Immobilization induces abnormal bone metabolism and rapid decalcification. Measurements of bone mineral content disclosed rapid decalcification, especially in lumbar vertebral and metacarpal bones in our short-term 20-day bed rest study. Many factors could contribute to the marked demineralization. The activities of osteoclasts and osteoblasts were studied by following serum levels of tartrate-resistant acid phosphatase and alkaline phosphatase, biomarkers for osteocyte activity. There were no alterations in these enzymes during bed rest. However, urinary excretion of pyridinium cross-links, resorption markers of bone matrix itself, increased by day 10 with subsequent decrease at day 20. So decalcification was induced without any relation to osteoclast activity. As cytokines strongly modulate the function of osteoclasts, peripheral monocyte release of interleukin 1 alpha and tumor necrosis factor alpha were assayed to determine the contribution to this rapid demineralization. Cytokines were released transiently by day 7 and later rapidly decreased. However, there was no correlation between cytokine release and bone matrix resorption.