coronal reconstructed computed tomography images
were evaluated. Three-dimensional analysis was used tomeasure volumes and volumetric bone mineral densities(vBMDs) at the upper cervical spine (UCS).
Results
The VS group had higher age, longer RA
symptom duration, and lower BMD at the lumbar spinecompared to the non-VS group. Volumes and vBMDs at
the UCS in RA group were greater than those in the OPgroup. In accordance with VS development, the lateral
masses at the UCS became shorter, the C1 facet angle
became sharper, and the volumes at the UCS decreased.
However, there was no statistically significant relationshipbetween vBMDs at the UCS and the VS development.
Conclusion The C1 facet angle became sharper with
VS progression. Although 3-dimensional analysis revealed that decreases in the volumes at the UCS wereassociated with VS development, no significant relationship between OP and the VS development was observed.

Key words bone mineral density; osteoporosis; rheumatoid arthritis; vertical subluxation

Atlantoaxial vertical subluxation (VS) is one of the common instabilities and the most fatal complication forpatients with rheumatoid arthritis (RA). Several crosssectional studies revealed that the incidence of VS ranges from 4 to 35%.1, 2 Since patients with atlantoaxial instabilities are not always symptomatic, the real incidenceof VS may actually be higher. VS may be caused byrheumatoid synovitis at the upper cervical spine (UCS),
following the joint destruction of atlanto-occipital joint(AOJ) and atlantoaxial joint (AAJ).3–7 However, there
have been few reports on the development of lateralmass collapse in the UCS with progression of VS.8, 9
Symptoms include headache, myelopathy, dyspnea andsometimes death. Therefore, to detect subclinical VS
patients and to prevent the VS progression, it is important to reveal the morphological changes at the UCS andprognostic factors for VS progression.
Many prognostic factors for VS have been reported
previously, including age, sex, menopausal status, duration of RA symptoms, severity of RA, number of erosive
peripheral joints, a subset with mutilating disease, anduse of glucocorticoids.10–16 Some of the reported prognostic factors for VS are also risk factors for osteoporosis (OP). RA, itself, is one of the causes for secondary
OP. Moreover, it has been reported that lumbar vertebral
deformity in RA patients had an association with areal
bone mineral density (BMD).17, 18 Therefore, we hypothesize that OP could affect the progression of VS. This
study had 2 aims: to identify the morphological changes
in VS progression, and to evaluate the relationship between the progression of VS and OP.

Corresponding author: Hiroshi Hagino
hagino@med.tottori-u.ac.jp
Received 2012 December 4
Accepted 2012 December 27
Abbreviations: 3D-TBSAS, 3-dimensional TEIJIN Bone Structure
Analysis System; AAJ, atlantoaxial joint; AOJ, atlanto-occipital
joint; BMD, bone mineral density; CI, confidence interval; CT,
computed tomography; FA, facet angle; LMH, lateral mass height;
OP, osteoporosis; R-J, Redlund-Johnell; RA, rheumatoid arthritis;
UCS, upper cervical spine; V, volume; vBMD, volumetric BMD;
VS, vertical subluxation

SUBJECTS AND METHODS
Subjects

Subjects were recruited from outpatient clinics at
Tottori University Hospital between April 2008 andMarch 2009. Female patients were eligible if they had
21T. Dokai et al.

a definitive diagnosis of RA, met the revised criteria of
the American College of Rheumatology,19 and had theability to understand and complete a written informed
consent form. Patients with postmenopausal OP wererecruited as controls. Patients were defined as having OP
if they: i) were over 45 years of age, ii) had no history ofsymptoms or medication use that can induce OP (including glucocorticoids) and iii) had BMD below 70% or a
T-score of −2.6 below the young adult mean as measured
by a Hologic QDR bone densitometer (Hologic, Bedford, MA) or osteopenia (BMD below 80% or T-score of−1.7 below the young adult mean) with at least 1 fragility fracture, as defined by the criteria of the JapaneseSociety for Bone and Mineral Research. A total of 111
patients (86 patients with RA and 25 with OP) fulfilled
these inclusion criteria. Investigators provided written
and verbal explanations of the study and obtained a written informed consent from each subject.
To investigate the etiology of VS, RA patients weredivided into 2 groups, those with VS (VS group) andthose without VS (non-VS group). VS was diagnosed
when the Redlund-Johnell (R-J) value was less than 29
mm on plain lateral radiographs.20

