Evaluation of Metal-on-Metal Wear of Orthopedic Implants - The Role of Serum Chromium and Cobalt Analysis
Joint replacement is a successful treatment for advanced joint disease with more than 1 million total hip replacements performed worldwide each year. Wear over time of the plastic components in hip replacement has traditionally been the limitation in the durability of these implants, especially in young patients. Improved weight-bearing surfaces such as ceramic-on-ceramic and metal-on-metal were brought into the market with the expectation that wear would no longer be an issue with these types of implants and, thus, they could be used in younger, more active individuals. Metal-on-metal (MoM) hip replacements specifically have the advantage of increased toughness and decreased wear. Additionally, metal-on-metal implants allow the use of large-sized femoral heads, which wear better than smaller ones and significantly decrease the chance of the hip dislocating. While most recipients benefit from joint replacement with improved mobility and quality of life, a small number of patients experience implant-specific local and systemic adverse effects. Continuous motion at the MoM surfaces is the main reason for wear of the implant. This causes release of microparticles of metal debris into the surrounding tissue, sometimes referred to as metallosis. These metal microparticles can corrode, resulting in the release of metal ions into the circulation. The condition that causes adverse effects related to sensitivity to the metal or due to wear of the metal surfaces is called adverse reaction to metal debris, or ARMD.
Pain in patients with MoM hip replacement should be thoroughly investigated. Failures associated with MoM implants are not necessarily due to the bearing surface itself, therefore, an evaluation to rule-out implant loosening and infection is important.1,2 Pain is a characteristic symptom; groin or buttock pain is a common symptom in MoM wear and in patients with pseudotumors (a fluid-filled periprosthetic mass present around the lateral aspect of the hip). Flexion around the hip from activities such as going up stairs or sliding into a car is particularly painful and may point towards iliopsoas irritation or impingement, which may be a complication of these implants.3 Patients with pain should undergo a full clinical assessment to include an anterior and posterior pelvic radiograph and a lateral radiograph and screening blood work including a complete blood cell count with differential, erythrocyte sedimentation rate, and C-reactive protein concentration as a baseline to rule-out infection. If infection is suspected, hip aspiration followed by microbial evaluation of the synovial fluid should be performed. Once infection is ruled out and ARMD is suspected, ultrasound or magnetic resonance imaging of the hip with metal suppression (to allow accurate visualization around the implant) should be performed to rule-out the presence of pseudotumor. In the absence of loosening, infection, or pseudotumor, the patient should be evaluated for ARMD.
Composition of Orthopedic Implants
Orthopedic implants are created from various metal alloys. Porous titanium is frequently employed in the acetabular cup or stem to facilitate osteointegration; the porous titanium surface allows bone to grow into the implant, creating a strong bond between bone and the implant. The articular interface, the ball and socket joint where motion occurs, is usually made from very hard alloys comprised of various combinations of aluminum, chromium, cobalt, iron, magnesium, molybdenum, nickel, and vanadium. The most commonly used alloy is a combination of cobalt and chromium. This hard alloy allows for the smooth motion and facilitates the great weight bearing required of a successful joint.
The Role of Chromium and Cobalt
Serum Chromium and Cobalt
Reports from a number of abstracts, peer-reviewed articles, and reviews4-9 indicate that the degree of MoM wear can be assessed by evaluation of serum chromium and cobalt concentration (Table 1).
