EXTENDED REPORT |
1 Department of Internal Medicine, Division of
Rheumatology, University Hospital Maastricht, Maastricht, Netherlands
2
Biomedical Research Institute, University Hasselt, Campus Diepenbeek, Belgium
3 Department of Rheumatology, University Hospital Gent, Gent, Belgium
4 Department of Rheumatology, H?ital Cochin, Paris, France
Correspondence to:
Debby Vosse
Department of Internal Medicine, Division of Rheumatology, University
Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, Netherlands; dvo{at}sint.azm.nl
Accepted 2 October 2005
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ABSTRACT |
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Methods: Spinal hyperkyphosis was assessed by occiput to wall distance (OWD) in 135 patients participating in the OASIS cohort and defined as OWD >0. Disease activity was assessed by the Bath ankylosing spondylitis disease activity index (BASDAI). Wedging of the vertebrae was calculated as the Ha/Hp ratio. Structural damage of the spine was assessed by the modified Stoke ankylosing spondylitis spine score (mSASSS). Hip involvement was assessed by the Bath ankylosing spondylitis radiology index (BASRI) and defined as a score >2. Data were analysed by multiple regression analysis on van der Waerden-normal OWD values, with mean Ha/Hp ratio, mSASSS, hip involvement, and BASDAI as explanatory variables, and age, sex, and disease duration after diagnosis as covariates.
Results: 61 patients (45.2%) had an OWD >0 cm. Of these, 81% were male, v 57% in the group with normal OWD (p<0.001). Forty two patients had wedged thoracic vertebrae, and 27 of these (44%) had an increased OWD, compared with 15 of 74 with a normal OWD (20%) (p = 0.005). OWD was correlated with mean wedging of the thoracic spine (r = ?0.45, p = 0.01), mSASSS (r = 0.56, p = 0.01), and hip involvement (r = 0.2, p = 0.05). Multivariate analysis showed that mSASSS (standardised ß (stß) = 0.52; p<0.001), wedging of the thoracic spine (stß = ?0.28; p = 0.01), and BASDAI (stß = 0.15; p = 0.05) were independent determinants of OWD.
Conclusions: Radiological damage of the cervical and lumbar spine, thoracic wedging, and disease activity are determinants of hyperkyphosis in patients with ankylosing spondylitis. These findings could be important in determining treatment goals in this disease.
Abbreviations: BASDAI, Bath ankylosing spondylitis disease activity index; BASFI, Bath ankylosing spondylitis functional index; BASRI, Bath ankylosing spondylitis radiology index; mSASSS, modified Stoke ankylosing spondylitis spine score; Ha, anterior height of vertebra; Hp, posterior height of vertebra; ICC, intraclass correlation coefficient; OASIS, Outcome in Ankylosing Spondylitis International Study; OWD, occiput to wall distance
Keywords: ankylosing spondylitis; occiput to wall distance; osteoporosis; radiological damage
Hyperkyphosis of the upper part of the spine is a common clinical problem among patients with ankylosing spondylitis.1?3 In our prevalence cohort of patients with ankylosing spondylitis (Outcome in Ankylosing Spondylitis International Study (OASIS) cohort) with a mean disease duration of 9.4 years, 49% of the patients have some degree of hyperkyphosis, if it is expressed as an occiput to wall distance (OWD) of more than 0 cm.4 The prominent position of the head and neck may give rise to functional and psychological impairment in these patients.5 They may be unable to see straight ahead and may have difficulties in activities of daily living; furthermore, severe hyperkyphosis may result in compression of the abdominal viscera.6
The degree of hyperkyphosis in patients with ankylosing spondylitis is related to radiological damage.7 In general, hyperkyphosis is also associated with vertebral osteoporosis, and it is increasingly recognised that osteoporosis is a problem in patients with ankylosing spondylitis.8,9,10,11,12 Vertebral deformities are regarded as one of the classical hallmarks of vertebral osteoporosis. In a population based study, the relative risk of vertebral morphometric deformities in patients with ankylosing spondylitis was 7.6 compared with the control population.13 Other investigators found a prevalence of vertebral deformities in 10?17% of the patients with ankylosing spondylitis seen in the clinic.14?17 In a pilot study we have shown that thoracic but not lumbar vertebral deformities are related to an increase of OWD in patients with ankylosing spondylitis.17 However, it is not known how all potential contributory factors (such as disease activity, structural damage visible on radiographs, hip involvement, and vertebral wedging) interrelate with respect to explaining increased OWD in patients with ankylosing spondylitis. We therefore investigated the independent contribution of various factors that may explain hyperkyphosis in a cross sectional study of patients with ankylosing spondylitis.
