RUOLO DEGLI INIBITORI DEL SISTEMA WNT-Beta CATENINA NELL’ARTRITE REUMATOIDE E NELLA SPONDILITE ANCHILOSANTE

BACKGROUND: bone involvement in Rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS) is important, complex and multiform. There are reported and described various manifestations of osteoporosis, excessive bone neoformation or erosions. Nowadays it is possible to measure serum concentrations of physiological inhibitors of Wnt/ß-catenin pathway, i.e. Dickkopf-1 (DKK1) and Sclerostin, which modulate osteoblastic and osteoclastic activities.PURPOSE OF THE STUDY : To evaluate serum concentrations of DKK1 and Sclerostin in patients with Rheumatoid Arthritis and Ankylosing Spondylitis, and any correlations with bone manifestations and with other clinical parameters.CASE STUDY AND METHODS: The study included patients from the Rheumatology Department (U.O.C.) of the UNIVERSITY HOSPITAL of Verona, namely 154 patients with RA and 71 patients with AS, and involved collection of anthropometric, anamnestic, clinical and laboratory data. We collected also X-ray imaging, like hands and feet X-rays for RA and lateral radiographs of the total spine for SA. Bone mineral density (BMD) was assessed in all patients and controls using dual X-ray absorptiometry at lumbar spine, hip and total body site. We also collected blood samples to measure DKK1, Sclerostin, PTH and bone turnover markers serum levels. The control group included 196 age-sex matched healthy volunteers.RESULTS: Average DKK1 and PTH serum levels were remarkably higher in patients with RA than in the control group; DKK1 serum levels were positively correlated with age only in healthy subjects, while they were correlated with PTH serum levels only in RA patients. Among RA patients, DKK1 levels were significantly higher in patients with bone erosions and positively correlated with CTX in patients not treated with bisphosphonates. DKK1 levels were negatively correlated with total hip BMD. On average, both DKK1 and Sclerostin serum levels were lower in patients with AS than in the control group; furthermore, DKK1, but not Sclerostin serum levels, were remarkably higher in patients with syndesmophytes or vertebral fractures. DKK1 levels were negatively correlated with lumbar spine Z-score BMD and positively correlated with PTH and BASFI. Finally, a positive correlation was found between DKK1 levels and CRP. CONCLUSIONS: The data we collected support the key role of Wnt/ß-catenin pathway and its physiological inhibitors, especially DKK1, in the pathogenesis of bone involvement in RA and AS and suggest a possible clinical role of DKK1 serum concentration as a new biomarker.