Aims. The aims of this study were to determine if an increasing serum cobalt (Co) and/or chromium (Cr) concentration is correlated with a decreasing Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Score (HOOS) in patients who received the Articular Surface Replacement (ASR) hip resurfacing arthroplasty (HRA), and to evaluate the ten-year revision rate and show if sex, inclination angle, and Co level influenced the revision rate. Methods. A total of 62 patients with an ASR-HRA were included and monitored yearly postoperatively. At follow-up, serum Co and Cr levels were measured and the HHS and the HOOS were scored. In addition, preoperative patient and implant variables and the need for revision surgery were recorded. We used a linear mixed model to relate the serum Co and Cr levels to different patient-reported outcome measures (PROMs). For the survival analyses we used the Kaplan-Meier and Cox regression model. Results. We found that an increase of one part per billion (ppb) in serum Co and Cr levels correlated significantly with worsening of the HHS in the following year. This significant correlation was also true for the HOOS-Pain and HOOS-quality of life sub scores. The overall ten-year survival rate in our cohort was 65% (95% confidence interval (CI) 52.5 to 77.6). Cox regression analysis showed a significant hazard ratio (HR) of 1.08 (95% CI 1.01 to 1.15; p = 0.028) for serum Co level. No significance was found with sex or inclination angle. Conclusion. This study shows that increasing serum Co and Cr levels measured in patients with an ASR-HRA are predictive for deterioration in HHS and HOOS subscales in the following year. Increasing serum Co and Cr should forewarn both surgeon and patient that there is a heightened risk of failure. Continued and regular review of patients with an ASR-HRA implant by measurement of serum Co/Cr levels and PROMs remains essential. Cite this article: Bone Joint J 2023;105-B(7):775–782

Aims. To find out if there is an inverse association between estimated glomerular filtration rate (eGFR) and whole blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasties and renal insufficiency, suggesting that renal insufficiency could cause accumulation of Co and Cr in blood. Methods. Out of 2,520 patients with 3,013 MoM hip arthroplasties, we identified 1,244 patients with whole blood Co, Cr, and creatinine measured within no more than a one-year interval. We analyzed the correlation of blood metal ion levels and eGFR to identify a potential trend of accumulating Co or Cr with decreasing eGFR. Results. Of the 1,244 patients, 112 had normal renal function (eGFR > 90 ml/min/1.73 m. 2. ), 715 had mild renal insufficiency (eGFR 60 to 89), 384 had moderate renal insufficiency (eGFR 30 to 59), 27 had severe renal insufficiency (eGFR 15 to 29), and six had end-stage renal insufficiency (eGFR < 15). Median eGFR was 68 ml/min/1.73 m. 2. (interquartile range (IQR) 56 to 82), median whole blood Co was 3.3 µg/l (IQR 1.1 to 9.9), and median Cr was 2.0 µg/l (IQR 1.2 to 3.6). We did not observe an association between decreased eGFR and increased whole blood Co and Cr concentrations, but instead both increased Co and Cr were associated with higher eGFR, indicating better kidney function. Conclusion. As patients with MoM hip arthroplasties get older, the prevalence of renal insufficiency among them will increase, and orthopaedic surgeons will increasingly have to evaluate whether or not this affects patient follow-up. The USA Food and Drug Administration suggests that closer follow-up may be needed for MoM patients with renal insufficiency. We did not observe accumulation of blood Co or Cr in MoM hip arthroplasty patients with mild to severe renal insufficiency. Cite this article: Bone Joint J 2021;103-B(7):1231–1237

