The risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders with cobalt-chrome-containing total hip arthroplasty implants : an analysis of the National Joint Registry.

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. METHODS: Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. RESULTS: There were 158,677 individuals (42.4%) with an implant containing CoCr. There were 47,963 deaths, 27,332 heart outcomes, 35,720 cancers, and 22,025 neurodegenerative disorders. There was no evidence of an association between patients with CoCr implants and higher rates of any of the outcomes. CONCLUSION: CoCr-containing THAs did not have an increased risk of all-cause mortality, or clinically meaningful heart outcomes, cancer, or neurodegenerative disorders into the second decade post-implantation. Our findings will help reassure clinicians and the increasing number of patients receiving primary THA worldwide that the use of CoCr-containing implants is not associated with significant adverse systemic effects. Cite this article: Bone Joint J 2022;104-B(3):359-367.

Hemiarthroplasties: the choice of prosthetic material causes different levels of damage in the articular cartilage.

BACKGROUND: Hemiarthroplasty has clear advantages over alternative procedures and is used in 20% of all shoulder joint replacements. Because of cartilage wear, the clinical outcome of hemiarthroplasty is unreliable and controversial. This paper suggests that the optimal choice of prosthetic material may reduce cartilage degeneration and improve the reliability of the procedure. The specific objectives were to assess 3 materials and assess how the severity of arthritis might affect the choice of prosthetic material. METHODS: A CoCr alloy, an AL2O3 ceramic, and a polycarbonate urethane polymer (PCU) were mechanically tested against 5 levels of human osteoarthritic cartilage (from intact to severely arthritic, n = 45). A high friction coefficient, a decrease in Young's modulus, an increase in permeability, a decrease in relaxation time, an increase in surface roughness, and a disrupted appearance of the cartilage after testing were used as measures of cartilage damage. The biomaterial that caused minimal cartilage damage was defined as superior. RESULTS: The CoCr caused the most damage. This was followed by the AL2O3 ceramic, whereas the PCU caused the least amount of damage. Although the degree of arthritis had an effect on the results, it did not change the trend that CoCr performed worst and PCU the best. DISCUSSION AND CONCLUSION: This study indicates that ceramic implants may be a better choice than metals, and the articulating surface should be as smooth as possible. Although our results indicate that the degree of arthritis should not affect the choice of prosthetic material, this suggestion needs to be further investigated.

Neural cell responses to wear debris from metal-on-metal total disc replacements.

PURPOSE: Total disc replacements, comprising all-metal articulations, are compromised by wear and particle production. Metallic wear debris and ions trigger a range of biological responses including inflammation, genotoxicity, cytotoxicity, hypersensitivity and pseudotumour formation, therefore we hypothesise that, due to proximity to the spinal cord, glial cells may be adversely affected. METHODS: Clinically relevant cobalt chrome (CoCr) and stainless steel (SS) wear particles were generated using a six-station pin-on-plate wear simulator. The effects of metallic particles (0.5-50 µm3 debris per cell) and metal ions on glial cell viability, cellular activity (glial fibrillary acidic protein (GFAP) expression) and DNA integrity were investigated in 2D and 3D culture using live/dead, immunocytochemistry and a comet assay, respectively. RESULTS: CoCr wear particles and ions caused significant reductions in glial cell viability in both 2D and 3D culture systems. Stainless steel particles did not affect glial cell viability or astrocyte activation. In contrast, ions released from SS caused significant reductions in glial cell viability, an effect that was especially noticeable when astrocytes were cultured in isolation without microglia. DNA damage was observed in both cell types and with both biomaterials tested. CoCr wear particles had a dose-dependent effect on astrocyte activation, measured through expression of GFAP. CONCLUSIONS: The results from this study suggest that microglia influence the effects that metal particles have on astrocytes, that SS ions and particles play a role in the adverse effects observed and that SS is a less toxic biomaterial than CoCr alloy for use in spinal devices. These slides can be retrieved under Electronic Supplementary Material.

Local Biological Reactions and Pseudotumor-Like Tissue Formation in relation to Metal Wear in a Murine In Vivo Model.

