Systemic metal ion monitoring (Co;Cr) has proven to be a useful screening tool for implant performance to detect failure at an early stage in metal-on-metal hip arthroplasty. Several clinical studies have reported elevated metal ion levels after total knee arthroplasty (TKA), with fairly high levels associated with rotating hinge knees (RHK) and megaprostheses. 1. In a knee simulator study, Kretzer. 2. , demonstrated volumetric wear and corrosion of metallic surfaces. However, prospective in vivo data are scarce, resulting in a lack of knowledge of how levels evolve over time. The goal of this study was to measure serum Co and Cr levels in several types TKA patients prospectively, evaluate the evolution in time and investigate whether elevated levels could be used as an indicator for implant failure. The study was conducted at Ghent University hospital. 130 patients undergoing knee arthroplasty were included in the study, 35 patients were lost due to logistic problems. 95 patients with 124 knee prostheses had received either a TKA (primary or revision) (69 in 55 patients), a unicompartimental knee arthroplasty (7 UKA), a RHK (revision −7 in 6 patients) or a megaprosthesis (malignant bone tumours − 28 in 27 patients). The TKA, UKA and RHK groups were followed prospectively, with serum Co and Cr ions measured preoperatively, at 3,6 and 12 months postoperatively. In patients with a megaprosthesis, metal ions were measured at follow-up (cross-sectional study design). In primary knees, we did not observe an increase in serum metal ion levels at 3, 6 or 12 months. Two patients with a hip arthroplasty had elevated preTKA Co and Cr levels. There was no difference between unilateral and bilateral knee prostheses. In the revision group, elevated pre-revision levels were found in 2 failures for implant loosening. In both cases, ion levels decreased postoperatively. In revisions with a standard TKA, there was no significant increase in metal ions compared to primary knee arthroplasty. RHK were associated with a significant increase in Co levels even at short-term (3–12 months). The megaprosthesis group had the highest metal ion levels and showed a significant increase in Co and Cr with time in patients followed prospectively. With the current data, we could not demonstrate a correlation between metal ion levels, size of the implant or length of time in situ. In primary knee arthroplasty with a standard TKA or UKA, metal ion levels were not elevated till one year postoperatively. This suggests a different mechanism of metal ion release in comparison to metal-on-metal hip arthroplasties. In two cases of revision for implant loosening, pre-revision levels were elevated, possibly associated with component wear, and decreased after revision. With RHK, slightly elevated ion levels were found prospectively. Megaprostheses had significantly elevated Co and Cr levels, due to corrosion of large metallic surfaces and/or wear of components which were not perfectly aligned during difficult reconstruction after tumour resection. Further research is needed to assess the clinical relevance of metal ion levels in knee arthroplasty

Hip resurfacing arthroplasty (HRA) became a popular procedure in the early 90s because of the improved wear characteristic, preserving nature of the procedure and the optimal stability and range of motion. Concerns raised since 2004 when metal ions were seen in blood and urine of patients with a MoM implant. Design of the prosthesis, acetabular component malpositioning, contact-patch-to-rim distance (CPR) and a reduced joint size all seem to play a role in elevated metal ion concentrations. Little is known about the influence of physical activity (PA) on metal ion concentrations. Implant wear is thought to be a function of use and thus of patient activity levels. Wear of polyethylene acetabular bearings was positively correlated with patient's activity in previous studies. It is hypothesized that daily habitual physical activity of patients with a unilateral resurfacing prosthesis, measured by an activity monitor, is associated with habitual physical activity. A prospective, explorative study was conducted. Only patients with a unilateral hip resurfacing prosthesis and a follow-up of 10 ± 1 years were included. Metal ion concentrations were determined using ICP-MS. Habitual physical activity of subjects was measured in daily living using an acceleration-based activity monitor. Outcome consisted of quantitative and qualitative activity parameters. In total, 16 patients were included. 12 males (75%) and 4 females (25%) with a median age at surgery of 55.5 ± 9.7 years [43.0 – 67.9] and median follow-up of 9.9 ± 1.0 years [9.1 – 10.9]. The median cobalt and chromium ion concentrations were 25 ± 13 and 38 ± 28 nmol/L. A significant relationship, when adjusting for age at surgery, BMI, cup size and cup inclination, between sit-stand transfers (p = .034) and high intensity peaks (p = .001) with cobalt ion concentrations were found (linear regression analysis). This study showed that a high number of sit-stand transfers and a high number of high intensity peaks is significantly correlated with high metal ion concentrations, but results should be interpreted with care. For patients it seems save to engage in activities with low intensity peaks like walking or cycling without triggering critical wear or metal ions being able to achieve important general health benefits and quality of life, although the quality (high intensity peaks) of physical activity and behaviour of patients (sit-stand-transfers) seem to influence metal ion concentrations

