Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover

The aim of this study was to analyse the effect of glucocorticoid therapy (GCCT) on Wnt signalling antagonists (sderostin and Dkk-1) and their relationship with bone turnover. 25 patients (8 M/17 F, aged 48 +/- 19 yrs) recently initiating GCCT (>= 7.5 mg/day, <= 6 months) were prospectively included. Bone turnover markers (bone formation: P1NP, osteocalcin [OC], bone ALP; bone resorption: sCTx) and Wnt antagonists (serum sclerostin and Dkk-1) were assessed in all patients (short-term and 12 months after initiating GCCT). Bone mineral density (BMD) was performed to assess osteoporosis. The results were compared with 60 healthy controls. At short-term patients on GCCT showed a significant decrease in bone formation markers versus controls (P1NP: 19 +/- 9 vs. 43 16 ng/mL, p < 0.001; OC: 7.4 +/- 2.4 vs. 18.4 +/- 5.2 ng/mL, p = 0.001) and in Dkk-1 levels (24.5 +/- 20.1 vs. 36.8 +/- 13.7 pmol/L, p = 0.008) with similar sclerostin values (41.8 +/- 21.8 vs. 42.1 +/- 13.9 pmol/L, p = 0.950). Sderostin correlated positively with GCCT doses (r = 0.449, p = 0.024) and lumbar BMD (r = 0.424, p = 0.035), and negatively with bone ALP (r = -0398, p = 0.049). A progressive decrease in Dkk-1 levels was observed at 12 months, (19.1 +/- 14.9, p = 0.001), whereas sclerostin increased compared to controls (48.9 +/- 11.6, p = 0.045). In conclusion, the effect of GCCT on the serum levels of the Wnt signalling parameters differs depending on the antagonist evaluated. Whereas sclerostin values increased and showed a relationship with the dose and bone AP, Dkk-1 levels decreased throughout the study suggesting a counter-regulatory mechanism of this factor thereby reducing the deleterious effect of GCCT in the bone. (C) 2013 Elsevier Inc. All rights reserved.