In a randomized study of 60 patients allergic reactions are evaluated in three joint prosthesis groups, a resurfacing arthroplasty (ReCap), a non-cemented, large metal-on-metal head (Bimetric Magnum) and a non-cemented, alumina ceramic-on-ceramic bearing in a titanium shell (Bimetric C2a). The inclusion criteria were osteoarthritis, ASA I–II, MRI-scan without caput necrosis, DXA-scan without osteoporosis. The exclusion criteria were short neck (<2cm.), large cysts (>1cm.), medical treatment affecting the bone metabolism, severe deformity of the femoral head, impaired kidney function and inability to co-operate. Blood samples were drawn prior to and 6 weeks, 6 months, 1 year, and 3 years after surgery; two tubes from which plasma was prepared, and two tubes for serum. From the last included 20 patients in each group was also taken blood one and three years after surgery for an in vitro lymphocyte assay for scoring of possible hypersensitivity to prosthesis metals. The isolated lymphocytes were subjected to measurement of proliferation and expression of CD69 by flow cytometry and measurement of the Migration Inhibitory Factor (MIF) by ELISA. Plasma concentrations of the cytokines IL-1, IL-4, IL-6, IL-8, IL-12p70, IL-15, interferon-and osteoprotegerin were determined by multiplex-immunoassay. Serum concentrations of chromium and cobalt were determined by graphite furnace atomic absorption spectrometry. The serum concentrations of chromium and cobalt were lowest in patients with the C2a implant and highest with Magnum, some of these differences were significant at 6 weeks, 6 months, and 1 year after surgery. No patient had a very high serum metal concentration. The values of the variables measured in the in vitro lymphocyte assay mainly changed in the expected direction depending on the concentration of the same metal in the serum sample drawn at the same time, but no significant correlation was seen. One patient had uncertain symptoms of metal hypersensitivity and relatively high serum metal concentrations 3 years after arthroplasty with a Magnum prosthesis and was assessed extraordinarily, and elicited the marginally highest MIF responses in the lymphocyte assay. A strong correlation was found between the plasma concentrations of most cytokines, but the cytokine concentrations were not correlated to contemporary metal concentrations

Introduction. The advantages of metal on metal (MOM) hip replacement are decreased wear rate, preservation of bone stock, anatomical restoration and enhanced stability. Large amounts of metal wear particles and metal ions are released which may induce adverse reactions including local soft tissue toxicity, hypersensitivity reactions, bone loss and risk of carcinogenesis. Aseptic loosening can be the result of a peri prosthetic osteolysis generated as a result of a biological response to particulate wear debris. Our aim in this study was to determine whether a steeply inclined acetabular component would give rise to a higher concentration of metal ions. Patients and methods. Between April 2003 and June 2006, 22 patients had MOM hip replacement for osteoarthritis by a single Surgeon. There were 12 male and 10 female patients. The average age at the time of surgery was 56 years (Range: 44–69 years). We divided the 22 patients into 2 groups, one group (A) of 11 patients with the acetabular inclination angle more than 50 degrees and the other group (B) of 11 patients with the angle less than 50 degrees. The inclination of the acetabular cup was measured using a standard AP radiograph of the pelvis. The patients had metal ion levels (blood chromium and serum cobalt) measured at an average follow up of 3.2 years (Range 2.4 to 5 years). Results. Mean blood chromium level in the group A (146 nM/L) was significantly higher (p=0.005) than in Group B (92 nM/L). Mean serum cobalt level in the group A (245 nM/L) was significantly higher (p=0.002) than in Group B (110 nM/L). Discussion. The early to mid term published results of MOM hip replacements have been encouraging. There are, however, a number of concerns about the MOM bearing. Although its wear rate is low, it still releases metal ions into the body particularly cobalt and chromium since most metal on metal bearings are made of a cobalt chromium alloy. The long-term consequences of increased levels of these ions in the body are not known. High concentrations of Co and Cr are toxic and are known to interfere with a number of biological functions. There also have been recent reports of soft tissue reactions with MOM hip replacement. In the light of these concerns, it is important to examine factors which may influence the release of metal ions after MOM hip replacement. It has been reported in the recent literature that the position of the acetabular component will influence the bearing wear inturn leading to the release of metal ions after MOM hip replacement. Our findings indicate that steeply inclined acetabular components with an inclination angle greater than 50 degrees gives rise to higher concentration of metal ions

