Elevated Cobalt Levels Research Articles

Elevated cobalt levels in metal-on-polyethylene knee megaprostheses: a prospective 1-year cohort study of 56 patients with hip and knee megaprostheses.

Concerns have emerged regarding elevated levels of cobalt and chromium in patients with metal-on-metal megaprostheses. This prospective study aims to identify systemic cobalt and chromium levels in metal-on-polyethylene knee and hip megaprostheses and their associations with other factors. 56 patients underwent knee or hip megaprosthesis surgery at 2 sarcoma centers. Serum cobalt and chromium levels were measured preoperatively and thrice within the first year using inductively coupled plasma mass spectrometry. A statistically significant difference in serum cobalt levels (1.4 ppb; 95% confidence interval [CI] 0.0-3.3) was observed 1 year after knee megaprosthesis surgery compared with preoperative levels. In contrast no difference in chromium levels was observed after 1 year compared with preoperative levels (0.05 ppb; CI 0.0-0.8). An association between younger age, higher eGFR, and increased cobalt levels was observed. No significant correlations were found between ion levels and resection length or the number of modular connections. We found elevated serum ion levels in metal-on-polyethylene knee megaprostheses in contrast to metal-on-polyethylene hip megaprostheses. Furthermore, a positive correlation between cobalt and chromium levels, and between cobalt and eGFR was identified, along with a negative correlation between cobalt and age. This study highlights the importance of monitoring systemic cobalt and chromium levels in patients with megaprostheses.

No Difference in Revision Rates and High Survival Rates in Large-head Metal-on-metal THA Versus Metal-on-polyethylene THA: Long-term Results of a Randomized Controlled Trial.

Pseudotumor formation is a well-known complication in metal-on-metal (MoM) THA. Pseudotumors combined with elevated serum ion levels and complaints from patients can lead to high revision rates. Long-term (> 10 years) results obtained from randomized trials comparing large-head MoM THA and conventional metal-on-polyethylene (MoP) THA are lacking regarding revision and survival rates, pseudotumor formation, functional outcomes, and serum ion levels. At 10 years of follow-up, (1) what is the difference in survival and revision rates between large-head (38 to 60 mm) MoM THA and conventional 28-mm MoP THA? (2) What is the difference in pseudotumor formation between large-head MoM THA and MoP THA? (3) Is there a difference in functional outcome between large-head MoM THA and MoP THA? (4) What is the difference in serum ion levels between large-head MoM THA and MoP THA? Between January 2006 and December 2008, 104 patients were randomized to receive either cementless MoM THA (50 patients) or cementless MoP THA (54 patients). In all, 78% (81 of 104) of patients completed the 10-year postoperative follow-up: 36 patients with MoM THA (72%; six patients lost to follow-up) and 45 with MoP THA (83%; four lost to follow-up). In the MoM group, 47% (17) were men, and the patients had a mean ± SD age of 60 ± 5 years. In the MoP group, 38% (17) were men, and the patients had a mean age of 61 ± 5 years. All baseline characteristics were similar between the groups. At 10 years of follow-up, all patient records were screened for revision surgery or complications, and the primary endpoint was survivorship free from revision for any cause at the 10-year follow-up interval, which we analyzed using a Kaplan-Meier survival analysis. All patients had a CT scan to determine the pseudotumor classification, which was reviewed by an independent radiologist. Functional outcome was measured using the patient-reported Oxford Hip Score and Harris Hip Score; the latter was assessed by a blinded nurse practitioner. Finally, serum ion cobalt and chrome concentrations were measured at 10 years postoperatively. Because the a priori sample size calculation for this randomized controlled trial was based on a different endpoint, a post hoc power analysis was performed for this long-term follow-up study, with survival as the primary outcome. It showed that considering the number of included patients, this study would have sufficient power (one-sided testing, alpha 0.05, power 80%) to discern a difference of 20% in the survival rate between the MoP and MoM groups (95% versus 75%). With the numbers available, there was no difference in survivorship free from revision for any cause between the MoP group and MoM group at 10 years (95% [95% CI 85% to 98%] versus 92% [95% CI 82% to 98%]; p = 0.6). A higher percentage of patients in the MoM group had pseudotumors on CT than those in the MoP group did, but pseudotumors were observed in both groups (56% [20 of 36] in the MoM group versus 22% [10 of 45] in the MoP group, relative risk 1.8 [95% CI 1.2 to 2.6]; p = 0.002). A higher proportion of elevated cobalt and chrome levels was found in the MoM group (19% and 14%, respectively) than in the MoP group (0% for both cobalt and chrome) (cobalt: RR 1.2 [95% CI 1.1 to 1.5]; p = 0.002; chrome: RR 1.2 [95% CI 1.0 to 1.3]; p = 0.01). In 25% of the patients with pseudotumors (5 of 20 patients), there were elevated serum cobalt levels. None of the 23 patients without pseudotumors had elevated cobalt levels (RR 1.3 [95% CI 1.0 to 1.7]; p = 0.01). There was no difference in functional outcome between study groups, nor a difference between patients with a pseudotumor and those without. This study showed that the survival of patients with large-head MoM THA was high and comparable to that of those with MoP THA, which contrasts with the high revision rates reported by others. Although some patients with MoP THAs experienced pseudotumors, the risk of a pseudotumor was much greater in MoM hips, and serum ion levels were higher in patients who received an MoM THA. For these reasons and unknown future complications, continued surveillance of patients with MoM THAs seems important. Level I, therapeutic study.

