Metal on Metal, How Safe are the implants, Derek McMinn Replies

On May 30, 2012, at 7:36 AM, Derek McMinn wrote:

Dear Dr Godlee,

We write in relation to the comment by Dr Carome in Dr Deborah Cohen's piece on 28th February 2012 that “this is one very large uncontrolled experiment exposing millions of patients to an unknown risk.”  Dr Carome has not responded to or acknowledged my e-mail dated 16th April 2012 (see below)  despite further e-mail communication being sent to both himself and his secretary.  We do appreciate that the comment was not made by yourself or Dr Cohen, which is why we asked Dr Carome to reply himself.  In the absence of a response from Dr Carome, surely the BMJ has to shoulder responsibility here as it is unreasonable to make such a far reaching and damaging statement in the BMJ without either justifying or withdrawing that statement.

We would be grateful if you would publish our letter in full in the BMJ please?
 
Yours sincerely,
Joseph Daniel FRCS MS(Orth)
Director of Research
McMinn Centre

Derek McMinn MD FRCS
Consultant Orthopaedic Surgeon
McMinn Centre
 
April 16, 2012

How safe are metal-on-metal hip implants?

Dear Dr Carome

We read with interest the comments attributed to you by Deborah Cohen in her piece¹ in the British Medical Journal on the 28th of February 2012, that “this is one very large uncontrolled experiment exposing millions of patients to an unknown risk.” These comments are being quoted as first principles by the newspapers and law firms around the world. The comments have been widely reported in the lay press and have caused massive patient alarm and helped bring the profession of orthopaedic surgery, the regulatory bodies, the medical device industry and the operation of hip replacement into disrepute.

The earliest successful total hip replacements (THRs) which were introduced into clinical usage by McKee in 1960² were made of cobalt-chrome metal-on-metal bearings. It was only a few years later in 1962 that Sir John Charnley started using metal on ultrahigh molecular weight polyethylene bearings in what are today termed conventional total hip replacements.

The Swedish National Hip Arthroplasty Register in its report in 2000³ noted that in young patients (men and women under the age of for 55 years with osteoarthritis) the performance of conventional hip replacements was dismal with a 19% implant failure rate at 10 years and a 67% failure rate at 16 years. In contrast the performance of conventional total hip replacements in older patients is very satisfactory. There was therefore a need to develop more robust implant types for use in younger more active patients. We have been involved in that development and one of us is the co-designer of the Birmingham Hip Resurfacing (BHR).

Our results with the BHR⁴ in patients under the age of 55 years with osteoarthritis show less than 2% implant failure at 10 years and < 3% failure at 14.5 years. Very promising results have been reported with the BHR from other sources^{5 6 7 8 9} and from national joint registers in predominantly young patients. Of course we acknowledge that the BHR with its high clearance, metallurgy and acetabular coverage is strongly based on the successful first generation metal-on-metal devices used since 1960. This is no surprise as our development of the BHR started with a detailed forensic analysis of the first generation MoM implants. This was specifically performed to ensure that key bearing characteristics were faithfully transferred to the BHR so that a new bearing experiment was not initiated.¹⁰

In a few patients still alive with long term historic MoM devices the metal ion levels are not significantly different to our BHR patients with 12+ year followup.11 This shows that patients with BHR devices do not have a greater metal ion exposure compared to the historic MoM devices.

Newer devices such as Johnson-Johnson’s ASR and Zimmer’s Durom with their low radial clearance and other bearing characteristics have no basis in history and these resurfacings^{12 13 14} have shown high failure rates, in some cases up to 25% failure at 7 years. The ASR XL^{15 16 17} and Durom MoM THRs^{18 19} also have high failure rates, and in particular they appear to fail with head-neck taper failures as a major issue. It has been shown that the deformation of the ASR and Durom cups during cup implantation^{20 21} exceeds the initial clearance²² and leads to clamping between the head and the cup. This can lead to high frictional torque at the bearing being transmitted to the taper junctions eventually leading to taper failures.  Accelerated cup loosening in these low clearance MoM THRs is also a feature.

