We have evaluated the effect of aging, menopause and osteoporosis on the measurements of both nonisomerized type I collagen C-telopeptide breakdown products (alpha-CTx) by radioimmunoassay (RIA) and beta-isomerized type I collagen C-telopeptide breakdown products (beta-CTx) by enzyme-linked immunosorbent assay (ELISA). In 86 premenopausal healthy women (PRE), 144 postmenopausal healthy women (POST), 74 patients with vertebral fractures (VX) and 61 patients with hip fractures (HX), urinary CTx excretion was measured by both ELISA and RIA assays. Samples were collected more than 6 months after fracture in the VX group and within 48 h after fracture in the HX group. In all subjects a highly significant correlation was found between alpha-CTx and beta-CTx (r = 0.85). The values of beta-CTx in the POST group greatly increased compared with those in the PRE group (% mean increase: 82%), while the values of alpha-CTx in the POST group moderately increased compared with those in the PRE group (% mean increase: 47%). The values of both alpha-CTx and beta-CTx in the HX group were significantly higher than those in the other groups, but particularly the increase in mean alpha-CTx (211% for HX versus POST) was very high compared with the increase in mean beta-CTx (68% for HX versus POST). Moreover, the alpha-CTx/beta-CTx ratio in the HX group was significantly higher than in the other groups. These results suggest that both assays well reflect the increase in bone resorption associated with high bone turnover, especially, in osteoporotic patients with hip fracture. However, there was a difference between the urinary excretion of alpha-CTx and beta-CTx in patients with hip fracture, so the alpha-CTx/beta-CTx radio might be a good indicator reflecting the characteristics of bone metabolism for osteoporosis with hip fracture.