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Pathological new bone formation is a critical feature of the progression of ankylosing spondylitis (AS), and spine ankylosis is a distinctive feature of this condition. Ligaments are the primary regions of pathological new bone formation in AS. Here, it is demonstrated that ligament tissue‐derived extracellular vesicles (EVs) and their interleukin‐17A (IL‐17A) cargo mediate the communication between the tissue and other cells. The investigation revealed that IL‐17A in EVs can activate the JAK‐STAT3 pathway, thereby stimulating the expression of MMP14 in AS ligament. Overexpression of MMP14 can lead to changes in the cytoskeleton and mechanical signaling of mesenchymal stem cells and other cells. These alterations in cellular cytoskeleton and mechanical signaling at ligament sites in patients with AS or in stem cells treated with EVs can result in pathological new bone formation. Finally, inhibiting IL‐17A activity and EV endocytosis effectively controlled inflammation and pathological new bone formation. Overall, these data suggest that ligament‐derived EVs and the enclosed IL‐17A have a potential role in driving pathological new bone formation in AS, and targeting EVs may therefore emerge as a novel approach to delaying ectopic ossification in AS. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is an immune chronic inflammatory disease, resulting in back pain, stiffness, and thoracolumbar kyphotic deformity. Based on the reported anti‐inflammatory and antioxidant capacities of cynarin (Cyn), this study explored its protective role and molecular mechanisms in mesenchymal stem cells (MSCs) from AS. The target pathways and genes were verified using Western blotting, quantitative real‐time polymerase chain reaction, and immunofluorescent staining, while molecular docking analysis was conducted. In AS‐MSCs, we found that the expression levels of p‐NF‐κB, IL‐6, IL‐1β, and TNF‐α were higher and IκB‐α, Nrf‐2, and HO‐1 were lower compared with healthy control (HC)‐MSCs. With molecular docking analysis, the biding affinities between Cyn and Keap1‐Nrf‐2 and p65‐IκB‐α were predicted. The mRNA and protein expression of p‐NF‐κB, IL‐6, IL‐1β, and TNF‐α and the reactive oxygen species (ROS) generation were downregulated following Cyn administration. Meanwhile, the expression level of IκB‐α, Nrf‐2, and HO‐1 were significantly increased after Cyn pretreatment. The results suggested that the protective mechanisms of Cyn in AS‐MSCs were based on enhancing the antioxidation and suppression of excessive inflammatory responses via Nrf‐2/ROS/NF‐κB axis. Our findings demonstrate that Cyn is a potential candidate for alleviating inflammation in AS. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study. Objectives: To analyze the change in acetabular anteversion (AA) after lumbar pedicle subtraction osteotomy (PSO) in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis who have already undergone total hip arthroplasty (THA). Methods: AS patients with thoracolumbar kyphosis following lumbar PSO from January 2005 to January 2020 were retrospectively reviewed. Only the patients performed with THA prior to the PSO were included. AA was measured on the full-length standing posterior-anterior radiographs using the ellipse method. Results: Twenty patients (34 hips) with a mean age of 36.8 years (range, 22 to 63 years) were included. After lumbar PSO, AA was reduced from 18.59° to 5.85° (P < 0.001). Postoperative change in AA was correlated with the spinal deformity correction. Additionally, the change in AA postoperatively was correlated with pelvic incidence (PI) (R = 0.346, P = 0.045). Although the postoperative change in sagittal vertical axis (SVA) was larger in the patients after L2 or L3 PSO (153.97 mm vs 70.03 mm, P = 0.006), no difference was found in the postoperative change in AA (12.83° vs 10.96°, P = 0.540) compared with the patients following L1 PSO. Conclusions: AA was significantly decreased following lumbar PSO and the postoperative change in AA was correlated with the magnitude of spinal deformity correction. Notably, the effect of osteotomy level on the postoperative change in AA was limited in the AS patients underwent 1-level PSO. [ABSTRACT FROM AUTHOR]

