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

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


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

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


The Bone & Joint Journal
Vol. 95-B, Issue 1 | Pages 31 - 37
1 Jan 2013
Zywiel MG Brandt J Overgaard CB Cheung AC Turgeon TR Syed KA

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


The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 359 - 367
1 Mar 2022
Deere K Matharu GS Ben-Shlomo Y Wilkinson JM Blom AW Sayers A Whitehouse MR

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


The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 28 - 32
1 Jan 2018
Goodnough LH Bala A Huddleston III JI Goodman SB Maloney WJ Amanatullah DF

Aims. Many case reports and small studies have suggested that cobalt ions are a potential cause of cardiac complications, specifically cardiomyopathy, after metal-on-metal (MoM) total hip arthroplasty (THA). The impact of metal ions on the incidence of cardiac disease after MoM THA has not been evaluated in large studies. The aim of this study was to compare the rate of onset of new cardiac symptoms in patients who have undergone MoM THA with those who have undergone metal-on-polyethylene (MoP) THA. Patients and Methods. Data were extracted from the Standard Analytics Files database for patients who underwent MoM THA between 2005 and 2012. Bearing surface was selected using International Classification of Diseases ninth revision codes. Patients with a minimum five-year follow-up were selected. An age and gender-matched cohort of patients who underwent MoP THA served as a comparison group. New diagnoses of cardiac disease were collected during the follow-up period. Comorbidities and demographics were identified and routine descriptive statistics were used. Results. We identified 29 483 patients who underwent MoM THA and 24 175 matched patients who underwent MoP THA. Both groups had a mean Charlson comorbidity index score of 4. There were no statistically significant differences in 30 of 31 pre-existing comorbidities. Patients undergoing MoM THA had a slightly lower incidence of cardiac failure compared with those undergoing MoP THA at three years (6.60% versus 7.06%, odds ratio (OR) 0.93, 95% confidence interval (CI) 0.87 to 0.99) and four years (8.73% versus 9.49%, OR 0.91, 95% CI 0.86 to 0.97) postoperatively, with no difference in the incidence of new cardiac failure in between the groups at five years. There was no statistically significant difference in the incidence of arrhythmia, myocardial infarction and cardiomyopathy at any time between the two groups. Conclusion. MoM THA is not associated with cardiac complications. Initial reports may have represented individual instances of cardiac disease in patients with a failing MoM articulation rather than an emerging epidemiological trend. Cite this article: Bone Joint J 2018;100-B:28–32


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 3 | Pages 388 - 390
1 Apr 2001
Katz K Fogelman R Attias J Baron E Soudry M

We have had experience of an 18-month-old boy with a cardiomyopathy who died a few minutes after removal of his cast with a saw, apparently from a malignant cardiac arrhythmia triggered by anxiety. We therefore examined the anxiety reaction to this method of removal of a plaster cast in 20 healthy children; ten were provided with hearing protectors and ten were not. The level of anxiety was assessed by measuring the heart rate, a known physiological indicator of anxiety, before, during and five minutes after removal of the cast. The noise level was also measured. The results showed a mean increase in heart rate during the procedure of 27.9 beats per minute (bpm) (26.9%) in the children with no hearing protectors and 10.4 bpm (11.1%) in children who used hearing protectors (p < 0.001). Five minutes after the procedure the heart rate had returned to the baseline rate in all patients. We recommend that hearing protectors should be used in children undergoing removal of a plaster cast to decrease the anxiety reaction. If possible, clinicians should avoid the use of a saw for this purpose in children with a cardiomyopathy


Bone & Joint Research
Vol. 11, Issue 8 | Pages 548 - 560
17 Aug 2022
Yuan W Yang M Zhu Y

Aims

We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

Methods

Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

Aims

Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro.

Methods

MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.


Bone & Joint Open
Vol. 3, Issue 1 | Pages 85 - 92
27 Jan 2022
Loughenbury PR Tsirikos AI

The development of spinal deformity in children with underlying neurodisability can affect their ability to function and impact on their quality of life, as well as compromise provision of nursing care. Patients with neuromuscular spinal deformity are among the most challenging due to the number and complexity of medical comorbidities that increase the risk for severe intraoperative or postoperative complications. A multidisciplinary approach is mandatory at every stage to ensure that all nonoperative measures have been applied, and that the treatment goals have been clearly defined and agreed with the family. This will involve input from multiple specialities, including allied healthcare professionals, such as physiotherapists and wheelchair services. Surgery should be considered when there is significant impact on the patients’ quality of life, which is usually due to poor sitting balance, back or costo-pelvic pain, respiratory complications, or problems with self-care and feeding. Meticulous preoperative assessment is required, along with careful consideration of the nature of the deformity and the problems that it is causing. Surgery can achieve good curve correction and results in high levels of satisfaction from the patients and their caregivers. Modern modular posterior instrumentation systems allow an effective deformity correction. However, the risks of surgery remain high, and involvement of the family at all stages of decision-making is required in order to balance the risks and anticipated gains of the procedure, and to select those patients who can mostly benefit from spinal correction.


