Total knee arthroplasty (TKA) leads to a loss of periprosthetic bone mineral density (BMD). Great importance is attached to the prevention of periprosthetic bone loss with a view to ensuring a long service life of the prosthesis. In order to provide appropriate recommendations for preventive movement therapy measures to combat peri-implant bone loss, it is necessary to know the predictors of periprosthetic BMD. The aim of this study was (1) to determine the change of periprosthetic BMD of the femur and tibia and (2) to analyse the effects of different predictors on periprosthetic BMD. Twenty-three patients with primary TKA were evaluated 10 days and 3 months postoperatively. The data analysis comprised (1) the change in periprosthetic BMD from pretest to posttest and (2) the correlations between BMD and the variables isometric maximum voluntary force, lean mass, physical activity (step count), and BMI using multiple linear regression and structural equation modelling (SEM). BMD of the distal femur was significantly reduced by 19.7% (P = 0.008) 3 months after surgery, while no changes were found in BMD of the tibia. The results of SEM demonstrate that 55% of the BMD variance was explained by the model (χ(2) = 0.002; df = 1; P = 0.96; χ(2)/df = 0.002; RMSEA < 0.01; TLI = 1.5; CFI = 1.0). A significant direct effect was only evidenced by the variable lean mass (β = 0.38; b = 0.15; SE = 0.07; C.R. = 2.0; P = 0.046). It can be assumed that a large muscle mass with accompanying distribution of high mechanical load in the bones can contribute to local changes of periprosthetic BMD. Concrete recommendations for preventing peri-implant bone loss therefore include exercises which have the aim of maintaining or building up muscle mass.