title: RANKL in the osteolysis of AES total ankle replacement implants.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Rheumaorthopaedic unit, Paimio Hospital, Turku University Hospital, Alvar Aallon tie 275, 21540 Preitila, Finland. helka.koivu@gmail.com
authors.forename: H
authors.initials: H
authors.lastname: Koivu
authors.forename: Z
authors.initials: Z
authors.lastname: Mackiewicz
authors.forename: Y
authors.initials: Y
authors.lastname: Takakubo
authors.forename: N
authors.initials: N
authors.lastname: Trokovic
authors.forename: J
authors.initials: J
authors.lastname: Pajarinen
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000368:Aged; D000842:Ankle / Q000473:pathology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D058737:Arthroplasty, Replacement, Ankle; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010014:Osteolysis / Q000378:metabolism* / Q000473:pathology; D019736:Prostheses and Implants; D011475:Prosthesis Failure; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011956:Receptors, Cell Surface