Glucocorticoids-induced osteoporosis is a serious problem for patients with systemic autoimmune disease requiring relatively long-term glucocorticoid treatment. Effectiveness of alendronate for the prevention of glucocorticoids-induced osteoporosis was evaluated in comparison with that of alfacalcidol in Japanese women with autoimmune disease excluding rheumatoid arthritis. Loss of bone mass was evaluated with bone mineral density (BMD) of lumber vertebrae, bone resorption was with urinary N-telopeptide for type I collagen (NTX), and bone formation was with serum bone-specific alkaline phosphatase (B-ALP). A total of 33 patients who were treated with oral glucocorticoids (>= 5 mg/day of prednisolone equivalence) for more than 6 months were randomized into two groups; alendronate group (n = 17) received 5 mg/day of alendronate, and alfacalcidol group (n = 16) received 1.0 mu g/day of alfacalcidol for 24 months with glucocorticoids. The dose of alendronate was the maximal dose approved in Japan. BMD had tendency to decrease with alfacalcidol, while increase with alendronate. The difference in BMD change between the two groups was significant by 4.3% at 18 months and by 4.2% at 24 months (both P < 0.05). Bone resorption was significantly reduced only with alendronate; NTX was decreased by 28 to 35% at 6 to 24 months (P < 0.05), but not changed with alfacalcidol at 24 months. The bone formation was found to be unchanged according to the B-ALP measured between the two groups. In conclusion, the treatment of 5 mg alendronate daily is more effective than alfacalcidol for preventing the glucocorticoid-induced osteoporosis by the mechanism of reducing bone resorption in Japanese women with systemic autoimmune disease.