• PSO away from pseudarthrosis was a feasible method for AS-related kyphosis. • GK correction consisted of three parts: OV, pseudarthrosis and interbody disc space. • Contribution of pseudarthrosis should be considered for surgical decision-making. The correction of global kyphosis (GK) for ankylosing spondylitis (AS) patients with pre-existing pseudarthrosis were frequently over 45°. Mismatch between kyphosis correction of GK and pedicle subtraction osteotomy (PSO) may be ascribed to contribution of pseudarthrosis. The aim of the present study was to evaluate surgical outcomes of PSO away from the level of pseudarthrosis and to elucidate the contribution of pre-existing spinal pseudarthrosis in surgical correction of thoracolumbar kyphosis caused by AS. Eighteen AS patients with pre-existing pseudarthrosis were included. PSO outside the level of pseudarthrosis were performed for all the patients. The average follow-up period were 29 months. Radiographs were analyzed for correction and complications. Significant improvement in all sagittal parameters were found postoperatively without obvious correction loss at the final follow-up. Local kyphosis (LK) improved from 23.88° preoperatively to 12.67° postoperatively with a mean correction of 11.47°. Average correction of per PSO segment, GK and sum of disc wedging within fused region (SDW) were 33.53°, 49.27° and 4.00°, respectively. PSO away from the level of pseudarthrosis, but with posterior instrumentation crossing it was a feasible method and was able to maintain sustained surgical outcomes. Regarding GK correction, PSO accounted for 68.1% while pre-existing pseudarthrosis provided 23.3%, which resulted from anterior column opening postoperatively. Thus, extra kyphosis correction attributed to pre-existing pseudarthrosis should be considered for surgical-decision making to prevent overcorrection. [ABSTRACT FROM AUTHOR]

Background: Short-term studies have demonstrated good surgical outcomes after pedicle subtraction osteotomy (PSO) in ankylosing spondylitis (AS) patients, but there is a paucity of literature focused on middle-term results, especially regarding patterns of loss of correction. The objective of this study is to assess the durability of surgical outcomes and the patterns of loss of correction in thoracolumbar kyphosis secondary to AS following lumbar PSO with over 5-year follow-up.Methods: We performed a retrospective review of 155 consecutive AS patients undergoing lumbar PSO from January 2001 to December 2011. Twenty-four patients were included with an average follow-up of 6.9 years (range, 5-15 years). Radiographical evaluations included global kyphosis (GK), lumbar lordosis (LL), sagittal vertical axis, spinal-sacral angle, kyphosis of proximal non-fused segments (KPNS), angle of fused segments (AFS), osteotomized vertebra angle (OVA), distal intervertebral disc wedging (DIDW) and proximal junctional angle. Meanwhile, clinical outcomes were assessed by the Oswestry disability index (ODI) and Numerical rating scale (NRS).Results: The average correction per PSO segment was 34.9°. Significant improvement in sagittal parameters were found postoperatively, and no obvious deterioration was noticed during the follow-up. Mild loss of correction in GK (2.82°) and LL (3.77°) were observed at the final follow-up (P < 0.05). The KPNS and DIDW increased from 26° and -5.0° postoperatively to 30° and -2.2° at the final follow-up (P < 0.05), respectively. In contrast, no significant diminishment was identified in OVA and AFS (P > 0.05). The ODI and NRS improved significantly from 20.6 and 6.6 preoperatively to 5.9 and 2.3 at the final follow-up (P < 0.05).Conclusions: PSO is an effective procedure for treating AS-related thoracolumbar kyphosis and can maintain sustained surgical outcomes during the middle-term follow-up. The loss of correction was mainly attributable to non-instrumented segments without fully ossified bridging syndesmophyte in the thoracolumbar region instead of instrumented levels. [ABSTRACT FROM AUTHOR]

Objective To compare the efficacy of long and short segment instrumentation after pedicle subtraction osteotomy (PSO) for thoracolumbar kyphosis caused by ankylosing spondylitis (AS). Methods Sixty-four consecutive AS patients were analyzed and divided into groups according to length of instrumentation. We defined short segment instrumentation (SSI) as construct length <7 levels (≤3 levels above and below the osteotomy) (n = 17). By contrast, long segment instrumentation (LSI) was defined as construct length ≥7 levels (≥4 levels above and ≥3 levels below the osteotomy) (n = 47). Both groups were matched cohorts. Radiographs were analyzed for correction, ossification, and complications. Results Correction loss in global kyphosis (GK) and lumbar lordosis (LL) of the LSI group was slightly higher than that of SSI group. Notably, a significantly higher modified Stokes Ankylosing Spondylitis Spinal Score (mSASSS) was noted in the SSI group. Pearson correlation analysis demonstrated that thoracic and lumbar spine mSASSS were significantly associated with correction loss in GK and LL, respectively. Two cases of proximal junctional kyphosis and 1 case of rod fracture occurred in the LSI group. Conclusions Both approaches were able to maintain sustained surgical outcomes. Short segment instrumentation is recommended for AS patients with bridging syndesmophytes. Long constructs are better indicated for patients without fully ossified anterior longitudinal ligaments. Nevertheless, extension of the length of instrumentation might not prevent complications such as proximal junctional kyphosis or rod fracture in patients without fully ossified vertebrae. [ABSTRACT FROM AUTHOR]

