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

doi:10.1016/j.jtemb.2019.09.005

Journal of Trace Elements in Medicine and Biology

Volume 57, January 2020, Pages 9-17

https://doi.org/10.1016/j.jtemb.2019.09.005 Get rights and content

Highlights

•
Reference range for blood/plasma Ti in patients with well-functioning THA defined.
•
Blood Ti level not influenced by gender, age or activity level.
•
Blood and plasma Ti concentrations positively correlated.

Abstract

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.

Graphical abstract

Introduction

Components of joint replacements are usually manufactured from cobalt-chromium (Co-Cr) or titanium (Ti) alloys. Once implanted, all metals degrade through wear and corrosion, releasing ions and particles into the surrounding tissue and bloodstream. The greatest wear usually occurs during the first 1–2 years after surgery [1], which is followed by a low, but steady, rate of wear over subsequent years. The amount of metal debris released is a surrogate marker of implant wear [2], and can inform on the risk of local adverse effects and need for a revision surgery.

In the case of cobalt and chromium, a blood level of 2 μg L⁻¹ implies a well-functioning metal-on-metal hip implant, while concentrations exceeding 7 μg L⁻¹ indicate potential for local tissue damage and a failing implant [3]. It is now believed that measurement of titanium could also be used to gain insights into implant performance [[4], [5], [6], [7]], though “normal” and “abnormal” blood levels have not been established. This is partly due to the technical challenges involved in the measurement of titanium in biological samples. Traditional techniques, such as graphite furnace atomic absorption spectroscopy (GF AAS) and quadrupole inductively-coupled plasma mass spectrometry, suffer from a range of interferences, which can lead to overestimation of analyte concentration. Several groups have reported blood/serum titanium levels associated with different types of well-functioning and malfunctioning prostheses [8]. However, in addition to unreliable analytical techniques used, majority of the studies suffered from small sample size.

We present a series of 95 patients with well-functioning, unilateral hip implants inserted by the same surgeon. We used a high resolution inductively-coupled plasma mass spectrometer (HR ICP-MS) to investigate how much titanium is released by the implants at medium-to-long term follow up (when the wear rate is thought to have normalised), and established a normal reference range for blood/plasma titanium in this population.

As uncemented hip replacements and 3D-printed implants are gaining popularity, the use of titanium in orthopaedics is growing. Additionally, constant ageing of the population means that the overall demand for total joint replacements is on the rise [9]. Taken together, these points underscore the potential impact of the present study. The proposed guidelines could be a useful tool to assess patients with titanium-based implants, and help predict which might develop clinical problems.

Section snippets

Patients and methods

This study protocol was approved by our institutional review board after ethical approval by Riverside Research Ethics Committee (ref. 07/Q0401/25).

All patients who received one type of titanium alloy femoral stem (see below for details) between 2007–2014 at a participating institution were identified using the National Joint Registry database (N = 1036). Inclusion criteria stipulated unilateral, primary, uncemented ceramic-on-ceramic (CoC) hip implants inserted by the same surgeon. All

Results

The demographic data and study results are summarised in Table 1.

Discussion and conclusions

This study proposes laboratory threshold values for blood (2.20 μg L⁻¹) and plasma (2.56 μg L⁻¹) titanium in patients with well-functioning titanium hip implants at medium-to-long term follow up. These guidelines are an essential starting point for further studies to explore the clinical usefulness of blood titanium as a biomarker of orthopaedic implant performance, and come at a time of considerable controversy regarding the use of certain titanium alloys in hip arthroplasty.

Compared to cobalt

Funding

This work was supported by Gwen Fish Orthopaedic Trust, Norwich, UK and The Horder Centre, Crowborough, UK. The funding sources did not have involvement in the analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication.

Declaration of Competing Interest

None that hold relevance to the manuscript.

Acknowledgments

The authors would like to thank The Horder Centre for their invaluable support and assistance, with a special thank you to the radiology and phlebotomy teams, and Ms Tracy Young.

