ARTHRITIS & RHEUMATISM Vol. 60, No. 1, January 2009, pp 93–102 DOI 10.1002/art.24132 © 2009, American College of Rheumatology Inflammatory Lesions of the Spine on Magnetic Resonance Imaging Predict the Development of New Syndesmophytes in Ankylosing Spondylitis Evidence of a Relationship Between Inflammation and New Bone Formation Walter P. Maksymowych, 1 Praveena Chiowchanwisawakit, 2 Tracey Clare, 1 Susanne J. Pedersen, 3 Mikkel Østergaard, 4 and Robert G. W. Lambert 1 Objective. To determine whether a vertebral cor- ner that demonstrates an active corner inflammatory lesion (CIL) on magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) is more likely to evolve into a de novo syndesmophyte visible on plain radiography than is a vertebral corner that demon- strates no active inflammation on MRI. Methods. MRI scans and plain radiographs were obtained for 29 patients recruited into randomized placebo-controlled trials of anti–tumor necrosis factor  (anti-TNF) therapy. MRI was conducted at baseline, 12 or 24 weeks (n  29), and 2 years (n  22), while radiography was conducted at baseline and 2 years. A persistent CIL was defined as a CIL that was found on all available scans. A resolved CIL was defined as having completely disappeared on either the second or third scan. A validation cohort consisted of 41 AS patients followed up prospectively. Anonymized MRIs were assessed independently by 3 readers who were blinded with regard to radiographic findings. Results. New syndesmophytes developed signifi- cantly more frequently in vertebral corners with inflam- mation (20%) than in those without inflammation (5.1%) seen on baseline MRI (P < 0.008 for all reader pairs). They also developed more frequently in vertebral corners where inflammation had resolved than in those where inflammation persisted after anti-TNF treatment. This was confirmed in the analysis of the prospective cohort, in which significantly more vertebral corners with inflammation (14.3%) compared with those without inflammation (2.9%) seen on baseline MRI developed new syndesmophytes (P < 0.003 for all reader pairs). Conclusion. Our findings indicate that a syndes- mophyte is more likely to develop from a prior inflam- matory lesion, supporting a relationship between in- flammation and ankylosis. Ankylosing spondylitis (AS) is a chronic inflam- matory disorder that primarily targets the joints of the axial spine and entheses. A hallmark of the disease is new bone formation in the spine, which typically leads to ankylosis across disc spaces and is thought to follow the onset of inflammation (1). Bone proliferation typically starts at the vertebral rim and grows in the direction of the annulus fibrosus, perpendicular to the vertebral axis (2). Ossification may extend across the vertical length of the disc and becomes visible on radiographs as a syndes- mophyte. The hypothesis that such ankylosis is invariably preceded by inflammation has, in fact, never been Dr. Maksymowych is a Scientist of the Alberta Heritage Foundation for Medical Research. 1 Walter P. Maksymowych, MD, FRCPC, Tracey Clare, BSc, RN, Robert G. W. Lambert, MB BCh, FRCPC: University of Alberta, Edmonton, Alberta, Canada; 2 Praveena Chiowchanwisawakit, MD: University of Alberta, Edmonton, Alberta, Canada, and Siriraj Hos- pital, Mahidol University, Bangkok, Thailand; 3 Susanne J. Pedersen, MD: Copenhagen University Hospital at Herlev, Copenhagen, Den- mark; 4 Mikkel Østergaard, MD, PhD, DMSc: Copenhagen University Hospital at Herlev, Copenhagen, and Copenhagen University Hospital at Hvidovre, Hvidovre, Denmark. Dr. Maksymowych has received consulting fees, speaking fees, and/or honoraria from Schering-Plough, Amgen/Wyeth, and Abbott (less than $10,000 each). Address correspondence and reprint requests to Walter P. Maksymowych, MD, FRCPC, Professor, Department of Medicine, University of Alberta, 562 Heritage Medical Research Building, Edmonton, Alberta T6G 2S2, Canada. E-mail: walter. maksymowych@ualberta.ca. Submitted for publication May 23, 2008; accepted in revised form September 5, 2008. 93