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Periprosthetic bone loss is an important factor in tibial implant failure mechanisms in total knee arthroplasty (TKA). The purpose of this study was to determine the effect of postoperative knee alignment and population variation on tibial bone remodeling, to assess long-term stability of a knee replacement. Strain-adaptive finite element (FE) remodeling simulations were conducted following kinematic and mechanical alignment of a cemented fixed-bearing implant after TKA; kinematic TKA alignment was assumed to be more consistent with the preoperative varus alignment, while mechanical alignment was defined according to the neutral mechanical axes. To account for the effect of tibial variation on the outcome, bone remodeling was considered over a population of 47 subjects. Bone mineral density (BMD) was analyzed over three regions of interest (ROIs); medial, lateral and distal. The two proximal ROIs showed an average decrease in BMD in both alignments after two years. Greater overall proximal bone loss was found in the mechanical postoperative knees in comparison with kinematically aligned implants. Bone resorption was also concentrated more medially in mechanical alignment: increased medial ROI bone loss was found in every subject compared to kinematic alignment; while in the lateral ROI, higher regional two-year BMD was found in 39 of the 47 cases (82.9%) following mechanical alignment. Two distinct remodeling pathways were identified over both alignments, based on the variance in density change over the population; displaying predominant bone apposition either around the distal tip of the keel or at the lateral cortex. This study demonstrates that correction of native varus alignment to neutral mechanical alignment leads to an increase in medial bone resorption. Large variation between specimens illustrates the benefit of population-based FE analyses over single model studies. [ABSTRACT FROM AUTHOR]