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

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

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

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

Study design: Cross-sectional study of 10 patients to measure the serum levels of cobalt and chromium after TDA. Summary of Background Data: In total hip endoprosthetics and consequently for TDA (total disc arthroplasty), metal-on-metal combinations are used with the aim of reducing wear debris. In metal-on-metal TDA the release of metal ions has until now been secondary to the main discussion. Objectives: To investigate the release of cobalt and chromium ions into the serum following implantation of the metal-on-metal MaverickTM type artificial lumbar disc. Materials and methods: We investigated the serum cobalt and chromium concentration following implantation of 15 Maverick™ TDAs (monosegmental L5/S1 n=5; bisegmental L4/5 and L5/S1 n=5; average age = 36.5 years). 5 healthy subjects (no metal implants) acted as a control group. The measurements of the metals were carried out using the HITACHI Z-8200 AAS polarized Zeeman atomic absorption spectrometer after an average of 14,8months. Results: The concentrations of cobalt and chromium ions in the serum amounted on average to 4.75μg/l (standard deviation 2,71) for cobalt and 1.10μg/l (standard deviation 1,24) for chromium. Compared to the control group, both the chromium and cobalt levels in the serum showed significant increases (Mann-Whitney Rank Sum Test, p=0.0120). At follow-up the Oswestry Disability Score was on average significantly decreased by 24.4 points (L5/S1) (t-test, p < 0.05) and by 26.8 points (L4-S1)(t-test, p < 0.05). The improved clinical situation is also represented by a significant decrease of the Visual Analog Pain Scale of 42,2points after the follow-up (t-test, p< 0,05). Conclusion: Significant systemic release of Cr/Co was proven in the serum compared to the control group. The concentrations of Cr/Co measured in the serum are similar in terms of their level to the values measured in THA metal-on-metal combinations or exceed these values given in the literature. Long-term implication of this metal exposuere in unknown and should be studied further

Aim:. To compare the degree of deformity correction achieved using cobalt chromium versus titanium alloy rods in patients with Adolescent Idiopathic Scoliosis. Method:. A retrospective comparison of two cohorts of patients with Adolescent Idiopathic Scoliosis treated with posterior segmental pedicle screw fixation using either Titanium or Cobalt Chromium rods. The radiographs of 50 patients treated before 2009 (Ti group) and 50 patients after 2009 (CoCr group) were reviewed for changes in: Main Coronal Curvature Sagittal Balance (C7 Plumb Line) Kyphosis (T5-12). Results:. Thirteen were excluded because of incomplete radiographs. 38 patients received CoCr, 45 Ti and 4 patients received hybrid constructs. Correction rate of curves measuring >50 was significantly improved with CoCr (81% vs 69%, p=0.02). Sagittal balance was improved in both groups (CoCr 27.8, Ti 28.0 mm) but no significant difference was seen (p=0.84). Within the Ti group 12 patients moved for normal kyphosis (20–40) to abnormal (<20, >40) while 9 patients moved from abnormal to normal (p=0.66). Within the CoCr Group 10 patients were normalised while only 2 patients moved from normal to abnormal (p=0.04). Mean change in kyphosis showed a trend towards improved correction with CoCr (4.2 vs 2.9) but failed to reach significance (p=0.62). Discussion:. We have demonstrated that CoCr rods significantly improve coronal correction in patient with >50 curves. No difference in overall sagittal balance was seen between metal alloys. There is a trend towards better restoration of T5-12 kyphosis with CoCr however it is unclear if this small difference is clinically relevant. Conflict Of Interest Statement: No conflict of interest

