- Email: [email protected]
Metal-on-Metal: Ion Levels as an Intervention Strategy
Metal-on-Metal: Ion Levels as an Intervention Strategy Michael M. Morlock, Dr habil, PhD,* Joachim Kunze, Dipl-Ing,* Markus A. Wimmer, Dr-Ing,† and Christoph H. Lohmann, Dr med habil‡ Due to the wear-related problems with large diameter metal-on-metal THA components, ion levels of cobalt and chromium in blood or serum are used to identify bearings with high-wear rates. Threshold levels for critical concentrations for these two alloys are published and quite frequently revised. Patients and doctors are confused, if measured values are close to thresholds. A new approach is presented by an international expert panel endorsed by EFFORT and several national organizations suggesting the use of a range instead of a specific value as threshold. This approach supports the philosophy that metal ion concentrations by themselves are not a diagnosis but one – important – piece in the assessment of a patient with a metal-onmetal hip articulation. Semin Arthro 23:283-285 C 2012 Elsevier Inc. All rights reserved. KEYWORDS metal-on-metal, ions, resurfacing, large heads, wear, adverse effects
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rthroplasty bearings articulating against PE have shown minor increases of metal ion concentrations (Co, Cr, Ni, Mo, Mn, and Ti) in blood or periprosthetic tissue.1 This increase is due to unavoidable wear and corrosion of metal components in the body. At minor levels no proven or known consequences have been reported.2 This situation and reports about occasionally well-working ‘‘old’’ metal-on-metal (MoM) hip prosthesis (THR) with large diameters3 and large numbers of successful MoM THRs with small diameters (‘‘Metasul’’)4 facilitated the enthusiasm about the revival of MoM THRs in the form of ‘‘resurfacing’’. This enthusiasm was based on the good results presented by the developers,5,6 even though experts had always warned of the unknown role of the metallic debris and ions.7 The initial enthusiasm has come to an abrupt end. The problems encountered were first reported anecdotally and cautiously but recently the number of reports pointing out soft tissue (‘‘Pseudotumors’’) and hard tissue problems (osteolysis) as well as elevated metal ion concentrations are increasing quickly, especially for large MoM THRs.8-10 Simultaneously the revision rates presented in the registries continued to rise above the long-term standards with polyethylene–metal articulation.11 *Institute of Biomechanics, TUHH Hamburg University of Technology, Germany. †Section of Tribology, Department of Orthopedics, Rush University Medical Center, Chicago, IL. ‡Department of Orthopedics, University Hospital Magdeburg, Leipziger, Magdeburg, Germany. Address reprint requests to Michael M. Morlock, Dr habil, PhD, Institute of Biomechanics, TUHH Hamburg University of Technology, Denickestrasse 15, 21073 Hamburg, Germany. E-mail: [email protected]
1045-4527/12/$-see front matter & 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.sart.2012.12.002
The determination of ion levels has since become part of the standard diagnosis for MoM THRs. A fixed ‘‘value’’ for an established biological threshold (local and systemic) and whether there is a direct relationship between observed ion concentration and biological response is presently unknown. Ion concentrations determined in blood, serum and urine are derived with different protocols, converted from one into another unit and difficult to compare directly. The importance of sample preparation has been recognized and is receiving increased attention. It has been established that acid digestion of fluid samples is necessary to determine metal ion concentrations accurately so that meaningful comparisons can be made between studies.12-14 Published threshold values are continuously changing. In 2008, critical serum Cr-ion levels of 417 mg/L and serum Coion levels of 419 mg/L have been reported as most likely associated with metallosis.15 Around the same time another study showed that a combined cobalt and chromium threshold level of 5 mg/L comes along with immune suppression,16 but this level was not adopted. In 2011, the threshold levels were lowered to 7 mg/L by the MHRA. Since no critical blood or serum limits for critically exposed persons have been established, the sensitivity and specificity of a certain threshold has to be investigated in clinical studies. Two new studies showed the presently suggested threshold of 7 mg/L to present low sensitivity (57% re. 52% of the affected patients correctly classified) and decent specificity (64% re. 89% of the unaffected correctly classified).17,18 This explains why 50% of the patients undergoing revision exhibited ion concentrations below this threshold.19 Hart et al proposed cutoff level for the maximum of cobalt or chromium at 4.97 mg/L with a 283