Cobalt Neurotoxicity: Transcriptional Effect of Elevated Cobalt Blood Levels in the Rodent Brain.

Metal-on-metal (MoM) hip implants made of cobalt chromium (CoCr) alloy have shown early failure compared with other bearing materials. A consequence of the abnormal wear produced by these prostheses is elevated levels of cobalt in the blood of patients, which can lead to systemic conditions involving cardiac and neurological symptoms. In order to better understand the implications for patients with these implants, we carried out metal content and RNA-Seq analysis of excised tissue from rats treated intraperitonially for 28 days with low concentrations of cobalt. Cobalt blood levels in dosed rats were found to be similar to those seen in some patients with MoM implants (range: 4–38 μg/L Co in blood). Significant accumulation of cobalt was measured in a range of tissues including kidney, liver, and heart, but also in brain tissue. RNA-Seq analysis of neural tissue revealed that exposure to cobalt induces a transcriptional response in the prefrontal cortex (pref. cortex), cerebellum, and hippocampus. Many of the most up- and downregulated genes appear to correspond to choroid plexus transcripts. These results indicate that the choroid plexus could be the brain tissue most affected by cobalt. More specifically, the differentially expressed genes show a disruption of steroidogenesis and lipid metabolism. Several other transcripts also demonstrate that cobalt induces an immune response. In summary, cobalt exposure induces alterations in the brain transcriptome, more specifically, the choroid plexus, which is in direct contact with neurotoxicants at the blood–cerebrospinal fluid barrier.

An analysis of heavy metals contamination and estimating the daily intakes of vegetables from Uganda

Background: Environmental contamination with elevated levels of copper (Cu), cobalt (Co), iron (Fe), zinc (Zn), lead (Pb), chromium (Cr6+), cadmium (Cd), and nickel (Ni)—all states of which are found in Uganda—raises health risk to the public. Pb, Cr6+, Cd, and Ni for instance are generally considered nonessential to cellular functions, notwithstanding the importance of the oxidative state of the metals in bioavailability. As such, we aimed in this study (i) to evaluate heavy metal concentrations in four vegetables from a typical open-air market in Uganda, (ii) to assess the safety of consuming these vegetables against the World Health Organization (WHO) recommended limits of heavy metals consumption, and (iii) to formulate a model of estimated daily intake (EDI) among consumers in the country. Methods: This was a cross-sectional study conducted in five georeferenced markets of Bushenyi district in January 2020. Amaranthus, cabbages, scarlet eggplants, and tomatoes were collected from open markets, processed, and analyzed by atomic absorption spectrometry. Modeled EDI, principal component (PCA) and cluster analysis (CA) were conducted to identify relationships in the samples. Results: The levels of essential elements in the four vegetables were found to fall from Co > Cu > Fe > Zn. Those of non-essential metals were significantly higher and followed the pattern Cd > Cr > Pb > Ni. The highest EDI values were those of Cu in scarlet eggplants, Zn in amaranthus, Fe in amaranthus, Co in amaranthus, Pb in cabbages, total Cr in scarlet eggplant, Cd in cabbages and tomatoes, and Ni in cabbages. In comparison to international limits, EDIs for Zn, Cu, Co and Fe were low while Ni in cabbages were high. PCA showed high variations in scarlet eggplant and amaranthus. The study vegetables were found to be related with each other, not according to the location of the markets from where they were obtained, but according to their species by CA. Conclusion: The presence of non-essential elements above WHO limits raises policy challenges for the consumption and marketing of vegetables in the study area. Furthermore, low EDIs of essential elements in the vegetables create demand for nutritious foods to promote healthy communities.