Metal wear debris and released ions (CoCrMo), which are widely generated in metal-on-metal bearings of hip implants, are also found in patients with metal-on-polyethylene bearings due to the mechanically assisted crevice corrosion of modular taper junctions, including head-neck and neck-stem taper interfaces. The resulting adverse reactions to metal debris and metal ions frequently lead to early arthroplasty revision surgery. National guidelines have since been published where the blood metal ion concentration of patients must consistently be monitored after joint replacement to prevent serious complications from developing after surgery. However, to date, the effect of metal particles and metal ions on local biological reactions is complex and still not understood in detail; the present study sought to elucidate the complex mechanism of metal wear-associated inflammation reactions. The knee joints in 4 groups each consisting of 10 female BALB/c mice received injections with cobalt chrome ions, cobalt chrome particles, and ultra-high-molecular-weight polyethylene (UHMWPE) particles or PBS (control). Seven days after injection, the synovial microcirculation and knee joint diameter were assessed via intravital fluorescence microscopy followed by histological evaluation of the synovial layer. Enlarged knee diameter, enhanced leukocyte to endothelial cell interactions, and an increase in functional capillary density within cobalt chrome particle-treated animals were significantly greater than those in the other treatment groups. Subsequently, pseudotumor-like tissue formations were observed only in the synovial tissue layer of the cobalt chrome particle-treated animals. Therefore, these findings strongly suggest that the cobalt chrome particles and not metal ions are the cause for in vivo postsurgery implantation inflammation.

Unicondylar knee arthroplasty using cobalt-chromium implants in patients with self-reported cutaneous metal hypersensitivity.

AIMS: The treatment of patients with allergies to metal in total joint arthroplasty is an ongoing debate. Possibilities include the use of hypoallergenic prostheses, as well as the use of standard cobalt-chromium (CoCr) alloy. This non-designer study was performed to evaluate the clinical outcome and survival rates of unicondylar knee arthroplasty (UKA) using a standard CoCr alloy in patients reporting signs of a hypersensitivity to metal. PATIENTS AND METHODS: A consecutive series of patients suitable for UKA were screened for symptoms of metal hypersensitivity by use of a questionnaire. A total of 82 patients out of 1737 patients suitable for medial UKA reporting cutaneous metal hypersensitivity to cobalt, chromium, or nickel were included into this study and prospectively evaluated to determine the functional outcome, possible signs of hypersensitivity, and short-term survivorship at a minimum follow-up of 1.5 years. RESULTS: At a mean follow-up of three years (1.5 to 5.7), no local or systemic symptoms of hypersensitivity to metal were observed. One patient underwent revision surgery to a bicondylar prosthesis due to a tibial periprosthetic fracture resulting in a survival rate of 98.8% (95% confidence interval (CI) 91.7 to 99.8; number at risk, 28) at three years with the endpoint of revision for any reason and a survival rate of 97.6% (95% CI 90.6 to 99.3; number at risk, 29) for the endpoint of all reoperations. Clinical outcome was good to excellent with a mean Oxford Knee Score of 42.5 (sd 2.5; 37 to 48). CONCLUSION: This study is the first demonstrating clinical results and survival analysis of UKA using a CoCr alloy in patients with a history of metal hypersensitivity. Functional outcome and survivorship are on a high-level equivalent to those reported for UKA in patients without a history of metal hypersensitivity. No serious local or systemic symptoms of metal hypersensitivity could be detected, and no revision surgery was performed due to an adverse reaction to metal ions.

Taper-Trunnion Interface Stress Varies Significantly With Head Size and Activity.

