In a randomized study of 60 patients allergic reactions are evaluated in three joint prosthesis groups, a resurfacing arthroplasty (ReCap), a non-cemented, large metal-on-metal head (Bimetric Magnum) and a non-cemented, alumina ceramic-on-ceramic bearing in a titanium shell (Bimetric C2a). The inclusion criteria were osteoarthritis, ASA I–II, MRI-scan without caput necrosis, DXA-scan without osteoporosis. The exclusion criteria were short neck (<2cm.), large cysts (>1cm.), medical treatment affecting the bone metabolism, severe deformity of the femoral head, impaired kidney function and inability to co-operate. Blood samples were drawn prior to and 6 weeks, 6 months, 1 year, and 3 years after surgery; two tubes from which plasma was prepared, and two tubes for serum. From the last included 20 patients in each group was also taken blood one and three years after surgery for an in vitro lymphocyte assay for scoring of possible hypersensitivity to prosthesis metals. The isolated lymphocytes were subjected to measurement of proliferation and expression of CD69 by flow cytometry and measurement of the Migration Inhibitory Factor (MIF) by ELISA. Plasma concentrations of the cytokines IL-1, IL-4, IL-6, IL-8, IL-12p70, IL-15, interferon-and osteoprotegerin were determined by multiplex-immunoassay. Serum concentrations of chromium and cobalt were determined by graphite furnace atomic absorption spectrometry. The serum concentrations of chromium and cobalt were lowest in patients with the C2a implant and highest with Magnum, some of these differences were significant at 6 weeks, 6 months, and 1 year after surgery. No patient had a very high serum metal concentration. The values of the variables measured in the in vitro lymphocyte assay mainly changed in the expected direction depending on the concentration of the same metal in the serum sample drawn at the same time, but no significant correlation was seen. One patient had uncertain symptoms of metal hypersensitivity and relatively high serum metal concentrations 3 years after arthroplasty with a Magnum prosthesis and was assessed extraordinarily, and elicited the marginally highest MIF responses in the lymphocyte assay. A strong correlation was found between the plasma concentrations of most cytokines, but the cytokine concentrations were not correlated to contemporary metal concentrations.
A major concern in metal on metal bearings has been the elevated serum concentrations of cobalt and chromium. Recent papers have suggested that metal hypersensivity in a few cases could cause periprostetic lymphocyte accumulation leading prosthetic loosening. To measure the lymphocyte activation and proliferation in vitro by re-exposure of the cells to cobalt, chromium, nickel and titanium. To correlate the lymphocyte assay data to the serum concentration of metals and plasma cytokines. A prospective clinical study with the ASR (DePuy) and ReCap (Biomet) resurfacing hip implants. Blood samples were collected one and two years postoperatively, lymphocytes were isolated by density gradient centrifugation, cultured in a medium containing the patient’s serum and exposed to metal salts. Cells were analyzed by flow cytometry, evaluating number, viability, size and CD69 activation. A negative control and a positive control (phytohaemagglutinine) were included in the assay, and the responses to the metals were calculated in proportion to controls. 11 patients were assessed at one and two years follow up, 16 patients were assessed only at two years. Serum chromium and cobalt were measured preoperatively, six months, one year and two years postoperatively by graphite furnace absorptiometry. Plasma cytokines were measured by multiplexed immunoassay. In the assay the negative and positive controls gave the expected responses. When exposed to metals no response was found in the lymphocytes in any patients. There were no difference in response between one and two years. The results seems to indicate that the metal hypersensitivity is a rare condition in metal on metal arthroplasty. The results indicate that the method can be used to monitor hypersensitivity to implant metals.
At present we conduct a clinical study on four bearing combinations in hip arthroplasty. Our main purpose is to assess changes in bone mineral density (BMD), function of the joint, and to monitor serum concentrations of prosthetic metals as well as plasma concentrations of a range of cytokines, chemokines, and related proteins during a ten-year follow-up. This is done in order to evaluate the potential role of these variables as predictors of dysfunction or loosening of the arthroplasty. A total of 300 patients were randomly allocated to four bearing combinations. Four years after surgery the following number of patients were available for follow-up: Type A: Zirconia ceramic head, polyethylene cup insert in the Universal RingLoc metal backed shell (n=50); Type B: Cobalt-Chrome-Molybdenum head and cup insert in the Universal RingLoc metal backed shell (n=57); Type C: Zirconia ceramic head, polyethylene moulded on the Titanium shell of the Asian cup (n=55); Type D: Alumina head and cup insert in the Universal RingLoc metal backed shell (n=45). A BiMetric Titanium-Aluminium-Vanadium (Ti6Al4V) stem was used with all four combinations (n=207). All patients, but two with rheumatoid arthritis, had primary osteoarthritis or avascular necrosis of the femoral head. Five patients had astma and eight had diabetes. At the time of surgery the groups were equal with regard to age, gender distribution, body height and weight, side of arthroplasty, and BMD in all seven Gruen zones. Harris Hip Score prior to arthroplasty was equally low in all groups (mean ± SD) (42 ± 17), and increased in all groups, with no significant differences between them (87 ± 10). At follow-up there was a significant decrease in BMD in all Gruen zones ranging from −1.9 % in zone 4 in group C to −21.7% in zone 7 in group D. However, there were no significant differences between groups. There were significantly higher blood concentrations of Chromium and Cobalt in group B patients compared to all other groups (p <
0.001). Plasma concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, TNF-α, TNF-R1, VEGF, OPG, GM-CSF, or TGF-β1 did not differ significantly between groups. Instead, elevated levels of IL-1β, IL-10 and TNF-R1 were found in patients with asthma. IL-6, TNF-α and VEGF were elevated in patients with rheumatoid arthritis or asthma. IL-8 and TGF-β1 were higher in patients with osteoarthritis, whereas GM-CSF was high in patients with asthma or diabetes.
