Circulating Metal Ion Research Articles

Persistently Raised Serum Titanium Levels After Spinal Instrumentation in Children.

Prospective study of patients undergoing elective spinal deformity surgery with repeated testing for circulating metal ions including preoperative levels acting as controls. The aim was to determine if levels of particular circulating metal ions are maintained to two years postsurgery including different implant systems and rods. Adults having hip replacements, especially metal-on-metal bearings, may develop high metal ion levels. Pediatric spinal implants are known to cause circulating metal ions, notably titanium, chromium, cobalt, and nickel. Fifty-six children having spinal deformity surgery were studied with repeated testing for circulating metal ions, using high-resolution inductively coupled plasma mass spectrometry. Linear mixed-effects models adjusting for repeated measurements over time were used to analyze levels of titanium, cobalt, chromium, and nickel. Titanium levels showed a rapid increase by seven days and a peak at 30 days that was essentially maintained at the two-year assay. At two years, titanium levels were 5.14 times greater compared with the presurgery control level (P<0.0001). Cobalt levels were shown to gradually rise to a peak at 30 days and then slowly decline but remained 1.74 times above mean baseline level at two years (P=0.0004), with a declining trajectory. Chromium and nickel levels rose immediately postoperatively and then steadily declined to baseline by six months and remained at baseline at two years. The five implant systems tested had generally equivalent results. The persistent and rising levels of titanium, in a predominantly female population, is concerning. Titanium is known to cross the placental barrier and enter the circulation of the fetus in rodents and humans, and to accumulate in solid organs especially the liver, spleen, heart, and lymph nodes in humans. This potentially exposes the offspring of mothers with spinal implants to titanium, with potential teratogenic effects.

Estropause, Sex Hormones and Metal Homeostasis in the Mouse Brain.

Alterations in brain metal ion homeostasis have been reported with aging and are implicated in the pathogenesis of neurodegenerative diseases. To assess whether age-related changes in hypothalamic-pituitary-gonadal (HPG) hormones might be involved in modulating brain metal ion homeostasis, we treated 7.5-month intact, sham-ovariecomized and ovariectomized C57B6SJL mice with vehicle or leuprolide acetate (for 9-months) to differentiate between whether sex steroids or gonadotropins might modulate brain metal ion concentrations. Unlike other aging mammals, there was no increase in plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations following estropause in mice, suggesting there was sufficient residual production by the follicle depleted ovary, of sex steroids like estrogens and protein hormones like the inhibins, in order to suppress pituitary LH/FSH production. Castration on the other hand induced significant increases in circulating LH and FSH. Modulation of plasma sex steroid and gonadotropin levels did not significantly alter the concentrations of brain metals tested (Fe, Zn, Cu, Mn, Co, Ni, Al, Li), although there was a tendency for a decrease in all brain metals following ovariectomy (low estrogens and progesterone, high gonadotropins), a response that was reversed with leuprolide acetate treatment (low sex steroids, low gonadotropins). Brain Cu concentration was the only metal correlated with plasma LH (−0.37, n = 30, p < 0.05) and FSH (−0.42, n = 29, p < 0.01). This study demonstrates that sex hormones do not markedly alter brain metal ion homeostasis, unlike previously reported studies of circulating metal ion homeostasis. The role of gonadotropins in regulating metal ion homeostasis does however warrant further study.

Do Children With Spinal Deformity Who Have Metal Implants and Frequent Exposure to X-Rays Increase Their Risk of Cancer?

Spinal surgery cohort. The authors assess the risk of cancer in children who have undergone frequent radiographs and have metal implants for the treatment of spinal deformity. Concerns have been raised regarding the cancer risk to children exposed to repeated radiological examinations as part of routine surveillance to monitor progression of spinal deformity. Additionally, there are reports of increased cancer risk in adults having joint replacement with metal implants causing raised metal ion levels in the blood. A large number of consecutive children undergoing instrumented spinal surgery since 1979 were examined for their development of malignancy. High quality data on all invasive cancers from the South Australian Cancer Registry and deaths were linked to the spinal surgery cohort with the calculation of standardized incidence ratios (SIRs) using the Quinquinquennium method. The study cohort was formed by 865 children. The average follow-up time from date of surgery to either death or censoring date was 18 years with a maximum of 36 years. A total of 15,921 person years were examined. There was no increased rate of cancer in these patients. For the total cohort, the SIR was 1.00 (95% confidence interval [CI] 0.50-1.79). For females the SIR was 0.83 (95% CI 0.33-1.70) and for males the SIR was 1.33 (95% CI 0.36-3.40). The male SIR reflected an expected cancer incidence of three cases, when four cases were observed, and was not statistically significant. This study has found that radiation exposure and possible exposure to circulating metal ions as a result of routine instrumented spine surgery in children since 1979 is not associated with an increased risk of cancer in up to 36 years of follow up. 2.

Challenges in the Measurement and Interpretation of Serum Titanium Concentrations.

