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Extended report
Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography
  1. X Baraliakos1,
  2. F Heldmann1,
  3. J Callhoff2,
  4. J Listing2,
  5. T Appelboom3,
  6. J Brandt4,
  7. F Van den Bosch5,
  8. M Breban6,
  9. GR Burmester7,
  10. M Dougados8,
  11. P Emery9,
  12. H Gaston10,
  13. M Grunke11,
  14. I E Van Der Horst-Bruinsma12,
  15. R Landewé13,
  16. M Leirisalo-Repo14,
  17. J Sieper15,
  18. K De Vlam16,
  19. D Pappas17,
  20. U Kiltz,1,
  21. D Van Der Heijde18,
  22. J Braun1
  1. 1Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Germany
  2. 2Epidemiology Unit, German Rheumatism Research Center, Berlin, Germany
  3. 3Hopital Erasme, Brussels, Belgium
  4. 4Rheumapraxis Steglitz/Charité, Berlin, Germany
  5. 5Department of Rheumatology, Universitair Ziekenhuis Ghent, Gent, Belgium
  6. 6Department of Rheumatology, Hopital Ambroise Paré, University of Versailles Saint-Quentin-en-Yvelines, Boulogne, France
  7. 7Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Campus Mitte, Berlin, Germany
  8. 8Department of Rheumatology B, Paris-Descartes University; AP-HP, Cochin Hospital, Paris, France
  9. 9Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  10. 10Department of Rheumatology, Addenbrookes Hospital, University of Cambridge, Cambridge, UK
  11. 11Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany
  12. 12Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands
  13. 13Department of Clinical immunology & Rheumatology, AMC Amsterdam, Academisch Ziekenhuis Maastricht, Amsterdam, The Netherlands
  14. 14Department of Medicine, Division of Rheumatology, University Central Hospital Helsinki, Helsinki, Finland
  15. 15Medical Department I, Rheumatology, Charité University Medicine Berlin, Campus Steglitz, Berlin, Germany
  16. 16University Hospital Leuven, Leuven, Belgium
  17. 17Center for Orthopaedics and Traumatology, St. Anna Hospital, Herne, Germany
  18. 18Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Professor J Braun, Rheumazentrum Ruhrgebiet, Ruhr-University Bochum Landgrafenstr. 15, Herne D-44652, Germany, juergen.braun{at}


Objective To study the relationship of spinal inflammation and fatty degeneration (FD) as detected by MRI and new bone formation seen on conventional radiographs (CRs) in ankylosing spondylitis (AS).

Methods CRs at baseline, 2 years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients treated with infliximab in European AS Infliximab Cohort were available. Relative risks (RR) were calculated with a general linear model after adjustment for within-patient variation.

Results In a total of 1466 vertebral edges (VEs) without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the majority of which (57.4%) had no corresponding detectable MRI lesions at baseline. VEs with both inflammation and FD at baseline had the highest risk (RR 3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while inflammation at baseline with no FD at 2 years had the lowest risk for syndesmophyte formation at 5 years (RR=0.8). Of the VEs with inflammation at baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only 1 syndesmophyte developed within 5 years.

Conclusions Parallel occurrence of inflammation and FD at baseline and development of FD without prior inflammation after 2 years were significantly associated with syndesmophyte formation after 5 years of anti-tumour necrosis factor (TNF) therapy. However, the sequence ‘inflammation–FD–new bone formation’ was rarely observed, an argument against the TNF-brake hypothesis. Whether an early suppression of inflammation leads to a decrease of the risk for new bone formation remains to be demonstrated.

  • Ankylosing Spondylitis
  • Magnetic Resonance Imaging
  • Anti-TNF

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