Continuum-level finite element (FE) models became standard computational tools for the evaluation of bone mechanical behavior from in vivo computed tomography scans. Such scans do not account for the anisotropy of the bone. Instead, local mechanical properties in the continuum-level FE models are assumed isotropic and are derived from bone density, using statistical relationships. Micro-FE models, on the other hand, incorporate the anisotropic structure in detail. This study aimed to quantify the effects of assumed isotropy, by comparing continuum-level voxel models of a healthy and a severely osteoporotic proximal femur with recently analyzed micro-FE models of the same bones. The micro-model element size was coarsened to generate continuum FE models with two different element sizes (0.64 and 3.04 mm) and two different density–modulus relationships found in the literature for wet and ash density. All FE models were subjected to the same boundary conditions that simulated a fall to the side, and the stress and strain distributions, model stiffness and yield load were compared. The results indicated that the stress and strain distributions could be reproduced well with the continuum models. The smallest differences between the continuum-level model and micro-level model predictions of the stiffness and yield load were obtained with the coarsest element size. Better results were obtained for both continuum-element sizes when isotropic moduli were based on ash density rather than wet density.