Objective To explore the predictive efficiency of serum Dickkopf-1 protein （DKK-1） and C1q tumor necrosis factor-related protein 3 （CTRP3） levels for thoracolumbar fractures in patients with osteoporosis （OP）. Methods Between January 2020 and August 2024， 124 OP patients treated at the hospital were recruited into the OP group. Based on the occurrence of thoracolumbar fractures， these OP patients were divided into a non-fracture group （n = 70） and a fracture group （n = 54）. Additionally， 124 healthy individuals who underwent physical examinations served as the control group. The enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of serum DKK-1 and CTRP3. Multivariate logistic regression analysis was utilized to analyze the influencing factors of thoracolumbar fractures in OP patients. Receiver operating characteristic （ROC） curves were used to evaluate the predictive value of serum DKK-1 and CTRP3 for thoracolumbar fractures in OP patients. Results In comparison with the control group， the serum level of DKK-1 was significantly higher， while the serum level of CTRP3 was significantly lower in the OP group （P < 0.05）. When compared with the non-fracture group， the fracture group exhibited prominently higher serum DKK-1 levels， age， duration of OP， and proportion of OP grade Ⅲ， whereas the serum CTRP3 level was significantly lower （P < 0.05）. High expression of DKK-1 was identified as an independent risk factor for thoracolumbar fractures in patients with osteoporosis， while high expression of CTRP3 was found to be an independent protective factor for thoracolumbar fractures in such patients （P < 0.05）. The area under the curve （AUC） values of serum DKK-1 and CTRP3 levels for predicting thoracolumbar fractures in OP patients were 0.790 and 0.753， respectively. The AUC of the combined prediction of the two was 0.888， which was superior to the individual predictions of either one （ZDKK-1 - combined = 3.351， ZCTRP3 - combined = 3.172， both P < 0.05）. Conclusions In the serum of OP patients， the expression of DKK-1 is upregulated， while the expression of CTRP3 is downregulated. Both are factors influencing the occurrence of thoracolumbar fractures in OP patients. The combination of the two has a high predictive value for the occurrence of thoracolumbar fractures in OP patients.