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La « trunnionite » de la prothèse totale de la hanche (PTH) avec couple métal sur métal avec tête de grand diamètre (TGD) a été liée à des taux systémiques élevés d’ions chrome (Cr) et cobalt (Co) et à des réactions indésirables aux débris métalliques (RIDM). L’innocuité de la PTH composée d' une TGD, d’un couple céramique (CoC) et une tige fémorale en titane (Ti) n’est pas encore validée à moyen terme. Cette étude avait pour but de déterminer : 1) si le taux sanguin d’ions Ti des patients porteurs d’une PTH TGD CoC après un minimum de 5 ans de suivi se situe dans les valeurs attendues pour une PTH en Ti similaire, 2) si le taux de Ti augmente significativement dans le temps ; ce qui suggérerait un usure de la jonction modulaire tête-col, 3) si des manifestations cliniques ou radiographiques de dysfonctionnement de l’implant sont présentes.
Les taux sanguins de Ti d’une PTH TGD CoC reflètent indirectement la corrosion passive des implants et sont stables dans le temps.
Nous rapportons les taux sanguins de Ti, Cr et Co à 5 ans minimum de 57 patients ayant une PTH TGD CoC primaire unilatérale avec des tailles de tête allant de 36 à 48 mm et une tige fémorale ainsi qu’un composant acétabulaire en Ti. Chez 25 patients, une mesure antérieure (1–3 ans) du taux d’ions Ti était disponible et fut comparée à leurs derniers résultats de suivi (> 5 ans) afin de détecter une éventuelle modification dans le temps. Il est admis que le taux moyen de Ti dans les PTHs en Ti asymptomatiques est d’environ 2,0 μg/L et nous avons établi un seuil de sécurité à 10 μg/L.
Au suivi moyen de 79 mois, le taux moyen de Ti était de 1,9 μg/L (1,2–4,4) et tous les sujets avaient des valeurs inférieures au seuil de sécurité de 10 μg/L. Dans le sous-groupe de 25 cas ayant fait l’objet d’une mesure antérieure, nous avons constaté une diminution des taux moyens de Ti entre 20 mois et 78 mois de suivi (2,2 μg/L [1,6–3,9] contre 2,0 μg/L [1,4–2,8], p = 0,007). Au dernier recul, aucune relation statistiquement significative n’a été observée entre le taux de Ti et le diamètre du couple de frottement (ρ = 0,046, p = 0,0734) ou la présence ou non d’un manchon adaptateur en Ti (p = 0,454) : 1,94 μg/L (1,20–2,80) avec, contre 1,90 μg/L (1,20–4,40) sans. Au dernier suivi, aucun patient n’a présenté de signe d’ostéolyse radiographique, ni de signe de RIDM ou n’a été réopéré. La plupart des patients présentaient des résultats cliniques excellents, 98 % d’entre eux ayant signalé une limitation fonctionnelle mineure (29 %) ou nulle (69 %) et 44 % percevaientt leur PTH comme une articulation naturelle. Trois patients (3/57, 5 %) ont présenté un grincement temporaire et 18/57 (31 %) ont signalé un cliquetis.
Avec la PTH TGD CoC testée, les taux de Ti sanguins étaient faibles et secondaires à la corrosion passive inévitable et sans issue des surfaces de l’implant. La mesure à moyen terme du Ti chez les sujets porteurs d’une PTH TGD CoC n’a révélé aucun signe indirect de « trunnionite ».
IV, étude rétrospective.

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

Highlights

Abstract

Background

Patients and methods

Results

Conclusion

Graphical abstract

Introduction

Section snippets

Patients and methods

Results

Discussion and conclusions

Funding

Declaration of Competing Interest

Acknowledgments

J. Arthroplasty

J. Arthroplasty

J. Trace Elem. Med. Biol.

J. Arthroplasty

J. Arthroplasty

J. Arthroplasty

Acta Biomater.

J. Arthroplasty

J. Arthroplasty

J. Trace Elem. Med. Biol.

J. Arthroplasty

In vitro analyses of the toxicity, immunological, and gene expression effects of cobalt-chromium alloy wear debris and Co ions derived from metal-on-metal hip implants

Lubricants

Clinical usefulness of blood metal measurements to assess the failure of metal-on-metal hip implants

Ann. Clin. Biochem.

Sensitivity and specificity of blood cobalt and chromium metal ions for predicting failure of metal-on-metal hip replacement

Bone Jt. J.

Elevated serum titanium level as a marker for failure in a titanium modular fluted tapered stem

Orthopedics

Dissemination of wear particles to the liver, spleen, and abdominal lymph nodes of patients with hip or knee replacement

J. Bone Jt. Surg. Am.

Future young patient demand for primary and revision joint replacement: national projections from 2010 to 2030

Clin. Orthop. Relat. Res.

Head taper corrosion causing head bottoming out and consecutive gross stem taper failure in total hip arthroplasty

J. Arthroplasty

Catastrophic femoral neck failure after THA with the Accolade® I stem in three patients

Clin. Orthop. Relat. Res.

Do ceramic femoral heads reduce taper fretting corrosion in hip arthroplasty? A retrieval study

Clin. Orthop. Relat. Res.

Metal ion release from bearing wear and corrosion with 28 mm and large-diameter metal-on-metal bearing articulations: a follow-up study

J. Bone Jt. Surg.-Br.

The Fitness for Purpose of Analytical Methods a Laboratory Guide to Method Validation and Related Topics