No association between blood count levels and whole-blood cobalt and chromium levels in 1,900 patients with metal-on-metal hip arthroplasty

Background and purpose — The accelerated wear of poorly functioning metal-on-metal (MoM) hip implants may cause elevated whole-blood cobalt (Co) and chromium (Cr) levels. Hematological and endocrinological changes have been described as the most sensitive adverse effects due to Co exposure. We studied whether there is an association between whole-blood Co/Cr levels and leukocyte, hemoglobin, or platelet levels. Patients and methods — We analyzed whole-blood Co and Cr values and complete blood counts (including leukocytes, hemoglobin, platelets) from 1,900 patients with MoM hips. The mean age at the time of whole-blood metal ion measurements was 67 years (SD 10). The mean time from primary surgery to whole-blood metal ion measurement was 8.2 years (SD 3.0). The mean interval between postoperative blood counts and metal ion measurements was 0.2 months (SD 2.7). Results — The median Co value was 1.9 µg/L (0.2–225), Cr 1.6 µg/L (0.2–125), mean leukocyte count 6.7 × 109/L (SD 1.9), hemoglobin value 143 g/L (SD 13), and platelet count 277 × 109/L (SD 70). We did not observe clinically significant correlations between whole-blood Co/Cr and leukocyte, hemoglobin, or platelet counts. Interpretation — Elevated whole-blood Co and Cr values are unlikely to explain abnormal blood counts in patients with MoM hips and the reason for possible abnormal blood counts should be sought elsewhere.

F-18 FDG PET brain imaging in symptomatic arthroprosthetic cobaltism

PurposeImaging studies of cobalt toxicity from cobalt-chromium alloy arthroprosthetics have focused on the local intra-articular and peri-articular presentation from failing joint replacements. Most studies investigating neurological findings have been small case series focused on the clinical findings of memory loss, diminished executive function, tremor, hearing and vision loss, depression, and emotional lability. This study utilizes software-based quantitative analysis of brain metabolism to assess the degree of hypometabolism and areas of susceptibility, determine if a pattern of involvement exists, and measure reversibility of findings after prosthetic revision to cobalt-free appliances.MethodsOver 48 months, 247 consecutive patients presenting to an orthopedic clinic with an arthroprosthetic joint containing any cobalt-chromium part were screened with whole blood and urine cobalt levels. A clinically validated inventory of 10 symptoms was obtained. Symptomatic patients with a blood cobalt level above 0.4 mcg/L or urine cobalt greater than 1 mcg/L underwent F-18 FDG PET brain imaging. Analysis was performed with FDA-approved quantitative brain analysis software with the pons as the reference region. Control group was the normal brain atlas within the software.ResultsOf the 247 consecutively screened patients, 123 had blood and urine cobalt levels above the threshold. The 69 scanned patients had statistically significant regional hypometabolism and higher symptoms inventory. Fifty-seven patients were retained in the study. Distribution of hypometabolism was in descending order: temporal, frontal, Broca’s areas, anterior cingulate, parietal, posterior cingulate, visual, sensorimotor, thalamic, and lastly caudate. Metal-on-metal (MoM) and metal-on-plastic (MoP) joint replacements produced similar patterns of hypometabolism. Of 15 patients with necessary revision surgery, 8 demonstrated improved metabolism when later re-scanned.ConclusionAll scanned patients had regions of significant hypometabolism. Neurological toxicity from elevated systemic cobalt levels following arthroprosthetic joint replacement has a pattern of regional susceptibility similar to heavy metals and solvents, differing from classical dementias and may occur at blood and urine cobalt levels as low as 0.4 mcg/L and 1 mcg/L, respectively. Presently accepted thresholds for cobalt exposure and monitoring may need revision. Quantitative F-18 FDG PET brain imaging may aid in the decision process for treatment options and timing of possible medical versus surgical intervention.

An Analysis of the FDA MAUDE Database and the Search for Cobalt Toxicity in Class 3 Johnson & Johnson/DePuy Metal-on-Metal Hip Implants.

