An interview with AAOS Second Vice-President Joshua J. Jacobs, MD
AAOS Second Vice-President Joshua J. Jacobs, MD, is no stranger to the issue of biomaterials in hip and knee replacement implants. As chair of the department of orthopaedic surgery at Chicago’s Rush University Medical Center, Dr. Jacobs has conducted extensive research on this topic and has served as a consultant on the development, regulation, and testing of orthopaedic devices.
Joshua J. Jacobs, MD
AAOS Now: Dr. Jacobs, just what is the FDA asking for?
Dr. Jacobs: The letters issued by the FDA are asking orthopaedic device manufacturers to conduct postmarket surveillance studies. A component of those studies will involve an analysis of cobalt (Co) and chromium (Cr) levels in the bloodstream and how those levels may or may not relate to the performance of the implant and the presence of either local or remote symptoms related to the hip replacement.
Before issuing these letters, the FDA spent considerable time deliberating on this matter. It requested clinical input from the AAOS, the American Association of Hip and Knee Surgeons, and the Hip Society on the issues that we as orthopaedic surgeons are seeing in our patients with MOM total hip replacements and surface replacements. The FDA has also considered information from regulatory agencies in other countries and data from international registries. Just recently, the FDA hosted a meeting with leaders from all the prominent international registries to discuss how registries can help with postmarket surveillance for a variety of hip and knee replacement devices, including MOM hip replacements.
AAOS Now: Do we know what form these studies will take?
Dr. Jacobs: Not yet. The manufacturers have 30 days to respond to the FDA, outlining their ideas and protocols. The FDA then has 60 days to respond to the manufacturers. Therefore, these studies won’t be initiated for several months.
AAOS Now: Much of the concern with MOM implants focuses on the level of metal ions in the patient’s bloodstream, so we can probably assume that these measurements will be a component of the studies. What are the challenges that companies—and orthopaedic surgeons—face in conducting such an analysis?
Dr. Jacobs: Using Co and Cr levels as a diagnostic test to evaluate the status of a hip replacement is a relatively new phenomenon. Serum and/or whole blood Co and Cr levels can provide insight into the performance of the device, because increased wear and/or corrosion can lead to the accelerated release of these metallic elements from the Co-Cr alloy components that comprise MOM implants. Metal release can take the form of particles (primarily in the nanometer size range) or metal ions. Both can be measured in the bloodstream or in the joint fluid, and it is difficult to distinguish between the two.
One of the challenges in measuring serum or whole blood concentrations of Co and Cr is that they’re extremely low, at the level of parts per billion. Therefore, samples can be easily contaminated by Co or Cr in the environment. Appropriate attention must be paid to how the blood is acquired and handled so that these processes don’t introduce any contamination.
Presently, national standards for these tests do not exist. We need to establish such standards so that we can be confident that we can reliably compare Co and Cr concentrations from different laboratories. Currently, some labs test serum while others test whole blood. Labs may use different methods to measure the levels, such as high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) or atomic absorption spectrometry (AAS). This variability in matrix (serum vs. whole blood) and method (HR-ICP-MS vs. AAS) may lead to different detection limits and different absolute values of Co and Cr. Successfully conducting the kind of studies that the FDA is asking the companies to organize requires reproducible, precise, and accurate metal ion data.
AAOS Now: Do we know the normal levels of these elements in the bloodstream?
Dr. Jacobs: Data from various studies establish normal values in the patient with normal renal function and without a metal implant. For such a patient, the normal level of serum cobalt is less than 0.3 μg/L or parts per billion (PPB), and for serum chromium, it is less than 0.1 mg/L. Establishing the ‘normal’ level in a patient with a metal-containing implant is harder to establish and requires an extensive database of patients who have well-functioning total hips with of variety of designs and bearing surfaces, including metal-on-metal, metal-on-polyethylene, and ceramic-on-ceramic. Once we have that normative data, we could identify any outliers that may signify accelerated wear and/or corrosion.
