Blood Cobalt Levels Research Articles

Nonlinearity association of blood cobalt with the risk of anemia among middle-aged and older adults: National Health and Nutrition Examination Survey

ABSTRACT Objective The use of cobalt alloys in medical implants poses a high risk of cobalt exposure, yet there is a lack of evidence regarding the association between blood cobalt levels and anemia. This study aimed to explore the link between blood cobalt levels and the onset of anemia and to identify potential threshold levels of blood cobalt that could affect anemia. Methods The US National Health and Nutrition Examination Survey data from 2017 to 2020 were analyzed for this cross-sectional study. This study primarily employed multivariate logistic regression, stratified interaction analysis, restricted cubic splines (RCS), and threshold effect analysis to explore the relationship between blood cobalt concentration and anemia. Results The study included 5510 participants and among them 12.2% were diagnosed with anemia. Logistic regression model indicates a positive correlation between blood cobalt levels and the risk of anemia. RCS shows that the relationship between ln cobalt concentration and anemia was non-linear (J-shaped). The ln cobalt inflection point was approximately 0.81. The odds ratio of anemia with ln cobalt ≥ 0.81 was 4.00 (95% CI: 2.95–5.43, p < 0.001), the odds ratio of anemia with ln cobalt < 0.81 was 0.73 (95% CI: 0.45–1.18, p = 0.201). Conclusions The analysis unveiled a non-linear relationship, indicating that elevated blood cobalt levels were linked to a heightened likelihood of developing anemia in middle-aged and older adults; the cut-off value of ln cobalt was approximately 0.81. The findings of this study warrant further investigation.

Cardiac function may be compromised in patients with elevated blood cobalt levels secondary to metal-on-metal hip implants.

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. 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. 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). 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.

Investigating the association between blood cobalt and gallstones: a cross-sectional study utilizing NHANES data.

With the use of cobalt alloys in medical prosthetics, the risk of cobalt exposure has increased. The objective of this study was to investigate the correlation between blood cobalt levels and the occurrence of gallstones utilizing data from the National Health and Nutrition Examination Survey (NHANES). Data collected between 2017 and 2020 were analyzed, encompassing a total of 5,610 participants. Cobalt concentrations in whole blood specimens were directly measured using inductively coupled plasma mass spectrometry (ICP-MS). The presence of gallstones was ascertained through a standardized questionnaire. To assess the association between blood cobalt levels and the presence of gallstones, logistic regression analysis, restricted cubic spline analysis, and subgroup analysis were utilized. The results of logistic regression analysis revealed a heightened risk of developing gallstones in the Quartiles 2 and Quartiles 4 groups based on blood cobalt levels when compared to the Quartiles 1 group (OR = 1.54, 95% CI: 1.15-2.07; OR = 1.35, 95% CI: 1.03-1.77). The restricted cubic spline analysis exhibited a positive linear correlation between blood cobalt levels and the occurrence of gallstones. Subgroup analyses further demonstrated a statistically significant correlation between the Quartiles 4 category of blood cobalt levels and an elevated risk of gallstones, particularly among individuals aged 60 years or older, females, those with a body mass index (BMI) equal to or exceeding 25, serum total cholesterol levels below 200 mg/dL, as well as individuals diagnosed with hypertension or diabetes. Our study findings indicate a notable association between elevated blood cobalt levels and an increased risk of gallstones. To establish a causal relationship between blood cobalt levels and the elevated risk of developing gallstones, further prospective cohort studies are warranted.

Traditional Food Consumption and Other Determinants of Exposure for Lead, Cobalt, Manganese, and Hexachlorobenzene in Northern Canada

Results of a 2019 human biomonitoring study indicated that several parameters, including lead, cobalt, manganese, and hexachlorobenzene, were elevated in blood and urine samples in Old Crow, Yukon, in comparison to the general Canadian population. This study aims to identify possible local determinants of levels of these parameters, including consumption of locally harvested traditional foods, lifestyle factors, and demographics, in Old Crow and, for comparison, two other northern populations: communities in the Dehcho and Sahtú regions of the Northwest Territories. We ran generalized linear models to identify possible associations between individual determinants of exposure and key biomarkers, controlling for age and sex. In Old Crow, several variables were associated with elevated exposure levels of these biomarkers, including drinking untreated river water (29% higher blood manganese levels and 120% higher blood lead levels), eating caribou kidneys (22% higher blood manganese levels and 58% higher blood lead levels), and eating whitefish (28% higher blood cobalt levels). Additionally, in order to differentiate results in Old Crow from those in other northern regions and to identify trends across regions, we observed relationships between consumption of moose and caribou organs and lead and hexachlorobenzene levels in the reference populations and pooled population groups. Though levels of particular contaminants may be elevated in some traditional foods, these foods remain an important source of nutrients for members in these communities and provide other benefits, including increased physical activity through harvesting, mental health improvements, and spiritual wellness.

