BACKGROUND: C-telopeptide and N-telopeptide cross-linked collagen type Ⅰ (CTx and NTx, respectively) are specific biochemical bone markers that can reflect bone formation and resorption. OBJECTIVE: To analyze the association of CTx with disuse osteoporosis. METHODS: Male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into control and disuse osteoporosis groups. Right hind limbs of the rats in the disuse osteoporosis group were immobilitzed for 4 weeks by ankle-tail fixation to establish the rat model of disuse osteoporosis. Peritoneal venous blood was collected before and after modeling, and the femur was then removed to measure the serum CTx level and bone mineral density of the bilateral femurs. RESULTS AND CONCLUSION: The serum CTx level did not differ significantly between groups before modeling (P > 0.05). At 4 weeks after modeling, the serum CTx level in the disuse osteoporosis group was significantly higher than that in the control group and at baseline (P <0.01). The serum CTx level showed no significant change in the control group before and after modeling (P > 0.05). The increment of serum CTx in the disuse osteoporosis group exhibited a negative correlation with the bone mineral density of the bilateral femurs (r=0.426, P < 0.01). The bone mineral density of the right femur in the disuse osteoporosis group was significantly lower than that of the left one in the disuse osteoporosis group and the right one in the control group (P < 0.01), and there was no significant difference in the bone mineral density between left and right femurs in the control group (P > 0.05). These results imply that the model of disuse osteoporosis by ankle-tail fixation is established successfully. Disuse osteoporosis can promote the production of CTx further reducing bone mineral density; CTx is positively correlated with the degree of bone loss, so it can be used for therapeutic assessment and diagnosis of osteoporosis.