Background. Metal-on-metal hip implants can produce adverse tissue reactions to wear debris. Increased metal ion concentrations in the blood are measured as a proxy to wear and the complications it can trigger. Many studies have examined various factors influencing the metal ion concentrations. This is the first study to investigate the effect of physical activity level, as objectively measured in daily life, on blood ion levels, expecting higher concentrations for higher patient activity. Methods. Thirty-three patients (13F/20M, 55.8 ± 6.2 years at surgery) with a unilateral resurfacing hip prosthesis were included. At last follow-up (6.8 ± 1.5 years) cobalt and chromium concentrations in the blood were determined by inductively coupled plasma mass spectrometry. Physical activity was measured during 4 successive days using a 3D-acceleration-based activity monitor. Data was analysed using validated algorithms, producing quantitative and qualitative parameters. Acetabular cup position was measured radiographically. Correlations were tested with Pearson's r'. Results. Wide ranges in cobalt (10-833nmol/l) and chromium (16-592nmol/l) concentrations were measured. No correlations were found between metal ion concentrations and patient characteristics. The mean time of walking per day of was 5475 ± 2730 seconds (≈ 91 minutes) per day, with 6953 ± 3104 steps made during the day. The cadence, the number of steps per minute, was 99.5 ± 7.4. The subjects performed 41 ± 13 sit-stand transfers per day. The number of peak intensity declines when peaks where more intense. No correlations were found between quantitative or qualitative parameters and metal ion concentrations. Conclusions. Higher metal ion concentrations were not correlated with higher activity levels contrary to original expectations. Based on the results the orthopaedic surgeons is able to reassure his or her patients that physical activity in daily living is presumably safe en does not influence metal ion concentrations. Level of Evidence. 2b. Approval. the ethics committee of the Atrium MC, Heerlen approved this study

The biological significance of cobalt-chromium wear particles from metal-on-metal hip replacements may be different to the effects of the constituent metal ions in solution. Bacteria may be able to discriminate between particulate and ionic forms of these metals because of a transmembrane nickel/cobalt-permease. It is not known whether wear particles are bacteriocidal. We compared the doubling time of coagulase negative staphylococcus, Staphylococcus aureus and methicillin resistant S. aureus when cultured in either wear particles from a metal-on-metal hip simulator, wear particles from a metal-on-polyethylene hip simulator, metal ions in solution or a control. Doubling time halved in metal-on-metal (p = 0.003) and metal-on-polyethylene (p = 0.131) particulate debris compared with the control. Bacterial nickel/cobalt-transporters allow metal ions but not wear particles to cross bacterial membranes. This may be useful for testing the biological characteristics of different wear debris. This experiment also shows that metal-on-metal hip wear debris is not bacteriocidal

Bone related adverse events including failure of implant osseo-integration, periprosthetic fracture, femoral neck narrowing, and unexplained pain occur more frequently following metal-on-metal hip resurfacing (MoMHR) versus total hip arthroplasty (THA). The exact mechanism for the adverse effects is still unclear and may be due to the direct effect on bone cells of metal ions released from the prostheses. The aim of the present study was to determine the effect of clinically relevant combinations of metal ions on osteoblast cell survival and function. To assess cell proliferation and alkaline phosphatase (ALP) activity of osteoblasts, human osteoblast cells (SaOS-2), were cultured in 96-well plates for 24-hours and then treated with metal ions. Cell proliferation was measured at day 3 and day 7 using MTS assay, whilst ALP activity was assessed at day 3 by measuring pNPP substrate hydrolysis by the cell lysate. Mineralisation ability of the cells was assessed in 24-well plates cultured until day 21 and staining the calcium deposits using Alizarin red. All cultures were treated with the IC50 concentration of Co(II) (135μM) and an equivalent Cr(III) concentration (1Co(II):1Cr(III)). After 3 days, Co(II) at an IC50 concentration decreased osteoblast proliferation as expected, but no further decrease in proliferation was observed with the 1Co(II):1Cr(III) combination treatment. However, after 7 days, a further significant decrease (P<0.05) in proliferation was observed with the combination treatment compared to Co(II) IC50. A similar significant decrease (P<0.01) was observed for ALP activity at day 3 with 1Co(II):1Cr(III) compared to Co(II) alone. For mineralization, a significant reduction (P<0.0001) was observed for Co(II) IC50 concentration, however no further reduction was seen with the 1Co(II):1Cr(III) combination treatment. The observed decrease in cell proliferation and ALP activity with combination treatments suggest an additive detrimental effect compared to single ions alone. The mineralisation ability did not show any additive effect due to cell toxicity of chronic exposure to IC50 concentrations calculated from 3 day proliferation cultures. The results suggest that presence of both cobalt and chromium ions in the periprosthetic environment have more severe detrimental effect on osteoblasts than single ions alone and extend our understanding of the periprosthetic bone health

