Metal-on-metal hip implants and the risk of cancer

Osteoarthritis of the hip is a common disease, and in the past 50 years it has been possible to treat it successfully with joint replacement surgery. Surgery in younger people with higher demands for activity is increasingly being undertaken owing to modern implants and refined surgical techniques. However, in such situations, implants need to have extended longevity and no long term adverse effects. Two linked research studies examine large national datasets from Finland (doi:10.1136/bmj.e4646) and the United Kingdom (doi:10.1136/bmj.e2383) to estimate the risk of cancer in patients with metal-on-metal hip implants.1 2

With potentially lower wear,3 lower risk of dislocation, and better outcomes than metal-on-polyethylene articulations,4 modern metal-on-metal implants, including large metal heads and hip resurfacing, have become popular. These implants currently account for 35% of hip replacements in United States and 14% in the United Kingdom. Recent reports of peri-prosthetic adverse soft tissue reactions and high blood metal ion concentrations have raised concern that exposure to metal ions may increase the risk of cancer.5 6

After hip replacement, metal ions and particles with potential to damage DNA (mainly chromium and cobalt) can be found throughout the body.7 Particles emanating from metal-on-metal articulations are much smaller than those that come from metal-on-polyethylene implants. Because exposure is internal and chronic, direct comparison with the effects of occupational exposure to metals is not possible.7

Several long term register studies and meta-analyses of patients with metal-on-polyethylene and older metal-on-metal hip articulations (1950s and 1960s) suggest no increase in overall cancer risk for patients with joint replacement (some studies also included patients who had undergone knee replacement surgery).8 9 10 11 Increased risk for melanoma and possibly urinary tract and prostate cancers were, however, reported in some studies. The question of whether the increased risk is associated with the underlying disease (osteoarthritis) or the treatment (joint replacement) remains unclear.

A recent long term register study of patients who had knee replacement in Sweden, with up to 30 years’ follow-up,12 did find an increased overall risk of cancer (relative risk of 1.1 to 1.26 in different groups compared with the general population). Increased risks were found for several specific cancer types, but the authors inferred that only myelodysplastic syndrome and possibly melanoma and prostate cancer might be linked to metal exposure from the implant.

In one of the linked studies Mäkelä and colleagues examined data from 10 728 patients with modern metal-on-metal replacements from the Finnish Arthroplasty Register alongside linked data from the Finnish Cancer Register.2 Mean follow-up was 3.6 years. They found no overall increased risk of cancer. Compared with other bearings, however, metal-on-metal implants conferred a non-significantly increased risk of soft tissue sarcoma (relative risk 2.69, 95% confidence interval 0.89 to 6.71) and a significantly increased risk of basal cell carcinoma (1.32, 1.06 to 1.66).

In the second linked study, Smith and colleagues examined data on 40 576 patients with metal-on-metal hip replacements from the National Joint Registry of England and Wales linked to data from NHS hospital episode statistics on cancer diagnosis (excluding non-melanoma skin cancers).1 Mean follow-up was three years and 23% of patients were followed for more than five years. They found no overall increased or type specific (melanoma, haematological, prostate, or renal tract) risk of cancer.

The follow-up in these two studies is short, considering both the latency of cancer development and the potentially long duration of remaining life in younger patients.1 2 Despite the size of the Finnish study it lacked the statistical power needed to analyse risk by specific cancer type, making the findings inconclusive.2 Use of aggregated data from several national arthroplasty registers would facilitate such analyses and might make implant specific evaluations possible. Currently available data do not allow patient specific factors, such as smoking, concomitant disease, and drugs, to be adjusted for; this problem needs to be rectified in the future.

A recent study confirmed that patients who undergo arthroplasty have lower 10 year mortality than is seen in the general population. However, beyond 20 years after surgery mortality increased in those who had undergone arthroplasty (standardised mortality ratio 1.20, 1.04 to 1.37), partly as a result of cardiovascular disease.13 The underlying cause of higher longer term mortality is unknown, but an association with debris and metal ions from joint replacement is possible and needs to be investigated.

The first short term results of modern metal-on-metal implants and cancer risk are reassuring,1 2 but questions remain. Longer follow-up is needed to monitor later adverse effects that include other diseases and mortality in addition to cancer. When advising younger patients about the risks of metal-on-metal arthroplasty, doctors should explain clearly that the long term risks of cancer are not known. Clinicians may consider restricting the use of metal-on-metal articulations in this patient group until more is known.