This study was designed to determine whether systemic cobalt toxicity as an adverse event could be documented using the Food and Drug Administration's (FDA) Manufacturer and User Facility Device Experience (MAUDE) database for cobalt-chromium containing hip implant recipients. Class 3 Johnson & Johnson (J&J)/DePuy devices were chosen for analysis because of the large number of adverse event reports related to their Pinnacle and ASR XL Acetabular hip replacement systems. A secondary goal was to characterize the reporters who are populating the information in the MAUDE database and to evaluate the quality of the data and information submitted. Using FDA MAUDE downloadable data files, 83,528 adverse event medical device narrative reports were identified with the product code of KWA (Prosthesis, Hip, Semiconstrained [Metal Uncemented Acetabular Component]) for J&J/DePuy (KWA Text File). These are class 3 devices and devices with known high failure rates. The ASR XL Acetabular hip replacement Systems and Pinnacle fall into this category. This group of implants was chosen because implant failure is associated with elevated cobalt levels. Two additional subfiles were created from Free Text records in the narrative reports containing key words that indicated a chromium or cobalt (CrCo) device and another for key words indicating elevated levels of cobalt or toxicity. These files were then searched for symptoms of systemic cobalt toxicity with Microsoft Excel using key words pertaining to symptom categories of: cognitive/memory loss, tremor, neuropathy, depression, auditory symptoms, visual symptoms, cardiac, and thyroid disease. Reports are submitted to the FDA at the device component level. It was common for multiple reports to be submitted for a single device. It was not possible to differentiate systemic versus local symptoms for adverse event reports in the neuropathy category. This category was not analyzed. The number of adverse event reports in the other categories ranged from 119 to 16 for the J&J/DePuy KWA Text File and 59 to 4 in the file of records having key words indicating potential elevation of CrCo or toxicity. Cardiac, visual, and auditory conditions were most frequently reported. With the possible exception of cardiomyopathy, the numbers of these reports are far below the prevalence expected in the general population of comparable age. The content of the MAUDE database records often contained little objective data. We found less than 4% of 14,714 records, which indicated cobalt elevation or toxicity contained units for quantitative measurement. There was also frequent use of nondescript, all-encompassing words and phrases such as "mental anguish," found in 321 KWA Text File records. Manufacturers submitted more than 99% of the reports and the most common reporter occupation was attorney, found in 42.24% of the 83,550 J&J/DePuy KWA Reporter File records. Physician was the reporter's occupation in 20.48% of reports but seldom reported directly to the FDA. We were not able find in the FDA MAUDE database meaningful warning signs to support the contention that chromium-cobalt-containing Class 3 J&J and DePuy hip implants caused systemic neurological or thyroid symptoms in patients. The incidence of reported cardiomyopathy was rare but frequent enough to be cause of concern. The redaction of most patient data along with the nonstructured nature of data entry would be expected to hinder the identification of warning signs. Even identification of the type of device could not be consistently carried out. In addition, the FDA needs to implement a methodology to identify and group all reports from a single device implanted into a patient, so duplication of event counting would not occur. Of 83,550 J&J/DePuy KWA Reporter File records, we found only two physician reports sent directly to the FDA. Almost all reports are submitted by manufacturers and are most commonly authored by attorneys. A standard of care needs to be set for physicians to report medical device adverse events to the FDA.

Core-satellite gold nanoparticle biosensors for monitoring cobalt ions in biological samples

Elevated cobalt levels in the bloodstream due to wear debris from metal-on-metal hip implants can cause adverse health effects. Herein, we report a highly sensitive and specific label-free assay for cobalt detection using cysteine-linked core-satellite gold nanoparticles. We demonstrate the detection of clinically relevant concentrations of cobalt ions in biological samples down to 10 nM within 15 minutes using a standard laboratory plate reader. This method can be developed as a valuable tool for prompt monitoring of cobalt ion levels in patients with metal-on-metal hip implants.

Cobalt and nickel affect the fluidity of negatively-charged biomimetic membranes

Elevated levels of the essential trace metals cobalt and nickel are associated with a variety of toxic effects, which are not well-understood, and may involve interactions with the lipid membrane. Fluidity changes of biomimetic lipid membranes upon exposure to CoCl2 and NiCl2 were studied using the fluorescent probe Laurdan, which senses changes in environment polarity. Liposomes were prepared by extrusion in 20 mM HEPES + 100 mM NaCl at pH 7.4. Additionally, dynamic light scattering was used to monitor metal induced size changes of liposomes composed of: phosphatidic acid (PA), cardiolipin (CL), phosphatidylglycerol (PG), phosphatidylserine (PS), and phosphatidylcholine (PC), with saturated and unsaturated acyl chains. Micromolar concentrations of both metals significantly rigidify negatively-charged liposomes and generally increase the melting temperature. Saturated acyl chains showed stronger metal effects in PS and PG, while no clear acyl chain preference was observed in CL and PA systems. The strength of the effect appears to be influenced greatly by both the head group and acyl chain. The rigidifying effects of cobalt were almost always much larger than those of nickel. In addition, size changes and aggregation by both metals was detected in PS or PA liposomes at molar metal/lipid ratios as low as 1/10.

