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Purpose The aim of this pilot study was to assay metal concentrations in the serum of patients who had undergone dental implant placement, orthognathic surgery using rigid metal fixation plates and screws, and total temporomandibular joint replacement (TMJ TJR). Materials and Methods Thirty patients were identified and included in this pilot study. Sixteen patients (9 men and 8 women), with an average age of 44 years (range, 19 to 79 yr), provided informed consent to participate and were divided into 3 study groups with 4 patients in each (group 1, orthognathic surgery; group 2, TMJ TJR; and group 3, dental implant placement). A control group consisted of volunteers without any implanted metallic devices. Blood samples for serum metal analysis were obtained and analyzed in accordance with the standardized collection and testing protocols used at the Trace Metal Analysis Laboratory of the Department of Orthopedic Surgery at the Rush University Medical Center (Chicago, IL). Results All control participants had levels below the normal reference range for all serum markers assessed. In the orthognathic group, 1 patient had an increased serum cobalt level. In the TMJ TJR group, 1 patient had an increased serum cobalt level and another patient had an increased serum chromium level. In the dental implant group, 1 patient had an increased serum titanium level and another had increased serum levels of titanium and chromium. Conclusions This is the first study to report on the release of metal into the bloodstream in patients with different maxillofacial implanted metallic objects. The results raise questions regarding the types and magnitude of metal released from maxillofacial reconstruction devices and their potential long-term local and systemic effects. Future large-scale prospective studies involving serial measurements in homogeneous groups of patients could further elucidate the impact of these findings.

Study design Prospective longitudinal study. Objective The serum titanium (Ti) concentrations were examined in patients implanted with a PRESTIGE LP Cervical Disc System (Medtronic, Inc., Memphis, TN). The metal-on-metal disc with ball-in-trough articulation is made of titanium alloy/titanium carbide composite (Ti-6Al-4 V/TiC). Summary of background data Cervical disc arthroplasty provides a motion-preserving treatment alternative to anterior cervical discectomy and fusion for degenerative cervical disc disease. The articulating surfaces have a tendency to generate in vivo wear in the form of insoluble particulates (debris) and soluble metal ions. Not much information is available on the long-term metal concentrations observed in cervical disc arthroplasty and how these compare with the metal concentrations in Ti-based posterior fixation devices and other joint replacement implants. Methods Thirty patients were enrolled after strict exclusion criteria that included no previous permanent metal implants and no professional exposure to metal particles. High-resolution inductively coupled plasma-mass spectrometry was used to assay blood serum titanium concentrations preoperatively and at 3, 6, 12, 24, 36, 60, and 84 months after surgery. The detection limit for Ti was 0.2 ng/mL. The Friedman test was used to make longitudinal statistical comparisons. Results The median serum Ti concentrations determined preoperatively, and at 3, 6, 12, 24, 36, 60, and 84 months were 0.10, 1.22, 1.15, 1.27, 1.21, 1.46, 1.34, and 1.42 ng/mL, respectively. The serum Ti concentrations at all postoperative time points were significantly higher than that at the preoperative time point (Friedman P Conclusion The long-term postoperative serum Ti concentrations were significantly higher than the preoperative concentrations. The observed serum Ti concentrations in this study are lower than the reported concentrations in patients receiving posterior spinal instrumentation and metal or ceramic-on-polyethylene hip prostheses with Ti-alloy based stems and acetabular components. Level of evidence 3.

