Fig. 1 A retrieved dual taper modular neck demonstrating the common clinical appearance of corrosion by-products at the modular interface.
Courtesy of Darwin Chen, MD


Published 9/1/2016
Nadim James Hallab, PhD; Mitchell C. Weiser, MD

Why Measure Systemic Metal Levels in Orthopaedic Patients?

The pursuit of longer lasting, wear-resistant designs in modern total hip arthroplasty (THA) has resulted in the introduction of alternative bearing surfaces (such as metal-on-metal [MoM]) and modularity options (such as modular THA necks). Some of these implant designs have had less-than-optimal performance and have also been correlated with elevated levels of systemic metal ions, highlighting the current usefulness of metal ion blood testing.

Unfortunately, the performance issues associated with MoM implants and modular neck stems were not recognized until early-to-midterm follow-up, after approximately 1 million of these devices had been implanted in the United States alone. Another source of concern is mechanically assisted crevice corrosion (MACC) at modular interfaces, including the neck-body and head-neck junctions (Fig. 1). The significance of these pathologies, loosely termed "trunnionosis," has increased with the popularity of dual modular necks (or modular trunnions).

Once implanted, all metal implants will release some degree of metal ions over time. These situations typically lead to increased release of metal degradation products. The degree of metal ion release and systemic effects from these ions are dependent on the mechanism of release. Wear (seen with MoM bearings) and corrosion (seen at modular junctions) are the only ways implants degrade in vivo. 

The degradation products from these processes take two basic forms: particulate and ionic (soluble), where the soluble ions readily complex with serum proteins.

Even though almost all metals in orthopaedic alloys are physiologically essential elements, local and systemic pathologies due to elevated metal ion exposure can occur, and do so as either elevated immune responses and/or tissue/organ toxicity responses. The presence of metal ions can result in systemic and local pathologies such as metal-hypersensitivity responses mediated by adaptive immune reactions (T-cells, B-cells, and others) and other adverse local tissue responses (ALTR), which can include excessive innate immune responses (eg, local macrophages) and/or tissue necrosis, osteolysis, and pseudotumor formation.

The monitoring of systemic metal ions in orthopaedic patients has been an important aspect of orthopaedic research for more than 30 years. It has been recognized that metal levels are generally elevated in people with orthopaedic implants. However, what constitutes an unsafe level of each of the circulating implant metal ions—cobalt (Co), chromium (Cr), molybdenum (Mo), titanium, aluminum, vanadium, iron, manganese, zirconium, and nickel (Ni)—is still unknown.

The interpretation of metal ion level depends on several factors including the following:

  • the type/number of implants (MoM versus metal-on-poly [MoP] THA)
  • patient symptoms (pain level)
  • patient history (diet, workplace, vitamin supplements, etc)
  • the type of metal elevated (Cr versus Co)
  • the change of metal ion levels over time

For example, all else being equal, a sudden increase in serum Co levels from 2 parts per billion (ppb or ug/L) at postoperative year 5 to 10 ppb at postoperative year 6 in a patient with an MoM THA indicates a fundamental change in implant degradation behavior and metal release. These findings would indicate using metal artifact reduction sequence magnetic resonance imaging (MARS MRI) to evaluate for the presence of tissue destruction and pseudotumor formation.

In contrast, if this same serum metal ion elevation was seen in a patient who had received a contralateral MoM THA a month earlier, then the sudden increase in metal ion levels would be more likely attributable to run-in wear of the new implant. These clinical scenarios illustrate the complexity of metal ion interpretation and the importance of understanding the interplay of patient, implant, and environmental factors.

MoM bearings
MoM THAs and hip resurfacings are known to release metal ions through mechanical wear of their metallic bearings. The process of wear and corrosion from Cobalt-alloy bearing wear releases primarily Co and Cr ions and, to a lesser degree, Mo and Ni ions. That results in local and systemic ion elevations, systemic absorption, and, ultimately, excretion.

Over time, a steady state is reached in which excretion matches production in well-performing implants. For MoM implants, this ranges from 1 ppb to 3 ppb for both Co and Cr. The acceptable level of serum Co and Cr ions from these implants has been widely debated in the literature. The current consensus statement by the American Association of Hip and Knee Surgeons (AAHKS) suggests the following:

  • Levels below 3 ppb (< 3 μg/L) are considered low risk and are associated with well-performing implants over the long term.
  • Levels between 3 ppb and 10 ppb are considered intermediate risk.
  • Levels greater than 10 ppb are considered high risk and have been associated with implant performance issues such as THA cup-neck impingement and subsequent ALTR.

Corrosion at modular junctions
Corrosion at modular junctions in all orthopaedic implants (modular necks, spinal screw-rod connections, and others) occurs through the MACC process. This process is initiated by a fluid-filled crevice in which corrosion begins, producing a locally acidic environment that causes more corrosion.

Mechanical micromotion of components (eg, head-neck) can abrade the passivation layer or protective oxide coating on all implant metals, which serves as a strong barrier to corrosion. This abrasion exposes the substrate metal alloy, increasing corrosion and further local acidification. It assists crevice corrosion with a resultant increase in corrosion products, including metal ion release. This phenomenon is a current concern in modular THA head-neck and neck-body junctions.

