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 (ß 0.47, 95% CI 0.4-0.6, p < 0.01 and ß 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.

Ankylosing spondylitis confers substantially increased risk of clinical spine fractures: a nationwide case-control study.

UNLABELLED: Ankylosing spondylitis (AS) leads to osteopenia/osteoporosis and spine rigidity. We conducted a case-control study and found that AS-affected patients have a 5-fold and 50% increased risk of clinical spine and all clinical fractures, respectively. Excess risk of both is highest in the first years and warrants an early bone health assessment after diagnosis. INTRODUCTION: Ankylosing spondylitis (AS) is related to spine rigidity and reduced bone mass, but data on its impact on fracture risk are scarce. We aimed to study the association between AS and clinical fractures using a case-control design. METHODS: From the Danish Health Registries, we identified all subjects who sustained a fracture in the year 2000 (cases) and matched up to three controls by year of birth, gender and region. Clinically diagnosed AS was identified using International Classification of Diseases, 8th revision (ICD-8; 71249), and International Classification of Diseases, 10th revision (ICD-10; M45) codes. We also studied the impact of AS duration. Conditional logistic regression was used to estimate crude and adjusted odds ratios (ORs) for non-traumatic fractures (any site, clinical spine and non-vertebral) according to AS status and time since AS diagnosis. Multivariate models were adjusted for fracture history, socio-economic status, previous medical consultations, alcoholism and use of oral glucocorticoids. RESULTS: We identified 139/124,655 (0.11%) AS fracture cases, compared to 271/373,962 (0.07%) AS controls. Unadjusted (age- and gender-matched) odds ratio (OR) were 1.54 [95% confidence interval (95%CI) 1.26-1.89] for any fracture, 5.42 [2.50-11.70] for spine and 1.39 [1.12-1.73] for non-vertebral fracture. The risk peaked in the first 2.5 years following AS diagnosis: OR 2.69 [1.84-3.92] for any fracture. CONCLUSIONS: Patients with AS have a 5-fold higher risk of clinical spine fracture and a 35% increased risk of non-vertebral fracture. This excess risk peaks early, in the first 2.5 years of AS disease. Patients should be assessed for fracture risk early after AS diagnosis.

Osteoporosis in rheumatoid arthritis and ankylosing spondylitis.

Bone is a target in many inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The generalized effect of inflammation on bone may result in a decreased quality of bone and is associated with an increased risk of fractures and deformities, both in RA and AS. RA is characterized by periarticular osteopenia, systemic osteoporosis and bone erosions. Periarticular osteopenia and bone erosions are mainly correlated with disease activity. Unlike postmenopausal osteoporosis, osteoporosis in RA is more characterised by marked loss of bone in the hip and the radius, while the axial bone is relatively preserved. In general, several cross-sectional studies documented a lower bone mineral density in patients with RA, with a two-fold increase in osteoporosis compared to age- and sex-matched controls and relates to an increased fracture risk. Several factors contribute to the increased risk: older age, little exercise, long-term use of corticosteroids, and high disability index. AS is characterized by an increase in bone fragility due to reduced bone mineral density. The reported prevalence of osteoporosis in AS patients varies largely. The large variation reflects the difficulties in assessing BMD in AS due to new bone formation. Bone fragility is also due to changes in structural properties resulting from inflammation-induced bone failure in the spine in combination with reduced capacity of shock absorption leading to vertebral fractures. Different types of spinal fractures in patients with AS are described, including wedging. Wedging vertebral fractures contribute to hyperkyphosis and impaired physical function. In contrast to RA , bone loss in AS is accompanied by new bone formation. The pathophysiology of osteoporosis in RA and AS probably is fundamentally similar, but with different clinical phenotypes. The implications for therapeutically intervening in its occurrence and progression might be fundamentally different.

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, 231,778 patients with fracture and 231,778 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.

Association of markers of bone- and cartilage-degradation with radiological changes at baseline and after 2 years follow-up in patients with ankylosing spondylitis.

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 (rho = 0.24; P

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

OBJECTIVE: To investigate the effect of etanercept therapy on radiographic progression in patients with ankylosing spondylitis (AS). METHODS: Patients 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). RESULTS: A 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). CONCLUSION: Unlike 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.

Comparing morphometric X-ray absorptiometry and radiography in defining vertebral wedge fractures in patients with ankylosing spondylitis.

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 (kappa 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.

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%) (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 beta (stbeta) = 0.52; p<0.001), wedging of the thoracic spine (stbeta = -0.28; p = 0.01), and BASDAI (stbeta = 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.

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.

High prevalence of thoracic vertebral deformities and discal wedging in ankylosing spondylitis patients with hyperkyphosis.

OBJECTIVE: To study the prevalence of deformities of vertebrae and intervertebral discs in patients with ankylosing spondylitis (AS) in relation to fixed hyperkyphosis of the spine. METHODS: Altogether 50 patients (15 women, 35 men) with AS were studied. Hyperkyphosis was measured by the occiput to wall distance (OWD). Anterior (Ha), mid- (Hm), and posterior height (Hp) of the vertebrae and intervertebral discs were measured on lateral radiographs of the thoracic (Th5-Th12) and lumbar spine (L1-L5). Vertebral shapes were analyzed according to McCloskey, et al. Wedging of discs was calculated as Ha/Hp. Hyperkyphosis was defined as OWD > 1 cm. RESULTS: In the thoracic spine, the prevalence of vertebral deformities was higher in patients with hyperkyphosis (n = 38) compared to patients without hyperkyphosis (n = 12) (45% vs 8%; p = 0.01). The prevalence of thoracic vertebral deformities in patients with hyperkyphosis differed little between men and women (39% vs 58%; p > 0.10) and among patients above and below the age of 45 years (50% vs 33%; p > 0.10). Patients with one or more deformed thoracic vertebrae had a higher mean OWD than patients without deformed vertebrae (12 +/- 7 vs 7 +/- 6 cm; p < 0.01). The total sum of deformities of the thoracic vertebrae and discs explained 43% of the variance of the age adjusted OWD (p < 0.001). Deformities of lumbar vertebrae and discs did not contribute to hyperkyphosis. CONCLUSION: In patients with AS and hyperkyphosis, deformities of the thoracic vertebrae occur frequently and, together with wedging of the thoracic discs, contribute significantly to fixed hyperkyphosis of the spine.

[Glucose-6-phosphate dehydrogenase deficiency in an 81-year-old]. / Glucose-6-fosfaat-dehydrogenase-deficiëntie bij een 81-jarige.

In a 81-year-old woman, who for many years had been treated with iron and vitamin B12 injections because of a 'tendency to anaemia', congenital haemolytic anaemia on the basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency was diagnosed. The iron and vitamin medication was discontinued and after a blood transfusion because of signs of heart failure, the patient could leave the hospital in good condition. After instruction with regard to provocative factors, like eating of broad beans, no more haemolytic events occurred. Of her children and grandchildren, 2 sons and 1 granddaughter were G6PD deficient.