BACKGROUND: Total hip arthroplasty is performed with modular parts. Either a metal or ceramic ball is fastened to the trunnion of a femoral stem via a Morse taper. This implant scenario has been successful. However, recently larger (36 mm or greater) metal heads have become more popular as a means to reduce the incidence of hip joint dislocation. Today, a number of clinical failures have occurred due to mechanically assisted crevice corrosion at the head (taper) stem (trunnion) interface necessitating revision surgery. The objective of this research is to investigate how trunnion stress varies with head size, and how taper-trunnion geometric parameters including horizontal lever arm (HLA), taper engagement level, and a new parameter called trunnion load offset affect trunnion stresses. We hypothesized that trunnion stress may increase with increasing head size and HLA. METHODS: This hypothesis was tested by conducting finite element analysis of a titanium hip stem and 4 commercially available cobalt-chromium femoral heads subjected to 4 different moderate to severe physiological loading conditions. RESULTS: Results showed that trunnion stress increases with increasing head size, increased HLA, and trunnion load offset. It was also found that under certain load cases the trunnion stresses get exceptionally high, especially for the larger head sizes. CONCLUSION: This study suggests trying to avoid larger femoral head sizes that may result in higher implant stresses under certain loading conditions.

Differential Effect of Cobalt and Chromium Ions as Well as CoCr Particles on the Expression of Osteogenic Markers and Osteoblast Function.

The balance of bone formation and resorption is the result of a regulated crosstalk between osteoblasts, osteoclasts, and osteocytes. Inflammation, mechanical load, and external stimuli modulate this system. Exposure of bone cells to metal ions or wear particles are thought to cause osteolysis via activation of osteoclasts and inhibition of osteoblast activity. Co2+ ions have been shown to impair osteoblast function and the expression of the three transforming growth factor (TGF)-ß isoforms. The current study was performed to analyze how Co2+ and Cr3+ influence the expression, proliferation, and migration profile of osteoblast-like cells. The influence of Co2+, Cr3+, and CoCr particles on gene expression was analyzed using an osteogenesis PCR Array. The expression of different members of the TGF-ß signaling cascade were down-regulated by Co2+, as well as several TGF-ß regulated collagens, however, Cr3+ had no effect. CoCr particles partially affected similar genes as the Co2+treatment. Total collagen production of Co2+ treated osteoblasts was reduced, which can be explained by the reduced expression levels of various collagens. While proliferation of MG63 cells appears unaffected by Co2+, the migration capacity was impaired. Our data may improve the knowledge of changes in gene expression patterns, and the proliferation and migration effects caused by artificial materials.

Outcomes of Revision Joint Arthroplasty Due to Metal Allergy and Hypersensitivity: A Systematic Review.

BACKGROUND: Lower extremity total joint arthroplasty (TJA) is one of the most successful orthopaedic procedures. However, it is estimated that as many as 10% to 20% of TJAs could fail due to various well-known causes. Furthermore, metal allergy-related complications have recently gained attention as one of the potential causes of failure when the common reasons have been excluded. Reported symptoms from metal allergy can include chronic eczema, joint effusions, joint pain, and limited range of motion. Few studies have explored the outcomes of patients undergoing revisions due to allergic complications. The aim of our study is to quantitatively evaluate the outcomes of revision joint arthroplasty due to metal allergy and hypersensitivity.

