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Objectives In this prospective cohort study, we investigated whether patient-specific finite element (FE) models can identify patients at risk of a pathological femoral fracture resulting from metastatic bone disease, and compared these FE predictions with clinical assessments by experienced clinicians.Methods A total of 39 patients with non-fractured femoral metastatic lesions who were irradiated for pain were included from three radiotherapy institutes. During follow-up, nine pathological fractures occurred in seven patients. Quantitative CT-based FE models were generated for all patients. Femoral failure load was calculated and compared between the fractured and non-fractured femurs. Due to inter-scanner differences, patients were analyzed separatelyfor the three institutes. In addition, the FE-based predictions were compared with fracture risk assessments by experienced clinicians.Results In institute 1, median failure load was significantly lower for patients who sustained a fracture than for patients with no fractures. In institutes 2 and 3, the number of patients with a fracture was too low to make a clear distinction. Fracture locations were well predicted by the FE model when compared with post-fracture radiographs. The FE model was more accurate in identifying patients with a high fracture risk compared with experienced clinicians, with a sensitivity of 89% versus 0% to 33% for clinical assessments. Specificity was 79% for the FE models versus 84% to 95% for clinical assessments.Conclusion FE models can be a valuable tool to improve clinical fracture risk predictions in metastatic bone disease. Future work in a larger patient population should confirm the higher predictive power of FE models compared with current clinical guidelines.

Introduction: Tibial slope was shown to majorly affect the outcomes of Total Knee Arthroplasty (TKA). More slope of the tibial component could help releasing a too tight flexion gap in cruciate-retaining (CR) TKA and is generally associated with a wider range of post-operative knee flexion. However, an excessive tibial slope could jeopardize the knee stability in flexion. The mechanism by which tibial slope affects the function of CR-TKA is not well understood. Moreover, it is not known whether the tibial bone resection should be performed by referencing the anterior cortex (AC) of the tibia or the center of the tibial plateau (CP) and whether the choice of either technique plays a role. The aim of this study was to investigate the effect of tibial slope on the position of tibiofemoral (TF) contact point, knee ligament forces, quadriceps muscle forces, and TF and patellofemoral (PF) joint contact forces during squat activity in CR-TKA. Methods: A previously validated musculoskeletal model of CR-TKA was used to simulate a squat activity performed by a 86-year-old male subject wearing an instrumented prosthesis [1,2]. Marker data over four consecutive repetitions of a squat motion were tracked using a motion optimization algorithm. Muscle and joint forces and moments were calculated from an inverse-dynamic analysis, coupled with Force-Dependent Kinematics (FDK) to solve knee kinematics, ligament and contact forces simultaneously. The tibial slope in the postoperative case was 0 degree and constituted the reference case for our simulations. In addition, eight additional cases were simulated with −3, +3, +6, +9 degrees of tibial slope, four of them simulating an AC referencing technique and four a CP technique. Results: Compared to the reference case with no added slope, the total excursion of the tibiofemoral contact point increased on both medial and lateral side when more slope was added using the AC referencing technique, and decreased with negative slope. The total excursion of the contact point remained about unchanged when using the CP technique but the contact point shifted of about 1 mm more posteriorly, on the lateral side, and 0.7 mm, on the medial side, on average. In both AC and CP techniques the quadriceps forces, TF and PF contact forces decreased with more slope, but the PF contact forces were more drastically reduced using CP, with 3.5% less force every 3 degrees of added slope in flexion, on average. Medial and lateral collateral ligament became slack in flexion already with +6 degrees of slope when AC technique was used, whereas they always maintained some residual tension using the CP technique even at the highest slope. Discussion and conclusion: Increasing the tibial slope affected substantially the knee function during squatting and the effects differed depending on the referencing technique. The CP referencing helps preserving the flexion gap and knee stability in flexion, by mantaining tension in both collateral ligaments. It also reduces the quadriceps forces and relieves the PF joint contact forces, which could potentially decrease pain in patients with a TKA and achieve a wider range of knee motion.

