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junctions and the eye. Commonly affected areas of bony involvement are the spine
and sacroiliac joints. Progression of AS is best characterized by abnormal bone
(syndesmophytes) formation along the margins of inter-vertebral disk spaces (IDS).
Syndesmophytes cause irreversible and progressive structural damage, and over
decades, can lead to spinal fusion [
1
,
2
].
Monitoring syndesmophyte evolution is essential for many clinical studies of
AS. Recently available treatments, tumor necrosis factor (TNF) inhibitors, have
attracted much attention and fostered new hope by substantially reducing signs of
in
5
]. However it is still an open
question whether they slow syndesmophyte growth or not. Most studies seem to
show a slight deceleration but without statistical signi
fl
ammation and improving quality of life [
3
-
10
]. The causes of
bone formation in AS are still poorly understood. In particular, the involvement of
in
cance [
6
-
ammation, which has face value plausibility, constitutes a perplexing and still
unanswered question. Evidence of the correlation between in
fl
ammation and syn-
desmophyte growth has been marginal at best despite extensive studies [
11
fl
18
]. To
elucidate the mechanisms of bone formation in AS at a molecular level, correlation
between syndesmophyte growth and various biomarkers of bone turnover has been
investigated [
19
,
20
]. Predictors of syndesmophyte formation have been sought
with only limited success [
21
,
22
]. New promising perspectives on syndesmophyte
growth have been opened by genetic studies [
23
,
24
]. In particular, Dickkopf-1
(DKK-1), a regulatory molecule of the Wnt pathway which controls embryonic
development, has attracted much attention [
25
-
27
].
Unfortunately, all those studies have been hampered by the fact that the current
standard for assessing syndesmophyte growth, the visual examination of radio-
graphs, has very poor sensitivity to change. This low sensitivity to change is not
only a re
-
ection of the slow growth rate of syndesmophytes. It is also caused by the
limitations of radiography, which projects 3D objects onto 2D images with atten-
dant losses of spatial information and ambiguities in density caused by superim-
position. Moreover, syndesmophytes on radiographs are usually rated using coarse
semi-quantitative reading systems [
28
,
29
]. The modi
fl
ed Stoke Ankylosing
Spondylitis Spinal Score (mSASSS) has emerged as the most widely used reading
system [
30
]. The crudeness of the scoring systems further limits sensitivity to
change [
31
]. Figure
1
shows an example of syndesmophyte growth visible on
reformatted CT but not radiography.
To overcome the limitations of radiographic methods, we designed a computer
algorithm that quantitatively measures syndesmophyte volumes in the 3D space of
CT scans [
32
,
33
]. The algorithm is described in the following section. In Sect.
3
,
we investigate its accuracy and precision. Results of a 2-year longitudinal study are
presented in Sect.
4
. We review the future challenges of the new method in Sect.
5
before concluding in Sect.
6
.
