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Serum levels of biomarkers of bone and cartilage destruction and new bone formation in different cohorts of patients with axial spondyloarthritis with and without tumor necrosis factor-alpha blocker treatment

Heiner Appel1*, Louise Janssen1, Joachim Listing2, René Heydrich1, Martin Rudwaleit1 and Joachim Sieper12

Author Affiliations

1 Department of Gastroenterology, Infectiology and Rheumatology, Charité Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany

2 Deutsches Rheumaforschungszentrum Berlin, Schumannstrassse 21/22, 10117 Berlin, Germany

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Arthritis Research & Therapy 2008, 10:R125  doi:10.1186/ar2537

See related editorial by Maksymowych,

Published: 22 October 2008



Recent data about radiographic progression during treatment with tumor necrosis factor-alpha (TNF-α) blocker agents in patients with ankylosing spondylitis (AS) have prompted an intensive discussion about the link between inflammation/bone destruction and new bone formation and the order of events. Therefore, we analysed parameters of cartilage degradation, neoangiogenesis, and new bone formation in different cohorts of patients with axial spondyloarthritis with and without treatment with TNF-α blocker agents.


TNF-α blocker-naïve AS patients were investigated for serum levels of metalloproteinase-3 (MMP-3) (n = 71), vasoendothelial growth factor (VEGF) (n = 50), and bone-specific alkaline phosphatase (BALP) (n = 71) at baseline and after 1 and 2 years. This was compared with 34 adalimumab-treated patients with axial spondyloarthritis (22 AS and 12 non-radiographic axial spondyloarthritis patients) before and after 36 to 52 weeks of treatment.


There were no significant changes in serum levels of MMP-3 (P > 0.05), VEGF (P > 0.05), and BALP (P > 0.05) in a large cohort of TNF-α blocker-naïve AS patients followed for 2 years. In contrast, adalimumab-treated spondyloarthritis (AS and non-radiographic axial spondyloarthritis) patients had a significant decrease of VEGF (P < 0.001) and MMP-3 (P = 0.022) after 36 to 52 weeks of therapy. Most interestingly, the level of BALP increased significantly after 36 to 52 weeks of therapy (P < 0.001). A decrease in MMP-3 serum levels correlated significantly to an increase of BALP (r = -0.398, P = 0.02). In the case of VEGF, there was a negative correlation without significance (r = -0.214, P > 0.05).


Rising levels of BALP and the negative correlation between MMP-3 and BALP in spondyloarthritis patients with TNF-α blocker treatment indicate that new bone formation in AS occurs if inflammation is successfully treated and might be part of a healing process.