Purpose: The purpose of this study was to monitor serum cobalt (Co) and chromium (Cr) levels in patients after metal-on-metal resurfacing hip arthroplasty with the Cormet 2000® prosthesis, and to evaluate the effect of patient characteristics, prosthesis characteristics, clinical and radiographic measures on metal levels. Methods: Serum Co and Cr levels were determined in 32 patients with Cormet resurfacing prostheses at 0.5, 1 and 2 years postoperatively using ICP-MS and are reported as & #61549;g/L. Control levels were measured in 20 patients without implants. Results: Medium Co and Cr were 0.21 and 0.16 in controls without implants. Medium Co at 6 months (2.65), 1 year (3.62) and 2 years (2.80), and Cr at 6 months (3.74), 1 year (4.73) and 2 years (4.68) were signifi-cantly increased in the Cormet group when compared to control levels (p < .0001). Metal levels did not correlate with cup inclination, component position, head size, age, weight, sex or Harris Hip scores. Markedly elevated Co (35, 63) and Cr (13, 70) levels were found in two patients with excessive cup abduction. In addition, one patient with a loose implant that required revision had markedly elevated Co (19) and Cr (44) levels. Conclusions: Significantly increased levels of cobalt and chromium were released from Cormet 2000 articulations at all time points. Excessive cup abduction was associated with markedly elevated ion levels indicating that accurate cup placement is an important consideration in resurfacing arthroplasty. The significantly increased trace metal levels following resurfacing with the Cormet prosthesis is a concern and warrants further monitoring

Introduction. Total hip replacement with metal-on-polymer (MoP) hip prostheses is a successful treatment for late-stage osteoarthritis. However, the wear debris generated from the polymer acetabular liners remains a problem as it can be associated with osteolysis and aseptic loosening of the implant. This has led to the investigation of more wear resistant polymers in orthopaedics. Cross-linked polyethylene (XLPE) is now the gold-standard acetabular liner material. However, we asked if carbon fibre reinforced polyether ether ketone (CFR-PEEK) might be a lower wear material. In addition, we sought to understand the influence of contact stress on the wear of both XLPE and CFR-PEEK as this has not previously been reported. Materials and Methods. A 50-station circularly translating pin-on-disc (SuperCTPOD) machine was used to wear test both XLPE and CFR-PEEK pins against cobalt chromium (CoCr) discs to investigate the influence of contact stress on their wear rates. Fifty XLPE and 50 CFR-PEEK pins were articulated against CoCr discs. The pins, 9 mm in outer diameter and 12 mm in height, were drilled with different diameter holes to generate different sized annuli and thus, different contact areas. The pins were tested at 1.10, 1.38, 1.61, 2.00 and 5.30 MPa, which are typical contact stresses observed in the natural hip joint. An additional pin for every test group was used as a control to track the lubricant uptake. The discs were polished to 0.015 μm Sa prior to testing. The test stations contained 16 ml of diluted newborn calf serum (protein concentration: 22 g/L). Wear was measured gravimetrically with a balance (resolution: 10 μm) every 500,000 cycles. A standardised cleaning and weighing protocol was followed. Results and Discussion. The wear rates for the XLPE pins were calculated as 1.05, 0.90, 0.77, 0.48 and 0.28 mg/million cycles for the different pin stress groups respectively. The wear rates decreased with increasing contact stress, which was similar to what was observed for ultra-high molecular weight polyethylene (UHMWPE). The change in weight of the discs was insignificant (p-value:0.85). For the CFR-PEEK pin groups, the wear rates were calculated as 0.56, 0.65, 0.61, 0.58 and 0.65 mg/million cycles respectively. The difference between the wear rates was insignificant (p-value: 0.92). However, the weight of the discs decreased significantly (p-value: 0.00). At 1.11 MPa and taking data for UHMWPE tested in the same way, comparison of the three polymers showed that CFR-PEEK produced the lowest wear against CoCr. Although the wear rates for CFR-PEEK were found to be the lowest, the decrease in weight of the CoCr discs articulated against CFR-PEEK was indicative of metallic wear. Conclusion. CFR-PEEK should not be used against orthopaedic metals. XLPE articulating against CoCr was found to be the optimum combination, producing low wear without causing weight change from the counterface, under varying contact stresses

Whole blood metal ion levels remain a concern in those patients undergoing total hip replacement with metal bearing surfaces. The determination of baseline reference levels are essential if useful information can be gleaned from in vivo studies of functioning implants. We set out to prospectively determine chromium and cobalt metal ion concentrations in patients undergoing total hip replacement to determine reference levels of these metal ions. 100 patients with normal renal function, no occupational or environmental exposure to cobalt and chromium, and an absence of implanted metals were recruited into the study. Metal ion levels were determined using two different assay methods. Both ICP-MS (Inductively Coupled Plasma Mass Spectroscopy) and GFAAS (Graphite Furnace Atomic Adsorption Spectroscopy) are well recognized analytical techniques for the quantification of trace elements. Levels were correlated with gender, age and place of residence. There was considerable variability in whole blood metal ion levels, with the ICPMS being more sensitive and consistent than the GFAAS method. Direct comparison of concentration levels determined by the two methods revealed no significant correlation. There was no correlation with age, gender and place of residence. Our findings would favour the use of the ICP-MS to determine reference levels and as a baseline for metal ion surveillance pre-operatively in patients undergoing metal-on-metal total hip replacements. We also determined that changes in whole blood metal ion levels are more significant than actual levels in patients who have undergone total hip replacement

