Dickkopf-1 Is Associated with Periarticular Bone Loss in Patients with Rheumatoid Arthritis*

Objective: To examine whether cytokines shown to suppress osteoblasts, Dickkopf-1 (DKK1) and hepatocyte growth factor (HGF), are associated with periarticular bone loss in rheumatoid arthritis (RA). Methods: RA patients with short disease duration were prospectively followed and hand bone mineral density was assessed by digital X-ray radiogrammetry (DXR) at baseline and after 1, 2 and 5 years. Plasma samples collected at baseline from 136 of the included patients were analyzed for HGF and DKK1. Group comparisons, correlation analyses and multivariate analyses were performed to evaluate the relationship between baseline cytokine levels and DXR-BMD. Results: Patients with hand bone loss after 1 year had significantly higher baseline plasma levels of DKK1 than patients without bone loss. Patients with periarticular bone loss after 2 and 5 years had significantly higher baseline plasma levels of HGF. Baseline DKK1 but not HGF levels were independently associated with periarticular bone loss after 1 year. Conclusion: High serum levels of DKK1 are weakly but independently associated with periarticular bone loss in RA. The importance of DKK1 and HGF for loss of periarticular bone needs to be defined in future studies.