The Bare Bones: a Primer with Dr. Bramlage

He hasn't got all day; nor, doubtless, do you. So let's cut to the chase. We won't dwell on the journey that has made Dr. Larry Bramlage a doyen of orthopedic science, in its daily application to the racehorse: not the alphabet soup of honors and distinctions, nor the long experience that has honed the sharpest diagnostic eye in the business through 23 years with Rood and Riddle. We have simply dropped into the clinic, on a recent visit to Lexington, to direct a brief sunbeam of his knowledge and insight into the practices of those who depend for a living on the miraculous but fragile equilibrium of the bones that support a Thoroughbred.

“Racehorses are so good because they produce their skeleton based upon what they do,” Bramlage begins. “They're not born with it. Their skeleton is the minimum weight that they can produce and still carry them around the racetrack. So they have a big engine, but their undercarriage is no heavier than it needs to be. And that's why they're fast.”

That's true, in some evolutionary measure, of all horses–and other animals, too, people included.

“The skeleton is different than hearts and lungs and muscles,” Bramlage explains. “Those train to a volume of work that you're doing. Skeleton trains to the level of work that you do.”

He recalls a series of experiments conducted on turkeys some years ago, where one wing was restricted and the fowls learned to flap the other to get food. The idea was to establish how many cycles of this activity were required to stimulate bone.

“Well, it's interesting,” Bramlage says. “Because when you reach 36 cycles in a day, that's the maximum the bone will respond to. You can go to 2,000 and it won't get any stronger than in those 36. And that's what makes a trainer's job tough. Because they have to push the horses hard enough, that they get strong enough to carry themselves around the racetrack. But if you do too much, then those extra cycles begin to be destructive.”

Those 36 cycles, for our purposes, apparently equate to about a furlong. Which, Bramlage explains, means that your fastest eighth will be the level for which your horse produces bone. Obviously that doesn't happen overnight, albeit bone is far more dynamic than most laymen assume.

“But the stimulus is there that it'll try to reach that next level before the exercise does,” Bramlage explains. “And then you repeat that over and over, and eventually the skeleton gets appropriate enough that you don't acquire any damage during those 36 cycles. So while there's some always ongoing wear-and-tear, the most important part of making a racehorse is usually up to four or five races. Once they get there, their skeleton is virtually made.”

The living nature of bone, however, does mean that the “made” skeleton can regress once taken out of training. But Bramlage is keen to address a misapprehension, which took root maybe a decade ago, that persistently galloping a young horse creates the foundation for a strong skeleton.

“Galloping a horse a lot helps the heart and lungs–but once you go past those 36 cycles in a day, the rest of them are just wear-and-tear,” he explains. “A lot of horses were actually harmed by excess galloping.”

Previously there had also been the attempt to extrapolate the principles of interval training, in human athletes. “I knew a couple of people who, as runners themselves, were going to interval train and beat everybody,” he recalls. “And they ended up with 4-year-old maidens with splints on their hind legs. Because the skeleton just can't take that that many fast intervals. In people, the limiting system is the heart and lungs, not the skeleton. Horses have such great heart and lungs that, unless they're bleeders, they virtually never limit. The horse's heart and lungs can respond to anything you throw at them. But the skeleton has to do it in little stair steps. And that's how, in young horses especially, the heart and lungs often get ahead of the skeleton.”

Though the tibia also registers trouble here–it absorbs a lot of force, in locking the reciprocal motion of stifle and hock–the most familiar symptom is shin trouble.

“You go too fast, the wear-and-tear begins to exceed the response and you get bucked shins,” Bramlage continues. “Shins have to triple in size. The front cortex of a cannon bone in a 'made' racehorse is three times thicker than in the yearling that started training.”

So how does this translate, ideally, into building up a young horse towards a race? Bramlage suggests a pretty familiar scenario: one or two furlongs at a rather higher level than the rest of the exercise, in effect showing the skeleton where it's going to be asked to go in three days' time. The real skill, in training, is monitoring attitude.

“People ask, what makes a good trainer?” he says. “For me, it's an easy question. It's being able to understand when the horse is happy and when he's not. When horses are adapting well, they're happy to train. When a horse starts not wanting to go to the track in the morning, not wanting to load in the gate, those are the kind of things you need to look out for. It's a real art for trainers to understand when to push a horse and when to back off.”

Obviously you would hope that trial and error, over the generations, should have brought horsemen's intuitions pretty close to where they might land through learned science.

