Joint Injury and Arthritis in Horses: Searching for Solutions
"I wanted to answer questions that hadn't been answered." So says Wayne McIlwraith, BVSc, PhD, FRCVS, DSc, Dr. med vet (hc), Dipl. ACVS, about his arrival some 30 years ago as an assistant professor and equine surgeon at Colorado State University's (CSU) Department of Clinical Sciences in the College of Veterinary Medicine and Biomedical Sciences. Those questions concerned how to better diagnose and treat musculoskeletal problems, particularly joint (articular) injuries and osteoarthritis: "Sixty percent of horses retire because of osteoarthritis--loss of articular cartilage and degradation of articular cartilage. It's a huge, frustrating disease."
The quest for those answers soon led the young New Zealander to form the Orthopaedic Research Center (ORC) at CSU in the mid-1980s. "I came to CSU in 1979 having just finished my PhD at Purdue and started doing relatively small research projects with surgical residents," recalls McIlwraith. "I had supervised three PhD students when Dr. Rick Howard started a PhD with me in 1993 and, working in Dr. Jenny Nyborg's lab (a very good molecular biology researcher), Rick cloned the gene sequences for interleukin-1 and interleukin- 1 receptor antagonist that set us on an upgraded pathway. Drs. Chris Kawcak and Dave Frisbie, during their residencies, set up a small laboratory in the Vet Teaching Hospital, where we started doing more sophisticated analyses, and this was when the ORC started to take off. I wanted to get to the next level of research, and this was aided by a foundation providing me with four years' salary for Drs. Kawcak and Frisbie to stay with us as assistant professors within the research program.
"We had a number of missions," says McIlwraith. "To get better methods to repair articular cartilage defects, to develop better methods of early diagnoses prior to earlier treatment and to treat these problems more effectively, and to see if we could predict catastrophic fracture. We'd gone through a phase where arthroscopy enabled us to treat a lot of things successfully, but not everything successfully; there were limitations, and if there was too much osteoarthritis or cartilage loss, the horse wasn't going to come back."
Since that beginning, the ORC has evolved into one of the premier orthopedic research institutions in the world, with ambitious research projects, cutting-edge facilities, and innovative treatments offered to client-owned horses. Having expanded from a three-person research program, the ORC now consists of 14 faculty members and research associates, approximately 15 collaborators from other CSU departments, and a large number of graduate, undergraduate, and veterinary students. In addition, ORC researchers collaborate with 20 affiliate faculty and researchers from other U.S. colleges and abroad.
At the ORC researchers have developed and advanced numerous diagnostic, preventive, and treatment options for musculoskeletal problems for both horses and humans. (The horse is an excellent model for osteoarthritis and cartilage repair in people, as tissue changes that occur in the horse mimic what happens in humans.)
"We validated many of the common treatments that are used for joint disease," McIlwraith states. "These include various intra-articular corticosteroids, hyaluronan (HA), and PSGAG (polysulfated glycosaminoglycan, known as Adequan), providing scientific proof of what these treatments do and what their level of effectiveness is, as well as newer biological therapies such as gene therapy and autologous conditioned serum (known as IRAP, an acronym for interleukin- 1 receptor antagonist protein). We've also done a lot of work in the better methods of healing articular cartilage. We were the first (in work led by David Frisbie, DVM, PhD, Dipl. ACVS) to do gene therapy against osteoarthritis. We're among those who are leading the way in terms of stem cell research for horses, and we're using stem cells clinically."
Many of the arthroscopic surgical techniques currently used for treating human and equine joint problems were developed at the ORC, techniques that have allowed for continued athletic performance.
The ORC also introduced the use of pressure algometry (a compressive-force gauge that measures the force in pounds/kilograms required to produce pain) to measure pain thresholds in horses with back pain. This important breakthrough provides a more objective assessment of back pain and also offers the ability to quantify the therapeutic effects of various pharmaceutical or nontraditional methods, such as chiropractic, physical therapy, or acupuncture.
Explains Kevin K. Haussler, DVM, DC, PhD, an assistant professor who has investigated the use of pressure algometry in horses, "Most of our current methods of pain assessment in horses are based on behavioral responses or scales or reactions to digital palpation, which are often very subjective. Pressure algometry demonstrated that some horses have a lot more widespread pain (sensitization) than previously appreciated: Some horses with presumed sacroiliac joint pain have had lowered pain thresholds all the way up to their withers, which I would have never been able to identify without the use of an objective pain measurement tool.
