Spinal implant debris-induced osteolysis.

Abstract

Generally, implant-induced osteolysis is a manifestation of an adverse cellular response to phagocytosable particulate wear and corrosion debris. Initially termed "cement disease," particle-induced loosening was recognized by Charnley in the early 1960s. Despite the plethora of information gained over the last 40 years on the basic science of periprosthetic bone loss, much remains unanswered. The effect of unintended debris resulting from wear and corrosion (e.g., micromotion between the interconnection mechanisms in spinal implants) remains a clinical concern. The current study highlights what is known of particle-induced osteolysis and how the presence of spinal implant particulate debris deleteriously influences osseointegration of posterolateral bone graft or disrupts an established posterolateral fusion mass. Tissue explant, animal, and cell culture studies have revealed the complexity of cellular reactivity involved in aseptic particle-induced osteolysis. The objectives of this study are twofold: 1) to highlight the dominant cellular participants in total joint arthroplasty particle induced osteolysis, which are purportedly the macrophage, osteoblast, fibroblast, and osteoclast and several of the dominant chemical mediators have been identified as well, which include prostaglandin E2, tumor necrosis factor-alpha, interleukin-1, and interleukin-6; and 2) to demonstrate the potential deleterious effects of spinal implant debris using animal models and analysis of soft tissue surrounding spinal implants in symptomatic patients. There are a growing number of proinflammatory and anti-inflammatory cytokines, prostenoids, and enzymes that have been shown to play important roles in the pathology of particle-induced osteolysis. Reports that aseptic granulomatous inflammation typical of that associated with corrosion debris appear to correlate with the complexity of the implant. Titanium particulate material was used to induce effects in 34 New Zealand White rabbits where analysis included serological quantification of systemic cytokines. Postmortem microradiographic, immunocytochemical, and histopathologic assessment of the intertransverse fusion mass quantified the extent of osteolysis, local proinflammatory cytokines, osteoclasts and inflammatory infiltrates. Clinical analysis of 12 patients more than 0.4 years after spinal implants (mean 4.03, range 0.4 to 11 years) presented with late operative site pain. Currently the etiology of this inflammation around spinal implants resembles particle-induced osteolysis around joint arthroplasties where there typically is a self-perpetuating fibroinflammatory zone adjacent to the implant, where macrophage exhaustion, reactive oxygen intermediates, and pro-inflammatory cytokines affect a host of local cell types and induce a widening zone of soft tissue damage and inflammation. Animal model analysis indicated increased levels of local inflammatory cytokines typically associated with osteolysis-tumor necrosis factor-alpha. Osteoclast cell counts and regions of osteolytic resorption lacunas were higher in the titanium-treated versus autograft-alone groups (P < 0.05), and the extent of cellular apoptosis was markedly higher in the titanium-treated sites at both time intervals. Electron microscopy indicated definitive evidence of phagocytized titanium particles and foci of local, chronic inflammatory changes in the titanium-treated sites. 11 of 12 clinical cases demonstrated elevated tumor necrosis factor-alpha levels and an increased osteoclastic response in the vicinity of wear debris caused by dry frictional wear particles of titanium or stainless steel. Resection of the wear debris and surrounding fibroinflammatory zone resolved clinical symptoms in all 12 cases. More basic science and clinical research is needed to develop novel strategies for gaining knowledge, and developing effective evaluation and treatment of patients with implant debris related osteolysis. Titanium debris simulating that produced by spinal implants introduced at the level of a spinal arthrodesis elicits an inflammatory cytokine mediated particulate-induced response through increased expression of intracellular TNF-alpha, increased osteoclastic activity and cellular apoptosis. This study highlighted the association between spinal implants particulate wear debris and increased potential for osteolysis. Aseptic osteolysis is among the primary reasons for failure of orthopedic implants. Increased awareness of this destructive process is becoming more important with the growing popularity of total disc arthroplasty and highly modular spinal implants.