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The Bone & Joint Journal
Vol. 106-B, Issue 3 Supple A | Pages 51 - 58
1 Mar 2024
Jenkinson MRJ Meek DRM Tate R Brady A MacMillan S Grant H Currie S

Aims. Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Methods. A total of 16 patients with documented blood cobalt ion levels above 13 µg/l (13 ppb, 221 nmol/l) were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty. All patients underwent echocardiography, including GLS, investigating potential signs of cardiomyopathy. Results. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29 µg/l (495 nmol/l) compared to 0.01 µg/l (0.2 nmol/l) in the control group. GLS readings were available for seven of the MoM cohort, and were significantly lower when compared with controls (-15.5% vs -18% (MoM vs control); p = 0.025)). Pearson correlation demonstrated that GLS significantly correlated with blood cobalt level (r = 0.8521; p < 0.001). However, there were no differences or correlations for other echocardiography measurements, including LVEF (64.3% vs 63.7% (MoM vs control); p = 0.845). Conclusion. This study supports the hypothesis that patients with elevated blood cobalt levels above 13 µg/l in the presence of a MoM hip implant may have impaired cardiac function compared to a control group of patients awaiting hip arthroplasty. It is the first study to use the more sensitive parameter of GLS to assess for any cardiac contractile dysfunction in patients with a MoM hip implant and a normal LVEF. Larger studies should be performed to determine the potential of GLS as a predictor of cardiac complications in patients with MoM arthroplasties. Cite this article: Bone Joint J 2024;106-B(3 Supple A):51–58


Bone & Joint Research
Vol. 10, Issue 6 | Pages 340 - 347
1 Jun 2021
Jenkinson MRJ Meek RMD Tate R MacMillan S Grant MH Currie S

Elevated levels of circulating cobalt ions have been linked with a wide range of systemic complications including neurological, endocrine, and cardiovascular symptoms. Case reports of patients with elevated blood cobalt ions have described significant cardiovascular complications including cardiomyopathy. However, correlation between the actual level of circulating cobalt and extent of cardiovascular injury has not previously been performed. This review examines evidence from the literature for a link between elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties and cardiomyopathy. Correlation between low, moderate, and high blood cobalt with cardiovascular complications has been considered. Elevated blood cobalt at levels over 250 µg/l have been shown to be a risk factor for developing systemic complications and published case reports document cardiomyopathy, cardiac transplantation, and death in patients with severely elevated blood cobalt ions. However, it is not clear that there is a hard cut-off value and cardiac dysfunction may occur at lower levels. Clinical and laboratory research has found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Further work needs to be done to clarify the link between severely elevated blood cobalt ions and cardiomyopathy. Cite this article: Bone Joint Res 2021;10(6):340–347


The Bone & Joint Journal
Vol. 96-B, Issue 9 | Pages 1172 - 1177
1 Sep 2014
Lawrence H Deehan D Holland J Kirby J Tyson-Capper A

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


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 775 - 782
1 Jul 2023
Koper MC Spek RWA Reijman M van Es EM Baart SJ Verhaar JAN Bos PK

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


The Bone & Joint Journal
Vol. 103-B, Issue 7 | Pages 1231 - 1237
1 Jul 2021
Manninen E Lainiala O Karsikas M Reito A Jämsä P Eskelinen A

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


The Bone & Joint Journal
Vol. 99-B, Issue 9 | Pages 1147 - 1152
1 Sep 2017
Lainiala O Reito A Jämsä P Eskelinen A

