Cite this article: Bone Joint Res 2021;10(6):348–350.
A total of 1.5 million metal-on-metal hip arthroplasties were enthusiastically implanted by orthopaedic surgeons around the world either side of the turn of the 21st century. However, this enthusiasm quickly soured with the recognition that these implants failed at higher rates than conventional total hip arthroplasties.1,2 Even patients rewarded with good hip function were not necessarily absolved of problems, and some patients with local adverse reactions to metal debris3 or raised circulating blood metal ions4 had few symptoms. A nightmare for patients, surgeons, and regulators ensued. It has been nearly 15 years since the initial Medical Device Alerts from the Medicines and Healthcare products Regulatory Agency (MHRA) relating to component size mismatch,5,6 and more than ten years since the first national guidelines on clinical follow-up.7
Concerns around systemic toxicity have received considerable attention, both in the scientific literature and the wider media. Perhaps most notable is the potential for cardiac toxicity. This had been singled out due to the sometimes dramatic presentation of patients with severe symptoms,8 and the known association between cobalt and dilated cardiomyopathy in susceptible individuals, first recognized nearly 50 years ago.9 The review by Jenkinson et al in this month’s issue shows that such presentations are serious, but extremely rare – a handful of cases over more than two decades. Their review also highlights the low quality of the majority of the evidence – largely limited to retrospective series and case reports. However, the few prospective, comparative studies deserve to be highlighted. These demonstrate impressive collaborations between orthopaedic surgeons and cardiologists, making use of advanced imaging technologies, barely imaginable a decade ago. Acknowledging the limitations of short-term follow-up and the absence of patients with extreme ion levels, these studies have not identified clinically important associations.10 Research questions around systemic effects are difficult to study and not amenable to experimental designs. Patients with extreme metal ion levels who choose surveillance over revision are rare.11 Few patients or surgeons would have equipoise for a randomized controlled trial of surveillance versus revision surgery under these circumstances, and nor should they. The decision to revise the implant is usually straightforward in these cases, though the surgery may be anything but.
Detecting more subtle systemic effects, potentially mediated over longer follow-up periods (perhaps decades) is a greater challenge. So far, the main approaches have been to use routine data sources to understand systemic effects on a population basis. These have returned reassuring results following the investigation of cancer and cardiac disease.12-14 However, these approaches only identify the tip of the iceberg: patients with the most severe diseases who died or were admitted to hospital with a new diagnosis.14 In addition, current routine datasets do not yet provide sufficient granularity to fully adjust for baseline differences necessary to eliminate confounding by indication. Patients who underwent hip resurfacing were typically healthier and more active than their peers who received other types of total hip arthroplasty, and this is a potential source of bias that may mask any effect. Blood tests are not yet integrated into routinely collected national datasets, explaining the absence of metal ion measurement from these studies. Linkage of the National Joint Registry (NJR) to primary care records in the future may be able to detect more subtle effects, such as a change in medication use. However, such designs at present entail substantial data attrition, since only a fraction of general practices are enrolled. Like all non-randomized studies, causal inference for any observed systemic effect will be challenging.
It is likely that mass screening of metal-on-metal hip arthroplasties over the past decade has resulted in earlier identification, and revision of patients with the highest metal ion exposures. While the MHRA ‘action level’ of 7 ppb has often been a target for criticism, we believe that this is often through misinterpretation of its purpose. The threshold was originally defined from simple outlier methodology and designed to prioritize the clinical evaluation of patients with the most abnormal circulating blood metal ion levels. It was generated at a time when 15% of new hip arthroplasties had metal-on-metal bearings15 and the burden of patients requiring enhanced follow-up loomed large. Blood metal ion testing has always been an adjunct to, rather than a substitute for, clinical and radiological assessment. Studies investigating ‘optimum’ cut-offs (often just mathematically) and dichotomizing outcomes or exposures are endemic in current medical research. Screening of metal-on-metal hips is a good example that the ‘true’ answer may be more complicated. It is testament to this that more recent research has prioritised the perspective of the patient - for example, using validated instruments to record and track symptoms.11
Many positives have emerged from our collective response to the high failure rate of metal-on-metal hip arthroplasties and, recently, the Cumberlege Report singled out the NJR as an exemplar registry.16 This is in part due to its willingness to embrace external validation of its data,17,18 and to develop robust audit processes and outlier methodology. Programmes to benchmark implant performance and closely monitor the introduction of new devices over the longer-term have emerged, including the Orthopaedic Data Evaluation Panel (ODEP),19 and UK Beyond Compliance programme.20 Implant retrieval centres have helped us to understand the mode of failure of hip, knee,21 spine, and other implants.22 As usage of metal-on-metal bearings has declined to below 1% over the past decade,23 there has been recognition of adverse reactions to metal debris from other orthopaedic devices (such as lengthening intramedullary nails) or from sources remote from the bearing surface (for example, the taper junction24 or stem25). New imaging technologies26 and methods for multidisciplinary team working27 have kept pace, and the future of surveillance of orthopaedic patients looks bright.