Aims. To determine whether there is any association between glomerular filtration rate (GFR) and blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasty. Patients and Methods. We identified 179 patients with a unilateral 36 mm diameter head as part of a stemmed Summit-Pinnacle MoM hip arthroplasty. GFR was calculated using the Modification of Diet in Renal Disease formula. Results. Normal renal function (GFR ≥ 90 ml/min/1.73 m. 2. ) was seen in 74 patients. Mild renal insufficiency (GFR 60 to 89 ml/min/1.73 m. 2. ) was seen in 90 patients and moderate renal insufficiency (GFR 30 to 59 ml/min/1.73 m. 2. ) in 15. There was no statistical difference in Co and Cr levels between patients with normal renal function and those with mild or moderate renal insufficiency. No correlation was seen between creatinine and blood metal ion levels or between GFR and blood metal ion levels. Linear regression analysis did not show any association between Co and Cr levels and GFR. Conclusion. We did not find any association between GFR and blood metal ion levels. Consequently, the accumulation of Co and Cr in blood due to renal insufficiency does not seem to be a major risk in patients with mild or moderate renal insufficiency. Cite this article Bone Joint J 2017;99-B:1147–52

Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on-metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry. Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 μg/l (0.55 to 2.55) and 1.28 μg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 μg/l (0.42 to 1.75) and 0.378 μg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p < 0.05). In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 μg/l (0.18 to 0.54) and 0.199 μg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 μg/l (0.17 to 0.5) and 0.194 μg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p > 0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p < 0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 μg/l) as in the controls (0.1934 μg/l), this difference was not statistically significant. (p > 0.05). The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer

Aims. This study compared the cobalt and chromium serum ion concentration of patients treated with two different metal-on-metal (MoM) hinged total knee arthroplasty (TKA) systems, as well as a titanium nitride (TiN)-coated variant. Methods. A total of 63 patients (65 implants) were treated using either a MoM-coated (n = 29) or TiN-coated (n = 7) hinged TKA (GenuX mobile bearing, MUTARS; Implantcast, Germany) versus the BPKS (Brehm, Germany) hinged TKA (n = 27), in which the weight placed on the MoM hinge is diffused through a polyethylene (PE) inlay, reducing the direct load on the MoM hinge. Serum cobalt and chromium ion concentrations were assessed after minimum follow-up of 12 months, as well as functional outcome and quality of life. Results. No differences in mean age (69 years, 40 to 86), mean age adapted Charlson Comorbidity Index (3.1 (SD 1.4)), mean BMI (29.2 kg/m. 2. (SD 5.8)), or number of other implants were observed between groups. Significant improvements in outcome scores and pain levels were achieved for all groups, and there was no difference in quality of life (12-Item Short-Form Health Survey questionnaire (SF-12)). Mean cobalt and chromium ion levels were significantly higher for the GenuX versus the BPKS hinged TKA (GenuX vs BPKS: cobalt: 16.3 vs 9.4 µg/l; chromium: 9.5 vs 5.2 µg/l). The TiN-coated implants did not appear to confer improvement in the metal ion levels. Metal ion concentrations above 7 µg/l were detected in 81%(29/36) of GenuX patients versus 41% (11/27) in the BPKS group. No GenuX patients had normal levels under 2 µg/l, versus 22% of BPKS patients. No significant reduction in outcome scores was observed regardless of the metal ion levels, whereas higher work-related activity was correlated with higher chromium concentrations. Conclusion. Hinged TKA, using MoM hinges, resulted in critically high cobalt and chromium ion concentrations. The BPKS hinged TKA showed significantly lower metal ion concentrations compared with the GenuX TKA. No benefits were observed using TiN coating. The different weightbearing mechanics might influence the wear of the component materials. Higher workloads and physical activity could influence chromium levels. Cite this article: Bone Joint J 2022;104-B(3):376–385

The recent resurgence in the use of metal-on-metal bearings has led to fresh concerns over metal wear and elevated systemic levels of metal ions. In order to establish if bearing diameter influences the release of metal ions, we compared the whole blood levels of cobalt and chromium (at one year) and the urinary cobalt and chromium output (at one to three and four to six years) following either a 50 mm or 54 mm Birmingham hip resurfacing or a 28 mm Metasul total hip replacement. The whole blood concentrations and daily output of cobalt and chromium in these time periods for both bearings were in the same range and without significant difference

