SMH researchers awarded $1.4 million
Grant will be used to investigate artificial joints

ach year about 700,000 patients nationwide bring home more than a few good anecdotes and vials of medicine from their trip to the hospital. They also pack within their bodies a nice shiny artificial joint--usually a knee or hip, but sometimes an ankle, elbow, shoulder, or finger or toe joint, made of titanium. Usually the new body part operates flawlessly for decades, but nearly 20 percent of patients end up with problems eventually because the new joint loosens. That means immobility and pain for the patient, either reducing the quality of life or making another joint replacement necessary.

Now, armed with a $1.4 million research grant, physicians at Strong Memorial Hospital are investigating the genetic roots of the problem. A team from the Department of Orthopaedics led by Regis O'Keefe and Edward Schwarz is one of the first in the nation to target the genes that contribute to joint loosening. The four-year project is being funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Though surgeons affix the new joints in the body as tightly as nature does, the body itself plays a big part in rejecting an artificial joint. Sometimes the body initiates an inflammatory reaction where white blood cells known as macrophages gang up and attack tiny particles of metal and plastic that have flaked off the artificial joint. This ultimately leads to cells known as osteoclasts that attack the body's remaining bone around the joint, tearing so much of the healthy bone down that the joint eventually loosens.

Recently scientists have begun identifying the key molecular players in the cascade of events that leads to the misdirected feeding frenzy. O'Keefe, professor of orthopaedics and a Dean's Professor, and Schwarz, assistant professor of orthopaedics, are studying ways to knock out two of the genes responsible. An important part of the effort is a virus known as an adeno-associated virus, a modified cold virus that will shuttle into cells genes that have been shown to inhibit inflammation and bone resorption.

"For many people who have severe arthritis, the treatment is total joint replacement, and this is becoming more common as the population ages," said O'Keefe. "Currently there is no way to prevent this bone loss and the loosening of an implant. This gene-therapy research is one attempt to change that, and to develop a therapy that could be delivered directly to the joint."

Brendan Boyce, professor of pathology and laboratory medicine, is a co-investigator on the project. Graduate students and research associates also are participating in the research.

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