Abstract: In the work we suggest an answer to the question: how is the local electronic and atomic structure as well as molecular architecture of bone tissue distorted in case of skeletal pathology? X-ray diffraction and photoelectron spectroscopy techniques are applied to medial and lateral condyles of the femoral bone resected during total knee arthroplasty in patients with medial compartmental knee osteoarthritis (OA). The measured data are examined and discussed. It is shown that the skeletal pathology affects local electronic and atomic structure of mineral matrix in bone. For the first time the site-dependent changes in cristallinity, binding energies and chemical composition of the intact and OA damaged areas of femur-saw-cuts are investigated. Specifically, in the sclerotic area crystallinity of the subchondral bone tissue increases, the binding energies of the Ca and P 2p core levels demonstrate opposite shifts and the widths of the core ⁻¹ photoelectron lines are maximal. The results show perspectives for development of novel approaches to medical imaging and diagnosis of bone tissue at the subcellular level. Graphical abstract: [Figure not available: see fulltext.].