Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression. . These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement. Cite this article: Bone Joint J 2014; 96-B:1172–7

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

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

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

Elevated blood cobalt secondary to metal-on-metal (MoM) hip arthroplasties has been shown to be a risk factor for developing cardiovascular complications including cardiomyopathy. Published case reports document cardiomyopathy in patients with blood cobalt levels as low as 13µg/l (13ppb, 221nmol/l). Clinical studies have found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than ejection fraction at diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Sixteen patients with documented blood cobalt ion levels above 13µg/l were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty with no history of cobalt implants. All patients underwent electrocardiogram and echocardiogram assessment for signs of cardiomyopathy including GLS. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29µg/l (495nmol/l) compared to 0.01µg/l (0.2nmol/l) in the control group. There was no difference or correlation in ejection fraction (EF), left ventricular (LV) end systolic dimension, LV end diastolic dimension, fractional shortening, ventricular wall thickness or E/e’ ratio. However, GLS was significantly reduced in patients with MoM hip arthroplasties compared to those without (−15.2% v −18%, (MoM v control) p= 0.0125). Pearson correlation demonstrated that GLS is significantly correlated with blood cobalt level (r= 0.8742, p=0.0009). For the first time, this study has demonstrated reduced cardiac function in the presence of normal EF as assessed by GLS in patients with elevated cobalt above 13µg/l. As GLS is a more sensitive measure of systolic function than EF, routine echocardiogram assessment including GLS should be performed in all patients with MoM hip arthroplasties and elevated blood cobalt above 13µg/l. Further work is recommended to assess if these cardiac changes are present in patients with elevated blood cobalt levels below 13µg/l

Elevated blood cobalt secondary to metal-on-metal (MoM) hip arthroplasties has been shown to be a risk factor for developing cardiovascular complications including cardiomyopathy. Published case reports document cardiomyopathy in patients with blood cobalt levels as low as 13µg/l. Clinical studies have found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. The extent of cardiovascular injury, measured by global longitudinal strain (GLS), in patients with elevated blood cobalt levels has not previously been examined. Sixteen patients with prospectively collected blood cobalt ion levels above 13µg/l were identified and matched with eight patients awaiting hip arthroplasty with no history of cobalt implants. Patients underwent echocardiogram assessment including GLS. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29µg/l compared to 0.01µg/l in the control group. There was no difference or correlation in EF, left ventricular (LV) end systolic dimension, LV end diastolic dimension, fractional shortening, ventricular wall thickness or E/e’ ratio. However, GLS was significantly reduced in patients with MoM hip arthroplasties compared to those without (−15.2% v −18%, (MoM v control) p= 0.0125). Pearson correlation demonstrated that GLS is significantly correlated with blood cobalt level (r= 0.8742, p=0.0009). For the first time, this study has demonstrated reduced cardiac function in the presence of normal EF as assessed by GLS in patients with elevated cobalt above 13µg/l. As GLS is a more sensitive measure of systolic function than EF, routine echocardiogram assessment including GLS should be performed in all patients with MoM hip arthroplasties and elevated blood cobalt

As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 μg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity. Take home message: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately. Cite this article: Bone Joint J 2016;98-B:14–20