Our experience with MoM THRs using BHR cups and modular heads on stems show 98% implant survival at 10 years and no observed head-neck taper failures. Analysis of the NJR (England and Wales National Joint Register) results of Smith & Nephew stems with a BHR cup show a failure rate superior to the NICE (National Institute of Clinical and Health Excellence) guidelines. Before beginning to use the BHR MoM THRs, we performed Metasul small diameter MoM THR's. These implants also have had excellent survival and metal ion levels no different to the BHR.²³

The BHR is made of cobalt-chrome alloy, which contains about 28% chromium, 6% molybdenum around 1% different trace materials and the rest (around 65%) cobalt, a material that has been in use in hip arthroplasty as Vitallium since 1938.^{24 25} With your expertise in renal medicine you would agree that these are essential trace elements with deficiency states described for each of them, that there is a renal clearance mechanism26 for these metals and that they are not nephrotoxic at the clinically relevant levels.^{27 28}

However there has been concern that these ions can cause chromosome and DNA changes with potential carcinogenic effects. For the last two decades the Bristol Implant Research Centre in the United Kingdom has been on a mission to establish a link between implant materials and early markers of cancer. In a cross-sectional study²⁹ they analysed chromosome changes in a group of patients at the time of revision arthroplasty (revision of predominantly metal on polyethylene replacements). They then compared the results with tests from controls presenting for primary arthroplasty. The Bristol study showed that there is an increase of translocations and aneuploidy in the study group, and that there were differences between cobalt-chrome and titanium-containing implants.

The same Centre then performed a longitudinal study³⁰ on patients with metal-on-metal (MoM) hip replacements but found that the increase of chromosome aberrations in these patients was not as great as that previously reported for the metal-on-polyethylene prostheses in the cross-sectional study mentioned above. No significant relationship was found between the chromosome changes and the blood levels of cobalt or chromium. Studies from the same centre also demonstrate that ceramic-ceramic bearing replacements also show similar chromosome changes in the peripheral blood.³¹ All three of these studies were performed in the same laboratory using the same techniques by the same team. Therefore chromosome changes in patients with MoM bearings are no greater than those with either M-PE or ceramic-ceramic bearings. On the basis of chromosome changes, the risk of carcinogenesis should be no greater in MoM bearings as compared to the other bearings.

Fairly extensive long term studies have been conducted and published on the effects of these metals in patients with metal-on-metal hip arthroplasties and compared to patients with metal-on-polyethylene hip arthroplasties and with the general population.

Anyone interested in hard evidence in the world literature will find the published life work of Prof Visuri³² and colleagues in Finland. They studied more than 2000 patients with hip replacements over 30 years and compared their causes of death with the general population. The patients included 579 who had metal-on-metal (MoM) THRs and 1585 who had metal-on-polyethylene (MPE) THRs, providing exposure risk of over 36000 person-years in patients with hip replacements. Patient records from the general population were used as controls.

They found that there was no significant increase in cancer rates or in organ system failure rates with the exception that those with conventional hip replacements had a higher likelihood of dying from Alzheimers disease (Table 1). This was after 30 years and although not in a randomized controlled trial setup, the effects were compared to those with metal-on-polyethylene hip replacements and to the general population. They also studied the site-specific incidence of cancer³³ and found no increase in the different cancers as compared to the general population.

Table 1

The effect of hip resurfacings and different replacements on the incidence of cancer has also been studied in the large England and Wales National Joint Register in a recent publication³⁴ in the British Medical Journal, where the data from nearly 300,000 hip replacements were independently analysed. They conclude that, “despite the theoretical risks, we did not find a link between metal-on-metal hip replacements (either stemmed or resurfacing) and increased incidence of cancer diagnosis.” They also state that “a comparison of one year observed diagnosis rates with expected rates showed that men and women with all types of hip replacement were less likely to receive a diagnosis of cancer than an age and sex matched general population. Patients with metal-on-metal bearing surfaces had lower observed incidence rates than those with other bearing surfaces, with a particularly low rate in younger patients in the resurfacing metal-on-metal group.” “Furthermore, our models indicated that patients undergoing resurfacing procedures were less likely than those with alternative bearings to get a diagnosis of prostate cancer, haematological cancers, or any cancer and had a lower risk of death.” This was after they had adjusted for age, gender, diagnosis, preoperative health status and comorbidities at the time of operation using flexible parametric analysis.