284 sensitivity of 63% and a specificity 86%. The newest proposed threshold i.e. safe upper limit is reported as Cr 4.6 mg/L/Co 4.0 mg/L for unilateral and Cr 7.4 mg/L/Co 5.0 mg/L for bilateral metal-on-metal hip resurfacing arthroplasty.20 However, lowering the threshold will always cause a decrease in specificity. In this particular study, as example for Cr in unilateral HRA, sensitivity was only 25% whereas specificity was 95%.20 This illustrates nicely the difficulty of the situation: if the threshold values are low, nearly all affected patients are identified, but also many unaffected patients undergo additional tests and imaging without reason. Furthermore, sensitivity and specificity achieved with quite similar cutoff values are greatly different between studies.17-20 The definition of a scientifically sound threshold value is, therefore, currently not possible. For this reason, at a recent expert meeting, it has been decided to use ranges instead (until more robust data become available). The second problem concerns the level of information available with regard to systemic effects. Some case reports point out ‘‘dramatic’’ consequences such as loss of sight and/or sound21,22 or neuropathy.23 The ion levels for these anecdotal reports are a multiple of the presently discussed values. Furthermore, the relation between local and systemic debris concentration is inconsistent and depends greatly on the way the samples are analyzed.14 It is universally agreed upon that high ion levels are an indication for a problem, but ion levels below a certain threshold should not be mistaken for a false sense of security. Similarly, ion levels above a low threshold do not necessarily indicate a problem. A recent expert meeting in Dresden has tried to take this finding into account by suggesting an approach, which is NOT relying on a single value. This is quite similar to the approach presented by van der Straeten et al.20 In conclusion, metal ions should not be interpreted as a sole parameter but in the broader context of clinical, radiographic and implant data (e.g. size, type, and hip resurfacing or big femoral head).20 The following is an excerpt of the Consensus statement ‘‘Current Evidence on the Management of Metal-on-Metal Bearings’’, April 16, 2012. The recommendations are based on expert opinions of an international multidisciplinary panel ¨ headed by Prof. K.P. Gunther (Dresden) and endorsed by the ‘‘European Federation of National Associations of Orthopaedics and Traumatology’’ (EFORT), the German ‘‘Arbeitsgemeinschaft Endoprothetik’’ (AE) and the ‘‘Deutsche Arthrosehilfe’’ (DAH).
Safety Assessment of Patients After Implantation of MoM Bearings a. Is systematic follow-up recommended? If yes—for which implants and patients? – YES, for all patients and all implants. For small MoM-heads in THR a systematic follow-up comparable to conventional THR is sufficient. For large
M.A. Morlock et al MoM-heads and resurfacing closer follow-up is recommended. b. How long and how frequently should asymptomatic patients be monitored? For the life of the joint: – Small heads: As frequent as conventional THR. – Large heads: Annually. – Resurfacing: Annually for the first 5 years, then according to local protocols for patients with conventional THR. If metal ion levels are normal at year one and two postoperatively, the frequency of further annual follow-up investigations may be changed to local protocols for conventional THR. In patients with risk factors such as small size (o50 mm femoral component), female gender, and low coverage arc annually for the life of the joint. c. Which imaging techniques should be applied during follow-up? – X-rays in all patients. – In case of clinical/radiographic abnormality additional imaging (ultrasound, CT-scan, and/or MARSMRI [ordinary MRI without MARS-technique is ineffective]). – In case of Co-values above a certain threshold (within the range of 2-7 mg/L; exact level still to be determined): ultrasound, CT-scan, and/or MARSMRI. d. How should monitoring of metal ions be performed: frequency, sources (blood/serum/urine), technique, reference values? – Frequency: Time of regular follow-up in asymptomatic patients; in all symptomatic patients additionally between regular follow-up. – Source: Metal ion determination of body fluids can be performed in blood, serum and urine. At present measurement of whole blood is most practicable. Co should be monitored as a reference substance. – Technique: Metal ion measurement must be performed under the rules of internal/external quality control. GF-AAS and ICP-MS are considered as valid. The preferred reporting units should be micrograms per liter (ppb). – Reference values: Co-values without clinical concern are at the moment: o2 mg/L. The threshold value for clinical concern is expected to be within the range of 2-7 mg/L (exact levels have still to be determined within this range). – For increased values above the threshold additional imaging, even in asymptomatic patients, is recommended.