Individual, sociodemographic, and lifestyle influence on blood chromium, cobalt, and nickel levels in healthy population living in Belgrade, Serbia.

The rapid trend of industrialization and urbanization can lead to greater exposure of the general population to chromium, cobalt, and nickel. Their total body burden from all routes of recent exposure, as well as interindividual variability in exposure levels, metabolism, and excretion rates, are reflected in the blood metal concentrations. The main goals in this study were as follows: observing the reference levels of chromium, cobalt, and nickel in the blood of the population living in Belgrade, identification of individual and sociodemographic factors that most affect their blood levels, and comprehension of recent exposure to chromium, cobalt, and nickel. Blood was sampled from 984 participants, voluntary blood donors, who agreed to participate in this study. Individual and sociodemographic data were collected using questionnaire adapted for different subpopulations. Blood metal analyses were measured using ICP-MS method (7700×, Agilent, USA). Our study provided reference values of chromium, cobalt, and nickel in blood for adult population (18-65 years) and confirmed that blood cobalt and nickel levels were mostly influenced by age and gender, and age, respectively. Furthermore, weight status affected blood chromium and cobalt levels, while national origin affected blood chromium levels. The present study highlighted the importance of human biomonitoring studies to monitor exposure status and identify subpopulations with increased exposure to chromium, cobalt, and nickel.

Long-term clinical outcomes of the Biomet M2a-38: a retrospective review of 335 total hip arthroplasty cases

BackgroundAt the turn of the century, over one-third of total hip arthroplasties comprised metal-on-metal bearings. As this patient population and their implants age, it is crucial to understand associated late failure modes and expected long-term functional outcomes. We report the long-term results of a large metal-on-metal uncemented total hip arthroplasty system with unique design characteristics compared to others that have been reported with high failure rates.MethodsWe retrospectively analyze our prospective clinical database to determine overall implant survivorship and functional outcomes. Further, we compare these results to the clinical outcomes reported in orthopedic registries and in other published studies with similar metal-on-metal total hip arthroplasty cohorts.ResultsImplant survivorship at 10 years was 99.1% and continued to 97.6% survivorship at 20 years. Implant survivorship at 20 years did not vary significantly between sexes (Male: 98.3%, Female: 97.2%; log-rank p-value = 0.46). Mean whole blood cobalt levels were 2.6 µg/L in unilateral cases, 5.3 µg/L in bilateral patients, and 3.4 µg/L for the combined cohort. Average blood chromium levels were 1.4 µg/L in unilateral patients, 2.9 µg/L in bilateral patients, and 1.8 µg/L for group combined. We observed a 0.9% rate of failure due trunnion corrosion at a mean of 13.1 years postoperatively (10.6–15.6 years) but had no bearing wear failures.ConclusionsOur 20-year implant survivorship of 97.6% with the M2a-38 bearing surpassed registry benchmarks for THA. This large-bearing (38 mm), full hemisphere coverage metal-on-metal system had no bearing wear failures, one failure of instability, one failure of fixation, and three trunnion failures, perhaps suggesting an optimum balance between stability of the joint and the trunnion.

Metal ion release after hip resurfacing arthroplasty and knee arthroplasty: a retrospective study of one hundred ninety-five cases.

