A recent British Medical Journal/BBC Newsnight investigtion published at BMJ2012,344:e1410doi: 10.1136/bmj.e1410 (2/28/12) and entitled, "How safe are metal-on-metal hip implants?", reveals the unsafe history of metal-on-metal hip implants and the inadequate response by European and U.S. regulatory bodies to the evidence of health risks posed by such implants. Cobalt-chromium implants are known to release metal ions that can seep into local tissue causing reactions that destroy muscle and bone and leave some patients with long-term disabilities. Id. at p. 1. This phenomenon was first described in detail as early as 1975. Id. Scientist now know that some metal-on-metal implants release metal ions on a much greater scale than previously thought. Id.
What are the genotoxic effects of cobalt-chromiummetal ion release into one's tissue and bloodstream? In 1990, the WHO listed hexavalent chromium as a carcinogen. The ion being released in metal joint implants is trivalent chromium. Nonetheless, the BMJ and Newsnight report that manufacturers of metal-on-metal implants were aware of the potential for genotoxicity, citing a July 2005 internal memo from DePuy that says: "In addition to inducing potential changes in immune function, there has been concern for some time that wear debris may be carinogenic." The DePuy memo also cites a study suggesting a threefold risk of lymphoma and leukaemia 10 years after joint replacement. Id.
Despite this concern, DePuy aggressively marketed its metal-on-metal hips, equipping its sales force with a 2006 paper written by one of DePuy's prosthesis designers, Thomas Schmalzreid, M.D. (who is currently a defendant in many DePuy ASR lawsuits), entitled, "Setting the record straight on metal hypersensitivity." Id. at 2. The BMJ article opines that the European and U.S. regulators failed to identify the design changes that made some of the metal implants, such as the DePuy ASR, more likely to release metal ions at a greater than expected rate. And the regulators failed to identify the consequences for patient safety. Id.
Here is an important table from the BNJ article:
How commercialism trumped safety
Why are patients still exposed to the harms of metal implant failures identified in 1975— implants that divided the orthopaedic community when they were reinvigorated in the 1990s?
The answer seems to be unfettered innovation coupled with a drive for commercial success unconcerned with patient safety.
The conventional total hip replacement consists of a metal head with a polyethylene cup. But these joints don’t last forever. Over time the plastic cup wears away against the hard metal head. Younger, more active people are especially likely to require early revision surgery to replace the worn out joint.32
Through the 1960s and ’70s, surgeons were looking at ways to preserve more bone. After a failed attempt in 1970 to develop the resurfacing technique with metal on polyethylene, attention turned to metal as a more durable option. In particular, a combination of cobalt and chromium—he same metals that had given rise to concerns when used in total hip implants in the 1970s.
Birmingham surgeon, Derek McMinn took to his garden shed to design a resurfacing prosthesis made of metal. If done correctly—arefully—he believed an implant could be made with metal surfaces that did not touch and surfaces that wore very little.
Once it hit the European market in 1997, the Birmingham Hip Resurfacing—cquired by Smith and Nephew—apidly gained popularity as it preserved more bone, was believed to last a lifetime, and virtually eliminated the risk of dislocation, allowing patients to get back to heavy jobs and playing sport.3
But the initial release of the BHR onto the market was tightly controlled. Mr McMinn, the designer, personally instructed selected surgeons and emphasised the need for good surgical technique and patient selection.
The positive results—lower wear, less risk of osteolysis, and less dislocation—soon piqued the interest of other manufacturers keen to be part of the metal revolution.17
But as the excitement over hip resurfacing grew through the early 2000s, surgeons continued to report the bodily spread of metal ions released through the wear of implants.33 The reinvigorated metal technology was controversial and the risks were too high for some.
As Ronan Treacy, a consultant trauma and orthopaedic surgeon at the Royal Orthopaedic Hospital in Birmingham, writes in Mr McMinn’s book about resurfacing,34 surgeons were branded as “maverick” and irresponsible for using metal on metal by both the “establishment” and industry. “But finally the issue grudgingly found its way on to the agendas of boardrooms around the world,” he said.
As competition grew the boundaries were pushed and the regulators were no match against the commercial pressure. Carefully crafted surgical innovations fell into the hands of the powerful multinationals and shareholder interests trumped patient safety.
