The predictive ability of a QCT-FE model of the proximal femoral stiffness under multiple load cases is strongly influenced by experimental uncertainties.

Despite significant improvements in terms of the predictive ability of Quantitative Computed Tomography based Finite Element (QCT-FE) models in estimating femoral strength (fracture load and stiffness), no substantial clinical adoption of this method has taken place to date. Narrowing the wide variability of FE results by standardizing the methodology and validation protocols, as well as reducing the uncertainties in the FEA process have been proposed as routes towards improved reliability. The aim of this study was to: First, validate a QCT-FE model of proximal femoral stiffness in multiple stance load cases, and second, using a parametric approach, determine the influence of select experimental and modeling parameters on the predictive ability of our model. Ten fresh frozen human femoral samples were tested in neutral stance, 15° adducted and 15° abducted load cases. Voxel-based linear-elastic QCT-FE models of the samples were generated to predict the models' stiffness values in all load cases. The base FE models were validated against the experimental results using linear regression. Thirty six deviated models were created using the minimum and maximum values of experiment-based "plausible range" for 18 parameters in 4 categories of embedding, loading, material, and segmentation. The predictive ability of the models were compared in terms of the coefficient of determination (R) of the linear regression between the measured and predicted stiffness values in all load cases. Our model was capable of capturing 90% of the variation in the experimental stiffness of the samples in neutral stance position (R = 0.9, concordance correlation coefficient (CCC) = 0.93, percent root mean squared error (RMSE%) = 8.4%, slope and intercept not significantly different from unity and zero, respectively). Embedding and loading categories strongly affected the predictive ability of the models with an average percent difference in R of 4.36% ± 2.77 and 2.96% ± 1.69 for the stance-neutral load case, respectively. The performance of the models were significantly different in adducted and abducted load cases with their R dropping to 71% and 70%, respectively. Similarly, off-axes load cases were affected by the parameters differently compared to the neutral load case, with the loading parameter category imposing more than 10% difference on their R, larger than all other categories. We also showed that automatically selecting the best performing plausible value for each parameter and each sample would result in a perfectly linear correlation (R> 0.99) between the "tuned" model's predicted stiffness and experimental results. Based on our results, high sensitivity of the model performance to experimental parameters requires extra diligence in modeling the embedding geometry and the loading angles since these sources of uncertainty could dwarf the effects of material modeling and image processing parameters. The results of this study could help in improving the robustness of the QCT-FE models of proximal femur by limiting the uncertainties in the experimental and modeling steps.