“If you go back to when Aiken, South Carolina, was the winter training center–because that's how far the railroad went south–they would have the Aiken trials and those 2-year-olds, early on, would be breezing an eighth,” Bramlage says. “Those short breezes were actually very useful to the horses. Especially when you're making the horse, it's a matter of trying to train heart and lungs–because you have to do that–without overtraining the skeleton.”

When a horse is past that stage, but has to be laid off training, the skeleton will not lose much strength through the first month but the situation will change pretty rapidly after two months. And a more significant spell, say four months, notoriously invites humeral or tibial stress fractures in a small number of horses: again, because heart and lungs train back so much faster than the skeleton.

Needless to say, by the time a horse is sent into the clinic, they have typically signaled a loss of form.

“If a horse has swelling in a knee or ankle, those guys at the racetrack pick it up,” Bramlage says. “These horses [sent into the clinic] don't have any obvious pain, heat or swelling, but their form has gone down. And a lot of times they have either bilateral lameness–two fronts or two hinds, sometimes all four–or they're just early wear-and-tear injuries. I think most of the really successful trainers today understand better than they did 10 years ago that the horse is subject to that wear-and-tear; and that whenever a horse is not giving you what it can, then you need to start looking.”

Parallel advances have been made in imaging technology. It is barely 30 years since radiographs were still processed on celluloid. Digital radiographs have themselves improved dramatically, and now scanning in three dimensions via CAT and MRI and ultimately PET is available.

“Nuclear imaging was a huge tool because those scans allowed us to look for stress fractures that didn't have any outward clinical signs,” Bramlage says. “But whenever regulators think in terms of needing a PET scan to monitor horses at the racetrack, that's not really true. You need to look at them and identify the horse that needs to be looked at, not scan them all. Most of those can be unraveled using all the tools we currently have. It's just a matter of knowing when you need to look. And so more than we need more equipment, we just need to look more often.”

The role of regulatory veterinarian is a contentious and evolving one. The process is being aided, however, by a growing injury database to succeed anecdotal assumption. Already Bramlage can see where this might take the profession.

“It may not hit during my lifetime, but I think the next really exciting revolution, which is going to totally change our care of racehorses, is digital timing,” he says. “It just makes sense that it will eventually move away from clockers and all be done passively, automatically, by the equipment. Well, when you have that data, it's not a real hard step to write an algorithm that identifies [problems that may be brewing].

“You could look at a horse's exercise fingerprint because stride length and stride cycle is pretty stable for individual horses. When the length begins to shorten, he's protecting something. And so each horse will have his own digital fingerprint, and this will be automatically recorded every time a horse works, every time they race. And all of a sudden you can say, 'This horse is getting into trouble.'”

Some early research has detected patterns that might anticipate injury as many as three races ahead. Bramlage can see a future where every horse will transmit data to central monitoring for red flags. For now, until the necessary technology is available, it falls to people like Bramlage to determine the level of risk that warrants its prohibitive cost.

“But I think that in the next generation beyond me, that will become automated,” he predicts. “And that will revolutionize the prevention of injuries. It'll be the best thing that ever happened.”

And that's one of the things that maintains such youthful enthusiasm in a septuagenarian who has already witnessed such transformation in the tools of his trade: the curve is only going to steepen.

Aside from digital radiography, the biggest leaps forward have been internal screws and plates; plus arthroscopy and its adaptation from diagnosis to treatment. For internal fixation, the initial debt was apparently to a Swiss cost-benefit analysis of chronic disagreement between tibias and ski-boots. Of arthroscopy, meanwhile, Bramlage muses: “Surgery never used to happen until there wasn't anything else you could do. Then with the arthroscope it became easier, quicker, better. And so now that is the first line of defense. The horse gets a chip fracture, they take it out right away. The joint doesn't degenerate, they go back to normal.”

Horsemen nowadays have gained faith that condylar fractures can be routinely secured. One of Bramlage's most celebrated patients, Personal Ensign, went a long way to changing perceptions. Nowadays you'll find many a Breeders' Cup winner with a screw lurking somewhere in its skeleton. It's a very different world from when Bramlage started out, and yet he feels we have barely started.

“Yeah, we were dipping X-rays in chemical solutions when I was a student,” he reflects. “But the young veterinarians right now will probably see the same explosion. Probably in the biologic areas: the understanding of cell biology, and cell communication, is doing the same ramp up. The ability to treat is going to be much more pointed and effective than now.”