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1392 - 1399
2 Aug 2021
Kang TW Park SY Oh H Lee SH Park JH Suh SW

Aims

Open discectomy (OD) is the standard operation for lumbar disc herniation (LDH). Percutaneous endoscopic lumbar discectomy (PELD), however, has shown similar outcomes to OD and there is increasing interest in this procedure. However despite improved surgical techniques and instrumentation, reoperation and infection rates continue and are reported to be between 6% and 24% and 0.7% and 16%, respectively. The objective of this study was to compare the rate of reoperation and infection within six months of patients being treated for LDH either by OD or PELD.

Methods

In this retrospective, nationwide cohort study, the Korean National Health Insurance database from 1 January 2007 to 31 December 2018 was reviewed. Data were extracted for patients who underwent OD or PELD for LDH without a history of having undergone either procedure during the preceding year. Individual patients were followed for six months through their encrypted unique resident registration number. The primary endpoints were rates of reoperation and infection during the follow-up period. Other risk factors for reoperation and infection were also evalulated.


Bone & Joint Research
Vol. 10, Issue 6 | Pages 348 - 350
1 Jun 2021
Skinner JA Sabah SA Hart AJ


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

Aims

To find out if there is an inverse association between estimated glomerular filtration rate (eGFR) and whole blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasties and renal insufficiency, suggesting that renal insufficiency could cause accumulation of Co and Cr in blood.

Methods

Out of 2,520 patients with 3,013 MoM hip arthroplasties, we identified 1,244 patients with whole blood Co, Cr, and creatinine measured within no more than a one-year interval. We analyzed the correlation of blood metal ion levels and eGFR to identify a potential trend of accumulating Co or Cr with decreasing eGFR.


Bone & Joint Open
Vol. 2, Issue 5 | Pages 338 - 343
21 May 2021
Harvey J Varghese BJ Hahn DM

Aims

Displaced distal radius fractures were investigated at a level 1 major trauma centre during the COVID-19 2020 lockdown due to the implementation of temporary changes in practice. The primary aim was to establish if follow-up at one week in place of the 72-hour British Orthopaedic Association Standards for Trauma & Orthopaedics (BOAST) guidance was safe following manipulation under anaesthetic. A parallel adaptation during lockdown was the non-expectation of Bier’s block. The secondary aim was to compare clinical outcomes with respect to block type.

Methods

Overall, 90 patients were assessed in a cross-sectional cohort study using a mixed, retrospective-prospective approach. Consecutive sampling of 30 patients pre-lockdown (P1), 30 during lockdown (P2), and 30 during post-lockdown (P3) was applied. Type of block, operative status, follow-up, and complications were extracted. Primary endpoints were early complications (≤ one week). Secondary endpoints were later complications including malunion, delayed union or osteotomy.


Bone & Joint 360
Vol. 7, Issue 2 | Pages 12 - 15
1 Apr 2018


The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 20 - 27
1 Jan 2018
Sabah SA Moon JC Jenkins-Jones S Morgan CL Currie CJ Wilkinson JM Porter M Captur G Henckel J Chaturvedi N Kay P Skinner JA Hart AH Manisty C

Aims

The aim of this study was to determine whether patients with metal-on-metal (MoM) arthroplasties of the hip have an increased risk of cardiac failure compared with those with alternative types of arthroplasties (non-MoM).

Patients and Methods

A linkage study between the National Joint Registry, Hospital Episodes Statistics and records of the Office for National Statistics on deaths was undertaken. Patients who underwent elective total hip arthroplasty between January 2003 and December 2014 with no past history of cardiac failure were included and stratified as having either a MoM (n = 53 529) or a non-MoM (n = 482 247) arthroplasty. The primary outcome measure was the time to an admission to hospital for cardiac failure or death. Analysis was carried out using data from all patients and from those matched by propensity score.


The Bone & Joint Journal
Vol. 101-B, Issue 9 | Pages 1122 - 1128
1 Sep 2019
Yombi JC Putineanu DC Cornu O Lavand’homme P Cornette P Castanares-Zapatero D

Aims

Low haemoglobin (Hb) at admission has been identified as a risk factor for mortality for elderly patients with hip fractures in some studies. However, this remains controversial. This study aims to analyze the association between Hb level at admission and mortality in elderly patients with hip fracture undergoing surgery.

Patients and Methods

All consecutive patients (prospective database) admitted with hip fracture operated in a tertiary hospital between 2012 and 2016 were analyzed. We collected patient characteristics, time to surgery, duration and type of surgery, comorbidities, Hb at admission, nadir of Hb after surgery, the use and amount of red blood cells (RBCs) transfusion products, postoperative complications, and death. The main outcome measures were mortality at 30 days, 90 days, 180 days, and one year after surgery.


The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 1 - 3
1 Jan 2018
Skinner JA Haddad FS


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

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging.

The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation.

The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity.

This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties.

Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications.

Cite this article: Bone Joint J 2016;98-B:6–13.


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

As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 μg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity.

Take home message: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately.

Cite this article: Bone Joint J 2016;98-B:14–20.