References
1. Smith AJ , Dieppe P , Vernon K , Porter M , Blom AW , National Joint Registry of England and Wales . Failure rates of stemmed metal-on-metal hip replacements: analysis of data from the National Joint Registry of England and Wales . Lancet . 2012 ; 379 ( 9822 ): 1199 – 1204 . Crossref PubMed Google Scholar
2. Smith AJ , Dieppe P , Howard PW , Blom AW , National Joint Registry for England and Wales . Failure rates of metal-on-metal hip resurfacings: analysis of data from the National Joint Registry for England and Wales . Lancet . 2012 ; 380 ( 9855 ): 1759 – 1766 . Crossref PubMed Google Scholar
3. Hart AJ , Satchithananda K , Liddle AD , Sabah SA , McRobbie D , Henckel J . Pseudotumors in association with well-functioning metal-on-metal hip prostheses: a case-control study using three-dimensional computed tomography and magnetic resonance imaging . J Bone Joint Surg Am . 2012 ; 94-A ( 4 ): 317 – 325 . Crossref PubMed Google Scholar
4. Hart AJ , Sabah S , Henckel J , et al. The painful metal-on-metal hip resurfacing . J Bone Joint Surg Br . 2009 ; 91-B ( 6 ): 738 – 744 . Crossref PubMed Google Scholar
5. Medicines and Healthcare Products Regulatory Agency (MHRA) . MDA/2007/067 - Hip resurfacing implants. Adept acetabular cups manufactured by Finsbury Orthopaedics . 2007 . https://webarchive.nationalarchives.gov.uk/20141205210130/http://www.mhra.gov.uk/Publications/Safetywarnings/MedicalDeviceAlerts/CON2032218 ( date last accessed 20February2021). Google Scholar
6. Medicines and Healthcare Products Regulatory Agency (MHRA) . MDA/2007/063 - Hip resurfacing implants. Birmingham Hip Resurfacing (BHR) acetabular cups manufactured by Smith & Nephew Orthopaedics Ltd . 2007 . https://webarchive.nationalarchives.gov.uk/20141205210146/http://www.mhra.gov.uk/Publications/Safetywarnings/MedicalDeviceAlerts/CON2032041 ( date last accessed 20February2021). Google Scholar
7. Medicines and Healthcare Products Regulatory Agency (MHRA) . Medical Device Alert: All metal-on-metal (MoM) hip replacements (MDA/2010/033) - SUPERSEDED ). 2010 . https://webarchive.nationalarchives.gov.uk/20130514010705/http://www.mhra.gov.uk/Publications/Safetywarnings/MedicalDeviceAlerts/CON079157 ( date last accessed 20February2021). Google Scholar
8. Tower SS . Arthroprosthetic cobaltism: neurological and cardiac manifestations in two patients with metal-on-metal arthroplasty: a case report . J Bone Joint Surg Am . 2010 ; 92-A ( 17 ): 2847 – 2851 . Crossref PubMed Google Scholar
9. Alexander CS . Cobalt-beer cardiomyopathy. A clinical and pathologic study of twenty-eight cases . Am J Med . 1972 ; 53 ( 4 ): 395 – 417 . Crossref PubMed Google Scholar
10. Berber R , Abdel-Gadir A , Rosmini S , et al. Assessing for cardiotoxicity from metal-on-metal hip implants with advanced multimodality imaging techniques . J Bone Joint Surg Am . 2017 ; 99-A ( 21 ): 1827 – 1835 . Crossref PubMed Google Scholar
11. Swiatkowska I , Henckel J , Sabah SA , Hart AJ . Self-reported neurotoxic symptoms in hip arthroplasty patients with highly elevated blood cobalt: A case-control study . J Patient Saf . 23, 2020 . Crossref PubMed Google Scholar
12. Kendal AR , Prieto-Alhambra D , Arden NK , Carr A , Judge A . Mortality rates at 10 years after metal-on-metal hip resurfacing compared with total hip replacement in England: retrospective cohort analysis of hospital episode statistics . BMJ . 2013 ; 347 : f6549 . Crossref PubMed Google Scholar
13. Smith AJ , Dieppe P , Porter M , Blom AW , National Joint Registry of England and Wales . Risk of cancer in first seven years after metal-on-metal hip replacement compared with other bearings and general population: linkage study between the National joint registry of England and Wales and hospital episode statistics . BMJ . 2012 ; 344 : e2383 . Crossref PubMed Google Scholar
14. Sabah SA , Moon JC , Jenkins-Jones S , et al. The risk of cardiac failure following metal-on-metal hip arthroplasty . Bone Joint J . 2018 ; 100-B ( 1 ): 20 – 27 . Crossref PubMed Google Scholar
