Health Risks of Metal on Metal Implants Proven in Mice

Following the release of an alert by the UK's Medicines & Healthcare Products Regulatory Agency (MHRA) in September 2010, a DePuy ASR Metal Hip Replacement was withdrawn from the market because of increased incidence of failure. The problem was caused by adverse reactions to wear debris and metal ions released from the implant and the concerns of patients have been well publicised.

Work carried out in the University of Strathclyde's Bioengineering Unit by a group of researchers led by Professor Helen Grant has investigated the mechanisms involved in adverse reactions to the metallic cobalt chromium (CoCr) alloy wear debris generated from the ASR hip joint. This manuscript, published by the UK Scientific Publisher The Royal Society Interface, represents the work of a PhD student, Moeed Akbar, funded by a UK Engineering and Physical Research Council (EPSRC) Case Award with De Puy International Ltd, in collaboration with Professor Jim Brewer and colleagues at Glasgow University.

The work demonstrates an inflammatory reaction in response to implantation of the CoCr wear debris into mice, and shows the presence of necrosis and fibrosis locally in adjacent tissues. Previous work by the group using the same animal model published in the Journal of Biomedical Material Research last month demonstrated the release of metal ions, particularly cobalt, from the wear debris. Cobalt ions disseminated rapidly into the blood, and were measured in organs including the liver, kidney, heart, lungs, spleen, brain and testes. These findings in the in vivo mouse model suggest that encapsulation of the wear debris with inflammatory cells and fibrotic tissue, as well as formation of necrotic tissue and release of cobalt ions into the circulation may contribute to the adverse reactions to metal debris observed in patients.

The manuscript from the Royal Society is as follows:

Adverse reactions to metal debris generated by metal-on-metal hip resurfacing are thought to be due to an inflammatory process in response to excessive particulate metal debris. To investigate this, the inflammatory response to cobalt chromium alloy (CoCr) wear debris from a metal-on-metal hip resurfacing implant was measured in a rodent air pouch model for up to 7 days. Air-pouches were injected with either sterile phosphate buffered saline, lipopolysaccharide (as positive control) or the CoCr debris. Inflammatory exudates showed that CoCr debris induced a specific inflammatory reaction. Debris accumulated in the pouch wall and this was accompanied by a vast infiltration of inflammatory cells, primarily monocytes/macrophages, as well as fibrosis and tissue necrosis around the debris. The CoCr debris also increased expression of chemokines and cytokines involved in promoting inflammation and fibrosis. Encapsulation of CoCr debris by fibrotic tissue and inflammatory cells may also contribute to the adverse reactions to metal debris seen in patients.

The work by Strathclyde's bioengineering unit demonstrates an inflammatory reaction in response to implantation of the CoCr wear debris into mice, and shows the presence of necrosis and fibrosis locally in adjacent tissues.