Hip arthroplasty femoral stems coated with Ti6Al4V beads were treated by anodic oxidation in H3 PO4 for enhanced bioactivity and were studied in a 6-month canine model to determine the effects of the treated surface on the ingrowth of bone and soft tissues. The area fractions of bone, marrow, and fibrous tissue in the porous coating of seven treated and seven untreated control implants were determined using histomorphological techniques. The area fraction of bone within the porous coating was greater for anodic oxide treated (23.6 ± 8.3%) compared to control implants (l2.7 ± 4.7%) (p = 0.013), and there was less fibrous tissue in the treated implants (18.0 ± 9.5%) compared to the controls (33.1 ± 7.9%) (p = 0.006). XPS, XRD, TEM, and SEM analyses of the treated implants revealed a 400 nm-thick titanium oxide layer of low crystallinity with an undulating surface, populated with more than 25 nm-size pores per square micrometer. There was no detectable increase in serum titanium or in generation of particulates locally compared to the control implants. Micro and nanoscale surface modification by anodic oxidation increased bone ingrowth and reduced fibrous tissue, which may extend the longevity of fixation, limiting pathways for particle migration, and impeding the progression of osteolysis and aseptic loosening of arthroplasty components. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 283-290, 2017.

Some tissues from metal-on-metal (MoM) hip arthroplasty revisions have shown evidence of adaptive-immune reactivity (i.e., excessive peri-implant lymphocyte infiltration/activation). We hypothesized that, prior to symptoms, some people with MoM hip arthroplasty will develop quantifiable metal-induced lymphocyte reactivity responses related to peripheral metal ion levels. We tested three cohorts (Group 1: n = 21 prospective longitudinal MoM hip arthroplasty; Group 2: n = 17 retrospective MoM hip arthroplasty; and Group 3: n = 20 controls without implants). We compared implant position, metal-ion release, and immuno-reactivity. MoM cohorts had elevated (p 2), compared with 76% of Group 2, and 15% of Group 3 controls (patch testing was a poor diagnostic indicator with only 1/21 Group 1 positive). Higher cup-abduction angles (50° vs. 40°) in Group 1 were associated with higher serum Cr (p < 0.07). However, sub-optimal cup-anteversion angles (9° vs. 20°) had higher serum Co (p < 0.08). Serum Cr and Co were significantly elevated in reactive versus non-reactive Group-1 participants (p < 0.04). CD4+CD69+ T-helper lymphocytes (but not CD8+) and IL-1β, IL-12, and IL-6 cytokines were all significantly elevated in metal-reactive versus non-reactive Group 1 participants. Our results showed that lymphocyte reactivity to metals can develop within the first 1-4 years after MoM arthroplasty in asymptomatic patients and lags increases in metal ion levels. This increased metal reactivity was more prevalent in those individuals with extreme cup angles and higher amounts of circulating metal.

Background: Cervical disc arthroplasty (CDA) has emerged as an alternative to anterior cervical discectomy and fusion for degenerative cervical disc disease. The artificial discs provide intervertebral motion using multicomponent articulation and thus tend to generate particulate debris and soluble metal ions. Limited information is available on the long-term metal concentrations and associated systemic adverse events observed in metal-on-metal CDA. Serum chromium (Cr) and nickel (Ni) concentrations were assessed in patients implanted with ball-in-trough stainless steel–based cervical disc through 7 years. Methods: A prospective, nonrandomized longitudinal study was conducted that included 25 patients following rigorous exclusion criteria that included no previous permanent metal implants and no professional exposure to metal particles. Blood serum Cr and Ni concentrations were assayed preoperatively and at 3, 6, 12, 24, 36, 60, and 84 months postoperatively using high-resolution inductively coupled plasma–mass spectrometry. Longitudinal statistical comparisons were made using the Friedman test with statistical significance at P Results: Median serum concentrations determined preoperatively and at 3, 6, 12, 24, 36, 60, and 84 months postoperatively were 0.074, 0.106, 0.132, 0.170, 0.172, 0.274, 0.192, and 0.203 ng/mL for Cr and 0.085, 0.178, 0.222, 0.175, 0.205, 0.284, 0.181, and 0.194 ng/mL for Ni. The serum Cr concentrations were statistically higher for all postoperative time periods compared to preoperative concentration (Friedman P Conclusions: The Cr concentrations detected at all postoperative times were statistically higher than preoperative concentrations, whereas Ni concentration was statistically higher than the preoperative concentration only at 84 months.

