Particle characterisation and cytokine expression in failed small-diameter metal-on-metal total hip arthroplasties.

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the 'biologically active area' of all metal wear particles may predict the type of peri-prosthetic tissue response. Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response. These results suggest that the 'biologically active area' predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA.

Periprosthetic tissue metal content but not serum metal content predicts the type of tissue response in failed small-diameter metal-on-metal total hip arthroplasties.

BACKGROUND: Tissue responses to periprosthetic metal wear debris are complex and poorly understood. There are two predominant tissue responses: a nonspecific macrophage-mediated granulomatous response and lymphocyte-dominated response, which has immunological memory and is mediated by T cells. Delayed hypersensitivity-type responses may accelerate aseptic loosening of arthroplasty implants. We hypothesized that the metal content of periprosthetic tissue but not of serum would be predictive of the type of tissue response to metal wear debris. METHODS: We examined twenty-eight total hip arthroplasty implant retrievals from twenty-seven patients who had undergone revision arthroplasty at one institution. Indications for revision were pain and/or osteolysis; one patient had recurrent dislocations. Tissue samples were analyzed microscopically and the metal (Co, Cr, and Ni) content was determined. Explanted prosthetic components were examined for linear wear. Intraoperatively, periprosthetic metallosis was observed in twelve cases and formation of a bursa (pseudotumor) was observed in thirteen. The acetabular cup was loose in eleven cases, the femoral stem was loose in five, and both components were loose in five. RESULTS: The metal (Co, Cr, and Ni) content of the periprosthetic tissue ranged from 1.4 to 4604.0 µg/g. Histologically, macrophages containing metal particles as well as diffuse and perivascular lymphocytic infiltration were observed. Fibrin exudation was also visible. Tissues that displayed a predominantly lymphocytic response had a mean metal content of 222.2 ± 52.9 µg/g, whereas those that displayed a macrophage-dominated response had a metal content of 3.0 ± 0.9 µg/g; this difference was significant (p = 0.001). The mean serum metal content did not differ significantly between the two subgroups (60.7 ± 13.4 compared with 43.7 ± 3.8 µg/L, p = 0.105). CONCLUSIONS: An association between periprosthetic tissue metal content and hypersensitivity appears likely but needs to be validated with larger-scale retrieval studies. CLINICAL RELEVANCE: This study contributes to the understanding of tissue responses to metal wear debris after joint replacement and the factors that are predictive of a type-IV lymphocyte-dominated hypersensitivity reaction.