At this practice we have been performing metal-on-metal resurfacing and total hip replacements for the past twenty one years. On our website we have the testimonials of patients who have enjoyed the benefits of hip resurfacing for over twenty years and a woman who underwent a metal-on-metal total hip replacement over forty years ago, and continues to benefit from it. You can watch her story at http://www.youtube.com/watch?v=KqQAnDJKqhU .

We would appreciate if you could explain which part of our practice is a large uncontrolled experiment.

Yours sincerely,

Joseph Daniel FRCS MS(Orth)
Director of Research
McMinn Centre
        
Derek McMinn MD FRCS
Consultant Orthopaedic Surgeon
McMinn Centre
 

The references below can be downloaded at http://www.mcminncentre.co.uk/bhr-resources.html

1. McMinn D, Development Perspectives In: McMinn D (ed). Modern Hip Resurfacing. Heidelberg, London, New York. Springer 2009
2. Daniel J, McMinn D, Ziaee H. Conference presentations, Metal ion exposure in BHRs and Historic MoM THR
3. Matthies AK, Henckel J, Skinner JA, Hart AJ. A retrieval analysis of explanted Durom metal-on-metal hip arthroplasties. Hip Int. 2011 Nov-Dec;21(6):724-31. doi: 10.5301/HIP.2011.8885
4. Cohen D. How safe are metal-on-metal hip implants? BMJ. 2012 Feb 28;344:e1410. doi: 10.1136/bmj.e1410
5.  Reynolds L A, Tansey E M. (eds) (2007) Early Development of Total Hip Replacement. Wellcome Witnesses to Twentieth Century Medicine, vol. 29. London: Wellcome Trust Centre for the History of Medicine at UCL http://www.history.qmul.ac.uk/research/modbiomed/Publications/wit_vols/44852.pdf
6. Malchau P, Herberts P, Söderman P, Oden A. Update and validation of results from the Swedish Hip Arthroplasty Registry 1979-1998. Procs 67th Annual Meeting of the American Academy of Orthopaedic Surgeons, 2000.
7. McMinn DJ, Daniel J, Ziaee H, Pradhan C. Indications and results of hip resurfacing. Int Orthop. 2011 Feb;35(2):231-7
8. Carrothers AD, Gilbert RE, Jaiswal A, Richardson JB. Birmingham hip resurfacing: the prevalence of failure. J Bone Joint Surg Br. 2010 Oct;92(10):1344-50
9. Pollard TC, Baker RP, Eastaugh-Waring SJ, Bannister GC. Treatment of the young active patient with osteoarthritis of the hip. A five- to seven-year comparison of hybrid total hip arthroplasty and metal-on-metal resurfacing. J Bone Joint Surg Br. 2006 May;88(5):592-600
10. Steffen RT, Pandit HP, Palan J, Beard DJ, Gundle R, McLardy-Smith P, Murray DW, Gill HS. The five-year results of the Birmingham Hip Resurfacing arthroplasty: an independent series. J Bone Joint Surg Br. 2008 Apr;90(4):436-41
