Abstract
The measurement of circulating metal ion levels in total hip arthroplasty patients continues to be an area of clinical interest. National regulatory agencies have recommended measurement of circulating cobalt and chromium concentrations in metal-on-metal bearing symptomatic total hip arthroplasty patients. However, the clinical utility of serum titanium (Ti) measurements is less understood due to wide variations in reported values and methodology. Fine-scale instrumentation for detecting in situ Ti levels continues to improve and has transitioned from graphite furnace atomic absorption spectroscopy to inductively coupled plasma optical emission spectrometry or inductively coupled plasma mass spectrometry. Additionally, analytical interferences, variable sample types, and non-standardized sample collection methods complicate Ti measurement and underlie the wide variation in reported levels. Normal reference ranges and pathologic ranges for Ti levels remain to be established quantitatively. However, before these ranges can be recognized and implemented, methodological standardization is necessary. This paper aims to provide background and recommendations regarding the complexities of measurement and interpretation of circulating Ti levels in total hip arthroplasty patients.
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References
Tanne JH (2013) FDA warns about metal-on-metal hip replacements. BMJ 346:f429 https://www.bmj.com/content/bmj/346/bmj.f429.full.pdf
Rasquinha VJ, Ranawat CS, Weiskopf J, Rodriguez JA, Skipor AK, Jacobs JJ (2006) Serum metal levels and bearing surfaces in total hip arthroplasty. J Arthroplast 21(6 Suppl 2):47–52
Medicines and Health Products Regulatory Agency (2017) Appendix: management recommendations for patients with metal-on-metal hip replacement implants 2012. Available from: https://assets.publishing.service.gov.uk/media/5485abf6ed915d4c10000273/con155767.pdf
Scientific Committee on Emerging Newly Identified Health Risks (2014) Opinion on: The safety of metal-on-metal joint replacements with a particular focus on hip implants
Levine BR, Hsu AR, Skipor AK, Hallab NJ, Paprosky WG, Galante JO, Jacobs JJ (2013) Ten-year outcome of serum metal ion levels after primary total hip arthroplasty: a concise follow-up of a previous report*. J Bone Joint Surg Am 95(6):512–518
Salib CG, Lewallen EA, Paradise CR, Tibbo ME, Robin JX, Trousdale WH, Morrey LM, Xiao J, Turner TW, Limberg AK, Jay AG, Thaler R, Dudakovic A, Sanchez-Sotelo J, Morrey ME, Berry DJ, Lewallen DG, van Wijnen AJ, Abdel MP (2018) Molecular pathology of adverse local tissue reaction caused by metal-on-metal implants defined by RNA-seq. Genomics
Lewallen EA et al (2016) Osteogenic potential of human adipose-tissue-derived mesenchymal stromal cells cultured on 3D-printed porous structured titanium. Gene 581(2):95–106
Yao JJ et al (2017) Local cellular responses to titanium dioxide from orthopedic implants. Bioresearch Open Access 6(1):94–103
Lewallen EA et al (2015) Biological strategies for improved osseointegration and osteoinduction of porous metal orthopedic implants. Tissue Eng Part B Rev 21(2):218–230
Laurencon J et al (2016) Systemic metal ion levels in patients with modular-neck stems: a prospective cohort study. J Arthroplast 31(8):1750–1755
Jacobs JJ et al (2003) Metal degradation products: a cause for concern in metal-metal bearings? Clin Orthop Relat Res 417:139–147
Cundy WJ, Mascarenhas AR, Antoniou G, Freeman BJ, Cundy PJ (2015) Local and systemic metal ion release occurs intraoperatively during correction and instrumented spinal fusion for scoliosis. J Child Orthop 9(1):39–43. https://doi.org/10.1007/s11832-015-0631-6
Cundy TP, Cundy WJ, Antoniou G, Sutherland LM, Freeman BJ, Cundy PJ (2014) Serum titanium, niobium and aluminium levels two years following instrumented spinal fusion in children: does implant surface area predict serum metal ion levels? Eur Spine J 23(11):2393–2400
Cundy TP, Antoniou G, Sutherland LM, Freeman BJ, Cundy PJ (2013) Serum titanium, niobium, and aluminum levels after instrumented spinal arthrodesis in children. Spine (Phila Pa 1976) 38(7):564–570. https://doi.org/10.1097/BRS.0b013e3182741961
Balcaen L, Bolea-Fernandez E, Resano M, Vanhaecke F (2014) Accurate determination of ultra-trace levels of Ti in blood serum using ICP-MS/MS. Anal Chim Acta 809:1–8
Golasik M, Herman M, Jasiewicz B, Tęsiorowski M, Piekoszewski W (2014) Development of a method for the determination of titanium in tissue by graphite furnace atomic absorption spectrometry for clinical analysis. J Anal At Spectrom 29(10):1844–1849
United States Environmental Protection Agency (1978) Method 283.2: titanium (atomic absorption, furnace technique), U.S.E.P. Agency, Editor