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


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_7 | Pages 108 - 108
1 May 2016
De Villiers D Banfield S Housden J Shelton J
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Introduction. Revision of total hip replacements (THRS) is predominantly due to aseptic loosening, pain and infection [1]. The current method used to address the risk of infection is to administer antibiotics and to include antibacterial agents into bone cement (if used) and on implant coatings [2–4]. Currently, silver (Ag) coatings have only been applied to titanium hip stems [3]. Cobalt chromium alloy (CoCr) is a widely used orthopaedic alloy which is commonly used as a bearing surface; revisions of joints using this material often describe adverse reactions to the particulate wear debris [1]. This study considers an Ag containing CrN based coating on a CoCr substrate with the aim to reduce cobalt (Co) release and promote antibacterial silver release. Methods. Silver Chromium Nitride (CrNAg) coatings were developed and applied onto the bearing surfaces of 48 mm diameter metal-on-metal THRs. Three coatings were evaluated: high Ag at the surface (CrNAg+), low Ag at surface (CrNAg-) and uniform Ag (CrNAg=). All bearings were tested under ISO 14242-3 conditions for 0.17 million cycles (mc) representing approximately 2 months use in vivo. Wear was determined gravimetrically; Ag and Co levels in the lubricant were measured using graphite furnace atomic absorption spectroscopy. Testing of the CrNAg= bearings were continued to 2mc under standard conditions; CrNAg- bearings to 5mc incorporating lateralisation, which created separation at swing phase and rim contact at heel strike. Wear volume and Ag/Co release were monitored at 0.33, 0.67, 1mc and every mc thereafter. Results. All bearings produced low levels of wear and released silver into the lubricating fluid. An increase in silver concentration at the surface of the bearings was found to increase both the silver released and wear, Figure 1. Negligible cobalt was released. Testing of the CrNAg= coating to 2mc showed the wear rate to decrease after 0.17mc, Figure 2. Ag release continued up to 2mc but at a decreased rate. The CrNAg- coating tested under lateralisation conditions to 5mc showed no coating failure and negligible cobalt release. Wear and silver release showed similar patterns and reached a steady state after 1mc, Figure 3. Discussion. The AgCrN coatings on bearing surfaces of a hip joint are capable of releasing Ag at concentrations within the ‘No Observable Adverse Effect Limit’ [5]. These coatings also prevented Co release while maintaining a low wear rate. All coatings remained intact and did not delaminate, even under adverse conditions. These coatings have been tested in a metal-on-metal hip bearing surface, the most controversial and challenging condition for a coating, wearing against itself. CoCr is used as a bearing surface against polyethylene in hips and knees, in stems and tapers, as tibial trays in knee replacement and as shells for acetabular cups. This coating may be applied to a wide range of applications, removing some of the challenges over the use of CoCr while reducing infections


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_11 | Pages 9 - 9
7 Jun 2023
Jenkinson M Meek D MacMillan S Tate R Grant MH Currie S
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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


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 477 - 477
1 Dec 2013
Barnes L Parks C Bushmiaer M
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PURPOSE:. Wright Medical has a long history of modular neck hip implants but had fracture issues with the original titanium necks. They subsequently changed to chrome cobalt modular necks. Direct contact between these dissimilar metal parts in the modular femoral component brings into consideration the possibility of similar adverse reactions of metal-on-metal articulations that have been previously described in other designs. METHODS:. A retrospective review of 10 patients with Wright Medical chrome cobalt modular necks who were evaluated with chromium and cobalt metal ion levels as well as Metal Artifact Reduction Sequence (MARS) MRI's was performed. Pseudotumors were classified by MRI based on wall thickness, T1/T2 signal, shape, and location and given a corresponding type of I, II, or III. For each patient, symptoms or lack thereof were recorded, and time since surgery noted. RESULTS:. Of 10 patients tested, 9 were symptomatic, and 1 was asymptomatic. The patient that was asymptomatic at last clinical visit at 14 months post-op while symptomatic patients averaged 18 months since initial surgery before symptoms began. Those with metal-poly articulation had an average cobalt level of 1.6, ceramic-ceramic articulation had level of <1, and metal-on-metal had level of 2.9. Five patients had pseudotumor by MRI (2 type I, 1 type II, and 2 type III pseudotumors). CONCLUSION:. It appears that an unintended consequence of changing from titanium to chrome cobalt modular neck may be occurring secondary to corrosion at neck-stem junction. SIGNIFICANCE: This reaction does not appear to be design-specific as these findings are similar to our findings in Stryker Rejuvenate stems. Surgeons evaluating patients with these and other similar stems should be aware of this complication and consider ion testing and MARS MRI