Note: Recommendations are based on local effects; critical values for systemic effects have not yet been established for patients after MoM implantation. In conclusion,
Metal ion based intervention – Co and Cr concentrations in blood or serum below 2 mg/L are unproblematic; – between 2 and 7 mg/L, further information is likely needed (imaging, base line values, and temporal changes) in order to decide, whether there is a reason for concern or not; – values above 7 mg/L should always be a reason for concern; – greatly elevated values (above 30-50 mg/L) should always be a reason for intervention. Finally, metal ions should not be interpreted as the sole parameter for determining the intervention strategy but in the broader context of clinical, radiographic and implant data (size, type, hip resurfacing or big femoral head etc.).20 The determination of ion levels is not a diagnosis, it is a test!
References 1. Pazzaglia UE, Apostoli P, Congiu T, et al: Cobalt, chromium and molybdenum ions 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, 2011 2. Pazzaglia UE, Minoia C, Gualtieri G, et al: Metal ions in body fluids after arthroplasty. Acta Orthop Scand 57:415-418, 1986 3. Clarke MT, Darrah C, Stewart T, et al: Long-term clinical, radiological and histopathological follow-up of a well-fixed Mckee-Farrar metal-onmetal total hip arthroplasty. J Arthroplasty 20:542-546, 2005 4. Delaunay CP, Bonnomet F, Clavert P, et al: THA using metal-on-metal articulation in active patients younger than 50 years. Clin Orthop Relat Res 466:340-346, 2008 5. McMinn D, Treacy R, Lin K, et al: Metal on metal surface replacement of the hip. Experience of the McMinn prothesis. Clin Orthop Relat Res (329 Suppl):S89-S98, 1996 6. Amstutz HC, Beaule PE, Dorey FJ, et al: Metal-on-metal hybrid surface arthroplasty: two to six-year follow-up study. J Bone Joint Surg Am 86:28-39, 2004 7. Jacobs JJ, Skipor AK, Doorn PF, et al: Cobalt and chromium concentrations in patients with metal on metal total hip replacements. Clin Orthop Relat Res (329 suppl):S256-S263, 1996 8. Garbuz DS, Tanzer M, Greidanus NV, et al: The John Charnley Award: metal-on-metal hip resurfacing versus large-diameter head metal-onmetal total hip arthroplasty: a randomized clinical trial. Clin Orthop Relat Res 468:318-325, 2010
285 9. Steffen RT, Pandit HP, Palan J, et al: The five-year results of the Birmingham Hip Resurfacing arthroplasty: AN INDEPENDENT SERIES. J Bone Joint Surg Br 90:436-441, 2008 10. Kwon YM, Thomas P, Summer B, et al: Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty. J Orthop Res 28:444-450, 2010 11. Australian Orthopaedic Association, National joint replacement registry annual report 2011 12. Kunze J, Wimmer MA, Koelling S, et al: Determination of titanium and zirconium wear debris in blood serum by means of HNO3/HF pressurized digestion using ICP-optical emission spectrometry. Fresen J Anal Chem 361:496-499, 1998 13. Catelas I, Bobyn JD, Medley JJ, et al: Effects of digestion protocols on the isolation and characterization of metal–metal wear particles. II. Analysis of ion release and particle composition. J Biomed Mater Res 55:330-337, 2001 14. Davda K, Lali FV, Sampson B, et al: An analysis of metal ion levels in the joint fluid of symptomatic patients with metal-on-metal hip replacements. J Bone Joint Surg Br 93:738-745, 2011 15. De Smet K, De Haan R, Calistri A, et al: Metal ion measurement as a diagnostic tool to identify problems with metal-on-metal hip resurfacing. J Bone Joint Surg Am 90(Suppl. 4):202-208, 2008 16. Hart AJ, Hester T, Sinclair K, et al: The association between metal ions from hip resurfacing and reduced T-cell counts. J Bone Joint Surg Br 88:449-454, 2006 17. Malek I, King M, Sharma H, et al: High serum metal ions (47 mg/l) cannot be used as an indirect screening test in metal on metal bearing hip surveillance. Presentation abstract, 2012. AAOS annual meeting. p. 315, 2012. 