This article is part of the supplement: Basic science, rationale, background and future of denosumab: a RANK ligand inhibitor
Aseptic loosening of total joint replacements: mechanisms underlying osteolysis and potential therapies
1 Department of Orthopaedic Surgery and Department of Cell Biology & Physiology, Washington University School of Medicine, Barnes Hospital Plaza, Saint Louis, Missouri 63110, USA
2 Department of Orthopaedic Surgery, Washington University School of Medicine, Barnes Hospital Plaza, Saint Louis, Missouri 63110, USA
Arthritis Research & Therapy 2007, 9(Suppl 1):S6 doi:10.1186/ar2170Published: 29 June 2007
Total joint replacement, although considered an excellent surgical procedure, can be complicated by osteolysis induced by implant particles and subsequent aseptic loosening of the implant. The pathogenesis of implant-associated osteolysis includes inflammatory and osteolytic processes. The sustained chronic inflammatory response initiated by particulate debris at the implant-bone interface is manifested by recruitment of a wide array of cell types. These cells include macrophages, fibroblasts, giant cells, neutrophils, lymphocytes, and – most importantly – osteoclasts, which are the principal bone resorbing cells. The 'cellular response' entails secretion of osteoclastogenic and inflammatory cytokines that favor exacerbated osteoclast activity and enhanced osteolysis. An appreciation of the complex network that leads to these cellular and inflammatory responses will form a foundation on which to develop therapeutic interventions to combat inflammatory periprosthetic bone loss.