Cobalt‐Chromium‐Molybdenum Alloy Causes Metal Accumulation and Metallothionein Up‐Regulation in Rat Liver and Kidney

Abstract

Cobalt-chromium-molybdenum (CoCrMo) metal-on-metal hip prosthesis has had a revival due to their excellent wear properties. However, particulate wear debris and metal ions liberated from the CoCrMo alloys might cause carcinogenicity, hypersensitivity, local and general tissue toxicity, genotoxicity and inflammation-generating qualities. Nine months after implanting small pieces of CoCrMo alloy intramuscularly and intraperitoneally in rats, we analysed the accumulation of metals with a multi-element analysis, and the levels of metallothionein I/II with real-time reverse transcriptase-polymerase chain reaction in liver and kidney. We found that metal ions are liberated from CoCrMo alloys and suggest that they are released by dissolucytosis, a process where macrophages causes the metallic surface to release metal ions. Animals with intramuscular implants accumulated metal in liver and kidney and metallohionein I/II were elevated in liver tissue. The present data do not tell whether kidney and liver are the primary target organs or what possible toxicological effect the different metal ions might have, but they show that metal ions are liberated from CoCrMo alloys that are not subjected to mechanical wear and that they accumulate in liver and kidney tissue. That the liberated metal ions affect the tissues is supported by an up-regulation of the detoxifying/pacifying metalloprotein I/II in the liver.Second-generation metal-on-metal hip prosthesis is made by cobalt-chromium-molybdenum (CoCrMo) alloy, because it is well-tolerated and possesses excellent wear properties [1,2] (Jakobsen et al., unpublished results). The alloy consists of 62-67% cobalt and 27-30% chrome, but also includes 5-7% molybdenum and all together less than 1% of manganese, iron, nickel and silicon [3]. However, unwanted side effects could be seen as a result of the released metal ions (Cr The number of metal wear particles has been found to be 13 to 500 times higher than the number of wear polyethylene particles released from conventional hip prostheses [6,9]. The large amount of nano-metal particles and the presumed high levels of metal ions in the tissues around hip prostheses have ignited concerns of carcinogenicity [10,11] and Bouchard et al. has previously suggested a carcinogenic effect of implanted CoCrMo (ASTM F-75); however, no differences in urine, faeces and blood metal concentration were observed [16]. Epidemiological studies have shown a possible increased cancer risk, although the data until now has been inconclusive or contradictory [17][18][19][20][21][22]. Particulate wear debris has been found to accumulate in tissue close to the implant, but also in distant lymph nodes, bone marrow, liver and spleen [23], and metal ions have been shown to be excreted in the urine [4] and through the bile [24]. However, it is still not known whether released metal ions accumulate in cells of different organs [25,26].In the present study, we found that the different metal atoms present in the implants were liberated and accumulated in th...

Metal-on-metal hip resurfacing arthroplasty: A review of periprosthetic biological reactions

“…Thus, they can only be eliminated from tissues by renal or gastrointestinal excretion (Cobb and Schmalzreid 2006). There is evidence from a recent animal study to suggest that Cr ions can accumulate in the liver (Jakobsen et al 2007). Marker et al (2007) investigated potential long-term effects on kidney function resulting from Co and Cr wear in MoM THA by measuring serum metal ion levels and creatinine clearance at 10-year follow-up in 75 patients.…”

How Has the Introduction of New Bearing Surfaces Altered the Biological Reactions to Byproducts of Wear and Modularity?

“…The existence of metals in both ionic and particulate form does initiate both innate and adaptive immune responses. Inflammatory, cytotoxic, and immunological responses appear to be interactive, because the exposure of metal debris to the acidic environment of the phagosome [49] or dissolucytosis at the macrophage surface [40] can elevate the generation of metal ions, intracellular metal ions can influence activities relevant to the immunological responses, and local hypersensitivity reactions can increase inflammation and tissue damage (Table 3). Genetic regulation of the responses will affect the overall pathology and outcome to metal debris, and thus it becomes impossible to generalize the outcome of metal debris exposure to the individual patient.…”

“…The air pouch model consistently responds with increased cellularity in response to Co-Cr debris, although the response is not elevated over reactions to conventional UHMWPE. Direct effects of metal ions on cellular functions have been reported and include an upregulation of metallothionein I/II and increased catalase and glutathione peroxidase activity in the liver [2,40], elevated apoptosis in the local tissue [68], and chromosomal aberrations (particularly increases in the percentage of aneuploidy gain) in patients with an MoM bearing [17].…”

“…Depending on the chemical properties of the biomaterial, there may be breakdown and corrosion products released, which may have both local and systemic effects [13,32,40]. The articulation of a joint prosthesis complicates this condition enormously, because the generation of wear is an inevitable consequence of movement at the bearing surface.…”

Macrophages adhesion rate on Ti-6Al-4V substrates: polishing and DLC coating effects

“…The particles resulting from wear Volume 32, Number 2, p. 144-152, 2016 of the prosthesis are harmful to the body and induce inflammation process (Grill, 2003;Hinüber et al, 2010). Many studies have shown that Co -, Cr -, and Mo -ions are considered toxic, carcinogenic and also able to promote inflammation (Andrews et al, 2011;Hinüber et al, 2010;Jakobsen et al, 2007). Aluminum is also considered to be a risk factor for the pathogenesis of Alzheimer's disease (McLachlan et al, 1990;Rusina et al, 2011).…”