Introduction. Metal-on-metal (MoM) articulations in total hip replacement (THR) have become an attractive option for young, active patients. Short-term reports have demonstrated elevated systemic metal ion levels in the blood and urine. Disseminated concentrations of cobalt and chromium have raised concern regarding cellular toxicity, chromosomal damage and adverse local soft tissue reactions. Long-term studies are required to support the increased use of MoM bearings in younger patients given their potential deleterious effects. The purpose of the current study was to report the 7–13 year clinical, radiographic, and metal ion results in patients following MoM THR. Methods. We prospectively followed 165 patients (196 hips) after second-generation MoM THR between July 1997 and November 2003. Functional outcome was measured using the Harris Hip Score (HHS) and the University of California Los Angeles (UCLA) Activity Score. Radiographic analysis was performed using Einzel-Bild-Roentgen-Analyse (EBRA) by two of the authors blinded to the study. Cobalt and chromium metal ions were measured from whole blood and analyzed using inductively coupled plasma-mass spectrometry. Results. 163 prostheses were analyzed. The mean age at surgery was 50.8 years (range, 17 to 66). There were 80 females and 83 males. The mean follow-up was 8.87 years (range, 7–13 years). Four hips (2.5%) were revised: 2 for infection at 0.2 and 7 years; 1 for a loose stem at 1.3 years; and 1 for a loose cup at 9 years. One patient received wound debridement for a superficial infection and did not have any components revised. The mean HHS and UCLA scores at the last follow-up were 91 and 6.8, respectively. The mean acetabular inclination and anteversion was 40 degrees (range, 24 to 57), and 19 degrees (range, 3 to 39), respectively. Median cobalt levels peaked at a value of 2.87 μg/L at 4 years (p<0.0001 vs. pre-operative) and subsequently decreased to 2.0 μg/L after 9 years (p=0.002 vs. 4-years). Median chromium levels maximally increased up to 0.75 μg/L after 5 years (p<0.0001 vs. pre-operative) and tended to decrease thereafter to values of 0.56 μg/L after 7 years. The Kaplan-Meier survivorship was 91.3% for revision for all causes, and 97.5% when excluding the hips revised for a manufacturer's defect at a mean of 8.87 years (range, 7–13 years). Conclusion. The present 7–13 years follow-up study of MoM THRs indicates that the clinical and radiological results are satisfactory with low revision rates. Furthermore, our study demonstrates the trend of metal ion levels in whole blood over a long-term. Both cobalt and chromium ion levels peaked at 4 and 5 years, respectively, and gradually decreased thereafter

MHRA guidance for patients with metal on metal hip replacements (MOM) was provided in 2012 and updated in 2017 to assist in the early detection of soft tissue reactions due to metal wear debris. A large number of metal on metal hip replacements were undertaken at our trust. A program of recall for all patients with metal on metal hip replacements was undertaken and MHRA guidelines implemented. Identification and recall of all patients from 2001 with MOM hip replacements using theatre logs, patient records and consultant log books. Two consultant review of X-rays and patient records. Postal questionnaires and GP requests for cobalt & chromium blood tests. Two consultant led MOM review clinics undertaken with metal artefact reduction scans (MARS) performed following consultation in 2017. 674 patients, 297 available for review. 59 refused follow up. 87 moved out of area, 36 untraceable, 26 not MOM, 147 RIP, 22 already revised. From 297 patients 126 female, 171 male, age range 39 – 95 yrs. 126 resurfacing, 171 MOM THR. 26 patients with elevated metal ions, MARS performed of which 17 positive, 9 negative. Of 17 positive scans 10 patients asymptomatic, 7 waiting revision. A time consuming effort and additional resource was needed and supported by the trust. From 297 hips 17 positive MARs were identified (5.7%). A new database registry has been developed to track MOM patients, clinics set up for ongoing follow up with radiological protocols for imaging. An arthroplasty advanced nurse practitioner (ANP) is now trained reviewing patients independently