The Effect of Alternative Bearing Surfaces on the Risk of Revision Due to Infection in Minimally Stabilized Total Knee Replacement: An Analysis of 326,603 Prostheses from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: The effect of alternative bearing materials on the risk of revision due to infection after total knee replacement remains uncertain. By reducing the immunomodulating polyethylene wear-particle burden and with different substrate bacterial adhesion properties, Oxinium oxidized zirconium and cross-linked polyethylene (XLPE) could alter infection risk. The purpose of the current study was to analyze the risk of revision for infection in 3 comparisons of bearing combinations. METHODS: To evaluate the risk of revision for infection with XLPE, cobalt-chromium (CoCr) on XLPE was compared with CoCr on non-cross-linked polyethylene (NXLPE). To evaluate Oxinium, Oxinium-NXLPE was compared with CoCr-NXLPE, and to evaluate the possibility of an additional beneficial effect of Oxinium on XLPE, Oxinium-XLPE was compared with CoCr-XLPE. The cumulative percent revision (CPR) and hazard ratio (HR) for revision for infection in primary total knee replacement for osteoarthritis were determined from registry data from September 1, 1999, to December 31, 2015. Revisions within 6 months following the primary surgery were censored from the analysis, while procedures with posterior stabilized or fully stabilized total knee replacements as well as prostheses with a known higher risk of revision were excluded. Analyses were stratified by age, sex, and fixation type. RESULTS: Of the 326,603 included primary total knee replacements, 1,511 (0.46%) were revised for infection. The risk of revision for infection was lower for CoCr-XLPE compared with CoCr-NXLPE (HR = 0.74; 95% confidence interval [CI] = 0.65 to 0.84; p < 0.001). This effect was apparent for both male and female patients overall, all fixation types, antibiotic cement use, those <65 years of age, and male patients ≥65 years of age. However, for female patients ≥65 years of age, there was no difference. Overall, Oxinium-NXLPE had the same revision risk as CoCr-NXLPE regardless of fixation; however, for cemented fixation, subanalysis showed a lower risk for Oxinium-NXLPE compared with CoCr-NXLPE (HR = 0.69; 95% CI = 0.51 to 0.94; p = 0.018). Oxinium-XLPE had the same revision risk for infection as CoCr-XLPE overall, among male patients, and when cemented fixation had been used. CONCLUSIONS: In this registry analysis, CoCr-XLPE had a 26% lower risk of revision for infection than CoCr-NXLPE, suggesting a reduction of wear particle-induced immunomodulation with XLPE. Oxinium-XLPE had the same risk as CoCr-XLPE. Overall, Oxinium did not reduce the infection risk. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Surface Microstructural Changes and Release of Ions from Dental Metal Alloy Removable Prostheses in Patients Suffering from Acid Reflux.

PURPOSE: To investigate the surface microstructural changes and the release of ions from metal alloys used in removable dental prostheses and the potential effects of acidic reflux found in patients suffering from gastroesophageal reflux disease (GERD). MATERIALS AND METHODS: Thirty-seven (37) patients were recruited. Data were gathered through a questionnaire and clinical examination. Samples of metal alloy from the dentures and patient's saliva were collected. GERD was confirmed using the GerdQ questionnaire. Denture samples were characterized using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), while salivary samples were tested for trace metal ions using inductively coupled plasma (ICP). RESULTS: Characterization of denture samples revealed the presence of nickel, cobalt, and chromium. Nickel-chromium exhibited an etched surface appearance, while cobalt-chromium exhibited no noticeable surface microstructural changes. Higher mean salivary levels of chromium and cobalt in patients wearing any metal alloy-based denture and of chromium and nickel in patients wearing Ni-Cr prostheses were found to be significant. No differences were found in salivary metal ion levels of patients suffering from GERD. CONCLUSIONS: Nickel-chromium alloy is prone to acid etching in the oral cavity, while cobalt-chromium alloy appears to be more resistant. Cobalt, chromium, and nickel are leached in saliva of patients using cast removable prostheses. The impact of gastric acid on metal ion release from dental metal alloys deserves further investigations. CLINICAL SIGNIFICANCE: This preliminary study suggests that metal-based removable prostheses leach trace metal ions in saliva. Nickel-chromium-based dentures exhibit an etched appearance unrelated to GERD.

Characteristics of Cobalt-Related Cardiomyopathy in Metal Hip Implant Patients: An Evaluation of 15 Published Reports.

Over 300,000 hip replacements occurred in the USA in 2010, and the frequency is likely increasing annually. Blood Cobalt (Co) concentrations in patients with well-functioning cobalt-chromium (Co-Cr) hip implants are usually elevated above background concentrations relative to the general population. Excessive Co exposure, in rare cases, can result in cardiomyopathy. The purpose of this review was to identify cases of cardiomyopathy in metal-containing hip implant patients and to evaluate the possible cause of each patient's cardiomyopathy. We evaluated 15 cases published between 2009 and 2016, and, based on a review of the preexisting risk factors, blood Co concentrations, and histopathological information published for each patient, they were stratified into one of four categories regarding the association between Co exposure and the development of cardiomyopathy: (1) Co was causal (five cases); (2) Co was contributory (two cases); (3) Co was possibly contributory (six cases); and (4) Co was non-causal (two cases). In all 15 cases, blood Co concentrations (14-6521 µg/L) were elevated beyond levels associated with the majority of metal-containing implant patients (0.1-10 µg/L), and, in many cases, there was evidence of a malfunctioning implant. The data indicate that individuals with well-functioning implants, even those with preexisting risk factors, are at no risk of developing cardiac effects. We conclude that blood Co measurements are informative, but should be interpreted with caution, and in context of other factors evaluated in this analysis. The mere presence of elevated Co is not sufficient to indicate causation for a patient's cardiomyopathy.

