title: Effect of glucocorticoid treatment on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover.
abstract: 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±19yrs) recently initiating GCCT (≥7.5mg/day, ≤6months) 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 12months 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±16ng/mL, p<0.001; OC: 7.4±2.4 vs. 18.4±5.2ng/mL, p=0.001) and in Dkk-1 levels (24.5±20.1 vs. 36.8±13.7pmol/L, p=0.008) with similar sclerostin values (41.8±21.8 vs. 42.1±13.9pmol/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 12months, (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.
authors: Rheumatology Department, Metabolic Bone Diseases Unit, Hospital Clínic of Barcelona, Spain. Electronic address: lgifre@clinic.ub.es.
authors: L
authors: L
authors: Gifre
authors: S
authors: S
authors: Ruiz-Gaspà
authors: A
authors: A
authors: Monegal
authors: B
authors: B
authors: Nomdedeu
authors: X
authors: X
authors: Filella
authors: N
authors: N
authors: Guañabens
authors: P
authors: P
authors: Peris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D005260:Female; D005819:Genetic Markers; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D011446:Prospective Studies; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human
keywords: BMD; BMI; Dickkopf; Dkk-1; GCC; GCCT; Glucocorticoid; OC; P1NP; SD; Sclerostin; Wnt antagonists; body mass index; bone ALP; bone alkaline phosphatase; bone mineral density; glucocorticoid; glucocorticoid therapy; osteocalcin; propeptide amino-terminal of type I procollagen; sCTX; serum carboxy-terminal telopeptide of type I collagen; standard deviation of the mean