UNMC researchers developing test to detect warning signs of joint replacement failure

More than 1.5 million total joint replacement operations are performed worldwide each year. While the success rate is 90 percent, almost 10 percent of implants fail and require additional surgery.
Now, University of Nebraska Medical Center researchers have discovered a promising test to detect the early stages of a major cause of failure in joint replacement implants, so patients can be treated and possibly avoid additional surgery.
The research, published online in the American Chemical Society’s Molecular Pharmaceutics, highlights the work of Dong Wang, Ph.D., associate professor of pharmaceutical sciences in the College of Pharmacy.
Researchers know that wear and tear in a joint replacement can create tiny bits of debris — micrometers in size — that cause local inflammation and lead to bone loss. When this happens, the implant can become loose and set the stage for failure. Treatment usually comes too late because it’s difficult to detect the problem in its early stages.
“Unfortunately,” Dr. Wang said, “when pain or clear X-ray evidence is noted, usually considerable bone loss already has occurred that often cannot be easily restored.”
Ed Fehringer, M.D., associate professor of orthopaedic surgery at UNMC, agrees. “If we can identify bone destruction earlier, it could be beneficial,” he said. “Ultimately, we hope to reduce the number of revision surgeries as they are incredibly expensive and less successful than primary or first-time replacements.”
To provide an early diagnostic tool for implant failure, Dr. Wang developed a polymer-based system for imaging the inflammation associated with the wear debris. Tests of the imaging agent in mouse bone suggest that it can help detect the early stages of bone loss that might cause a joint implant to become loose and/or painful.
Researchers also found that they could tether a powerful anti-inflammatory drug to the polymeric system, offering a way to locally treat inflammation and bone loss in these early stages of wear.
The novel idea originated on a Friday afternoon more than two years ago when Drs. Fehringer and Wang met to brainstorm potential collaborations. “Dong explained his research and I immediately knew we could work together,” Dr. Fehringer said.
Dr. Wang also credited Steven Goldring, M.D., chief scientific officer and St. Giles Chair at the Hospital for Special Surgery in New York, for his significant contributions. “Steve’s group not only helped us understand the working mechanism of our system, but also provided the very animal model that we used to validate our hypothesis.”
The next step for the team is to test the polymeric system in an animal model with a prosthetic joint and then in humans. Fortunately, the nanocarrier system already has been approved in Europe and the United States for human phase I or phase II trials to improve anticancer chemotherapies. 
In the end, the research team hopes to prolong the life of the implant with improved patient outcomes.
More about the project:
Additional collaborators: UNMC’s Ke Ren, Ling-dong Quan and Geoffrey Thiele, Ph.D., and P. Edward Purdue, Ph.D., and Lyndsey Burton from the Hospital for Special Surgery (HSS) of New York
Patent: UNMC and HSS investigators have filed a joint patent application on using the polymeric nanocarrier system for detecting prosthesis loosening.
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