Ceramic-on-ceramic (CoC) articulations in total hip arthroplasty (THA) have low wear, but the unique risk of fracture. After revision for CoC fracture, ceramic third bodies can lead to runaway wear of cobalt chrome (CoCr) causing extremely elevated blood cobalt. We present five cases of ceramic liner fractures revised to a CoCr head associated with the rapid development of severe cobalt toxicity. We identified 5 cases of fractured CoC THA treated with revision to CoCr on highly cross-linked polyethylene (HXLPE) – three to conventional bearings and two to modular dual mobility bearings (CoCr acetabular liner, CoCr femoral head, and HXLPE). Mean follow up was 2.5 years after CoCr/HXLPE re-revision. Symptoms of cobalt toxicity occurred at average 9.5 months after revision for ceramic fracture (range 6–12). All patients developed vision and hearing loss, balance difficulties, and peripheral neuropathy. Several had cardiomyopathy, endocrinopathy, and local skin discoloration. Two reported hip pain. Re-revision for cobalt toxicity occurred at an average of 22 months (range 10–36) after revision for ceramic fracture. Average serum cobalt level at re-revision was 991 μg/L (range 734–1302, normal <1 μg/L). All CoCr heads exhibited massive wear with asphericity; deep tissues exhibited prominent metallosis. Treatment consisted of debridement and revision to a ceramic head with HXLPE. Serum cobalt improved to an average of 25 μg/L at final follow up. All patients reported partial improvement in vision and hearing; peripheral neuropathy and balance did not recover. Systemic cobalt toxicity is a rare but devastating complication of ceramic fracture in THA treated with cobalt-alloy bearings. Cobalt alloy bearings should be avoided in this setting. The diagnosis of systemic cobalt toxicity requires a high index of suspicion and was typically delayed following systemic symptoms. Debridement and revision to a ceramic-on-HXLPE leads to improvement but not resolution of cobalt toxicity complications

Aims. Large-diameter metal-on-metal (MoM) total hip arthroplasty (THA) has demonstrated unexpected high failure rates and pseudotumour formation. The purpose of this prospective cohort study is to report ten-year results in order to establish revision rate, prevalence of pseudotumour formation, and relation with whole blood cobalt levels. Methods. All patients were recalled according to the guidelines of the Dutch Orthopaedic Association. They underwent clinical and radiographical assessments (radiograph and CT scan) of the hip prosthesis and whole blood cobalt ion measurements. Overall, 94 patients (95 hips) fulfilled our requirements for a minimum ten-year follow-up. Results. Mean follow-up was 10.9 years (10 to 12), with a cumulative survival rate of 82.4%. Reason for revision was predominantly pseudotumour formation (68%), apart from loosening, pain, infection, and osteolysis. The prevalence of pseudotumour formation around the prostheses was 41%, while our previous report of this cohort (with a mean follow-up of 3.6 years) revealed a 39% prevalence. The ten-year revision-free survival with pseudotumour was 66.7% and without pseudotumour 92.4% (p < 0.05). There was poor discriminatory ability for cobalt for pseudotumour formation. Conclusion. This prospective study reports a minimum ten-year follow-up of large-head MoM THA. Revision rates are high, with the main reason being the sequelae of pseudotumour formation, which were rarely observed after five years of implantation. Blood ion measurements show limited discriminatory capacity in diagnosing pseudotumour formation. Our results evidence that an early comprehensive follow-up strategy is essential for MoM THA to promptly identify and manage early complications and revise on time. After ten years follow-up, we do not recommend continuing routine CT scanning or whole cobalt blood measurements, but instead enrolling these patients in routine follow-up protocols for THA. Cite this article: Bone Jt Open 2022;3(1):61–67

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

In a randomised study, 28 patients with a mean age of 62.2 years (32 to 81) with osteoarthritis or avascular necrosis of the hip received either a ceramic-on-ceramic or a metal-on-metal total hip replacement. Apart from the liners the acetabular and femoral components were made of Ti-Al-Nb alloy. The serum aluminium and cobalt levels were measured before, and at one year after surgery. The 15 patients in the ceramic-on-ceramic group had a median pre-operative aluminium level of 1.3 μg/l (0.25 to 8.4) and a cobalt level below the detection limit. At one year the aluminium level was 1.1 μg/l (0.25 to 2.3) and the cobalt level was 0.4 μg/l (0.15 to 0.7). The 13 patients in the metal-on-metal group had a median pre-operative aluminium level of 1.9 μg/l (0.25 to 4.4) and a cobalt level below the detection limit. At one year the median aluminium level was 0.9 μg/l (0.25 to 3.9) whereas the cobalt level was 1.4 μg/l (0.5 to 10.5). This increase in the cobalt level at one year was significant (p < 0.001). Our findings indicate that ceramic-on-ceramic bearings do not cause elevated levels of serum aluminium in the first post-operative year