15. Emsley D , Newell C , Pickford M , et al. National Joint Registry for England and Wales: 6th Annual Report . 2009 . https://www.rcseng.ac.uk/-/media/files/rcs/standards-and-research/research/national-joint-registry-report-2009.pdf ( date last accessed 11May2021). Google Scholar
16. The Independent Medicines & Medical Devices Safety Review . First Do No Harm-The report of the IMMDSReview . 2018 . https://immdsreview.org.uk/Report.html ( date last accessed 30January2021). Google Scholar
17. Sabah SA , Henckel J , Koutsouris S , et al. Are all metal-on-metal hip revision operations contributing to the National joint registry implant survival curves? Bone Joint J . 2016 ; 98-B ( 1 ): 33 – 39 . Crossref PubMed Google Scholar
18. Sabah SA , Henckel J , Cook E , et al. Validation of primary metal-on-metal hip arthroplasties on the National joint Registry for England, Wales and Northern Ireland using data from the London implant retrieval centre: a study using the NJR dataset . Bone Joint J . 2015 ; 97-B ( 1 ): 10 – 18 . Crossref PubMed Google Scholar
19. ODEP . Orthopaedic Data Evaluation Panel . 2021 . https://www.odep.org.uk/ ( date last accessed 21 February 2021 ). Google Scholar
20. No authors listed . Beyond Compliance: Protecting Patients, Supporting Innovation . 2021 . https://www.beyondcompliance.org.uk ( date last accessed 21 May 2021 ). Google Scholar
21. Cerquiglini A , Henckel J , Hothi H , et al. Analysis of the Attune tibial TraY backside: a comparative retrieval study . Bone Joint Res . 2019 ; 8 ( 3 ): 136 – 145 . Crossref PubMed Google Scholar
22. Panagiotopoulou VC , Davda K , Hothi HS , et al. A retrieval analysis of the Precice intramedullary limb lengthening system . Bone Joint Res . 2018 ; 7 ( 7 ): 476 – 484 . Crossref PubMed Google Scholar
23. National Joint Registry (NJR) . 17th Annual Report . 2020 . https://reports.njrcentre.org.uk/Portals/0/PDFdownloads/NJR%2017th%20Annual%20Report%202020.pdf ( date last accessed 10May2021). Google Scholar
24. Hothi HS , Whittaker RK , Meswania JM , Blunn GW , Skinner JA , Hart AJ . Influence of stem type on material loss at the metal-on-metal pinnacle taper junction . Proc Inst Mech Eng H . 2015 ; 229 ( 1 ): 91 – 97 . Crossref PubMed Google Scholar
25. Di Laura A , Hothi HS , Meswania JM , et al. Clinical relevance of corrosion patterns attributed to inflammatory cell‐induced corrosion: a retrieval study . J Biomed Mater Res B Appl Biomater . 2017 ; 105 ( 1 ): 155 – 164 . Google Scholar
26. Ranzini MBM , Groothuis I , Kläser K , Cardoso MJ , Henckel J , Ourselin S . Combining multimodal information for metal artefact reduction: An unsupervised deep learning framework . 2020 IEEE 17th International Symposium on Biomedical Imaging (ISBI . IEEE , 2020 : 600 – 604 . Google Scholar
27. Berber R , Skinner J , Board T , et al. International metal-on-metal multidisciplinary teams: do we manage patients with metal-on-metal hip arthroplasty in the same way? an analysis from the International specialist centre collaboration on mom hips (ISCCoMH) . Bone Joint J . 2016 ; 98-B ( 2 ): 179 – 186 . Crossref PubMed Google Scholar
Author contributions
J. A. Skinner: Wrote and edited the manuscript.
S. A. Sabah: Wrote and edited the manuscript.
A. J. Hart: Wrote and edited the manuscript.
Funding statement
Although none of the authors has received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this article, benefits have been or will be received but will be directed solely to a research fund, foundation, educational institution, or other non-profit organization with which one or more of the authors are associated.
ICMJE COI statement
S. A. Sabah has received funding from the Royal College of Surgeons and Rosetrees Trust, outside of this work. J. Skinner reports consultancy payments from Medacta, outside of this work. A. J. Hart reports an institutional grant from DePuy related to this work, and institutional grants from Medacta and Lima, outside of this work.
Follow S. A. Sabah @bonedoc247
Follow A. J. Hart @The_LIRC
© 2021 Author(s) et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/.