11. Coulter G, Young DA, Dalziel RE, Shimmin AJ. Birmingham hip resurfacing at a mean of ten years: results from an independent centre. J Bone Joint Surg Br. 2012 Mar;94(3):315-21
12. Treacy RB, McBryde CW, Shears E, Pynsent PB. Birmingham hip resurfacing: a minimum follow-up of ten years. J Bone Joint Surg Br. 2011 Jan;93(1):27-33
13. de Steiger RN, Hang JR, Miller LN, Graves SE, Davidson DC. Five-year results of the ASR XL Acetabular System and the ASR Hip Resurfacing System: an analysis from the Australian Orthopaedic Association National Joint Replacement Registry. J Bone Joint Surg Am. 2011 Dec 21;93(24):2287-93
14. Jameson SS, Langton DJ, Nargol AV. Articular surface replacement of the hip: a prospective single-surgeon series.J Bone Joint Surg Br. 2010 Jan;92(1):28-37
15. Long WT, Dastane M, Harris MJ, Wan Z, Dorr LD. Failure of the Durom Metasul acetabular component. Clin Orthop Relat Res. 2010 Feb;468(2):400-5.
16. Langton DJ, Jameson SS, Joyce TJ, Gandhi JN, Sidaginamale R, Mereddy P, Lord J, Nargol AV. Accelerating failure rate of the ASR total hip replacement.J Bone Joint Surg Br. 2011 Aug;93(8):1011-6
17. Steele GD, Fehring TK, Odum SM, Dennos AC, Nadaud MC. Early failure of articular surface replacement XL total hip arthroplasty. J Arthroplasty. 2011 Sep;26(6 Suppl):14-8. Epub 2011 May 8.
18. Bernthal NM, Celestre PC, Stavrakis AI, Ludington JC, Oakes DA. Disappointing Short-Term Results With the DePuy ASR XL Metal-on-Metal Total Hip Arthroplasty. J Arthroplasty. 2012 Apr;27(4):539-44. Epub 2011 Oct 13
19. Garbuz DS, Tanzer M, Greidanus NV, Masri BA, Duncan CP. The John Charnley Award: Metal-on-metal hip resurfacing versus large-diameter head metal-on-metal total hip arthroplasty: a randomized clinical trial. Clin Orthop Relat Res. 2010 Feb;468(2):318-25
20. Springer BD, Habet NA, Griffin WL, Nanson CJ, Davies MA. Deformation of 1-piece metal acetabular components. J Arthroplasty. 2012;27:48-54.
21. Squire M, Griffin WL, Mason JB, Peindl RD, Odum S. Acetabular component deformation with press-fit fixation. J Arthroplasty. 2006;21(6 Suppl 2):72-7
22. Grimes JB, Haider H, Weisenburger JN, Langton DJ, Joyce TJ, Negative Net Clearance of Large Diameter Metal-Metal Bearings is Associated with Early Clinical Failure. Orthopaedics Research Society Transactions #1210, Vol. 36, Long Beach, CA, 2011
23. Daniel J, Ziaee H, Salama A, Pradhan C, McMinn DJ. The effect of the diameter of metal-on-metal bearings on systemic exposure to cobalt and chromium. J Bone Joint Surg Br. 2006 Apr;88(4):443-8
24. Aufranc OE. Constructive hip surgery with the vitallium mold; a report on 1,000 cases of arthroplasty of the hip over a fifteen-year period. J Bone Joint Surg Am. 1957 Apr;39-A(2):237-48

     