Wear of metal-on-metal bearings causes elevated levels of cobalt and chromium in blood and body fluids. Metal-on-metal bearings have two distinct wear phases. In the early phase, the wear rate is high. Later, it decreases and the bearing enters a steady-state phase. It is expected that as the wear rates decline, the level of cobalt detected in plasma will also decrease. We studied the baseline and exercise-related cobalt rise in 21 patients (13 men and eight women) with a mean age of 54 years (38 to 80) who had undergone successful hip resurfacing at a mean of 44 months (10 to 96) earlier. Our results showed that circulating baseline cobalt levels were not significantly correlated with the time since implantation (r = 0.08, p = 0.650). By contrast, the exercise-related cobalt rise was directly correlated with the inclination angle of the acetabular component (r = 0.47, p = 0.032) and inversely correlated with the time since implantation (r = −0.5, p = 0.020). Inclination of the acetabular component should be kept less than 40° to decrease the production of wear debris

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

Introduction/Aims. The Exeter Stem can be used with metal femoral head that are made of either cobalt chrome, or stainless steel. The aim of this study was to compare the rates of revision of these two metal femoral head types when used with this femoral component. Method. Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) Data from September 1999 until December 2015 for all primary THRs using an Exeter or an Exeter v40 stem with the diagnosis of osteoarthritis were analysed. Only bearing couples that used a metal head with polyethylene were included. The cumulative percent revision (CPR) calculated using Kaplan-Meier estimates were compared for the two metal head types. CPR were further analysed by age, polyethylene type and head size. Reasons for revision and types of revision were assessed. Results. There were 51666 THR that used Exeter or Exeter v40 stems of which 12554 had femoral heads made of cobalt chrome and 39112 had heads made of stainless steel. There was no difference in the rate of revision overall when head types were compared. There was also no difference in CPR between the two head types with age. Hips that used cobalt chrome heads had a higher CPR than stainless steel heads when these were used against non-crosslinked polyethylene. When heads with a diameter of 32mm or greater were compared, those made of cobalt chrome had a higher rate of revision than stainless steel HR 1.38 (1.15, 1.66) P<0.001). Conclusion. There was no difference comparing cobalt chrome or stainless-steel heads, except where non-crosslinked polyethylene was used, or where the heads size was 32mm or greater. In these comparisons, heads made from cobalt chrome had a higher rate of revision

We compared the incidence of pseudotumours after large head metal-on-metal (MoM) total hip arthroplasty (THA) with that after conventional metal-on-polyethylene (MoP) THA and assessed the predisposing factors to pseudotumour formation. . From a previous randomised controlled trial which compared large head (38 mm to 60 mm) cementless MoM THA with conventional head (28 mm) cementless MoP THA, 93 patients (96 THAs: 41 MoM (21 males, 20 females, mean age of 64 years, standard deviation (. sd. ) 4) and 55 MoP (25 males, 30 females, mean age of 65 years, . sd. 5) were recruited after a mean follow-up of 50 months (36 to 64). . The incidence of pseudotumours, measured using a standardised CT protocol was 22 (53.7%) after MoM THA and 12 (21.8%) after MoP THA. Women with a MoM THA were more likely to develop a pseudotumour than those with a MoP THA (15 vs 7, odds ratio (OR) = 13.4, p < 0.001). There was a similar incidence of pseudotumours in men with MoM THAs and those with MoP THAs (7 vs 5, OR = 2.1, p = 0.30). Elevated cobalt levels (≥ 5 microgram/L) were only associated with pseudotumours in women with a MoM THA. There was no difference in mean Oxford and Harris hip scores between patients with a pseudotumour and those without. . Contrary to popular belief, pseudotumours occur frequently around MoP THAs. Women with a MoM THA and an elevated cobalt level are at greatest risk. In this study, pseudotumours had no effect on the functional outcome after either large head MoM or conventional MoP THA. Cite this article: Bone Joint J 2015;97-B:1481–7