18. Hart AJ, Sabah SA, Bandi AS, et al: Sensitivity and specificity of blood cobalt and chromium metal ions for predicting failure of metal-on-metal hip replacement. J Bone Joint Surg Br 93:1308-1313, 2011 19. Hart AJ, Matthies A, Henckel J, et al: Understanding why metal-on-metal hip arthroplasties fail: a comparison between patients with wellfunctioning and revised birmingham hip resurfacing arthroplasties. AAOS exhibit selection. J Bone Joint Surg Am 94:e22, 2012 20. Van der Straeten C, Grammatopoulos G, Gill HS, et al: The 2012 Otto Aufranc Award: the interpretation of metal ion levels in unilateral and bilateral hip resurfacing. Clin Orthop Relat Res e08, 2012 21. Gallinaro P, Piolatto G: Blind and deaf after total hip replacement? Lancet 373:1944-1945, 2009 22. Arbuthnot JE, Journeaux SF, Clark DI: The Birmingham hip resurfacing procedure: a rare complication. J Arthroplasty 18:666-667, 2003 23. Harvie P, Giele H, Fang C, et al: The treatment of femoral neuropathy due to pseudotumour caused by metal-on-metal resurfacing arthroplasty. Hip Int 18:313-320, 2008
A
rthroplasty bearings articulating against PE have shown minor increases of metal ion concentrations (Co, Cr, Ni, Mo, Mn, and Ti) in blood or periprosthetic tissue.1 This increase is due to unavoidable wear and corrosion of metal components in the body. At minor levels no proven or known consequences have been reported.2 This situation and reports about occasionally well-working ‘‘old’’ metal-on-metal (MoM) hip prosthesis (THR) with large diameters3 and large numbers of successful MoM THRs with small diameters (‘‘Metasul’’)4 facilitated the enthusiasm about the revival of MoM THRs in the form of ‘‘resurfacing’’. This enthusiasm was based on the good results presented by the developers,5,6 even though experts had always warned of the unknown role of the metallic debris and ions.7 The initial enthusiasm has come to an abrupt end. The problems encountered were first reported anecdotally and cautiously but recently the number of reports pointing out soft tissue (‘‘Pseudotumors’’) and hard tissue problems (osteolysis) as well as elevated metal ion concentrations are increasing quickly, especially for large MoM THRs.8-10 Simultaneously the revision rates presented in the registries continued to rise above the long-term standards with polyethylene–metal articulation.11 *Institute of Biomechanics, TUHH Hamburg University of Technology, Germany. †Section of Tribology, Department of Orthopedics, Rush University Medical Center, Chicago, IL. ‡Department of Orthopedics, University Hospital Magdeburg, Leipziger, Magdeburg, Germany. Address reprint requests to Michael M. Morlock, Dr habil, PhD, Institute of Biomechanics, TUHH Hamburg University of Technology, Denickestrasse 15, 21073 Hamburg, Germany. E-mail: [email protected]
1045-4527/12/$-see front matter & 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.sart.2012.12.002
The determination of ion levels has since become part of the standard diagnosis for MoM THRs. A fixed ‘‘value’’ for an established biological threshold (local and systemic) and whether there is a direct relationship between observed ion concentration and biological response is presently unknown. Ion concentrations determined in blood, serum and urine are derived with different protocols, converted from one into another unit and difficult to compare directly. The importance of sample preparation has been recognized and is receiving increased attention. It has been established that acid digestion of fluid samples is necessary to determine metal ion concentrations accurately