Total knee arthroplasty is a well-established treatment for degenerative joint disease, on the other hand metal ion release of cobalt or chromium and particle formation can trigger intolerance reactions. Biotribological examinations can help to assess the metal ion release in different settings. The purpose of this study was the evaluation of inter-laboratory differences in the metal ion concentration analysis. Samples were generated in a 3+1 station knee wear simulator (EndoLab GmbH, Thansau, Germany) with a medium size Columbus Knee System with or without AS multilayer coating. The wear simulation was performed under highly demanding activity (HDA) profile and samples were taken after 0.5, 5.0, 5.5. and 8.0 million cycles. The samples were blinded and sent to three different laboratories and the content of chromium, cobalt, molybdenum, nickel, and zirconium was assessed by inductively coupled plasma mass spectrometry (ICP-MS). The AS multilayer coating clearly reduced the release of chromium, cobalt and molybdenum. Mean levels were: Chromium 9329.78µg/l ± 985.44 vs 503.75µg/l ± 54.19, cobalt 10419.00µg/l ± 15.517.53 vs 2.60µg/l ± 1.35, molybdenum 2496.33µg/l ± 102.62 vs 2.46µg/l ± 2.31. Interestingly we found especially for nickel and zirconium big inter-laboratory differences in the metal assessment. There were up to 10-fold higher values in comparison of one laboratory to another. The data demonstrate that results of metal ion assessment should be evaluated by interlaboratory comparison and should be critically interpreted

Metal on metal (MoM) bearings in hip surgery may result in increased blood levels of metal ions. The nature of the relationship between ion levels and failure is still not fully understood. We compared three cohorts of resurfacing patients, grouped for brand and diameter of femoral component. We measured the blood level of Cobalt and Chromium ions at an average of 4 years postoperatively. The results were grouped as follows: Birmingham Hip Resurfacing ≥50 mm diameter, Durom resurfacing ≥50 mm diameter and Durom resurfacing <50 mm diameter. 120 patients were included in each group. There were significant differences in Cobalt levels between the groups. The median cobalt level for the BHR group was 8 nmol/L higher than the Durom ≥50 mm group (P<0.005). The Durom <50 mm group recorded cobalt levels 8.5 nmol/L higher than the Durom ≥50 mm group (P=0.0004). Revision rates were equal in the Large BHR's and Large Durom HRA (both 3.3%) however the small Durom HRA had a revision rate of 8.3%. Elevated blood ion levels can indicate a failing MoM bearing. When similar ion levels were reported for BHR and small Durom the latter had significantly higher revision rates. The large BHR and large Durom HRA have similar revision rates yet the large Durom HRA had significantly lower metal ion levels. Only one of the patients having revision surgery (n=18) had metal ion levels above the MHRA threshold. This suggests ion levels do not absolutely predict the rate of HRA failure. Given similar revision rates with different ion levels between the large BHR and large Durom hips, mechanisms of failure leading to revision must be isolated from the release of metal ions. Therefore clinical and image based follow up are recommended in addition to ion level monitoring

The aim of this study is to investigate whether MoM implants result in more chromosome aberrations and increased blood metal ions postoperatively whe compared to MoP implants. MoM arthroplasties are being inserted in increasing numbers of younger patients due to the increased durability and reduced requirements for revision in these implants. Recent studies have raised many concerns over possible genotoxicity of MoM implants. This is a prospective study of patients who have undergone elective total hip replacement, they were selected and then randomised into two groups. Group A received a MoP implant and group B received a MoM implant. Patients are reviewed pre-operatively (control group), at 3 months, 6 months, 1 year and 2 years post-operatively. On each occasion blood tests are taken to quantify metal ion levels (chromium, cobalt, titanium, nickel and vanadium) using HR-ICPMS method and chromosome aberrations in T lymphocytes using 24 colour fluorescent in situ hydridisation (FISH). 51 patients have been recruited to date, 23 of whom had MoP prosthesis and 28 a MoM. 47 of these had their 1 year follow-up with blood analysis and 38 have had 2 year follow up. There appeared to be a bedding period for both MoM and MoP groups, with an increase in metal ion release. The blood concentration of chromium, cobalt and titanium rise significantly in the MoM group at the 2 year stage. Chromosome aberrations occurred in both groups. Both the MoM and MoP groups showed increase frequency of aneuploidy aberrations and structural damage. The greatest increase in metal ion levels occurred at the 1 to 2 year interval corresponding to significant rise in chromosome aberrations. Preliminary results of this study show that the levels of chromium, cobalt and titanium are significantly higher in the MoM group compared to the MoP group. This corresponds to increases in chromosome aberrations in the groups with increases in structural chromosome damage after two years