Adverse Reaction to Metal Debris in a Consecutive Series of DUROM™ Hip Resurfacing: Pseudotumour Incidence and Metal Ion Concentration

The aim of this study was to evaluate the incidence of adverse reactions to metal debris (ARMD) in a consecutive series of DUROM™ Hip Resurfacing Arthroplasty (HRA) at mid-term follow-up. Between October 2003 and March 2007 a total of 134 consecutive DUROM™ HRA in 121 patients were performed at our institution. Follow-up could be obtained in 101 unrevised patients (83%) at a mean time of 8.51 ± 0.97 years postoperatively and included patient-related outcome measurement, plain radiographs, MARS-MRI as well as whole blood metal ion assessment. 17 (16.5%) out of 103 hips revealed pseudotumour occurrence in MRI investigation, 1 (10.6%) with a diameter of ≥2 cm. Higher incidence of pseudotumours was found patients with femoral component size <50 mm. 38 patients had elevated cobalt levels, 36 of them (35%) in the range of 2-7 μg/l and 2 patients (1.9%) at a rate of >7 μg/l. In contrast to cobalt determination, only elevated chromium values showed a positive association with pseudotumour occurrence and size. A significant proportion of patients developed pseudotumours and metal ion elevation in a consecutive cohort of DUROM™ HRA after mid-term follow-up. The incidence, however, seems not to differ from results of other well performing resurfacing brands; clinical relevance of our findings is unclear. Regarding potential local as well as systemic effects of metal particle release, close follow-up of patients is essential, even with clinically well-performing implants.

Goals and Challenges of Identifying Asymptomatic Pseudotumors in Patients Treated with Total Hip Arthroplasty

This paper sheds light on the management of patients who have a recalled dual-taper modular total hip replacement in place. The authors report on 83 patients divided into 2 groups: symptomatic (23) and asymptomatic (60). A pseudotumor was identified with metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) in 30 (36%) of the 83 patients. Nine (15%) of the 60 asymptomatic patients and 21 (91%) of the 23 symptomatic patients had a pseudotumor. Patients with a pseudotumor had a significantly higher cobalt level (8.0 μg/L) compared with those with no pseudotumor (2.0 μg/L). On the basis of this finding, the authors recommend MARS-MRI for all patients with elevated cobalt levels, even in the absence of hip symptoms. If the goal is to minimize cost associated with MRI scans, then the authors’ recommendation of obtaining them only when the metal-ion level is elevated is sound. If the goal is to minimize any irreversible soft-tissue …

Asymptomatic Pseudotumors in Patients with Taper Corrosion of a Dual-Taper Modular Femoral Stem: MARS-MRI and Metal Ion Study.

Modularity in total hip arthroplasty facilitates intraoperative restoration of patient anatomy. Although dual-taper modular total hip arthroplasty offers potential advantages for optimizing the hip center of rotation, it has been associated with modular taper corrosion. This corrosion has led to adverse local tissue reactions (pseudotumors) at the neck-stem junction and elevated metal-ion levels. However, the occurrence of taper-corrosion-related pseudotumors in patients who remain asymptomatic following total hip arthroplasty with a dual-taper modular femoral stem remains largely unknown. The aims of this study were (1) to determine the prevalence of asymptomatic pseudotumors by utilizing metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) and (2) compare serum metal-ion levels between symptomatic and asymptomatic patients with a dual-taper modular stem total hip replacement. We performed a retrospective cross-sectional study of 97 consecutive patients who had been treated with a dual-taper modular femoral stem total hip arthroplasty. Eighty-three patients were stratified into symptomatic and asymptomatic groups and evaluated with MARS-MRI, measurement of serum metal-ion levels, and the University of California at Los Angeles (UCLA) functional hip score. The prevalence of pseudotumors as determined with MARS-MRI was 15% in our asymptomatic patients and 36% in the overall cohort. The median serum cobalt level and cobalt/chromium ratio were significantly higher in patients with a pseudotumor than in those without a pseudotumor (8.0 versus 2.0 μg/L [p = 0.004] and 10.3 versus 2.4 μg/L [p = 0.012], respectively). However, there was no significant difference in the serum cobalt level or cobalt/chromium ratio between symptomatic patients with a pseudotumor and asymptomatic patients with a pseudotumor (7.6 versus 6.2 μg/L [p = 0.37] and 8.3 versus 10.6 μg/L [p = 0.46], respectively). The UCLA scores of asymptomatic patients with a pseudotumor were similar to those of patients without a pseudotumor (6.7 versus 6.6). The prevalence of asymptomatic taper-corrosion-related pseudotumors on MARS-MRI in this study demonstrated that the absence of symptoms does not exclude the presence of adverse local tissue reactions. Elevated cobalt levels and cobalt/chromium ratios were associated with the presence of pseudotumors in asymptomatic and symptomatic patients. Cross-sectional imaging such as MARS-MRI is indicated for patients with elevated metal-ion levels. A longitudinal study is required to determine whether asymptomatic patients with taper-corrosion-related pseudotumors will develop symptoms with time. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Cobalt serum levels differ in well functioning Birmingham resurfacing and Birmingham modular THA.

