Monitoring for potential toxicity in patients with metal-on-metal hip prostheses: advice for health professionals

 

Hip arthroplasty can be a highly successful procedure | Concerns over long-term safety of MoM implants | Cobalt–chromium ions — how much is too much? | Signs of cobalt–chromium toxicity — advice for GPs | GP practice points | What the professional organisations and regulators say | References

Summary

The safety of metal-on-metal (MoM) hip prostheses is currently under review because of higher-than expected-rates of revision with some, and  emerging concern about the potential for metal ion toxicity due to erosion of chromium and cobalt from metal surfaces.

GPs have an important role in monitoring metal ion levels in people with MoM prostheses; an understanding of the likely presentation of metal ion toxicity will assist in interpreting the relevance of abnormal findings and in deciding when to consider specialist intervention (see GP Practice Points).
It is important to consider cobalt–chromium toxicity even in patients who had total hip replacement (THR) surgery many years before emergence of symptoms.

Conventional total hip replacement (THR) prostheses consist of a metal head that fits into a polyethylene or ceramic cup; however, concern about the potential for wear and tear of the plastic or ceramic components prompted increased use of the MoM alternative. MoM joints made of a cobalt–chromium alloy have been used since the very early days of THR, with first-generation prostheses implanted in the 1930s.1

With the advent of new designs and engineering modifications, including increased femoral head size, reduced neck diameter and shortened taper length, newer THR implants promised an increased range of motion and lower risk of dislocation for patients.1 Whereas for conventional THR, prostheses may consist of metal, plastic or ceramic components, for resurfacing hip replacement, when existing bone is capped with new surface material, there are limited alternatives to MoM components.

Over time, wear of MoM implant surfaces produces metal wear debris in the form of nano- and microparticles, resulting in metal ion release, which together may affect both the local tissue and other body systems. Extended exposure to metal debris and released metal ions may produce a range of adverse effects (see Box 1). There are reports of potential local and systemic adverse effects of MoM implants emerging, often within 5 years of surgery.1

Hip arthroplasty can be a highly successful procedure

Hip arthroplasty generally has a high success rate, restoring pain-free mobility to many elderly and, increasingly, younger patients.2 It is considered among the most successful and most cost-effective surgical interventions for improving quality of life.1  With Australia's ageing population, the number of THRs performed here is forecast to increase from the 37,000 currently carried out each year.3 The long-term success of new-generation implants has encouraged younger and more active people to consider THR, with some manufacturers specifically targeting this patient demographic due to the forecast longevity of new prostheses.4

The Australian Orthopaedic Association reports that 95% of people undergoing total hip replacement will have a functioning joint 10 years after surgery.2

Concerns over long-term safety of MoM implants

The aim of a THR is to maintain a fully functional joint while delaying as long as possible the need for surgical revision or replacement. But with the shift from conventional-sized to large-diameter femoral head prostheses with metal bearing surfaces, comes the need for vigilance regarding their long-term safety.1

One concern with this type of joint replacement is that the combination of shorter taper connections and larger heads in the prosthetic hips causes instability of the joint. Unintended consequences include increased wear at the joint interface — a concern for the physical longevity of THR with MoM prostheses — and the potential for microparticulate metal debris and high rates of metal ion release locally into surrounding tissue and systemically into the bloodstream.2

First reports of adverse tissue reactions to metal debris from MoM THR appeared in 2008.1,2 They described the development of pseudotumors — soft-tissue masses thought to occur as a result of either a toxic reaction to an excess of particulate metal wear debris or a hypersensitivity reaction to a normal amount of metal debris. In 2011 there were in excess of 5500 people in Australia with MoM THR implants, and approximately 7.8% of these had required revision surgery within 5 years.5

People with MoM prostheses may be exposed to cobalt and chromium particles and elevated tissue ion levels for decades.4 Nanoparticles of implanted ionic metals can disseminate systemically with possible cytotoxic, genotoxic and immunological consequences, so, given the long latency of particle-mediated disease, there is an understandable call for vigilance.2