Total knee arthroplasty is a well established treatment for degenerative joint disease with good clinical results. However, complications may occur due to a biological response to polyethylene wear particles, leading to osteolysis and aseptic loosening, as well as local and systemic hypersensitivity reactions triggered by metal ions and particles such as chromium, cobalt and molybdenum. Moreover, there is an increasing demand on the performance of these implants, as this treatment is also performed in heavier, younger and middle-aged adults who have a significant physical activity and higher life expectancy. The purpose of the following study was to compare the wear characteristics and performance of a zirconium nitride (ZrN) coated knee implant, designed for patients with metal ion hypersensitivity, against the clinically established cobalt-chromium (CoCr) version under a high demanding activities wear simulation. Medium size AS Columbus® DD (Aesculap AG, Tuttlingen, Germany) femoral and tibial components with a ZrN surface were tested in comparison with the cobalt-chromium version Columbus® DD. For both groups, ultra-high-molecular weight polyethylene (UHMWPE) gliding surfaces (size T3, high 10 mm) were used. Wear simulation was performed on a load controlled 4 station knee wear simulator (EndoLab GmbH, Thansau, Germany) capable of reproducing loads and movement of daily activities measured in vivo (Bergmann et al, 2014) on 8 patients and normalized to a patient weight of 100 kg (Schwiesau et al, 2014). The load profiles were applied for 5 million cycles in a combination of 40% stairs up, 40% stairs down, 10% level walking, 8% chair raising and 2% deep squatting. Test serum was changed every 0.5 million cycles and all the components were cleaned and analyzed according to ISO 14243-2:2009(E). The gliding surfaces were evaluated for gravimetric wear and wear patterns, femur components analyzed for scratches and the test medium analyzed for metal ion concentration (cobalt, chromium, molybdenum and zirconium) using ICP-MS according to ISO 17294-2. The present study showed a wear rate reduction for the ZrN group (1.01 ± 0.29 mg/million) in comparison with the CoCr group (2.40 ± 1.18 mg/million cycles). The articulation surface of the ZrN coated femurs remained polished after the testing period, whereas the uncoated femurs showed wear scratches. Furthermore, the metal ion release from the ZrN coated implants was reduced orders of magnitude in comparison with the CoCr implants through the entire test. These results demonstrate the efficiency of ZrN coated knee implants to reduce wear as well as to prevent metal ion release in the knee joint

Metal-on-metal (MOM) bearings for hip arthroplasty are increasing in popularity. Concern remains, however, regarding the potential toxicological effects of the metal ions which these bearings release. The serum levels of cobalt and chromium in 22 patients who had undergone MOM resurfacing arthroplasty were compared with a matched group of 22 patients who had undergone 28 mm MOM total hip arthroplasty (THA). At a median of 16 months (7 to 56) after resurfacing arthroplasty, we found the median serum levels of cobalt and chromium to be 38 nmol/l (14 to 44) and 53 nmol/l (23 to 165) respectively. These 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) respectively. Since the upper limit for normal patients without implants is typically 5 nmol/l, both groups had significantly raised levels of metal ions. MOM bearings of large diameter, however, result in a greater systemic exposure of cobalt and chromium ions than bearings of small diameter. 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 surfaces of the component or of the wear particles produced