Off-resonance based assessment of metallic wear debris near total hip arthroplasty.

PURPOSE: The presence of metallic debris near total hip arthroplasty can have a significant impact on longitudinal patient management. Methods for magnetic resonance imaging-based quantification of metallic debris near painful total hip replacements are described and applied to cohorts of symptomatic and control subject cases. METHODS: A combination of metal artifact reduction, off-resonance mapping, off-resonance background removal, and spatial clustering methods are utilized to quantify off-resonance signatures in cases of suspected metallosis. These methods are applied to a cohort of symptomatic hip arthroplasties composed of cobalt-chromium alloys. Magnetostatic simulations and theoretical principles are used to illuminate the potential sources of the measured off-resonance effects. Reported metrics from histological tissue assays extracted during surgical revision procedures are also correlated with the proposed magnetic resonance imaging-based quantification results. RESULTS: The presented methods identified quantifiable metallosis signatures in more than 70% of the symptomatic and none of the control cases. Preliminary correlations of the MR data with direct histological evaluation of retrieved tissue samples indicate that the observed off-resonance effect may be related to tissue necrosis. CONCLUSIONS: Magnetostatic simulations, theoretical principles, and preliminary histological trends suggest that disassociated cobalt is the source of the observed off-resonance signature. Magn Reson Med 79:1628-1637, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Failure of a Polyaryletheretherketone-Cobalt-Chromium Composite Femoral Stem Due to Coating Separation and Subsidence: A Case Report.

CASE: A 52-year-old man who previously had undergone total hip arthroplasty with use of an Epoch (Zimmer) extensively porous-coated femoral stem presented with hip pain after a high-energy motor-vehicle accident. Radiographs demonstrated delamination at the polyaryletheretherketone-cobalt-chromium (PEEK-CoCr) core interface, which led to loosening. At revision, the implant demonstrated gross evidence of debonding at the PEEK-CoCr interface. CONCLUSION: We demonstrate clinical and tribologic evidence of a rare failure mode involving the PEEK-metal interface in a composite femoral stem, which surgeons should be aware of when evaluating patients with this type of implant.

Metallosis in a Dog as a Long-Term Complication Following Total Hip Arthroplasty.

Metallosis is the accumulation of metallic debris in soft tissues resulting from wear following total joint replacement. A dog was evaluated for lameness 4 years after total hip arthroplasty using a titanium alloy and cobalt chromium total hip system. Radiographs revealed severe acetabular component wear, implant-bone interface deterioration, and peri-acetabular osteolysis. During surgical revision, black periarticular tissue surrounded the implants. Histologically, there was fibrosis and granulomatous inflammation with abundant, intra- and extracellular, black, granular material and smaller amounts of clear punctate to acicular material. Laser capture microdissection followed by x-ray fluorescence microscopy indicated the material contained large amounts of titanium with smaller amounts of vanadium, cobalt, and chromium, confirming the diagnosis of metallosis. The clear material was birefringent under cross-polarized light, stained positive with Oil-Red-O, and thus was consistent with polyethylene. Metallosis exhibits characteristic gross and histologic lesions and is a differential diagnosis for aseptic loosening of hip implants.

Rod stiffness as a risk factor of proximal junctional kyphosis after adult spinal deformity surgery: comparative study between cobalt chrome multiple-rod constructs and titanium alloy two-rod constructs.

