Orthopedic Research at North Carolina State University

"We have all these new treatment options for lameness in the horse, but with no controlled studies to indicate whether their utilization is warranted or even effective," laments Rich Redding, DVM, MS, Dipl. ACVS, associate professor of equine surgery at North Carolina State University. And he's certainly not alone in wishing for more research on equine veterinary medical therapies.

Luckily for Redding and the rest of us, the new Equine Orthopedic Research Laboratory under the direction of Michael Schramme, DrVetMed, CertEO, PhD, DECVS, has several equine orthopedic research projects underway. Dianne Little, BVSc, PhD, MRCVS, Dipl. ACVS, Postdoctoral Fellow in Equine Orthopedics and Director of the Equine Outpatient Imaging Service, recently discussed their current research projects with The Horse.

Suspensory ligament investigation "We have funding from the Grayson-Jockey Club Research Foundation to look at normal hind limb suspensory ligaments and compare magnetic resonance imaging (MRI) findings with ultrasound findings and ultimately histology (microscopic tissue examination)," she says. This work will help researchers learn more about normal suspensory ligament architecture and patterns of sub-clinical injury so they can better understand injuries that ultimately cause lameness.

New model of tendonitis "Other models of tendonitis use collagenase (to create lesions), which is an enzyme that breaks down tendon fibers," Little says. "The trouble with that is that you get a very unpredictable lesion size and shape, whereas we burr out the center of the tendon—physically creating a lesion. These lesions are much more similar to what you'd see with a clinical case. After surgery, we MRI the legs, and then we'll look at the gross lesions all the way down to histology and electron microscopy, and compare that to the ultrasound and MRI as they heal.

"With this model we can compare different treatments, because you can create identical lesions in both legs and deposit a known volume of cells or other treatments into the lesion," she adds. "We've got an ongoing study funded by U.S. Equestrian (Federation) at the moment that's looking at efficacy of bone marrow-derived stem cells using this model."

Stem cells There are two companies doing veterinary stem cell work (for hastening healing of tendon and ligament injuries) worldwide, says Little. One is VetStem in California, which uses use fat-derived cell fractions, and the other is VetCell, which produces stem cells derived from bone marrow and is based in London, England. "We are licensed by VetCell to grow bone marrow-derived stem cells for research use in tendon injuries, so what we grow here doesn't go out into the clinic, although these cells are now available commercially within the U.S." she says.  She says this study will probably run for another five months.

Bone edema "We're also looking at a common injury of racing Thoroughbreds—fetlock disease," Little adds. "We have access to some front legs from Kentucky horses that broke down on the racetrack or were euthanized for other reasons. But we expect that a lot of them will have very early signs of fetlock disease, such as bone edema (bone ‘bruise’) in the distal cannon bone, which should show up on MRI. We'll also do histology to see what sort of microscopic injury there is and see how that correlates with the MRI exam, to see if the MRI might be a good way of screening these horses before they go on to develop palmar condylar osteonecrosis (a localized area of bone death due to trauma) or potentially catastrophic condylar fractures.”

In other words, they will investigate the potential value of MRI as an early diagnostic tool. "If a horse isn't running quite right, or isn't performing quite as expected, or has fetlock pain, we could put him through the MRI and say, 'OK, he's got some bone edema here, maybe that's going to predispose him to potentially career-ending fetlock disease, so we need to back off on training,' " she explains.

IRAP Interleukin-1 receptor antagonist protein, or IRAP, has received lots of attention lately as a joint treatment for osteoarthritis and synovitis, particularly in horses that are showing a poor or short-lived response to conventional medications such as corticosteroids. Little says they are using this type of treatment from Arthrex Vet Systems. "We pull 50 mL of blood into the syringe with chromium sulfate-coated beads (to stimulate production of IRAP and other anti-inflammatory proteins from the blood)," she says. "Then you put it in an incubator for 24 hours, spin the serum off of it, then filter the serum and freeze it as single dose aliquots. We culture it for a week, which a lot of people don’t do, so we know we're putting something sterile into the joint." There is still a lot of work to be done and clinical studies to be completed to fully evaluate this treatment, which has been used extensively in Germany; much of this basic research is being conducted by Wayne McIlwraith, BVSc, PhD, DSc, FRCVS, Dipl. ACVS, at Colorado State University.

Clinical studies Not every study takes place in a lab; another part of NC State's research efforts include investigation of clients' horses. One is an MRI study funded by the Bernice Barbour Foundation, which subsidized MRIs of horses with suspected high suspensory lesions for horses whose owners could not afford it. "We get to MRI more high suspensories, and the owners and horses get the best diagnostics possible," says Little. "The owners kept asking, ‘Can we bring more horses in?’ They found that frequently these horses have other lesions in the high suspensory region besides just a ligament injury--and they have been able to better direct treatment for these horses as a result.”
Another study will provide foot radiographs of horses with various lameness problems presented for MRI. "This will tell us, for example, if horses with suspensory ligament injury are most likely to have a particular kind of foot conformation," she explains.

"Right now we're running three major funded studies, and then probably another five or six clinical studies that we're doing without funding, as well as maybe three or four pilot projects," she reports.

Challenges and Collaboration
"The biggest challenge in equine research is the expense," states Little. "For our research horses, next year it will cost $15 per day just to keep them standing in a stall, whereas for a mouse it's about 10 cents per day. So you burn through large amounts of cash very fast when doing horse research. 

"The ultimate aim for us is to do something that has applications for the human field because that opens up many more funding opportunities," she says. "For example, this stem cell work has potential human applications. The horse's superficial digital flexor tendon (SDFT) is the only tendon to experience similar or greater loads than the human Achilles tendon. So some of the work we're doing with stem cells in the SDFT could potentially have applications for the human Achilles tendon or other human tendons because if it produces a more functional tendon after injury in the horse, it will probably be of benefit in humans (and small animals)."

Work and ideas are also shared with small animal clinicians at NC State, and with colleagues in the comparative pain laboratory (who study ways of detecting and managing pain in small animals). "It really helps having the exchange of ideas and the possibility you could translate some stuff from small animals to large animals, and vice versa," says Little.

Yet another source of research collaboration is pharmaceutical companies. "Some drug companies are becoming more interested in collaborative research, because it's cheaper if you're already set up like we are here, rather than having to set up their own study facility," Little says. "So they'll contract with us to do these studies. We have a separate large animal surgery facility dedicated for research purposes. It's nice because we don't have to worry about scheduling research surgeries in at the beginning or end of day to fit around clinical work."

Perhaps Dick Mansmann, VMD, PhD, clinical professor and director of NC State's Equine Health Program, says it best: "There is a very small number of people trying to advance horse health for a very small number of horse owners compared to dog or cat owners. So the more we can all work together, the better off we'll be."

About the Author

Christy M. West

Christy West has a BS in Equine Science from the University of Kentucky, and an MS in Agricultural Journalism from the University of Wisconsin-Madison.

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