Clinical consequences of cobalt–chromium toxicity may be due to both local (soft-tissue reactions) and systemic (arthoprosthetic cobaltism) effects.1

There is evidence that pseudotumours occur as a secondary reaction to wear and the creation of cobalt–chromium nano- and microparticles but are also associated with duration of exposure to the MoM prosthesis. Although the pathway is not fully understood, it is thought that a combination of macrophage-induced necrosis and T-lymphocyte-mediated hypersensitivity reactions explains the large variance in response between patients. However, there is significant variability in individual sensitivity and thresholds of toxicity.1

Cobalt–chromium ions — how much is too much?

While both chromium and cobalt ion levels are elevated in patients with MoM implants, cobalt is the most important contributor to metal ion toxicity.6 When cobalt was used to treat refractory anaemia in patients in the 1960s, symptoms of cobaltism were described and subsequently confirmed to include neurological, cardiac and endocrine symptoms.1,2

Pathology laboratories are reporting an increasing number of people who have had an MoM THR and have very high serum cobalt concentration (> 1000 nmo/L).7 Serum reference ranges for cobalt and chromium are 0–20 nmol/L and 0–100 nmol/L, respectively.7 In individual case reports, patients with high serum cobalt concentrations who undergo revision surgery with ceramic–plastic revisions experience a rapid fall in serum cobalt and significant improvement in neurological and cardiovascular function.8

The essential link between symptoms and peak metal ion levels or the length of exposure to these ions remains unclear. Consequently there is a lack of consensus worldwide as to whether metal ions released from MoM implants may cause systemic problems in addition to those that may occur at the site of implantation, and more research is required to establish levels at which the presence of metal ions may cause toxicity.1 Many people with MoM THRs and high cobalt levels have fully functioning athroplasties and no signs or symptoms of toxicity. Neither the Australian Therapeutic Goods Administration nor the U.S. Food and Drug Administration has specified the concentration of heavy metal ions necessary to produce adverse systemic events.9,10

Signs of cobalt-chromium toxicity —
advice for GPs

Cobalt–chromium toxicity produces a symptom complex that may include neurosensory, endocrine, respiratory, neurocognitive, cardiac and neurological symptoms, such as loss of auditory and visual acuity (see Box 1). When presented with a seemingly disparate cluster of symptoms, it may be difficult for the clinician to identify metal ion toxicity as a potential precipitating cause, even in people who have had MoM THR.

While opinion is divided about levels at which the presence of metal ions may cause systemic toxicity, increasing levels of chromium and/or cobalt on serial review should prompt referral to the treating surgeon for further investigation and review.11 It is important that serial tests are performed by the same laboratory to exclude variability between test sites and test methods.12

Box 1: Some reported symptoms of arthroprosthetic cobaltism7

  • Tinnitus
  • Deafness
  • Vertigo
  • Visual disturbances
  • Skin rashes
  • Hypothyroidism
  • Tremor
  • Dyspnoea on exertion
  • Mood disorders
  • Dementia
  • Heart failure
  • Peripheral neuropathy


GP practice points

  • Identify patients in your practice who have undergone MoM THR and assess them no less than annually for local (pain or decrease in joint function) and systemic (loss of auditory or visual acuity) symptoms.9,10
  • In all patients with MoM implants screen for serum cobalt and chromium at least annually and every 3 months thereafter if levels continue to rise.9
  • Consider orthopaedic referral for those with increasing serum cobalt or chromium concentrations on serial review and/or if they have persistent symptoms.11
  • Be aware that patients with renal failure are at particularly high risk for cobaltism.13
  • Consider the effects of cobalt–chromium toxicity in the context of the individual patient, their symptoms and risk factors. Differing individual thresholds to metal ion toxicity and sensitivity are likely.1
  • Follow up patients with MoM THRs who are asymptomatic no less than annually.9,10 Ensure they have a structured regular review process in place with their treating surgeon.
  • When assessing metal ion levels, consider whether there are other reasons to explain abnormal findings, such as occupational exposure, other metal implants, renal insufficiency or inappropriate use of dietary supplements.10

