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

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

Symptomatic cobalt toxicity from a failed total hip replacement is a rare but devastating complication. It has been reported following revision of fractured ceramic components, as well as in patients with failed metal-on-metal articulations. Potential clinical findings include fatigue, weakness, hypothyroidism, cardiomyopathy, polycythaemia, visual and hearing impairment, cognitive dysfunction, and neuropathy. We report a case of an otherwise healthy 46-year-old patient, who developed progressively worsening symptoms of cobalt toxicity beginning approximately six months following synovectomy and revision of a fractured ceramic-on-ceramic total hip replacement to a metal-on-polyethylene bearing. The whole blood cobalt levels peaked at 6521 µg/l. The patient died from cobalt-induced cardiomyopathy. Implant retrieval analysis confirmed a loss of 28.3 g mass of the cobalt–chromium femoral head as a result of severe abrasive wear by ceramic particles embedded in the revision polyethylene liner. Autopsy findings were consistent with heavy metal-induced cardiomyopathy. We recommend using new ceramics at revision to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components. Cite this article: Bone Joint J 2013;95-B:31–7

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

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

Ceramic bearing fractures are rare events, but mandate revision and implantation of new bearings. Revisions using metal heads have been reported to lead to gross volumetric head wear (due to abrasive retained ceramic micro-debris), cobalt toxicity, multi-organ failure and death. Such complications are widely published (50+ reports), yet we know that patients continue to be put at risk. Using data from the NJR and AOANJRR, this study seeks to compare the risk of re-revision and death by revision bearing combination following a ceramic bearing fracture. Data were extracted from the NJR and AOANJRR, identifying revisions for ceramic bearing fracture. Subsequent outcomes of survival, re-revision and death were compared between revision bearing combinations (ceramic-on-ceramic, ceramic-on-polyethylene, and metal-on-polyethylene). 366 cases were available for analysis from the NJR dataset (MoP=34, CoP=112, CoC=221) and 174 from the AOANJRR dataset (MoP=17, CoP=44, CoC=113). The overall incidence rate of adverse outcome (revision or death) was 0.65 for metal heads and 0.23 for ceramic head articulations (p=0.0012) across the whole time period (NJR). Kaplan-Meir survival estimates demonstrate an increased risk of both re-revision and death where a metal head has been used vs a ceramic head following revision for ceramic fracture. There are few decisions in arthroplasty surgery that can lead to serious harm or death for our patients, but revision using a metal head following ceramic bearing fracture is one of them. This study enhances the signal of what is already known but previously only reported as inherently low-level evidence (case reports and small series) due to event rarity. Use of a metal head in revision for ceramic fracture represents an avoidable patient safety issue, which revision guidelines should seek to address

Background. The second generation metal-on-metal (MoM) prosthesis of the hip became a worldwide success in the 90s. However, after the placement of a MoM prosthesis the cobalt ion concentrations raise significantly. This may lead to systemic complaints and even cobalt toxicity. Methods. Sixty-one patients (26F/35M) with both an unilateral and bilateral resurfacing or large-head MoM (LHMoM) hip prosthesis were included. At last follow-up (5.77 ± 1.57 yrs) cobalt concentrations in the blood were determined by ICP-MS. Based on the known cobalt toxicity symptoms we developed a non-validated questionnaire. Analysis was done on two groups; a low cobalt concentration group and a high cobalt concentration group. We used 170 nmol/L as the upper limit of well functioning prosthesis as defined by the Dutch Orthopaedic Society (NOV). Independent samples T test and Pearson correlation coefficient were done. Results. In 61 patients, 70 prosthesis were implanted: 44 resurfacings and 26 LHMoM. Mean cobalt and chromium ion concentrations were 110 ± 138 (9 – 833) and 104 ± 138 (6 – 592) nmol/L. The low cobalt concentration group consisted of 52 patients, while the high cobalt concentration group consisted of 9 hips. With respect to the systemic complaints, the subjects in the high or low group reported no significant differences. A trend towards more complaints with visual problems (75% vs 51.9%, P = .089) and dizziness (62.5% vs 38.9%, P = .098) was notable in the high cobalt concentration group. Conclusions. Metal on metal hip arthroplasty stays controversial for the possible side-effects. This study shows trends, but no significance, in systemic complaints from high cobalt ion concentrations. Complaints of neuro-ocular toxicity are most common. This is in correspondence with other literature, although the upper limit for cobalt ion concentrations remains uncertain. Level of Evidence. 2b. Disclosure. no financial or nonfinancial relationships to disclose