Hip arthroplasty with metal-on-metal bearings like hip resurfacing results in the release of metallic ions. In parallel, like every metallic implant, knee arthroplasty implants undergo passive corrosion. We analyzed blood levels of cobalt and chromium ions in patients who have a hip resurfacing arthroplasty and compared them to patients who have undergone knee arthroplasty at a minimum follow-up of one year. The hypothesis was that there is no difference in the ion release between hip resurfacing and knee arthroplasty. Sixty-three patients who underwent knee arthroplasty were compared to a cohort of 132 patients who underwent hip resurfacing. The blood levels of cobalt and chromium ions were determined preoperatively and at six and 12 months postoperatively and then compared between groups. We analyzed the relationship between ion release and the change in clinical outcome scores (Harris Hip score, Oxford Hip score, Merle D'Aubigné Postel score, Oxford Knee score, International Knee Society score), the BMI, sex, physical activity, implant size and inclination of the acetabular implant (hip resurfacing patients only). Mixed linear models were used to assess the changes in ion blood levels over time. The cobalt blood levels were higher in the first 6 months in the resurfacing group (0.87 ug/L vs 0.67 ug/L; p = 0.011), while it was higher in the knee arthroplasty group at 12 months (1.20 ug/L vs 1.41 ug/L; p = 0.0008). There were no significant differences in chromium levels during the follow-up period. The increase in metal ion release after knee arthroplasty is as high as after hip resurfacing at the oneyear follow-up. The monitoring of this parameter probably should not be recommended in case of good clinicals outcomes.

Metal-on-metal (MoM) hip implants and pregnancy: are MoM implants good for mom?-a systematic review.

Metal-on-metal (MoM) bearing surfaces were historically used for young patients undergoing total hip arthroplasty (THA), and remain commonplace in modern hip resurfacing. A substantial number of female patients with MoM bearings subsequently gave birth following implantation of the bearings before a full understanding of metal ions exposure in these patients was established. In theory, it has been postulated that metal ions released from such implants may cross the placental barrier and cause harm to the fetus. In light of this potential risk, recommendations against the use of MoM components in women of child-bearing age have been advocated. The purpose of this systematic review was to evaluate: (I) the MoM bearing types and ion levels found; (II) the concentrations of metals in maternal circulation and the umbilical cord; and (III) the presence of abnormalities in the fetus or delivered child. A comprehensive literature review was conducted of studies published between January 1st, 1975 and April 1st, 2019 using specific keywords. We defined the inclusion criteria for qualifying studies for this review as follows: (I) studies that reported on the women who experienced pregnancy and who had a MoM hip implant; (II) studies that reported on maternal metal ions blood and umbilical cord levels; and (III) studies that reported on the occurrence of fetal complications. Data on cobalt and chromium ion levels in the maternal blood and umbilical cord blood, as well as the presence of adverse effects in the infant were collected. Age at parturition and time from MoM implant to parturition were also collected. A total of six studies were included in the final analysis that reported on a total of 21 females and 21 infants born. The mean age at parturition was 31 years (range, 24 to 41 years), and the mean time from MoM implantation to parturition was 47 months (range, 11 to 119 months). Maternal blood cobalt levels were found as a weighted average of 34.09 µg/L (0.425 to 138 µg/L), while umbilical cord blood cobalt levels were found to be 22.61 µg/L (0.52 to 51.11 µg/L). Cobalt levels were reduced by an average of 34% between maternal and umbilical cord blood. Maternal cord blood chromium levels were found as a weighted average of 18.18 µg/L (0.225 to 75 µg/L), while umbilical cord chromium levels were found to be 3.96 µg/L (0.14 to 11.96 µg/L). Chromium levels were reduced by an average of 78% between maternal and umbilical cord blood. No cobalt or chromium was detected in the umbilical cord blood of three patients. Out of the 21 infants born to women with MoM implants, 20 were born healthy with no adverse effects or complications. Only one complication was recorded in single infant that did not appear to be related to the maternal MoM implant. To date, there is a lack of consensus as to whether MoM hip arthroplasty implants are to be avoided in the child-bearing female population and whether they constitute a hazard to the fetus in utero. Both chromium and cobalt ions were markedly reduced in levels when transitioning from maternal to cord blood. In particular, chromium showed a greater reduction on average than cobalt (78% vs. 34%). Based on the current evidence, there appears to be no correlation between the presence of metal ions in umbilical cord blood and complications, as none of the infants experienced abnormalities uniquely attributable to the presence of metal ions.

CARDIAC FUNCTION IS COMPROMISED IN PATIENTS WITH ELEVATED BLOOD COBALT LEVELS SECONDARY TO METAL-ON-METAL HIP IMPLANTS

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.

CARDIAC FUNCTION IS COMPROMISED IN PATIENTS WITH ELEVATED BLOOD COBALT LEVELS SECONDARY TO METAL-ON-METAL HIP IMPLANTS

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.

