Subchondral trabecular bone (STB) undergoes adaptive changes during osteoarthritic (OA) disease progression. These changes alter both the mineralization patterns and structure of bone and may contribute to variations in the mechanical properties. Similarly, when images are downsampled – as is often performed in micro finite element model (microFEM) generation – the morphological and mineralization patterns may further alter the mechanical properties due to partial volume effects. MicroFEMs accounting for material heterogeneity can account for these tissue variations, but no studies have validated these with robust full-field testing methods. As such, this study compared homogeneous and heterogeneous microFEMs to experimentally loaded trabecular bone cores from the humeral head combined with digital volume correlation (DVC). These microFEMs were used to compare apparent mechanical properties between normal and OA STB. Morphological and mineralization patterns between groups were also compared. There were no significant differences in tissue or bone mineral density between groups. The only significant differences in morphometric parameters were in trabecular thickness between groups. There were no significant differences in linear regression parameters between normal and OA STB apparent mechanical properties estimated using heterogeneous microFEMs with an element-wise bilinear elastic-plastic constitutive model. Clinical significance:​ Validated heterogeneous microFEMs applied to STB of the humeral head have the potential to significantly improve our understanding of mechanical variations in the bone that occur during OA progression.