INTRODUCTION. Studies have suggested that there is a reduction in head-neck-ratio (HNR) associated with MoMHRA. A reduction in HNR at operation would decrease range of movement and increase impingement risk. Impingement could lead to 20 edge loading, increasing wear. Serum ion levels of Chromium (Cr) and Cobalt (Co) are surrogate markers of wear. Although acetabular component orientation has been shown to contribute to wear and PT development, the role of a decrease in HNR has only been highlighted in PT development. This study aimed to measure changes in HNR that occur at resurfacing and determine any gender- and component size-specific differences. In addition it aimed to determine whether changes in HNR could be associated with increased wear. METHODS. 84 patients (56M: 28F) with unilateral MoMHRA were included. The mean age at surgery was 57 years. The mean femoral component was 49mm. Components were considered small if <45mm, average if between 45–50mm and large if >50mm. Three designs were implanted; BHR, C+ and Recap. The average follow up was 4 years. All patients had Cr/Co levels measured at follow up. Patients were considered to have high ions if Cr and Co levels were 5.1ppb and 4.4ppb respectively. Pre-operative HNR (HNRpre) and the post-operative HNR (HNRpost) were made from the respective pelvic radiographs. Assuming a 2mm thick cartilage layer, the HNR based on the diameter of the articular cartilage pre-operatively (HNRart) was calculated. The immediate changes in HNR as a result of the operation were expressed relative to articular HNR pre-op:. HNRartpost=HNRpost–HNRart. RESULTS. The changes in HNR at operation were significantly negatively correlated with HNRpre, (p<0.001), (rho=−0.77). Females had greater ion levels (p=0.013) and smaller components (p<0.001). Females had bigger pre-operative HNRart and were downsized more (p<0.001). Similarly, patients with small components had higher ions (p=0.032). They had greater HNRart and were downsized more (p<0.001) Twelve patients comprised the high ion group. These patients had smaller components (p=0.004), greater HNRart and were down-sized significantly more at resurfacing (p<0.001). DISCUSSION. This study highlights HNR changes that occur in resurfaced hips. Females, patients with small components and patients in the high ion group had higher pre-operative HNR and were downsized more at operation. Femoral downsize, would probably increase impingement risk, lead to secondary edge loading and contribute to greater incidence of wear related problems

INTRODUCTION. Although simulation studies have shown superior wear properties of metal-on-metal articulations, increased concern exists regarding the excess in-vivo wear of a small number of Metal-on-Metal-Hip-Resurfacing (MoMHRA) implants. Serum ion levels of Chromium (Cr) and Cobalt (Co) are surrogate markers of wear. Risk factors associated with increased wear include female gender, small components, dysplasia, cup orientation outside safe zone and femoral head downsize during surgery with an associated decrease in Head-Neck-Ratio (HNR). However, these factors are interlinked. This study aims to identify the factors that are most important for subsequent wear of MoMHRA, by performing a multivariate analysis. METHODS. 206 patients (124M: 82F) with unilateral MoMHRA were included in this study. The average follow up was 3.3 years. All patients had Cr/Co levels measured at follow up. Inclination and anteversion of each cup were measured using EBRA. Cups were analysed as being within or outside the previously defined optimum-zone. HNR measurements were made from pre-operative (HNRpre) and post-operative (HNRpost) radiographs. The immediate changes in HNR (downsize/upsize of femoral head) as a result of the operation were expressed as:. HNRprepost=HNRpost–HNRpre. Multivariate linear regression modelling was used to explore the association between measures of ions with the following predictor variables (gender, age, diagnosis, femoral component size, orientation of the acetabular component, head/neck ratio and position of femoral stem). Analyses were carried out separately for each outcome (Cr and Co). Classification and Regression Tree (CART) models were fitted as a complimentary approach to regression modelling. RESULTS. Articular surface downsize followed by cup orientation within/outside optimum zone, followed by cup anteversion followed by gender were the strongest predictors of ion levels. A percentage decrease in HNRartpost, predicted an increase in Cr ion level by 5% (and 6% for Co). If the cup was within the optimum zone this was associated with decreased levels of Cr and Co ions. As acetabular component anteversion increased, levels of ions increased. Gender had a strong effect on ion levels. Adjusting for other variables, the effect of gender was attenuated due to a confounding effect of component size and the amount of femoral head downsize. Predictors identified as important in regression analyses were similar to those produced in the CART model, where the highest levels of ions were seen in patients with a percentage decrease in pre-operative HNR −11.3. DISCUSSION. This analysis shows that (surgical) factors, such as amount of femoral head downsize at operation and whether the cup was orientated within the optimum zone, explained the majority of the variability in ion levels in MoMHRA