BACKGROUND CONTEXT: Little is known about the effect of rod stiffness as a risk factor of proximal junctional kyphosis (PJK) after adult spinal deformity (ASD) surgery. PURPOSE: The aim of this study was to compare radiographic outcomes after the use of cobalt chrome multiple-rod constructs (CoCr MRCs) and titanium alloy two-rod constructs (Ti TRCs) for ASD surgery with a minimum 1-year follow-up. STUDY DESIGN: Retrospective case-control study in two institutes. PATIENT SAMPLE: We included 54 patients who underwent ASD surgery with fusion to the sacrum in two academic institutes between 2002 and 2015. OUTCOME MEASURES: Radiographic outcomes were measured on the standing lateral radiographs before surgery, 1 month postoperatively, and at ultimate follow-up. The outcome measures were composed of pre- and postoperative sagittal vertical axis (SVA), pre- and postoperative lumbar lordosis (LL), pre- and postoperative thoracic kyphosis (TK)+LL+pelvic incidence (PI), pre- and postoperative PI minus LL, level of uppermost instrumented vertebra (UIV), evaluation of fusion after surgery, the presence of PJK, and the occurrence of rod fracture. MATERIALS AND METHODS: We reviewed the medical records of 54 patients who underwent ASD surgery. Of these, 20 patients had CoCr MRC and 34 patients had Ti TRC. Baseline data and radiographic measurements were compared between the two groups. The Mann-Whitney U test, the chi-square test, and the Fisher exact test were used to compare outcomes between the groups. RESULTS: The patients of the groups were similar in terms of age, gender, diagnosis, number of three-column osteotomy, levels fused, bone mineral density, preoperative TK, pre- and postoperative TK+LL+PI, SVA difference, LL change, pre- and postoperative PI minus LL, and location of UIV (upper or lower thoracic level). However, there were significant differences in the occurrence of PJK and rod breakage (PJK: CoCr MRC: 12 [60%] vs. Ti TRC: 9 [26.5%], p=.015; occurrence of rod breakage: CoCr MRC: 0 [0%] vs. Ti TRC: 11 [32.4%], p=.004). The time of PJK was less than 12 months after surgery in the CoCr MRC group. However, 55.5% (5/9) of PJK developed over 12 months after surgery in the Ti TRC group. CONCLUSIONS: Increasing the rod stiffness by the use of cobalt chrome rod and can prevent rod breakage but adversely affects the occurrence and the time of PJK.

Damage mechanisms at the cement-implant interface of polished cemented femoral stems.

The occurrence of damage on polished femoral stems has been widely reported in the literature, and bone cement has been implicated in a tribocorrosive failure process. However, the mechanisms of cement-mediated damage and the impact of cement formulation on this process are not well understood. In this study, 13 Zimmer CPT polished femoral stems, and the corresponding cement specimens were retrieved at revision surgery and analyzed using high-resolution imaging techniques. Surface damage attributed to tribocorrosion was observed on all stems. Corrosion product, in the form of black flaky surface debris, was observed on the surface of cement specimens; both energy-dispersive X-ray spectroscopy and inductively coupled plasma mass spectrometry(ICP-MS) confirmed the presence of cobalt and chromium, with the ICP-MS showing much higher levels of Cr compared to Co when compared to the original stem material. Agglomerates of ZrO2 radiopacifier were also identified on the cement surface and, in some cases, showed evidence of abrasive wear; the size of these particles correlated well with elliptical pitting evident on the surfaces of the corresponding stems. This evidence supports the hypothesis that agglomerates of hard radiopacifier particles within the cement may induce a wear-dominated tribocorrosive interaction at the stem-cement interface that damages the surface of polished CoCr femoral stems. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2027-2033, 2017.

The induction of CXCR4 expression in human osteoblast-like cells (MG63) by CoCr particles is regulated by the PLC-DAG-PKC pathway.