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

The purpose of this study was to precisely measure the 10-year polyethylene wear rate of primary total hips using Radiostereometric analysis (RSA) comparing Oxidized Zirconium (OxZi) to cobalt chrome (CoCr) femoral heads articulating with highly cross-linked polyethylene (XLPE). RSA was performed on 46 patients who underwent total hip arthroplasty − 23 who received OxZi femoral heads and 23 who received CoCr heads in combination with XLPE at a minimum of 10 years follow-up. All patients had identical THR systems implanted except for the femoral head utilized. The Centre Index method was utilised to assess total wear rates (from index surgery until final evaluation) using a dedicated RSA Software program (UmRSA Digital Measure v.2.2.1). In addition, the Martell technique was used to subtract head penetration occurring in the first 1–2 years (i.e. bedding-in phase) to allow calculation of the ‘steady state’ wear rates. There were no significant differences in demographics (i.e age, BMI, gender) between the groups. The average time from surgery of the RSA examinations was 11.7 and 12.6 years for the CoCr and OxZi groups respectively. Using the Centre Index Method to calculate total head penetration, wear rates were slightly higher in the OxZi group (0.048 +/− 0.021mm/year) compared to the CoCr group (0.035 +/− 0.017mm/year) with no statistical difference between the groups (p= 0.02). After correction for the bedding-in period, there was no statistically significant difference in mean ‘steady-state’ wear rate between OxZi (0.031 +/− 0.021mm/year) and CoCr (0.024 +/− 0.019mm/year) at 10 year follow up (p= 0.24). A comparison of preoperative and postoperative SF12, HHS, and WOMAC scores showed no statistical difference between the groups. RSA demonstrated the 10 year in-vivo wear rates of both bearing combinations to be well below the threshold for osteolysis. There was no significant difference between either the total or ‘steady-state’ wear rates of the OxZi and CoCr groups at 10 years

The issues surrounding raised levels of metal ions in the blood following large head metal-on-metal total hip replacement (THR), such as cobalt and chromium, have been well documented. Despite the national popularity of uncemented metal-on-polyethylene (MoP) THR using a large-diameter femoral head, few papers have reported the levels of metal ions in the blood following this combination. Following an isolated failure of a 44 mm Trident–Accolade uncemented THR associated with severe wear between the femoral head and the trunnion in the presence of markedly elevated levels of cobalt ions in the blood, we investigated the relationship between modular femoral head diameter and the levels of cobalt and chromium ions in the blood following this THR. A total of 69 patients received an uncemented Trident–Accolade MoP THR in 2009. Of these, 43 patients (23 men and 20 women, mean age 67.0 years) were recruited and had levels of cobalt and chromium ions in the blood measured between May and June 2012. The patients were then divided into three groups according to the diameter of the femoral head used: 12 patients in the 28 mm group (controls), 18 patients in the 36 mm group and 13 patients in the 40 mm group. A total of four patients had identical bilateral prostheses in situ at phlebotomy: one each in the 28 mm and 36 mm groups and two in the 40 mm group. There was a significant increase in the mean levels of cobalt ions in the blood in those with a 36 mm diameter femoral head compared with those with a 28 mm diameter head (p = 0.013). The levels of cobalt ions in the blood were raised in those with a 40 mm diameter head but there was no statistically significant difference between this group and the control group (p = 0.152). The levels of chromium ions in the blood were normal in all patients. The clinical significance of this finding is unclear, but we have stopped using femoral heads with a diameter of ≤ 36 mm, and await further larger studies to clarify whether, for instance, this issue particularly affects this combination of components. Cite this article: Bone Joint J 2014;96-B:43–7