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METHODS |
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). In a previous experiment we determined that
intraobserver (intraclass correlation coefficient (ICC) = 0.98) and
interobserver (ICC = 0.99) reliability on mSASSS status scores of
this observer were excellent.22 Radiographic hip
involvement determined according to the Bath ankylosing spondylitis
radiology index (BASRI)-hip23 was as follows: 0, no involvement; 1,
(possible) focal joint space narrowing; 2, definite narrowing leaving
a circumferential joint space >2 mm; 3, narrowing with
circumferential joint space 
2 mm or bone on bone apposition of <1 cm; 4, bone deformity
or bone on bone apposition 
1 cm. Grades 1 and 2 increase by one grade if two of the
following bony changes were present: erosions, osteophytes,
protrusion. Scores are applied to both hips. For the purpose of this
article, hip involvement was defined as a BASRI-hip >2. Anterior (Ha)
and posterior (Hp) height of the vertebrae was measured on lateral
radiographs of the thoracic (T4?12) and lumbar spine (L1?5) in
millimetres by one observer (DV) (fig 2) Imaging of the first three thoracic vertebrae is
mostly inadequate so we omitted them in the analyses. Wedging of a
vertebra was calculated as the Ha/Hp ratio. This was defined as mild
if the ratio was >0.75 but 0.80, moderate if the ratio was >0.60 but 0.75, and severe if the ratio was 0.60.24 We calculated the mean wedge (mean Ha/Hp ratio)
of all thoracic and lumbar vertebrae per patient, as well as
for the lumbar and thoracic spine separately.
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To quantify hyperkyphosis the distance between occiput and wall (OWD) was assessed with the patient standing with the heels and back against the wall, with hips and knees as straight as possible. The chin was held at the usual carrying level and the patient exerted maximum effort to touch the head against the wall. The distance between the wall and the occiput was measured in centimetres to one decimal place. The better of two tries was recorded.25,26 Patients were grouped as having a normal OWD ( = 0 cm) or an increased OWD (>0 cm).
Statistical analysis
We used 
2 tests to test
differences in proportions. Spearman?s correlation coefficients were
calculated to investigate univariate associations between OWD and
mean wedging, mSASSS, and BASDAI. Linear regression analysis was
undertaken to investigate the independent contribution of BASDAI,
mean wedging, hip involvement, and mSASSS to explain variation in the
dependent variable OWD. Covariates in the analysis were age, disease
duration, and sex. Variables that were not normally distributed were
first normalised by the Van der Waerden technique.
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RESULTS |
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presents some baseline characteristics of the
patients. Of the 135 patients with complete data, 50 of the 90
male patients (56%) and 11 of the 45 female patients (24%) had an OWD
>0 cm (p = 0.001). Compared with patients with a normal OWD, patients
with an increased OWD were older, had a longer mean disease duration,
and were more often of male sex. Disease activity (BASDAI) was
similar in the two groups with a higher level of physical limitation
(BASFI) and radiographic damage of the spine (mSASSS). In our cohort,
12 patients (9%) had severe radiological hip involvement; eight of
these had an OWD of >0 cm.
0.80. When comparing fracture rates in patients with normal
OWD (n = 74) and increased OWD (n = 61), 15 patients in the normal
OWD group (20%) had vertebral fractures compared with 27 (44%) with
OWD >0 cm. Of these 89 fractures, 59 (66%) were mild, 29 (33%)
moderate, and one (1%) severe. All fractures were found in the
thoracic spine except for four (three moderate, one mild) in the
first lumbar vertebra and one mild fracture in the fourth lumbar
vertebra (table 2). When comparing the number of fractures with OWD
we found significant correlations, both when analysing all fractures
and when analysing fracture groups (no, 1, or >1 fracture and yes/no
fractures) versus OWD (p = 0.002, p = 0.01, p = 0.003, respectively). ). To explore the independent contribution of
different variables in explaining the variation in OWD (as a
continuous measure), linear regression analysis was undertaken.