It is critical to realize that the metal being measured in the bloodstream can come from a variety of sources, not just the bearing surfaces of a total hip replacement. For example, fretting of a loose femoral stem against bone or bone cement, fretting corrosion at modular junctions, or the presence of other implants—such as cerclage cables used in the setting of a periprosthetic fracture—could contribute to the overall Co and/or Cr level if the components are made of Co-Cr alloy or stainless steel.
When I talk to other orthopaedic surgeons about the issue of interpretation of whole blood or serum metal testing, I stress that the metal level is just one piece of information that should be used to make clinical decisions. It can be very helpful at times if the testing is done by a lab that has reproducible and accurate data, but whole blood or serum metal levels should not be used in isolation when evaluating and treating a patient with a metal-containing implant, including an MOM hip replacement.
Right now, no “threshold value,” above which the patient should definitely undergo revision surgery, has been established. The decision for revision surgery is multifactorial, taking into account all the clinical, imaging, and laboratory information that is available. We hope that data from the FDA-requested studies, as well as data from other ongoing clinical research, will help establish additional guidance for clinical decision-making.
AAOS Now: What can retrieval analysis tell us about MOM hips?
Dr. Jacobs: A component of the FDA request was that the companies perform an analysis of any devices that are retrieved from patients. Retrieval analysis is a critical process to understand those factors that are associated with success or failure of an implanted device, not only in this case of MOM bearings, but for any implant (Fig. 1). We also need to look at both devices that have failed and those that have performed well. The latter involves postmortem retrieval studies that are difficult to conduct and are rarely reported in the literature.
Retrieval analyses on MOM implants that have been revised for cause (such as loosening, infection, or adverse local tissue reaction) have been quite helpful in enabling us to understand the patterns of wear and corrosion, the interaction of wear and corrosion products with local tissues, and implant-related factors that are associated with clinical failure.
AAOS Now: How concerned should patients and their surgeons be that the FDA has made this request?
Dr. Jacobs: Orthopaedic surgeons should be aware of this action by the FDA and carefully counsel their patients on its implication. To date, most hip replacements (both total hip replacement and hip resurfacing) are functioning well and as intended. This is true for MOM total hip replacements and surface replacements as well. Nonetheless, routine periodic surveillance is recommended for all patients with total hip replacements.
Furthermore, patients who have local symptoms such as pain or swelling are encouraged to seek timely follow-up with their orthopaedic surgeons. A new onset of any systemic neurologic, endocrinologic, or cardiac symptoms should be discussed. It is appropriate to stress the importance of considering the entire clinical picture—the patient’s symptoms, the orientation of the components, the findings on conventional and advanced imaging studies (such as a metal artifact reduction sequence [MARS]-MRI), the track record of the implant, and whole blood or serum Co and Cr levels when evaluating the patient with a MOM hip replacement.
Some elements of the media have been raising concerns that serious, systemic problems involving the cardiovascular and neurologic systems have been linked to elevated Co and Cr levels. It is important to note that only six such cases have been reported in the world literature, and only two of the six are in patients with MOM bearings. Although additional cases that have not been reported may exist, symptomatic systemic toxicity does seem to be a very rare event given that millions of patients worldwide have metal-containing hip replacements. Orthopaedic surgeons and primary care physicians need to be aware of possible systemic effects, but the rarity of these cases needs to be understood.
Cobalt and chromium containing devices have decades-long track records of safety and effectiveness. Joint registries and studies such as those requested by the FDA are aimed at identifying and addressing problems with these devices, and the AAOS supports these efforts. As orthopaedic surgeons, we are concerned about patient safety, and we support ongoing clinical research on these devices. The AAOS will continue to work collaboratively with researchers and the FDA to alert members to developments in a timely manner and to share information that will help keep patients safe.
Disclosure information: Dr. Jacobs—Johnson & Johnson; Medtronic Sofamor Danek; Smith & Nephew; Spinal Motion; Zimmer; Implant Protection; Taylor and Francis.