The following table from the BMJ article speaks for itself:
Timeline: Metal-on-metal hips
1975: Study describeslocal tissue reactions caused by cobalt and chromium ions from metal-on-metal hips6
1988: Study shows human synoviocytes killed by cobalt in vitro (Rae T. Clin Orthop 1988;232:244–54)
1989: Metal-on-metal hip resurfacing designs start in Birmingham
1990: WHO International Agency for the Research on Cancer lists trivalent chromium as a potential carcinogen and cobalt ions as a probable carcinogen
1991: First metal-on-metal hip resurfacing device is implanted in Birmingham
1994: Study shows dissemination of cobalt and chromium ions into lymph, liver, and spleen5
1996: Patients with metal-on-metal hips found to be at increased risk of cancer compared with those with metal-on-plastic hips: relative risk of haematopoietic cancer 1.59 (95% confidence interval 0.8 to 2.8) and leukaemia 3.77 (0.9 to 17.6) (Visuri T, et al. Clin Orthop 1996;329 (suppl):S280–9)
1997: Birmingham Hip Resurfacing (BHR) implant comes onto the European market
1998: Particles of cobalt and chromium shown to be toxic to monocytes in culture (Haynes DR, et al. Clin Orthop 1998;352:223-30)
2000: NICE guidance on selection of prostheses for primary hip replacement and resurfacing sets a benchmark revision rate for conventional hip replacement of ≤10% at 10 years
2003: Derek McMinn and Ronan Treacy publish paper showing positive results with BHR. This kickstarts the trend for larger heads in total hip replacement
2004 McMinn, designer of the BHR, says, “Caution still needs to be exercised until longer term results are available”
2004 One of DePuy’s modified stems with a shortened trunnion is cleared by the FDA, which says the modified design “does not raise any new issues of safety or effectiveness”
2005: Internal DePuy memo reflects early concerns about health risks of wear debris from metal on metal hips. “In addition to inducing potential changes in immune function, there has been concern for some time that wear debris may be carcinogenic”
2006: MHRA Committee on Safety of Devices says there’s growing concern over the biological risks of metal wear debris
2006: The Department of Health’s Committee on Mutagenicity concludes that “some metal on metal (those using cobalt-chromium) hip replacements may be associated with increased DNA-changes, and increased genotoxicity in patients.” It says this “may present a potential risk of carcinogenicity in humans”
2007: Implantation of large diameter metal-on-metal hips starts to increase rapidly in the UK, and resurfacing peaks. Metal-on-metal hips account for 20% of market this year
2007: UK expert advisory group chooses not to contraindicate metal-on-metal hips in women of child bearing age—ven though metal ions had been detected in the umbilical cord and placental blood
2007: The MHRA’s Committee on Safety of Devices recommends that all patients sign a consent form setting out the risks associated with metal wear debris. But this recommendation is not widely communicated
2008: Study shows 20% of patients with DePuy’s Pinnacle hip system have metal ion levels over the upper limit accepted by occupational health experts
2009: Japanese surgeons raise concerns with the design of DePuy’s large diameter metal-on-metal system. They report seeing “generated metal debris between stem taper and head, and final necrosed tissue” and blame it on the poor connection between the two
2009: All joint replacement implants are re-classified as class III devices after the implementation of Directive 2005/50/EC
2010: In an internal email obtained by the BMJ, a senior figure in DePuy writes: “I feel the problem [with large diameter metal on metal] is emerging as more serious than first thought.”
2010: DePuy recalls its ASR hip prostheses. Some studies show a failure of the total hip replacement secondary to adverse reactions to metal debris of 50% at 6 years
2010: DePuy promotes Pinnacle—ncluding metal-on-metal—s “an alternative for the majority of patients”
2011: Tony Nargol and his team warn the MHRA of failures with the Pinnacle implants
2011: British Orthopaedic Association writes to surgeons to say that large diameter metal-on-metal total hip replacements should be “carefully considered and possibly avoided”
2011: A two year follow-up study in 144 patients shows an incremental increase in metal levels over the study period in a range of large head metal-on-metal implants made by companies including Zimmer, DePuy, and Smith and Nephew26
2011: FDA writes to about 20 manufacturers to say that it is requiring post-marketing studies in cases where an implant’s failure could have serious consequences. Companies would be expected to take blood samples from patients to measure metal ions.
2011: National Joint Register describes large diameter metal-on-metal and resurfacing prostheses in some people as a “cause for concern”
2011 Trial comparing large diameter Birmingham hip replacement with conventional hip is terminated after 2 years. Metal ion levels were raised above the MHRA advised safety level (7 μg/L) in 20% of the metal-on-metal group and in one patient in metal-on-polyethylene group (who had a metal-on-metal implant on the contralateral side)27
2012: At the annual American Academy of Orthopedic Surgeons conference manufacturers promote metal-on-metal products to the 40 000 attendees.
Although it is currently in vogue in this county for politicians to espouse the elimination of all government regulations, this case screams out for better, more proactive regulation. Proactive regulation may have prevented hundreds of thousands of patients from their current health crisis. Indeed, British regulators said yesterday that patients who received certain all-metal artificial hips, such as the type that was widely used in the U.S., should undergo annual examinations for as long as they have the device to make sure they are not suffering metal debris-induced tissue damage or other problems.