What the professional organisations say

The Australian Orthopaedic Association (AOA) has published an update on MoM hip replacements and states that it is aware of the issues and is currently monitoring the latest research. The AOA recognises that all patients with MoM hip prostheses will have higher levels of cobalt and chromium, but that the relationship between elevated levels and toxicity has not been established.2

The AOA update acknowledges that MoM hip prostheses have been safely used for the past 40 years and therefore recommends against revisions based solely on increased serum metal ion concentrations or because a patient has an MoM prosthesis. Elevated levels must be evaluated in conjunction with symptoms and X-ray results. The Australian Athroplasty Society (AAS) together with the AOA recommend all joint replacements are monitored regularly.2

View the Australian Orthopaedic Association's Update on Metal on Metal (Mom) Hip Replacements

Opinion of the US Food and Drug Administration

Opinions from the UK

References

  1. Gill HS, Grammatopoulos G, Adshead S, et al. Molecular and immune toxicity of CoCr nanoparticles in MoM hip arthroplasty. Trends Mol Med 2012;18:145–55. [PubMed]
  2. Australian Orthopaedic Association. Update on metal on metal (MoM) hip replacements. 2011. http://www.aoa.org.au/Libraries/Patient_Information/Patients_MoMUpdate_110711.sflb.ashx (accessed 21 March 2012).
  3. Australian Orthopaedic Association. National Joint Replacement Registry. Hip procedures reported. 2012. www.dmac.adelaide.edu.au/aoanjrr/statistics.jsp?section=hips (accessed 24 April 2012).
  4. Cohen D. How safe are metal-on-metal hip implants? BMJ 2012;344:e1410. [PubMed]
  5. Commonwealth of Australia. Senate Committe of Inquiry: The regulatory standards for the approval of medical devices in Australia. Canberra: Commonwealth of Australia, 2011. http://www.aph.gov.au/Parliamentary_Business/Committees/Senate_Committees?url=clac_ctte/medical_devices/report/index.htm (accessed 10 May 2012).
  6. Rizzetti MC, Catalani S, Apostoli P, et al. Cobalt toxicity after total hip replacement: a neglected adverse effect? Muscle Nerve 2011;43:146–7; author reply 7. [PubMed]
  7. Mao X, Wong AA, Crawford RW. Cobalt toxicity – an emerging clinical problem in patients with metal-on-metal hip prostheses? Med J Aust 2011;194:649–51. [PubMed]
  8. Tower SS. Arthroprosthetic cobaltism associated with metal on metal hip implants. BMJ 2012;344:e430. [PubMed]
  9. Australian Government Department of Health and Ageing Therapeutic Goods Administration. Metal-on-metal hip replacement implants. Information for general practitioners, orthopaedic surgeons and other health professionals. 2012. http://www.tga.gov.au/hp/information-devices-mom-hip-implants.htm (accessed 21 September 2012).
  10. U.S. Food and Drug Administration.FDA Safety Communication: Metal-on-metal Hip Implants. 2013. http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm335775.htm (accessed 20 March 2013).
  11. Smolders JM, Bisseling P, Hol A, et al. Metal ion interpretation in resurfacing versus conventional hip arthroplasty and in whole blood versus serum. How should we interpret metal ion data. Hip International : The Journal of Clinical and Experimental Research on Hip Pathology and Therapy 2011;21:587–95. [PubMed]
  12. Daniel JP. Metal ion testing. US Food and Drug Administration. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/OrthopaedicandRehabilitationDevicesPanel/UCM310311.pdf (accessed 24 September 2012).
  13. Tower S. Arthroprosthetic cobaltism: identification of the at-risk patient. Alaska Med 2010;52:28–32. [PubMed]