Background Context: Rod fracture (RF) has a negative impact on the surgical outcome of patients with ankylosing spondylitis (AS) after lumbar pedicle subtraction osteotomy (PSO). However, there is a paucity of published studies analyzing the risk factors for RF in PSO-treated patients with AS with thoracolumbar kyphosis.Purpose: The objective of this study was to investigate the risk factors for RF after PSO for thoracolumbar kyphosis secondary to AS.Study Design/setting: This is a retrospective single-center study.Patient Sample: Patients with AS who underwent PSO for thoracolumbar kyphosis between January 2002 and December 2016 were included.Outcome Measures: Demographic data, including age, sex, body mass index, and smoking status, were summarized. The surgical data analyzed included the levels of osteotomy, the fusion levels, the upper instrumented vertebra, the lower instrumented vertebra, the osteotomy site, the rod material, the rod diameter, and the rod contour angle (RCA). Radiographic parameters included the sagittal vertical axis, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence. Radiographic parameters were measured at baseline, immediately after the operation, and at the final follow-up. Adequate ossification of the anterior longitudinal ligament (ALL) at the PSO level was defined by a total bony bridge. Adequate ossification of the ALL was also measured at baseline, immediately after the operation, and at the final follow-up.Methods: Patients with a minimum of 2 years' follow-up or patients who developed RF were enrolled in the study. Recruited patients were divided into the RF group and the no-RF group based on whether they developed RF. Patient demographics, operative data, radiographic parameters, and adequate ossification of the ALL were analyzed to determine the risk factors for RF. For patients with RF, the fusion status at the PSO level, the time course to the development of RF, the site of RF, and the corresponding solution were also recorded.Results: Rod fracture occurred in 11 (8.9%) of the 123 recruited patients. Solid fusion at the PSO level was found in all patients in the RF group. The average duration to the onset of RF was 31.4 months (range, 12-68 months). All RFs occurred at or immediately adjacent to the PSO level. The RCA was greater in the RF group than in the no-RF group (27.8° vs 22.9°, p=.031). A greater proportion of patients with a rod diameter of 5.50 mm were found in the RF group than in the no-RF group (100.0% vs 68.8%, p=.033). There was a larger proportion of patients with adequate ossification of the ALL at the final follow-up visit in the no-RF group than in the RF group (67.0% vs 27.3%, p=.018). Multivariate analyses demonstrated that the RCA (odds ratio, 1.174; 95% confidence interval, 1.018-1.354; p=.028) and adequate ossification of the ALL at the final follow-up visit (odds ratio, 0.079; 95% confidence interval, 0.014-0.465; p=.005) were independent factors for RF. Notably, revision surgery was performed among six patients, whereas conservative treatment was used for the remaining five patients.Conclusions: In patients with AS after PSO for thoracolumbar kyphosis with solid fusion at the PSO level, the incidence of RF was 8.9%. Rod diameter was identified as a risk factor for RF. Furthermore, the RCA was identified as an independent risk factor for RF. In contrast, adequate ossification of the ALL around the PSO level at the final follow-up visit was identified as an independent protective factor for RF. [ABSTRACT FROM AUTHOR]