|Chao EY, et al4||Metal ion release in patients with porous coated megaprostheses.||1996||Serum aluminum, cobalt, chromium, molybdenum, titanium, and vanadium increased proportional to the surface area of the implant in human subjects.|
|Jacobs JJ, et al5||Metal release in patients who have had a primary total hip arthroplasty. A prospective, controlled, longitudinal study.||1998||Serum cobalt and chromium concentration increased with the duration of implant.|
|Lhotka C, et al6||Four-year study of cobalt and chromium blood levels in patients managed with 2 different metal-onmetal total hip replacements.||2003||Whole blood cobalt and chromium concentration increased with duration of MoM implant.|
|Liu TK, et al7||Concentration of metal elements in the blood and urine in the patients with cementless total knee arthroplasty||1998||Implant loosening correlates with whole blood concentration of cobalt and chromium.|
|Keegan GM, et al8||A systematic comparison of the actual, potential, and theoretical health effects of cobalt and chromium exposures from industry and surgical implants.||2008||Clinical findings associated with metal exposure in steel
workers and implant patients show the following:
1) The inflammatory response observed in deteriorating implants is caused by macrophage accumulation and the usual release of inflammatory regulators in tissues surrounding the implant in response to accumulating debris
2) This inflammatory response results in ulceration and tissue necrosis
3) These findings are similar in steel industry-related lung exposure and orthopedic implant-related exposure to cobalt-chromium particles
4) Cobalt-chromium particle size and chromium species (Cr+6 vs Cr+3) differentiate the exposure observed in steel industry-related exposure (Cr +6) from orthopedic implant-related exposure (Cr+3)
5) Steel industry-related exposure involves higher-level acute exposure, while orthopedic implant-related exposure is associated with low level, continuous exposure
6) Health care providers could not associate clinical findings in steel industry-related exposure to orthopedic implant-related exposure
|Madathil BK, et al9||Hypoxia-like effect of cobalt chromium alloy micro particles on fibroblasts in vitro.||2010||A hypoxia-like environment is created in the periprosthetic tissue surrounding metallic implants that contributes to an inflammatory response that may lead to aseptic loosening.|
|De Hann R, et al10||Correlation between inclination of the acetabular component and metal ion levels in metal-on-metal hip resurfacing replacement.||2008||Smaller-sized components placed at abduction angles greater than 55 degrees cause high serum cobalt and chromium ion levels.|
|De Smet K, et al11||Metal ion measurement as a diagnostic tool to identify problems with metalon- metal hip resurfacing.||2008||Measurements of serum chromium and cobalt concentrations can be used to estimate the amount of wear taking place in metal-on-metal hip-replacement devices. Serum chromium levels of >17 mcg/L and serum cobalt levels of >19 mcg/L are more likely to be associated with metallosis.|
|Tower SS12||Arthroprosthetic cobaltism: neurological and cardiac manifestations in 2 patients with metal-on-metal arthroplasty - A case report.||2010||Serum cobalt and chromium concentrations correlated with the degree of tissue degradation observed during replacement surgery, but joint fluid cobalt and chromium concentrations varied by an order of magnitude between patients.|
Table 1. Summary of notable findings in several studies on the correlation between metal ion concentrations and adverse outcomes in metal-on-metal joint replacement
Serum chromium and cobalt ion concentrations increase in proportion to the surface area and duration of the implant. Studies have also shown a relationship between postsurgical abduction cup angle and metal ion concentrations.10 Some patients experienced edge loading–a situation where the ball of the implant binds against the edge of the cup–flaking off metal debris. Edge loading tended to be more common in implants with smaller-sized cups placed at greater than 55 degrees of abduction and this situation resulted in higher metal ion concentration.
Serum cobalt and chromium are recommended as the optimal tests for evaluation of joint implant wear. All patients with MoM implants have modestly elevated serum chromium and cobalt concentrations: approximately 10 times elevated as compared to serum concentrations found in unexposed individuals. Clinically important implant wear is indicated when serum chromium exceeds 15 ng/mL and cobalt exceeds 10 ng/mL; these symptomatic patients are likely to have significant implant deterioration. Based on our laboratory’s experience, and corroborated by observations of others,6,7 serum cobalt and chromium are highest in the first year after implant. In subsequent years, and after run-in wear (initial wear of a hip implant that produces the greatest amount of metal ion release), cobalt and chromium concentrations decline, then reach steady state around 3 years after implant. This is important when evaluating patients, especially those who are asymptomatic. It would be advisable to repeat serum cobalt and chromium at 6 months and yearly to see if the concentrations have dropped before recommending revision.
Chromium and Cobalt in Joint Fluid
De Smet11 provided well-founded data relating serum and joint fluid concentrations to orthopedic implant status and metallosis (Table 2). Joint fluid concentrations of metal ions were at least an order of magnitude higher than those measured in the serum. Joint fluid represents the total metal implant environment, whereas the serum reflects implant wear-related microparticles that have undergone corrosive dissolution.
Without Metallosis (ng/mL)
With Metallosis (ng/mL)
Table 2. Serum and joint fluid metal-ion concentrations in patients with and without metallosis found at revision arthroplasty11
Relating measurements of MoM wear, the median serum chromium and cobalt concentrations in the patients with MoM wear were approximately 10 times higher than those in the patients without MoM wear (p <0.001). The median joint fluid chromium concentration was 28 times higher and the median joint fluid cobalt concentration was 20 times higher in the patients with MoM wear (p=0.001). Joint fluid cobalt and chromium concentrations correlated with serum cobalt and chromium concentrations. There was greater overlap in joint fluid cobalt and chromium concentration between patients with MoM wear and those without than seen with serum.
Tower12 provided a case report of 2 patients (1 patient was the author ) requiring joint replacement. Serum cobalt and chromium correlated with the degree of tissue degradation observed during replacement surgery, but joint fluid cobalt and chromium varied by an order of magnitude between patients.
