ObjectivesTo evaluate a novel calcium-only imaging technique (VCa) with subtracted bone marrow in osteoporosis in dual-layer CT (DLCT) compared to conventional CT images (CI) and dual-energy X-ray absorptiometry (DXA). Material and methodsImages of a multi-energy CT phantom with calcium inserts, quantitative CT calibration phantom, and of 55 patients (mean age: 64.6 ± 11.5 years) were acquired on a DLCT to evaluate bone mineral density (BMD). CI, calcium-suppressed images, and VCa were calculated. For investigating the association of VCa and CI with DXA a subsample of 30 patients (<90 days between DXA and CT) was used. Multiple regression analysis was performed to identify further factors improving the prediction of DXA BMD. ResultsThe calcium concentrations of the CT phantom inserts were significantly associated with CT numbers from VCa (R2 = 0.94) and from CI (R2 = 0.89–0.92). VCa showed significantly higher CT numbers than CI in the phantom (p ≤ 0.001) and clinical setting (p < 0.001). CT numbers from VCa were significantly associated with CI (R2 = 0.95, p < 0.001) and with DXA (R2 = 0.31, p = 0.007), whereas no significant association between DXA and CI was found. Prediction of DXA BMD based on CT numbers derived from VCa yielded R2 = 0.76 in multiple regression analysis. ROC for the differentiation of normal from pathologic BMD in VCa yielded an AUC of 0.7, and a cut-off value of 126HU (sensitivity: 0.90; specificity: 0.47). ConclusionVCa images showed better agreement with DXA and known calcium concentrations than CI, and could be used to estimate BMD. A VCa cut-off of 126HU could be used to identify abnormal bone mineral density.