Bone formation in ankylosing spondylitis

Introduction Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disorder with unclear pathogenesis. Bone formation is a hallmark feature of AS, precise mechanisms of which are unknown. The aim of this review was to summarize the current knowledge regarding both clinical significance and pathogenesis of bone formation in AS. Materials and methods Articles, published in the medical literature and chapters in textbooks related to the discussed topic, were critically reviewed and relevant data were selected, collated and organized for the purpose of this manuscript. Results Conventional radiography is the most valuable classical tool for identification of structural changes in AS. The typical manifestations of bone formation in AS usually involve the axial skeleton, including spine, sacroiliac and hip joints, and, if properly recognized, have an important role in diagnosing, classifying and monitoring patients. Molecular pathways leading to bone formation in AS have not been elucidated sufficiently. Abnormally active signalling by wingless-type (wnt)-like and bone morphogenic protein (BMP)-mediated pathways have been suggested as major contributors to diseaserelated ossification in AS. The only medicines, shown currently to delay the process of bone formation in AS patients, are nonsteroidal anti-inflammatory drugs. Conclusion Better understanding and prediction of structural damage would help to improve and individualize management of patients suffering from AS. Introduction Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disorder with unclear pathogenesis. The prevalence of AS in the general population is estimated at 0.5%, and its prominent features include sacroiliitis, spondylitis, asymmetric peripheral arthritis, enthesitis and an association with the histocompatibility allele HLA-B27. AS disease activity can be appreciated by clinical and laboratory measures, such as the severity of the inflammatory back pain, presence of synovial or entheseal inflammation, acute uveitis, constitutional symptoms and elevated indices of inflammation in the blood such as erythrocyte sedimentation rate and/ or serum levels of C-reactive protein (CRP). The pathologic progression of AS is measured by new bone formation, appearance of syndesmophytes at vertebral body margins and, eventually, ankylosis of the sacroiliac joints and vertebral column. The presence of inflammation at the areas of subsequent osseous proliferation is considered to be a necessary trigger; but, on the other hand, the rate of new bone formation in AS does not seem to be a simple function of the inflammatory activity of the disease, and the precise mechanisms of the progressive ankylosis are unknown. It is also well appreciated that the rate and course of new bone formation can be individually determined, with some AS patients having radiographic ankylosis already upon first clinical presentation, while others do not develop ankylosis even after longstanding disease. The factors influencing this significant variability in both rate and magnitude of new bone formation in individuals with AS have not been elaborated. The aim of this review was to summarize the current knowledge regarding both clinical significance and pathogenesis of bone formation in AS. Materials and methods A literature search of the PUBMED database using the crossover of keywords ‘bone formation’ and ‘ankylosing spondylitis’ was conducted, with 227 papers listed. These manuscripts, as well as other articles published in the medical literature and chapters in textbooks related to the discussed topic, were critically reviewed and relevant data were selected, collated and organized for the purpose of this article. Results Radiographic features of bone formation in AS Bone formation is a characteristic feature of AS, which, if properly recognized, has an important role in diagnosing, classifying and monitoring patients suffering from the disease. Conventional radiography, while unable to visualize active inflammation, is the most valuable classical tool for identification of structural changes in AS1. The typical manifestations of bone formation in AS usually involve the axial skeleton, including spine, sacroiliac and hip joints, while ossification of the entheses may occur also peripherally. The characteristic radiographic changes in AS, related to bone formation, include2: * Corresponding author Email: [email protected] 1 Department of Internal Medicine A, Bnai Zion Medical Center, Haifa, Israel 2 Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel 3 Rheumatology Unit, Bnai Zion Medical Center, Haifa, Israel