Whole blood metal ion levels remain a concern in those patients undergoing total hip replacement with metal bearing surfaces. The determination of baseline reference levels are essential if useful information can be gleaned from in vivo studies of functioning implants. We set out to prospectively determine chromium and cobalt metal ion concentrations in patients undergoing total hip replacement to determine reference levels of these metal ions. 100 patients with normal renal function, no occupational or environmental exposure to cobalt and chromium, and an absence of implanted metals were recruited into the study. Metal ion levels were determined using two different assay methods. Both ICP-MS (Inductively Coupled Plasma Mass Spectroscopy) and GFAAS (Graphite Furnace Atomic Adsorption Spectroscopy) are well recognised analytical techniques for the quantification of trace elements. Levels were correlated with gender, age and place of residence. There was considerable variability in whole blood metal ion levels, with the ICP-MS being more sensitive and consistent than the GFAAS method. Direct comparison of concentration levels determined by the two methods revealed no significant correlation. There was no correlation with age, gender and place of residence. Our findings would favour the use of the ICP-MS to determine reference levels and as a baseline for metalion surveillance pre-operatively in patients undergoing metal-on-metal total hip replacements. We also determined that changes in whole blood metal ion levels are more significant than actual levels in patients who have undergone total hip replacement

Metal on metal total hip arthroplasty provides the potential improvement in articular wear and the use of large-diameter femoral heads following the prospect for reduction in the risk of dislocation. The purpose of this study was to compare the clinical and radiographic outcomes as well as serum metal ion level between the two different component designs with small and large femoral heads in metal on metal total hip arthroplasty. We studied 39 patients with large head (Magnum®, Biomet; cup size minus 6 mm) and 37 patients with small head (M2a taper®, Biomet; 28 or 32 mm head) of metal on metal total hip arthroplasty between December 2009 to October 2011 with follow-up of 2.1 years (1.0–3.3 years) after surgery. Harris Hip Score, UCLA activity score, EQ-5D, radiographic assessment, and serum cobalt and chromium ion levels were evaluated. Harris Hip Score, UCLA activity score, and EQ-5D were improved after surgery in small and large head groups, however, no significant differences were observed between both groups. Cup inclination was below 50 degree in all prosthesis. No loosening and no osteolysis were observed. Cobalt and chromium ion was not detected before surgery; however, metal ion levels of both groups were increased after surgery in time dependent manner. There was no significant difference between two groups at one year after surgery. One patient in each group showed the increase of cobalt ion level over 7 ppb (15.4 ppb, 12.9 ppb) without any clinical symptom including pain. Cup inclination was 29 degree in both patients and cup anteversion was 38 and 41 degree, respectively. There was no significant difference of ion levels between both groups. No dislocation was observed in large head group while one dislocation occurred in small head group. No patients required the revision surgery. This metal on metal component, especially with large femoral heads, showed the good clinical results at the maximum follow up of 3.3 year after surgery. However, the ion level of two patients increased over 7 ppb and longer follow-up will be needed