Head-neck corrosion
Head-neck corrosion, so-called "trunnionosis," can occur in a number of different designs, albeit to different degrees, via the MACC process. However, the causes of trunnionosis are controversial and appear to be multifactorial, with head size, taper flexural rigidity, taper surface topography, taper geometry, and material composition all playing a potential role.

Head-neck corrosion causes a differential elevation of Co:Cr because most of the released Cr ions are presumed to precipitate locally on the taper in the form of chromium orthophosphate, resulting in a systemic ratio of Co:Cr > 5-10:1. This contrasts with the approximate 3:1 ratio of Co:Cr in the bulk metal of the implant. Reference values have not yet been established for assessing the risk of head-neck corrosion. Past studies have suggested that the serum Co level in a well-functioning MoP THA should be < 1 ppb.

Neck-body corrosion
With pronounced neck-body corrosion, a two- to five-times differential elevation of serum Co:Cr ratio is typical. This is due to Cr being sequestered into a more chemically stable oxide form (eg, orthophosphate), which builds up locally as a precipitate. Cobalt does not form a precipitate and is more readily transported away. Cobalt is three times more prevalent in the parent alloy but is not typically released at higher concentrations than Cr when subjected to mild corrosion conditions. However, under more aggressive wear and corrosion conditions, Co begins to be released more readily and is disseminated and detected systemically by a higher serum Co:Cr ratio.

The current AAHKS consensus statement suggests the following:

  • Levels below 1 ppb and a Co:Cr ratio < 1 can be considered low risk.
  • Levels of 1 ppb to 5 ppb with a ratio of 1:5 are considered moderate risk.
  • Levels of > 5 ppb with a Co:Cr ratio > 5 are considered high risk.

When is high too high?
A universally applicable "safe" threshold level has not been established, due to the complexity of patient, implant, and environment. In the United States, levels of 5 ppb to 10 ppb have been suggested as indications for further analysis, surveillance, and/or action. The British Medicines and Healthcare products Regulatory Agency (BMHRA) suggests a threshold of 7 ppb for Co or Cr for all types of MoM hip implants as an indication for cross-sectional imaging.

The literature contains some reports of metal ion referable systemic toxicity (albeit at levels generally exceeding 100 ppb). To date, established systemic effects have been limited to altered immune responses (developed delayed-type hypersensitivity to metals). Environmental Co exposure and toxicity can manifest in the form of blindness, hearing loss, tinnitus, cognitive decline, peripheral neuropathy, hypothyroidism, and cardiac dysfunction. However, these have not yet been definitively established in any orthopaedic populations for implant-referable toxicity.

Talking to patients
A high level of suspicion of ALTR should be maintained if patients complain of groin, thigh, or buttock pain after a year or two of being pain-free following THA. These complaints are not pathognomonic for ALTR and a wide differential for the cause of pain should be considered. Pain after THA is a common finding in many pathologic conditions that could be either intrinsic or extrinsic to the hip.

During the physical examination, the patient should be evaluated for unilateral swelling, erythema, and wound drainage. The patient's gait pattern and abductor strength should be assessed for the presence of weakness or Trendelenburg gait. Plain radiographs should be obtained to evaluate for signs of osteolysis in Gruen zones 1 and 7, consistent with ALTR. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) serum values should be obtained to screen for periprosthetic joint infection. Lastly, serum or whole blood Co and Cr levels should be obtained in trace metal-free blood tubes and sent to a specialized laboratory for testing. The interpretation of the results of the serum Co and Cr levels is largely dependent on the laboratory performing the analysis and the type of implant present.

Metal ion release from THA and hip resurfacings can be pathogenic, as has been established over the last decade. Measuring systemic (whole blood or serum) Co and Cr ions is a minimally invasive assessment tool in the surgeon's armamentarium when dealing with patients who have a painful THA. Metal ion testing may also indicate the general status of some types of implants over time. Systemic levels of circulating metal ions can be used as an adjunct to diagnose implant-associated pathology, but only as one aspect of a complete clinical assessment. Ultimately, it is important for surgeons to be able to interpret serum metal ion levels so they can adequately counsel their patients and take appropriate action.

Nadim James Hallab, PhD, is a researcher in the department of orthopaedic surgery at Rush University Medical Center, in Chicago. Mitchell C. Weiser, MD, is an adult reconstruction fellow in the department of orthopaedics at New York University Hospital for Joint Diseases.

Bottom Line

  • The introduction of highly modular joint implants and the poor performance associated with some metal-on-metal hip implants underscores the need for metal ion testing in some patients.
  • Patient, implant, and environmental factors should be considered when interpreting metal ion levels.
  • Although no standards have been established, both the AAHKS and the BRMHA provide suggested thresholds for metal ion levels in patients with painful THAs.
  • Metal ion levels are only one part of the differential diagnosis in patients with painful THAs; surgeons should screen for other conditions as part of a complete clinical assessment.


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