Background: Osteoporosis is a common complication of long-term glucocorticoid therapy for which there is no well-proved preventive or restorative treatment. Methods: We carried out two 48-week, randomized, placebo-controlled studies of two doses of alendronate in 477 men and women, 17 to 83 years of age, who were receiving glucocorticoid therapy. The primary end point was the difference in the mean percent change in lumbar-spine bone density from base line to week 48 between the groups. Secondary outcomes included changes in bone density of the hip, biochemical markers of bone turnover, and the incidence of new vertebral fractures. Results: The mean (±SE) bone density of the lumbar spine increased by 2.1±0.3 percent and 2.9±0.3 percent, respectively, in the groups that received 5 and 10 mg of alendronate per day (P<0.001) and decreased by 0.4±0.3 percent in the placebo group. The femoral-neck bone density increased by 1.2±0.4 percent and 1.0±0.4 percent in the respective alendronate groups (P<0.01) and decreased by 1.2±0.4 percent in the placebo group (P<0.01). The bone density of the trochanter and total body also increased significantly in the patients treated with alendronate. There were proportionally fewer new vertebral fractures in the alendronate groups (overall incidence, 2.3 percent) than in the placebo group (3.7 percent) (relative risk, 0.6; 95 percent confidence interval, 0.1 to 4.4). Markers of bone turnover decreased significantly in the alendronate groups (P<0.001). There were no differences in serious adverse effects among the three groups, but there was a small increase in nonserious upper gastrointestinal effects in the group receiving 10 mg of alendronate. Conclusions: Alendronate increases bone density in patients receiving glucocorticoid therapy.