Background Context: Radiographic realignment objectives for the surgical correction of adult spinal deformity (ASD) have been well-described. However, the optimal sagittal spinopelvic alignment after corrective osteotomy for thoracolumbar kyphosis secondary to ankylosing spondylitis (AS) is still unknown so far.Purpose: To comprehensively investigate the relationship between radiographic parameters and clinical outcomes measured by Oswestry Disability Index (ODI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in thoracolumbar kyphosis patients caused by AS following one-level pedicle subtraction osteotomy (PSO) and to determine the optimal sagittal alignment at a minimum of 2-year follow-up.Study Design: A retrospective review of consecutive AS patients from one institution (2006-2016).Patient Sample: One hundred AS-related thoracolumbar kyphosis patients who underwent one-level PSO with a minimum of 2-year follow-up (range, 2-10 years).Outcome Measures: Spinopelvic parameters at final follow-up (≥2 years) included thoracic kyphosis, lumbar lordosis, osteotomized vertebra angle, pelvic tilt (PT), sacral slope (SS), pelvic incidence, sagittal vertical axis, spinosacral angle (SSA), T1 pelvic angle (TPA), spinopelvic angle (SPA), and global kyphosis. Clinical outcomes at final follow-up (≥2 years) was evaluated by ODI and BASDAI, and ODI<20 was defined as good clinical outcome.Methods: Pre- and postoperative radiographic and clinical outcomes were compared by paired samples t test. The correlation between the postoperative radiographic parameters and clinical outcomes was investigated by Pearson correlation analysis. Linear regression analysis was performed to construct predictive models of the clinically relevant radiographic parameters based on ODI scores and to determine the realignment goals. Multiple stepwise regression analysis was applied to figure out the major radiographic contributors of ODI score at the final follow-up.Results: In total, 100 AS patients (92 males and 8 females) with a mean age of 34.7±9.5 years (range, 17-63 years) were followed up for 38.6±17.5 months (range, 24-120 months). At the final follow-up, PT and TPA were positively correlated with both ODI and BASDAI score (p<.05). Although SS, SSA, and SPA were negatively associated with the score of ODI (p<.05), and BASDAI was negatively related to SPA (p<.05). Predicting regression models of the clinically-relevant radiographic parameters were built based on the ODI score at the last follow-up.Conclusions: Based on the regression models, the optimal sagittal alignment of AS patients satisfying good clinical outcome (ODI<20) at a minimum of 2-year follow-up was: PT<24°, SSA>108°, TPA<22°, and SPA>152°. Realizing the aforementioned realignment goals may contribute to satisfied clinical outcome for AS patients with thoracolumbar kyphosis undergoing one-level PSO. [ABSTRACT FROM AUTHOR]

The present study evaluated the severity of syndesmophytes and its correlation with the spinopelvic and clinical outcomes in patients with ankylosing spondylitis (AS). The data from 41 consecutive patients with AS who had undergone pedicle subtraction osteotomy surgery at our institution were reviewed. The computed tomography syndesmophyte score (CTSS), a novel method of evaluating the severity of syndesmophytes, was applied to assess the syndesmophytes of the whole, cervical, thoracic, and lumbar spine. The measured spinopelvic parameters included global kyphosis, sagittal vertical axis, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope. The Oswestry disability index questionnaire, C-reactive protein, and erythrocyte sedimentation rate were used to evaluate the clinical outcome. The Pearson correlation test was performed to identify correlations between syndesmophyte severity and the spinopelvic and clinical parameters. The Pearson correlation analysis demonstrated that the whole CTSS (WCTSS), cervical CTSS, thoracic CTSS, and lumbar CTSS (LCTSS) correlated significantly with each other (P < 0.05). All the CTSSs correlated positively with age, disease duration, and pelvic tilt (P < 0.05). In addition, both sagittal vertical axis and lumbar lordosis were significantly related to the WCTSS, cervical CTSS, and LCTSS (P < 0.05). The Oswestry disability index correlated negatively with the WCTSS (r = −0.312; P < 0.05), thoracic CTSS (r = −0.314; P < 0.05), and LCTSS (r = −0.343; P < 0.05). In advanced AS, old age and a long disease duration are risk factors for the progression of syndesmophytes. The progression of syndesmophytes might contribute to spinal sagittal malalignment. With serious syndesmophytes, pelvic retroversion seems to be the major compensatory mechanism for spinal sagittal malalignment. [ABSTRACT FROM AUTHOR]

