Anastasia K. Skipor

Metal release in patients who have had a primary total hip arthroplasty a prospective, controlled, longitudinal study

There is an increasing recognition that, in the long term, total joint replacement may be associated with adverse local and remote tissue responses that are mediated by the degradation products of prosthetic materials. Particular interest has centered on the metal-degradation products of total joint replacements because of the known toxicities of the metal elements that make up the alloys used in the implants. We measured the concentrations of titanium, aluminum, cobalt, and chromium in the serum and the concentration of chromium in the urine of seventy-five patients during a three-year prospective, longitudinal study. Twenty patients had had a so-called hybrid total hip replacement (insertion of a modular cobalt-alloy femoral stem and head with cement and a titanium acetabular cup without cement), fifteen had had insertion of an extensively porous-coated cobalt-alloy stem with a cobalt-alloy head and a titanium-alloy socket without cement, and twenty had had insertion of a proximally porous-coated titanium-alloy stem with a cobalt-alloy head and a titanium socket without cement. The remaining twenty patients did not have an implant and served as controls. The results of our study showed that, thirty-six months postoperatively, patients who have a well functioning prosthesis with components containing titanium have as much as a threefold increase in the concentration of titanium in the serum and those who have a well functioning prosthesis with cobalt-alloy components have as much as a fivefold and an eightfold increase in the concentrations of chromium in the serum and urine, respectively. The predominant source of the disseminated chromium-degradation products is probably the modular head-neck junction and may be a function of the geometry of the coupling. Passive dissolution of extensively porous-coated cobalt-alloy stems was not found to be a dominant mode of metal release. CLINICAL RELEVANCE: Increased concentrations of circulating metal-degradation products derived from orthopaedic implants may have deleterious biological effects over the long term that warrant investigation. This is a particularly timely concern because of recent clinical trends, including the reintroduction of metal-on-metal bearing surfaces and the increasing popularity of extensively porous-coated devices with large surface areas of exposed metal. Accurate monitoring of the concentrations of metal in the serum and urine after total hip replacement also can provide insights into the mechanisms of metal release. Our findings suggest that fretting corrosion at the head-neck coupling is an important source of metal release that can lead to increased concentrations of chromium in the serum. Determinations of the concentrations of metal in the serum and urine may be useful in the diagnosis of patients who are symptomatic after a total joint replacement as increased levels are indicative of at least one mode of mechanical dysfunction (for example, fretting corrosion) of the device.

Cobalt and chromium concentrations in patients with metal on metal total hip replacements.

There has been a resurgence of interest in the use of metal on metal bearings in total hip arthroplasty. Although the use of metal on metal bearing couples would eliminate or substantially reduce particulate polyethylene generation (depending on the presence or absence of polyethylene in the implant system), there is concern about the potential for increased particulate and ionic metal generation in comparison with polyethylene on metal bearings. These metallic degradation products may be transported away from the implant site and distributed systemically. Chromium concentrations in the serum and urine and cobalt concentrations in the serum were measured in subjects with cobalt chromium alloy metal on metal total hip replacements and in controls without implants. Eight subjects with long term (> 20 years) McKee-Farrar total hip replacements had 9-fold elevations in serum chromium, 35-fold elevations in urine chromium, and at least 3-fold elevations in serum cobalt concentrations in comparison with controls. Six subjects with short term (< 2 years) metal on metal surface replacement arthroplasties had 3-fold elevations in serum chromium, 4-fold elevations in urine chromium, and 4-fold elevations in serum cobalt concentrations in comparison with subjects with McKee-Farrar implants. Although the toxicologic importance of these trace metal elevations has not been established, serum and urine metal concentrations may be useful markers for the tribologic performance of metal on metal bearings.

Release and excretion of metal in patients who have a total hip-replacement component made of titanium-base alloy.

Serum concentration and urinary excretion of titanium, aluminum, and vanadium were measured for patients who had a well functioning cementless primary total hip replacement of one of two different designs, for patients who had a loose total hip replacement that was to be revised, and for control subjects who had no implant. Serum concentrations of titanium were elevated approximately twofold in the patients who had a loose implant, compared with the values for the control subjects. No major differences in terms of urine concentration of titanium, serum concentration of aluminum, or urine concentration of aluminum were observed among any of the groups that were studied. Concentrations of vanadium were uniformly low in all groups.

Local and distant products from modularity.

