Debby Vosse

Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept

OBJECTIVEnTo investigate the effect of etanercept therapy on radiographic progression in patients with ankylosing spondylitis (AS).nnnMETHODSnPatients with AS who had previously participated in a 24-week randomized, double-blind, placebo-controlled trial of etanercept therapy were enrolled in a 72-week open-label extension. Radiographs of the cervical and lumbar spine from patients who received etanercept (25 mg twice weekly) for up to 96 weeks were compared with radiographs from patients in a large prevalence cohort (Outcome Assessments in Ankylosing Spondylitis International Study [OASIS]) who had not been treated with anti-tumor necrosis factor alpha (anti-TNFalpha) agents. Radiographs obtained at 2 time points up to 96 weeks apart from patients in both study populations were digitized and read by 2 independent readers who were blinded with regard to patient group and sequence. The primary end point was the 96-week change in the modified Stoke AS Spine Score (mSASSS).nnnRESULTSnA total of 257 patients treated with etanercept were compared with 175 unselected patients from the OASIS study. There was no significant difference in the change in the mSASSS from baseline among patients who received etanercept (mean +/- SD 0.91 +/- 2.45) versus those from the OASIS group (0.95 +/- 3.18).nnnCONCLUSIONnUnlike other inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis, structural progression in AS seems to be independent of TNF, despite the fact that TNF is responsible for the signs and symptoms due to inflammation in this disease.

Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case-control study

Background and aims: Ankylosing spondylitis (AS) is associated with bone loss in the vertebrae and an increased prevalence of vertebral fractures, but literature about the magnitude of the risk of fracturing is limited. One retrospective cohort study provided evidence of an increased risk of clinical vertebral fractures but not of non-vertebral fractures. This study further explores the risk of clinical vertebral and non-vertebral fractures in a large population database. Methods: In a primary care-based nested case-control study, 231u2009778 patients with fracture and 231u2009778 age- and sex-matched controls were recruited. A history of AS was assessed from the medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for medication, other illnesses, smoking and body mass index when known. Results: AS was diagnosed in 758 subjects. The prevalence of AS was 0.18% in patients with fracture and 0.15% in controls. Patients with AS had an increased risk of clinical vertebral fracture (OR 3.26; 95% CI 1.51 to 7.02). The risk of fractures of the forearm and hip was not significantly increased (OR 1.21; 95% CI 0.87 to 1.69 and OR 0.77; 95% CI 0.43 to 1.37, respectively). The risk of any clinical fracture was increased in patients with AS with a history of inflammatory bowel disease (OR 2.79; 95% CI 1.10 to 7.08), whereas it was decreased in patients with AS taking non-steroidal anti-inflammatory drugs (OR 0.65; 95% CI 0.50 to 0.84). The risk was not associated with recent back pain, psoriasis, joint replacement therapy and use of sulfasalazine. Conclusions: Patients with AS have an increased risk of clinical vertebral fracture but not of non-vertebral fractures, while the risk of any clinical fracture is increased in patients with concomitant inflammatory bowel disease. The mechanism by which non-steroidal anti-inflammatory drugs reduce the risk of any clinical fracture warrants further research.

Prevalence and annual incidence of vertebral fractures in patients with ankylosing spondylitis

Objectives To evaluate the prevalence and annual incidence of clinically-manifest vertebral fractures among patients with ankylosing spondylitis (AS). Method: Coordinated by the Ankylosing Spondylitis International Federation, a self-administered general questionnaire which included some questions on gender, age, age at onset of disease, and a history of vertebral fracture was inserted in one issue of the membership journals of the AS patient organizations in Germany and Austria. Results: Among the 1,071 patients responding who all had indicated that the diagnosis of AS had been established or confirmed by a physician, 61 (5.7%) indicated a history of vertebral fracture, 15 of them (1.4%) without an accident. The prevalence of vertebral fractures was 6.2% among male AS patients and 4.6% among females (NS), and 4.8% among HLA-B27+ patients and 9.9% among HLA-B27− patients (p<0.05). Spinal fractures occurred more often among AS patients with peripheral arthritis (7.1%) than among patients with axial involvement only (3.1%, p<0.01). The average delay between disease onset and diagnosis of AS was 10.5xa0years for patients with a vertebral fracture, compared to 8.7xa0years for patients without any such event (p<0.05). Among patients with a disease duration ≥42xa0years, the prevalence of vertebral fractures was 14%. The annual incidence of vertebral fractures which occurred without an accident had a maximum of 0.1% per annum at a disease duration of 20–35xa0years, whereas the incidence of vertebral fractures caused by an accident increased continuously with increasing disease duration, amounting to 1.3% per annum after a disease duration of 45xa0years. Conclusion: A considerable proportion of AS patients will experience a vertebral fracture during the course of the disease, in particular if peripheral joints are also involved.

Determinants of hyperkyphosis in patients with ankylosing spondylitis

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 (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%) (pu200a=u200a0.005). OWD was correlated with mean wedging of the thoracic spine (ru200a=u200a−0.45, pu200a=u200a0.01), mSASSS (ru200a=u200a0.56, pu200a=u200a0.01), and hip involvement (ru200a=u200a0.2, pu200a=u200a0.05). Multivariate analysis showed that mSASSS (standardised β (stβ)u200a=u200a0.52; p<0.001), wedging of the thoracic spine (stβ u200a=u200a−0.28; pu200a=u200a0.01), and BASDAI (stβ u200a=u200a0.15; pu200a=u200a0.05) 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.