Introduction and Aims: Elevated chromium ion levels can be detected in serum following spinal arthrodesis with stainless steel. Comparing characteristics of spinal implants with chromium levels has not been done extensively before. The aim of our study was to compare an extensive range of implant characteristics with chromium levels. Methods: Cross-sectional study of 30 patients (26 females and 4 males) who underwent posterior instrumented spinal arthrodesis using Isola implants including cables for adolescent scoliosis between 1998 and 2002. Patients who had postoperative complications and implants removed were excluded. Serum levels of chromium were analysed between October 2006 and June 2007. Post-operative radiography was used to measure rod length and count hooks, screws, cross-connectors and cables. Surface areas of each component of the implant was estimated and totalled. Metal-on-metal interfaces were calculated. Ethics approval was obtained from the WCH Research Ethics Committee. Results: Both total surface area and total rod length were correlated with serum chromium levels (p = 0.04 and 0.05 respectively). This is the first study to identify a characteristic of spinal implants, other than the late signs of corrosion identified by radiographs, which has significance for serum chromium levels. None of our patients had signs of corrosion, pseudoarthrosis or rod breakage on radiological examination. Compared to raised serum chromium levels, the number of metal-onmetal interfaces approached significance (p = 0.09). Individual numbers of screws, hooks, cables or cross-connectors were not significantly associated with chromium levels. Conclusions: Total rod length may contribute to elevated chromium levels in patients with stainless steel Isola spinal implants and warrants further investigation

Introduction: The potential adverse effects of metal ion elevation in patients with metal-metal bearings continue to be assessed. We reported earlier that metal ions cross the placenta. The present report is a comparison of the rate of transfer in 14 study patients (with MM devices) and 24 control subjects (with no metal devices). Methods: Whole blood from concurrent specimens of maternal and umbilical cord blood obtained at the time of delivery were analysed with high resolution inductively coupled plasma mass spectrometry. Results: Cobalt and chromium were detectable in all specimens in the control subjects and study patients. The mean difference between maternal and cord blood cobalt concentrations was 0.56 μg/l (p < 0.001) in the study group and 0.03 μg/l (p > 0.5) in the control group respectively (figure). The mean difference between maternal and cord blood chromium concentrations was 0.96 chromium (p < 0.0005) in the study group and 0.002 chromium (p > 0.5) in the control group respectively. The mean cord cobalt in the study patients was significantly higher than that in the control subjects (difference 0.38μg/l, p < 0.01) but the difference in the cord levels of chromium between study and controls (difference 0.13μg/l, p> 0.05) was not significant. Discussion: There was almost no difference between the maternal and cord blood levels in the control group implying that the placenta offers almost no resistance to their passage in subjects without a metal device. In the study patients the mean cord cobalt level was 59% of the maternal level and the mean cord chromium level was 26% of the maternal level suggesting that the placenta exerts a modulatory effect on the rate of metal transfer when the maternal levels are higher