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.

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. Level of Evidence: Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.

Cell-mediated hypersensitivity associated with metal components may be related to levels of implant debris. We tested this hypothesis by comparing lymphocyte reactivity to soluble Co, Cr, Ni, and Ti of patients with metal-on-polyethylene and metal-on-metal arthroplasties with healthy controls, and patients with osteoarthritis. The metal-on-metal group (n=9) demonstrated significantly elevated serum Co and Cr concentrations (13- and 58-fold, P.05, respectively) and significantly elevated lymphocyte reactivity to Co (SI5, P.004) and Ni (SI2.5, P.01) when compared to controls (n=12) and subjects with metal-on-poly implants (n=7). These elevated in vivo metal levels demonstrated positive linear correlation with lymphocyte reactivity supporting our hypothesis that lymphocyte metal-induced reactivity increases with increased metal exposure. These results represent the first direct link between in vivo metal exposure and lymphocyte reactivity. Whether this lymphocyte reactivity to metal debris is etiologically linked to poor implant performance remains uncertain.

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.

There is concern regarding elevated metal ion levels in the blood during pregnancy and the potential fetal effects in women with metal-on-metal (MOM) implants. We obtained maternal and umbilical cord blood samples from 3 patients with a MOM hip arthroplasty and 7 control subjects without any metallic implants. Serum metal ion levels including chromium, cobalt, titanium, and nickel were tested using high-resolution sector-field inductively-coupled plasma-mass spectrometry. Mothers with MOM-bearing implants had significantly elevated levels of serum cobalt and chromium compared with control-group mothers, and umbilical cord blood from mothers with MOM implants also had significantly higher serum metal ion levels compared with control-group mothers. The results of this study show that circulating serum levels of metal ion degradation products from MOM bearings cross the placenta and expose the fetus to metal ions. However, the placenta exerts a modulatory effect on cord blood, resulting in decreased levels compared with maternal samples (approximately 15% of maternal chromium and 50% of maternal cobalt). Physicians and women of child-bearing age should be aware of this potential effect when considering the use of MOM-bearing implants.

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

Metal toxicity from sources such as orthopaedic implants was investigated in terms of immune system hyper-reactivity to metal implant alloy degradation products. Lymphocyte response to serum protein complexed with metal from implant alloy degradation was investigated in thisin vitrostudy using primary human lymphocytes from healthy volunteers (n = 10). Cobalt chromium molybdenum alloy (Co-Cr-Mo, ASTM F-75) and titanium allay (Ti-6A1-4V, ASTM F-136) beads (70 um) were incubated in agitated human serum at 37 degrees Celsius to simulate naturally occurring metal implant alloy degradation processes. Particulate free serum samples, which were 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 autologaus 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 180-330 kDa). High molecular weight serum proteins 180 kDa) demonstrated greater lymphocyte reactivity when complexed with metal released from Co-Cr-Mo alloy and Ti alloy than with 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, MPCRI), Cr from Co-Cr-Mo alloy degradation demonstrated approximately 10 fold greater reactivity than Ti in the higher molecular weight serum proteins (~ 180-250 kDa). Thisin vitrostudy 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. (Mol Cell Siochem222:127-136, 2001)

A case is presented in which an elevated serum titanium level was used to make the diagnosis of a failed metal-backed patellar component. The preoperative serum titanium level was 536.8 ppb, which was 98 times higher than the patient's previous level (taken 1 year earlier, when he was asymptomatic) and 2 orders of magnitude higher than the expected level with a well-functioning implant of this type. Revision surgery confirmed that the polyethylene portion of the patellar component had worn through, leaving the titanium portion of the patellar implant to articulate with the femoral component. Wear-through was not evident on preoperative radiographs or clinical examination. As knowledge about the expected ranges for serum metal ion levels after total joint arthroplasty continues to increase, the diagnostic utility of serum metal ion testing in the evaluation of joint arthroplasty function will continue to improve.

