Abstract
Safety concerns regarding cobalt-containing metal alloy hip prosthetics (Co-HP) have resulted in product recalls, a medical device alert, and issuance of guidance for clinicians. Recently, cases of suspected prosthetic hip-associated cobalt toxicity (PHACT) from Co-HP have been reported. Although little is known about suspected PHACT, these patients may be referred to medical toxicologists for evaluation and management recommendations. We searched MEDLINE, EMBASE, and unpublished abstracts from toxicology scientific meetings for references relevant to PHACT. Authors independently screened publications for inclusion criteria: publication in English, human study population, subject(s) are symptomatic (except for isolated hip pain), and cobalt values in any matrix (blood, serum, urine, CSF, synovial fluid) available for review. Data from 10 cases are reviewed. Patients with suspected PHACT had findings consistent with cobalt toxicity, including thyroid, cardiac, and neurologic dysfunction. Signs and symptoms appeared between 3 and 72 months after arthroplasty (median 19 months). Neurologic symptoms were most common. Ancillary testing varied considerably. All patients had elevated cobalt levels in one or more matrices. Enhanced elimination was attempted in 27 % of patients. At this time, the information currently available regarding patients with suspected PHACT is inadequate to guide clinical decision making. No consensus has been reached regarding the management of Co-HP patients with systemic symptoms. Indications for chelation have not been established and require further study. Improved case definitions, improved surveillance, and controlled studies are needed to elucidate the scope of this problem and guide future investigations.
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References
The United Kingdom Medicines and Healthcare Products Regulatory Agency (2012) Medical device alert: metal-on-metal (MoM) total hip replacements. Ref: MDA/2012/016. Issued 02 April 2012. http://mhra.gov.uk/publications/safetywarnings/ medicaldevicealerts/CON79157. Accessed 11 July 2012
The United States Food and Drug Administration (2013) Information for orthopaedic surgeons. Released January 17, 2013. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/MetalonMetalHipImplants/ucm241667.htm#3a. Accessed 17 Jan 2013
The United States Food and Drug Administration (2013) Information on soft tissue imaging and metal ion testing. Released January 17, 2013. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/MetalonMetalHipImplants/ucm331971.htm#metal. Accessed 17 Jan 2013
The United States Food and Drug Administration (2013) Information for all health care professionals who provide treatment to patients with a metal-on-metal hip implant. Released January 17, 2013. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/MetalonMetalHipImplants/ucm241744.htm. Accessed 17 Jan 2013
Steens W, Von Foerster G, Katzer A (2006) Severe cobalt poisoning with loss of sight after ceramic-metal pairing in a hip—a case report. Acta Orthop 77(5):830–832
Oldenburg M, Wegner R, Baur X (2009) Severe cobalt intoxication due to prosthesis wear in repeated total hip arthroplasty. J Arthroplast 24(5):e15–e20
Rizzetti MC, Liberini P, Zarattini G, Catalani S, Pazzaglia U, Apostoli P, Padovani A (2009) Loss of sight and sound. Could it be the hip? Lancet 373(9668):1052
Ikeda T, Takahasi K, Kabata T, Sakagoshi D, Tomita K, Yamada M (2010) Polyneuropathy caused by cobalt–chromium metallosis after total hip replacement. Muscle Nerve 42:140–143
Tower SS (2010) Arthroprosthetic cobaltism: neurological and cardiac manifestations in two patients with metal-on-metal arthroplasty: a case report. J Bone Joint Surg 92(17):2847–2851