The prevalence of vertebral fractures in spondyloarthritis: relation to disease characteristics, bone mineral density, syndesmophytes and history of back pain and trauma

IntroductionAn increased risk of vertebral fracture (VF) is one of the extra-articular manifestations of spondyloarthropathy (SpA). The prevalence of moderate to severe VFs visualized by radiography (Rx) in patients with SpA in daily practice is unknown until imaging of the full spine is available, as most VFs do not present with clinical signs and symptoms of an acute fracture.MethodsWe evaluated the prevalence of VFs (>25xa0% loss in height) on available Rx and dual-energy X-ray absorptiometry (DXA) images in 390 consecutive patients with SpA in daily practice. We assessed their association with disease characteristics, bone mineral density, the modified Stoke Ankylosing Spondylitis Spinal Score, and history of trauma.ResultsForty-six patients (11.8xa0%) had Rx VF (56.4xa0% men, 93.5xa0% in the thoracic spine), and 44.5xa0% had multiple VFs. Compared with patients without VF, patients with VF were older (52.2 vs. 47.3xa0years, pu2009<u20090.01; range 25–84 years), had lower femoral neck T-scores (−1.1 vs. −0.7; pu2009<u20090.05), and had a marginally higher modified Stoke Ankylosing Spondylitis Spinal Score (11.7 vs. 7.0; pu2009=u20090.06). Among patients with VFs, 15.2xa0% had a history of trauma with acute back pain (pu2009<u20090.001 vs. no VF). The reliability of DXA for diagnosing radiographic VFs was high (κ 0.90).ConclusionsModerate to severe VFs are found in more than 10xa0% of patients with SpA before the age of 40xa0years in 5xa0% of women and 9xa0% in men. Most VFs are located in the thoracic region, are related to low femoral neck bone mineral density and to stiffening of the spine, and are only rarely related to trauma history. DXA is a useful alternative for diagnosing VFs.

Recovery from Severe Glucocorticoid-Induced Osteoporosis in an Adolescent Boy

An 18-yr-old boy presented with extreme back pain as the result of multiple vertebral fractures. At age 16 he had developed a tumor of the mesencephalon. A ventriculoperitoneal shunt was established surgically. One year later, he developed progressive neurologic deficits in his upper and lower limbs with an increase in the size of the tumor. He was treated by irradiation and high doses of glucocorticoids. Although the neurologic deficits progressively improved, he developed severe back pain resulting in complete immobilization for 3 mo in spite of neurologic recovery. Multiple vertebral fractures were diagnosed by X-ray. Bone density was extremely low (Z-score of -5.5 in the spine and -3.1 in the femoral neck). The patient was treated with calcium and vitamin D, calcitonin, bisphosphonates, physiotherapy, and progressive mobilization. Glucocorticoids were decreased and could be stopped as the neurologic deficits fully recovered. After 1 yr of treatment with intermittent i.v. pamidronate, bone density had increased by 40% in the spine and by 25% in the femoral neck despite growth arrest. He progressively recovered from back pain and is now, at age 20, fully ambulant, studying mechanical engineering, without neurologic sequelaes and free of glucocorticoids. Magnetic resonance imaging revealed that the tumor had disappeared. This case proves that treatment of symptomatic glucocorticoid-induced osteoporosis during puberty can be rewarding, even when multiple and invalidating vertebral fractures already exist.

Structural damage and inflammation on radiographs or magnetic resonance imaging are associated with cortical interruptions on high-resolution peripheral quantitative computed tomography: a study in finger joints of patients with rheumatoid arthritis and healthy subjects.

Objectives: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). Method: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. Results: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean ± sd 0.33 ± 0.63 vs 0.38 ± 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH ≥ 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5–21.4, p < 0.01 and OR 4.8, 95% CI 1.9–11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (β 0.47, 95% CI 0.4–0.6, p < 0.01 and β 1.9, 95% CI 0.6–3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. Conclusion: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated.

Comparison of tests for lumbar flexion and hip function in patients with and without axial spondyloarthritis.

To compare the 15‐cm Schober test with the 10‐cm Schober test and the intermalleolar distance (IMD) with the internal hip rotation (IHR).

Development of a scoring method to visually score cortical interruptions on high-resolution peripheral quantitative computed tomography in rheumatoid arthritis and healthy controls

Objectives To develop a scoring method to visually score cortical interruptions in finger joints on High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), determine its intra- and inter-reader reliability and test its feasibility. Methods The scoring method was developed by integrating results from in-depth discussions with experts, consensus meetings, multiple reading experiments and the literature. Cortical interruptions were scored by two independent readers in an imaging dataset with finger joints from patients with rheumatoid arthritis (RA) and healthy controls and assessed for adjacent trabecular distortion. Reliability for the total number of cortical interruptions per joint and per quadrant was calculated using intraclass correlation coefficient (ICC). Feasibility was tested by recording the time to analyze one joint. Results In 98 joints we identified 252 cortical interruptions, 17% had trabecular distortion. Mean diameter of the interruptions was significantly larger in patients with RA compared with healthy controls (0.88 vs 0.47 mm, p = 0.03). Intra-reader reliability was ICC 0.88 (95% CI 0.83;0.92) per joint and ICC 0.69 (95% CI 0.65;0.73) per quadrant. Inter-reader reliability was ICC 0.48 (95% CI 0.20;0.67) per joint and ICC 0.56 (95% CI 0.49;0.62) per quadrant. The time to score one joint was mean 9.2 (SD 4.9) min. Conclusions This scoring method allows detection of small cortical interruptions on HR-pQCT imaging of finger joints, which is promising for use in clinical studies.