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.

There is continued interest in the measurement of degradation products of metallic implants in biological tissues and fluids. A study was conducted to compare analytical results obtained by the Zeeman Background Corrected Atomic Absorption Spectrometric and Inductively Coupled Plasma Mass Spectrometric techniques on a uniform set of triple-element (Ti, Al, and V) spiked human serum specimens over concentration ranges up to 20 ppb (20 ng/ml). The results indicate that the two methods are comparable. The positive and negative aspects of each method of instrumental analysis are discussed.

Improved understanding of the clinical outcomes of orthopedic implants requires the study of implants at the end of their service life. Previous studies focused on the retrieval of so-called failed implants during surgical revision. Interest is now moving to the study of successful implants, which are those still in place at the patient's death. A procedure was developed for recruitment of implant patients and their families and for safe and effective device and tissue retrieval after death. More than 50 retrievals were performed to support various research efforts.

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.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.

The systemic distribution of corrosion and wear products from total joint replacement devices in the human body needs to be better understood. This requires the measurement of metal ions, especially Al, Ti and V, at ppb and sub-ppb levels in serum and other organic matrices. Both ETAAS and NAA have been reported for determining some of the elements, but neither is completely suitable for determining all three elements in serum at the levels encountered in control subjects and in patients with well-functioning devices. A method is described for the simultaneous determination of Al, Ti and V in serum using ETV–ICP-MS. Spectral interferences from the serum matrix were circumvented or alleviated by the careful selection of analytical masses, chemical modifiers and the temperature programme of the electrothermal vaporizer. The serum matrix was found to influence the transport of analytes (carrier effect) from the furnace to the plasma. The carrier effect was corrected by using major component matrix matching with internal standardization, and good recovery was obtained. Detection limits of 0.7, 0.4 and 0.1 ppb in serum were obtained for Al, Ti and V, respectively. NIST SRM 1598 Bovine Serum and a pooled human serum were analysed. The Al concentration found was 3.8±0.8 ppb while the V concentration was below the detection limit of 0.1 ppb, compared with the certified value for Al of 3.7±0.9 ppb and the information value for V of 0.06 ppb (no value is given for Ti in SRM 1598). The Ti value obtained for the pooled human serum sample was within the concentration range previously reported for normal human serum.

Serum metal ion levels increase after primary total hip arthroplasty (THA) regardless of bearing surface. We conducted a study to determine the effect of a second joint arthroplasty on existing serum metal ion levels at long-term followup. Twelve patients underwent primary THA and then either another THA (8 patients) or total knee arthroplasty (TKA) (4 patients). The secondary procedures were performed a mean of 102.7 months (range, 36-144 months) after the index surgeries. The secondary THA group had significantly elevated levels of cobalt ion at 36 and 48 months, chromium ion at 12 and 24 months, and titanium ion at 48 and 72 months. The TKA group had no significant differences in cobalt, chromium, or titanium ion levels up to 72 months after surgery. Overall, when metal-polyethylene THA was performed after primary THA, there was a trend toward elevated serum metal ion levels at all follow-up intervals. This trend should be investigated with larger clinical trials.