1

2

4

3
5

Fig. 1. Anatomical parameters are defined as follows:
1: odontoid height (OH)
2: lateral mass height of the atlas, LMH(C1)
3: lateral mass height of the axis, LMH(C2)
4: facet angle of the atlas, FA(C1)
5: facet angle of the axis, FA(C2)distance from the upper to the lower peak of the C1 lateral mass. LMH(C2) was defined as the length between
the lower endplate to the upper surface of the C2 facet.
FA(C1) was the angle between the upper and lower facet
surfaces, and FA(C2) was the angle between the lower
endplate of the axis and upper facet surface of the axis.
Odontoid height was defined as the perpendicular distance from the tip of the odontoid process to the lower
endplate of the axis. Morphological changes at the AOJ
and AAJ on the coronal reconstructed CT images wereclassified into 3 types: normal, erosive and ankylosing.21
Bone defects in the odontoid process were classified into
3 types: spot, small and large.22

Morphological analysis by using reconstructed CT
imagesThe morphological parameters of the UCS were evaluated on coronal reconstructed computed tomography(CT) images (Aquilion 64; Toshiba Medical Systems,
Otawara, Japan). During CT scanning, subjects were ina supine position with their necks in an extended position using a special pillow. Bone mineral reference phantoms, made of hydroxylapatite (Kyoto Kagaku, Kyoto,
Japan), were placed on the neck to quantify volumetric
BMD (vBMD) at the UCS. In patients with dentures andimplants around the occipitocervical junction, several
artifacts (including halation) affected the CT data. To
avoid the influence of artifacts, the CT gantry was tilted
30˚ caudally. After locating the region from the basiocciput to C3 on a lateral scout-view of the UCS, these levels were encompassed with 0.5 mm slices at 120 kV/200
mA, with a 0.5-s/rot pitch and a 153.8-mm diameterfield of view.
The coronal CT images were reconstructed withthe axis parallel to the odontoid process. Using coronalreconstructed CT views, AOJ and AAJ were morphologically evaluated. The anatomical parameters included
the odontoid height, lateral mass height (LMH) of theatlas and axis [LMH(C1) and LMH(C2), respectively],
and the facet angle (FA) of the atlas and axis [FA(C1)and FA(C2), respectively] (Fig. 1). We defined theseparameters as follows: LMH(C1) was the perpendicular

BMD measurements at the lumbar spine and hip

The measurements of BMD at the lumbar spine (L24) [BMD(lumbar)] and right hip were performed using
postero-anterior dual X-ray energy absorptiometry with
the QDR Discovery instrument (Hologic). For the BMDof the hip [BMD(hip)], we used the neck BMD value.
vBMD measurements at the UCS

To measure vBMD at the UCS, we employed the 3-dimensional TEIJIN Bone Structure Analysis System (3DTBSAS; Teijin Pharma, Tokyo, Japan), which was basedon the theory of Azuma et al.23
The original raw CT data in DICOM format was obtained from the same CT device (described above) witha slice thickness of 0.5 mm and pixel width of 0.35 mm
and used by 3D-TBSAS to construct a 3-dimensionalmodel. The system could distinguish and separate each22

Vertical subluxation in RA/osteoporosis
Table 1. Characteristics of study patients
OP group

Non-VS group

VS group

P value

Total
19		
Postmenopausal 19		
72.6 (59–84)
Age (yr)		

70		
68		
63.3 (34–87)

10		
10		
69.9 (60–82)––< 0.001

Body mass index (kg/m2)		
LumbarBMD (g/cm2)

22.0 (16.9–29.8)
0.692 (0.450–0.867)

22.2 (13.7–33.8)
0.879 (0.614–1.224)

21.5 (17.3–27.4)
NS
0.768 (0.542–1.083)
0.002

Femoral neck
Ranawat classification classification
0
1
2a
RA symptom duration (mo)		
Glucocorticoid usage: n [%]		
CRP (mg/dL)		
ESR (mm/h)		
RF (IU/mL)		
MMP-3 (ng/mL)		
DAS 28		

0.646 (0.486–0.841)*0.670 (0.406–0.911)

0.590 (0.245–0.788) NS

Number

***
**

19		
0		
0		
–		
–		
–		
–		
–		
–		
–		

*

70		
0		
0		
72.4 (12–456)
38.8 [54.3]
0.66 (0.04–4.41)
43.9 (8–117)
140.8 (5.0–980.1)
134.9 (21–561)
4.02 (1.46–7.33)