Mao X, Wong AA, Crawford RW (2011) Cobalt toxicity—an emerging clinical problem in patients with metal-on-metal hip prostheses? Med J Aust 194(12):649–651
Pazzaglia UE, Apostoli P, Congiu T, Catalani S, Marchese M, Zarattini G (2011) Cobalt, chromium, and molybdenum ion kinetics in the human body: data gained from a total hip replacement with massive third body wear of the head and neuropathy by cobalt intoxication. Arch Orthop Trauma Surg 131:1299–1308
Pelclova D, Sklensky M, Janicek P, Lach K (2012) Severe cobalt intoxication following hip replacement revision: clinical features and outcome. Clin Toxicol 50:262–265
Machado C, Appelbe A, Wood R (2012) Arthroprosthetic cobaltism and cardiomyopathy. Heart Lung Circ 21(11):759–760
Loke YK, Price D, Herxheimer A (2007) Systematic reviews of adverse effects: framework for a structured approach. BMC Med Res Method 7(32):1–9
Lantin AC, Mallants A, Vereulen J, Speybroeck N, Hoet P, Lison D (2011) Absence of adverse effect on thyroid function and red blood cells in a population of workers exposed to cobalt compounds. Toxicol Lett 201(1):42–46
Kriss JP, Carnes WH, Gross RT (1955) Hypothyroidism and thyroid hyperplasia in patients treated with cobalt. JAMA 157(2):117–121
Christensen JM, Poulsen OM (1994) A 1982–1992 surveillance programme on Danish pottery painters. Biological levels and health effects following exposure to soluble or insoluble cobalt compounds in cobalt dyes. Sci Total Environ 150(1–3):95–104
Morin Y, Daniel P (1967) Quebec beer-drinkers' cardiomyopathy: etiological considerations. Can Med Assoc J 97:926–928
McDermott PH, Delaney RL, Egan JD, Sullivan JF (1966) Myocardosis and cardiac failure in men. JAMA 198(3):163–166
Linna A, Oksa P, Groundstroem K, Halkosaari M, Palmroos P, Huikko S, Uitti J (2004) Exposure to cobalt in the production of cobalt and cobalt compounds and its effect on the heart. Occup Environ Med 61:877–885
Baborik M, Dusek J (1972) Cardiomyopathy accompanying industrial cobalt exposure. Br Heart J 34(1):113–116
Jarvis JQ, Hammond E, Meier R, Robinson C (1992) Cobalt cardiomyopathy: a report of two cases from mineral assay laboratories and a review of the literature. J Occup Med 34(6):620–626
Kennedy A, Dornan JD, King R (1981) Fatal myocardial disease associated with industrial exposure to cobalt. Lancet 1(8217):412–414
Bowie EA, Hurley PJ (1975) Cobalt chloride in the treatment of refractory anaemia in patients undergoing long-term hemodialysis. Aust NZ J Med 5:306–314
Licht A, Oliver M, Rachmilewitz EA (1972) Optic atrophy following treatment with cobalt chloride in a patient with pancytopenia and hypercellular marrow. Isr J Med Sci 8:61–66
Schirrmacher UOE (1967) Case of cobalt poisoning. Br Med J 1:544–545
Catalani S, Rizzetti MC, Padovani A, Apostoli P (2011) Neurotoxicity of cobalt. Hum Exp Toxicol 1:1–17
Barceloux DG (1999) Cobalt. Clin Toxicol 37(2):201–216
Seghizzi P, D'Adda F, Borleri D, Barbic F, Mosconi (1994) Cobalt myocardiopathy. A critical review of literature. Sci Total Environ 150:105–109
Holly RG (1955) Studies on iron and cobalt metabolism. JAMA 158(15):1349–1352
Evans EM, Freeman MAR, Miller AJ, Vernon-Roberts BV (1974) Metal sensitivity as a cause of bone necrosis and loosening of the prosthesis in total joint replacement. J Bone Joint Surg 56(4):626–642
Jones DA, Lucas HK, O'Driscoll M, Price CHG, Wibberly B (1975) Cobalt toxicity after McKee hip arthroplasty. J Bone Joint Surg 57(3):289–296
Polyzois I, Nikolopoulos D, Michos I, Patsouris E, Theocharis S (2012) Local and systemic toxicity of nanoscale debris particles in total hip arthroplasty. J App Toxicol 32:255–26940
Alexanderssen R (1988) Blood and urinary concentrations as estimators of cobalt exposure. Acrh Environ Health 43(4):29–303
