Objectives: Wnt signaling pathway may be crucial in the pathogenesis of disuse-induced bone loss. Sclerostin and DKK1, antagonists of the Wnt signaling pathway, were assessed during immobilization by bed rest in young, healthy people. Methods: Two bed rest studies were conducted at the German Aerospace Center in Cologne. 14 days of 6° head-down-tilt bed rest were applied to eight healthy young male test subjects in study 1 and 21 days of head-down-tilt bed rest to seven healthy male subjects in study 2. Results: Sclerostin levels increased in both studies during bed rest (study 1, 0.64±0.05 ng/ml to 0.69±0.04 ng/ml, P=0.014; study 2, 0.42±0.04 ng/ml to 0.47±0.04 ng/ml, P=0.008) and they declined at the end of the 14- and 21-day bed rest periods. DKK1 decreased during the bed rest period in study 1 (P