In this study, the local and distant distribution of solid and soluble products of corrosion from the head and neck junction of modular femoral total hip prosthetic components were characterized. Particulate corrosion products from retrieved implants and surrounding tissues were analyzed. Serum transport and urinary excretion of metal was measured in correlation with the degree of corrosion at the head and neck junction. Particles of metal oxides, metal chlorides, and chromium phosphate corrosion products were identified on implants of 10 designs from 6 manufacturers. The most abundant solid corrosion product on the implant and within the periprosthetic tissues (size range, < 1-200 micrometers) was an amorphous chromium orthophosphate hydrate-rich material. Serum cobalt and urine chromium concentrations were elevated significantly in patients with implants that had moderate to severe corrosion in comparison with those with no to mild corrosion. Solid corrosion products from modular femoral stems may accelerate articular wear via a 3-body mechanism. Phagocytosable particles of these corrosion products may stimulate macrophage-mediated periprosthetic bone loss. Systemic dissemination of metallic corrosion products raises the issue of systemic toxicity; however, no overt evidence of metal toxicity was observed in this study.

Differences in the fretting corrosion of metal–metal and ceramic–metal modular junctions of total hip replacements

The use of modular interlocking components is a central design feature of total joint replacements. In this investigation we hypothesized that clinically available ceramic–metal modular connections used in total hip arthroplasty release more metal through fretting corrosion than traditional metal–metal modular connections. This was investigated using an in vitro comparison of ceramic (zirconia, ZrO2) and metal (Co‐alloy) femoral‐head fretting upon Co‐alloy stem components. In vitro fretting corrosion testing consisted of potentiodynamic monitoring and analysis of metal release from zirconia and Co‐alloy 28 mm femoral heads with similar surface roughnesses (Ra = 0.46 μm) on identical Co‐alloy stems at 2.2 kN for 1 × 106 cycles at 2 Hz. In contrast to our original hypothesis, we found greater metal release (approximately 11‐fold increase in Co and 3‐fold increase in Cr) and potentiodynamic fretting of metal–metal modular junctions when compared to ceramic–metal. Potentiodynamic testing demonstrated that lower initial voltages (−266 < 153 mV), greater maximum voltage changes (116 > 56 mV, p < 0.05, t‐test) and voltage variability (3 > 0.5 mV, p < 0.05, t‐test) were associated with the open circuit potentials of Co‐alloy on Co‐alloy junctions when compared to zirconia on Co‐alloy junctions. In this study of a single total hip replacement stem and head design, zirconia heads mated with Co‐alloy stems produced less fretting than Co‐alloy heads mated with Co‐alloy stems. Although further studies are necessary with a variety of implant designs and under different experimental conditions, the evidence presented here should, in part, alleviate concerns of increases in fretting corrosion at modular junctions of ceramic–metal coupled components.

Metal-on-metal bearing surfaces.

Metal-on-metal bearing couples remain a popular option in total hip arthroplasty and are the only currently available option for surface replacement arthroplasty. In general, the intermediate-term clinical performance of metal-on-metal bearings has been favorable. There are, however, lingering concerns about the biologic consequences of metal release from these bearings in terms of both local tissue effects, including delayed-type hypersensitivity reactions in a subset of patients, and potential systemic effects as a consequence of chronic elevations in serum cobalt and chromium content. Advances in the understanding of the operant wear mechanisms in these bearings provide strategies for reducing the burden of metal released into the periprosthetic milieu, which in turn will mitigate the concerns about the biologic response to the metal debris. Continued surveillance of patients with these bearings is warranted to determine whether metal-on-metal bearing couples provide a long-term survivorship advantage over other bearing couple options and to evaluate whether chronic elevations in the body burden of cobalt and chromium is well tolerated over the long term.

Serum and urine metal levels in patients with metal-on-metal surface arthroplasty.

The resurgence of metal-on-metal articulating surfaces for hip arthroplasty has also heightened concerns about the degree and magnitude of metal particle generation and the accompanying increase in circulating metal ion concentrations. In this study, we measured the concentration of chromium in serum and urine and the concentration of cobalt in serum in twenty-five patients with modern metal-on-metal surface arthroplasty of the hip in a prospective manner. The results showed that the mean post-operative chromium in serum levels were 22-fold, 23-fold and 21-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative cobalt in serum levels were 8-fold, 7-fold and 6-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative chromium in urine levels were 9-fold, 10-fold and 14-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The values seen in this study with the current generation of surface arthroplasties are: (a) lower than those seen in an earlier generation of surface arthroplasties; (b) in the same range as those observed in association with metal-on-metal conventional total hip replacements, which typically have smaller head sizes; (c) higher than values observed in patients with conventional metal-on-polyethylene articulating couples.

