Purpose <p>This study aimed to establish a novel index, three-dimensional Hounsfield unit (3D-HU), to assess bone density, and evaluated its correlation with dual-energy X-ray absorptiometry (DXA) scores.</p> Methods <p>This study reviewed the electronic medical records of patients who underwent lumbar spine computed tomography (CT) and DXA at our hospital within one week. Patients were divided into osteoporotic and non-osteoporotic groups according to T-score. Demographics information and radiological parameters were compared. Using preoperative CT scanning of the lumbar spine, the novel 3D-HU was measured for each patient. DXA scores were obtained and were compared to 3D-HU using multivariate logistic regression analyses and Pearson correlation.</p> Results <p>This study involved 612 vertebrae from 191 patients. Among them, 134 were found to have a T-score ≤ -2.5. Multivariate analysis showed that lower 3D-HU and body mass index (BMI) were independent predictors for osteoporosis. Correlation analysis revealed that 3D-HU was highly correlated with bone mineral density (BMD) measured by DXA, and this correlation was consistently stronger than that of traditional HU. Receiver operating characteristic curve (ROC) analysis showed that 3D-HU has high accuracy, excellent sensitivity, and specificity in the diagnosis of osteoporosis.</p> Conclusions <p>This is the first study to directly correlate the novel 3D-HU with the diagnosis of osteoporosis. We identified this novel index as a significant predictor of osteoporosis, and established a strong correlation between 3D-HU and the BMD of the lumbar spine.</p>