After surgical bone tumor removal, filling of the bone defect is frequently performed using a bone graft or bone graft substitute. During follow-up, precise quantification of changes in bone mineral density, within the treated bone defect, is very difficult using conventional X-ray examinations. The objectives of this study were to characterize the pattern of resorption/biodegradation of a composite calcium sulfate/hydroxyapatite bone graft substitute and to quantify the bone defect healing with repeated dual-energy X-ray absorptiometry (DXA) measurements. Seventeen patients treated for 18 benign bone lesions, with subsequent defect filling using 2 variants of a composite ceramic bone graft substitute (CERAMENT™|BONE VOID FILLER or CERMAMENT™|G, BONESUPPORT AB, Lund, Sweden), were scanned postoperatively and after 2, 6, 12, 26, and 52 wk using DXA. After an initial increase in bone mineral density after implantation of the bone graft substitute, bone mineral density decreased in the bone defect region throughout the 52 wk: rapidly in the first 12 wk and slower in the remaining weeks. Despite this continuous decrease, bone mineral density remained, on average, 25% higher in the operated extremity, compared with the nonoperated extremity, after 52 wk. The observed pattern of reduction in bone mineral density is consistent with the anticipated resorption of calcium sulfate within the bone graft substitute during the first 12 wk after surgery. We believe the DXA technique provides a precise method for quantification of bone graft resorption, but for evaluation of new bone formation, 3-dimensional imaging is needed.