Summary. Five year migration results of 49 large-head metal-metal (MoM) total hip arthroplasties show good implant stability and no association between implant migration and metal-ions levels, stem and cup position, or femoral bone mineral density. Introduction. The failure mechanism of metal-metal (MoM) total hip arthroplasty has been related to metal wear-debris and pseudotumor, but it is unknown whether implant fixation is affected by metal wear-debris. Patients and Methods. In July-August 2012 41 patients (10 women) at a mean age of 47 (23–63) years with a total of 49 MoM hip arthroplasties (ReCap Shell/M2a-Magnum head/Bi-Metric stem; Biomet Inc.) participated in a 5–7 year follow-up with blood tests (chrome and cobalt serum ions), questionnaires (Oxford Hip Score (OHS) and Harris Hip Score (HHS), measurement of cup and stem position and periprosthetic BMD. Further the patients had been followed with stereo-radiographs post-operative and at 1, 2 and 5 years for analysis of implant migration (Model-Based RSA 3.32). Results. 4 patients (6 hips) had elevated metal-ion levels (>7ug/l). The mean cup inclination was 45°(sd 6), the mean cup anteversion was 17°(sd7), and the mean stem anteversion was 19°(sd7). The difference between genders was statistically insignificant (p>0.09). At 5 years follow-up total translation (TT) for the stems (n=39 hips) was a mean 0.79mm (sd 0.53) and total rotation (TR) was a mean 1.99° (sd 1.53). Between 1–2 years there was no significant difference in mean TT (p=0.49)for the stems and between 2–5 years TT was mean 0.13 mm (sd 0.35) which was significant (p=0.03) but clinically very small and within the precision limits of the method. We found no significant migration along the 3 separate axes. There was no significant association between stem migration and metal ion levels >7ug/l (p=0.55), female gender (p=0.86), stem anteversion > 25° (p=0.29), T-scores < −1 (p=0.23), total OHS < 40 (p=0.19) or total HHS < 90 (p=0.68). Between 1–5 years there was no significant change in neither subsidence (p=0.14) nor in version (p=0.91) of the stems. At 5 years TT for the cups (n=36) was mean 1.21 mm (sd 0.74) and TR was mean 2.63° (sd 1.71). Between 1–2 years cup migration along the z-axis was mean 0.29 (sd 0.73) (p=0.03), which was also within precision limits of the method. There was a positive association between total OHS below 40 (n=4) and cup migration (p=0.04), but no association between cup migration and metal ion levels >7ug/l (p=0.80), female gender (p=0.74), cup inclination > 50° (p=0.93), cup anteversion > 25° (p=0.88) or HHS < 90 (p=0.93). Proximal cup migration at 5 years was mean 0.46 mm (sd 0.47), which was similar to the cup migration at 1 year (p=0.91) and 2 years (p=0.80) follow-up. No patients were revised before the final 5–7 year follow-up. Patient satisfaction was high (94%). Conclusion. All cups and stems were well-fixed between 1–5 years. We found no statistical significant correlation between implant migration and other factors that have been associated with failure of MoM hip arthroplasty such as elevated metal ion levels, component position, and female gender. Cup migration was higher in patients with a total OHS below 40. In conclusion, metal wear-debris does not seem to influence fixation of hip components in large-head MoM articulations at mid-term follow-up

Summary. Management of metal on metal hip replacements can be accomplished with a simple algorithm including easily available metal ion levels and hip MRI with metal artifact reducing software. After revision serum metal ion levels can be expected to fall rapidly. Introduction. Metallic ion release may be related to bearing surface wear and thus serves as an indicator of the in-vivo performance of metal on metal articulations. The purpose of this prospective, controlled study was to compare new large head metal on metal hip components with established modular metal on metal and metal on polyethylene and to determine their effects on serum metal levels before and after revision. Patients & Methods. We performed a multi-surgeon, prospective, controlled trial to compare clinical, radiographic, and metal ion concentration in serum (cobalt and chrome) results across multiple devices including the Large Head ASR XL System (MoM-1), the Ultamet Advanced Modularity System (MoM-2), and as the control the Pinacle Acetabular Cup System with polyethylene liner (MoP). One hundred and fifty-one consecutive patients undergoing THA were enrolled in the study: MoM-1 n=97; MoM-2 n=22; MoP n=32. Clinical, radiographic, and venous blood assessments were performed pre-operatively, and post-operatively at 6 months, 1 year and 2 years, and after revision (1,3,6,12 months). All serum ion concentrations are reported in nmol/L. We are following metal ion levels after revision and have developed an algorithm to diagnose and manage patients with MoM THA. Results. MoM-1 patients had significantly increased average cobalt and chromium levels. Clinical scores improved after surgery in all groups and continued to improve in MoM-2 and MoP patients after 2 years but decreased slightly in the MoM-1 patients at 2 years. Average cup inclination angle did not differ significantly between the groups: MoM-1 50.2, MoM-2 47.8, and MoP 51.7. In the MoM-1 group 11 patients (11%) had significantly elevated ion levels (MoM-1 Outliers). Nine hips (9.3%) in 8 MoM-1 outlier patients required revision. Metal ion levels were not significantly different between MoM-2 and MoP groups. Metal ion levels after revision in the MoM-1 group decreased rapidly but at one year post-operatively have still not returned to an equivalent baseline comparable to the MoM-2 and MoP groups. All revisions were in the MoM-1 group. Chromium levels decreased more slowly than Cobalt levels. Discussion. To our knowledge this is the only data in the literature prospectively comparing ion levels among groups and reporting post revision ion levels. Average serum ion levels were elevated at all post-operative samples in the MoM-1 group but this was due to significantly elevated levels in a subset of outliers who required revision. Excluding the outliers there is not a significant difference in post-operative ion levels between the groups. There was no radiographic evidence of component malposition or aseptic loosening in any of the groups. Control groups (MoM-2, MoP) performed comparatively across all variables. We present an algorithm to diagnose and manage patients with metal on metal THA and offer evidence that metal ion levels do decrease after revision but still remain abnormally elevated at one-year post revision compared to the control group. A significant portion of MoM-1 performs comparatively to the controls in terms of ions

