We studied the differences of therapeutic effects on regional bone mineral density (BMD) and markers of bone mineral metabolism between alendronate and alfacalcidol in Japanese osteoporotic women. Ninety-two Japanese women suffering from primary osteoporosis without osteoporotic fractures, aged 55 to 81 years, were divided into two groups: women treated orally with alendronate for one-year (5mg/day) (alendronate group, n=35) and women treated orally with alfacalcidol for one year (0.5 microg/day) (alfacalcidol group, n=57). The mean BMD of the 2nd to 4th lumbar vertebrae (L2-4BMD) and regional BMD were measured using dual energy X-ray absorptiometry. In the alendronate group, the percentage changes of L2-4BMD, lumbar spine BMD, thoracic spine BMD, pelvis BMD in the alendronate group were 106.3+/-4.6%, 104.2+/-6.6%, 107.1+/-10.4%, 107.1+/-10.5%, respectively. The percentage changes of L2-4BMD and regional BMD except for head BMD in the alendronate group were significantly greater than those in the alfacalcidol group. In the alfacalcidol group, L2-4BMD, thoracic spine BMD and lumbar spine BMD were maintained at respective pretreatment levels, whereas other regional BMD were decreased. Both serum bone-specific alkaline phosphatase and urinary type I collagen cross-linked N-telopeptide of the alendronate group were decreased, whereas these markers of bone mineral metabolism of alfacalcidol group were increased compared with the respective pre-treatment levels. The results suggest that one-year treatment with alendronate increased L2-4BMD, lumbar spine BMD, thoracic spine BMD and pelvis BMD, and that markers of both bone formation and bone resorption were decreased following one-year treatment with alendronate.