Metal-on-metal (MoM) bearings are known to release metal ions secondary to wear and corrosion. This may cause local reactions (adverse soft tissue reactions and osteolysis) and systemic effects. Little is known about the exact pattern and the differences between large head MoM total hip replacements (THA) and resurfacings (HR). (1) Is there a difference in metal ion concentrations between HR and MoM-THR using the same bearing design (Birmingham Hip Resurfacing System, Smith & Nephew, Inc. Memphis, TN, USA)? (2) Are metal ion levels changing over time in MoM-THA or HR? (3) Do acetabular inclination angle and femoral component size influence cobalt and chromium levels? Is there a correlation between clinical outcome and metal ion levels? A retrospective analysis was conducted in 77 well functioning unilateral Birmingham HR and 42 well functioning unilateral modular Birmingham MoM-THA (Smith & Nephew, Inc. Memphis, TN, USA) operated on between 2007 and 2012. Blood samples were taken at a minimum of 13months and subsequent during annual follow-ups. (1) Cobalt levels were significantly higher in MoM-THA compared to HR (p<0.001). There was no significant difference in chromium levels (p=0.313). (2) Cobalt is increasing over time in MoM-THA (p=0.030) whereas metal ions remain stable in HR. (3) Metal ion levels were not affected by acetabular inclination angle and femoral component size in MoM-THA. Chromium levels correlate with the femoral component size (r=-0.240; p=0.037), the UCLA activity score (r=-0.344; p=0.003) and the VAS (r=0.263; p=0.38) in HR. Considering that HR and MoM-THA used the same MoM bearing design, increased cobalt levels may be related to trunnion wear or corrosion. Elevated cobalt levels should raise concern for corrosion related failure in MoM-THA.

Elevated Cobalt, Chromium and Molybdenum Levels in Peripheral Blood Have No Effect on the Development of Heterotopic Ossifications after Metal-on-Metal Total Hip Arthroplasty

Metal debris from metal-on-metal (MoM) total hip arthroplasties (THA) has been suspected to cause periprosthetic heterotopic ossifications (HO). We determined the influence of disseminated cobalt, chromium and molybdenum on the development of HO. Native blood samples from patients with 86 high-carbon and 16 low-carbon Co28Cr6Mo articulations were analysed by high-resolution inductively coupled plasma mass-spectrometry (HR ICP-MS). The results revealed that high-carbon metal-on-metal articulations showed lower metal blood levels (Co 1.03 to 1.60 μg/l, Cr 0.77 to 0.88 μg/l, Mo 0.45 to 0.56 μg/l) whereas low-carbon articulations achieved higher metal blood levels (Co 2.59 to 6.85 μg/l, Cr 1.25 to 3.55 μg/l, Mo 0.45 to 0.64 μg/l), but no correlation between metal ion blood level or carbon content and the development of HO could be found in these MoM articulations. Hence, metal debris from MoM articulation does not stimulate heterotopic bone formation despite other well-known local reactions.

