Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis

Arthritis Rheum. 2009 Nov;60(11):3257-62. doi: 10.1002/art.24888.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Biomarkers / metabolism
  • Bone Morphogenetic Proteins / metabolism*
  • Bone and Bones / diagnostic imaging*
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Case-Control Studies
  • Cell Death
  • Disease Progression*
  • Female
  • Genetic Markers
  • Humans
  • Male
  • Osteoarthritis / diagnostic imaging
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Osteocytes / metabolism
  • Osteocytes / pathology
  • Osteogenesis
  • Radiography
  • Spondylitis, Ankylosing / diagnostic imaging*
  • Spondylitis, Ankylosing / metabolism*
  • Spondylitis, Ankylosing / pathology


  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Bone Morphogenetic Proteins
  • Genetic Markers
  • SOST protein, human