BACKGROUND: Osteolysis which leads to aseptic loosening of implants is a fundamental problem in joint replacement surgery (arthroplasty) and the leading cause for implant failure and revision surgery. Metal (CoCr) particles separated from implants by wear cause osteolysis and the failure of orthopedic implants, but the molecular mechanism is not clear. The chemokine receptor CXCR4 has been shown to play a pivotal role in periprosthetic osteolysis. The aim of this study was to determine which signal transduction pathway (PLC-DAG-PKC or MAPK/ERK) induces CXCR4 expression in osteoblast-like cells (MG63) cells. METHODS: MG63 and Jurkat cells were stimulated with different amounts of particles (107 , 106 , and 105 ) for different time periods (30 min to 24 h), in the presence and absence of specific inhibitors (chelerythrine for the PLC-DAG-PKC pathway and PD98059 for the MAPK/ERK pathway). The expression of CXCR4-specific mRNA was determined by real-time polymerase chain reaction (PCR), and the PKC activity was measured by Western Blot using an antibody specific for PKC-related phosphorylation. RESULTS: Real-time PCR data showed that CXCR4 mRNA expression in MG63 cells induced by CoCr particles was significantly diminished by the PKC-specific inhibitor chelerythrine. This effect was not observed with the MAPK/ERK inhibitor PD98059. The involvement of PKC was also confirmed by an intensified phosphorylation pattern after stimulation with CoCr particles. In Jurkat cells, none of the inhibitors exhibited any effect. CONCLUSION: The induction of CXCR4-specific mRNA expression in MG63 cells after stimulation with CoCr particles is regulated by the PLC-DAG-PKC pathway and not by the MAPK/ERK pathway. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2326-2332, 2017.

Cobalt-Chromium Metallosis With Normal Electroretinogram.

BACKGROUND: Ocular cobalt toxicity is a rare phenomenon reported with increased frequency due to the rise of cobalt-chromium metal hip implants. We report the case of a 66-year-old previously healthy man who developed decreased vision due to cobalt-chromium toxicity from a metal-on-metal hip arthroplasty. Our objective was to determine whether the origin of his visual loss was due to toxicity of the optic nerve, of the retina, or of both. METHODS: Ocular examination, 10-2 SITA-Standard Humphrey Visual Field (VF), standard full-field electroretinogram (ERG) as indicated by the International Society for Clinical Electrophysiology of Vision (ISCEV), multifocal electroretinogram (mfERG), multifocal visual evoked potentials (mfVEP), and optical coherence tomography (OCT) were conducted. RESULTS: Ocular examination revealed decreased visual acuity, poor color vision, normal funduscopy, and cecocentral scotomas on VF testing. Because his right eye was amblyopic since childhood, test results from only the left eye are shown. Electrophysiology studies revealed an ISCEV standard full-field ERG with photopic and scotopic responses within normal limits, mfERG with amplitudes and latencies within normal limits, and mfVEP with latencies within normal limits, but with decreased central amplitudes. Peripapillary and macular OCT showed retinal nerve fiber layer and retinal ganglion cell-inner plexiform layer thickness within normal limits. CONCLUSION: Because decreased color vision and cecocentral scotoma on 10-2 VF are most consistent with toxic optic neuropathy, and decreased central amplitudes on mfVEP are suggestive of neural dysfunction, we hypothesize that our patient presented with an early stage of optic nerve toxicity that was not yet apparent as a structural abnormality on OCT.

Macrophage responses to 316L stainless steel and cobalt chromium alloys with different surface topographies.

The surface topography of a biomaterial plays a vital role in determining macrophage interactions and influencing immune response. In this study, we investigated the effect of smooth and microrough topographies of commonly used metallic biomaterials such as 316 L stainless steel (SS) and cobalt-chromium (CoCr) alloys on macrophage interactions. The macrophage adhesion was greater on CoCr compared to SS, irrespective of their topographies. The macrophage activation and the secretion of most pro-inflammatory cytokines (TNF-α, IL-6, and IP-10) were greater on microrough surfaces than on smooth surfaces by day-1. However, by day-2, the macrophage activation on smooth surfaces was also significantly increased up to the same level as observed on the microrough surfaces, with more amount of cytokines secreted. The secretion of anti-inflammatory cytokine (IL-10) was significantly increased from day-1 to day-2 on all the alloy surfaces with the effect most prominently observed on microrough surfaces. The production of nitric oxide by the macrophages did not show any major substrate-dependent effect. The foreign body giant cells formed by macrophages were least observed on the microrough surfaces of CoCr. Thus, this study demonstrated that the nature of material (SS or CoCr) and their surface topographies (smooth or microrough) strongly influence the macrophage responses. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2658-2672, 2016.