Self-Reported Neurotoxic Symptoms in Hip Arthroplasty Patients With Highly Elevated Blood Cobalt: A Case-Control Study.

OBJECTIVES: This study aimed to investigate the prevalence of self-reported neurotoxicity and cognitive defects in hip replacement patients with markedly raised blood cobalt. METHODS: Case group comprised 53 patients with metal-on-metal (MoM) implants and a history of blood Co ≥20 µg/L for a median of 3 years (interquartile range, 2-5 years). The control group comprised 53 patients with ceramic-on-ceramic prostheses and blood Co <1 µg/L. Median age was 67 years (interquartile range, 60-74 years). The participants completed the Neurotoxic Symptom Checklist-60, Diabetic Neuropathy Score, Douleur Neuropathique-10, and Systemic Symptom Checklist, and underwent the Mini-Mental State Examination. RESULTS: The MoM and ceramic-on-ceramic groups were compared, the results were as follows: Neurotoxic Symptom Checklist-60 (median): cognitive defects (2.0 versus 1.9; P = 0.002), chest complaints (1.3 versus 1.3; P = 0.042), balance disturbances (1.3 versus 1.0; P < 0.001), sleep disturbances (2.7 versus 2.0; P = 0.004), mood disorders (2.0 versus 1.5; P = 0.001), sensorimotor disorders (1.6 versus 1.2; P < 0.001), physical complaints (2.0 versus 1.4; P = 0.009), fatigue (2.0 versus 1.6; P = 0.001), and total score (108 versus 90; P < 0.001); abnormal Diabetic Neuropathy Score/Douleur Neuropathique-10 (%): 60.3/13.2 versus 24.5/1.9 (P < 0.001/P = 0.028). Systemic Symptom Checklist (in percent): feeling cold (37.7 versus 17; P = 0.01), weight gain (18.9 versus 1.9; P = 0.008), metallic taste (26.4 versus 3.8; P = 0.002), worsening eyesight (37.7 versus 15.1; P = 0.008) and hearing (24.5 versus 7.5; 0.032), ankle swelling (32.1 versus 7.5; P = 0.002), shortness of breath on exertion (9.4 versus 5.7; P = 0.015), and generalized rash (28.3 versus 7.5; P = 0.01); and Mini-Mental State Examination (median): 29 versus 30 (P = 0.017). Patients in the MoM group were aware of their high cobalt levels and displayed a higher tendency to overreport symptoms (P < 0.001), which could have contributed to the higher scores. CONCLUSIONS: Frequency of reporting a number of symptoms was markedly higher in MoM patients, but clinically significant neurotoxicity was not observed (possibly due to the short exposure to elevated cobalt). Patients with repeated blood Co ≥20 µg/L measurements should be questioned about possible systemic health complaints at follow-up.

Blood and plasma titanium levels associated with well-functioning hip implants.

BACKGROUND: Hip implants are usually manufactured from cobalt-chromium and titanium alloys. As the implants wear and corrode, metal debris is released into the surrounding tissue and blood, providing a potential biomarker for their function. Whilst there are laboratory reference levels for blood cobalt and chromium in patients with well and poorly functioning hip implants, there are no such guidelines for titanium. This is despite the increasing use of titanium implants worldwide. PATIENTS AND METHODS: We recruited a consecutive series of 95 patients (mean age 71 years, mean time after surgery 8.5 years) with one hip implant type, inserted by the same surgeon. We assessed clinical and radiological outcome, and measured blood and plasma titanium using high resolution inductively-coupled plasma mass spectrometry. RESULTS: The upper normal reference limit for blood and plasma titanium was 2.20 and 2.56 µg L-1, respectively, and did not differ significantly between males and females. CONCLUSION: We are the first to propose a laboratory reference level for blood and plasma titanium in patients with well-functioning titanium hip implants. This is an essential starting point for further studies to explore the clinical usefulness of blood titanium as a biomarker of orthopaedic implant performance, and comes at a time of considerable controversy regarding the use of certain titanium alloys in hip arthroplasty.

Blood titanium level as a biomarker of orthopaedic implant wear.

BACKGROUND: Joint replacement implants are usually manufactured from cobalt-chromium or titanium alloys. After the device is implanted, wear and corrosion generate metal particles and ions, which are released into local tissue and blood. The metal debris can cause a range of adverse local and systemic effects in patients. RESEARCH PROBLEM: In the case of cobalt and chromium, a blood level exceeding 7 µg L-1 indicates potential for local toxicity, and a failing implant. It has been repeatedly suggested in the literature that measurement of titanium could also be used to assess implant function. Despite an increasing interest in this biomarker, and growing use of titanium in orthopaedics, it is unclear what blood concentrations should raise concerns. This is partly due to the technical challenges involved in the measurement of titanium in biological samples. AIM: This Review summarises blood/serum titanium levels associated with well-functioning and malfunctioning prostheses, so that the prospects of using titanium measurements to gain insights into implant performance can be evaluated. CONCLUSION: Due to inter-laboratory analytical differences, reliable conclusions regarding "normal" and "abnormal" titanium levels in patients with orthopaedic implants are difficult to draw. Diagnosis of symptomatic patients should be based on radiographic evidence combined with blood/serum metal levels.

Synchrotron analysis of human organ tissue exposed to implant material.

BACKGROUND: Orthopaedic implants made of cobalt-chromium alloy undergo wear and corrosion that can lead to deposition of cobalt and chromium in vital organs. Elevated cardiac tissue cobalt levels are associated with myocardial injury while chromium is a well-established genotoxin. Though metal composition of tissues surrounding hip implants has been established, few investigators attempted to characterize the metal deposits in systemic tissues of total joint arthroplasty patients. METHODS: We report the first use of micro-X-ray fluorescence coupled with micro-X-ray absorption spectroscopy to probe distribution and chemical form of cobalt, chromium and titanium in postmortem samples of splenic, hepatic and cardiac tissue of patients with metal-on-polyethylene hip implants (n = 5). RESULTS: Majority of the cobalt was in the 2+ oxidation state, while titanium was present exclusively as titanium dioxide, in either rutile or anatase crystal structure. Chromium was found in a range of forms including a highly oxidised, carcinogenic species (CrV/VI), which has never been identified in human tissue before. CONCLUSIONS: Carcinogenic forms of chromium might arise in vital organs of total joint arthroplasty patients. Further studies are warranted with patients with metal-on-metal implants, which tend to have an increased release of cobalt and chromium compared to metal-on-polyethylene hips.