Abstract
The world-wide experience with metallic implants provides the evidence for biocompatibility of modern cobalt- and titanium-based alloys. However, a corrosion process leading to release of ions has to be taken into account, and controversial data are available about the ‘endogenous’ metal exposure resulting from implants.
Adverse tissue reactions, cytotoxicity and toxic/ sensitizing effects of corrosion products on the immune system, as well as an involvement of metal ions in the pathogenesis of prosthesis loosening, are the main undesired effects. Moreover, metal ions could be responsible of long-term toxic effects, such as genotoxicity and carcinogenicity.
The aim of our study was to analyze the levels of serum metal ions in a large series of patients who underwent total hip and knee replacement (THR and TKR, respectively); both stable and loosened implants were considered. Furthermore, a group of subjects with fracture fixation devices was evaluated.
A consecutive series of 471 individuals (193 M; 278 F) was enrolled in the study, including 151 with hip prosthesis loosening (Group A: 52 M; 99 F; median age 67; median follow up 90 months) and 100 patients with stable hip prosthesis (Group B: 44 M; 56 F; median age 59; median follow up 34 months). Group A and B comprised implants with different coupling, i.e. ceramic-on-ceramic (alumina), metal-on-metal and metal-on-polyethylene, and different stem alloy (TiAlV-THR and CoCrMo-THR). 20 patients with knee prosthesis loosening (Group C: 3 M; 17 F; median age 67; median follow up 25 months), and 12 subjects with failed fracture fixation devices (Group D: 6 M; 6 F; median age 35; median follow up 12 months) were enrolled, too. Osteoarthritis was the most frequent disease that led to joint replacement (59%), followed by hip dysplasia (19%), and trauma (13%). Ion reference ranges were obtained from 188 subjects (88 M; 100 F; median age 52), including 56 healthy subjects and 132 candidates to primary THR or TKR. Serum samples were analyzed for chromium (Cr), cobalt (Co), molybdenum (Mo), nickel (Ni), aluminum (Al), titanium (Ti) and vanadium (V) content, in relation with the presence in the implant alloy, using a graphite furnace atomic absorption spectrometer (GFAAS), equipped with double background correction Deuterium/ Zeeman, autosampler and pyrolytic carbon-coated graphite tubes (Unica Solaar 939 QZ, Cambridge, UK). The highest value found for subjects with no implant was considered the upper reference limit for each element.
Group A (loosened THR) and B (well-fixed THR) patients, compared with controls, showed different behaviour depending on the prosthesis coupling and stem composition.
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Metal-on-PE coupling and CoCrMo/Ni stem: a significant increase of Cr and Co serum values was observed, in both groups, even if the increase in loosened implants was higher than in the stable ones. Mo and Ni concentration did not show a significant variation.
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Ceramic-on-ceramic coupling: a high Cr release, and a high Al, Ti release was shown in loosened implants with CoCrMo stem, and TiAlV stem, respectively, whereas normal values were measured in patients with stable prostheses.
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Metal-on-metal coupling and CoCrMo stem: a significantly higher Co and Cr release, both in group A and B patients. The conspicuous corrosion rate in metal-on-metal implants, even if stable, was confirmed in the same population in the short- and medium-term.
A serum Co, Cr increase was demonstrated in Group C patients, too, who had a failed knee prosthesis, and a Cr, Ni increase was observed in Group D patients with stainless steel fracture fixation devices.
Metal corrosion leading to ion release needs further consideration, because it may enhance the inflammatory reaction, depress the immune system, and facilitate peri-prosthetic bacterial growth. Especially metal-on-metal coupling introduces additional biologic risks associated with increased degradation products of prosthetic materials. Otherwise, histiocytic/giant-cell reaction and peri-prosthetic osteolysis induced by polyethylene particles represent the main problem in knee and hip joint implants with metal/PE coupling, and the systemic effects due to the ion release become negligible. On the contrary, ceramic-on-ceramic coupling represents a good alternative, as demonstrated by the absence of metal release in stable implants, even if, in case of loosening, a serum ion increase is observed, probably due to the fretting at the head/neck connection.
Also, metal corrosion of fixation devices is a concern; consequently, it could be appropriate to remove the implants, as early as their function is accomplished.
In conclusion, ion profile should be carefully monitored and the epidemiological survey implemented, in order to establish the tolerance values in patients with implants, especially in young patients, where a long-term ‘endogenous’ exposure has to be faced. In particular, concerning systemic toxic effects, the ‘gene expression profiling’, through the use of microarray technology, could contribute to an improved understanding of the biological responses to metal ions released from orthopedic implants. In such a way a real risk-to-benefit ratio for the patient could be established.
Finally, ion monitoring, as demonstrated by the different serum ion levels in stable and loosened implants, could allow to detect early signs of failure, when radiographic and clinical data are unclear, and to avoid the need of revision using a proper treatment.
The abstracts were prepared by Ms Grazia Gliozzi. Correspondence should be addressed to her at the Italian Orthopaedic Research Society, Laboratory for Pathophysiology, Instituti Ortopedici Rizzoli, University of Bologna, Bologna, Italy.
