No abstract

Objective. Osteocytes are considered to be sensors of bone damage and regulators of bone mass by specifically expressing sclerostin, an inhibitor of bone formation. The contribution of osteocytes in regulating local bone remodeling in arthritis is unknown. The aim of this study was to investigate the role of osteocytes as contributors to bone remodeling in ankylosing spondylitis (AS).Methods. Sclerostin expression and osteocyte death were assessed by immunohistochemistry in joints derived from patients with AS, patients with rheumatoid arthritis (RA), and patients with osteoarthritis (OA), as well as from control subjects. In addition, the serum level of sclerostin was assessed by enzyme-linked immunosorbent assay in healthy subjects and patients with AS; this assessment included the longitudinal correlation of sclerostin serum levels and radiographic progression in the spine of patients with AS.Results. Sclerostin expression was confined exclusively to osteocytes. Whereas the majority of osteocytes in healthy individuals and patients with RA were sclerostin positive, expression was significantly reduced in patients with OA and was virtually absent in patients with AS. Moreover, serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. Importantly, low serum sclerostin levels in patients with AS were significantly associated with the formation of new syndesmophytes (P ‫؍‬ 0.007).Conclusion. Sclerostin expression is impaired in patients with AS, suggesting a specific alteration of osteocyte function in this disease. A low serum level of sclerostin in the setting of AS is linked to increased structural damage, emphasizing the role of sclerostin in the suppression of bone formation.Ankylosing spondylitis (AS) is an inflammatory disease that predominantly affects axial joints and intervertebral spaces. AS is characterized by tight interplay between chronic inflammation and bone formation (1), which is only partly understood. Local inflammation appears to be crucial for bony proliferations along periosteal and entheseal sites (1). Inflammatory lesions are typically located in the subchondral bone marrow (2-4) and are preferentially seen at sites that later develop bony proliferations and ankylosis (3,4), suggesting a link between inflammation and bone formation.These observations, which suggest a functional link between inflammatory lesions inside the cortical bone barrier and bony proliferations outside this barrier, indicate that there is certain kind of "communication"Drs.

IntroductionIn this study, we analysed the number of IL-17+ cells in facet joints, in the peripheral blood (PB) and synovial fluid (SF) of spondyloarthritis (SpA) patients and compared these results with those of patients with other rheumatic diseases and controls.MethodsImmunohistochemical analysis of IL-17+ cells was performed in facet joints of 33 ankylosing spondylitis (AS) patients and compared with data from 20 osteoarthritis (OA) patients. The frequency of IL-17+CD4+ T cells in PB and SF of SpA patients (PB n = 30, SF n = 11), rheumatoid arthritis (RA) patients (PB n = 14, SF n = 7), OA patients (PB n = 10) and healthy controls (PB n = 12) was analysed after stimulation with Staphylococcus aureus Enterotoxin B and phorbol 12-myristate 13-acetate/ionomycin and quantified by flow cytometry.ResultsIn AS facet joints, the frequency of IL-17-secreting cells was significantly higher than in samples obtained from OA patients (P < 0.001), with a slight predominance of IL-17+ cells among the mononuclear cells (61.5% ± 14.9%) compared to cells with polysegmental nuclei. Immunofluorescence microscopy revealed that the majority of IL-17+ cells were myeloperoxidase-positive (35.84 ± 13.06/high-power field (HPF) and CD15+ neutrophils (24.25 ± 10.36/HPF), while CD3+ T cells (0.51 ± 0.49/HPF) and AA-1+ mast cells (2.28 ± 1.96/HPF) were less often IL-17-positive. The frequency of IL-17+CD4+ T cells in the PB and SF of SpA patients did not differ significantly compared to RA patients, OA patients or healthy controls.ConclusionsOur data suggest an important role for IL-17 in the inflammatory processes in AS. However, the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response.

Objective. Zygapophyseal joints of the spine are often affected in ankylosing spondylitis (AS). In this study, we undertook a systematic immunohistologic evaluation of the immunopathology of the zygapophyseal joints in patients with advanced AS.Methods. We obtained zygapophyseal joints from 16 AS patients undergoing polysegmental correction of kyphosis and from 10 non-AS controls (at autopsy). Immunohistologic analysis of the bone marrow was performed by analyzing the number of infiltrating T cells (CD3, CD4, CD8), B cells (CD20), osteoclasts (CD68), bone marrow macrophages (CD68), and microvessel density (CD34) per high-power field.Results. Zygapophyseal joints from 6 of 16 AS patients, but from none of the controls, exhibited 2 or more CD3؉ T cell aggregates, signifying persistent inflammation. Interstitial CD4؉ and CD8؉ T cells were significantly more frequent in AS patients compared with non-AS controls (P ‫؍‬ 0.002 and P ‫؍‬ 0.049, respectively). While there was no clear difference between the number of CD20؉ B cells in AS patients overall compared with controls, there was a significant difference when persistently inflamed joints from patients with AS were compared with joints without active inflammation from patients with AS or joints from controls (both P ‫؍‬ 0.03). Microvessel density in bone marrow from AS patients with active inflammation was significantly higher than that in bone marrow from controls.Conclusion. This immunohistologic study of bone marrow from zygapophyseal joints demonstrates persistent inflammation in the spine of patients with AS, including those with longstanding disease. The findings of increased numbers of T cells and B cells and neoangiogenesis suggest that these features play a role in the pathogenesis of AS.