We previously reported on the metal ion concentrations of cobalt, chromium, and titanium that were found in the serum of patients three years after they had undergone primary total hip arthroplasty as compared with the concentrations found in the serum of control patients who did not have an implant. This study is a concise update on the serum metal levels found in a cohort of these patients ten years after the time of hip implantation. Of the original seventy-five subjects, metal ion levels were available for forty patients (53%). Ten patients (hybrid group) had received a hybrid total hip replacement that consisted of a modular cobalt-alloy femoral stem with a cobalt-alloy femoral head that had been inserted with cement and a titanium acetabular socket that had been inserted without cement. Nine patients (cobalt-chromium [CoCr] group) had received an implant with an extensively porous-coated modular cobalt-alloy femoral stem and femoral head along with a titanium acetabular socket; the femoral and acetabular components had each been inserted without cement. Eight patients (titanium group) had undergone insertion of a proximally porous-coated modular titanium-alloy femoral stem with a cobalt-alloy femoral head and a titanium acetabular socket; the femoral and acetabular components had each been inserted without cement. Thirteen patients (control group) from the original control group of patients who had not received an implant served as control subjects. Serum metal levels were measured with use of high-resolution sector field inductively coupled plasma mass spectrometry. The hybrid total hip arthroplasty group had mean cobalt levels that were 3.2 times higher at 120 months than they were at baseline, and the cobalt levels in that group were significantly higher than those in the titanium total hip arthroplasty group at thirty-six, sixty, eighty-four, ninety-six, and 120 months (p < 0.01). The hybrid group had mean chromium levels that were 3.9 times higher at 120 months than they were at baseline, and the CoCr total hip arthroplasty group had chromium levels that were 3.6 times higher at 120 months than they were at baseline. The serum titanium levels were higher in the titanium group at all follow-up time intervals as compared with the levels in all other groups, and the level in the titanium group at 120 months was eighteen times higher than it was at baseline (p < 0.01). Patients with well-functioning primary metal-on-polyethylene total hip replacements had elevated serum metal levels for as many as ten years postoperatively. Furthermore, metal release at the modular femoral head-neck junctions, rather than passive dissolution from porous ingrowth surfaces, was likely the dominant source of serum cobalt and chromium.

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.

Metal-on-metal total disc replacement is a recent alternative treatment for degenerative disc disease. Wear and corrosion of these implants can lead to local and systemic transport of metal debris. This prospective longitudinal study examined the serum chromium and cobalt levels in 24 patients with cobalt-chromium alloy metal-on-metal lumbar disc replacements.Serum was assayed for chromium (Cr) and cobalt (Co) using high-resolution inductively-coupled plasma-mass spectrometry. Detection limits were 0.015 ng/mL for Cr and 0.04 ng/mL for Co.Median serum Co levels at pre-op, 3, 6, 12, 24, and 36-months post-op were 0.10, 1.03, 0.96, 0.98, 0.67, and 0.52 ng/mL, respectively. Median serum Cr levels were 0.06, 0.49, 0.65, 0.43, 0.52, and 0.50 ng/mL, respectively.In general, these results indicated that serum Co and Cr levels are elevated at all postoperative time points and are of the same order of magnitude as those observed in well-functioning metal-on-metal surface replacements of the hip and in metal-on-metal total hip replacements at similar postoperative time points.

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.

A prospective study of serum and urinary ion levels was undertaken in a triathlete who had undergone a metal-on-metal resurfacing arthroplasty of the hip four years previously. The one month study period included the final two weeks of training, the day of the triathlon, and the two weeks immediately post-race. Serum cobalt and chromium levels did not vary significantly throughout this period, including levels recorded on the day after the 11-hour triathlon. Urinary excretion of chromium increased immediately after the race and had returned to pre-race levels six days later. The clinical implications are discussed.

This study evaluates steady-state serum metal levels in patients with 4 different combinations of fixation modalities, materials, and bearing couples. Forty patients with a minimum of 5 years of follow-up and with well-functioning primary total hip arthroplasty were recruited to have serum metal levels measured. Serum chromium and cobalt levels in the metal-on-metal cohort were significantly higher (P < .05) than the other 3 cohorts. The noncemented ceramic-polyethylene cohort had significantly lower (P < .05) serum chromium levels compared to cemented and noncemented metal-polyethylene cohorts and significantly higher serum titanium levels compared to the cemented metal-polyethylene cohort which had no titanium-containing implants. Debris generated at the metal head/neck modular junction likely accounts for the significantly lower serum chromium concentration in ceramic-polyethylene bearing couples.