Bramlage is acutely aware of our industry's exposure to an ever more urban society that professes ever fiercer vigilance on behalf of animals with which it typically has little interaction, certainly compared with generations past. In that respect, veterinary regulation manifestly has a front-line role. He's excited, then, that a digital fingerprint might give mute animals a new way of telling doctor what's wrong.

Even with the advent of such tools, however, Bramlage believes that the essential mystique of the Thoroughbred will endure. We might be able to explain how everything fits together, and learn how to put things back together, but the key to performance will remain elusive.

“And actually I hope we never do get to that point where we understand everything about a horse,” he admits. “Because I think that's what's intriguing to people. You can improve your odds by improving your breeding. You can keep the horse healthy, you can have a trainer that's capable to that level. You can do all those things, but you still can't just go buy a Derby winner.

“Every horse is a product of a dip out of the gene pool. It's not a one-to-one combination of the mare and the stallion. There are all sorts of units. Like you've got four genes that cause eye color in people. There are all those different combinations of things. So to combine whatever comes out of that gene pool with the mental capacity, to train hard enough and compete hard enough, you never know which horse is going to have it.”

He chuckles, and asks whether you ever heard of a racing mule named Black Ruby?

“Well, she was on the California fair circuit for about 10 years and there was only one other mule could occasionally beat her,” he explains. “But they cloned her several times, and none of them could beat me. They had the exact same genetic makeup, but none of them would run like that. So that elusive factor, I think, is what keeps people intrigued. And I hope we never identify that.”

Even his exceptionally intimate professional relationship with horses, ranging from Personal Ensign to claimers at Ellis Park, has only marginally clarified the enigma.

“I don't know that there's any one thing,” he says with a shrug. “Good horses are always physically attractive, well balanced. They're almost always smart, they're very intelligent, very adaptable.”

Does that make better horses better patients, too?

“Absolutely,” he replies. “But racehorses are the best patients anyway, in my opinion. The worst patient is the 4H horse that's never felt anything but a rub rag, because when they have to deal with pain, you never know how they're going to handle it. But racehorses are just like people who train hard: you're stiff and sore next day and then it goes away and you feel better than you did before you started. They have better survival instinct.”

And while recruitment to equine practice is becoming harder, given the reduced social exposure nowadays between young people and horses, Bramlage guarantees endless fascination to the next generation. The measure of your work, he says, is so much more gratifying than in small animal practice.

“I think equine practitioners tend to practice a lot longer because there's another level of assessment,” he says. “Your horses have to go back and run. They have to win barrel races. They have to win ribbons, if they're a backyard horse they have to trail-ride. There's a couple of books I read, discussing why do armies fight? It's mostly not for abstract ideals. They fight for the people next to them, the people they trained with, the things they know and the fear of failure. And I think this level of assessment, with the possibility that you'll fail, but the rewards when you succeed, it's higher in horses.”

And there are literally hundreds of horsemen in the Bluegrass who will be relieved to hear him say that. “I could easily be retired,” he says. “At some point, physically it's not going to be possible to continue. But I think that's why people stick around. I mean, when the success barometer is the dog being able to get up on the sofa? That's not quite as intriguing!”

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From The Beginning: A Conversation With An Equine Orthopedic Pioneer

Do you ever wonder how someone becomes an expert in a given field? Brilliance, tenacity, ambition, savvy, every one in heaping measure? And then some, likely! Without question, Wayne McIlwraith proved a forerunner in the field of equine orthopedics, influencing how skeletal problems are treated in high-performance horses. In a candid interview with Kentucky Equine Research, he described his childhood in rural New Zealand and how he ended up in the United States. Along the way, you'll learn of the extraordinary contributions he has made to the horse industry.

The complete transcript of the interview can be found in the proceedings of the 2018 Kentucky Equine Research Conference.

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Can you give us a little insight into your background?

I was brought up in a small town in New Zealand, but I spent quite a lot of my school holidays at my aunt and uncle's high-country sheep station. They had cattle and sheep, and it's relatively remote. I thought the lifestyle was great and when the vets came up, I thought it was a really interesting career. My aunt also rode and competed at show jumping. She taught me to ride, which transitioned me from looking at racehorses to actually riding horses, and I was hooked. I also spent time, as a high school student, in one of the local veterinary practices. I made the decision to pursue veterinary school at Massey University in New Zealand. I was interested, initially, in large-animal practice—sheep, cows and horses. I actually worked in a mixed-animal practice for two years after I graduated, with a lot of surgery involved, because of sheepdog injuries. That was my start in orthopedic surgery. Sheepdogs get a lot of cruciate ruptures and bone fractures.

