There has been an increasing amount of media attention questioning the risks of metal-on-metal hip implants in the past few years. The issue became of particular interest in 2010, when DePuy, a subsidiary of Johnson & Johnson, was forced to recall two of its products due to a high rate of failure. Then, in a seemingly unexpected move last May, the FDA required that all metal-on-metal hip manufacturers conduct studies analyzing the health effects of these metal implants. Now, the British Medical Journal (BMJ) has published an article by investigations editor Deborah Cohen, whose retrospective analysis shows that this move is not only long overdue, but also a result of regulators’ and manufacturers’ failure to act in the interest of the patients who relied on them.
Cohen not only analyzes the dangers of metal-on-metal hips, but also highlights in detail the ways in which manufacturers and health regulators contributed to this medical catastrophe. She states, “Despite the fact that these risks have been known and well documented for decades, patients have been kept in the dark about their participation in what has effectively been a large uncontrolled experiment.” DePuy recalled the ASR XL Acetabular System and ASR Hip Resurfacing System only two years ago, but curiosity arises as to how the products found their way into the market at all, considering the fact that tissue damage associated with debris from metal-on-metal hips has been extensively documented since 1975.
The damaging, potentially carcinogenic effects of metal ions such as cobalt and chromium debris have are a major, and familiar, concern. Cohen cites a DePuy internal memo acknowledging among other things “…One study suggested a threefold risk of lymphoma and leukaemia 10 years after joint replacement… However, the ultimate test is the long term human experience.” Apparently, DePuy knew about the cancer risks, yet continued with their marketing. Perhaps even more unsettling is the ambiguity surrounding the risks of metal ions. Cohen notes that there are no regulatory standards in place concerning cobalt ion levels in orthopedic implant patients. While Dr. Schmalzried (who is a designer and consultant for DePuy) recommends that cobalt ions should be less than 2 micrograms per liter and the MHRA thinks that levels above 7 warrant investigation, studies have found cobalt levels reaching over 300 micrograms per liter in recent metal-on-metal hip implants. High levels had been found in implants such as DePuy Pinnacle hip system, along with similar designs manufactured by Smith and Nephew and Zimmer.
Perhaps one of the most disconcerting things pinpointed in this article is the regulatory failure leading up the recent events. It began as early as 1997, when a mere mechanical simulation was all that was needed to approve the invasive device that was to be implanted in thousands of unsuspecting patients.
In 2004, manufacturers made slight changes to the implants by shortening a portion of the stem, known as the trunnion or taper. Due to a regulatory loophole called 510(k), these design tweaks were approved by the FDA without any clinical testing to prove their efficacy. The agency had commented in 2004, saying “The design, while not identical to the predicates, does not raise any new issues of safety or effectiveness.” So the design changes were approved and the experimentation began.
As it turns out, these small changes had large consequences. In conjunction with increasingly large head diameters, the modifications resulted in elevated metal ion concentrations and significant joint failure. Tony Nargol, an orthopedic surgeon at University Hospital of North Tees, tells Cohen “We’re seeing patients with tapers which are blackened, destroyed, metal getting into the tissues of the hip, damaging the muscles, taking out some of the bone, so destroying parts of the pelvis,”
To make matters worse, manufacturers were well aware of these concerns. In fact, the article reveals an internal email showing that Japanese surgeons had raised concerns over DePuy Pinnacle in 2009. They had identified dead tissue associated with the metal debris, and attributed this to Pinnacle’s design. Despite the fact that DePuy had this information, they continued to advertise the product, pushing it forward as an “alternative” during the massive ASR recall that followed the year after.
In response to fears over whether or not the metal-on-metal hips produced carcinogenic debris, the Medicines and Healthcare Products Regulatory Agency (MHRA) created an eight member advisory group to assess the risks versus benefits of the device in 2006. However, certain members within the group call its credibility into question. Rather than including a statistician or epidemiologist, the MHRA allowed three members who had a conflict of interest; two members were DePuy consultants and one was a product director for Smith & Nephew. Despite having evidence of the association between metal hips and genotoxicity, including knowledge of metal ions being passed to unborn children, the advisory group chose to promote the device and boast its benefits.
These preceding events reveal that DePuy’s recall and the FDA-ordered studies have been a long time coming. The move ordering all metal-on-metal hip manufacturers to perform studies is one done in hindsight. Michael Carome, deputy director of Public Citizen’s Health Research, sums it up best when he tells Cohen, “This is one very large uncontrolled experiment exposing millions of patients to an unknown risk. We will only find out about the safety of these devices after large numbers of people have already been exposed.”