Case-only approach applied in environmental epidemiology: 2 examples of interaction effect using the US National Health and Nutrition Examination Survey (NHANES) datasets

IntroductionBy substituting the general ‘susceptibility factor’ concept for the conventional ‘gene’ concept in the case-only approach for gene-environment interaction, the case-only approach can also be used in environmental epidemiology. Under the independence between the susceptibility factor and environmental exposure, the case-only approach can provide a more precise estimate of an interaction effect.MethodsTwo analysis examples of the case-only approach in environmental epidemiology are provided using the 2015–2016 and 2017–2018 US National Health and Nutritional Examination Survey (NHANES): (i) the negative interaction effect between blood chromium level and glycohemoglobin level on albuminuria and (ii) the positive interaction effect between blood cobalt level and old age on albuminuria. The second part of the methods (theoretical backgrounds) summarized the logic and equations provided in previous studies about the case-only approach.Results(i) When a 1 μg/L difference of both blood chromium level (mcg/L) and a 1% difference in blood glycohemoglobin level coincide, the multiplicative interaction contrast ratio (ICRc/nc) was 0.72 (95% CI 0.35–1.60), with no statistical significance. However, when only the cases were analyzed, the case-only ICR (ICRCO) was 0.59 (95% CI 0.28–0.95), with a statistical significance (a negative interaction effect). (ii) When a 1 μg/L difference of both blood cobalt levels and a 1-year difference in age coincide, the multiplicative interaction contrast ratio (ICRc/nc) was 1.13 (95% CI 0.99–1.37), with no statistical significance. However, when only the cases were analyzed, the case-only ICR (ICRCO) was 1.21 (95% CI 1.06–1.51), with a statistical significance (a positive interaction effect).DiscussionThe discussion suggested the theoretical background and previous literature about the possible protective interaction effect between blood chromium levels and blood glycohemoglobin levels on the incidence of albuminuria and the possible aggravating interaction effect between blood cobalt levels and increasing ages on the incidence of albuminuria. If the independence assumption between a susceptibility factor and environmental exposure in a study with cases and non-cases is kept, the case-only approach can provide a more precise interaction effect estimate than conventional approaches with both cases and non-cases.

The incidence of adverse local tissue reaction due to head taper corrosion after total hip arthroplasty using V40 taper and 36 mm CoCr head

Aims Head-taper corrosion is a cause of failure in total hip arthroplasty (THA). Recent reports have described an increasing number of V40 taper failures with adverse local tissue reaction (ALTR). However, the real incidence of V40 taper damage and its cause remain unknown. The aim of this study was to evaluate the long-term incidence of ALTR in a consecutive series of THAs using a V40 taper and identify potentially related factors. Methods Between January 2006 and June 2007, a total of 121 patients underwent THA using either an uncemented (Accolade I, made of Ti12Mo6Zr2Fe; Stryker, USA) or a cemented (ABG II, made of cobalt-chrome-molybdenum (CoCrMo); Stryker) femoral component, both with a V40 taper (Stryker). Uncemented acetabular components (Trident; Stryker) with crosslinked polyethylene liners and CoCr femoral heads of 36 mm diameter were used in all patients. At a mean folllow-up of 10.8 years (SD 1.1), 94 patients (79%) were eligible for follow-up (six patients had already undergone a revision, 15 had died, and six were lost to follow-up). A total of 85 THAs in 80 patients (mean age 61 years (24 to 75); 47 (56%) were female) underwent clinical and radiological evaluation, including the measurement of whole blood levels of cobalt and chrome. Metal artifact reduction sequence MRI scans of the hip were performed in 71 patients. Results A total of 20 ALTRs were identified on MRI, with an incidence of 26%. Patients with ALTR had significantly higher median Co levels compared with those without ALTR (2.96 μg/l (interquartile range (IQR) 1.35 to 4.98) vs 1.44 μg/l (IQR 0.79 to 2.5); p = 0.019). Radiological evidence of osteolysis was also significantly associated with ALTR (p = 0.014). Median Cr levels were not significantly higher in those with ALTR compared with those without one (0.97 μg/l (IQR 0.72 to 1.9) v 0.67 μg/l (IQR 0.5 to 1.19; p = 0.080). BMI, sex, age, type of femoral component, head length, the inclination of the acetabular component, and heterotopic ossification formation showed no significant relationship with ALTR. Conclusion Due to the high incidence of local ALTR in our cohort after more than ten years postoperatively, we recommend regular follow-up investigation even in asymptomatic patients with V40 taper and metal heads. As cobalt levels correlate with ALTR occurrence, routine metal ion screening and consecutive MRI investigation upon elevation could be discussed. Cite this article: Bone Joint J 2022;104-B(7):852–858.