I left New Zealand in 1973 to lead a climbing expedition in the Peruvian Andes. After three months climbing and three months traveling in South America, I went to England and worked as a relief veterinarian in a large-animal practice in Wales for six weeks and a small-animal practice in the East End of London for about four months.

Then, after three months climbing in the European Alps, I started a one-year internship at the University of Guelph in Canada. At that time, surgeons were starting to save horses with colic. So the first thing that attracted me to equine surgery was the challenge of fixing horses with twisted bowels because many horses with colic were euthanized at that time. The internship involved all facets of equine surgery, including orthopedics and lameness, and I became excited about all these pursuits. I decided, “This is what I want to do.” So I applied for residencies and got a residency at Purdue University in Indiana, and by then I was certainly proceeding down the road to specialty surgery.

What drew you further into work with horses? And, ultimately, why did you view the horse as an ideal model for orthopedic research, specifically in surgery?

My internship at Guelph was in large-animal surgery, principally horses. I found that I enjoyed working around horses and I worked well with horses. My initial goal when I went to Purdue was to be trained as a specialist in equine surgery. My advisor and mentor, Dr. Jack Fessler, gave me a research project in synovitis, inflammation of the lining of the joint, as part of my master's degree, which we did simultaneous with the residency program. This was a really critical juncture for me because two things happened.

First of all, I was working with an experimental model of synovitis and started to read the literature, which was virtually nonexistent in the horse. This was 1975 and 1976. The human literature on osteoarthritis was also quite confusing, being described as the arthritis just happening, with any inflammation secondary. What we showed in this study was that if you inflamed a joint and you did nothing else—if you didn't destabilize it or cause physical trauma—you could still get cartilage degradation. That was contrary to medical thinking in humans, and as I said, there wasn't much literature on the horse.

Then Dr. David Van Sickle asked me if I'd continue the work into a doctorate, in the same model, but looking at more outcome parameters and more questions. So I got very good training in joint disease because he had done so much research on the pathology of joints and established the Bone and Articulation Research Laboratory at the Purdue School of Veterinary Medicine. Much of his work was in canine joints, so I had the opportunity to learn a lot from him and to take it into the horse. And it was a big opportunity because there'd been hardly anything done.

The second thing that was pivotal for my career was that I read about the arthroscope. The arthroscope was just beginning to be used as a diagnostic tool in humans. The state-of-the-art then was that if you had knee pain, you had an arthrotomy and your meniscus was taken out, based on the positioning of the pain. This was before MRI. Dr. Lanny Johnson, who was a professor at the medical school at Michigan State University, was having a course in diagnostic arthroscopy. And I guess I was cheeky enough to call him up and say, “I'd like to come to your course. I'm a veterinary surgery resident, not a human surgery resident.” And he said, “Oh, it'd be great to have you. Come on up. I won't charge you a registration fee.” So I drove up to Michigan State, and a couple hundred medical doctors and I learned how to do a diagnostic arthroscopy of the human knee.

So I went back to Purdue, and the university bought me an arthroscope so I could do diagnostic arthroscopy in analogous fashion to what they were doing in humans. I finished my doctorate degree, and I'd done a lot of arthroscopy, but just diagnostically. Then I got the job as an assistant professor at Colorado State University (CSU) in 1979.

That's when I started, with the help of a human orthopedic surgeon, Dr. Ron Grober, who visited me from Florida for a day, developing triangulation techniques to do surgery. So, in other words, rather than just look, we were working to perform the surgical manipulation and visualization with the arthroscope. Those were the early days, when we were looking at the joint directly through the scope, and human orthopedists were doing it the same way. Those were early, pioneering days, and there was resistance to the technique both in human medicine and in the horse.

So I came to CSU equipped with a reasonable knowledge of joint disease. Plus, I had started using the arthroscope. Then we developed the surgical techniques. So my career has involved a research pathway and a clinical pathway. And, of course, they both join together.

Much of your clinical path has involved racehorse patients. How and why did you gain an affinity for racehorses and working with those patients?

