Systemic metal-protein binding associated with total joint replacement arthroplasty

The distribution of titanium [Ti] and chromium [Cr] in serum protein fractions of patients with and without total joint replacements containing Cr and Ti was studied. Three groups were evaluated: 10 patients with cobalt-chromium [CoCr] alloy prostheses and known elevated levels of Cr; 10 patients with Ti containing implants and known elevated levels of Ti; and 10 age matched controls without prostheses. Metal-protein binding was also examined by adding various concentrations of Cr(+3) (CrCl(3)) to control serum. Cr and Ti were bound to serum proteins within specific molecular weight ranges in both patient groups. Two molecular weight ranges were found to bind Cr (at approximately 70 and approximately 180 kDa) in patients with CoCr alloy prostheses, whereas a single molecular weight range (at approximately 70 kDa) was found to bind Ti in patients with Ti alloy implants. This metal-protein binding was reproduced in vitro by adding CrCl(3) at concentrations of approximately 100 and 1000 ppb Cr, which is orders of magnitude higher than that contained in the serum of patients with CoCr alloy implants ( approximately 3 ppb Cr). This suggests that protein binding is initiated in the periprosthetic space where metal concentrations are typically 2-3 orders of magnitude higher than that observed systemically in the serum. In vitro, high molecular weight proteins including immunoglobulins demonstrated the highest affinity to Cr. Determination of specific protein carriers of metal degradation products is an essential component in the assessment of the long-term biological affects of total joint replacement devices.