Research Article: The Inflammatory Phenotype in Failed Metal-On-Metal Hip Arthroplasty Correlates with Blood Metal Concentrations

Date Published: May 26, 2016

Publisher: Public Library of Science

Author(s): Erja-Leena Paukkeri, Riku Korhonen, Mari Hämäläinen, Marko Pesu, Antti Eskelinen, Teemu Moilanen, Eeva Moilanen, Amir A. Zadpoor.


Hip arthroplasty is the standard treatment of a painful hip destruction. The use of modern metal-on-metal (MOM) bearing surfaces gained popularity in total hip arthroplasties during the last decade. Recently, worrisome failures due to adverse reaction to metal debris (ARMD), including pseudotumor response, have been widely reported. However, the pathogenesis of this reaction remains poorly understood. The aim of the present study was to investigate the ARMD response by flow cytometry approach.

Sixteen patients with a failed Articular Surface Replacement (ASR) hip prosthesis were included in the study. Samples of pseudotumor tissues collected during revision surgery were degraded by enzyme digestion and cells were typed by flow cytometry. Whole blood chromium and cobalt concentrations were analyzed with mass spectrometry before revision surgery.

Flow cytometry analysis showed that the peri-implant pseudotumor tissue expressed two principal phenotypes, namely macrophage-dominated and T-lymphocyte-dominated response; the average portions being 54% (macrophages) and 25% (T-lymphocytes) in macrophage-dominated inflammation and 20% (macrophages) and 54% (T-lymphocytes) in T-lymphocyte-dominated response. The percentages of B-lymphocytes and granulocytes were lower in both phenotypes. Interestingly, the levels of blood chromium and cobalt were significantly higher in patients with macrophage-dominated response.

The results suggest that the adverse tissue reactions induced by MOM wear particles contain heterogeneous pathogeneses and that the metal levels are an important factor in the determination of the inflammatory phenotype. The present results support the hypothesis that higher metal levels cause cytotoxicity and tissue injury and macrophages are recruited to clear the necrotic debris. On the other hand, the adverse response developed in association with lower metal levels is T-lymphocyte-dominated and is likely to reflect hypersensitivity reaction.

Partial Text

Total hip arthroplasty (THA) is an established and well documented operative treatment of a painful hip destruction associated with osteoarthritis (OA) or rheumatoid arthritis (RA). Although the conventional hip arthroplasty has a good reputation, the factor limiting its durability especially in younger THA patients has been the wear of polyethylene (PE) socket [1,2]. Metal-on-metal articulation (MOM) has been used for decades as a more wear-resistant alternative to conventional metal-on-polyethylene bearing in THA [3]. The recent MOM hip boom was initiated by the encouraging early results obtained using hip resurfacing and THA implants [4,5]. Most major companies introduced their versions of the resurfacing implant, followed by adaptation of MOM bearing surfaces into conventional stemmed THA devices. Early clinical reports of these second generation MOM hips were promising, and the method was soon widely used: for example, in the US the proportion of MOM bearing surface was 35% of total hip arthroplasties in 2005–2006 [6].

The adverse tissue reactions related to MOM implants are presently a major topic in hip arthroplasty debates, but the understanding on the detailed cellular mechanisms eventually resulting in the development of the reaction remains limited and various hypotheses have been presented [7,20,23–27]. The present study shows that the inflammatory activation related to failed ASR implants is heterogeneous and can be characterized either as s macrophage or as a T-lymphocyte dominated reaction. Interestingly, the two types of responses differed also according to the blood metal ion concentrations in a manner that the macrophage-dominated phenotype was associated with higher blood levels of chromium and cobalt.