During aging and in osteoporosis, cortical bone becomes more porous, making it more fragile and susceptible to fractures. The aim of this study was to investigate the intracortical compression- induced strain energy distribution, and determine whether intracortical pores associated with high strain energy density (SED) in the surrounding bone matrix have a different morphology and distribution, as well as different remodeling characteristics than matrix with normal SED. Fibular diaphyseal specimens from 20 patients undergoing a jaw reconstruction (age range 41 to 75 years; 14 men and 6 women) were studied. Bone specimens were µCT-scanned, plastic embedded, and sectioned for histology. Three-dimensional microfinite element models of each specimen were tested in compression, and the SED of the bone immediately surrounding the intracortical pores was calculated within a plane of interest corresponding to the histological sections. The SED of a pore, relative to the distribution of the SED of all pores in each specimen, was used to classify pores as either a high or normal SED pore. Pores with high SED were larger, less circular, and were located closer to the endosteal surface of the cortex than normal SED pores (p < 0.001). Histological analysis of the remodeling events generating the pores revealed that the high SED pores compared with normal SED pores had 13.3-fold higher odds of being an erosive (70%) or formative (7%) pore versus a quiescent pore (p < 0.001), 5.9-fold higher odds of resulting from remodeling upon existing pores (type 2 pore) versus remodeling generating new pores (type 1 pore) (p < 0.001), and 3.2-fold higher odds of being a coalescing type 2 pore versus a noncoalescing type 2 pore (p < 0.001). Overall, the study demonstrates a strong relationship between cortical bone mechanics and pore morphology, distribution, and remodeling characteristics in human fibular bone.