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Duke researchers make advances in arthritis prevention

Herald-Sun (Durham, NC) - 3/30/2015

March 29--DURHAM -- For the first time anywhere, Duke Medicine researchers have limited the development of arthritis after a joint fracture.

Their work was with mice, but the results hold out promise of treatments that could prevent arthritis after joint fractures in humans.

Post-traumatic osteoarthritis accounts for 12 percent of all cases, affecting 6 million people in the United States each year.

The researchers earned the highest honor for their research in orthopedic surgery recently in Las Vegas, where they received the Kappa Delta Award from the American Academy of Orthopaedic Surgeons and the Orthopaedic Research Society.

The team developed the first closed-joint experimental model of a knee fracture to study post-traumatic inflammation and the onset of osteoarthritis in mice.

They found that injecting a rheumatoid arthritis drug called anakinra immediately after the fracture reduced the severity of inflammation and arthritis -- the first successful intervention to limit the development of arthritis after fracture of a weight-bearing joint.

The researchers also found that infusing a joint fracture with stem cells increased bone volume while the fracture healed. But they learned that the rheumatoid arthritis drug was a more effective treatment to reduce the severity of arthritis in the joint.

Dr. Steven Olson, principal investigator for the research and an orthopedic surgeon at Duke, said the team's work is based on a holistic view of injury in the knee joint.

"The traditional approach is to take a complicated problem like a knee fracture, and dissect it and look at each element -- the load that goes across the joint, the force that's transmitted to the bone and cartilage, the blood and inflammation," Olson said. "While these pieces are interesting, all of these things are happening at once. It's hard to make sense of these pieces in isolation. We needed to look at the joint as a whole. The big step was creating the model."

The development of the knee fracture model in 2003 was followed by years of research in animal models and examination of their joints, microscopic slice by microscopic slice, for more than 10 years. This helped the team better understand the fracture, inflammation and genetic and environmental factors that allow some animals to recover quickly while others had more severe arthritis.

Olson said that currently, surgeons can't do much to prevent arthritis in human patients after a joint fracture except to align the joint as precisely as possible. But he said the findings from the rheumatoid arthritis drug are promising, although they require injection soon after injury.

"What's interesting and exciting is that this is the first time anyone has shown that there's a drug of any kind that improved arthritis after an injury like this," Olson said. "It's beginning to point in the direction that we need to go. The challenge is that it's rare that you get to a person very quickly after an injury."

But one day, the drug might be used on the football field and at other sporting events, Olson said.

"This is total speculation on my part, but there may be a role for a medication like this immediately after injury in a sports setting, to prevent inflammation that could lead to arthritis," he said.

If doctors can stop the initial inflammation after injury, he said, cartilage damage might be prevented.

"Right now, the only thing we can offer many people is surgery," Olson said. "But with this much better understanding of why arthritis develops, in the future we may be able to offer additional treatment to actually prevent its onset."

Duke has applied to the U.S. Department of Defense to fund a pilot human trial, which would involve injecting patients with the drug after joint fractures to see if it's effective.

The DOD, which helped fund the Duke research, is interested because so many soldiers become unfit for duty after joint fractures.

In addition to Olson, other Duke researchers were Farshid Guilak, Virginia Kraus, Bridgette Furman and Janet Huebner.

Olson said it was a team effort from start to finish.

"It's a good example of collaboration in science," Olson said. "I couldn't have done it without them."

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