Loss of bone stock as a response to the bone trauma, immobilization, and stress shielding related to joint replacement surgery increases the risk of fracture of the distal femur after total knee arthroplasty. Previous studies of uncemented femoral components have reported very high levels of bone loss in the distal femur. This study investigates the adaptive bone remodeling of the distal femur after uncemented total knee arthroplasty. We performed a 2-year follow-up of 53 patients (mean age 61.5 [38–70] years, F/M = 27/26, body mass index 29.5) who because of osteoarthritis received an uncemented total knee arthroplasty. All patients received a NexGen CR-Flex Porous Femoral Component. Measurements of bone mineral density of the distal femur using dual-energy X-ray absorptiometry were performed postoperatively and after 3, 6, 12, and 24 months. Bone mineral density (g/cm2) was measured in 3 regions of interest in the periprosthetic bone of the distal femur. Repeated measures analysis of variance and Tukey post hoc test for bone mineral density changed over time (p < 0.05 were considered significant). In the distal femur, significant changes in bone mineral density were seen after 24 months of follow-up, and bone mineral density decreased by 23.6% in the anterior region behind the anterior flange of the prosthesis (p < 0.001), 10.1% in the posterior region (p < 0.001), and 5.5% in the most proximal region (p < 0.001). We found highly significant bone mineral change in the distal femur after uncemented total knee arthroplasty, most pronounced in the anterior region, where a decrease in bone mineral density of almost 25%, was seen. Taking the expected age-related decay in bone mineral density in this age group into consideration, the decrease was substantial and must be considered to predispose to periprosthetic fractures.