Association of blood cobalt concentrations with dyslipidemia, hypertension, and diabetes in a US population: A cross-sectional study.

Various heavy metal elements in the human body have been reported to be associated with dyslipidemia, hypertension, and diabetes. The role of cobalt in these conditions is unclear. The current study aimed to investigate the association of blood cobalt concentrations with dyslipidemia, hypertension, and diabetes.Using the data collected from the National Health and Nutrition Examination Survey (2015-2018), we performed logistic regression to explore the association of blood cobalt concentrations with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, hypertension, and diabetes.A total of 6866 adults were included in this study. Participants with higher blood cobalt levels appeared to be older and have a lower body mass index and, were more likely to be female (P for trend < .05). After fully adjusting for demographic characteristics (Model 2), compared with the lowest quartile, the highest quartile of blood cobalt concentrations had lower odds ratios (ORs) for elevated TC [OR: 0.62, 95% confidential interval (CI): 0.53 to 0.72, P < .001], elevated LDL-C (OR: 0.65, 95% CI: 0.53-0.80, P < .001) and low HDL-C (OR: 0.81, 95% CI: 0.69-0.96, P = .013). The adjusted ORs for elevated TC, elevated LDL-C and low HDL-C were negatively correlated with increased blood cobalt concentrations (P for trend < .05). The adjusted ORs for hypertension and diabetes were not associated with blood cobalt concentrations (P > .05 and P for trend > .05).In conclusion, higher blood cobalt concentrations were associated with a lower risk of dyslipidemia. However, blood cobalt concentrations were not associated with the risk of hypertension or diabetes.

Ten-year results of a prospective cohort of large-head metal-on-metal total hip arthroplasty : a concise follow-up of a previous report.

AimsLarge-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.MethodsAll 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.ResultsMean 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.ConclusionThis 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.

Case-Only Approach Applied in Environmental Epidemiology: Two Examples of Interaction Effect Using the NHANES Dataset

BACKGROUND AND AIM: By substituting the general ‘susceptibility factor’ concept for the conventional ‘gene’ concept in the gene-environment interaction case-only approach, this study can broaden the applicability of the case-only approach to environmental epidemiology. METHODS: This study collectively summarized the logics and equations previously reported in methodology studies with a case-only approach. RESULTS:(1) When 1 unit of both blood chromium level (mcg/L) and blood glycohemoglobin level (%) increased coincidentally, the multiplicative interaction risk ratio was 0.72 (95% CI 0.47-1.05), with no statistical significance. However, when only the cases were analyzed (case-only approach), the case-only interaction odds ratio was 0.67 (95% CI 0.44-0.90), with a statistical significance (a negative interaction effect). (2) When 1 unit of both blood cobalt level (mcg/L) and age in years increased coincidentally, the multiplicative interaction risk ratio was 1.13 (95% CI 0.99-1.37), with no statistical significance. However, the case-only interaction odds ratio of 1.21 (95% CI 1.06-1.51) was calculated using the case-only approach with a fine-tuning. CONCLUSIONS:If the independence assumption between susceptibility factor and environmental exposure in the entire population is kept, this case-only approach can provide (ⅰ) a more precise interaction effect estimate or (ⅱ) a reliable interaction effect estimate when appropriate controls were not available. The two examples using the NHANES dataset must be investigated meticulously in the following studies. In summary, the case-only approach can be useful either in environmental epidemiology, not only in genetic epidemiology. KEYWORDS: Environmental epidemiology, Heavy metals

Chromium and cobalt in blood and serum in the surveillance of metal-on-metal hip implants