Well, it was more a case of them getting affinity for me, because I had a technique that most other equine surgeons were not doing yet. I came here in August 1979 as one of four surgeons. Dr. Simon Turner soon got engaged in arthroscopic surgery here as well. By 1981, we had developed techniques to arthroscopically remove carpal chip fragments. We could also take chip fragments off the front of the fetlock joint arthroscopically. These were the two main surgical conditions in racehorses. So horses started coming here from 10 surrounding states. There were a couple of veterinarians doing some arthroscopy on the East Coast, but nobody else in the West. So we would get horses from Utah, Nevada, California, Nebraska, Kansas, Wyoming, Montana. There was strong racing in a number of those states at that time.

Starting in 1983, Dr. Turner and I started giving six arthroscopic surgery courses a year, and we could only take 12 people at a time because we're looking through the arthroscope. It was before we had video cameras, so it was very laborious.

Dr. Nancy Goodman, who was a CSU veterinary graduate, was in a racetrack practice in California, and she couldn't get into one of our courses because they were booked up. So she asked me to come down and do surgery on a couple of horses. I flew down to that clinic, and we operated on four horses and got done at 2 a.m. And then she had me back the following week for another four. And then I went for a weekend, and I ended up marrying Dr. Goodman. That started my surgical referral practice in Orange County, California. The first 16 years that Nancy and I were married, she worked eight months a year in California, and I was down there every other weekend doing surgery. When Nancy retired from racetrack practice after 20 years, in 2001, surgical practice continued with her as my primary assistant.

Fast-forward to now. A lot of horses that undergo arthroscopic surgery here at CSU are Quarter Horses in western performance disciplines. In the early days, we didn't have the techniques to treat stifle injuries, which are often seen in these equine athletes, such as cutting horses and reining horses. The stifle, which includes the femoropatellar and femorotibial joints, was the endgame because doing surgery on femorotibial joints, in particular, was more complicated. We developed a technique for femoropatellar joints and published it in 1986, but femorotibial joints came along after that.

Other techniques came pretty quickly with multiple techniques developed by other equine arthroscopic experts in addition to our group. In the early 1980s, I certainly would not have predicted how far we would go with arthroscopic surgery and that we would be able to treat many racehorses for their injuries and have them come back to full athletic ability. Because of their multiple injuries, racehorses became the poster child for arthroscopic surgery. But it is now a powerful tool for treatment of joint injuries as well as problems of the tendon sheaths and bursae in all breeds.

A lot of people who get involved in racehorses are brought up with them. I wasn't, but I was always fascinated by racehorses. I used to bike up to the racetrack in my hometown of Oamaru when they had a meet. My mother didn't like it because that was gambling and she was a good Presbyterian. But I was always fascinated by it. I got heavily involved in the racing industry, both racing Quarter Horses and racing Thoroughbreds, by virtue of operating on them. I love it and I'm passionate about it. I still do surgery on them. For a long time, Nancy said the only way I liked horses was when they were on their backs with surgical drapes on them! I think she retracts that now and we currently have 12 horses at home. We did revolutionize things for racehorses with arthroscopic surgery in similar fashion to human orthopedics.

Arthroscopic surgery for equine athletes was the biggest revolution at the time in being able to treat musculoskeletal problems and get them back to their previous level of racing. While we developed a lot of the techniques for arthroscopic surgery, other equine surgeons did their share as well. We put on our first advanced arthroscopic surgery course at CSU in 1988, and we became the place where most veterinarians came to learn it. Our textbook on Diagnostic and Surgical Arthroscopy in the Horse, whose fourth edition was published in 2015, has 454 pages reflecting the evolution.

You mentioned that you were fascinated by racehorses as a child and continue to be. Why? What about them have you found so captivating?

They are beautiful. And you see them with the jockeys dressed in their colors. It was fascinating, the whole thing—the speed and the excitement. Horse races were much better attended when I was growing up. In New Zealand, at that time, every race from across the country was on the radio on Saturdays. This was pre-television, as we got a black-and-white TV at home in my last year of high school. It was just like the days of Seabiscuit over here. Thousands of people went to the races; it was a real happening.

So let's fast-forward. Set the scene for us, in 1979, you're being interviewed to come to CSU. Whom did you interview with? What drew you to CSU? And what did you hope to accomplish here?

I interviewed here in 1979, and they had just opened the Veterinary Teaching Hospital on Drake Road. It had been open for two weeks. Dr. Jim Voss was head of the Department of Clinical Sciences. He had me stay at the Thunderbird Motel on the corner of College and Drake. The vet hospital was basically the only place on Drake that existed. Dr. Voss had a two-day interview process. You talk to everybody, and you give a seminar.

