A model of rheumatoid arthritis, implicating subchondral osteitis and RANKL-mediated osteoclastogenesis in the development of bone erosion. (a) Resting subchondral trabecular bone. (b) Osteitis (bone edema on MRI) characterised by infiltrates of macrophages, lymphocytes and plasma cells adjacent to osteoclasts. RANKL staining abundant adjacent to trabeculae . (c) Activated osteoclasts resorb trabecular bone leading to intra-osseous erosion formation (subchondral bone defects on MRI). (d) Cortical bone erosion develops. MRI = magnetic resonance imaging; RANK, receptor activator for nuclear factor κB; RANKL, RANK ligand.