25. Smith-Petersen MN, Larson CB, et al Complications of old fractures of the neck of the femur; results of treatment of vitallium-mold arthroplasty. J Bone Joint Surg Am. 1947 Jan;29(1):41-8
26. Daniel J, Ziaee H, Pradhan C, Pynsent PB, McMinn DJ. Renal clearance of cobalt in relation to the use of metal-on-metal bearings in hip arthroplasty. J Bone Joint Surg Am. 2010 Apr;92(4):840-5.
27. Marker M, Grübl A, Riedl O, Heinze G, Pohanka E, Kotz R. Metal-on-metal hip implants: do they impair renal function in the long-term? A 10-year followup study. Arch Orthop Trauma Surg. 2008;128:915-919
28. Corradi M, Daniel J, Ziaee H, Alinovi R, Mutti A, McMinn DJ. Early markers of nephrotoxicity in patients with metal-on-metal hip arthroplasty. Clin Orthop Relat Res. 2011 Jun;469(6):1651-9
29. Doherty AT, Howell RT, Ellis LA, Bisbinas I, Learmonth ID, Newson R, Case CP. Increased chromosome translocations and aneuploidy in peripheral blood lymphocytes of patients having revision arthroplasty of the hip. J Bone Joint Surg Br. 2001 Sep;83(7):1075-81.
30. Ladon D, Doherty A, Newson R, Turner J, Bhamra M, Case CP. Changes in metal levels and chromosome aberrations in the peripheral blood of patients after metal-on-metal hip arthroplasty. J Arthroplasty. 2004 Dec;19(8 Suppl 3):78-83
31. Ladon D, Bhamra M, Turner J, Case CP Changes In Chromosome Aberrations And Metal Levels In The Peripheral Blood Of Patients After Ceramic-On- Ceramic Hip Replacement. Poster No: 1145.  51st Annual Meeting of the Orthopaedic Research Society  Washington, DC, 2005
32. Visuri T, Borg H, Pulkkinen P, Paavolainen P, Pukkala E. A retrospective comparative study of mortality and causes of death among patients with metal-on-metal and metal-on-polyethylene total hip prostheses in primary osteoarthritis after a long-term follow-up. BMC Musculoskelet Disord. 2010 Apr 23;11:78

     

33. Visuri T, Pukkala E. Does metal-on-metal hip prosthesis have influence on cancer? A long-term follow-up study. In: Reiker C, Oberholzer S, Wyss U, eds. World Tribology Forum in Arthroplasty Bern, Toronto, Seattle: Hans Huber, 2001: 181–188
34. Smith AJ, Dieppe P, Porter M, Blom AW; on behalf of the 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 Apr 3;344:e2383. doi: 10.1136/bmj.e2383

Update on June 5, 2012

On Jun 5, 2012, at 2:23 AM, Derek McMinn wrote:

Dear Dr Carome
 
Thank you for your response although disappointingly you have again missed the point. You cannot imagine the irritation and concern that your generalised remarks have caused in our clinical practices.
 
Ensuring patient safety clearly remains of paramount importance to us all but our roles differ in this process. Whereas you function as a policeman advocate for the patient, our daily contact with patients' hopes, aspirations and fears has encouraged us to pursue innovation.
 
The BHR was introduced in a step-wise manner. It was developed in 1997 after a decade of preliminary research and in the early years was made available only to experienced hip surgeons who were specifically trained in its implantation through an extensive and thorough surgeon training programme. Simultaneously a follow-up mechanism was established for all these patients operated in the different centres. The Outcomes Centre in Oswestry, United Kingdom was commissioned to follow-up all these patients independently. At the same time an RSA study was conducted to measure component migration.
 
Published 2-year RSA results were therefore available before introduction of the BHR into the USA. The FDA went through a very rigorous exercise before permitting the introduction of the BHR into the US market. The pre-market approval was based on the 5-year results of the BHR at the McMinn Centre with a 100% audit of the clinical documentation relating to these patients. A 100% audit of the records at the Oswestry Outcomes Centre followed. These were complemented by the results of RSA analysis and published metal ion results.
 
Furthermore the FDA’s approval was contingent on three pre-conditions: i. surgeon training in Birmingham of all potential BHR user surgeons, ii. documentation and analysis of results of all BHRs performed in the USA, iii. post-10 year clinico-radiological follow-up of the first 350 patients with BHRs performed at Birmingham. All the three conditions above were fully complied with and reported to the FDA. These are now supported by Registry data up to 10 years.
 
We congratulate the FDA on the meticulous and most rigorous manner in which they handled the introduction of the BHR into the US market. This should be held up as an example of how new devices ought to be introduced.
 
We would have appreciated a focused short answer to our question, ‘which part of our practice is a large uncontrolled experiment?’, but that is sadly missing in your response. Your current comment that, several “medical devices – including many metal-on-metal and other hip implants” have been allowed into the US market under the 510K process is perhaps true, but quite different from your earlier comment (that this is one very large uncontrolled experiment exposing millions of patients to an unknown risk). Your comments were made fully knowing that they would be used specifically in relation to an article dealing exclusively with metal-on-metal hip implants, giving the profession and the public a distorted view of reality.
 
