CAN OSTEOCLAST BIOMARKERS DETECT EXCESSIVE SUBCHONDRAL BONE RESORPTION IN RACEHORSES?

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Racehorses are afflicted with catastrophic fractures and joint degeneration that occur at specific sites. They are caused by the excessive repetitive trauma of racing and training. This problem is an important economic and welfare issue. These traumatic stress fractures often arise in the dense bone, underlying the cartilage (subchondral bone- SCB), of the joints and can lead to intra-articular fracture or post-traumatic osteoarthritis. Focal bone microdamage first accumulates and then osteoclast cells, that digest bone, are recruited to remove the damaged bone. However, they create focal lysis, that can further weaken the bone and lead to fracture. The active osteoclasts remain in the sites for approximately 2 weeks. There is a great unmet need to identify this problem early to prevent its progression and sometimes catastrophic consequences. It is currently difficult to do so clinically in horses as the early damage is microscopic and radiographs cannot detect it. My research program, investigating questions related to equine joints for over 20 years, will focus on the important topic of the contribution of excessive osteoclastic activity in racehorse bones to both fractures and joint degeneration. Our prior studies, funded by NSERC, have paved the way to our current hypothesis that osteoclast-specific products in blood reflect equine SCB resorption in vivo and may prove of value as biomarkers (tests) for the detection of early excessive SCB resorption. A biomarker, or biological marker, is a measurable indicator of a disease process or response to a treatment and, in the case of this proposal, are proteins or molecules released by osteoclasts or their degradation of bone and are specific for this process. There is presently no test (biomarker) available to specifically monitor equine osteoclastic activity in relation to early SCB resorption, the subject of this application. The long term objective of the program is to develop a specific diagnostic serum test for equine osteoclastic activity that will reflect excessive, pre-clinical, SCB resorption. This test could permit its detection and/or prevent its progression by early tailoring of the exercise program to preserve bone. Specifically, we will study the release of known and novel biomarkers of equine osteoclast activity in cell cultures. We will then employ state of the art technology to discover specific proteins released by equine osteoclasts to discover new better biomarkers. We will then assess promising candidate biomarkers for the detection excessive subchondral bone resorption in racehorse body fluids.  The research program addresses a novel, emerging, important field in equine veterinary medicine that holds the promise to close the knowledge gap on the early pathogenesis of excessive subchondral resorption in racehorses and prevent its progression.