8		
1
1
91.7 (11–384)
7.0 [70]
1.10 (0.05–4.95)
47.6 (12–99)
115.4 (12.8–69.3)
140.9 (10–345)
3.68 (2.09–5.53)

NS< 0.001
NS
NS
NS
NS
NS
NS

Data are expressed as means (range).
BMD, bone mineral density; CRP, C-reactive protein; DAS, disease activity score; ESR, erythrocyte sedimentation rate; MMP-3, matrix
metalloproteinase-3; NS, not significant; OP, postmenopausal osteoporosis; RA, rheumatoid arthritis; RF, rheumatoid factor; VS, verticalsubluxation.
P < 0.05 was considered statistically significant among 3 groups. When there was a statistical significance between 2 groups, we showed
the relationships as follows in the table: *P < 0.05. **P < 0.01. ***P < 0.001.

3D-TBSAS could neither distinguish each structure nor
calculate the correct vBMDs. RA patients with severerheumatoid changes at the UCS were unable to calculate
vBMDs at the UCS. The remaining 33 patients with
RA in the non-VS group and 18 with OP were analyzed
3-dimentionally.

structure according to bone continuity. The watershedof discontinuity was set at 0.5 mm. For each structure,
3D-TBSAS calculated the whole tissue volume, bonevolume, the percentage of bone tissue (bone volume/
tissue volume) and the average CT value for the wholetissue. We analyzed each phantom (200, 300, 400, 500,
600 mg/mL, made with hydroxylapatite and 1,550 mg/
mL phantom, made with alumina) and the structuresin the UCS. Once each structure was distinguished,
we could unite the separate bones and calculate the
combined vBMD using this system. Since a linear correlation between vBMD and averaged CT values of thephantom was confirmed, the average CT value of eachskeletal structure was calculated. Finally, the vBMD was
calculated as follows: vBMD = average CT value × (bonevolume/tissue volume).
The percentage of coefficient of variation in thissystem was evaluated by 105 repeated measurements
for the phantoms (300, 400, 500 and 600 mg/mL). The
percentage of coefficient of variation was defined as lessthan 0.1%.
Using 3D-TBSAS, we could calculate the volumeof the atlas, axis and C1-2 [V(C1), V(C2) and V(C1-2),
respectively], and the vBMD of the atlas, axis and C1-2
[vBMD(C1), vBMD(C2) and vBMD(C1-2), respectively].
In cases of severely destructed or fused bony structures,

Statistical analysis

Differences in demographic data and characteristics between 2 groups were analyzed using the Mann-Whitney
U test, and those for 3 groups were analyzed using the
Kruskal-Wallis test and the Steel-Dwass test for multiple
comparisons. Pearson’s chi-square test or Fisher’s exact
test were used to compare the categories or ratios ofvariables. Spearman’s rank correlation coefficient wasused for the analysis between 2 parameters. P < 0.05
was considered to indicate statistical significance.
To clarify the effects of OP, we performed multiple
logistic regression analysis for the development of VS
by using the statistical significant factors from the comparison between the VS and non-VS groups. Statisticalanalyses were performed using PASW Statistics version
18.0.0 (SPSS, Chicago, IL).
The present study was approved by the Ethics Committee of Tottori University (No. 1088).
23

T. Dokai et al.

Differences in BMD

BMD(lumbar) in the OP group was significantly lower
than in the VS and non-VS groups, but there was no
significant difference between the VS and non-VSgroup (Table 1). There were no statistical differences in
BMD(hip) among the 3 groups.
Morphological findings on coronal reconstructed
CT images

Left and right levels of LMH(C1) in the VS group weresignificantly lower than in the OP group (Fig. 2). Leftand right levels of LMH(C2) in the VS group weresignificantly lower than in the non-VS and OP groups;
however, there was no statistical difference between
the non-VS and OP groups (Fig. 3). Right FA(C1) in the
VS group was significantly more acute than in the OPgroup. There were no significant differences in left andright FA(C2) levels and odontoid height (Table 2).
Compared with the non-VS and OP groups, erosive
and ankylosing changes in AOJ and AAJ were more
frequently recognized in the VS group, and larger bone
defects in the odontoid process were also found in the
VS group (Table 2).

Fig. 2. Measurements of LMH(C1) in the OP, non-VS and
VS groups. The VS group shows lower levels of right and left
LMH(C1) than the OP group. There is no statistical difference between the VS and non-VS groups. P < 0.05 was considered statistically significant. LMH(C1), lateral mass height of the atlas; OP,
osteoporosis; VS, vertical subluxation. [ ], number of subjects.