INTRODUCTION: Simultaneous prediction of body-level dynamics and detailed joint mechanics in the frame of musculoskeletal (MS) modeling represents still a highly computationally demanding task. Marra et al. (2014) recently presented and validated a MS model capable of concurrent prediction of muscle forces, knee ligament forces, tibiofemoral (TF) and patellofemoral (PF) contact forces in a MS model of Total Knee Arthroplasty (TKA) [1]. Simulation time for one complete gait cycle was in the order of 3 hours, and the iterative process that solved the equilibrium in the knee joint was thought to be the main source of overhead. Surrogate modeling techniques were suggested [2]. In this study, we develop a surrogate contact model of TKA to decrease the simulation time in the MS simulation. We hypothesize that the algorithm that allows the muscle fibers to wrap around the bones constitutes another source of overhead in the MS model. Therefore, we will also evaluate the performances of the surrogate model with and without muscle wrapping. METHODS: The original tibial component from our TKA model [1] was split in a medial and lateral hemi-part and fixed to the ground, whereas the femoral part was left with 6 degrees of freedom (DOF). The contacting pairs exchanged three forces and three moments, which were assumed functions of the relative pose only. Translations (X, Y, Z) were defined relative to the tibial component frame and rotations of the femoral component (RotX, RotY, RotZ) were described with Cardan angles, using the z-y-x rotation sequence. Similarly to Lin et al (2010) [3] we identified two sensitive directions, Y and RotX and, therefore, we defined a sample point as composed by four pose parameters and the two loads in the sensitive directions: X, Fy, Z, Tx, RotY, RotZ. Reference load-pose data were obtained from four simulations of gait, squat, chair-rise, and right-turn trials using the original contact model. The design space was populated using the Hammersley quasi-random sequence and adopting a multi-domain approach, as proposed by Eskinazi and Fregly (2015) [2]. One domain consisted of 20 data points per each frame of the four dynamic simulations, spanning the boundaries of ± 1 standard deviation from the time-varying reference envelopes. A second domain of 2500 points was generated in the principal component space of the reference load-pose data of each dynamic simulation, with boundaries enlarged by 50%. A third domain of 1000 data points represented one-side-contact situations, in which Tx was bounded to ± 4 Nm. In total, 36000 data points were sampled in the three different domains. Data points were evaluated using the original contact model (Fig. 1) by repeated Force-Dependent Kinematics (FDK) analyses. Data points which did not lead to equilibrium were discarded. The remaining 27620 points were randomly subdivided into a training (70%) and testing (30%) group. Three separate Feed-Forward Artificial Neural Networks (FFANN), consisting of four inner layers of 20 hyperbolic tangent sigmoid neurons each, were configured within the Neural Network Toolbox in MATLAB 8.1 (The MathWorks Inc., Natick, MA, 2013). The first network was trained to learn the relationships between the four –two medial and two lateral– sensitive loads (output) and the six pose parameters (input). Two other networks –one medial and one lateral– were trained separately to learn the relationships between the remaining loads of each side (output) and all the pose parameters plus the two sensitive loads from each side (input). We used the popular Levenberg-Marquardt training algorithm in conjunction with Bayesian regularization to avoid over-fitting. Stopping criterion was a training time of two hours for each network. The trained networks were translated to custom C++ DLL functions for successive inclusion in our MS model. The surrogate contact model replaced the original contact model and one gait trial was simulated with 4 different combination of the following model settings: original versus surrogate contact model, wrapping enabled versus disabled. RESULTS: The contact sampling model required 238 hours to evaluate the 36000 data points. Predicted tibiofemoral compressive forces under all simulated cases are shown in Fig. 2. A comparison with experimental measurements (eTibia line) is also shown. Surrogate model predictions showed a very good agreement with the original model counterparts. Fig. 3 summarizes the computation times: simulations took the longest when muscle wrapping was enabled and the benefits of using the surrogate model became evident only when the wrapping algorithm was switched off, leading to a 6x speed-up. Simulation time with the original contact model decreased by a factor of 8 by switching off the wrapping algorithm. DISCUSSION: The use of FFANN-based surrogate contact model, in place of the original rigid contact model, could substantially reduce the simulation time of a full gait cycle down to 3 minutes, when the wrapping algorithm was turned off. Such improvement could not be achieved when using the wrapping algorithm. This enlightens another important source of overhead in MS modeling –the muscle wrapping algorithm– which unexpectedly was found to dominate the simulation time. At each FDK iteration, the wrapping algorithm needs to be solved as well, introducing overhead. If the wrapping algorithm is slower than the contact algorithm, then the computation time of each step will be dominated by the former, leaving only a small fraction to be gained from the latter. SIGNIFICANCE: We showed that surrogate contact model could reduce the simulation time in a MS model of TKA down to a level which allows parametric studies and/or optimization to be feasible. We also discovered that the muscle wrapping algorithm constituted an unexpectedly large source of overhead during dynamic simulations. These represent new and important findings for the MS modeling community. REFERENCES: [1] M. A. Marra, V. Vanheule, R. Fluit, B. H. F. J. M. Koopman, J. Rasmussen, N. J. J. Verdonschot, and M. S. Andersen, “A Subject-Specific Musculoskeletal Modeling Framework to Predict in Vivo Mechanics of Total Knee Arthroplasty.,” J. Biomech. Eng., Nov. 2014. [2] I. Eskinazi and B. J. Fregly, “Surrogate modeling of deformable joint contact using artificial neural networks.,” Med. Eng. Phys., Jul. 2015. [3] Y.-C. Lin, R. T. Haftka, N. V Queipo, and B. J. Fregly, “Surrogate articular contact models for computationally efficient multibody dynamic simulations.,” Med. Eng. Phys., vol. 32, no. 6, pp. 584–94, Jul. 2010. ACKNOWLEDGEMENTS: This study was conducted within the ERC ‘BioMechTools’ project, funded by the European Research Council.