In this review, the prospects for using blood, serum, and/or urine metal levels for monitoring the performance of metal-on-metal hip arthroplasty systems are explored. This approach does have substantial potential for serving this function; however, the methodology is technically challenging and the interpretation of the values requires an extensive database with correlative clinical information. At this time, it is premature to recommend metal concentration analysis on a routine clinical basis for patients with metal-on-metal total hip arthroplasties. Nonetheless, metal concentration analysis remains a powerful research tool in the evaluation of metal-on-metal hip arthroplasty systems.

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.

In the majority of patients, orthopaedic implants are biocompatible. However, there is an increasing recognition that, in the long-term, permanent orthopaedic implants may be associated with adverse local and remote tissue responses in some individuals. These adverse effects are mediated by the degradation products of implant materials. The recent reintroduction of metal-on-metal bearings for total hip arthroplasty has heightened concerns about the biologic response to metal degradation products in light of the fact that the serum and urine metal concentrations in patients with these implants typically are higher than those seen in patients with conventional metal-on-polyethylene bearings. From previous studies of long-term metal-on-metal McKee-Farrar implants, it seems that these elevated levels may persist for the duration of the implant's lifetime. This is of particular concern in the younger and more active patient in whom life expectancy after implantation may exceed 30 years. The association of metal release from orthopaedic implants with any metabolic, bacteriologic, immunologic, or carcinogenic toxicity currently remains conjectural because cause and effect have not been established in human subjects. However, continued surveillance of patient populations with metal implants, particularly those with metal-metal bearings, is warranted.

Metal-on-metal bearings have demonstrated low wear after many years in vivo1,2. Consequently, there has been a resurgence of interest in metal-on-metal bearings. There are, however, concerns about potential adverse effects due to local accumulation and systemic distribution of cobalt-chromium wear moieties and ions, especially after several decades in situ3-5. Cobalt and chromium particles have been shown to induce carcinoma in animal models6, giving rise to the concern that such alloys could have the same effect in human tissue, if present in sufficient amounts for a sufficient length of time. Autopsy retrievals provide the opportunity to assess the distribution of wear products in the tissues immediately surrounding as well as at a distance from the implant7. The aim of this study was to assess the distribution and histological effects of wear particles from a McKee-Farrar metal-on-metal-bearing total hip replacement after nearly thirty years in situ. Amoderately obese, forty-seven-year-old woman fell and sustained a transcervical fracture of the right femur, which was treated initially with internal fixation and a spica cast. A subsequent nonunion was treated with a Judet prosthesis, which was eventually removed, leaving the patient with a Girdlestone resection of the right hip. In 1970, at the age of sixty-eight years, the patient underwent total hip arthroplasty of the left hip for the treatment of extensive osteoarthritis, and a metal-on-metal McKee-Farrar total hip prosthesis was implanted. In 1995, the patient was contacted by our research group, and she agreed to be evaluated as part of a long-term study of McKee-Farrar total hip replacements8,9. She also consented to join the “Willed Joint” program of the Joint Replacement Institute, thereby agreeing to donate her hip joints and to permit postmortem biopsies of her organs. The patient …

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 microm) on identical Co-alloy stems at 2.2 kN for 1x10(6) 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 (-266153 mV), greater maximum voltage changes (11656 mV, p0.05, t-test) and voltage variability (30.5 mV, p0.05, 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.

