Objective: To investigate of the Wnt pathway serum regulator expression levels and their relationship with bone metabolism (BM) in thoracolumbar osteoporotic vertebral compression fracture (OVCF) patients. Methods: In this study, 40 healthy controls (group A), 33 osteoporotic patients (group B), and 47 thoracolumbar OVCF patients (group C) were recruited as the study cohort during the same period. The Wnt pathway serum regulator levels, bone density, BM-related inflammatory cytokines, bone formation markers, and bone resorption markers were compared among the three groups, and the correlation between the Wnt pathway serum regulators and BM was analyzed. Results: The beta-catenin levels, the BALP, the densities at the femoral neck and lumbar spine, and the PINP, IL-10, OPG and BGP in groups B and C were lower than they were in group A, and the above indices in group C were lower than they were in group B (P < 0.05). Groups B and C showed higher CDKK-1, RANKL, TRACP-5b, 6-CTX, IL-2, IL-6, MMP-2, MMP-9, Leptin, and TNF-alpha levels than group A, and the above indicators in group C were higher than they were in group B (P < 0.05). A Pearson's correlation analysis showed that the MMP-2, MMP-9, RANKL, beta-CTX, and TRACP-5b levels were negatively correlated with 6-catenin (r < 0, P < 0.05) and were positively correlated with DKK1 (r > 0, P < 0.05). The BGP, PINP, OPG, and BALP levels were positively correlated with beta-catenin (r > 0, P < 0.05) and were negatively correlated with DKK-1 (r < 0, P < 0.05). Conclusion: Patients with thoracolumbar OVCF have abnormal Wnt pathway serum regulator expression levels, low bone density, and abnormal BM, and the patients' Wnt/beta-catenin and DKK-1 levels are closely related to BM, so they may be potential targets for the prevention and treatment of metabolic bone diseases.