US researchers have reported success in suppressing post-traumatic osteoarthritis (PTOA), also known as secondary arthritis, following an ankle injury.
PTOA is a type of arthritis that can develop after a joint injury. It tends to affect young and active patients, who are not good candidates for joint replacements. As such, there is a compelling need to prevent PTOA in this group, the University of Iowa said.
“The time to complete joint destruction can be as fast as two to four years,” explained the study’s corresponding author, Mitchell Coleman, PhD, research assistant professor of orthopaedics and rehabilitation in the University of Iowa Carver College of Medicine. “That can be devastating for an 18-year-old who injures an ankle falling off a ladder or playing sports.”
Previous work has shown that relatively few chondrocytes — the cells that make up healthy cartilage tissue — are killed at the moment of impact when a joint is fractured. Instead, cell death increases in the 48 hours following the injury, suggesting that biologic activity unleashed by the impact may contribute to early causes of disease.
The University of Iowa study, published in the journal Science Translational Medicine, focused on reducing oxidative stress in the mitochondria of chondrocytes after injury.
Using a pig model of ankle fracture, the researchers employed two approaches to limit oxidative damage: inhibiting mitochondrial metabolism with amobarbital, and boosting antioxidants in the chondrocytes with N-acetylcysteine (NAC).
“We demonstrated that the post-traumatic osteoarthritis that occurs in an ankle after a severe injury can be significantly blunted by inhibiting mitochondrial metabolism or adding key antioxidants immediately after injury,” Coleman said. “These treatments were only given twice, once right after injury and once a week later. No chronic therapy was used. Our data suggests that there might be a way to treat people acutely after they break their ankle to prevent PTOA.”
Next, the researchers hope to conduct preliminary clinical trials of the approach.