Realistic macro-level finite element simulations of the mechanical behavior of trabecular bone, a cellular anisotropic material, require a suitable constitutive model;​ a model that incorporates the mechanical response of bone for complex loading scenarios and includes post-elastic phenomena, such as plasticity (permanent deformations) and damage (permanent stiffness reduction), which bone is likely to experience. Some such models have been developed by conducting homogenization-based multiscale finite element simulations on bone micro-structure. While homogenization has been fairly successful in the elastic regime and, to some extent, in modeling the macroscopic plastic response, it has remained a challenge with respect to modeling damage. This study uses a homogenization scheme to upscale the damage behavior from the tissue level (microscale) to the organ level (macroscale) and assesses the suitability of different damage constitutive laws. Ten cubic specimens were each subjected to 21 strain-controlled load cases for a small range of macroscopic post-elastic strains. Isotropic and anisotropic criteria were considered, density and fabric relationships were used in the formulation of the damage law, and a combined isotropic/anisotropic law with tension/compression asymmetry was formulated, based on the homogenized results, as a possible alternative to the currently used single scalar damage criterion. This computational study enhances the current knowledge on the macroscopic damage behavior of trabecular bone. By developing relationships of damage progression with bone's micro-architectural indices (density and fabric) the study also provides an aid for the creation of more precise macroscale continuum models, which are likely to improve clinical predictions.