Serum Metal Levels in Maxillofacial Reconstructive Surgery Patients: A Pilot Study.

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.

Do ion concentrations after metal-on-metal hip resurfacing increase over time? A prospective study.

Thirteen male and five female patients received a Conserve Plus hip resurfacing and prospectively provided blood samples to measure cobalt and chromium levels for up to 11 years. Trends in metal levels over time in unilateral and bilateral patients were studied. A multi-variate regression model was used to account for potential covariates. For unilaterals over all time intervals, the median Serum Cobalt level (CoS) was 1.06 µg/L, while the median Serum Chromium level (CrS) was 1.58 µg/L. For bilaterals, the median post operative CoS was 2.80 µg/L, while the median CrS was 5.80 µg/L. Metal levels increased within the first year then decreased and stabilized. These results show that serum metal levels in well-functioning implants can be low and do not increase with time.

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.

Chromium and Nickel Concentrations in Subjects with a Stainless Steel Metal-on-Metal Cervical Disc Arthroplasty: Results from a Prospective Longitudinal Study with 7 Years Follow-Up.

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 < .05. 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 <.01), whereas serum Ni concentration was statistically higher at the 84-month postoperative time period than the preoperative concentration (Friedman P <.01) and then the concentration at 3, 12, 24, and 60 months postoperatively (Friedman P < .03). 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.

Nanoscale surface modification by anodic oxidation increased bone ingrowth and reduced fibrous tissue in the porous coating of titanium-alloy femoral hip arthroplasty implants.

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.

Serum Metal Concentrations in Patients With Titanium Ceramic Composite Cervical Disc Replacements.

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 < 0.01). 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.

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.

Metal ion levels in maternal and placental blood after metal-on-metal total hip arthroplasty.

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.

Effect of a second joint arthroplasty on metal ion levels after primary total hip arthroplasty.

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.

Ten-year outcome of serum metal ion levels after primary total hip arthroplasty: a concise follow-up of a previous report*.

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.

Serum metal levels and bearing surfaces in total hip arthroplasty.

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.

Metal degradation products: a cause for concern in metal-metal bearings?

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.

Can metal levels be used to monitor metal-on-metal hip arthroplasties?

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.

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.