RESULTS
Demographic data

Ultimately, 99 eligible patients [80 patients with RA
and 19 with OP (OP group)] agreed to participate in thisstudy. Six patients with RA and 6 with OP did not agree
to participate, and 4 patients with OP withdrew theirconsents. There were 10 patients in the VS group and 70
in the non-VS group (Table 1). The incidence of VS in
the present study was 12.5% (10 out of 80 RA subjects)
and all but 1 patient were asymptomatic (1 patient wasclassified as Ranawat I24).
Demographic data are shown in Table 1. All subjects
were postmenopausal, except for 2 in the non-VS group.
The mean age of the non-VS group was significantly
lower than in the VS and OP groups, but there were noother significant differences between the VS and OP
groups.
Between VS and non-VS groups, there were no significant differences in glucocorticoid usage, neurological
function and severity of RA (Table 1). The duration of
RA in the VS group was significantly longer than in the
non-VS group.

Three-dimensional analysis using 3D-TBSAS

The average V(C1) in the RA and OP groups was 6.91
mL (4.33–8.96 ) and 5.68 mL (3.22–8.67), respectively.
The average V(C2) in the RA and OP groups was 7.69
mL (4.08–11.96) and 5.91 mL (3.60–8.62), respectively.
The average V(C1-2) in the RA and OP groups was 14.32
mL (9.25–21.63) and 12.67 mL (6.81–19.97), respectively. The average vBMD(C1) in the RA and OP groups
was 809.7 mg/mL (625.4–1067.9) and 755.5 mg/mL(639.9–842.6), respectively. The average vBMD(C2) in
the RA and OP groups was 762.3 mg/mL (639.6–1106.8)
and 741.7 mg/mL (673.3–840.2), respectively. The average vBMD(C1-2) in the RA and OP groups was 782.4
mg/mL (633.6–1086.2) and 740.9 mg/mL (590.1–902.0),
respectively. Volumes and vBMDs at UCS in the RA
group were larger than in the OP group, but the difference was not significant. vBMD(C1) was greater thanvBMD(C2) in both the RA and OP groups. V(C2) was
larger than V(C1) in both the RA and OP groups.
vBMD(C1), vBMD(C2) and vBMD(C1-2) showed apositive significant correlation with BMD(lumbar) but
not BMD(hip) [vBMD(C1) versus BMD(lumbar): r =0.580, P < 0.001, vBMD(C2) versus BMD(lumbar): r =0.466, P = 0.003, vBMD(C1-2) versus BMD(lumbar): r= 0.466, P = 0.001]. vBMDs at the UCS were strongly
positively correlated with each other [vBMD(C1) versusvBMD(C2): r = 0.950, P < 0.001, vBMD(C1) versusvBMD(C1-2): r = 0.972, P < 0.001, vBMD(C2) versusvBMD(C1-2): r = 0.992, P < 0.001].

Fig. 3. Measurements of LMH(C2) in the OP, non-VS and
VS groups. The VS group shows lower levels of right and left
LMH(C2). P < 0.05 was considered statistically significant.
LMH(C2), lateral mass height of the axis; OP, osteoporosis; VS,vertical subluxation. [ ], number of subjects.

24Vertical subluxation in RA/osteoporosis
Table 2. Morphological findings on coronal reconstructed CT images
Odontoid height (mm)		
LMH(C1) (mm)L
		R
L
LMH(C2) (mm)		
R
L
FA(C1) (˚)		
		
R
L
FA(C2) (˚)		
		
R
AOJ changes Normal
L		R
ErosiveL		R
Ankylosing
L		RL
AAJ changes Normal
		R
ErosiveL		R
Ankylosing
L		R
Bone defects in the odontoid process
Spot		
Small		Large		

OP group [n = 19]

Non-VS group [n = 70]

VS group [n = 10]

