The purpose of the present study was to examine the early response of lumbar bone mineral density (BMD), bone resorption, and back pain to alendronate after treatment with cyclical etidronate in postmenopausal women with osteoporosis. Forty postmenopausal women with osteoporosis, 60-83 years of age, without any vertebral fractures in the lumbar spine, were randomly divided into two groups with 20 patients in each group: 18 months of cyclical etidronate (200mg daily for 2 weeks every 3 months) group and 12 months of cyclical etidronate followed by 6 months of alendronate (5 mg daily) group. BMD of the lumbar spine (L1-L4) measured by DXA, urinary cross-linked Nterminal telopeptides of type I collagen (NTX) level measured by enzyme-linked immunosorbent assay, and back pain evaluated by face scale score were assessed at baseline and every 6 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two groups. Cyclical etidronate significantly reduced urinary NTx level and face scale score over 12 months, but did not significantly increase lumbar BMD. After 12 months of treatment, the switch to alendronate significantly reduced urinary NTX level and face scale score, and significantly increased lumbar BMD, while continued cyclical etidronate did not significantly alter these parameters. These results suggest that switching to alendronate after treatment with cyclical etidronate produces a greater response of lumbar BMD, bone resorption, and back pain than continued cyclical etidronate in postmenopausal women with osteoporosis.