The aim of this cohort study was to evaluate the long-term effects of TNF inhibitors (TNFis) on BMD and the incidence of vertebral fractures (VFxs) in patients with ankylosing spondylitis (AS). Consecutive patients with active AS with TNFi treatment duration up to 4 years with available DXA scans and spine X-rays were included. BMD (classified according to the WHO criteria for osteoporosis) of the hip and lumbar spine, the VFx (classified as a Genant score !1/!20% height loss), and radiological progression (modified stoke ankylosing spondylitis spinal score [mSASSS]) scores were obtained at baseline and at 4 years of TNFi treatment. Overall, 135 AS patients were included. At baseline, 40.1% of patients had low BMD of the hip and 40.2% of the lumbar spine. This decreased to 38.1% (p ¼ 0.03) with low hip BMD and 25.3% (p < 0.001) of the lumbar spine BMD after 4 years of TNFi treatment. VFxs were present at baseline in 11.1% of the 131 patients, which increased to 19.6% after 4 years of TNFi treatment. A Genant score !2, was found at baseline in 3 out of 14 VFx (21.4%) patients, which increased to 7 out of 27 VFx (25.9%) patients after 4 years. All disease activity parameters-the ankylosing spondylitis disease activity scale, the C-reactive protein, the erythrocyte sedimentation rate, and the bath ankylosing spondylitis disease activity index-decreased significantly (p < 0.001). The mean radiological progression (n ¼ 80) increased significantly from a median mSASSS of 4.0 (1.5 to 16.0) at baseline to 6.5 (2.1 to 22.9) after 4 years of TNFi treatment (p < 0.001). Despite the improvement in BMD and the decrease in disease activity, we still found new VFxs, an increase in severity in the number and grade of VFxs, and radiographic progression during 4 years of treatment with TNFis in AS patients with long disease duration.
BackgroundAnkylosing Spondylitis (AS) is not only characterized by pathological bone formation leading to ankylosis, but also by bone loss which may lead to vertebral fractures (VFx). TNF-alpha inhibitors (TNFi) have proven to be effective in blocking the inflammation process. A few studies also showed an increase of Bone Mineral Density (BMD) in AS patients treated with TNFi 1–3 but the incidence of VFx after two years of treatment was increased.3–4ObjectivesTo evaluate the long-term effect of TNFi on BMD and the incidence of VFx in patients with AS.MethodsConsecutive TNFi naive patients diagnosed with AS according to the Modified New York criteria were included. Patients were recruited from the VUmc and the Amsterdam Outpatient clinic Reade and were treated with TNFi for 4 years. BMD at hip and lumbar spine (LS) were measured at baseline, after 2 and 4 years. T-scores were categorized as “normal BMD”, “osteopenia” and “osteoporosis”, based on the WHO osteoporosis criteria.5 The incidence of VFx was determined by two observers using the Genant method.6ResultsIn total, 70 AS patients with complete datasets (67.1% male) were included. The mean age was 41.6 years and the disease duration (time since diagnosis) was 9.8 years. At baseline 42% of the patients had a decreased BMD of the hip and 34% of the spine, of whom 19 patients (27%) had both a decreased hip BMD as well as a decreased lumbar BMD. The BMD of spine and hip improved after 2 and 4 years of TNFi treatment (Table 1). In 7 patients (10%), 8 VFx were observed both at baseline and after 2 years. After 4 years of TNFi-treatment 11 VFx were observed in 9 patients.After 4 years, 2 out of 9 patients with ≥1 VFx had a decreased BMD at hip and lumbar spine whereas the other 7 patients had a normal BMD. The majority of VFx was localized in the mid or lower thoracic spine.Table 1, BMD measurement in spine and hip of 70 AS patients treated with TNFiBaselineAfter 2 years of TNFiAfter 4 years of TNFi Osteopenia LS*23 (32.9)19 (27.1)21 (30.0)Osteoporosis LS6 (8.6)3 (4.3)2 (2.9)Abnormal BMD LS29 (41.5)21 (31.4)23 (32.9)Osteopenia total hip22 (31.4)19 (27.1)16 (22.9)Osteoporosis total hip2 (2.9)2 (2.9)3 (4.3)Abnormal BMD total hip**24 (34.3)21 (30.0)19 (27.2)Patients with VFx7 (10.0)7 (10.0)9 (12.9)Total number of VFx8811*Lumbar Spine; **N=68, because 2 patients had a total hip replacement. Abnormal BMD = osteopenia and/or osteoporosis according to WHO guideline6. Vertebral fractures (VFx) are presented in number of patients with a VFx and the actual prevalence of VFx. Outcomes are presented in n (%).ConclusionsThe percentage of relatively young AS patients with a decreased BMD at baseline of the hip and lumbar spine was high (34–41%). After 4 years of TNFi-treatment the BMD of the lumbar spine improved in 8.6% of the patients and of the hip in 7.2% of the patients. At baseline, several vertebral fractures were found and a few additional vertebral fractures were observed after 4 years of treatment.References Visvanathan S et al. Ann Rheum Dis 2009.Arends S et al. Arthrit...
Background Strictures develop in over half of Crohn’s Disease (CD) patients and can lead to complaints of bowel obstruction, requiring treatment. A study showed that strictures and pre-stricture small bowel (SB) have lower motility measured with cine-MRI, compared to normal bowel in CD. However, stricture motility has not been correlated with disease duration or Harvey Bradshaw Index (HBI). Investigating this correlation can provide insight in the physiologic behavior of a stricture in relation to the extent of bowel damage (disease duration) and clinical complaints (HBI). This could possibly support the clinician in treatment decisions. Our aim is to investigate correlations between stricture motility measured with cine-MRI and disease duration and HBI, respectively. Methods At a tertiary center CD patients (≥18yrs) with SB strictures were included. Patients fasted 4 hours, after which they drank 1600 mL (2.5%-mannitol-solution) in 60 minutes prior to 3T MRI. All underwent coronal dynamic 2D bFFE scans of the most stenotic SB and the pre-stenotic dilation if present, during a 20-second expiration breath-hold. Bowel motility was assessed with a validated displacement mapping technique (GIQuant, Entrolytics, Motilent, UK). Strictures (wall thickening >3mm and ≥50% luminal reduction) and pre-stenotic dilations (luminal diameter >3cm) were delineated on a reference image and motility was quantified on a motility map within these regions of interest (ROI), producing a single, numerical motility score (Arbitrary Units=AU). Stricture and pre-stenotic dilation motility scores are presented in medians [IQR]. Correlation was tested between stricture motility, disease duration and HBI by means of spearman’s rank correlation test. Results Twenty-two patients (55% male, age 37yrs [IQR 25-55], disease duration 7yrs[IQR 4-12]) were included. SB stricture motility was 57AU[IQR 48-71]. Pre-stenotic dilation motility (n=6) was 131AU[IQR 88-340]. Disease duration and stricture motility showed no correlation(r=0.2, p=0.4). HBI and stricture motility were inversely correlated(r=-0.6, p<0.01). Conclusion We found an inverse correlation between SB stricture motility and HBI. No correlation was found between SB stricture motility and disease duration. The inverse correlation between HBI and stricture motility suggests that lower motility is associated with poorer clinical condition. This finding can possibly lead to earlier endoscopic or surgical intervention, since it indicates lower motility is associated with poorer clinical condition. Interestingly, we also measured higher pre-stenotic dilation motility compared to stricture motility, presumably a physiological response of the pre-stenotic dilation to the distal stricture and ongoing proximal peristalsis.
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