Metal release and excretion from cementless titanium alloy total knee replacements

Concentrations of titanium, aluminum, and vanadium were measured in the serum and urine of patients with titanium alloy cementless primary total knee arthroplasty components. Patients were categorized in one of five groups. In Group 1, the patellar and tibial articulating surfaces were made of carbon fiber reinforced ultrahigh molecular weight polyethylene. In Group 2, the patellar and tibial surfaces were made of ultrahigh molecular weight polyethylene. In Group 3, the femoral titanium alloy articulating surface was nitrogen ion implanted with ultrahigh molecular weight polyethylene patellar and tibial articulating surfaces. Patients in Group 4 had failed patellar components, and Group 5 was comprised of age and gender matched control subjects without implants. Serum concentrations of titanium were approximately 50 times greater in patients with failed patellar components (Group 4) and approximately 10 times greater in patients with carbon fiber reinforced polyethylene bearing surfaces (Group 1) when compared with Groups 2 and 3 and the control subjects (Group 5). For aluminum and vanadium, no detectable differences were observed among any of the groups. In addition, analysis of 24-hour urine samples showed no significant differences in titanium, aluminum, or vanadium concentrations among any of the groups. Elevated serum titanium levels may serve as a marker of patellar component failure or accelerated femoral component wear in total knee replacements with titanium alloy bearings. The toxicologic ramifications of these findings are unknown.

The relationship between activity and ions in patients with metal-on-metal bearing hip prostheses.

BACKGROUND Total hip replacements with metal-on-metal bearings are frequently implanted in young, active patients. The relationship between patient activity and cobalt and chromium ion levels has not been investigated, to our knowledge. METHODS Seven patients with well-functioning metal-on-metal bearing hip prostheses and one control subject (no implants), all with normal renal function, were monitored during a two-week-long activity protocol. Lower-extremity activity was continuously assessed with use of a computerized, two-dimensional accelerometer. During the first week, the subjects were requested to limit physical activity. The subjects then completed an hour-long treadmill test followed by a week in which they were encouraged to be as physically active as practically possible. Serum levels of cobalt and chromium ions and urine levels of chromium were assessed at ten time-points during these two weeks. RESULTS Regardless of activity, the serum ion levels for a given patient were essentially constant and no correlation was found between patient activity and serum levels of cobalt or chromium, or urine levels of chromium. A mean increase in activity of 28% during the week of high-intensity activity was associated with a mean decrease of 2.7% in the serum cobalt level and a mean increase of 2.0% in the serum chromium level. During the treadmill test, a mean increase in activity of 1621% was associated with a mean increase of 3.0% in the serum cobalt level and a mean increase of 0.8% in the serum chromium level. These results fall within the variability for the measurement accuracy of these tests. CONCLUSIONS For these patients, serum cobalt and chromium ion levels were not acutely affected by patient activity. Periodic measurements of serum ion levels could be used to monitor the tribologic (lubrication, friction, and wear) performance of a metal-on-metal bearing without adjusting for patient activity. Additional research is needed into the kinetics of ion production, transport, and excretion.

Differential lymphocyte reactivity to serum-derived metal-protein complexes produced from cobalt-based and titanium-based implant alloy degradation

The lymphocyte response to serum protein complexed with metal from implant alloy degradation was investigated in this in vitro study using primary human lymphocytes from healthy volunteers (n = 10). Cobalt chromium molybdenum alloy (Co-Cr-Mo, ASTM F-75) and titanium alloy (Ti-6Al-4V, ASTM F-136) beads (70 microm) were incubated in agitated human serum at 37 degrees C to simulate naturally occurring metal implant alloy degradation processes. Particulate free serum samples that had been incubated with metal were then separated into molecular weight based fractions. The amounts of soluble Cr and Ti within each serum fraction were measured and correlated with lymphocyte proliferation response to the individual serum fractions. Lymphocytes from each subject were cultured with 11 autologous molecular weight based serum fractions either with or without added metal. Two molecular weight ranges of human serum proteins were associated with the binding of Cr and Ti from Co-Cr-Mo and Ti implant alloy degradation (at <30 and 180-250 kDa). High molecular weight serum proteins ( approximately 180 kDa) demonstrated greater lymphocyte reactivity when complexed with Cr alloy and Ti alloy than low (5-30 kDa) and midrange (30-77 kDa) serum proteins. When the amount of lymphocyte stimulation was normalized to both the moles of metal and the moles of protein within each fraction (metal-protein complex reactivity index), Cr from Co-Cr-Mo alloy degradation demonstrated approximately 10-fold greater reactivity than Ti in the higher molecular weight serum proteins ( approximately 180 kDa). This in vitro study demonstrated a lymphocyte proliferative response to both Co-Cr-Mo and Ti alloy metalloprotein degradation products. This response was greatest when the metals were complexed with high molecular weight proteins, and with metal-protein complexes formed from Co-Cr-Mo alloy degradation.