Predicting Distal Femur Bone Strength in a Murine Model of Tumor Osteolysis

Abstract

Predicting pathologic fractures of long bones caused by metastatic disease continues to be a challenging clinical problem. We assessed the ability of noninvasive imaging and computational techniques to predict the strength of bones with osteolytic lesions. A murine model of induced tumor osteolysis to the distal femur was used as a model system resulting in a wide range of lesion sizes. Microcomputed tomography scans were obtained and specimen-specific, voxel-based, finite element analyses were performed and results were compared with direct measurement of biomechanical strength via axial compressive loading of the distal femur. Additional indirect surrogates of bone strength included dual-energy xray absorptiometry to determine bone mineral density, radiographic scoring, and computed tomography volume/ mineral estimates. Predicted bone strength was weakest (r 2 = 0.55) for the dual-energy xray absorptiometry measure and strongest (r 2 = 0.91) for the direct computed tomography voxel-based, finite element analysis. The relative success of the voxel-based, finite element modeling approach to estimate bone strength in a murine osteolytic tumor model indicates this approach, with further development and validation, could serve as a way to nondestructively estimate bone strength in a clinical setting.

CT-based Structural Rigidity Analysis Is More Accurate Than Mirels Scoring for Fracture Prediction in Metastatic Femoral Lesions

“…Other studies suggest Mirels is less predictive than other criteria but agree that a more specific predictor accounting for comorbidities and prognosis is needed [10,29]. Although finite element modeling has been used successfully for accurate fracture risk prediction in the laboratory, it has yet to be applied in human subjects and suffers from the potential to be a cumbersome, slow means of evaluation for individual patients in real time [18,22].…”

Local irradiation alters bone morphology and increases bone fragility in a mouse model

“…Axial compression tests of the distal femur (Mann et al, 2008) were performed to failure in displacement control (0.5 mm/min) at room temperature on all specimens using a mechanical test frame (Q-Test, MTS Corporation, Eden Prairie, MN). This test configuration was chosen as it loads all elements of the distal femur (epiphyseal, metaphyseal, and diaphyseal bone) with the same magnitude of load.…”

“…The distal 5 mm of each femur was meshed with 8-noded hexahedral elements (36 mm voxels) resulting in meshes numbering between 250,000 and 300,000 elements. The elements were assigned elastic modulus on an element-by-element basis using hydroxyapatite (HA) mineral equivalent densities (Mann et al, 2008). A Poisson's ratio of 0.3 was assumed.…”

Predicting mouse vertebra strength with micro-computed tomography-derived finite element analysis

“…Of the few studies comparing FEA predictions to experimental measurements of strength in rodent tissues, long bones were tested with limited examination of material definitions. [31][32][33] In effect, mFEAs of rodent bones rely on assumptions of material properties and failure criteria from the many correlation studies involving cadaveric bone from larger species.…”

“…One study fit a nonlinear equation to a compilation of E t and tissue mineral density (TMD) data acquired from different species and anatomical sites and using different modalities (for example, nanoindentation, tensile tests, scanning acoustic microscopy), 28 whereas another developed a linear scaling factor to determine tissue modulus from TMD based on the ratio of whole bone stiffness (determined experimentally by threepoint bending of a mouse femur) to the predicted stiffness derived from a mFEA of the same bone under similar boundary conditions. 31 In addition to the uncertainty regarding material behavior assumptions and directional dependence of rodent bone, failure criteria used in mFEA have also not been rigorously tested.…”