Devitt BM, Queally JM, Vioreanu M, Butler JS, Murray D, Doran P, O'Byrne JM (2010) Cobalt ions induce chemokine secretion in a variety of systemic cell lines. Acta Orthop 81(6):756–764
Simonsen LO, Harbak H, Bennejou P (2012) Cobalt metabolism and toxicology—a brief update. Sci Total Environ 432:210–215
Howie DW, Rogers SD, McGee MA, Haynes DDR (1996) Biological effects of cobalt chrome in cell and animal models. Clin Orthop Relat Res 329s:s217–s232
Kwon Y, Xia Z, Glyn-Jones S, Beard D, Gill HS, Murray DW (2009) Dose-dependent cytotoxicity of clinically relevant cobalt nanoparticles and ions on macrophages in vitro. Biomed Mater 4:1–8
Hallab N, Merritt K, Jacobs J (2001) Metal sensitivity in patients with orthopaedic implants. J Bone Joint Surg 83(3):428–436
Witzleb WC, Ziegler J, Krummenauer F, Neumeiste V, Guenther KP (2006) Exposure to chromium, cobalt and molybdenum from metal-on-metal total hip replacement and hip resurfacing arthroplasty. Acta Orthop 77(5):697–705
Macnair RD, Wynn-Jones H, Wimhurst JA, Toms A, Cahir J (2012) Metal ion levels not sufficient as a screening measure for adverse reactions in metal-on-metal hip arthroplasties. J Arthroplasty 28(1):78–83
Smolders JMH, Bisseling P, Hol A, Van Der Straeten C, Schreurs BW, van Susante JLC (2011) Metal ion interpretation in resurfacing versus conventional hip arthroplasty and in whole blood versus serum. How should we interpret metal ion data? Hip Int 21(5):587–595
Kwon Y, Ostlere SJ, McLardy-Smith P, Athanasou NA, Gill HS, Murray DW (2011) “Asymptomatic” pseudotumors after metal-on-metal hip resurfacing arthroplasty. J Arthroplasty 26(4):511–518
Alexandersson R (1988) Blood and urinary concentrations as estimators of cobalt exposure. Arch Environ Health 43(4):299–303
Learmonth ID, Case CP (2007) Metallic debris from orthopaedic implants. Lancet 369:542–544
Leavelle DE (2001) Mayo Medical Laboratories. Mayo Medical Laboratories interpretive handbook: interpretive data for diagnostic laboratory tests. The Laboratories, Rochester, MN
Barry J, Lavigne M, Vendittoli PA (2013) Evaluation of the method for analyzing chromium, cobalt, titanium ion levels in the blood following hip replacement with metal-on-metal prosthesis. J Anal Toxicol 37(2):90–96
Harrington CF, Taylor A (2012) UK quality assurance of blood cobalt and chromium after hip implants. BMJ 344:e4017
Sampson B, Hart A (2012) Clinical usefulness of blood metal measurements to assess the failure of metal-on-metal hip implants. Ann Clin Biochem 49:118–131
Llobet JM, Domingo JL, Corbella J (1988) Comparative effects of repeated parenteral administration of several chelators on the distribution and excretion of cobalt. Res Commun Chem Pathol Pharmacol 60(2):225–233
Cory-Slechta DA, Weiss B, Cox C (1987) Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy. J Pharmacol Exp Ther 243(3):804–813
Oxman AD (1994) Systematic reviews: checklists for review articles. BMJ 309:648–651
Murphy CM (2012) Writing an effective review article. J Med Toxicol 8:89–90
Conflict of Interest
The authors report no declarations of interest. The opinions in this Review are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Dr. Brent reports that he has provided background scientific research as a paid consultant for DePuy Companies.
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Devlin, J.J., Pomerleau, A.C., Brent, J. et al. Clinical Features, Testing, and Management of Patients with Suspected Prosthetic Hip-Associated Cobalt Toxicity: a Systematic Review of Cases. J. Med. Toxicol. 9, 405–415 (2013). https://doi.org/10.1007/s13181-013-0320-0
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DOI: https://doi.org/10.1007/s13181-013-0320-0