Glucocorticoid use is the most common cause of osteoporosis in young individuals. In the current study, we investigated the effects of glucocorticoid treatment on circulating sclerostin concentrations and serum bone turnover markers in healthy young men. We performed additional measurements in two combined randomized, placeboâcontrolled, doubleâblind, doseâresponse intervention studies: 64 healthy men (age: 22âÂąâ2âyears; BMI: 22.1âÂąâ1.7âkg/m2) were allocated to receive placebo (n = 16), prednisolone 7.5âmg once daily (n = 24), or prednisolone 30âmg once daily (n = 24) for 2âweeks using block randomization. Primary outcome variables were serum sclerostin and serum bone turnover markers (CTx and P1NP), before and after the intervention. Baseline characteristics and variables did not differ between intervention groups. Compared with placebo, prednisolone highâdose decreased serum sclerostin concentrations (â8.5 [â28.0 to 7.3] versus 1.5 [â6.5 to 20.0] pg/mL, p = 0.048), decreased P1NP concentrations (â28.0 [â39.3 to â18.3] versus â1.5 [â15.3 to 11.3] Îźg/L, pâ<â0.001) and increased CTx concentrations (108.0 [55.0 to 177.0] versus 64.0 [â24.3 to 120.0] ng/L, p = 0.038). Compared with placebo, prednisolone lowâdose did not alter sclerostin concentrations (p = 0.5) or CTx concentrations (pâ= 0.7), but tended to decrease P1NP concentrations (â9.0 [â24.0 to â1.3] versus â1.5 [â15.3 to 11.3] Îźg/L, p = 0.095). At baseline concentrations of sclerostin were positively correlated with concentrations of CTx (Spearman's rank correlation coefficient Ď = +0.409, p = 0.001), but not with P1NP. No significant correlations were observed between changes in outcome variables during the interventions. Shortâterm highâdose, but not lowâdose, prednisolone treatment reduces serum sclerostin concentrations in healthy young men. Whether this reflects a counter regulatory mechanism to compensate glucocorticoidâinduced negative effects through other mechanisms remains to be elucidated. Š 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.