The goal of this study was to explore the role of diffraction enhanced X-ray imaging (DEI) for assessing changes in osteoarthritic cartilage and correlating the findings with concurrent changes in the underlying bone imaged using micro-computed tomography (microCT). DEI was used to image femoral head specimens at various beam energies. DEI utilizes a monochromatic, highly collimated beam, with an analyzer crystal that selectively weights out photons according to the angle they have been deviated with respect to the original direction. This provides images of very high contrast, with the rejection of X-ray scatter. The underlying bone was imaged using microCT and measures quantifying the bone structure were derived. Confirmation of cartilage degeneration was obtained from histology and polarized light microscopy. DEI allowed the visualization of articular cartilage and reflected the fibrillations and fissures in tissues from degenerated joints. The trabecular bone underlying the most degenerated articular cartilage showed increased bone volume fraction and more plate-like characteristics, compared with that underlying normal appearing cartilage. The histology and polarized light microscopy images reflected the DEI based features of cartilage architecture. These data reflect the ability of X-ray based emerging technologies to depict cartilage-bone interactions in joint degeneration.