Serum Biomarkers for Musculoskeletal Disease (AAEP 2005)

A Colorado State University (CSU) researcher recently reported that he and his colleagues have found significant patterns of six different signals of damage or "biomarkers" in the serum of racehorses with certain musculoskeletal diseases. This means veterinarians are much closer to being able to anticipate the injuries or problems a horse might develop by testing a serum sample.

"This is certainly an exciting time and the culmination of 10 years of work for us," said David D. Frisbie, DVM, PhD, Dipl. ACVS, an assistant professor in CSU's Equine Orthopaedic Research Laboratory. He presented the study results at the 2005 American Association of Equine Practitioners' Convention in Seattle, Wash., on Dec. 6.

Biomarkers are indicators of abnormal skeletal tissue turnover, and they are often made up of molecules that are the normal products and byproducts of metabolic processes in the skeletal tissues. "There's a large palette of different biomarkers that can be broken down into cartilage, bone, and tendon," Frisbie said. These biomarkers have been validated as useful predictors of damage in the laboratory, but only one prior study, performed at the Royal Veterinary College in London, examined biomarkers in a clinical setting. That study showed significant biomarker differences in horses with dorsal metacarpal disease (bucked shins) compared to horses with normal shins.

Frisbie and colleagues built on that research and looked at six serum biomarkers in 2- and 3-year-old Thoroughbred racehorses in training that sustained a single musculoskeletal injury. The injuries included intra-articular fragmentation (bone chip off a joint surface), injury to a tendon or ligament, an incomplete or complete non-articular fracture, and periostitis (inflammation of the periosteum, the membrane that covers bone in areas other than joints).

"We broke out of the box and expanded past joint disease," explained Frisbie. "We wanted to look at what was really going on with the disease process and potentially find out if we could predict that this horse was going to go on and have an injury."
Here's what the scientists found:

In horses with bone chips: There was a trend of glycosaminoglycans (GAGs, molecules that help hold joint tissue together) dropping at the time of the injury. "This was interesting to us because maybe the horse couldn't sustain a normal production of GAG," Frisbie said.

In horses with tendon or ligament injuries: A significant increase in a bone specific type I collagen was observed most likely originating from the attachment of tendons/ligaments to the bone.

In horses with incomplete or complete non-articular fractures:  This group showed a significant increase in type I collagen levels (which could have originated from either bone or tendons/ligaments).

Periostitis:  The research did not yield any information specific to this injury.

In control horses (those without injuries):  "GAG levels increased throughout the study," Frisbie said. "There was a drop in osteocalcin throughout the study, which isn't surprising because bone synthesis starts to decline with exercise.
"Of interest to us is the fact that chip fractures or incomplete or complete fractures did not increase the horses' GAGs significantly throughout the study, which suggests they are unable to respond in a similar fashion to the control horses (thus, potentially making them more vulnerable to fractures)."

Frisbie and his colleagues fashioned a computer model using biomarkers that were important or changed significance over the course of the study and found it was about 67% sensitive in predicting which problems these horses exhibited.

The study clearly showed that each of the investigated injuries had a unique biomarker pattern. "I think this certainly gave us an insight into the pathophysiology of these different disease processes, and it gives us useful information on prediction of disease," Frisbie said. He was also encouraged that these patterns were visible in "real world," clinical cases.

Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.