Background The recent characterization of the canonical WNT pathway in the regulation of bone modeling and remodeling provided important insights for our understanding of the pathophysiology of bone involvement in… Click to show full abstract
Background The recent characterization of the canonical WNT pathway in the regulation of bone modeling and remodeling provided important insights for our understanding of the pathophysiology of bone involvement in chronic arthritis [1]. Dkk-1 and sclerostin are the main regulators of WNT/b-catenin signaling, regulating both bone formation and resorption [2]. In a previous our study we showed that in patients with Rheumatoid Arthritis (RA) Dkk-1 is significantly increased and associated with the presence of typical erosions and lower BMD [3]. Objectives we decided to perform this study in order to compare the serum levels of WNT-pathway regulators alongside bone turnover markers (BTM) and Parathyroid Hormone (PTH) between a group of female patients with PsA and healthy controls (HC) or patients with Rheumatoid Arthritis (RA). Methods this is a cross-sectional study including 18 patients with PsA classified with the CASPAR criteria, 35 HC, and 28 patients with RA classified with the ACR/EULAR 2010 criteria. Intact N-propeptide of type I collagen (PINP), C-terminal telopeptide of type I collagen (CTX-I), Dickkopf-related-protein 1 (Dkk-1), sclerostin, PTH and 25OH-Vitamin D serum levels were dosed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Results the PsA group showed significantly lower Dkk-1 levels when compared to the HC and RA groups. Dkk-1 in the RA group was also significantly higher than in the HC group. A similar trend was documented also for PTH, however a statistically significant difference was observed only when we comparing the PsA vs RA group (table 1, figure 1). No other statistically significant differences in the other markers were found.Table 1. Values of bone turnover markers (CTX-I, PINP), Dkk-1 and sclerostin of PsA, RA patients and control group (mean ± SD) PsA RA HC P (ANOVA) PINP ng/ml 42,80±16,670 39,19±21,38 42,49±11,52 NS CTX-I ng/ml 0,21±0 ,17 0,32±0,21 0,28±0,10 NS Dkk-1 pmol/l 19,45±11,30 44,51±17,81 27,29±11,48 <0,001 Sclerostin pmol/l 30,82±11,25 30,75±10,25 34,23±17,29 NS PTH pg/ml 21,12±16,63 35,83±13,02 29,69±11,43 <0,005 Conclusions this study demonstrated for the first time that Dkk-1 levels in PsA are lower than HC, in contrast with RA where they are higher. These results might contribute to explain the different bone involvement of the two different diseases. References Xie W, Zhou L, Li S, et al. Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis. Ann N Y Acad Sci 2016;1364:25–31. doi:10.1111/nyas.12968. 2 Spencer GJ, Utting JC, Etheridge SL, et al. Wnt signalling in osteoblasts regulates expression of the receptor activator of NFkappaB ligand and inhibits osteoclastogenesis in vitro. J Cell Sci 2006;119:1283–96. doi:10.1242/jcs.02883. 3 Rossini M, Viapiana O, Adami S, et al. In patients with rheumatoid arthritis, Dickkopf-1 serum levels are correlated with parathyroid hormone, bone erosions and bone mineral density. Clin Exp Rheumatol 2015;33:77–83. Disclosure of Interest None declared
               
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