Metal-Particle Inflammation Causes Joint-Implant Failure

The very joint implants that bring pain relief and restore freedom of motion to patients’ extremities can be their own undoing, setting off a metal-induced immunological defense mechanism that causes the implants to loosen and fail, according to a recent study. The study, funded by the National Institutes of Health and to be published in the Journal of Orthopaedic Research , was conducted by researchers at Rush University Medical Center. It won an award for scientific merit from the Orthopaedic Research Society.

Up to 10 percent of total joint replacements – of which there are 600,000 a year in the United States – loosen and fail, requiring a second surgery to correct them. This failure is often caused by inflammation from particles of metallic debris that break loose as the metal components of the joint implant wear against each another.

“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,” said Nadim Hallab, associate professor at Rush University Medical Center and the study author.

Inflammation in the body can develop along two pathways – one that starts from bodies that cause infection, such as viruses and bacteria, and another triggered by non-infectious factors, such as ultraviolet light and oxidative stress. This study is the first to show that metal dust and ions from implants can begin this second inflammation cascade.

Describing this cascade, Hallab said that specialized immune-system “cleanup” cells, known as macrophages, first attack the metal dust. They “engulf it in sacs called lysosomes and try to get rid of the debris by digesting it with enzymes.” But the particles damage the lysosomes, Hallab said, “and the cells start screaming ‘danger.’”

Then large complexes of proteins, called inflammasomes, detect these chemical danger signals. The inflammasomes gather, setting off the cascade of chemical events causing inflammation.

Now that light has been shed on this pathway, Hallab and his colleagues said, the door may be open to developing new therapies to head off early failure of joint implants.

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Metal-Particle Inflammation Causes Joint-Implant Failure

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