Objectives. Recently, high failure rates of metal-on-metal (MOM) hip implants have raised concerns of cobalt toxicity. Adverse reactions occur to cobalt nanoparticles (CoNPs) and cobalt ions (Co. 2+. ) during wear of MOM hip implants, but the toxic mechanism is not clear. Methods. To evaluate the protective effect of zinc ions (Zn. 2+. ), Balb/3T3 mouse fibroblast cells were pretreated with 50 μM Zn. 2+. for four hours. The cells were then exposed to different concentrations of CoNPs and Co. 2+. for four hours, 24 hours and 48 hours. The cell viabilities, reactive oxygen species (ROS) levels, and inflammatory cytokines were measured. Results. CoNPs and Co. 2+. can induce the increase of ROS and inflammatory cytokines, such as tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, Zn pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co. 2+. , decrease ROS production, and decrease levels of inflammatory cytokines in Balb/3T3 mouse fibroblast cells. Conclusion. These results suggest that Zn pretreatment can provide protection against inflammation and cytotoxicity induced by CoNPs and Co. 2+. in Balb/3T3 cells. Cite this article: Y. Liu, H. Zhu, H. Hong, W. Wang, F. Liu. Can zinc protect cells from the cytotoxic effects of cobalt ions and nanoparticles derived from metal-on-metal joint arthroplasties? Bone Joint Res 2017;6:649–655. DOI: 10.1302/2046-3758.612.BJR-2016-0137.R2

We report a case of fatal heart failure caused by cobalt intoxication after revision THR in the patient who successfully underwent re-revision THR. 53-year old male presented to emergency room in our hospital with progressive shortness of breath. Symptom was started about 6 months ago so he visited local hospital. He worked up for worsening dyspnea. Simple chest radiograph and enhanced heart MRI study were performed and they showed bilateral pericardial and pleural effusion. There was no evidence of ischemic change. Transthoracic echocardiogram showed the evidence of heart failure, left ventricular ejection fraction(EF) was 40%. He was admitted at local hospital and started on vasopressors but urine output was decreased and follow-up echocardiogram showed a 25% of EF. Patient recommended heart transplantation and transferred our hospital emergency room. He underwent sequential bilateral total hip arthroplasties using CoP bearing surfaces. At 12 years postoperatively, he presented to the other hospital with acute onset of left hip pain. He was diagnosed ceramic head fracture on his left hip. Head and liner change revision surgery was performed using Cobalt-Chrome alloy 28mm metal head and Protruded cross-linked polyethylene liners. In our hospital, the patient admitted cardiovascular department of internal medicine. Patient complained nonspecific fatigue and general weakness but had no other symptoms such as visual and hearing loss, cognitive dysfuction. During work-up, patient presented progressive left hip pain and complaint of discomfort for the mass on the left groin. He also complained Left leg weakness and numbness. Simple radiograph and enhanced CT study was done. Simple radiograph image shows radiodense area around the hip joint and radiologist suspected heterotopic ossification. The cardiovascular department consulted orthopedic department. In the image findings showed huge mass combined hemorrhagic component lining acetabular component extending psoas compartment and eccentric wear on cobalt-chrome alloy metal head. Also highly radiodense material was seen around neck inferor portion and severly deformed metal head was seen. It was highly suspected that metal related granuloma, which means severe metallosis. Performed heavy metals screen, cobalt levels were 397,800 μg/Land chrome levels were 236,000 μg/L suggesting cobalt toxicity. Hip joint aspiration was done for decompression as radiologic intervention and EDTA (ethylenediamine tetraacetate) chelation therapy started immediately. After 10 cycle chelating therapy, metal level was lowered cobalt levels by 255.2μg/L and chrome levels by 39.5 μg/L. When hospital day after 134, Medical condition of the patient was getting improved, we underwent revision surgery using ceramic on ceramic bearing surface. The patient discharged postoperative 79 days. Final heavy metals screen results were 27.79μg/L on cobalt and 22.17μg/L on chrome. Although there were also reported a good clinical result of revision surgery using MoP bearing, and some surgeons reluctant to use CoC articulation because of concerns about re-fracture of ceramic. But take into account like this devastating complication after cobalt-chrome wear caused by remained ceramic particles, we should carefully select which bearing is safer

