BACKGROUND : Kashin-Beck disease (KBD) is an endemic and chronic osteoarthropathy. At present, the diagnosis of KBD mainly depends on the X-ray examination and which could not reflect early damage of cartilage sensitively. So, the aim of this study was to find effective and sensitive biomarkers for early diagnosis of pediatric KBD. METHODS : A total of 122 children aged 7-15 years old from 3 villages of Qinghai Province were eligible for the study. Thirty-one, 41, and 50 children were assigned in case, internal, and external control groups, respectively. The levels of CTX-II, C2C, and PYD in urine were measured by using ELISA and compared statistically. In addition, the receiver operating characteristic curve (ROC) analysis was used to assess the performance of diagnostic biomarkers. RESULTS : There were significant differences in levels of CTX-II, C2C, and PYD in urine of subjects among three groups. The levels of CTX-II and PYD in the case group were significantly higher than those in external and internal control groups. On the contrary, the level of C2C in the case group was lower than that in the external control group. Compared to the external control group, the area under the curve (AUC) of CTX-II, C2C, and PYD were 0.857, 0.837, and 0.79, and the AUC of CTX-II significantly higher than that of PYD. Compared to the internal control group, the AUC of CTX-II, C2C, and PYD were 0.911, 0.875, and 0.839, and there were no significant differences in the AUC among three indicators. CONCLUSIONS : Both CTX-II and PYD in urine could be used as biomarkers for early diagnosis of pediatric KBD, and the prediction accuracy of CTX-II was relatively superior.