There are several component position and design variables that increase the risk of edge loading and high wear in metal-on-metal hip resurfacing (MOM-HR). In this study we combined all of these variables to calculate the ‘contact patch to rim distance’ (CPRD) in patients undergoing revision of their MOM-HR. We then determined whether CPRD was more strongly correlated with component wear and blood metal ion levels, when compared to any other commonly reported clinical variable. This was a retrospective study of 168 consecutively collected MOM-HR retrieval cases. All relevant clinical data was documented, including pre-revision whole blood cobalt and chromium ion levels. Wear of the bearing surfaces was then measured using a roundness-measuring machine. We found four variables to be significantly (p < 0.05) correlated with component wear and blood metal ion levels: (1) cup inclination angle, (2) cup version angle, (3) arc of cover, and (4) CPRD. The correlations between CPRD and both wear and ion levels were significantly stronger than those seen with any other variable (all p < 0.0001). Our study has shown that CPRD is the best predictor of component wear and blood metal ion levels, and may therefore be a useful parameter to help determine those patients who are at risk of high wear and require more frequent clinical surveillance

The biological reaction in metallosis and pseudotumor generation after metal on metal total hip arthroplasty or corroding metal implants remains unsettled. Clinically, still lethal cases appear with massive bone loss and metal ions are suspected to be responsible for this inflammatory reaction, solid metal wear particles instead are usually not observed in the common literature. The aim of this study was to compare the biological reactions of metal ions and metal wear particles in a murine in vivo model. Metal ions (CoCr), metal particles (CoCr), polyethylene particles (UHMWPE) and phosphate buffered saline (PBS) were injected into the left knee joint of female BALB/c mice. 7 days after injection, the microcirculation was observed using intravital fluorescence microscopy, followed by euthanasia of the animals. After the assessment of the knee diameter, the knees underwent histological evaluations of the synovial layer. Throughout all recorded data, CoCr particles caused higher inflammatory reactions compared to metal ions and UHMWPE particles. The mice treated with the solid particles showed enlarged knee diameters, more intensive leukocyte–endothelial cell interactions and an elevated functional capillary density. Pseudotumor-like tissue formations in the synovial layer of the mice were only seen after the exposition to solid CoCr particles. Even if the focus of several national guidelines concerning metallosis and pseudotumor generation is on metal ions, the present data reveal that solid CoCr particles have the strongest inflammatory activity compared with metal ions and UHMWPE particles in vivo