The return to the use of big diameter femoral heads is now a well-established reality. The certainty of a better result is not only for young patients with an high functional demand, but also for elderly people, who need a reduction of enticement time and an increase of intrinsic Materials optimization and “hard to hard” bearings allowed surgeons to reduce the problem of volumetric wear and to guarantee some undeniable advantages such as: -better articular stability, thanks to the off-set restore -better range of motion -reduction of dislocation risk Increasing the femoral head diameter means increasing the off-set therefore the lever arm of the gluteus medius which is a great articular stabilizer. With the old metal to polyethylene and ceramic to polyethylene bearings, the bigger contact surface between the head and the cotyle interior certainly increased the volumetric wear in the past. The introduction of bearings at “low friction coefficient” ceramic-to-ceramic and metal-to-metal solved this problem and the undeniable improvement of the polyethylene preparation made this material to be considered safe even with big diameter heads. All articular stability parameters, in primis for the off-set, can be improved by the use of those solutions which are all efficient and able to give the surgeon the right mean to solve every single case. The eventuality to break ceramic heads is reported in literature and has fortunately reference to a low percentage, about 1.5% (“Biolox 28 mm ceramic-ceramic THR: 1.5% fractures 7 years f.u.” Toni, Alt.Bearings, NYC, 2002), but it maybe limits this kind of choice in cases of hip dysplasia, in which a bigger acetabulum uprightness increases the percentage of mistake in placing the cotyle. Nowadays, the diameter of the available heads is progressively increasing with the cotyle diameter (32, 36), so ceramic-ceramic is anyway an excellent solution for all other fatigued coxofemural articulations, above all if they are still eumorphic, and for female patients in which a worst bone quality reduces the choice of metal-metal. The metal-metal bearing finds instead a great indication in all patients, above all male patients with a good bone quality with high functional demand. The only reasons to go back preferring the metal-metal bearing are the reduction of the average age of the prosthesized patient and the increasing performance need. New techniques of superficial finish of the chrome-cobalt allowed surgeons to optimize the clearance, the self-smoothing ability in case of “streaks” of third body. Tests drawn in gate analysis demonstrated a reduced detachment between the two prosthesis components when the metal-metal operated patient makes the step, not only in favour of the bearing, but also of the choice of big diameters (“Metal on metal and distraction: an in vivo comparison.” Komistec et al; JBJS; October 2002). Moreover, other indications in literature show that there is no direct correlation between the cancer development and the metal-metal bearing prosthesis implant (Visuri, COOR 1996) (“The risk of cancer following total hip or knee arthroplasty” Tharani et al., JBJS May 2001), and even that there were no cobalt toxic serum levels able to justify cardio-pneumatie (Brodner, JBJS 1997). Independently by the materials choice, the bearing with big diameter heads undeniably reduces dislocation risk and accelerates the post-operative recovery even in old patients surgically treated for fracture. The larger distance a big diameter head has to cover in order to come out of the acetabular cavity (Jump distance) certainly reduces the number of dislocation cases. (“Large versus small femoral heads in metal on metal total hip arthroplasty” –. Cucler J.M. et al., . JoA. , Vol . 19. , num 8, suppl. 3., . 2004. ) (“Effect of femoral head diameter and operative approach on risk of dislocation after primary total hip arthroplasty” Berry DJ et al., JBJS Am. 2005 Nov; 87(11):2456–63). All those reasons pushed us to believe in “hard to hard” bearings with big diameter, whose results could not be more satisfying. Nevertheless, there are some complications which can make us think, such as cases of pseudocancer for metal-metal bearing and the squeaking in the ceramic-ceramic bearing. The introduction of last generation polyethylene could bring the golden standard near the ceramicpolyethylene again

Aims

A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database.

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells. We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression. Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo

Aims

Surface replacement arthroplasty (SRA), compared with traditional total hip arthroplasty (THA), is more expensive and carries unique concern related to metal ions production and hypersensitivity. Additionally, SRA is a more demanding procedure with a decreased margin for error compared with THA. To justify its use, SRA must demonstrate comparable component survival and some clinical advantages. We therefore performed a systematic literature review to investigate the differences in complication rates, patient-reported outcomes, stress shielding, and hip biomechanics between SRA and THA.

There is increasing global awareness of adverse reactions to metal debris and elevated serum metal ion concentrations following the use of second generation metal-on-metal total hip arthroplasties. The high incidence of these complications can be largely attributed to corrosion at the head-neck interface. Severe corrosion of the taper is identified most commonly in association with larger diameter femoral heads. However, there is emerging evidence of varying levels of corrosion observed in retrieved components with smaller diameter femoral heads. This same mechanism of galvanic and mechanically-assisted crevice corrosion has been observed in metal-on-polyethylene and ceramic components, suggesting an inherent biomechanical problem with current designs of the head-neck interface.

We provide a review of the fundamental questions and answers clinicians and researchers must understand regarding corrosion of the taper, and its relevance to current orthopaedic practice.

Cite this article: Bone Joint J 2016;98-B:579–84.

Metallosis after shoulder replacement has not previously been described in the literature. We report a patient who developed extensive metallosis after implantation of an uncemented Nottingham shoulder replacement. He underwent a revision procedure.

Examination of the retrieved prosthesis showed that the titanium porous coating was separating from the humeral stem and becoming embedded in the ultra-high-molecular-weight polyethylene glenoid component, resulting in abrasive wear of the humeral component. There was metallosis despite exchange of the modular humeral head. Both components had to be exchanged to resolve the problem.