Debby Vosse

Objective. There is a lack of knowledge on factors that reliably can predict radiological changes in patients with AS. We have investigated whether urinary C-terminal cross-linking telopeptide of type I (CTX-I) and type II (CTX-II) collagen, as specific biochemical markers of bone and cartilage degradation, respectively, are associated with radiological damage and progression, and with BMD in patients with AS. Methods. Eighty-three patients with AS [mean (s.d.) age: 50.4 (12) yrs, 65% male, mean (s.d.) disease duration after diagnosis: 16.7 (10) yrs] who participate in an ongoing cohort study of patients with AS [Outcome in AS International Study (OASIS) cohort] were assessed for urinary CTX-I and -II. Results of both biochemical markers were compared with baseline scores for radiological damage (modified modified Stoke Ankylosing Spondylitis Spine Score, primarily reflecting syndesmophyte-formation and -growth), and with scores for radiological progression after 2 yrs follow-up. Markers were also associated with disease activity parameters and BMD. Results. Mean duration of complaints was 28.6 yrs. At that time, 54% of patients had signs of radiological damage, and 35% of them showed radiological progression after 2 yrs. Baseline radiological damage (ρ = 0.24; P ≤ 0.05) correlated with CTX-II, but not with CTX-I. CTX-II correlated with serological markers of inflammation (ESR ρ = 0.29 and CRP ρ = 0.30; P ≤ 0.01), but not with baseline BASDAI or BMD. There was a negative correlation between CTX-I and BMD of the trochanter (ρ = −0.31; P ≤ 0.01) In multivariate analyses, CTX-II significantly and independently contributed to explaining variation in radiological damage (standardized β = 0.27; P = 0.03) and progression (standardized β = 0.27; P = 0.05). Conclusion. In AS, cartilage degradation plays a role in explaining radiological-damage and -progression in the spine.

Objective. To compare the level of agreement of quantitative morphometry of the vertebrae on lateral views of the spine using conventional X-ray and using a dual X-ray absorptiometry device (DXA) in determining the degree of wedging of vertebrae in patients with ankylosing spondylitis (AS). Methods. Thirty patients with AS underwent DXA to acquire single-energy morphometric X-ray absorptiometry (MXA) scans and conventional lateral radiography (MRX) of the thoracic and lumbar spine. Vertebral anterior and posterior heights were measured and the anterior/posterior (AP)-ratio was calculated. We analysed the level of agreement for vertebral wedging between MRX and MXA on the patient level and on the vertebral level, using average AP-ratios per patient, and per vertebra, as well as dichotomized AP-ratios (above or below cut-off levels that are commonly used to identify fractures). Results. Per-patient analysis showed good agreement between both methods in the whole spine [intraclass correlation coefficient (ICC) = 0.64], as well as in the thoracic (ICC = 0.66) and lumbar spine (ICC = 0.62) separately. Analysis on individual vertebrae showed differences in agreement dependent on which part of the spine was measured. The ICC on all vertebrae was 0.71, 0.76 in the lumbar and 0.43 in the thoracic vertebrae. If AP-ratios were translated into fractures (yes vs no) using different cut off levels for a fracture (AP-ratios 0.75, 0.80 or 0.85) between-method agreement became fair to good (κ 0.26–0.35 in the thoracic and 0.47–0.80 in the lumbar vertebrae). Differences in classifications were in both directions and in all vertebral fractures according to the Genant definition. In this study with a prevalence of 5% of vertebral fractures, the positive predicted value (PPV) was 39% and the negative predicted value (NPV) was 97%. Conclusion. Although the agreement between MRX and MXA in measuring global vertebral wedging, expressed as (mean) AP-ratio, was good, the reliability of both measures to assess wedging at the vertebral level was highly variable, ranging from fair to very good agreement, dependent on the level. If fracture studies are performed with either of both the methods, the results of wedging at the individual vertebral level cannot be generalized to the other method, except for wedging <0.75 at the lumbar spine. However, as the NPV was high, DXA could be of clinical value to select patients for further evaluation by X-ray to assess vertebral fractures as a sign of bone failure.

Objective: To determine clinical and radiographic determinants of hyperkyphosis in patients with ankylosing spondylitis. 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 (pr = −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 β (stβ) = 0.52; pConclusions: 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.

To evaluate the prevalence and characteristics of clinically confirmed vertebral fractures (CVF) in patients with ankylosing spondylitis (AS). Coordinated by the Ankylosing Spondylitis International Federation in Germany and in Denmark, a self-administered questionnaire was sent to all their members about age, diagnosis, disease duration, HLA-B27 status, and history of CVF. Patients who were aware of having had a CVF were asked to return the questionnaire with additional specification of the location of CVF, associated trauma, neurological complications, therapy for these complications, and recovery. We also reviewed available radiographs. Out of 15,097 questionnaires, 59 patients (0.4%) reporting 66 CVF returned the complete questionnaire (46 men, 13 women). Mean age at fracture was 50 +/- 9 years, after a mean duration of symptoms of 26 +/- 11 years. CVF with wedging or crush or transverse fracture were reported in the cervical (n = 21, 36%), thoracic (n = 21, 36%), and lumbar spine (n = 16, 27%), with one unspecified. In 37 fractures (56%), patients reported no/low or medium trauma in relation to the fracture. In 31 fractures (47%), patients reported neurological complications, occurring mostly without trauma (n = 11, 35%) or after minimal trauma (n = 7, 23%). Twenty (65%) of these patients did not have full neurological recovery. We found that 0.4% of patients with AS reported CVF at a mean age of 50 years, occurring after 2 decades of disease, mainly without trauma or after minimal trauma, with frequent neurological complications mostly followed by incomplete neurological recovery.