The measurement of circulating metal ion levels in total hip arthroplasty patients continues to be an area of clinical interest. National regulatory agencies have recommended measurement of circulating cobalt and chromium concentrations in metal-on-metal bearing symptomatic total hip arthroplasty patients. However, the clinical utility of serum titanium (Ti) measurements is less understood due to wide variations in reported values and methodology. Fine-scale instrumentation for detecting in situ Ti levels continues to improve and has transitioned from graphite furnace atomic absorption spectroscopy to inductively coupled plasma optical emission spectrometry or inductively coupled plasma mass spectrometry. Additionally, analytical interferences, variable sample types, and non-standardized sample collection methods complicate Ti measurement and underlie the wide variation in reported levels. Normal reference ranges and pathologic ranges for Ti levels remain to be established quantitatively. However, before these ranges can be recognized and implemented, methodological standardization is necessary. This paper aims to provide background and recommendations regarding the complexities of measurement and interpretation of circulating Ti levels in total hip arthroplasty patients.

Metal ion trend in patients with metal-on-metal total hip arthroplasty: a 10-year prospective study.

There have been reported adverse reactions in patients with large head metal-on-metal hip arthroplasty, therefore metal particle debris are a cause for concern. The aim of this study was to evaluate the release trend of metal ions and the correlated variables. 54 patients were prospectively enrolled into the study from 2004 to 2006. All patients had 36-mm metal head, Pinnacle acetabular component, Summit stem and Ultamet CoCr alloy liner (Depuy Inc.), and underwent clinical and radiological management. The haematic concentration of Cr-Co at 0, 6, 12, 24, 60 and 120 months after the implantation was analysed in a sub-cohort of 34 patients. 10-year revision rate for each case was 8.9%. The average concentration of Co at 120 months was 3.12 μg/L (median 2.20) with 53% values >2 μg/L and 1 >7 μg/L. After 6 months the median levels of Cr and Co were higher than time 0 ( p < 0.0001); no significant differences were found between 6 and 24 months; while Co had significant increase between 60 and 120 months ( p = 0.002). Overweight, University of California at Los Angeles (UCLA) >9 and <50 years old patients have significantly higher circulating metal ions. This is 1 of the few prospective studies on the argument. The revision rate is conforming to records. Our data shows ionic concentration is not predictive of revision or adverse reaction to metals. We described a 3-phase trend for Co probably due to the loss of integrity of the surfaces.

Femoral offset found not to affect metal ion levels in metal-on-metal total hip arthroplasty.

Failure to restore femoral offset in metal on polyethylene total hip arthroplasty (THA) causes polyethylene wear and aseptic loosening. To our knowledge, no study to date has investigated the relationship between femoral offset and wear in metal-on-metal (MOM) THA. In this study, we investigated the relationship between femoral offset and wear by measuring circulating metal ion levels in MOM THA. In this retrospective study, we identified patients who had undergone MOM THA with the ASR XL system (DePuy International Ltd., Leeds, UK). Femoral offset was measured using anteroposterior radiographs, and circulating metal ion levels (cobalt and chromium) were recorded. In total, 95 patients were included (68 males and 27 females). The mean age at the time of surgery was 64.9. Mean time from surgery to blood sampling was 15.4months. No statistically significant relationship was found between femoral offset and cobalt (p = 0.313) or chromium (p = 0.401) ions. It is known that failure to restore femoral offset during THA can lead to high rates of wear in metal-on-polyethylene articulations. In our study, no statistically significant relationship was found between femoral offset and serum cobalt or chromium ions. This study adds to the information available to surgeons regarding factors that increase wear in metal-on-metal total hip arthroplasty.

Do Hardened Femoral Heads Reduce Blood Metal Ion Concentrations after Hip Resurfacing?

Elevated cobalt and chromium ion concentrations have been associated with the use of metal-on-metal bearings in hip arthroplasty. The use of a differential hardness bearing may reduce metal particle release. The aim of our study was to compare circulating cobalt (Co) and chromium (Cr) ion levels between patients treated with a standard all 'as-cast' heat treated bearing and a differential hardness bearing. One hundred and thirty-two patients implanted with unilateral hip resurfacing arthroplasties and having had blood metal ion studies performed between one and six years after surgery were retrospectively selected. There were 73 patients in the standard all 'as cast' heat treated bearing group (group 1) and 59 in the differential hardness bearing group (group 2). Clinical and quality of life scores were comparable between groups. The median Co in group 1 was 1.01 µg/L and 1.23 µg/L in group 2 (p = 0.0566). The median Cr in group 1 was 1.60 µg/L and 1.34 µg/L in group 2 (p = 0.0505). Compared with conventional heat-treated CoCr bearings, differential hardness metal-on metal bearings do not confirm in vivo the hopes of a substantial reduction in circulating metal ions concentrations suggested by in vitro wear studies.

