Challenges in the Measurement and Interpretation of Serum Titanium Concentrations

Yao, Jie; Lewallen, Eric A.; Thaler, Roman; Dudakovic, Amel; Wermers, Michelle; Day, Patrick L.; Eckdahl, Steve; Jannetto, Paul J.; Bornhorst, Joshua A.; Larson, A. Noelle; Abdel, Matthew P.; Lewallen, David G.; Wijnen, André J. van

doi:10.1007/s12011-019-01891-4

Cited by 13 publications

(5 citation statements)

References 29 publications

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“…Our assessment of Ti concentrations using ICP-MS rather than inductively coupled plasma-optical emission spectroscopy (ICP-OES) is in accordance with current recommendations [29]. Our data description uses medians and statistical inference is based on non-parametric methods, which also complies with recommendations on the interpretation of Ti measurements that are referred to above.…”

Section: Strengths and Weaknesses Of This Studysupporting

confidence: 53%

Concentrations of Cobalt, Chromium and Titanium and Immunological Changes after Primary Total Knee Arthroplasty—A Cohort Study with an 18-Year Follow-Up

Brüggemann,

Hailer

2024

JCM

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Background: Total knee arthroplasty (TKA) generates elevated metal ion concentrations, but long-term changes in the concentrations of cobalt (Co), chromium (Cr) and titanium (Ti) after primary TKA and potential subsequent immune system activation—not limited to the joint but systemically—are not known. Patients and Methods: We conducted a cohort study on 26 patients with TKA (19 women; 16 with metal-backed and 10 with all-polyethylene tibial components) 18.3 years (min. 16.7, max. 20.5) after index TKA. A total of 69% of patients additionally underwent subsequent arthroplasty of the contralateral knee or either hip after the index surgery. Blood samples were analysed by inductively coupled plasma–mass spectrometry, and leukocytes were characterised by flow cytometry. Patients were clinically assessed using the Knee Society score and by plain radiography of the knee. Results: The median metal ion concentrations were 0.7 (0.1–13.0) µg/L for Co, 0.9 (0.4–5.0) µg/L for Cr, and 1.0 (0.2–13.0) µg/L for Ti. There was no relevant difference in systemic metal ion concentrations between patients exposed to single and multiple arthroplasties. The absolute count and proportion of CD3+CD4+CD8+ T cells was inversely correlated with both Co (rho −0.55, p = 0.003) and Cr concentrations (rho −0.59, p = 0.001). Conclusions: Between the first and second decades after primary TKA, in most patients, the concentrations of Co, Cr and Ti in blood samples were below the thresholds that are considered alarming. The negative correlation of Co and Cr concentrations with a subset of lymphocytes that commonly increases during immune activation is reassuring. This represents a worst-case scenario, underscoring that the investigated metal ions remain within reasonable ranges, even after additional hardware exposure.

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Section: Strengths and Weaknesses Of This Studysupporting

confidence: 53%

Concentrations of Cobalt, Chromium and Titanium and Immunological Changes after Primary Total Knee Arthroplasty—A Cohort Study with an 18-Year Follow-Up

Brüggemann,

Hailer

2024

JCM

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“…In this longitudinal study, at T0, the mean serum level of titanium observed were higher than the reference range set by mayo laboratories (< than 1 ng/L). 33 However actual numerical values cannot be compared because of differences in metallurgy, methods of analysis, and measurement units. The reasons for raised values may be attributed to dietary supplements, cosmetics, environment, water contamination due to industrial wastes, and occupation.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal surveillance of serum titanium ion levels in patients with indigenous 3D printed total temporomandibular joint replacement

Khandelwal

Roychoudhury

Bhutia

et al. 2022

Preprint

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Objective: The purpose of this longitudinal study was to surveil the serum titanium ion levels at various time intervals in patients with indigenous 3D-printed total temporomandibular joint replacement (TMJ TJR). Study design: The study was conducted on 11 patients (male: 8; female: 3) who had undergone unilateral or bilateral TMJ TJR. Blood samples were drawn preoperatively (T0), 3 months (T1), 6 months (T2), and 1 year (T3) postoperatively. Data were analyzed and a p value of <0.05 was considered statistically significant. Results: The mean serum titanium ion levels at T0, T1, T2, and T3 was 9.34 ± 8.70 microgram/L (mcg/L), 35.97 ± 20.27 mcg/L, 31.68 ± 17.03 mcg/L, and 47.91 ± 15.47 mcg/L respectively. The mean serum titanium ion levels increased significantly at T1 (p= 0.009), T2 (p= 0.032), and T3 (p=0.00) interval. There was no significant difference between unilateral and bilateral groups. Conclusion: Serum titanium ion continued to show increased levels till the last follow-up of 1 year. These initial serum titanium ion levels increase is due to the initial wear phase of the prosthesis which manifests over 1 year. Further studies with large sample sizes and long-term follow-ups are required to see the deleterious effect if any on the TMJ TJR.

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“…All patients provided consent to participate and had a blood draw (60 mL) for measurement of chromium, cobalt, titanium concentrations, inflammatory markers (C reactive protein [CRP], interleukin 6 [IL 6] and tumor necrosis factor alpha [TNF]) and systemic distribution of immune cells. Metal concentrations were assayed using inductively-coupled plasma mass spectrometry (ICP-MS) within an International Organization for Standardization Class-7 cleanroom in the Metals Laboratory ( 9 , 10 ). Whole blood cobalt and chromium concentrations were measured using ICP-MS. Serum titanium was measured using Triple-Quadrupole ICP-MS.…”

Section: Methodsmentioning

confidence: 99%

Cross-sectional association between systemic metal concentrations and immune markers in patients with total joint arthroplasty

et al. 2023

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Total joint arthroplasty (TJA) implants are composed of metal components. Although they are regarded safe, the long-term immunological effects of chronic exposure to the specific implant materials are unknown. We recruited 115 hip and/or knee TJA patients (mean age 68 years) who provided a blood draw for measurement of chromium, cobalt, titanium concentrations, inflammatory markers and systemic distribution of immune cells. We examined differences between the immune markers and the systemic concentrations of chromium, cobalt and titanium. CD66-b neutrophils, early natural killer cells (NK), and eosinophils were present in higher percentages in patients with chromium and cobalt concentrations greater than the median. The opposite pattern was observed with titanium where the percentages of CD66-b neutrophils, early NK, and eosinophils were higher in patients with undetectable titanium. Cobalt concentrations were positively correlated with a higher percentage of gamma delta T cells. Both chromium and cobalt concentrations were positively correlated with higher percentages of plasmablasts. Titanium concentrations were positively correlated with higher CD4 effector memory T cells, regulatory T cell count and Th1 CD4 helper cells. In this exploratory study, we observed altered distribution of immune cells in TJA patients with elevated systemic metal concentrations. Although these correlations were not strong, these exploratory findings warrant further investigation into the role of increased metals circulating in blood and its role in immune modulation.

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Challenges in the Measurement and Interpretation of Serum Titanium Concentrations

Cited by 13 publications

References 29 publications

Concentrations of Cobalt, Chromium and Titanium and Immunological Changes after Primary Total Knee Arthroplasty—A Cohort Study with an 18-Year Follow-Up

Concentrations of Cobalt, Chromium and Titanium and Immunological Changes after Primary Total Knee Arthroplasty—A Cohort Study with an 18-Year Follow-Up

Longitudinal surveillance of serum titanium ion levels in patients with indigenous 3D printed total temporomandibular joint replacement

Cross-sectional association between systemic metal concentrations and immune markers in patients with total joint arthroplasty

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