INTRODUCTION. The advantages of large diameter metal on metal total hip arthroplasty (MoM THA) and hip resurfacing arthroplasty are decreased wear rate, preservation of bone stock, anatomical restoration and enhanced stability. Large amounts of metal wear particles and metal ions are released which may induce adverse reactions including local soft tissue toxicity, hypersensitivity reactions, bone loss and risk of carcinogenesis. Aseptic loosening can be the result of a peri-prosthetic osteolysis generated as a result of a biological response to particulate wear debris. No reports in the literature exist as to whether circulating levels of Chromium (Cr) and Cobalt (Co) decrease upon removal of a symptomatic large diameter MoM implant or whether levels remain high due to the effect of metal ions debris left behind in the soft tissues after revision surgery. PATIENTS AND METHODS. Between June 2006 and June 2009 we undertook 44 revision surgeries of both large head MoM THAs (femoral head diameter 38mm) and metal-on-metal hip resurfacings for suspected metallosis. Mean time from original implant to revision was 4 years, 8 months (1yr 4mo–7yr 9mo). The mean follow up evaluation was 2 years and 2 months (1yr 2mo–4 years). Blood samples were taken for whole blood Cr and serum Co according to a recognised protocol and compared with reference levels indicated by the Medicines and Healthcare Regulatory Agency recommendation of less than 7ppb for Cr (130nM/L) and Co (119nM/L). RESULTS. 42 patients were found to have histological evidence of either metal allergy, metal toxicity or foreign body reaction. 2 patients had evidence of infection with no features of metal reaction. 3 patients suffered early dislocation requiring closed reduction. 1 patient had infective complications necessitating Girdlestones. 11 patients were lost to follow up, 8 patients were diagnosed pre operatively on Co and Cr levels in urine or synovial fluid aspirate alone. 23 patients had pre revision blood or serum metal ion level results available for direct comparison. Median serum Co level pre revision was 176.6nM/L, falling post revision to 5.1nM/L (p=<0.001∗). The median whole blood Cr level pre revision was 117nM/L and 19nm/L post revision (p=<0.001∗). Mean Oxford Hip Score was 23.7. DISCUSSION. This study demonstrates that at greater than one year post removal of a large diameter MoM hip implant for the indication of symptomatic metallosis or metal hypersensitivity, metal ion levels fall to almost normal levels and that outcome of revision surgery in terms of patient satisfaction is not adversely affected

Introduction. Metal on metal articulations produce chromium (Cr) and cobalt (Co) debris, particularly when the articulations are worn in. High levels in the peripheral blood are indicative of excess wear and may cause adverse effects. The present RCT investigates metal ion levels and the relationship of Co, Cr ions and lymphocyte counts during the running-in period. Materials and Methods. Following randomization to RHA (ASRTM, DePuy) or THA we obtained whole blood (wb), and serum (s) samples at baseline, 8 w, 6 m and 1 y. We measured the Co and Cr concentrations, the total lymphocyte count as well as the CD3+, CD4+, CD8+, CD19+ and CD16+/CD56+ sub populations. Cup inclination and anteversion angles came from conventional radiographs. Activity was measured as steps by pedometer and UCLA activity. Data are presented as median (range). Results. We had 19 patients in each group. Age 57 (46–64) y (RHA) and 55 (44–64) y (THA). RHA only: head size: 51 (47 to 57)mm, cup inclination: 45.0 (40- 56)° and anteversion: 23 (7–38)°. The ion concentrations stayed below 0.2 ppb for THAs. For RHAs the Co and Cr concentrations generally rose markedly in the initial 8 weeks, followed by a slower ascent up to 1 year to wb Co: 1.0 (0.6–5.2), s Co: 1.3 (0.7–6.5), wb Cr: 1.3 (0.4–8.0) and s Cr: 1.7 (0.6–15) ppb. A high ion level was correlated to a small head size (p<0.03) and a cup inclination around 45° (p<0.04). We could not correlate the ion concentrations to the anteversion or the activity levels. The absolute lymphocyte counts were not always identical in the groups (eg. lower CD8+ for RHA) but there was no group difference when we analysed the change from baseline. We did not demonstrate any correlation between metal ion levels and lymphocyte subpopulations. Discussion. The findings of this study does not support the theory that metal ions suppress the lymphocytes or the CD8+ in particular (Hart et al., 2009). Our conclusions are limited by low numbers, but we suspect the theory could be biased by missing baseline values. Our study did not demonstrate the same 6–9 months ion peak found in other running-in studies (Back et al., 2005, Heisel et al., 2008), but rather a slow continuous rise with lower median ion concentrations. It could indicate lower wear or perhaps a longer running in period in our slightly older population. Contrary to our expectations we found that cups placed in optimal inclination displayed a higher ion level. Most of the smallest cups were found in this group, and the majority of the steep cups had very large heads. For this implant head size may be more important than cup position