"Pressure algometry has also shown that phenylbutazone (Bute) is not very effective for reducing pain thresholds in normal ridden horses, compared to massage therapy or chiropractic care," notes Haussler. (See TheHorse.com/11573 for his review of studies using this device.)
Among the dozens of projects under way, McIlwraith cites biomarker work for preventing catastrophic injury, stem cell therapy, inhibiting osteoarthritis with gene therapy, continued work with cartilage repair, and analysis of racetrack surfaces as among the critical investigations.
"The one I have a real passion for at the moment are factors to reduce catastrophic injury, (in) particular the biomarker work," he says. Serum biomarkers could detect early articular cartilage and subchondral bone damage consistent with joint disease, as well as pre-fracture disease. "It's difficult work, we're not there yet, but I think it's the best potential answer to identifying a horse at risk before he fractures," he says.
In regard to catastrophic injury, another project in the works is designing computer models that help identify racehorses predisposed to catastrophic injury of the fetlock joint. Explains Kawcak, DVM, PhD, Dipl. ACVS, now an associate professor at CSU and a senior scientist in the ORC, "We just completed a study in which we discovered that horses that have fractured had a significant change in the shape of their fetlock joints compared to those that did not. We can detect this with computed tomography (CT) and are currently comparing this to radiographs. We think this may develop as a foal, and we are currently evaluating the effects of abnormal conformation on joint shape. The hope is that we can better monitor and manipulate the limbs in foals in order to maximize safety during training and racing."
The goal of the gene therapy research currently being done by Laurie R. Goodrich, DVM, PhD, Dipl. ACVS, an assistant professor in Equine Surgery and Lameness, is to genetically reprogram cells in the joint to overproduce a protein that halts and reverses joint inflammation. This might be achieved by using and delivering to the joint a specific viral vector that's encoded with a DNA sequence that blocks the inflammatory process.
"This work has come along by leaps and bounds in the lab testing part," reports Goodrich. "We hope to test it and apply it to horses in the next 12 to 18 months. This would be the most biological way to stop inflammation and to promote cartilage and joint healing in an arthritic joint."
Other projects at the ORC include:
- Validating manual therapies, such as chiropractic treatment, to identify specific mechanisms of action and to assess their efficacy in reducing pain and muscle hypertonicity (increased rigidity, tension, and spasticity) and improving spinal mobility and performance in equine athletes.
- Validating rehabilitation techniques (i.e., underwater treadmill rehabilitation and hyperbaric therapy) to identify which specific disease conditions or injuries certain modalities are effective in managing, and to develop optimal treatment protocols for select disease processes.
- Continued development of novel imaging techniques, including ongoing validation of MRI, CT, and ultrasound.
- Continuing to evaluate new treatments, including pentosan polysulfate, oral nutraceuticals, biologic therapies, and shock wave therapy.
- Using blood samples to monitor the effects of exercise on musculoskeletal development in foals, as well as in mature athletes.
- Evaluating the use of the Dynamix shoe (a novel polyurethane shoe) in treating navicular syndrome, and comparing the Dynamix shoe to regular egg bar shoes and "natural balance" shoes.
- Validating instrumented shoes and development of lightweight sensors (Equusys) to monitor forces in the galloping horse.
- Assessing racetrack surface and safety (in several collaborative projects with Mick Peterson, PhD, professor of engineering at the University of Maine).
In 2001 McIlwraith became the full-time director of CSU's orthopedic research program (now called the Gail E. Holmes Equine Orthopaedic Research Center), and in 2009 he was made a University Distinguished Professor (CSU's highest honor). He was bestowed the honor due to his work as a researcher, clinician, and educator, his leadership skills, and for the development of numerous programs at Colorado State, including the musculoskeletal research program.
Despite the successes and the achievements of the ORC, the quest continues for answers to familiar challenges: How to devise better diagnostics, achieve better cartilage repairs, develop better osteoarthritis treatments, and find better prevention measures.
About the Author
Marcia King is an award-winning freelance writer based in Ohio who specializes in equine, canine, and feline veterinary topics. She's schooled in hunt seat, dressage, and Western pleasure.
POLL: University Equine Hospitals