Introduction. The observation of elevated heavy metal ions in arthroplasty patients in association with complications has led to concern on the part of patients and surgeons. The aim of this study was to determine the levels of cobalt chromium ions in three compartments, the joint fluid, plasma, and CSF. Method. Patients were divided into 3 groups:. 239 without any implant(M132F108). 50 having a supplementary implant, with a well performing contralateral THR. – 16 large head MoM arthroplasty (Birmingham modular M7F9). – 44 a Birmingham resurfacing(M39F5). 6 revisions of MoM bearings(M3F3). Blood and CSF specimens were harvested at the time of induction of anaesthesia. Joint fluid was aspirated before the surgical incision was made under sterile conditions. Cobalt was assayed using an Agilent7500ce inductively coupled plasma mass spectrometer. Chromium was assayed with a graphite furnace atomic absorption spectrometer (Varian240zlGFAAS). Bivariate correlations were used to determine similarities between group. Results. All results are in nanomoles/litre. Primary group. Blood: Co4.62±3.86; Cr6.10+I-4.17. CSF: Co2.43±3.44; Cr4.82±3.24. Supplementary group:. THR. Blood: Co37.3±62.96; Cr29.2±45.2. CSF: Co3.7±2.6;Cr7.4±4.9. BHR. Blood: Co35.2+I-48.8; Cr66.5+I-1 01.03. CSF: Co4.7±11.6;Cr6.6-'-I-4.1. Revision Group. Joint Fluid: Co5184.5±4662.9; Cr4452.7 ±3302.9. Blood: Col 07.5+1–77.6, Cr127.5±90.2. CSF: Co6.3±3.0, Cr8.3+I-6.2. Comparing with total hip with resurfacing patients, cobalt levels were not significantly different, but chromium levels were higher in resurfacing patients. The CSF levels, however, were not significantly different in the two groups. The CSF chromium level in all circumstances was higher than the cobalt. In patients with well functioning prostheses the blood ion levels were some 50% to 100% higher than patients without prostheses. While cobalt was higher in the joint fluid and the blood measurements, chromium was higher in the CSF. CSF measurements in the three groups of patients with pre-existing implant either well functioning or not, were not significantly different. The blood levels obtained are consistent with that described as reference values” for cobalt and chromium provided in pathology reports. On that basis, we believe that the CSF levels in the samples tested are an accurate representation of the levels. Conslusion. Blood sample chromium levels were higher than cobalt levels with the exception of total hip replacements. In spite of high levels and joint fluid, and less than 5% of the ion level was found in the blood. Of the blood level, less than 15% of was reflected in the CSF

Introduction: The aim of this study was to compare the serum cobalt and chromium levels in patients with Oxford Universal hips and Cenator hips. Both systems are composed of cobalt chromium alloy and have modular cobalt chromium heads, however only the Oxford hip has a sliding mechanism. Material: The serum levels of chromium and cobalt were measured in 20 patients with Oxford Universal Hip replacement (Group 1). This was compared to the serum levels of chromium and cobalt in 17 patients with Cenator Hip replacement (Group 2) and 20 patients with no implants (Group 3). Patients in Group 1 and 2 were assessed clinically and with plain radiographs. Patients were excluded if there was evidence of loosening, if they had other joint implants or any other known cobalt or chromium implant and if they had impaired renal function. All hip replacements were performed as primary procedures. Specimens were analysed by electrothermal atomization atomic absorption spectrometry. Results: There was no statistically significant difference in serum cobalt and chromium levels between groups 1 and 2. Patients in groups 1 and 2 had statistically significant higher serum levels of chromium and cobalt than group 3 patients. Discussion: This study demonstrates that serum levels of chromium and cobalt are elevated in patients with stable hip implants composed of this alloy but not in a normal population. Although it is not known what the long-term effects of chronic low-grade exposure to these ions are, these levels are many order of magnitude below the toxic range. Furthermore, our results show that the Oxford Universal Hip releases no more metal ions into the circulation than an implant without a sliding mechanism

We evaluated the concentrations of chromium and cobalt ions in blood after metal-on-metal surface replacement arthroplasty using a wrought-forged, high carbon content chromium-cobalt alloy implant in 64 patients. At one year, mean whole blood ion levels were 1.61 μg/L (0.4 to 5.5) for chromium and 0.67 μg/L (0.23 to 2.09) for cobalt. The pre-operative ion levels, component size, female gender and the inclination of the acetabular component were inversely proportional to the values of chromium and/or cobalt ions at one year postoperatively. Other factors, such as age and level of activity, did not correlate with the levels of metal ions. We found that the levels of the ions in the serum were 1.39 and 1.37 times higher for chromium and cobalt respectively than those in the whole blood. The levels of metal ions obtained may be specific to the hip resurfacing implant and reflect its manufacturing process