Introduction Clinical fracture risk assessment in metastatic bone disease is extremely difficult, but subject-specific finite element (FE) modelling may improve these assessments in the future [Derikx, 2015]. By coupling to musculoskeletal modelling, realistic loading conditions can be implemented in FE analysis. However, it is unknown whether such analyses require complex elastic-plastic material models, or whether a linear elastic calculation already provides a reasonable prediction of fracture. Moreover, plastic deformation may accumulate over time, which is ignored by linear elastic calculations. In this study we compared linear and non-linear fracture predictions under realistic loading conditions in two patients with metastatic bone disease. Methods Two patients (P1, P2) with lytic lesions were included. Patient-specific femoral geometry and bone density were retrieved from quantitative CT-scans; the latter was used for implementing element-specific material behaviour [Keyak, 2005]. Muscle forces and hip contact forces acting on the femur during walking were calculated using musculoskeletal modelling (one typical case, adapted from [Wesseling, 2014]), and subsequently normalized to the patient’s body weight. Muscle forces were applied to attachment points that were morphed onto the patient femurs. Hip contact forces were applied to a cup mimicking the acetabulum, via a control node in the hip joint centre. Two simulations were run for each patient: a linear elastic analysis simulating a single walk cycle and a non-linear elastic-plastic analysis simulating 10 subsequent walk cycles. The safety factor (SF; yield stress/Von Mises stress) and plasticity were studied as measures of femoral failure in the linear and non-linear simulations, respectively, and compared between patients. Results The volume of elements with SF

There is continued interest in the maintenance and functional response of the cement-bone interface to loads that act across the interface. Recent experimental work has found that the interface is quite compliant (~10 microns/MPa) with sliding and opening occurring from shear and tensile loading conditions, respectively. In addition, this interface becomes more compliant following in vivo service (~50 microns/MPa). The question remains as to whether this micromotion is loading angle dependent. To address this question we performed multiloading angle experiments on cement-bone interface specimens. We asked three research questions: (1) does interface compliance depend on loading angle?, (2) are there appreciable coupled transverse motions?, and (3) can interface compliance be explained by contact fraction between cement and bone and source of bone (lab prepared or postmortem retrieval)?

Fatigue failure of the cement mantle in terms of cement cracking is one of the failure mechanisms that leads to aseptic loosening in cemented hip reconstructions. Recently, experiments have demonstrated that there is substantial motion at the cement-bone interface, which may compromise cemented reconstructions [1]. In Finite Element (FE) models of cemented hip reconstructions, the cement-bone interface has been implemented as (I) an infinitely stiff interface, (II) a soft tissue layer with constant stiffness, or (III) a layer of cohesive elements with a mixed-mode behavior based on experimental data on failure in tension and shear. Recently μFE-models have been utilized to study the mixed-mode behavior of the cement-bone interface in more detail [2]. It is, however, unknown whether it is necessary to include the complex mixed-mode response of the cement-bone interface in FE models of cemented hip reconstructions. The following research questions were stated: (1) What is the evaluation of cement crack formation as a result of different cement-bone interface characteristics? (2) Is cement-bone interface failure likely? (3) Does fatigue failure of the cement mantle increase or decrease the probability of failure of the cement-bone interface?

In cemented total hip arthroplasty, the implant needs a mechanically stable cement-bone interface for its survival. This can be achieved by adequate cement penetration into the bone lacunar and trabecular spaces. Many studies have been conducted to investigate the strength of the cement-bone interface in relation to the amount of cement penetration, but mainly on a macro-scale [1]. However, to gain a more detailed insight into the mechanical aspects of this geometrically complex interface, the cement-bone interface should be studied on a micro-scale. We developed micro Finite Element (FE) models of the cement-bone interface and varied the cement penetration depth. Subsequently, we loaded the FE models until failure and asked the following questions: (1) Is there a relationship between penetration depth, contact area and strength?; (2) Is the interface stronger in shear than in tension?; (3) How valid are the FE models compared to experimental findings?

Objective: Wolff’s law states that bone remodeling is driven by external loads on bone. When loads increase, bone mass will increase accordingly, making it stronger, while bone mass will decrease when loading forces are lower. This may cause problems when bone is stress shielded by rigid metal[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 74. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 96. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 51. Tagung des Berufsverbandes der Fachärzte für Orthopädie