ALTERED SKELETAL EXPRESSION OF SCLEROSTIN AND ITS LINK TO RADIOGRAPHIC PROGRESSION IN ANKYLOSING SPONDYLITIS

Background: Osteocytes are considered as 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 spondylitis/arthritis is unknown. Objectives: To investigate the role of osteocytes as contributor to bone remodeling in ankylosing spondylitis (AS). Methods: Sclerostin expression and osteocyte death were assessed by immunohistochemistry in joints derived from patients with AS, rheumatoid arthritis (RA), and osteoarthritis (OA) as well as controls without joint or spinal diseases. In addition, serum level of sclerostin was assessed by enzyme-linked immunosorbent assay in patients with AS and healthy subjects. Finally, longitudinal assessment of sclerostin serum levels at baseline and 2 years were performed in 46 AS patients and correlated with radiographic progression of the spine between baseline and 2 years. Results: In situ sclerostin expression was exclusively confined to osteocytes. Whereas the majority of osteocytes in healthy individuals and RA patients showed sclerostin expression, it was significantly reduced in OA and virtually absent in AS (p<0.05). Less than 20% of osteocytes from AS patients expressed sclerostin. Moreover, serum levels of sclerostin were significantly lower in AS patients (614±180 pg/ml) than in healthy individuals (2832±169 pg/ml, p<0.05). Even more interestingly, sclerostin serum levels over time were significantly higher in AS patients without syndesmophyte growth than in AS patients with syndesmophyte growth (p=0.007). Conclusion: Sclerostin expression is impaired in AS patients suggesting a specific alteration of osteocyte function in this disease. Low sclerostin serum level in AS is linked to increased osteoproliferation, emphasizing the role of sclerostin in the suppression of bone formation. Disclosure of Interest: none declaredCitation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 641Session: Spondylarthropathies Clinical aspects (other than treatment) (Poster Presentations )