The biocompatibility of metallic implant surfaces is governed in large part by the interfacial kinetics associated with metal release and protein binding. The kinetics of metal release from, and protein binding to, cobalt- and titanium-based implant alloys in human serum were investigated by (1) measuring the temporal release of Cr and Ti into serum from Co-Cr-Mo (ASTM F-75) and Ti implant alloys (Ti-6Al-4V: ASTM F136, and commercially pure Ti, cpTi: ASTM F67), respectively; (2) examining the composition of human serum proteins adsorbed onto the surfaces of Co- and Ti-based implant alloys; and (3) identifying the serum proteins associated with the binding of soluble Cr and Ti degradation products. Analysis of metal dissolution kinetics found that Cr was released from Co-based implant alloy at an order of magnitude higher than Ti was released from Ti-based implant alloys. Serum became saturated with soluble CR and Ti at levels as high as 3,250 ng/mL Ti from cpTi; 3,750 ng/mL Ti from Ti-6Al-4V; and 35,400 ng/mL Cr from Co-Cr-Mo degradation. The observation that human serum binds more released metal from Co-based alloy dissolution was consistent with the observed differences in biofilm composition between the two alloys, where additional serum protein(s) of approximately ≈140 (kDa) molecular weight were detected on Co-based implant alloy surfaces. However, both Cr and Ti released from Co- and Ti-based alloys exhibited a bimodal binding pattern to both low molecular weight serum protein(s) (

Background: There has been a resurgence in the interest and use of metal-on-metal (MOM) bearing surfaces in hip arthroplasty. However, concerns remain regarding elevated metal levels in blood and urine and possible effect on the fetus of a pregnant female with a MOM bearing surface. Purpose: The purpose of this study is to compare metal concentrations in maternal and fetal serum in subjects with MOM hip arthroplasty to subjects without metal-containing implants. Methods: Maternal and umbilical cord blood was obtained from three patients with a MOM hip arthroplasty and seven patients without implants who served as controls. Maternal and placental serum metal levels were tested using inductively-coupled plasma-mass spectrometry. The serum concentrations of titanium, nickel, cobalt, and chromium were measured. Intergroup comparisons were made independent of the means with use of the Wilcoxon-Mann-Whitney test. Correlations were established with use of the Spearman rank-order correlation test. Results: Mothers with implants have statistically significant elevations in serum Cr and Co levels in comparison to control mothers. Babies from mothers with implants have statistically significant elevations in serum Co and Cr levels in comparison to control babies. Conclusions: The Cr and Co serum levels obtained from both mothers with implants and the offspring of mothers with implants are elevated in comparison to the control maternal and

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.

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.

The purpose of this study was to evaluate the occurrence of bone ingrowth in a porous coated tibial component of a canine total condylar design knee replacement model. The entire undersurface of the tibial prosthesis was covered by a titanium fiber metal porous composite pad. Projecting from this surface were three short, cylindrical, fiber metal coated pegs that along with a posterior screw provided initial stabilization of the device. Left total knee replacements were performed on six dogs using alignment and cutting jigs to prepare the bony surfaces. The dogs were killed 6 months following surgery. Extensive bone ingrowth was present in all pegs of every tibial component. Bone ingrowth was present in 12% of the pad area of one component, 22.7 to 41.6% in four components, and 81.1% in another. The void spaces in other areas were filled with fibrous tissue or in the periphery of the device with fibrocartilage. Bone ingrowth in the pad was consistent in the vicinity of the pegs and was variable in regions not adjacent to the pegs, suggesting that the pegs exerted a strong influence on the pattern of bone ingrowth into the pad.

Porous titanium fiber implants for cementless skeletal fixation by bone ingrowth were treated with a calcium phosphate coating applied by a plasma flame-spray technique. In a paired experiment, treated and control implants were inserted in the humeri and olecranons of 36 adult dogs for periods of 1, 2, 4, and 6 weeks. After the animals were sacrificed, a biomechanical evaluation of the strength of skeletal fixation of the implants and a histologic evaluation of bone ingrowth was done. The mean shear strength of skeletal fixation at four weeks for the calcium phosphate-coated implants was 24% greater (P less than .01) than for paired controls. No difference in strength of fixation between treated and control implants was present at other time periods. The osteoconductive properties of the ceramic coating were demonstrated by bone forming in direct contact with the calcium phosphate coating on the metal fibers of the treated implants. No significant increase for the volume of bone ingrowth was established for treated implants compared to paired controls at any time period.