It is a luxury for those sitting on the sidelines who have never been involved in the introduction of any  treatment for the relief of human suffering, to criticize the FDA and the MHRA (Medicines and Healthcare products Regulatory Agency of the United Kingdom) with remote contempt. These regulatory bodies in fact do a commendable job in trying to walk the tightrope of preventing the entry of clinically untried and untested devices, while not being obstructive to those which have a scientifically and clinically proven record of providing relief in otherwise unsolved clinical situations.
 
The dilemma between regulation and innovation will continue to occupy us all, but in your enthusiasm to protect the health of the nation, please do not embroil specific technology that has mastered one of the greatest challenges of modern day medicine in your worthy crusade.
 
Yours sincerely,
JosephDaniel FRCS MS(Orth)
Director of Research
McMinn Centre

Derek McMinn MD FRCS
Consultant Orthopaedic Surgeon
McMinn Centre

How safe are metal-on-metal hip implants?

Dear Dr. McMinn and Dr. Daniel,
 
Thank you for your email letters. I did not have time to review you original detailed letter and the references cited therein until now.
 
In providing comments to Deborah Cohen for her February 28 article in the British Medical Journal (BMJ), I was speaking primarily within the context of the inadequacies of the U.S. Food and Drug Administration’s review process for clearing moderate- to high-risk medical devices – including many metal-on-metal and other hip implants — under the 510(k) process. Under this process, most moderate- to high-risk medical devices are cleared for marketing in the U.S. based solely on the determination that a newly proposed device is substantially equivalent to an already marketed device (known as a predicate device), without any requirement for premarket clinical trials demonstrating that the new device is safe and effective. The prestigious U.S. Institute of Medicine in a comprehensive report issued last year found that the 510(k) process is seriously flawed and needs to be replaced because it is not intended to evaluate the safety and effectiveness of medical devices, with some exceptions. It is Public Citizen’s view that the widespread clinical use of moderate- to high-risk medical devices, such as metal-on-metal hip implants, that have been cleared for marketing under the 510(k) process without appropriate, well-designed, rigorous premarket clinical trials essentially represents poorly designed, uncontrolled experimentation on large numbers of patients. Data on the safety and effectiveness of such devices typically is collected and reported in a haphazard manner during the postmarket period, after large numbers of patients have been treated with — and in some cases harmed by — these inadequately tested devices.
 
It is my understanding that many medical devices, such as metal-on-metal hips, are also approved or cleared for marketing in Europe based on little or no clinical trial data, particularly safety data.    
 
A review of your April 16 letter and the references cited therein reaffirms the validity of my original quoted statement in the February 28 BMJ article by Deborah Cohen, and I stand by it. You provide no data demonstrating that metal-on-metal hip implants underwent rigorous premarket clinical trials prior to marketing in any country. Indeed, all of the studies cited in your letter appear to have been conducted in the postmarket period, after the hip implant devices had already been approved or cleared for marketing and introduced into clinical practice. Furthermore, it appears that only one of the cited studies was a randomized controlled study; the rest represented retrospective or prospective case series or registries of patients undergoing hip implant surgery with various hip implant devices (predominantly metal-on-metal). Thus, nearly all of the cited studies represented attempts to collect data on the safety and efficacy of various metal-on-metal hip implants during the postmarket period on patients unwittingly involved in the uncontrolled experimentation to which I was referring. Finally, the results of the various studies cited — whether they show favorable or unfavorable outcomes with respect to a particular device — are ultimately irrelevant to the assertion made in my statement quoted in the BMJ article by Deborah Cohen.
 
Thank you for the opportunity to respond to your comments, and for your patience.
 
Sincerely,
 
Michael A. Carome, M.D.
Deputy Director, Health Research Group
Public Citizen
1600 20th Street, NW
Washington, DC 20009
 
Tele: 202-588-7781
Fax:  202-588-7796
email: mcarome@citizen.org
web: www.citizen.org