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_12 | Pages 31 - 31
23 Jun 2023
Meek D Jenkinson M Macmillan S Tate R Grant H Currie S
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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


Bone & Joint Research
Vol. 9, Issue 3 | Pages 146 - 151
1 Mar 2020
Waldstein W Koller U Springer B Kolbitsch P Brodner W Windhager R Lass R

Aims. Second-generation metal-on-metal (MoM) articulations in total hip arthroplasty (THA) were introduced in order to reduce wear-related complications. The current study reports on the serum cobalt levels and the clinical outcome at a minimum of 20 years following THA with a MoM (Metasul) or a ceramic-on-polyethylene (CoP) bearing. Methods. The present study provides an update of a previously published prospective randomized controlled study, evaluating the serum cobalt levels of a consecutive cohort of 100 patients following THA with a MoM or a CoP articulation. A total of 31 patients were available for clinical and radiological follow-up examination. After exclusion of 11 patients because of other cobalt-containing implants, 20 patients (MoM (n = 11); CoP (n = 9)) with a mean age of 69 years (42 to 97) were analyzed. Serum cobalt levels were compared to serum cobalt levels five years out of surgery. Results. The median cobalt concentration in the MoM group was 1.04 μg/l (interquartile range (IQR) 0.64 to 1.70) at a mean of 21 years (20 to 24) postoperatively and these values were similar (p = 0.799) to cobalt levels at five years. In the CoP control group, the median cobalt levels were below the detection limit (< 0.3 μg/l; median 0.15 μg/l, IQR 0.15 to 0.75) at 20 years. The mean Harris Hip Score was 91.4 points (61 to 100) in the MoM group and 92.8 points (63 to 100) in the CoP group. Conclusion. This study represents the longest follow-up series evaluating the serum cobalt levels after 28 mm head MoM bearing THA and shows that serum cobalt concentrations remain at low levels at a mean of 21 years (20 to 24) after implantation. Cite this article:Bone Joint Res. 2020;9(3):145–150


The Bone & Joint Journal
Vol. 98-B, Issue 1 | Pages 14 - 20
1 Jan 2016
Zywiel MG Cherian JJ Banerjee S Cheung AC Wong F Butany J Gilbert C Overgaard C Syed K Jacobs JJ Mont MA

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


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 66 - 66
19 Aug 2024
Terhune EB Sutter EG Balkissoon R Pallante GD Specht L Leikin JB Kwon YM Lewallen DG Gerlinger TL Jacobs JJ
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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


The Bone & Joint Journal
Vol. 98-B, Issue 1 | Pages 6 - 13
1 Jan 2016
Cheung AC Banerjee S Cherian JJ Wong F Butany J Gilbert C Overgaard C Syed K Zywiel MG Jacobs JJ Mont MA

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging. . The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation. . The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity. . This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties. Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications. Cite this article: Bone Joint J 2016;98-B:6–13


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 124 - 124
1 Mar 2021
Jelsma J Schotanus M Kleinveld H Grimm B Heyligers I
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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


The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 376 - 385
1 Mar 2022
Gramlich Y Hofmann L Kress S Ruckes C Kemmerer M Klug A Hoffmann R Kremer M

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


Bone & Joint Open
Vol. 3, Issue 1 | Pages 61 - 67
18 Jan 2022
van Lingen CP Ettema HB Bosker BH Verheyen CCPM

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


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 3 | Pages 301 - 305
1 Mar 2007
Ziaee H Daniel J Datta AK Blunt S McMinn DJW

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


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 8 | Pages 1003 - 1005
1 Aug 2006
Grübl A Weissinger M Brodner W Gleiss A Giurea A Gruber M Pöll G Meisinger V Gottsauner-Wolf F Kotz R

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


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 9 | Pages 1152 - 1157
1 Sep 2008
Khan M Kuiper J Richardson JB

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