Background Inflammation, glucocorticoid use and functional disability are major contributors to bone loss or fragility in patient with rheumatoid arthritis (RA).The serum proteins sclerostin and Dickkopf-1(dkk-1) inhibits bone formation by suppression of Wnt-β-catenin signaling. Recently it is reported that the serum levels of sclerostin and dkk-1 increase in patient with RA (1-3) and TNF-alpha contribute to their increase (2,4), however, other possible contributors to the increase in these two Wnt antagonists, such as glucocorticoid use, functional disability or clinically evaluated inflammation level remains to be elucidated.
Objectives The present clinical study aimed to investigate the association between serum level of sclerostin and dkk-1 with inflammatory marker, daily glucocorticoid dose and functional class in patients with RA.
Methods Ambulatory female RA patients (n=83) with normal renal function (inclusion criteria Cre≤1.0) enrolled in this cross-sectional study. Mean age was 62.5±12.6 (average ± SD) years old. Level of sclerostin and dkk-1 were measured using a commercially available ELISA (Biomedica, Vienna, Austria, and R&D Systems, Mineapolis, MN, respectively). Correlation with serum sclerostin or dkk-1 levels and inflammatory markers, such as CRP, MMP3, RF, Hb, WBC, age, anthropometric factor, Steinblocker’s functional class and daily dose of prednisolone was analyzed using PASW statistics 18 (SPSS An IBM COMPANY, Illinois USA).
Results Mean serum level of sclerostin was 36.8±18.4 (average ± SD) ranged from 5.0 to 119.0 pmol/L and dkk-1 was 3084±970 ranged from 1130 to 6490 pg/mL. Daily dose of prednisolone was 2.98±3.28 ranged from 0 to 13.0 mg. There was no correlation between serum level of sclerostin and dkk-1. Both Wnt antagonists were not correlated with any of age, body weight and height. Serum sclerostin level was negatively correlated with CRP (Spearman’s correlation coefficient and p-value, -0.289, 0.009) and positively correlated with Hb (0.221, 0.047), while it was not correlated with MMP-3 and RF. The daily dose of prednisolone was negatively correlated with the sclerostin level (-0.275, 0.024). On the other hand, serum level of dkk-1 was positively correlated with WBC count (0.320, 0.003) but not with CRP, MMP-3, RF, Hb and daily dose of prednisolone. There was no difference in sclerostin and dkk-1 level between functional class 1 and 2.
Conclusions Although two Wnt antagonist sclerostin and dkk-1 could contribute to bone loss in patients with RA, discrete association of them with inflammation markers and prednisolone dose was revealed. Serum level of sclerostin was negatively correlated with CRP and daily dose of prednisolone, whereas dkk-1 level was positively correlated with WBC count. These data suggested the different role of these two Wnt antagonists in pathogenesis of bone loss occurred in patients with RA.
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Disclosure of Interest None Declared