Overview on local bone turnover in tumor necrosis factor transgenic mice. (a) Schematic overview of a healthy joint with only scarce osteoblasts (cubic-shaped blue cells) and osteoclasts (multinucleated red cells) in cortical bone channels and the endosteal bone surface. (b) In arthritis, synovial inflammatory tissue comprised of synovial fibroblasts (yellow spindle-shaped cells), macrophages (purple cells), T cells (green cells), B cells (dark blue cells) and other cells invade the subchondral bone and trigger massive local osteoclastogenesis and – as a reactive process – osteoblastogenesis. Also, osteoclast and osteoblast accumulation occurs in cortical bone channels but not at the endosteal bone surface distant from synovitis. (c) TNF blockade efficiently diminishes bone erosion and suppresses osteoclastogenesis in subchondral bone erosions and cortical bone channels. In contrast, enhanced osteoblast activity can be detected in both regions, suggesting an increased reparative response when TNF is blocked. (d) Receptor activator of NF-κB ligand blockade inhibits bone erosion but not synovitis. Osteoclastogenesis is efficiently blocked in all compartments but, in contrast to anti-TNF, osteoblasts are also massively reduced. OPG, osteoprotegerin.