Abstract
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.
Highlights
Bone loss presents as focal joint erosions, periarticular bone loss and generalized osteoporosis in rheumatoid arthritis (RA)
In a previous study on the same cohort we found that plasma level of hepatocyte growth factor (HGF), but not DKK1, was an independent predictor of radiographic damage of joints both at short- and long-term follow-up [10]
In the present study we wanted to investigate if DKK1 and HGF were associated with periarticular hand bone loss assessed by digital X-ray radiogrammetry (DXR) in RA
Summary
Bone loss presents as focal joint erosions, periarticular bone loss and generalized osteoporosis in rheumatoid arthritis (RA). Periarticular bone loss occurs within the bone adjacent to inflamed joints and has been shown to precede and predict development of erosions [1]. TS designed the study, acquired and interpreted data and wrote the paper. Central signaling pathways in osteoblast differentiation are the wingless (Wnt)-signaling pathway and the bone morphogenetic protein (BMP) pathway Inhibitors of these pathways, Dickkopf-1 (DKK1) and hepatocyte growth factor (HGF), respectively, inhibit osteoblast differentiation and are associated with bone destruction in RA and multiple myeloma [4,5,6,7,8]. Dickkopf-1 Is Associated with Periarticular Bone Loss in Patients with Rheumatoid Arthritis radiogrammetry (DXR) [1], whereas presence of focal erosions is commonly evaluated by scoring radiographs according to the Sharp Heijde method [9]. In the present study we wanted to investigate if DKK1 and HGF were associated with periarticular hand bone loss assessed by DXR in RA
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