Over the last decades, biodegradable metals emerged as promising materials for various biomedical implant applications, aiming to reduce the use of permanent metallic implants and, therefore, to avoid additional surgeries for implant removal. However, among the important issue to be solved is their fast corrosion - too high to match the healing rate of the bone tissue. The most effective way to improve this characteristic is to coat biodegradable metals with substituted calcium phosphates. Tricalcium phosphate (β-TCP) is a resorbable bioceramic widely used as synthetic bone graft. In order to modulate and enhance its biological performance, the substitution of Ca2+ by various metal ions, such as strontium (Sr2+), magnesium (Mg2+), iron (Fe2+) etc., can be carried out. Among them, copper (Cu2+), manganese (Mn2+), zinc (Zn2+) etc. could add antimicrobial properties against implant-related infections. Double substitutions of TCP containing couples of Cu2+/Sr2+ or Mn2+/Sr2+ ions are considered to be the most perspective based on the results of our study. We established that single phase Ca3−2x(MˊMˊˊ)x(PO4)2 solid solutions are formed only at x ≤ 0.286, where Mˊ and Mˊˊ—divalent metal ions, such as Zn2+, Mg2+, Cu2+, Mn2+, and that in case of double substitutions, the incorporation of Sr2+ ions allows one to extend the limit of solid solution due to the enlargement of the unit cell structure. We also reported that antimicrobial properties depend on the substitution ion occupation of Ca2+ crystal sites in the β-TCP structure. The combination of two different ions in the Ca5 position, on one side, and in the Ca1, Ca2, Ca3, and Ca4 positions, on another side, significantly boosts antimicrobial properties. In the present work, zinc-lithium (Zn-Li) biodegradable alloys were coated with double substituted Mn2+/Sr2+ β-TCP and double substituted Cu2+/ Sr2+ β-TCP, with the scope to promote osteoinductive effect (due to the Sr2+ presence) and to impart antimicrobial properties (thanks to Cu2+ or Mn2+ ions). The Pulsed Laser Deposition (PLD) method was applied as the coating's preparation technique. It was shown that films deposited using PLD present good adhesion strength and hardness and are characterized by a nanostructured background with random microparticles on the surface. For coatings characterization, Fourier Transform Infrared Spectroscopy, X-ray Diffraction, and Scanning Electron Microscopy coupled with Energy Dispersive X-ray and X-ray Photoelectron Spectroscopy were applied. The microbiology tests on the prepared coated Zn-Li alloys were performed with the Gram-positive (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative (Salmonella typhimurium, Escherichia coli) bacteria strains and Candida albicans fungus. The antimicrobial activity tests showed that Mn2+/Sr2+ β-TCP -coated and Cu2+/Sr2+ β-TCP coated Zn-Li alloys were able to inhibit the growth of all five microorganisms. The prepared coatings are promising in improving the degradation behavior and biological properties of Zn-Li alloys, and further studies are necessary before a possible clinical translation

An increase in metal ion levels is seen after implantation of all MoM hip prosthesis due to release from the surface directly, more so during articulation and corrosion of the bearing surfaces. The bearing surfaces in MoM prosthesis consist of cobalt, chromium and molybdenum. Several case-reports of cobalt toxicity due to a MoM prosthesis have been published in the last decade. Cobalt intoxication may lead to a variety of symptoms: neuro-ocular toxicity (tinnitus, vertigo, deafness, blindness, convulsions, headaches and peripheral neuropathy), cardiotoxicity and thyroid toxicity. Nausea, anorexia and unexplained weight loss have been described. Systemic effects from metal ions even with well functioning implants or with ion concentrations lower than those associated with known adverse effects may exist and warrant investigation. The aim of this study is to investigate self-reported systemic complaints in association with cobalt ion concentrations in patients with any type of MoM hip prosthesis. A cohort study was conducted. Patients with both unilateral and bilateral, resurfacing and large head metal on metal total hip arthroplasties were included for the current study. Blood metal ion concentrations (cobalt and chromium) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Based on the known cobalt toxicity symptoms of case-reports and toxicology reports a new non-validated questionnaire was developed. questions were subdivided in general questions/symptoms, vestibular symptoms, neurological symptoms, emotional health and cardio- and thyroid toxicity symptoms. Independent samples T test, Fishers Exact Test and Pearsons (R) correlation were used. Analysis was performed on two groups; a low cobalt ion concentration group and a high cobalt ion concentration group A total of 62 patients, 36 (58%) men and 26 (42%) women, were included with a mean age at surgery of 60.8 ± 9.3 years (41.6 – 78.1) and a mean follow up of 6.3 ± 1.4years (3.7 – 9.6). In these patients a total of 71 prosthesis were implanted: 53 unilateral and 9 bilateral. Of these, 44 were resurfacing and 27 large head metal on metal (LHMoM) total hip arthroplasties. Mean cobalt and chromium ion concentrations were 104 ± 141 nmol/L (9 – 833) and 95 ± 130nmol/L (6 – 592), respectively. Based on the different thresholds (120 – 170 or 220 nmol/L) the low cobalt ion concentration group consisted of 44 (71%), 51 (82%) or 55 (89%) subjects respectively. No differences were found in general characteristics, independently of the threshold. The composite score of vestibular symptoms (vision, hearing, tinnitus, dizziness) was significantly higher (p < .050) in all high cobalt ion concentrations groups, independent of the threshold value This study aimed to detect a trend in self-reported systemic complaints in patients with metal-on-metal hip arthroplasty due to raised cobalt ion concentrations. Vestibular symptoms were more common in high cobalt ion concentration groups independent of the three threshold levels tested. The upper limit of acceptable cobalt ion concentrations remains uncertain. With regards to proactively inquired, self-reported symptoms the threshold where effects may be present could be lower than values currently applied in clinical follow-up. It is unknown what exposure to elevated metal ion concentrations for a longer period of time causes with aging subjects. Further research with a larger cohort and a more standardized questionnaire is necessary to detect previously undiscovered or under-reported effects

