The functional signal of bone internal structure has been widely studied. Isolated form-function relationships have often been assumed from the observation of presumed morphofunctional relationships, but have never been truly tested. Indeed, distinct bone microanatomical feature co-evolve in response to various constraints that are difficult to detangle. This study tested for the first time the impact of various microanatomical parameters taken one by one, plus some in pairs, on bone strength under compression using biomechanical modelling. We carried out finite element analyses on humerus models, obtained from a white rhinoceros, with different heterogeneous internal structures, and analysed the magnitude and distribution of von Mises stresses. These tests validated earlier hypotheses of form-function relationships about the greater resistance to compression provided by the thickening of the cortex and the filling of the medullary area by trabecular bone and highlighted the stronger impact of increasing trabecular bone compactness than of avoiding an open medullary cavity. By making it possible to estimate the relative impact of each parameter and ofcombinations of microanatomical features, they also showed the more limited impact of the trabecular bone compactness in the epiphyses to resist compression, and the fact that microanatomical changes of opposite but of similar amplitude impact can compensate each other, but that the impact of the sum of two negative microanatomical changes far exceeds the sum of the impacts of each of the two changes taken separately. These results contribute to a better understanding of bone adaptation and form-function relationships so that they later can be used with confidence for palaeobiological inferences on fossil specimens, contributing to a better understanding of skeletal evolution during the evolutionary history of vertebrates. They also highlight the potential of taking internal structure into account in the bone biomechanical analyses. In addition, they can be used in bioinspiration to design resistant structures subjected to compression.