Giant cell interstitial pneumonia in patients without hard metal exposure: analysis of 3 cases and review of the literature

Giant cell interstitial pneumonia is a rare lung disease and is considered pathognomonic for hard metal lung disease, although some cases with no apparent hard metal (tungsten carbide cobalt) exposure have been reported. We aimed to explore the association between giant cell interstitial pneumonia and hard metal exposure. Surgical pathology files from 2001 to 2004 were searched for explanted lungs with the histopathologic diagnosis of giant cell interstitial pneumonia, and we reviewed the associated clinical histories. Mass spectrometry, energy-dispersive x-ray analysis, and human leukocyte antigen typing data were evaluated. Of the 455 lung transplants, 3 met the histologic criteria for giant cell interstitial pneumonia. Patient 1 was a 36-year-old firefighter, patient 2 was a 58-year-old welder, and patient 3 was a 45-year-old environmental inspector. None reported exposure to hard metal or cobalt dust. Patients 1 and 2 received double lung transplants; patient 3 received a left single-lung transplant. Histologically, giant cell interstitial pneumonia presented as chronic interstitial pneumonia with fibrosis, alveolar macrophage accumulation, and multinucleated giant cells of both alveolar macrophage and type 2 cell origin. Energy-dispersive x-ray analysis revealed no cobalt or tungsten particles in samples from the explanted lungs. None of the samples had detectable tungsten levels, and only patient 2 had elevated cobalt levels. The lack of appropriate inhalation history and negative analytical findings in the tissue from 2 of the 3 patients suggests that giant cell interstitial pneumonia is not limited to individuals with hard metal exposure, and other environmental factors may elicit the same histologic reaction.

Pseudotumour incidence, cobalt levels and clinical outcome after large head metal-on-metal and conventional metal-on-polyethylene total hip arthroplasty: mid-term results of a randomised controlled trial.

We compared the incidence of pseudotumours after large head metal-on-metal (MoM) total hip arthroplasty (THA) with that after conventional metal-on-polyethylene (MoP) THA and assessed the predisposing factors to pseudotumour formation. From a previous randomised controlled trial which compared large head (38 mm to 60 mm) cementless MoM THA with conventional head (28 mm) cementless MoP THA, 93 patients (96 THAs: 41 MoM (21 males, 20 females, mean age of 64 years, standard deviation (sd) 4) and 55 MoP (25 males, 30 females, mean age of 65 years, sd 5) were recruited after a mean follow-up of 50 months (36 to 64). The incidence of pseudotumours, measured using a standardised CT protocol was 22 (53.7%) after MoM THA and 12 (21.8%) after MoP THA. Women with a MoM THA were more likely to develop a pseudotumour than those with a MoP THA (15 vs 7, odds ratio (OR) = 13.4, p < 0.001). There was a similar incidence of pseudotumours in men with MoM THAs and those with MoP THAs (7 vs 5, OR = 2.1, p = 0.30). Elevated cobalt levels (≥ 5 microgram/L) were only associated with pseudotumours in women with a MoM THA. There was no difference in mean Oxford and Harris hip scores between patients with a pseudotumour and those without. Contrary to popular belief, pseudotumours occur frequently around MoP THAs. Women with a MoM THA and an elevated cobalt level are at greatest risk. In this study, pseudotumours had no effect on the functional outcome after either large head MoM or conventional MoP THA.

Blood metal ions after hybrid metal-on-polyethylene Exeter-Trident total hip replacement.

BackgroundMetal-on-metal total hip replacements (THRs) with large femoral heads have been associated with elevated levels of cobalt (Co) and chromium (Cr), which have been attributed to high levels of wear at the articular surface. Our unit recently published data showing a significant increase in the mean levels of Co ions in patients with a 36-mm diameter femoral head with the metal-on-polyethylene Trident−Accolade system. The aim of this study is to assess the levels of Co and Cr in the Exeter−Trident hybrid system, as similar findings would raise concern over the V40 taper trunnion.Materials and methodsThe study included 83 patients (45 male and 38 female with a mean age of 75.6 years) who received Exeter−Trident hybrid metal-on-polyethylene THRs. The patients were then divided into two groups according to the diameter of the femoral head used—38 patients in the 28-mm group (control), and 45 in the 36-mm (experimental) group. Serum levels of blood Co and Cr were analysed for all recruited patients.ResultsIn the control group (28-mm femoral head) all Co and Cr values were normal (under the abnormal threshold), as were the experimental group (36-mm femoral head). The data values were below <10 nmol and <40 nmol for Co and Cr, respectively.ConclusionSince the National Joint Registry (NJR) states that the Exeter femoral stem is the commonest cemented femoral stem prosthesis used in the UK, we found it imperative that these results are documented given the corresponding findings in the Trident−Accolade system in our previous study. This study provides relative reassurance that the issue does not lie with the V40 taper trunnion, but raises suspicion that the issue may be with the titanium Accolade stem with large diameter femoral heads.Level of evidence III.

