A recent large-scale study revealed that glucocorticoid treatment increased fracture risk, which occurred at a far smaller dose and by a shorter duration than previously thought. To study the underlying mechanism for the increased risk of fracture, we studied the early changes in bone mineral density (BMD) and body composition by dual energy X-ray absorptiometry (DXA) after initiating high-dose glucocorticoid treatment. High-dose glucocorticoid treatment was arbitrarily defined as daily doses of >or=40 mg of a predonisolone equivalent. The 33 patients enrolled in this study had not received glucocorticoid treatment before. Only 2 months of treatment resulted in substantial BMD loss, most markedly in the lumbar spine, followed by the femoral neck and total body, which suggests the preferential trabecular bone loss. Body composition was also greatly affected. Thus, 2-month treatment with glucocorticoid significantly reduced bone mineral content (BMC), lean body mass (LBM) and increased fat mass (FAT). Our results are likely to have some clinical relevance. First, BMD loss occurs quite rapidly after starting glucocorticoid treatment, and patients receiving glucocorticoid treatment should be more carefully monitored for their BMD. Second, LBM, which mainly represents muscle volume, decreases rapidly after initiating glucocorticoid treatment. Decreased LBM might be also responsible for the increased risk of fracture, since falling is a well-known risk factor for fracture, and patients receiving glucocorticoid treatment should also be evaluated for their body composition.