Introduction. Metal-on-metal (MoM) hip resurfacing arthroplasty is a popular choice for young and active patients. However, there are concerns recently regarding soft tissue masses or pseudotumours. The appearance of these complications is thought to be related blood metal ion levels. The level of metal ions in blood is thought to be the result of MoM wear. In the present study the contribution of acetabulum orientation to stress distribution was investigated. Methods. Four subjects with MoM resurfacings and with known blood metal ion levels underwent motion analysis followed by CT scans. The positions of the acetabular (cup) and femoral components were determined the CT data relative to local coordinate systems in the pelvis (PCS) and the femur (FCS). Transformations, calculated from the motion analysis data, between the PCS and FCS gave the position of the cup relative to the femoral component for each frame of captured motion data. Hip reaction forces were taken from published data1. The intersection of hip reaction force with each subject's cup and the increase in inclination required to move the force to the edge of the cup was calculated for 2% intervals during the stance phase of gait. Finite element models representing each subject's cup and femoral components were created and contact stresses were determined for the native cup inclination angle. For each model, the effect of increasing the inclination of the cup, by up to 10°, in 1° increments, was determined. Results and Discussion. The two subjects with high metal ion levels had inclination angles of 60.2° and 53.7° whereas the two with low metal ion levels had inclination angles of 45.6° and 46.5°. The subjects with high metal ion levels required very little increase to their inclination angle to cause the hip reaction force vector to intersect at the edge. The contact stress on the cup increased dramatically when the inclination angle was such that the hip reaction force intersected with the edge. The average increase in contact stress under edge-loading conditions was 57% for the two subjects with high metal ions. In contrast, the subjects with low metal ions exhibited no change in contact stress when the inclination angle of their cups was increased by 10°. The inter-subject variability in the measured hip reaction forces was greater than the amount of increase in cup inclination required to induce edge-loading for the subjects with high metal ion levels. These results suggest that poor positioning of the cup during surgery may result in edge-loading, a greater rate of wear and adverse biological reactions associated with metal ion release

Metal-on-metal (MOM) hip arthroplasty, including resurfacing, has become the subject of recent research and debate. There is the perceived benefit of improved wear rates of bearing surfaces leading to superior durability and performance of these types of implant. An associated feature of MOM bearing surfaces is the generation of metal ions. These can have local and systemic cytotoxic effects. An immunoloigical response has been suggested, however, metal wear debris may cause direct damage to cellular DNA. Studies have shown that release of these ions is related to bearing diameter and component alignment. However, little is known about the relationship between metal ion levels and implant survivorship. The MHRA has published guidelines on the follow-up of patients with MOM implants including measurement of serum ion levels and cross sectional imaging. Between February 2001 and November 2009, 135 patients (164 hips) had MOM resurfacing arthroplasty at our institution. We report a retrospective analysis of the data generated by review of these patients. Of the 135 patients, 91 were identified for clinical review. Each patient had serum metal ion levels measured, plain AP radiographs of the pelvis examined and, in the presence of raised metal ions, a Metal Artefact Reduction Sequence (MARS) MRI performed. 27 patients (35 hips) had raised metal ion levels (Cobalt and Chromium). Patients with raised metal ion levels had a mean acetabular cup inclination of 52.7 degrees compared with a mean inclination of 48.6 degrees in patients with normal ion levels (p<0.05). MARS MRI in the raised ion group revealed 9 patients with appearances suggestive of ALVAL. A number of these patients had hip revision surgery with the remainder awaiting potential revision. These findings reflect current evidence suggesting a relationship between sub-optimal component position and raised metal ion levels and an increased rate of ALVAL

Hip simulators have been used for ten years to determine the tribological performance of large-head metal-on-metal devices using traditional test conditions. However, the hip simulator protocols were originally developed to test metal-on-polyethylene devices. We have used patient activity data to develop a more physiologically relevant test protocol for metal-on-metal devices. This includes stop/start motion, a more appropriate walking frequency, and alternating kinetic and kinematic profiles. There has been considerable discussion about the effect of heat treatments on the wear of metal-on-metal cobalt chromium molybdenum (CoCrMo) devices. Clinical studies have shown a higher rate of wear, levels of metal ions and rates of failure for the heat-treated metal compared to the as-cast metal CoCrMo devices. However, hip simulator studies in vitro under traditional testing conditions have thus far not been able to demonstrate a difference between the wear performance of these implants. Using a physiologically relevant test protocol, we have shown that heat treatment of metal-on-metal CoCrMo devices adversely affects their wear performance and generates significantly higher wear rates and levels of metal ions than in as-cast metal implants

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 in13 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