P value

31.9 (27.6–35.5)
11.1 (7.5–15.2)
10.9 (7.0–13.7)
12.2 (9.8–14.1)
12.7 (10.9–15.7)
59.3 (47.8–70.0)
63.5 (51.3–76.5)
22.6 (17.2–28.9)
24.2 (16.8–31.1)
15 (78.6)
15 (78.6)
4 (21.4)
4 (21.4)
0 (0.0)0 (0.0)17 (89.5)
16 (64.2)2 (10.5)
2 (10.5)
0 (0.0)1 (5.3)32.2 (27.1–38.9)
9.4 (6.1–14.5)
9.7 (6.4–15.7)
12.6 (9.4–17.0)
12.9 (10.6–16.8)
55.6 (35.2–71.4)
54.8 (33.6–75.7)
21.1 (11.1–31.3)
21.3 (11.6–34.8)
35 (50.0)35 (50.0)30 (42.9)30 (42.9)
5 (7.1)5 (7.1)38 (54.3)
34 (48.6)
27 (38.6)
31 (44.3)
5 (7.1)5 (7.1)29.7 (27.4–32.0)
7.5 (4.1–10.5)
7.1 (3.1–10.4)
9.4 (3.8–13.8)
9.8 (8.4–13.0)
49.7 (42.1–58.0)
41.7 (8.5–58.5)
21.3 (14.0–29.7)
20.8 (9.3–27.0)
1 (10.0)
1 (10.0)
6 (60.0)
4 (40.0)
3 (30.0)
5 (50.0)
1 (10.0)
2 (20.0)
5 (50.0)
3 (30.0)
4 (40.0)
5 (50.0)

0.236
0.075
0.075
0.001
0.001
0.075
0.013
0.658
0.286

9
5
5

34
31
5

0
6
4

(47.4)(26.3)(26.3)(48.6)(44.3)(7.1)(0.0)(60.0)(40.0)

L: < 0.001
R: < 0.001

L: < 0.001
R: < 0.001< 0.001

Data of parameters are expressed as means (range) and non-parametrical data are expressed as the number of patients (%).
AAJ, atlantoaxial joint; AOJ, atlanto-occipital joint; CT, computed tomography; FA, facet angle; L, left; LMH, lateral mass height; NS,
not significant; OP, postmenopausal osteoporosis; R, right; VS, vertical subluxation.
Mann-Whitney’s U test was used to compare between non-VS and VS groups. Pearson’s chi-square test or Fisher’s exact test, when appropriate, was employed for comparisons.
P values were derived by the comparison between non-VS and VS groups.

Relationship between the progression of VS andother parameters

Table 3. Relationships between the development of VS
and other parameters

There were significant positive correlations between theR-J value and left and right LMH at C1 and C2. Additionally, left and right FA(C1) values were positively correlated with left and right LMH(C1) values and the R-Jvalue (Table 3).
V(C1-2) was significantly correlated with the R-Jvalue and V(C1) had a tendency to correlate positively
with the R-J value; however, there was no relationshipbetween V(C2) and the R-J value (Table 3).
There was no significant correlation between vBMDs at the UCS and the R-J value. vBMD(C1) was negatively correlated with left and right FA(C1) [r = −0.468 (P= 0.023) and r = −0.600 (P = 0.038), respectively].
In the present study, there were significant differences in age, duration of RA and BMD(lumbar). However,when we performed multiple regression logistic analysis
using the above factors as explanatory variables for VS,
we found that age [odds ratio: 1.089 for 1 SD, 95% confidence interval (CI): 1.004–1.183, P = 0.041] was the only
factor that contributed to the progression of VS [duration

Correlation
coefficient
R-J value versus LMH(C1)(R)
LMH(C1)(L)
LMH(C2)(R)
LMH(C2)(L)
FA(C1)(R)
FA(C1)(L)
V(C1)
V(C2)
V(C1-2)vBMD(C1)vBMD(C2)vBMD(C1-2)
FA(C1)(R) versus LMH(C1)(R)
FA(C1)(L) versus LMH(C1)(L)P value

0.525		< 0.001
0.287		0.013
0.401		0.003
0.414		< 0.001
0.473< 0.001
0.320		0.006
0.499		0.058–0.036		NS
0.418		0.047
0.018		NS0.045		NS0.084		NS0.276		 0.019
0.167		 0.015

FA, facet angle; L, left; LMH, lateral mass height; NS, not significant; R, right; R-J, Redlund-Johnell; V, volume; vBMD, volumetric bone mineral density; VS, vertical subluxation.
Spearman’s rank correlation coefficient was employed for the
analysis of relationships between the parameters.
Statistical significance was set at P < 0.05.

