ABSTRACT
Wear particles from orthopaedic implants stimulate a local inflammatory process that induces proresorptive cytokine production, osteoclast differentiation, bone resorption, osteolysis, implant loosening, pain, loss of implant function, and, ultimately, the need for revision surgery. This review will focus on four aspects of the host reaction to the particles: first, the role of particles themselves compared with other factors, including implant motion, mechanical forces, fluid pressure, and bacterial endotoxins; second, the ability of macrophages and other cell types to detect the particles; third, the actions of osteoclasts and osteoblasts as effector cells; and fourth, future directions for research in this area. The 12major conclusions of this review are that: (i) wear particles are the primary inducers of aseptic loosening; (ii) the effects of the wear particles are increased by other factors, including implant motion, mechanical forces, fluid pressure, and bacterial endotoxins; (iii) the most important type of wear particle in an individual patient is likely to be the type that is the most abundant; (iv) the macrophage is the primary cell type that detects and responds to the wear particles; (v) the wear particles activate multiple signal transduction pathways in the macrophages; (vi) the wear particles induce macrophages to produce proinflammatory cytokines [tumor necrosis factor-a (TNFa), interleukin (IL)-1, IL-6, etc] that synergistically induce osteoclast differentiation and osteolysis; (vii) the primary role of fibroblasts and other mesenchymal cells in aseptic loosening is to produce proresorptive cytokines [RANKL and macrophage colony stimulating factor (M-CSF)] in response to the proinflammatory cytokines produced by the macrophages; (viii) lymphocytes likely do not play a major role in aseptic loosening except, perhaps, in a subset of patients with metal sensitivity; (ix) increased osteoclast differentiation is the primary cause of osteolysis; (x) decreased bone formation plays an important, but secondary, role in aseptic loosening; (xi) a better understanding of the genetic regulation of aseptic loosening may lead to better methods for identifying higher risk patients; and (xii) approaches to accelerate osseointegration or to inhibit bacterial growth, wear particle migration, or osteoclast differentiation are promising future directions that deserve further study.