Introduction. Adverse local tissue reactions (ALTR) can result in devastating soft tissue and osseous destruction, while potentially increasing the risk of concomitant periprosthetic joint infection (PJI). The aims of this study were to evaluate cobalt (Co) and chromium (Cr) levels generated in simulators from metal-on-polyethylene (MoP) and ceramic-on-polyethylene (CoP) constructs, and determine their impact on native tissues and PJI risk through evaluation of human adipose-derived mesenchymal stem cells (AMSCs) and Staphylococcus epidermidis isolates. Methods. Ten hip simulator constructs were assembled with 36-mm high-offset femoral heads, highly cross-linked polyethylene liners, and titanium stems. Five constructs used CoCr femoral heads and five used ceramic. Constructs were submerged in bovine serum (BS) and run for 1,000,000 cycles. Samples of BS were collected and evaluated for CoCr concentration. Various concentrations of CoCr were chosen for further assessment of cytotoxicity and growth impact on AMSCs and S. epidermidis and compared to inert SiO2. Results. After 1,000,000 cycles, mean MoP and CoP Co concentration was 2264 ng/mL and 0.6 ng/mL, respectively (p<0.001). Mean MoP and CoP Cr concentration was 217 ng/mL and 4.3 ng/mL, respectively (p<0.001). Mean MoP Co:Cr ratio was 10. Co nanoparticles were significantly more toxic to human AMSCs than control SiO2 in a dose-response manner (p<0.001). S. epidermidis growth was not significantly impacted by Co concentrations derived from the simulators. Conclusions. MoP constructs built in ideal conditions generated substantial CoCr debris, highlighting a baseline risk with these implants that may be exacerbated by host factors or imperfect surgical technique. Evaluation of impact on AMSCs suggests that debris levels produced under ideal conditions can be cytotoxic. Additionally, these concentrations did not potentiate or inhibit S. epidermidis growth, suggesting elevated PJI rates with ALTR may be related to other factors potentially associated with tissue necrosis. For any tables or figures, please contact the authors directly

Introduction. Modular dual-mobility constructs reduce the risk of dislocation after total hip arthroplasty (THA). However, questions about metal ions from the cobalt-chrome (CoCr) liner persist, and are particularly germane to patients being revised for adverse local tissue reactions (ALTR) to metal. We determined the mid-term serum Co and Cr levels after modular dual-mobilities used in revision and complex primary THAs, and specifically included patients revised for ALTR. Methods. Serum Co and Cr levels were measured prospectively in 22 patients with a modular dual-mobility construct and a ceramic femoral head. Patients with CoCr heads or contralateral THAs with CoCr heads were excluded. Mean age 64 years with 50% female. The mean follow-up was 4 years. Indications for modular dual-mobility were: periprosthetic joint infection treated with 2-stage exchange and subsequent reimplantation (n=8), ALTR revision (n=7), complex primary THA (n=6), and periprosthetic femoral fracture (n=1). Mean preoperative Co and Cr in patients revised for an ALTR were 29.7 µg/L and 21.5 µg/L, respectively. Results. Mean Co and Cr levels were 0.26 µg/L and 0.82 µg/L, respectively, at most recent follow-up. No patients had a cobalt level ≥1 µg/L. Only one patient had a chromium level ≥1 µg/L. That patient's chromium level was 12 µg/L at 57 months after revision THA for ALTR (and decreased 10-fold from a preoperative Cr of 113 µg/L). Conclusion. At a mean of 4 years, no patient with a modular dual-mobility construct and ceramic femoral head had elevated cobalt levels, including seven patients revised specifically for ALTR. While further studies are required, we support selective use of a modular dual-mobility construct in revision and complex primary THAs for patients at high risk for instability. Summary. At a mean of 4 years after revision or complex primary THAs with a modular dual-mobility construct and a ceramic head, none of 22 patients had serum cobalt levels that measured ≥1 µg/L