Sorlie TM, Wibetoe G (2003) Determination of titanium by slurry sampling graphite furnace atomic absorption spectrometry with the use of fluoride modifiers. Anal Bioanal Chem 376(5):721–727
Slavin W, Manning DC, Carnrick GR (1981) Effect of graphite-furnace substrate materials on analyses by furnace atomic-absorption spectrometry. Anal Chem 53(9):1505–1509
Boss CB, Fredeen KJ (1999) Concepts, instrumentation and techniques in inductively coupled plasma optical emission spectrometry. Perkin Elmer, Norwalk
Einhauser TJ, Pieper TG, Keppler BK (1998) Titanium determination in human blood plasma by ICP-OES, longitudinally, and transversally heated Zeeman ETAAS. J Anal At Spectrom 13(10):1173–1176
Harrington CF, McKibbin C, Rahanu M, Langton D, Taylor A (2017) Measurement of titanium in hip-replacement patients by inductively coupled plasma optical emission spectroscopy. Ann Clin Biochem 54(3):362–369
Tatro ME, Amarasiriwardena D (2006) Optical emission inductively coupled plasma in environmental analysis. In: Meyers RA (ed) Encyclopedia of analytical chemistry. Wiley, Chichester
May TW, Wiedmeyer RH (1998) A table of polyatomic interferences in ICP-MS. At Spectrosc 19(5):150–155
MacDonald SJ, Brodner W, Jacobs JJ (2004) A consensus paper on metal ions in metal-on-metal hip arthroplasties. J Arthroplast 19(8 Suppl 3):12–16
Haddam N, Samira S, Dumont X, Taleb A, Lison D, Haufroid V, Bernard A (2011) Confounders in the assessment of the renal effects associated with low-level urinary cadmium: an analysis in industrial workers. Environ Health 10:37
McGuire BB, Bhanji Y, Sharma V, Frainey BT, McClean M, Dong C, Rimar K, Perry KT, Nadler RB (2015) Predicting patients with inadequate 24- or 48-hour urine collections at time of metabolic stone evaluation. J Endourol 29(6):730–735
Hallab NJ, Jacobs JJ, Skipor A, Black J, Mikecz K, Galante JO (2000) Systemic metal-protein binding associated with total joint replacement arthroplasty. J Biomed Mater Res 49(3):353–361
Engh CA Jr, MacDonald SJ, Sritulanondha S, Thompson A, Naudie D, Engh CA (2009) 2008 John Charnley award: metal ion levels after metal-on-metal total hip arthroplasty: a randomized trial. Clin Orthop Relat Res 467(1):101–111
American conference of governmental industrial hygienists. Committee on Industrial Ventilation, Industrial ventilation. Committee on Industrial Ventilation: Lansing, Mich. p volumes
Hawley GG, Lewis RJ (2002) Hawley’s condensed chemical dictionary, 14th edn. Wiley, New York xiii, 1223 p
International Agency for Research on Cancer and IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1988) IARC monographs on the evaluation of carcinogenic risks to humans. IARC: distributed for the International Agency for Research on Cancer by the secretariat of the World Health Organization: Lyon, France. p volumes
CDC (2011) Current intelligence bulletin 63: occupation exposure to titanium dioxide. D.o.H.a.H. Services, Editor
CLSI (1997) Control of preanalytical variation in trace element determinations; approved guideline. CLSI document C38-A. Clinical and Laboratory Standards Institute
Daniel J, Holland J, Quigley L, Sprague S, Bhandari M (2012) Pseudotumors associated with total hip arthroplasty. J Bone Joint Surg Am 94(1):86–93
Berry DJ et al (2014) What are the current clinical issues in wear and tribocorrosion? Clin Orthop Relat Res 472(12):3659–3664
Allen LA, Ambardekar AV, Devaraj KM, Maleszewski JJ, Wolfel EE (2014) Clinical problem-solving. Missing elements of the history. N Engl J Med 370(6):559–566
Gilbert CJ et al (2013) Hip pain and heart failure: the missing link. Can J Cardiol 29(5):639 e1–639 e2
Oldenburg M, Wegner R, Baur X (2009) Severe cobalt intoxication due to prosthesis wear in repeated total hip arthroplasty. J Arthroplast 24(5):825 e15–825 e20
Tower SS (2010) Arthroprosthetic cobaltism: neurological and cardiac manifestations in two patients with metal-on-metal arthroplasty: a case report. J Bone Joint Surg Am 92(17):2847–2851
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Eric A. Lewallen PhD reports grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, during the conduct of the study. Matthew P. Abdel MD reports personal fees from Stryker, outside the submitted work. Also outside the submitted work, David G. Lewallen MD reports personal fees from Zimmer Biomet, Link, Mako/Stryker, AJRR, Zimmer Biomet, and Pipeline, as well as other interests with Ketai Medical Devices, Accuitive, and Mako/Stryker. Additionally, David G. Lewallen MD reports grants from Corin.
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Yao, J.J., Lewallen, E.A., Thaler, R. et al. Challenges in the Measurement and Interpretation of Serum Titanium Concentrations. Biol Trace Elem Res 196, 20–26 (2020). https://doi.org/10.1007/s12011-019-01891-4
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DOI: https://doi.org/10.1007/s12011-019-01891-4