THU0034 Rheumatoid arthritis bone fragility is associated with increased DKK1 expression and disturbances in the bone turnover regulating genes. (23rd January 2014)

• Record Type: Journal Article
• Authors: Caetano-Lopes, J.; Rodrigues, A.; Lopes, A.; Vale, A.C.; Monteiro, J.; Vaz, M.F.; Nazarian, A.; Canhão, H.; Fonseca, J.E.
• Is Part Of: Annals of the rheumatic diseases. Volume 71(2012)Supplement 3
• Page Start: 164
• Page End: 165
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-eular.1999
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Rheumatoid arthritis (RA) and primary osteoporosis (OP) induce bone fragility. In this study we aimed at identifying differences in the mechanisms involved in bone fragility by comparing gene expression between RA and OP bone samples with similar fracture risk factors. Methods: Patients with RA submitted to hip replacement surgery were recruited. Trabecular bone microarchitecture was assessed by micro-computed tomography and bone mechanical behavior by compression tests. Bone cell activity was analyzed by studying gene expression. RA patients compared with OP patients were matched for bone mineral density (BMD) and major clinical fracture risk factors (age, gender, BMI, FRAX). Results: Seventeen patients were included, ten with RA and seven with primary established OP. Bone microarchitecture did not differ between the groups, but mechanical bone properties were similarly decreased in RA and primary OP patients. RA bone microenvironment, compared to primary OP, had a gene expression profile characterized by upregulated pro-osteoclastogenic cytokines and DKK1, increased RANKL/OPG ratio, paralleled by raised expression of factors that promote osteoblastic activity, but with low COL1A1 expression. Conclusions: Bone fragility in RA patients is induced by an unbalanced bone turnover that is qualitatively different from the pathobiologic phenomena that occur in primary OP. The type of bone gene disturbances is suggestive of a pivotal role for DKK1 in this process, suggesting that it could be used as a therapeutic target to prevent RA bone damage. Disclosure of Interest: None Declared