so that meaningful comparisons can be made between studies.12-14 Published threshold values are continuously changing. In 2008, critical serum Cr-ion levels of 417 mg/L and serum Coion levels of 419 mg/L have been reported as most likely associated with metallosis.15 Around the same time another study showed that a combined cobalt and chromium threshold level of 5 mg/L comes along with immune suppression,16 but this level was not adopted. In 2011, the threshold levels were lowered to 7 mg/L by the MHRA. Since no critical blood or serum limits for critically exposed persons have been established, the sensitivity and specificity of a certain threshold has to be investigated in clinical studies. Two new studies showed the presently suggested threshold of 7 mg/L to present low sensitivity (57% re. 52% of the affected patients correctly classified) and decent specificity (64% re. 89% of the unaffected correctly classified).17,18 This explains why 50% of the patients undergoing revision exhibited ion concentrations below this threshold.19 Hart et al proposed cutoff level for the maximum of cobalt or chromium at 4.97 mg/L with a 283
284 sensitivity of 63% and a specificity 86%. The newest proposed threshold i.e. safe upper limit is reported as Cr 4.6 mg/L/Co 4.0 mg/L for unilateral and Cr 7.4 mg/L/Co 5.0 mg/L for bilateral metal-on-metal hip resurfacing arthroplasty.20 However, lowering the threshold will always cause a decrease in specificity. In this particular study, as example for Cr in unilateral HRA, sensitivity was only 25% whereas specificity was 95%.20 This illustrates nicely the difficulty of the situation: if the threshold values are low, nearly all affected patients are identified, but also many unaffected patients undergo additional tests and imaging without reason. Furthermore, sensitivity and specificity achieved with quite similar cutoff values are greatly different between studies.17-20 The definition of a scientifically sound threshold value is, therefore, currently not possible. For this reason, at a recent expert meeting, it has been decided to use ranges instead (until more robust data become available). The second problem concerns the level of information available with regard to systemic effects. Some case reports point out ‘‘dramatic’’ consequences such as loss of sight and/or sound21,22 or neuropathy.23 The ion levels for these anecdotal reports are a multiple of the presently discussed values. Furthermore, the relation between local and systemic debris concentration is inconsistent and depends greatly on the way the samples are analyzed.14 It is universally agreed upon that high ion levels are an indication for a problem, but ion levels below a certain threshold should not be mistaken for a false sense of security. Similarly, ion levels above a low threshold do not necessarily indicate a problem. A recent expert meeting in Dresden has tried to take this finding into account by suggesting an approach, which is NOT relying on a single value. This is quite similar to the approach presented by van der Straeten et al.20 In conclusion, metal ions should not be interpreted as a sole parameter but in the broader context of clinical, radiographic and implant data (e.g. size, type, and hip resurfacing or big femoral head).20 The following is an excerpt of the Consensus statement ‘‘Current Evidence on the Management of Metal-on-Metal Bearings’’, April 16, 2012. The recommendations are based on expert opinions of an international multidisciplinary panel ¨ headed by Prof. K.P. Gunther (Dresden) and endorsed by the ‘‘European Federation of National Associations of Orthopaedics and Traumatology’’ (EFORT), the German ‘‘Arbeitsgemeinschaft Endoprothetik’’ (AE) and the ‘‘Deutsche Arthrosehilfe’’ (DAH).