The Effect of Acetabular Inclination on Metal Ion Levels Following Metal-on-Metal Hip Arthroplasty

Acetabular inclination angles have been suggested as a principal determinant of circulating metal ion levels in metal-on-metal hip arthroplasties. We aimed to determine whether inclination angle correlates with ion levels in arthroplasties using the Articular Surface Replacement (ASR) system. Patients undergoing ASR arthroplasties had blood metal ion levels and radiograph analysis performed a mean of 3.2 years after surgery. Inclination angle showed only a weak correlation with cobalt (r=0.21) and chromium (r=0.15) levels. The correlation between inclination angle and cobalt levels was significant only with small femoral components, although it was still weak. Multiple regression showed a complex interaction of factors influencing ion levels but inclination angle accounted for little of this variation. We conclude that the acetabular inclination angle is not a meaningful determinant of metal ion levels in ASR arthroplasties.

Cobalt and Chromium Ion Release After Large-Diameter Metal-on-Metal Total Hip Arthroplasty

Seventy-five patients underwent unilateral metal-on-metal total hip arthroplasty using a large-diameter head. Serum levels of cobalt and chromium were determined. Significant increases in both cobalt and chromium were observed at 3 months (cobalt, 1.4 μg/L; chromium, 1.4 μg/L) compared with preoperative values (P < .001). At 1 year, the median cobalt and chromium levels were 2.3 and 2.1 μg/L, respectively, and the levels had increased significantly compared with 3 months (P < .001). There were no significant differences between levels of either metal at 1 or 2 years (cobalt, 2.3 μg/L; chromium, 1.6 μg/L). Pseudotumor occurred in 2 hips. Patients with large-diameter metal-on-metal total hip arthroplasty had higher circulating metal ion levels at 3 months and 1 year, with no additional significant increases at 2 years.

Metal-on-metal: history, state of the art (2010)

The history of metal-on-metal bearing began with K. Mc Kee. Several "episodes" have marked the history of metal-on-metal articulations, and each has contributed to a better understanding of this type of tribology. But to date the indications for this bearing are debated and are subject to reservations because of the existence of permanently elevated levels of circulating metal ions. It therefore appears that the monitoring of our patients, the documentation of our revisions and the collaboration with our industry partners as well as communicating with our biology and pathology colleagues is necessary to help us solve these problems.

Surgical Variables Influence Metal Ion Levels After Hip Resurfacing

Metal-on-metal bearings in surface arthroplasty are associated with prolonged periods of elevated ion circulation. However, there exists some controversy regarding the effect of different surgical variables on the concentration of metal ions in whole blood of patients after hip resurfacing. We sought to confirm which clinical and radiographic parameters are associated with elevated levels of cobalt, chromium, and molybdenum after unilateral metal-on-metal surface arthroplasty. We retrospectively reviewed 91 patients with a minimum followup of 24months (mean, 37months; range, 24-55months). The clinical variables consisted of age, gender, preoperative severity of osteoarthritis, component size, and functional outcome measures using the Harris hip score and UCLA activity score. The radiographic parameters included acetabular inclination and version as well as femoral component alignment from both the anteroposterior and lateral radiographs. A smaller femoral head diameter was associated with larger levels of cobalt and chromium. We observed a negative correlation between ion levels and the Harris hip score or UCLA score. A larger acetabular inclination showed a direct relationship with the concentration of metal ions. Severity of preoperative osteoarthritis, acetabular version, femoral stem-shaft and valgus angle, and anterior orientation of the femoral component had no effect on the circulating metal ion levels. The data suggest a smaller implant diameter, larger cup inclination, and lower postoperative functional scores are associated with increased cobalt and chromium levels after metal-on-metal hip resurfacing.

Circulating levels of cobalt and chromium from metal-on-metal hip replacement are associated with CD8+ T-cell lymphopenia

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders. Laboratory-defined T-cell lymphopenia was present in 13 patients (15%) (CD8(+) lymphopenia) and 11 patients (13%) (CD3(+) lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8(+) lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.

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.

The genesis and isotopic composition of carbonates associated with some Permian Australian coals

Siderite and calcite are the two forms of carbonate commonly associated with Permian Australian coals. The former occurs as disseminated spherulites and is a product of the early post-depositional environment. Isotopic measurements show that the CO 2 fixed as siderite did not result from the direct oxidation of photosynthetically derived materials, but rather from the anaerobic fermentation of these. The higher concentrations of calcite are generally found towards the roofs of coal seams and are characterized by isotopic enrichments to δ 13C values of +25‰ PDB. Isotopic exchange between CO 2 and CH 4 within the coal seam is postulated as the mechanism which leads to the formation of isotopically heavy CO 2. At sites along the seam margins where the CO 2 escapes, interaction with circulating metal ions or preexisting calcite results in the deposition of “heavy” calcite. With increasing alteration of coal by thermal metamorphism, the 13C content of calcites and finally siderites decreases so that it more nearly approaches that of the associated coal.