Immune reaction to metal debris leads to early failure of joint implants

Researchers at Rush University Medical Center in Chicago have identified a key immunological defense reaction to the metals in joint replacement devices, leading to loosening of the components and early failure.

The study, funded by the National Institutes of Health, won the annual William H. Harris, MD Award for scientific merit from the Orthopaedic Research Society. Currently posted online, it is expected to be published in the June issue of the Journal of Orthopaedic Research.

More than 600,000 total joint replacements are performed in the United States each year. The vast majority of replacements are successful and last well over 10 years, but in up to 10% of patients, the metal components loosen, requiring the patient to undergo a second surgery, the authors said in a press release.

The loosening is often caused by localized inflammation, an immune reaction to tiny particles of debris from the components themselves as they rub against one another. No infection is involved.

“As soon as joint replacement devices are implanted, they begin to corrode and wear away, releasing particles and ions that ultimately signal danger to the body's immune system,” co-author Nadim Hallab, MD, said in the press release.

There are two different types of inflammatory pathways: one that reacts to foreign bodies like bacteria and viruses, which cause an infection, and another that reacts to “sterile” or non-living danger signals, including ultraviolet light and oxidative stress. This is the first time that researchers have shown that debris and ions from implants trigger this danger-signaling pathway, he said.

According to Hallab, when specialized cells of the immune system, called macrophages, encounter this metallic debris, they “engulf it in sacs called lysosomes and try to get rid of the debris by digesting it with enzymes.” However, the particles damage the lysosomes, “and the cells start screaming ‘danger,’” he said in the press release.

These danger signals are detected by large complexes of proteins, called inflammasomes. The inflammasomes mobilize, precipitating a chain of chemical events that cause inflammation, according to Hallab.

The researchers are hopeful that identification of this molecular pathway that triggers inflammation without infection could lead to new and specific therapeutic strategies to avoid the early failure of joint replacements.

Reference:
Caicedo M, Desai R, McAllister K, et al. Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: A novel mechanism for implant debris reactivity. J Orthop Res. DOI: 10.1002/jor.20826