In most situations, joint fluid is not an ideal specimen for chromium and cobalt determination. There are a number of reasons for this: 1) serum results show a greater spread in distribution between affected and unaffected as compared to joint fluid, 2) serum collection involves a much less costly collection procedure, and 3) collection of joint aspirate, performed predominantly for infection evaluation, is almost universally performed using syringes that will contaminate the specimen with chromium and cobalt. Properly collected and processed serum is the recommended specimen type.
Kwon, Willert, and colleagues have extensively studied the relationship between MoM implants and pseudotumor13,14 on 3 MoM hip resurfacing arthroplasty patient groups: 1) patients with pseudotumors, 2) patients without pseudotumors, and 3) age-matched control subjects without metal implants. The authors found that patients with a pseudotumor had up to 6 times the median cobalt serum concentrations and up to 7 times the median chromium serum concentrations compared to patients without pseudotumors. They found that evaluation of enhanced lymphocyte reaction to MoM was highly variable and possibly more related to nickel sensitivity than actual MoM wear.
Elevated chromium and cobalt concentrations may indicate implant wear, but they are not indications of toxicity. Chromium+3 compounds are not considered a health hazard, while the toxicity and carcinogenic properties of chromium+6 are well known. Chromium+6 is a by-product of electrolysis and is of concern in the chrome electroplating industry. Inhalation of chromium+6 vapors leads to pulmonary epithelial cancer. Chromium+6 that is exposed to tissues is instantly converted to chromium+3 by cellular-reducing enzymes, and this reduction releases electrons that are destructive to surrounding tissues, initiating the carcinogenic process. A key point to note is that chromium+3 is not toxic, and that only chromium+3 is released from orthopedic implants. A number of Internet blogs and Web sites rely on the experience with chromium+6 exposure from the electroplating industry to make comments on the toxicity of chromium from hip implant deterioration; it is inappropriate, however, to make that comparison because chromium+6 is not released during implant wear.
Cobalt is an essential element that is integral to vitamin B12 and required for carbonic anhydrase activity. Cobalt toxicity, known as cobaltism, can occur after ingestion of large amounts of cobalt. Symptoms associated with cobaltism include myocardial damage, renal failure, and hypothyroidism. Interstitial lung disease develops if cobalt-laden dust is inhaled. Several case reports of patients with MoM implants suggest a relationship between high serum cobalt and nonspecific neurologic manifestations (fatigue, ataxia, cognitive function decline). However, no case control studies confirm such relationships. There is no definitive proof that high serum cobalt associated with MoM wear either causes toxicity or is benign. Large population studies are underway; more definitive information will evolve over the next few years.
Specimen Collection and Processing for Metal-Free Analysis
Collection of uncompromised specimens for cobalt and chromium testing is difficult.15-17 Biological specimens for chromium and cobalt evaluation are easily contaminated. Most specimen collection products contain chromium in the rubber stopper or O-rings to add plasticity to the rubber. Plastic syringes with black rubber plunger seals commonly used in specimen collection are particularly problematic because the black rubber contains high concentrations of both cobalt and chromium. Special rubber was created to manufacture evacuated blood collection tubes suitable for use in trace metal testing. The Metals Laboratory at Mayo Clinic has tested numerous blood collection tubes and has found that most of them introduce contamination when used for trace metal specimen collection. Standard red-topped evacuated clot tubes and all plastic syringes with black rubber seals are grossly contaminated with zinc, and all contain varying amounts of heavy metals (lead, mercury, cadmium, nickel, chromium, and others). All rubber stoppers (except the royal blue-top Monoject Trace Element Blood Collection Tubes) have significant concentrations of aluminum and chromium in the rubber, which are carried into the specimen on the puncturing needle, contaminating the specimen.
Only 2 manufacturers make devices for sample collection that are suitable for chromium and cobalt analysis. The royal blue-top Monoject trace element blood collection tubes are approved by the FDA for chromium and cobalt analysis. If specimens require collection using a syringe, the only metal-free syringe approved by the FDA for use in human subjects is the Norm-Ject syringe by HSW.
The environment contains high chromium concentrations. Airborne dust contains chromium concentrations as high as 10,000 times more than the chromium concentration in blood; so the specimen that is exposed to room air after collection may very well be contaminated.
Mayo Medical Laboratories offers the following assays: COS/80084 Cobalt, Serum and CHR/8638 Chromium, Serum to assess serum chromium and cobalt. Analyses for trace metals at Mayo Clinic and Mayo Medical Laboratories are performed in an ultraclean laboratory environment using a system of positive-pressure filtered air to prevent specimen contamination due to dust. This allows for detection of many metals at the sub-part-per-billion concentration range.