Due to increased life expectancy of human population, the amount of total knee replacements (TKR) is expected to increase. TKR reached a high grade of quality and safety, but most often it fail because of aseptic implant loosening caused by polyethylene (PE) wear debris. Wear is generated at the articulating surfaces, e.g. caused by three body particles, like bone fragments or bone cement particles. The aim of this experimental study was to compare the wear of tibial PE inserts combined with metallic and ceramic femoral components at three body wear situation induced by polymethylmethacrylate (PMMA) and zirconia (ZrO2) particles from the bone cement. Wear testing was performed for 5 Mio load cycles, using tibial standard PE inserts combined with the same CR femoral component, in two different materials, Cobalt Chromium (CoCrMo) and Biolox delta ® ceramic (Multigen Plus Knee System, Lima Corporate, Italy). A knee wear simulator, according to ISO 14243 (EndoLab GmbH, Rosenheim, Germany), was used to carry out the tests. The tests were performed in temperature-controlled test chambers at 37 °C, containing calf serum with a protein content of 30 g/l. Polymethylmethacrylate (PMMA) and zirconia (ZrO2) bone cement particles (Palacos R ®) were manufactured to a size of 30 μm. The three body particles were added at all stations onto the articulating surface of the tibial PE insert (7mg per condyle) at every 500,000 cycles. Wear was determined gravimetrically and the surfaces of tibial inserts were analysed by scanning electron microscope (SEM) after finishing the 5 million cycles. Furthermore, roughness of the PE insert surfaces and the articulating surfaces of the different femoral components were detected and the PE wear particles were analysed by SEM. The average gravimetrical wear rates of the tibial PE inserts in combination with CoCr and Biolox delta ® ceramic femoral components amounted to 6.4 ± 0.9 mg and 2.6 ± 0.4 mg per million cycles, respectively. Beside bone cement particles on the articulating surface of the PE inserts, polished surfaces and scratches were detected by SEM. In comparison to the untreated surfaces of the PE inserts at both material pairings the surface roughness at the articulating areas showed deep scratches and polished regions. Analyses of the metallic femoral components showed scratches at the articulating surfaces, none on ceramics. The present study pointed out the effect of femoral component material in an abrasive three body wear situation on the wear properties of TKR. The wear simulator tests showed that wear of PE inserts under three body wear conditions, in combination with ceramic femoral components, was significantly lower than with metallic femoral components. With regard to anti-allergic properties, ceramic femoral components are promising products for TKR

INTRODUCTION. Femoral neck narrowing (NN) following Metal-on-Metal Hip Resurfacing Arthroplasty (MoMHRA) is a well-recognised clinical phenomenon. The incidence of resurfaced hips with NN > 10% is reported to be up to 27%. Its pathogenesis is thought to be multi-factorial secondary to stress shielding, impingement, osteolysis secondary to wear/ion particles and as a result of reduced vascularity and pressure effect on cancellous bone secondary to the presence of a soft-tissue mass around the resurfaced hip. Recognised risk factors for its development include: female gender and the presence of a pseudotumour. Serum Chromium (Cr) and Cobalt (Co) are recognised surrogate markers of in-vivo wear of MoMHRA. The aims of this study were to establish whether NN is associated with increased wear. METHODS. A cohort of 214 patients with unilateral MoMHRA (139M: 75F) was included in this study. Primary osteoarthritis was the diagnosis leading to surgery for the majority of patients (208). The average age at surgery was 54.1 years old (13–73). Six different implants were used; BHR (116), Conserve plus (92), Recap (2), ASR (2), Adept (1) and Cormet (1). The average femoral component size was 49.2mm (range: 38–59). The average follow up was 4.3 years (range: 2–10). Patients were subdivided into 3 groups as per implant size. Small size component group had implants <45mm, average size group had components 45–51mm and large component size group had components >51mm. All patients had Prosthesis-Junction-Ratio (PJR) measured from postoperative (PJRpost) and at latest follow up (PJRfollow) radiographs. Measurements were made using the method described by Lilikakis1. Metal ion levels (Cr/Co) were measured at last follow-up for all patients. Cr level >5.1g/ml and Co levels >4.4 g/ml were considered high2 and patients with such levels formed the high ion group. RESULTS. For the whole cohort, mean NN was 3.2% (range: 0–32%, SD:4.3). Females (4.7%, range: 0–32%, SD: 5.8) had significantly greater NN than males (2.4%, range: 0–23%, SD: 2.9) (p=0.001). Patients in the large component group had less NN (2.1%, SD: 2.3) in comparison to the average (3.2%, SD: 3.7%) (p=0.046) and the small (5.9%, SD: 7.9) (p=0.007) component size groups. There was no difference in NN between small and average sized components (p=0.1). Patients in the high ion group (25 patients) had significantly greater NN than patients with low ions (10.1%, range: 1%–32%, SD: 8.3 Vs 2.3%, range: 0–11, SD 2.3) (p<0.0001). NN >10% was seen in 16 hips (7.5%). The odds ratio of having high ions if NN >10% was 125 (p<0.001). DISCUSSION. The findings of this study showed that greater NN occurs in females and patients with small components and in patients with high ions. Furthermore, hips with NN >10% should be investigated further as they are more likely to have increased wear