The purpose of the present study was to evaluate the clinical usefulness of urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in predicting therapeutic effects of estrogen and alfacalcidol (1alpha-D3) in patients with postmenopausal osteoporosis. We measured urinary excretion of Pyr and Dpyr, and determined bone mineral density (BMD) using a dual-energy x-ray absorptiometry in 48 women with osteoporosis (average age, 55.9+/-8.4 years). Patients were treated with estrogen (HRT, n = 13), 1alpha-D3 (n = 20), or calcium alone (n = 15). Baseline mean levels of urinary Pyr and Dpyr were significantly higher in the 48 patients compared to those in the age-matched postmenopausal women. The levels of urinary Pyr and Dpyr were inversely correlated with BMD. After treatment with estrogen or 1alpha-D3, a significant decrease of urinary Pyr and Dpyr was observed, and elevated urinary Pyr and Dpyr were reduced to the level in premenopausal women. A significant inverse correlation was found in Pyr and Dpyr at 6 months and in lumbar BMD after 24 months of treatment (r = -0.43 to -0.52; P < 0.01). We concluded that urinary Pyr and Dpyr have clinical utility for predicting response to estrogen and 1alpha-D3 therapy of osteoporosis patients.