25

T. Dokai et al.

of RA, odds ratio: 1.000 for 1 SD, 95% CI: 0.992–1.007,
P = 0.911; BMD(lumbar), odds ratio: 0.665 for 1 SD,
95% CI: 0.006–75.23, P = 0.866].

at the AOJ may progress into VS. In general, it has beenthought that the orientation of the AAJ changes fromhorizontal to nearly vertical with progression of VS.8
However, the present study showed that the orientationof the AAJ did not significantly change even in VS patients and that FA(C1) became sharper with progressionof VS. We considered the following: RA patients withlong symptom duration had more destructive changes at
the AOJ than those with short symptom duration. If disease activity in RA patients were generally maintainedin moderate conditions for long periods, these patients
had lower LMH(C1), lower LMH(C2) and sharperFA(C1) than early-stage RA patients. On the other hand,RA patients with high disease activity, such as mutilating RA patients, tend to develop VS when the lateral
masses in the UCS collapse rapidly.
The risk factors for VS development was age, RA
symptom duration and BMD(lumbar). However, we
could not show statistical relationship between OP and
VS development. There were several limitations in thepresent study. First, the present study was an observational study. To investigate the etiology of VS and therelationship between the progression of VS and OP moreclearly, a prospective study should be performed. Second, 3D-TBSAS could not calculate vBMD at the UCS
in RA patients with severe rheumatoid changes. Since it
was able to measure vBMDs at the UCS in early-stage
RA, we should recruit more candidates with early-stage
RA and follow them prospectively.
In conclusions, VS progressed based on the collapseof the lateral masses at the UCS. The C1 facet angle became more acute with progression of VS. The VS group
had rheumatoid changes at the AAJ, AOJ or both, andhad more bone defects in the odontoid process than the
non-VS group. Three-dimensional analysis revealed adecrease in the volumes at the UCS with the development of VS.

DISCUSSION
We hypothesized that OP could promote the development of VS, because Neva et al.15 proposed BMD(hip) to
be a risk factor for VS. However, we could not find statistically significant relationships between BMD(spine,
hip or both) and the development of VS. To evaluate therelationship between OP and VS progression, it is essential to measure the BMD at the UCS.
To the best of our knowledge, there have been only
a few reports on the BMD at the UCS.25, 26 In thosereports, BMD levels at only subaxial regions were analyzed using quantitative CT. In the occipitocervical junction, there are many bony and artificial structures (false
teeth and implants), which produce halation and make it
difficult to perform BMD measurements with high precision and reproducibility. We resolved these issues byusing 3D-TBSAS.
Three-dimensional analysis revealed that RA patients had almost the same vBMD as OP patients at
the UCS, even though RA patients were significantly
younger and had significantly higher BMD(lumbar).
Moreover, the volumes at the UCS became smaller with
progression of VS. However, vBMDs at the UCS were
not significantly correlated with the development of VS.
These results were not consistent with our hypothesis,
perhaps for the following reasons. First, there is a possibility that vBMD at the UCS might become condensed
with progression of VS. Although we could not discerna relationship between the volumes and vBMDs at the
UCS (data not shown), we found that FA(C1) became
sharper with progression of VS. Additionally, FA(C1)
was negatively correlated with vBMD(C1). These findings could support this possibility. Second, there isanother possibility that a structural specificity at UCS
might affect vBMDs at the UCS. The ratio of cortical tocancellous bone is higher in the UCS than the lumbar
spine; therefore, the effects of RA itself or generalized
OP might be smaller. Moreover, instabilities at the UCS
cause sclerotic changes. These factors might affect themeasurements of vBMDs.
Our results indicated that VS could be induced by
the collapse of the lateral masses in the UCS. Althoughmany previous reports3, 6, 9, 27–30 referred to active synovial proliferation at unstable AAJs, these reports did notshow how the collapse of the lateral masses progressed.
Some reports21, 28 focused on the AOJ in RA patientsfound that rheumatoid changes (ankylosing and fusion)

Acknowledgments: The authors would like to thank Dr. J.
Hashimoto and Prof. H. Yoshikawa of Osaka University for theiradvice and help in performing this study. The authors would also
like to thank Mr. J. Kishimoto and other radiological technologistsof Clinical Radiology in Tottori University Hospital for their help
in performing this study.
Portions of this work were presented at the 2nd Annual Meeting of Cervical Spine Research Society, Asia Pacific Section in
Busan, Republic of Korea, on 28–30 April, 2011, and in poster
form at the Eurospine 2010 Annual Meeting in Vienna, Austria on
15–17 September, 2010.
The authors declare no conflict of interest.

26

Vertical subluxation in RA/osteoporosis
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