Serum cobalt and chromium are recommended as the optimal tests for evaluation of joint implant wear; concentrations of these elements are elevated in all patients with MoM orthopedic implants. The degree of elevation of serum chromium and cobalt correlates with MoM orthopedic implant deterioration. However, increased serum chromium and cobalt concentrations in the absence of symptoms such as joint pain do not, independently, indicate implant wear.
Joint synovial fluid concentration shows less capability in differentiating patients with metallosis from those without metallosis and therefore it is not a good discriminator for implant wear. So far, only De Smet11 has documented a relationship between MoM-related wear, tissue damage, and elevated synovial fluid cobalt and chromium. While this work is well founded, until it is corroborated by others and a clear differentiation between affected versus unaffected individuals is demonstrated, synovial fluid analysis remains a research tool.
Proper specimen collection is essential for successful evaluation of serum chromium and cobalt metal ion concentrations. Contamination of the specimen with chromium or cobalt from the environment or from blood collection devices will adversely affect the accuracy of the results. Proper steps must be taken during specimen collection to minimize contamination and provide a specimen that yields clinically useful results.
- Bartelt RB, Yuan BJ, Trousdale RT, Sierra RJ: The prevalence of groin pain after metal-on-metal total hip arthroplasty and total hip resurfacing. Clin Orthop Relat Res 2010;468:2346–2356
- Browne JA, Polga DJ, Sierra RJ, et al: Failure of larger-diameter metal-on-metal total hip arthroplasty resulting from anterior iliopsoas impingement. J Arthroplasty 2011;26:978
- Bartelt RB, Sierra RJ: Recurrent hematomas within the iliopsoas muscle caused by impingement after total hip arthroplasty. J Arthroplasty 2011;26 (665):1–5
- Chao EY, Frassica F, Prichard DJ, Moyer TP: Metal ion release in patients with porous coated megaprostheses. 41st Annual Meeting of the Orthopaedic Research Society, Orlando, Florida, 1995 February 13–16 (Abstract)
- Jacobs JJ, Skipor AK, Patterson LM, et al: Metal release in patients who have had a primary total hip arthroplasty. A prospective, controlled, longitudinal study. J Bone Joint Surg 1998;80:1447–1458
- Lhotka C, Szekeres T, Steffan I, et al: Four-year study of cobalt and chromium blood concentrations in patients managed with two different metal-on-metal total hip replacements. J Ortho Res 2003;21:189–195
- Liu TK, Liu SH, Chang CH, Yang RS: Concentration of metal elements in the blood and urine in the patients with cementless total knee arthroplasty. Tohoku J Exp Med 1998;185:253–262
- Keegan GM, Learmonth ID, Case CP: A systematic comparison of the actual, potential, and theoretical health effects of cobalt and chromium exposures from industry and surgical implants. Crit Rev Toxicol 2008;38:645–674
- Madathil BK, Lin O, Hew C-H, Mohantyn M. Hypoxia-like effect of cobalt chromium alloy micro particles on fibroblasts in vitro. J Ortho Res 2010;28:1360–1367
- De Haan R, Pattyn C, Gill HS, et al: Correlation between inclination of the acetabular component and metal ion concentrations in metal-on-metal hip resurfacing replacement. J Bone Joint Surg Br 2008;90:1291–1297
- De Smet K, De Haan R, Calistri A, et al: Metal ion measurement as a diagnostic tool to identify problems with metal-on-metal hip resurfacing. J Bone Joint Surg 2008;90:202–208
- Tower SS: Arthroprosthetic cobaltism: neurological and cardiac manifestations in two patients with metal-on-metal arthroplasty - A case report. J Bone Joint Surg 2010;92:1–5
- Kwon Y-M, Thomas P, Summer B, et al: Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty. J Orthop Res 2010;28:444–450
- Willert HG, Buchhorn GH, Fayyazi A, et al: Metal-on-metal bearings and hypersensitivity in patients with artificial hip joints: a clinical and histomorphological study. J Bone Joint Surg 2005;87:28–36
- Moyer TP, Mussmann GV, Nixon DE: Blood-collection device for trace and ultra-trace metal specimens evaluated. Clin Chem 1991;37:709–714
- Boeynaems JM, De Leener A, Dessars B, et al: Evaluation of a new generation of plastic evacuated blood-collection tubes in clinical chemistry, therapeutic drug monitoring, hormone, and trace metal analysis. Clin Chem Lab Med 2004;42:67–71
- Rodushkin I, Odman F: Assessment of the contamination from devices used for sampling and storage of whole blood and serum for element analysis. J Trace Elem Med Biol 2001;14:40–45