Aims. Several different designs of hemiarthroplasty are used to treat intracapsular fractures of the proximal femur, with large variations in costs. No clinical benefit of modular over monoblock designs has been reported in the literature. Long-term data are lacking. The aim of this study was to report the ten-year implant survival of commonly used designs of hemiarthroplasty. Methods. Patients recorded by the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) between 1 September 1999 and 31 December 2020 who underwent hemiarthroplasty for the treatment of a hip fracture with the following implants were included: a cemented monoblock Exeter Trauma Stem (ETS), cemented Exeter V40 with a bipolar head, a monoblock Thompsons prosthesis (Cobalt/Chromium or Titanium), and an Exeter V40 with a Unitrax head. Overall and age-defined cumulative revision rates were compared over the ten years following surgery. Results. A total of 41,949 hemiarthroplasties were included. Exeter V40 with a Unitrax head was the most commonly used (n = 20,707, 49.4%). The overall rate of revision was small. A total of 28,201 patients (67.2%) were aged > 80 years. There were no significant differences in revision rates across all designs of hemiarthroplasty in patients of this age at any time. The revision rates for all designs were < 3.5%, three years postoperatively. At subsequent times the ETS and Exeter V40 with a bipolar head performed well in all age groups. The unadjusted ten-year mortality rate for the whole cohort was 82.2%. Conclusion. There was no difference in implant survival between all the designs of hemiarthroplasty in the first three years following surgery, supporting the selection of a cost-effective design of hemiarthroplasty for most patients with an intracapsular fracture of the hip, as determined by local availability and costs. Beyond this, the ETS and Exeter bipolar designs performed well in all age groups. Cite this article: Bone Joint J 2023;105-B(8):864–871

Metal and their alloys have been widely used as implantable materials and prostheses in orthopaedic surgery. However, concerns exist as the metal nanoparticles released from wear of the prostheses cause clinical complications and in some cases result in catastrophic host tissue responses. The mechanism of nanotoxicity and cellular responses to wear metal nanoparticles are largely unknown. The aim of this study was to characterise macrophage phagocytosed cobalt/chromium metal nanoparticles both in vitro and in vivo, and investigate the consequent cytotoxicity. Two types of macrophage cell lines, murine RAW246.7 and human THP-1s were used for in vitro study, and tissues retrieved from pseudotumour patients caused by metal-on-metal hip resurfacing (MoMHR) were used for ex vivo observation. Transmission electron microscopy (TEM), scanning electron microscopy (SEM) in combination with backscatter, energy-disperse X-ray spectrometer (EDS), focused ion beam (FIB) were employed to characterise phagocytosed metal nanoparticles. Alamar blue assay, cell viability assays in addition to confocal microscopy in combination with imaging analysis were employed to study the cytotoxiticy in vitro. The results showed that macrophages phagocytosed cobalt and chromium nanoparticles in vitro and the phagocytosed metal particles were confirmed by backscatter SEM+EDS and FIB+EDS. these particles were toxic to macrophages at a dose dependent manner. The analysis of retrieved tissue from revision of MoMHR showed that cobalt/chromium metal nanoparticles were observed exclusively in living macrophages and fragments of dead macrophages, but they were not seen within either live or dead fibroblasts. Dead fibroblasts were associated with dead and disintegrated macrophages and were not directly in contact with metal particles; chromium but not cobalt was the predominant component remaining in tissue. We conclude that as an important type of innate immune cells and phagocytes, macrophages play a key role in metal nanoparticles related cytotoxicity. Metal nanoparticles are taken up mainly by macrophages. They corrode in an acidic environment of the phagosomes. Cobalt that is more soluble than chromium may release inside macrophages to cause death of individual nanoparticle-overloaded macrophages. It is then released into the local environment and results in death of fibroblasts and is subsequently leached from the tissue

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells. We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression. Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo

Aim. Adverse tissue reactions have been a concern in relation to metal components, particularly in hip replacements. We look at a possible correlation between hip joint effusion and metal ion levels. Materials and methods. 56 patients,(42M, 14F) agreed to the study. All had metal-on-mental arthroplasties. Average age was 64.2 (SD 9.8). All patients were asymptomatic. Ultrasound examination performed by one ultrasonographer, using a Sonosite M-Turbo machine with a C60X/5-2 MHz transducer. Cobalt levels were assessed using an inductively coupled plasma mass spectrometer. Chromium levels were assessed using a graphite furnace atomic absorption spectrometer. Results. Average blood ion levels were:. Cobalt 39.02 nmol/L. (SD41.18) range 3 to 215. Chromium 52.51 nmol/L (SD47.48) range 5 to 284. Average Volume: 10.38ml (SD21.3) Range 0 to 219. Conclusion. There was no statistically significant correlation between joint effusion and metal ion levels

Aims: Metal-on-Metal (MOM) bearings for Total Hip Arthroplasty (THA) are known to elevate the serum concentrations of metal ions, raising concern about possible long-term side-effects. One potential modifier of ion release is the bearing diameter used. Resurfacing MOM bearings have a large surface area available for corrosion, but may benefit from improved lubrication and reduced production of corrodible wear debris. The net effect of these two variables on metal ion release is unknown. Methods: In this study, we measured the serum cobalt and chromium levels from 22 large diameter MOM resurfacing arthroplasties (Cormet2000 & Birmingham Hip Resurfacing) and compared them to 22 THA (Ultima) with a bearing diameter of 28 mm. Patients were prospectively matched for activity level, weight and date after surgery. All were at least 6 months after surgery. Results: At a median of 16 months (range 7 to 56) after resurfacing arthroplasty, we found the median serum cobalt and chromium levels to be 38 nmol/l (14 to 44) and 53 nmol/l (23 to 165) respectively. Both these figures were significantly greater than the levels after 28 mm MOM THA, which were 22 nmol/l (15 to 87, p=0.021) and 19 nmol/l (2 to 58, p< 0.001) for cobalt and chromium respectively. Conclusions: As the upper limit of normal in patients without implants is typically 5 nmol/l, both groups had significantly raised metal ion levels, albeit at a relatively short median follow-up period. Large diameter MOM bearings resulted in a greater systemic release of cobalt and chromium ions than did small diameter bearings. This may be of relevance for potential long-term side-effects. It is not known to what extent this difference is due to corrosion of the component surfaces or of the wear particles produced

We measured the levels of cobalt and chromium in the serum in three groups of patients after uncemented porous-coated arthroplasty. Group 1 consisted of 14 consecutive patients undergoing revision for aseptic loosening. Group 2 comprised 14 matched patients in whom the arthroplasty was stable and group 3 was 14 similarly matched patients with arthritis awaiting hip replacement. Specimens were analysed using atomic absorption spectrophotometry. Aseptic loosening of a component resulted in a significant elevation of serum cobalt (p < 0.05), but not of serum chromium. The relative risk of a component being loose, if the patient had a serum cobalt greater than 9.0 nmol/l, was 2.8

Joint replacement failure is usually caused by the formation of wear debris resulting in aseptic loosening. Particulate metal and soluble metal ions from orthopaedic alloys (cobalt chromium or vanadium titanium aluminium) that are used in medical prostheses can accumulate in tissues and blood leading to increased chromosome aberrations in bone marrow and peripheral blood lymphocytes. This paper demonstrates that two of the metals used in orthopaedic prostheses, chromium and vanadium can produce delayed as well as immediate effects on the chromosomes of human fibroblasts in vitro. Fibroblasts were exposed to metal ions for only 24 hours and were then expanded over 30 population doublings involving ten passages. The initial increase of chromosomal aberrations, micronuclei formation and cell loss due to lethal mutations persisted over multiple population doublings, thereby demonstrating genomic instability. Differences were seen in the reactions of normal human fibroblasts and those infected with a retrovirus carrying the cDNA encoding hTERT that rendered the normal human fibroblasts telomerase-positive and replicatively immortal. This suggests that chromosomal instability caused by metal ions is influenced by telomere length or telomerase activity. Formerly this syndrome of genomic instability has been demonstrated in two forms following irradiation. One type is non-clonal and involves the appearance of lethal aberrations that cannot have been carried by the surviving cells. The other type is clonal and the aberrations are not lethal. These may arise as a result of complex rearrangements occurring at a high rate post-insult in surviving cells. The consequences of genomic instability are not yet known but it is possible that the increase of chromosomal aberrations that have been previously observed in human patients could be due to immediate and delayed expression of cellular damage after exposure to orthopaedic metals

