A failed joint replacement leaves patients and surgeons with big problems. Rutgers researchers homed in on the role of the immune system in the inflammation and bone loss that can occur after such as surgery.
Their study, “Sterile particle-induced inflammation is mediated by macrophages releasing IL-33 through a Bruton’s tyrosine kinase-dependent pathway,” appears in the January 21, 2019 edition of Nature Materials.
According to the Rutgers researchers, the study “found white blood cells, called macrophages, respond to the particles as if they were harmful invaders and engulf them. But the cells then die and secrete a specific molecule that triggers an even stronger immune response – including inflammation which can cause tissue damage and bone destruction which leads to loosening of the implants.”
“Bone degradation can occur within 10 to 15 years and often requires complex revision surgery to replace the implant and treat bone loss,” said lead author William Gause, director of the Center for Immunity and Inflammation at Rutgers New Jersey Medical School. “However, many people start experiencing pain from this inflammation shortly after surgery. They are prescribed medications for the pain, but the loosening continues.”
More generally, say the researchers, these studies reveal new insights into how inert and sterile microparticles, including pollutants such as diesel exhaust particles or silica, can cause robust and harmful inflammation, ultimately leading to disease.
“Although we typically think of infectious agents or toxins as causing disease, apparently the response of the body to these particles, which have essentially no intrinsic activities, can result in considerable tissue damage and pathology,” Dr. Gause said.
Dr. Gause told OTW, “We showed that sterile microparticles of a similar size and composition to wear debris particles trigger a type 2 inflammatory response in joint tissue and further showed that this could be inhibited by targeting specific signaling pathways including Bruton’s tyrosine kinase and IL-33.”
“Implant failure may result from harmful inflammation that leads to bone damage and aseptic loosening. This inflammation can be triggered by sterile microparticles that induce a particular type of immune response, which may be controlled by targeting Bruton’s tyrosine kinase or IL-33.”
Right. This is the problem with replacing living tissue with something foreign that the body will eventually decide to attack.
To get these replacements to work long term, you’d have to venture into immunology and get the patient on some kind of immunosuppressive drug for life.
With 7 promising cartilage regeneration drugs on the way in phase 2 or 3 trials, and 2 approved for use in other countries, we should be fast tracking these drugs and joint replacements should be reserved as an option of last resort.
I am 36 and staring down the barrel of joint replacements due to a lifelong bone deformity that has caused cartilage lesions. Patients in Japan, Korea, and now Australia have the ability to dodge this bullet as of last year. I don’t know what is holding up the United States.
Ty for this information. I was born with degenerative hips and no ball in right hip socket, so after many years of pain and full body casts and a leg four inches shorter than the other till age seventeen when had leg length surgery only gained two inches. Which then led to complete total hip reconstruction on both hips. After right one done it was OK but when left one dine major swelling and pain and I’m used to pain so have a high tolerance for it but this was beyond painful. The Dr has no idea what was wrong,he literally sat n a chair crossed his legs and said hmm this is a challenge. After they tried to see if fluid on hip three times which was very painful they decided still a challenge. Finally Dr said needed hip redone due to rod moving inside the bone, so went back to surgery. Ever since First one I’ve had major swelling and pain and hurts even walking I hear clicking and popping constantly. So Ty so much for ur information to know I’m not alone in this case.
There’s an interesting paper published in Cellular Physiology and Biochemistry 2018;50:1100-1112 by An et al. and entitled “Curcumin Inhibits Polyehtylene Induced Osteolysis via Repressing NF-kB Signaling Pathway Activation” that addresses the issue too. Interesting reading and a possible adjunct to delaying or suppressing osteolysis in total joint replacement.