Because age, sex, and disease duration may be associated with OWD
spuriously, these variables were included as covariates. Table 4 shows the main results of this analysis. Variation
in OWD was primarily explained by mSASSS. There was, however, an
independent contribution of both mean thoracic wedging and cross
sectional assessed BASDAI. In this analysis severe hip involvement
did not independently contribute to explaining variation in OWD,
although a positive trend could be recognised.
OWD was merely associated with wedging of
the thoracic part of the vertebral column. However, the mSASSS does
not take the thoracic spine into account, only the cervical and
lumbar spine. We analysed the contribution of the mSASSS of the
cervical spine and the lumbar spine separately in explaining OWD by
regression models, including the same variables as in the main model.
The contribution of both site specific mSASSSs in explaining
variation in OWD was approximately similar (stß = 0.62 for the
cervical mSASSS and 0.57 for the lumbar mSASSS).This is not
unexpected as the cervical and lumbar mSASSS values were highly
correlated (r = 0.64).
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DISCUSSION |
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In a multivariate analysis, in addition to mSASSS and mean
thoracic
wedging, disease activity (BASDAI) independently, although marginally,
contributed to spinal hyperkyphosis. Considering the hip involvement
in ankylosing spondylitis as a possible factor leading to limitation
of movement, one can assume the influence of fixed flexion of the
hips on the OWD. Therefore, we investigated the correlation between
hip involvement and hyperkyphosis. We analysed this by comparing OWD
in patients with severe hip involvement (BASRI >2) versus no or mild
hip involvement (BASRI 2). This analysis showed a trend, but did not reach
statistical significance in both the univariate and multivariate
analyses, possibly due to the low prevalence of hip involvement. It
should be stressed that the variables that we have investigated here
only in part explain hyperkyphosis. Other potentially contributory
factors include inflammation of ligaments, muscles and entheses. And
in a previous article we described the role of disc deformities in
hyperkyphosis.17 In this study we did not analyse these soft
tissues, as we focused on vertebral wedging and radiographic damage.
A shortcoming of our study is the cross sectional design. It would be preferable to have a prospective follow up of patients with ankylosing spondylitis in an early phase of their disease and to observe the development of the spine deformity. On the other hand, others could not find a relation between radiological damage and disease duration, age at diagnosis, or acute phase response in such prospective studies.7 In previous analyses Boonen et al28 concluded that there was no change in self reported health status over a period of four years. In a long term follow up study of the OASIS cohort, in which patients were followed every two months during the first two years and every year thereafter, mean BASDAI did not change (stß = 0.007 (95% CI, ?0.013 to 0.027)), which is why we believe a cross sectional approach is justified.
Possible confounders of the relation between wedging and OWD are age and sex, as OWD may increase with age, and as ankylosing spondylitis is a predominantly male disease with a more serious course in male than in female patients.1 However, we did not find a relation between age, sex, and OWD, either univariate or multivariate.
In ankylosing spondylitis the burden of illness is a result of longstanding inflammation and its consequences. Further, cumulative inflammation results in radiological damage reflected in mSASSS scores. In our study we found an independent significant relation between these factors and hyperkyphosis.
In analogy with periarticular bone loss in rheumatoid arthritis, we hypothesise that vertebral wedging is the result of periarticular bone loss in the spine.29 Inflammatory processes are found to be associated with increased bone loss and bone turnover.9,30 This results in reduced bone mineral density.
Osteoporosis is shown to be associated with inflammatory rheumatic diseases, such as rheumatoid arthritis31,32 and ankylosing spondylitis.11 Vertebral deformities are considered to be the main feature of osteoporosis. Our study confirmed an independent significant relation between wedging of (thoracic) vertebrae and hyperkyphosis.
Conclusions
We found three
independent significant contributory factors to hyperkyphosis:
structural damage of the spine, wedging of thoracic vertebrae, and
cross sectional disease activity. In addition we found a
significantly higher BASFI in patients with an OWD of >0 cm.
Therefore, in order to prevent or limit functional decline, future
studies on new treatments in ankylosing spondylitis should include
prevention, if possible, of the development of structural damage as
well as prevention of the development of vertebral osteoporosis and
its effect on hyperkyphosis.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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REFERENCES |
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