Objective. The aim of this study is to evaluate the relationship between serum and whole blood chromium and cobalt levels in a group of patients with metal-on metal total hip arthroplasty (Depuy ASR™). A conversion formula was developed to allow adequate evaluation of patients and correctly interpret the measured value. Methods. The authors retrospectively reviewed a series of 150 patients and prospectively analysed 64 patients who satisfied inclusion criteria. We collected data by taking simultaneously sample of chromium and cobalt ionemia from blood and serum.Results. Statistical analyses revealed significant differences between chromium and cobalt values in serum and whole blood (p 0.007), but with a strong positive correlation for both chromium (r 0.927) and cobalt (r 0.935). The authors also calculated a conversion formula to convert whole blood ion levels into serum levels, Cr se = -0.32582 + 1.39018*Cr WB for chromium and Co se = 0.239637 + 0.804279* Co WB, for cobalt. Conclusions. The difference between serum and blood values of chromium and cobalt is highlighted in a strong positive correlation. The development of the conversion formula allows to better interpret laboratory data and improve care and monitoring of patients.

Do cobalt or chromium accumulate in metal-on-metal hip arthroplasty patients who have mild, moderate, or severe renal insufficiency?

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. 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. Of the 1,244 patients, 112 had normal renal function (eGFR > 90 ml/min/1.73 m2), 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 m2 (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. 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 J2021;103-B(7):1231-1237.

Cobalt induces neurodegenerative damages through Pin1 inactivation in mice and human neuroglioma cells

Cobalt is a hazardous material that has harmful effects on neurotoxicity. Excessive exposure to cobalt or inactivation of the unique proline isomerase Pin1 contributes to age-dependent neurodegeneration. However, nothing is known about the role of Pin1 in cobalt-induced neurodegeneration. Here we find that out of several hazardous materials, only cobalt dose-dependently decreased Pin1 expression and alterations in its substrates, including cis and trans phosphorylated Tau in human neuronal cells, concomitant with neurotoxicity. Cobalt-induced neurotoxicity was aggravated by Pin1 genetic or chemical inhibition, but rescued by Pin1 upregulation. Furthermore, less than 4 μg/l of blood cobalt induced dose- and age-dependent Pin1 downregulation in murine brains, ensuing neurodegenerative changes. These defects were corroborated by changes in Pin1 substrates, including cis and trans phosphorylated Tau, amyloid precursor protein, β amyloid and GSK3β. Moreover, blood Pin1 was downregulated in human hip replacement patients with median blood cobalt level of 2.514 μg/l, which is significantly less than the safety threshold of 10 μg/l, suggesting an early role Pin1 played in neurodegenerative damages. Thus, Pin1 inactivation by cobalt contributes to age-dependent neurodegeneration, revealing that cobalt is a hazardous material triggering AD-like neurodegenerative damages.

Cobalt-induced cardiomyopathy - do circulating cobalt levels matter?

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.

Despite higher revision rate, MoM large-head THA offers better clinical scores than HR: 14-year results from a randomized controlled trial involving 48 patients

BackgroundThe high failure rates of metal on metal (MoM) large diameter head total hip arthroplasty (LDH THA) and hip resurfacing (HR) prevented their long-term comparisons with regards to clinical outcome. Such knowledge would be important as ceramic LDH bearing is now available. With long-term follow-up, we investigated the difference in 1) patient-reported outcome measures (PROMs); 2) revision and adverse events rates, and 3) metal ion levels between MoM LDH THA and HR.MethodsForty-eight patients were randomized for LDH THA (24) or HR (24) with the same MoM articulation. At a mean follow-up of 14 years, we compared between groups different PROMs, the number of revisions and adverse events, whole blood Cobalt (Co) and Chromium (Cr) ion levels, and radiographic signs of implant dysfunction.ResultsLDH THA (all cases: revised and well-functioning) had significantly better WOMAC (94 versus 85, p = 0.04), and more frequently reported having no limitation (p = 0.04). LDH THA revision rate was 20.8% (5/24) versus 8.3% (2/24) for HR (p = 0.4). Mean Co and Cr ion levels were higher in LDH THA compared to the HR (Co: 3.8 μg/L vs 1.7 μg/L; p = 0.04 and Cr: 1.9 μg/L vs 1.4 μg/L, p = 0.1). On radiographic analyses, 2 LDH THAs showed signs of adverse reaction to metal debris, whereas 1 loose femoral HR component was documented.ConclusionIn the long-term, MoM LDH THA had a high trunnion related revision rate but nonetheless showed better PROMs compared to HR. Provided with a well-functioning modular junction, non-MoM LDH THA would offer an appealing option.Trial registrationClinicalTrials.gov (NCT04516239), August 18, 2020. Retrospectively registered.