Safety Assessment of Patients After Implantation of MoM Bearings a. Is systematic follow-up recommended? If yes—for which implants and patients? – YES, for all patients and all implants. For small MoM-heads in THR a systematic follow-up comparable to conventional THR is sufficient. For large
M.A. Morlock et al MoM-heads and resurfacing closer follow-up is recommended. b. How long and how frequently should asymptomatic patients be monitored? For the life of the joint: – Small heads: As frequent as conventional THR. – Large heads: Annually. – Resurfacing: Annually for the first 5 years, then according to local protocols for patients with conventional THR. If metal ion levels are normal at year one and two postoperatively, the frequency of further annual follow-up investigations may be changed to local protocols for conventional THR. In patients with risk factors such as small size (o50 mm femoral component), female gender, and low coverage arc annually for the life of the joint. c. Which imaging techniques should be applied during follow-up? – X-rays in all patients. – In case of clinical/radiographic abnormality additional imaging (ultrasound, CT-scan, and/or MARSMRI [ordinary MRI without MARS-technique is ineffective]). – In case of Co-values above a certain threshold (within the range of 2-7 mg/L; exact level still to be determined): ultrasound, CT-scan, and/or MARSMRI. d. How should monitoring of metal ions be performed: frequency, sources (blood/serum/urine), technique, reference values? – Frequency: Time of regular follow-up in asymptomatic patients; in all symptomatic patients additionally between regular follow-up. – Source: Metal ion determination of body fluids can be performed in blood, serum and urine. At present measurement of whole blood is most practicable. Co should be monitored as a reference substance. – Technique: Metal ion measurement must be performed under the rules of internal/external quality control. GF-AAS and ICP-MS are considered as valid. The preferred reporting units should be micrograms per liter (ppb). – Reference values: Co-values without clinical concern are at the moment: o2 mg/L. The threshold value for clinical concern is expected to be within the range of 2-7 mg/L (exact levels have still to be determined within this range). – For increased values above the threshold additional imaging, even in asymptomatic patients, is recommended.
Note: Recommendations are based on local effects; critical values for systemic effects have not yet been established for patients after MoM implantation. In conclusion,
Metal ion based intervention – Co and Cr concentrations in blood or serum below 2 mg/L are unproblematic; – between 2 and 7 mg/L, further information is likely needed (imaging, base line values, and temporal changes) in order to decide, whether there is a reason for concern or not; – values above 7 mg/L should always be a reason for concern; – greatly elevated values (above 30-50 mg/L) should always be a reason for intervention. Finally, metal ions should not be interpreted as the sole parameter for determining the intervention strategy but in the broader context of clinical, radiographic and implant data (size, type, hip resurfacing or big femoral head etc.).20 The determination of ion levels is not a diagnosis, it is a test!
