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(HealthNewsDigest.com) – The hunt is on for a simple, new blood or urine test that can provide doctors with an early warning when particles shed from their patients’ synthetic joint replacements during daily use cause the bone around the new joints to deteriorate.
The two chief ways to diagnose this kind of failing replacement joint now are X-rays and a patient’s reports of pain. However, by the time either of those two markers can indicate the problem, the damage already may be irreparable by any means other than additional surgery.
Physicians in the United States alone replace more than 1 million hip and knee joints every year, but a significant number of joint replacement patients need what’s known as a revision surgery to replace the replacement joint itself. Of the more than 1 million hip and knee replacement performed annually in the U.S., approximately 20 percent are revisions.
‘These joints need to last’
Now a research team at Rush has received a $1.7 million, five-year grant from the National Institutes of Health to look for new “biomarkers,” or indicators of disease. The goal is to develop a simple blood or urine test that can flag osteolysis, the excessive bone erosion caused by minute particles sloughed off by a replacement joint.
“Osteolysis can happen in anybody who gets a joint replacement,” says D. Rick Sumner, PhD, chairman of theDepartment of Anatomy and Cell Biology at Rush, and the principal investigator for the study” It’s thought that since osteolysis is caused by particles shed from the implant, it probably has more to do with the usage of the implant, with wear and tear, than with an allergic reaction.
“We would like to have an early indication of osteolysis,” Sumner says. Specifically, the team is seeking a test that can identify which patients have osteolysis early enough to stop the process, or perhaps even reverse it, with drugs instead of surgery.
The effort comes at a time when joint replacement – and in many cases, osteolysis – have become commonplace. “Joint replacement has been one of the most effective procedures of the past century,” notes Joshua Jacobs, MD, a co-investigator on the study. Jacobs is Rush University’s associate provost for research and chairperson of the RushDepartment of Orthopedic Surgery. Before replacements became commonplace, he says, “people with end-stage osteoarthritis were condemned to a life of pain and disability.”
With the U.S. population aging, many individuals remaining very active late in life and others becoming heavier, knee replacements are projected to increase by 673 percent by 2030, and hip replacements by about 174 percent. “We need to find effective strategies to handle this demand. These joints need to last, if possible, for the rest of a patient’s life,” Jacobs says.
Biomarking breakdowns
The recent past president of the American Academy of Orthopaedic Surgeons, Jacobs worked on previous research that investigated the complications of a popular “metal-on-metal” replacement joint which have been all but abandoned. Debris cast off from that device in some cases caused significant damage to bone and soft tissue.
The new study at Rush is not aimed at tracking the actual debris from synthetic joints, though. It’s looking for the body’s responses to the debris.
The best prospect probably lies with a pair of biomarkers that indicate bone is breaking down: CTX-I, a particular sequence of amino acids that appears when collagen deteriorates; and protein CAT-K, an enzyme involved in bone resorption. Because inflammation of joint tissue is one cause of accelerated bone turnover, signs of inflammation in the body could provide an even earlier indication that a replacement joint is going bad.
These markers make their way into the blood and/or urine, where they would be detectable in a test. Elevated levels of these measures could be an indicator that normal bone turnover has accelerated into osteolysis.
Sumner and co-investigator Amarjit Virdi, PhD, associate professor of anatomy and cell biology, will be conducting basic science studies to determine if a blood or urine tests can identify patients who are experiencing accelerated bone decay, and if there are drugs that can slow or even reverse osteolysis once it has started.
Once one or more biomarkers are identified, the research team, which also includes Jeff Borgia, PhD, assistant professor of pathology, will try to confirm their usefulness by looking for elevated levels of those markers in urine samples of patients who later needed revision surgery.
Blood tests like the one the Rush team is seeking are coming on strong as a diagnostic tool in medicine. Reliable diagnostic blood tests recently have been deployed to detect the lethal Ebola virus and for irritable bowel syndrome, a common condition that is often mistaken for more serious diseases.
“We would like to have a set of three to four markers that would provide a good indication that there is a problem developing – a simple test,” Sumner says. “The point of the grant is the discovery of basic knowledge that someday may lead us to it.”
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