Introduction. Revision of total hip replacements (THRS) is predominantly due to aseptic loosening, pain and infection [1]. The current method used to address the risk of infection is to administer antibiotics and to include antibacterial agents into bone cement (if used) and on implant coatings [2–4]. Currently, silver (Ag) coatings have only been applied to titanium hip stems [3]. Cobalt chromium alloy (CoCr) is a widely used orthopaedic alloy which is commonly used as a bearing surface; revisions of joints using this material often describe adverse reactions to the particulate wear debris [1]. This study considers an Ag containing CrN based coating on a CoCr substrate with the aim to reduce cobalt (Co) release and promote antibacterial silver release. Methods. Silver Chromium Nitride (CrNAg) coatings were developed and applied onto the bearing surfaces of 48 mm diameter metal-on-metal THRs. Three coatings were evaluated: high Ag at the surface (CrNAg+), low Ag at surface (CrNAg-) and uniform Ag (CrNAg=). All bearings were tested under ISO 14242-3 conditions for 0.17 million cycles (mc) representing approximately 2 months use in vivo. Wear was determined gravimetrically; Ag and Co levels in the lubricant were measured using graphite furnace atomic absorption spectroscopy. Testing of the CrNAg= bearings were continued to 2mc under standard conditions; CrNAg- bearings to 5mc incorporating lateralisation, which created separation at swing phase and rim contact at heel strike. Wear volume and Ag/Co release were monitored at 0.33, 0.67, 1mc and every mc thereafter. Results. All bearings produced low levels of wear and released silver into the lubricating fluid. An increase in silver concentration at the surface of the bearings was found to increase both the silver released and wear, Figure 1. Negligible cobalt was released. Testing of the CrNAg= coating to 2mc showed the wear rate to decrease after 0.17mc, Figure 2. Ag release continued up to 2mc but at a decreased rate. The CrNAg- coating tested under lateralisation conditions to 5mc showed no coating failure and negligible cobalt release. Wear and silver release showed similar patterns and reached a steady state after 1mc, Figure 3. Discussion. The AgCrN coatings on bearing surfaces of a hip joint are capable of releasing Ag at concentrations within the ‘No Observable Adverse Effect Limit’ [5]. These coatings also prevented Co release while maintaining a low wear rate. All coatings remained intact and did not delaminate, even under adverse conditions. These coatings have been tested in a metal-on-metal hip bearing surface, the most controversial and challenging condition for a coating, wearing against itself. CoCr is used as a bearing surface against polyethylene in hips and knees, in stems and tapers, as tibial trays in knee replacement and as shells for acetabular cups. This coating may be applied to a wide range of applications, removing some of the challenges over the use of CoCr while reducing infections

Abstract

Commonly used alterations of prosthetic surfaces include grit-blasting (GB), plasma-sprayed titanium (Ti) or hydroxyapatite (HA) coating. Systemic concentrations of cobalt (Co) and chromium (Cr) are elevated in patients with metal-on-metal hip replacement, but can occur for all modular hip replacements. Here, we use whole genome microarrays to assess differential gene expression in primary human osteoblasts grown in vitro and on these prosthesis surfaces following exposure to clinically relevant concentrations of Co and Cr. Mesenchymal cells obtained from bone-fragments of 3 patients undergoing joint replacement surgery were differentiated into osteoblasts. Subsequently, cells were cultured in vitro on tissue-culture plates (TCP), or on GB, Ti and HA surfaces (JRI Orthopaedics Ltd, Sheffield, UK). Following 24hr exposure to a combination of clinically equivalent concentrations of Co2+:Cr3+, RNA was extracted and hybridized to SurePrint-G3 Gene Expression Microarray. Probe signals were normalised using ‘Limma’ package on R-Bioconductor and differential gene expression assessed with empirical Bayes approach (Log2FC>1.00, P<0.001 for differentially expressed genes). For cells grown on TCP, 11 genes were upregulated with 500μg/L Co2+:Cr3+. Of these, 4 were associated to HIF-1 signalling based on KEGG pathway analysis (P=5.4e-5). Exposure to 1000μg/L Co2+:Cr3+ altered expression at 164 loci for HA surfaces, and a separate 50 loci for Ti surfaces compared to GB surfaces. Genes for osteoblast differentiation (BMP2 and RGS2) were downregulated on HA surfaces compared to GB, whilst genes for cell-adhesion (ESAM), vesicular trafficking (RAB37) and protection against oxidative damage (NRF2) were upregulated. Ti surfaces caused an upregulation in ERBB3 and CNTF, which are associated with inhibition of osteoblast differentiation and mineralisation, when compared to GB surfaces. This study confirms the role of HIF-1 signalling in response to prosthesis generated metal ions, and is the first to provide a comprehensive genome-wide insight into transcriptional response of osteoblasts at prosthesis surface to clinically equivalent metal exposure