References 1. Pazzaglia UE, Apostoli P, Congiu T, et al: Cobalt, chromium and molybdenum ions 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, 2011 2. Pazzaglia UE, Minoia C, Gualtieri G, et al: Metal ions in body fluids after arthroplasty. Acta Orthop Scand 57:415-418, 1986 3. Clarke MT, Darrah C, Stewart T, et al: Long-term clinical, radiological and histopathological follow-up of a well-fixed Mckee-Farrar metal-onmetal total hip arthroplasty. J Arthroplasty 20:542-546, 2005 4. Delaunay CP, Bonnomet F, Clavert P, et al: THA using metal-on-metal articulation in active patients younger than 50 years. Clin Orthop Relat Res 466:340-346, 2008 5. McMinn D, Treacy R, Lin K, et al: Metal on metal surface replacement of the hip. Experience of the McMinn prothesis. Clin Orthop Relat Res (329 Suppl):S89-S98, 1996 6. Amstutz HC, Beaule PE, Dorey FJ, et al: Metal-on-metal hybrid surface arthroplasty: two to six-year follow-up study. J Bone Joint Surg Am 86:28-39, 2004 7. Jacobs JJ, Skipor AK, Doorn PF, et al: Cobalt and chromium concentrations in patients with metal on metal total hip replacements. Clin Orthop Relat Res (329 suppl):S256-S263, 1996 8. Garbuz DS, Tanzer M, Greidanus NV, et al: The John Charnley Award: metal-on-metal hip resurfacing versus large-diameter head metal-onmetal total hip arthroplasty: a randomized clinical trial. Clin Orthop Relat Res 468:318-325, 2010
285 9. Steffen RT, Pandit HP, Palan J, et al: The five-year results of the Birmingham Hip Resurfacing arthroplasty: AN INDEPENDENT SERIES. J Bone Joint Surg Br 90:436-441, 2008 10. Kwon YM, Thomas P, Summer B, et al: Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty. J Orthop Res 28:444-450, 2010 11. Australian Orthopaedic Association, National joint replacement registry annual report 2011 12. Kunze J, Wimmer MA, Koelling S, et al: Determination of titanium and zirconium wear debris in blood serum by means of HNO3/HF pressurized digestion using ICP-optical emission spectrometry. Fresen J Anal Chem 361:496-499, 1998 13. Catelas I, Bobyn JD, Medley JJ, et al: Effects of digestion protocols on the isolation and characterization of metal–metal wear particles. II. Analysis of ion release and particle composition. J Biomed Mater Res 55:330-337, 2001 14. Davda K, Lali FV, Sampson B, et al: An analysis of metal ion levels in the joint fluid of symptomatic patients with metal-on-metal hip replacements. J Bone Joint Surg Br 93:738-745, 2011 15. De Smet K, De Haan R, Calistri A, et al: Metal ion measurement as a diagnostic tool to identify problems with metal-on-metal hip resurfacing. J Bone Joint Surg Am 90(Suppl. 4):202-208, 2008 16. Hart AJ, Hester T, Sinclair K, et al: The association between metal ions from hip resurfacing and reduced T-cell counts. J Bone Joint Surg Br 88:449-454, 2006 17. Malek I, King M, Sharma H, et al: High serum metal ions (47 mg/l) cannot be used as an indirect screening test in metal on metal bearing hip surveillance. Presentation abstract, 2012. AAOS annual meeting. p. 315, 2012. 18. Hart AJ, Sabah SA, Bandi AS, et al: Sensitivity and specificity of blood cobalt and chromium metal ions for predicting failure of metal-on-metal hip replacement. J Bone Joint Surg Br 93:1308-1313, 2011 19. Hart AJ, Matthies A, Henckel J, et al: Understanding why metal-on-metal hip arthroplasties fail: a comparison between patients with wellfunctioning and revised birmingham hip resurfacing arthroplasties. AAOS exhibit selection. J Bone Joint Surg Am 94:e22, 2012 20. Van der Straeten C, Grammatopoulos G, Gill HS, et al: The 2012 Otto Aufranc Award: the interpretation of metal ion levels in unilateral and bilateral hip resurfacing. Clin Orthop Relat Res e08, 2012 21. Gallinaro P, Piolatto G: Blind and deaf after total hip replacement? Lancet 373:1944-1945, 2009 22. Arbuthnot JE, Journeaux SF, Clark DI: The Birmingham hip resurfacing procedure: a rare complication. J Arthroplasty 18:666-667, 2003 23. Harvie P, Giele H, Fang C, et al: The treatment of femoral neuropathy due to pseudotumour caused by metal-on-metal resurfacing arthroplasty. Hip Int 18:313-320, 2008