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

- The effect of GCC treatment on the levels of the Wnt signalling parameters differs depending on the antagonist evaluated.
- Dkk-1 levels showed a progressive decrease after the initiation of GCC therapy, whereas sclerostin values showed a progressive increase.
- Serum sclerostin levels were correlated with the dose of GCC and bone formation markers.
- Long-term evaluation of these parameters as well as their relationship to bone turnover and bone mass evolution is recommended.

The aim of this study was to analyse the effect of glucocorticoid therapy (GCCT) on Wnt signalling antagonists (sclerostin 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). Sclerostin 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 = − 0.398, 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.