We used laser Doppler flowmetry (LDF) with a high energy (20 mW) laser to measure perfusion of the femoral head intraoperatively in 32 hips. The surgical procedure was joint debridement requiring dislocation or subluxation of the hip. The laser probe was placed within the anterosuperior quadrant of the femoral head. Blood flow was monitored in specific positions of the hip before and after dislocation or subluxation. With the femoral head reduced, external rotation, both in extension and flexion, caused a reduction of blood flow. During subluxation or dislocation, it was impaired when the posterosuperior femoral neck was allowed to rest on the posterior acetabular rim. A pulsatile signal returned when the hip was reduced, or was taken out of extreme positions when dislocated. After the final reduction, the signal amplitudes were first slightly lower (12%) compared with the initial value but tended to be restored to the initial levels within 30 minutes. Most of the changes in the signal can be explained by compromise of the extraosseous branches of the medial femoral circumflex artery and are reversible. Our study shows that LDF provides proof for the clinical observation that perfusion of the femoral head is maintained after dislocation if specific surgical precautions are followed.

In the future, there will be an increased number of cervical revision surgeries, including 4-and more-levels. But, there is a paucity of literature concerning the geometrical and clinical outcome in these challenging reconstructions. To contribute to current knowledge, we want to share our experience with 4-and 5-level anterior cervical fusions in 26 cases in sight of a critical review of literature. At index procedure, almost 50% of our patients had previous cervical surgeries performed. Besides failed prior surgeries, indications included degenerative multilevel instability and spondylotic myelopathy with cervical kyphosis. An average of 4.1 levels was instrumented and fused using constrained (26.9%) and non-constrained (73.1%) screw-plate systems. At all, four patients had 3-level corpectomies, and three had additional posterior stabilization and fusion. Mean age of patients at index procedure was 54 years with a mean follow-up intervall of 30.9 months. Preoperative lordosis C2-7 was 6.5°in average, which measured a mean of 15.6°at last follow-up. Postoperative lordosis at fusion block was 14.4°in average, and 13.6°at last follow-up. In 34.6% of patients some kind of postoperative change in construct geometry was observed, but without any catastrophic construct failure. There were two delayed unions, but finally union rate was 100% without any need for the Halo device. Eleven patients (42.3%) showed an excellent outcome, twelve good (46.2%), one fair (3.8%), and two poor (7.7%). The study demonstrated that anterior-only instrumentations following segmental decompressions or use of the hybrid technique with discontinuous corpectomies can avoid the need for posterior supplemental surgery in 4-and 5-level surgeries. However, also the review of literature shows that decreased construct rigidity following more than 2-level corpectomies can demand 360°instrumentation and fusion. Concerning construct rigidity and radiolographic course, constrained plates did better than non-constrained ones. The discussion of our results are accompanied by a detailed review of literature, shedding light on the biomechanical challenges in multilevel cervical procedures and suggests conclusions.

Multilevel cervical spine procedures can challenge the stability of current anterior cervical screw-and-plate systems, particularly in cases of severe three-column subaxial cervical spine injuries and multilevel plated reconstructions in osteoporotic bone. Supplemental posterior instrumentation is therefore recommended to increase primary construct rigidity and diminish early failure rates. The increasing number of successfully performed posterior cervical pedicle screw fixations have enabled more stable fixations, however most cervical pathologies are located anteriorly and preferably addressed by an anterior approach. To combine the advantages of the anterior approach with the superior biomechanical characteristics of cervical pedicle screw fixation, the authors developed a new concept of a cervical anterior transpedicular screw-and-plate system. An in vivo anatomical study was performed to explore the feasibility of anterior transpedicular screw fixation (ATPS) in the cervical spine. The morphological study was conducted based on 29 cervical spine CT scans from healthy patients and measurements were performed on the pedicle sizes, angulations, vertebral body depth, height and width at C2 to T1. Significant morphologic parameters for the new technique are discussed. These parameters include the sagittal and transverse intersection points of the pedicle axis with the anterior vertebral body wall, as well as the distances between sagittal intersection points from C2 to T1. On the basis of these results, standard spine models were reconstructed and used for the conceptual development of a preclinical release prototype of an anterior transpedicular screw-and-plate system. The morphological feasibility of the new technique is demonstrated, and its indications, biomechanical considerations, as well as surgical prerequisites are thoroughly discussed. In the future, the technique of cervical anterior transpedicular screw fixation might diminish the number of failures in the reconstruction of multilevel and three-column cervical spine instabilities, and avoid the need for supplemental posterior instrumentation.

Objective. The interleukin-12 (IL-12) family of cytokines has been suggested to play a critical role in inflammatory autoimmune diseases, and recent studies analyzing peripheral blood and synovial fluid from patients with spondyloarthritides suggest that IL-23 might be a proinflammatory factor in these disorders. This study was undertaken to investigate the presence and source of IL-23 in the spines of patients with ankylosing spondylitis (AS).Methods