This is the first six-year report of a prospective longitudinal study of daily output of cobalt and chromium in urine and their levels in blood following hybrid metal-on-metal surface arthroplasty. Urine and whole blood specimens were analyzed before and periodically after hip resurfacing in 26 male patients after informed consent (mean age 52.9 years, mean BMI 27.9). Two of these patients have undergone contralateral hip resurfacings for progressive pain from end-stage arthritis and had to be excluded. All patients were found to have well-functioning resurfacings at 6-year follow-up. No patient complained of persistent pain or disability. The median 6-year Oxford hip score was 12. Urine chromium and cobalt at six years were 3.9 and 7.8 μg/24 hrs and blood levels were 1.11 and 1.17μg/l respectively. Both urine and blood levels show a statistically significant early increase reaching a peak six months to one year postoperatively followed by a steady decrease over the following five years, although the individual reductions are not statistically significant, except for blood chromium where the 4 and 6 year levels were significantly lower than the 1-year level. Elevated systemic metal exposure following MM bearing arthroplasty continues to cause concern. Our results show that metal release in these bearings shows a reducing trend after an initial peak dispelling the fear that a steady build-up of in vivo metal occurs with progressively increasing blood levels. However, as long as the significance of these elevated levels remains unknown, the need for continued vigilance persists

Purpose: Serum cobalt and chromium levels after metal-on-metal implantations are not well known. There has been little data on the correlation with clinical and radiological surveillance. This prospective analysis followed the changes in serum cobalt, chromium, and titanium levels in order to ascertain the behaviour of the femoral implant and the bearing. Material and methods: The series included 292 patients followed for 27–72 months who were free of kidney failure, were not given vitamin B12 supplementation, and did not have occupational exposure. The same cemented implants were used in all patients: titanium femoral stem, Metasuly heads (28 mm). Serum samples were drawn preoperatively and at three, six and twelve months then annually (systematic activity questionnaire). The limit for detection of serum cobalt and chromium was 1 nmol/l (0.05μg/l); for titanium it was 30 nmol/l (1.4m/l). Results: The main problems encountered were two impingements and two femoral loosenings. Four patterns were identified in the time courses of serum cobalt and chromium. In decreasing order, they were: type 1, low initial level (< 50 nmol/l) then no change; type 2, high initial level (> 50 nmol/l) then decrease; type 3 low initial level then progression; type 4, high initial level then further elevation. Bilateral prostheses showed a particular pattern with elevation after the second implantation. The serum levels rapidly returned to normal after revision in the two impingement cases. The titanium levels were correlated with femoral problems which were not initially detected on the x-rays. Discussion: Correlation between serum cobalt level and wear is difficult to establish. There was no specific pattern after dislocation. The kinetics showed certain patterns with possible prognostic significance: groups 1 (metallic silence) and 2 (breaking-in) would correspond to favourable evolution; type 3 would be difficult to interpret (missed impingement, foreign body, articular decoaptation or major change in activity level); type 4 is highly suggestive of premature wear or a biological problem (excepting bilateral implants). It is important to monitor serum cobalt and titanium simultaneously to detect an interface problem and or femoral loosening