Original Full Length ArticleRANKL in the osteolysis of AES total ankle replacement implants

Peri-implant tissue reactions in failed total ankle replacement (TAR) are characterized by early developing peri-implant osteolysis. The hypothesis of the study was that this reaction is mediated by receptor activator of nuclear factor kappa B ligand (RANKL).Samples of peri-prosthetic tissues from failed TAR implants were stained for macrophages, RANKL, its receptor RANK and osteoprotegerin (OPG), and compared to control samples.The failed TAR implants were surrounded by implant capsule, synovial lining-like interface membrane or necrotic tissues. Infiltrating scavenger receptor I positive CD163+ macrophages were frequent, in particular around necrotic soft tissues or bone sequestrate, and possibly in part formed due to ischemia and mechanical factors. In contrast, implant-derived wear debris was scanty. Still many RANK+ macrophages were often seen in close contact with RANKL+ mesenchymal cells, whereas OPG was mostly located at a distance in vascular endothelial cells. Foreign body giant cells were frequent.RANKL seems to stimulate locally accumulated CD163+ RANK-expressing cells to fusion, which leads to the local formation of multinuclear foreign body giant cells (and probably of osteoclasts). Therefore, peri-implant osteolysis in early TAR implant failure seems to be caused by the RANKL-driven chronic foreign body inflammation directed against, not implant-derived particles, but against necrotic autologous tissues.

► The aseptic loosening of total ankle replacement (TAR) is characterized by infiltrates of CD163+ and RANK+ macrophages. ► The aseptic loosening of TAR is mediated via RANKL, expressed by mesenchymal cells, driving the fusion of multinuclear cell progenitors. ► Implant-derived wear debris and particles are rarely seen. ► Tissue necrosis is extensive and seems to drive the chronic foreign body reaction.