Saturday, September 8, 2012

Lessons from the Metal-on-Metal Experience

 

What can we learn from the “unknowns” of new technology?

Mary Ann Porucznik

AAOS First Vice-President Joshua J. Jacobs, MD, is nationally recognized as a leading researcher on materials used in orthopaedic implants. At the 2012 annual meeting of the Association of Bone & Joint Surgeons, he addressed the ongoing investigations into the performance of metal-on-metal (MoM) hip implants, focusing on the lessons learned that can be applied to similar issues in the future.

Noting that not all MoM bearings are created equal, Dr. Jacobs pointed to the way the controversy about their use has served as a platform for the public to question the professionalism of orthopaedic surgeons and the entire U.S. medical device regulatory process. He also expressed concern about similar risks in the future as new technologies are introduced.

Needed: A U.S. joint registry

In particular, Dr. Jacobs called for a U.S. joint registry. “Registry data, especially from the United Kingdom (UK) and Australia, were key to identifying the problem, and the United States—which has more joint replacements than the UK, Sweden, Finland, and Australia combined—needs its own registry,” insisted Dr. Jacobs.

He pointed out that different patterns of use are found here, and U.S. surgeons have different training and use different types of implants. A registry would provide the data to enable researchers and physicians to know what’s happening in patients in real time.

Implant failure mechanisms
In reviewing the history of MoM implants, Dr. Jacobs admitted, “We didn’t know as much about implant failure mechanisms as we thought we did. Simply reducing volumetric wear isn’t enough. Wear-related arthroplasty failure is more complicated than that.”

Photograph of a retrieved large-head MoM hip replacement implant demonstrating signs of mechanically assisted crevice corrosion at the head/neck junction.
Courtesy of Joshua J. Jacobs, MD

 
The focus on wear prompted implant designers to turn to metals that didn’t wear as much on a volumetric basis as the polyethylene options that were available. Metals, however, produce nanometer-sized wear particles and are susceptible to corrosion by the nature of their chemistry. These features of metallic implants result in debris production that is different in character from that produced by polymeric materials, such as polyethylene.

“Because metal wear particles are significantly smaller (by a factor of 10) than polyethylene wear particles, there are actually more of them,” said Dr. Jacobs. “Now we have to ask what’s most important—the number of particles, the size, the shape, or some other factor(s)?”
Despite the use of highly corrosion-resistant alloys such as cobalt-chromium and titanium, electrochemical corrosion is an important mechanism of failure of a hip replacement and can result in both osteolysis and other adverse local tissue reactions.

Dr. Jacobs urged the audience to “ask patients about their general health.” He noted that patients with metal-on-polyethylene bearings may have serum metal ion levels two to four times higher than controls, and in patients with well-functioning MoM bearings, those levels can be elevated another 5- to 10-fold. He pointed to the potential for a systemic response due to chronically elevated levels of cobalt and chromium.

“These cases seem to be rare—only five have been reported in the medical literature in patients with MoM bearings—but there are likely cases that have not been reported,” he said. “Despite the relative rarity of these systemic responses, it’s important that orthopaedic surgeons ask patients if they’re having other general health problems, particularly with their nervous and cardiovascular systems.”

The immune response
A better understanding of the immune response to metal debris is also needed, because some of the reactions may be due to an adaptive immune response (hypersensitivity). Metal allergies to orthopaedic implants are believed to be a delayed type-IV hypersensitivity response.

According to Dr. Jacobs, 10 percent of the general population is allergic to certain metals, based on patch testing. Up to 25 percent of patients with well-functioning joint replacements who undergo patch-testing will show sensitivity to one of these metals; among patients who have a poorly functioning or loose implant, 60 percent will be sensitive to metals as determined by patch testing. “This finding does not demonstrate cause-and-effect,” he noted, “but there’s an interesting association between metal sensitivity and implant performance.”

He noted that making the diagnosis of metal hypersensitivity is challenging. (See “Skin Patch Testing and Associated Total Knee Outcomes, page 40). “Patch testing is a great test for contact dermatitis, but its applicability for assessing deep-tissue allergy is uncertain,” said Dr. Jacobs. “And the results of lymphocyte transformation testing (LTT) have not been widely clinically validated and may be difficult to interpret.”

He noted, however, that studies using LTT have again shown an association between total hip replacement failure and sensitivity. In one study, LTT identified metal sensitivity in 71 percent of patients with osteolysis, compared to 30 percent of controls.

“Why is this important?” he asked. “An activated lymphocyte not only can cause a delayed-type hypersensitivity response, but also release proinflammatory cytokines that upregulate the innate immune system, giving rise to a mechanism of osteolysis that can be termed hypersensitivity-induced osteolysis, which is different than what we saw in patients with metal-on-polyethylene bearings.”

Monitoring patients
Dr. Jacobs urged joint replacement surgeons to monitor their patients carefully, particularly patients who have MoM bearings. He indicated that although some patients may appear asymptomatic, they may be at risk for an adverse local tissue reaction.

“Waiting too long before intervention can allow these reactions to compromise the soft-tissue envelope, leading to relatively poor results in revision surgery,” he said. “On the other hand, if we, as clinicians, monitor patients closely, with metal ion levels and MRI scans when indicated, we can prevent the loss of integrity of the soft-tissue envelope around the hip that leads to these poor results.”

He noted that insufficient evidence exists to establish a whole blood or serum metal level threshold to trigger revision surgery, although the British Medicines and Healthcare Products Regulatory Agency (MHRA) has suggested 7 parts-per-billion as a marker to more closely monitor patients. “But many of us have seen patients with relatively low metal levels who have adverse local tissue reactions, as well as patients with metal ion levels of 20 to 30 parts-per-billion who don’t seem to have any clinical problems,” said Dr. Jacobs.

Preclinical testing
Dr. Jacobs called for more predictive preclinical testing of devices used in total joint replacement. He noted that, with MoM devices, hip simulations and mechanical tests failed to predict the clinical performance that has been observed. “There is urgency in developing more clinically relevant preclinical testing modalities,” he said.

The size of the femoral head is also an issue. “Bigger is not necessarily better,” he cautioned. In MoM stemmed total hip replacement devices, in particular, smaller heads generally are outperforming larger heads, although this is device-specific. As a result of the UK registry data, he noted, “the British Hip Society advised surgeons not to use large-diameter MoM stemmed total hip replacements.”

Finally, noted Dr. Jacobs, orthopaedic surgeons “need to be circumspect about how we adopt new technology in our practices. If we have a patient population that is not well served by current treatments, new technology is warranted. But for patient groups that have good results with existing devices, the bar should be much higher for introducing new technology.”

Disclosure information: Dr. Jacobs—Implant Protection; Medtronic Sofamor Danek; Nuvasive; Zimmer.
Mary Ann Porucznik is the managing editor of AAOS Now; she can be reached at porucznik@aaos.org

Bottom Line
  • The United States needs a joint registry to enable orthopaedic surgeons to track patient outcomes in real time and enable them to identify potential problems early.
  • Additional research into failure mechanisms, a better understanding of the immune response to implantable devices, and more predictive preclinical testing modalities are needed to anticipate and avoid problems with new technologies.
  • Patients who have MoM hip implants should be monitored closely to identify possible signs of adverse local tissue reactions; orthopaedic surgeons should ask these patients about general health problems that could result from systemic reactions to metal debris.
  • Orthopaedic surgeons should be circumspect in adopting new technologies, particularly in patient populations that respond well to current technologies.
AAOS Now
September 2012 Issue
http://www.aaos.org/news/aaosnow/sep12/clinical1.asp

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