Background Context: The head's center of gravity (COG) plumb line (PL) and C7 PL could be simultaneously positioned over the pelvis in adult spinal deformity with normal cervical mobility. However, the position of the head in relation to the global spinal alignment has yet to be investigated in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis.Purpose: The objective of this study was to analyze the position of head in relation to the global spinal alignment in AS-related thoracolumbar kyphosis.Study Design/setting: Retrospective single-center study.Patient Sample: AS patients who underwent lumbar pedicle subtraction osteotomy for thoracolumbar kyphosis from January 2010 to August 2016 were reviewed. Only patients with a visible ear canal on the preoperative, immediate postoperative, and final follow-up radiographs were included.Outcome Measures: The chin-brow angle, cervical range of motion (ROM), lumbar lordosis (LL), thoracolumbar angle, thoracic kyphosis (TK), L1 pelvic angle, pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), TK+LL+PI, PI-LL, maximal kyphosis (MK), deformity angular rate, T1 pelvic angle, T1 tilt, spinosacral angle, sagittal vertical axis (SVA) COG-C7, SVA COG-femoral head (FH), and SVA C7-S were evaluated. Data regarding the health-related quality of life, including the Oswestry disability index (ODI) and visual analogue scale (VAS)-back score, were also collected preoperatively, 2 years postoperatively, and at the latest follow-up.Methods: The cohort was divided into patients with occiput-trunk (OT) concordance or with OT discordance according to the SVA COG-C7 ≤30 mm or >30 mm, respectively. There was no funding in this study and there are no conflict of interest-associated biases.Results: A total of 43 patients (36 males and 7 females) with a mean age of 34.2 years (range, 18-59 years) were identified. There were 17 patients accompanied with OT concordance and 26 patients with OT discordance preoperatively. The cervical ROM was significantly lower (24.0° vs 56.1°, p<.001) and SVA COG-C7 was significantly larger (71.7 mm vs 7.4 mm, p<.001) in patients with OT discordance. Furthermore, the PT was larger (41.0° vs 33.5°, p=.010) in patients with OT discordance. After surgery, the whole cohort showed an improvement in LL (-8.6° vs -52.8°, p<.001). Moreover, the CBVA (25.4° vs 1.3°, p<.001) and SVA COG-C7 (46.2 mm vs 21.6 mm, p<.001) were significantly decreased following lumbar PSO. There were 13 patients accompanied with OT discordance postoperatively, and the cervical ROM was still lower (22.5° vs 42.8°, p=.024) in these patients. Postoperative PT was larger (26.5° vs 20.1°, p=.033) in the patients with OT discordance. At the latest follow-up, there were 17 patients accompanied with OT discordance. In these 17 patients, the cervical ROM was significantly lower (21.0° vs 47.0°, p=.001) and PT was significantly higher (26.2° vs 19.2°, p=.012). The ODI and VAS-back scores demonstrated no significant differences between the two groups preoperatively, 2 years postoperatively, or at the latest follow-up.Conclusions: OT discordance in AS-related thoracolumbar kyphosis could be caused by the reduced cervical ROM. To maintain global spinal balance, the pelvis rotated further backward in response to the larger SVA COG-C7. Moreover, the larger SVA COG-C7 could be decreased after the lumbar PSO. Although there were radiographic differences between the patients with OT concordance and with OT discordance, there was no difference in clinical outcomes, and that a larger sample size and longer follow-up are needed. [ABSTRACT FROM AUTHOR]

Objective To evaluate the accuracy and safety of freehand pedicle screw placement in surgical correction for thoracolumbar kyphosis caused by ankylosing spondylitis (AS). Methods We retrospectively reviewed 266 consecutive patients with AS who underwent osteotomy for kyphosis correction with freehand screw insertion from January 1998 to April 2015 at our institution. A total of 2314 pedicle screws in 158 patients with AS with postoperative computed tomography scans were included in the study. Postoperative computed tomography was performed to classify accuracy of screws, using the established Gertbein classification (grade 0: no perforation, grade 1: perforation <2 mm, grade 2: perforation between 2 and 4 mm, and grade 3: perforation >4 mm). Patients were divided into 2 groups according to coronal Cobb angle: group A ( n = 21, Cobb angle ≥10°), group B ( n = 137, Cobb angle <10°). Results Among the 2314 pedicle screws, 2168 pedicle screw placements were categorized as grade 0, 71 were grade 1, 51 were grade 2, and 24 were grade 3. Breaches occurred more frequently in L1–S1 than the thoracic spine (7.1% and 5.4%, respectively). T5 (25.0%) and S1 (17.7%) experienced the greatest breach rate, whereas T8, L1, and L3 had the lowest breach rate. The breach rate of group A was greater than that of group B (7.9% vs. 6.1%). None of the breaches resulted in either neurologic deficits or vascular complications. Conclusions Freehand pedicle screw placement can be performed safely with acceptable breach rate in patients with AS and thoracolumbar kyphosis. [ABSTRACT FROM AUTHOR]