The increase in cobalt release in metal-on-polyethylene hip bearings in tests with third body abrasives.

Hypersensitivity reactions in patients receiving metal-on-metal hip replacements have been attributed to corrosion products as observed by elevated cobalt and chromium ions in the blood. Although the majority of cases are reported in metal-on-metal, incidences of these reactions have been reported in the metal-on-polyethylene patient population. To date, no in vitro study has considered cobalt release for this bearing combination. This study considered four 28 mm and seven 52 mm diameter metal-on-polyethylene bearings tested following ISO standard hip simulator conditions as well as under established abrasive conditions. These tests showed measurable cobalt in all bearings under standard conditions. Cobalt release, as well as polyethylene wear, increased with diameter, increasing from 52 to 255 ppb. The introduction of bone cement particles into the articulation doubled polyethylene wear and cobalt release while alumina particles produced significant damage on the heads demonstrated by cobalt levels of 70,700 ppb and an increased polyethylene wear from a mean value of 9–160 mm3/mc. Cobalt release was indicative of head damage and correlated with polyethylene wear at the next gravimetric interval. The removal of third body particles resulted in continued elevated cobalt levels in the 52 mm diameter bearings tested with alumina compared to standard conditions but the bearings tested with bone cement particles returned to standard levels. The polyethylene wear in the bone cement tested bearings also recovered to standard levels, although the alumina tested bearings continued to wear at a higher rate of 475 mm3/mc. Cobalt release was shown to occur in metal-on-polyethylene bearings indicating damage to the metal head resulting in increased polyethylene wear. While large diameter metal-on-polyethylene bearings may provide an increased range of motion and a reduced dislocation risk, increased levels of cobalt are likely to be released and this needs to be fully considered before being widely adopted.

Prevalence of Pseudotumor in Patients After Metal-On-Metal Hip Arthroplasty Evaluated with Metal Ion Analysis and MARS-MRI

The purpose of this study is to quantify the prevalence of pseudotumors in patients with well-functioning and painful metal-on-metal total hip arthroplasty, to characterize the pseudotumor with the use of MARS-MRI, and to assess the relationship between pseudotumors and metal ions. We retrospectively reviewed 102 single surgeon patients. The results showed that 68.6% developed pseudotumor with 60.9% of the asymptomatic group developing pseudotumor. The symptomatic group had a higher proportion of patients with elevated serum cobalt levels (P=0.035). There was no difference found with elevated metal ions and prevalence of pseudotumor, but elevated cobalt levels were associated with larger pseudotumor size (P=0.001). The available evidence indicated that most patients that develop pseudotumors are asymptomatic, and that elevated serum cobalt levels may be associated with symptoms and pseudotumor size.

Self-reported neurological clinical manifestations of metal toxicity in metal-on-metal hip arthroplasty.

Adverse reactions to metal particle debris have been increasingly reported as a complication following large head metal-on-metal (MoM) hip arthroplasty. Elevated metal ion levels are a cause for concern. The aim of this study is to evaluate whether exposure to cobalt is associated with patient characteristics and symptoms of neuropathy, representing nervous system dysfunction. A cross-sectional study was conducted comparing patients with a MoM total hip arthroplasty and patients with a conventional hip arthroplasty. They received three questionnaires, one to assess neurotoxic complaints and two standardised self-administered questionnaires to identify symptoms that are suggestive of peripheral neuropathy. Current and historical data were available for whole blood cobalt levels in all patients. We analysed potential predictive factors for cobalt based on five different cut-off levels (0-2, 2-4, 4-10, 10-20, >20 µg/L). We performed 723 MoM total hip arthroplasties in 643 patients in our clinic. The response rate was 89%. Male-female ratio was 236/280, median age 63.6 years (30-72) with a mean follow-up of 50.6 months (20-86). We also sent the questionnaires to 98 patients in the control group. An increase in the incidence of reported symptoms was not consistent with higher serum cobalt levels. Female gender was the only consistent predictive factor for serum cobalt at different cobalt cut-off levels in the multivariate analysis. The study population did not show an increase in reported symptoms with elevated cobalt levels. Neurotoxic symptoms and whole blood cobalt levels did not show a consistent relationship with different dichotomised levels of cobalt exposure.