Then Dr. Voss was taking me to dinner with three other faculty members, including Dr. Simon Turner, who had been counseling me to shave off my beard, which I had at the time. So Dr. Voss picked me up in his pickup truck, and he was chewing tobacco, and I soon figured out I was in real cowboy country in the West. And he says, “OK, we've got 10 minutes for you to tell me what you think, what you like, what you don't like, and then we're going to get drunk.” Well, it wasn't badly drunk, but we had a great dinner at the Prime Minister, and drinks certainly loosened things up.

During dinner, Dr. Voss asked, “Why did you shave off your beard?” He had been at a meeting where I'd spoken three months earlier. I said, “Well, Dr. Turner told me I couldn't communicate with you guys with hair on my face.” He says, “Oh, that's no problem.” And I said, “Well, I'll grow it back then.” And Dr. Bob Shideler said, “Oh, it would be good if you didn't, Wayne.” That's one of the two main things I remember about the interview. The other main memory was how much I wanted to get the job at CSU. I did get offered the job as an assistant professor and I arrived in August 1979, still clean-shaven.

You're known at CSU as a University Distinguished Professor of Orthopaedics and as founding director of the Orthopaedic Research Center. But you've worn other hats through the years, including director of the undergraduate program in Equine Science. Tell us about those other roles.

That came about in 1994, when I'd been here 15 years. Dr. Bill Pickett started the Equine Sciences Program, which consisted of the undergraduate program in Equine Science and the Equine Reproduction Laboratory, and then he retired. Dr. Voss had become dean, and he was quite visionary. They had a search open for the new director of the Equine Sciences Program.

Dr. Voss called me and said, “I want to talk you into taking over Equine Sciences.” That would mean taking over the undergraduate program and the Equine Reproduction Lab. But he also said, “I want you to build the biggest equine orthopedic research program there is.” His plan was to replace me in the clinic and give me a tenure-track position in research as well. Nancy and I discussed it, and we decided it was a good opportunity if I was going to move forward. I wanted to continue surgery, and that was no problem because of my practice in Southern California.

For seven years, I was in charge of all three programs. I was building up the Orthopaedic Research Center and was director of the Equine Reproduction Laboratory, as well as the Equine Science undergraduate program. Then the Orthopaedic Research Center developed a critical mass, and I wanted to devote all my time to that. So that's how I had a seven-year swing through Equine Sciences.

You're an international pioneer in arthroscopic surgery and joint disease research in horses. And you've been honored many times by academic colleagues and others. As you survey your career, what do you consider your biggest achievements?

Pioneering arthroscopic surgery in the horse has been an achievement, along with teaching a lot of people how to do it, and writing the book on it (Diagnostic and Surgical Arthroscopy in the Horse, in its fourth edition). And the second is developing the Orthopaedic Research Center. It started as the Equine Orthopaedic Center, but because of research grants from the National Institutes of Health and corporations, we've just left it as Orthopaedic Research Center. That's how we've got where we are now.

What do you consider to be your biggest, most important research breakthroughs or innovations?

They build on each other, as research does. Going back to my doctoral work, even though it's just one paper in the veterinary literature, recognizing the critical nature of synovitis actually turned out to be very important long-term for translational purposes. At the time, human doctors emphasized that osteoarthritis was not inflammatory, which seemed a bit strange, because it certainly was in the horse. Understanding that led into evaluating different treatments for the synovitis, and thereby making a lot of horses better. It has been important to validate the various treatments in joint disease as good, bad, or otherwise, and that is all part of the recognition of synovitis.

Another big breakthrough was the gene therapy work that Dr. Dave Frisbie did with me for his doctorate, in collaboration with Dr. Christopher Evans, who was at the University of Pittsburgh and then moved to Harvard. We showed that interleukin-1 was the bad guy and that the equine interleukin-1 receptor antagonist gene, which is a natural antagonist, would shut down inflammation in the joint, and the consequent osteoarthritic change. This work was our first venture into the world of biologic therapies.

Our cartilage-healing research has been important, along with use of the horse as a model for cartilage repair in humans. Early diagnosis of musculoskeletal disease, because of the drastic consequences that you can have with catastrophic injury, is a huge part of our work. This started with Dr. Chris Kawcak's doctoral studies with Dr. Bob Norrdin and me showing how quickly microdamage could develop in the exercising horse and that this was the initial event in osteochondral fractures. While this microdamage could be displayed in pathology samples, we needed to be able to diagnose it before it became a critical fracture in the horse. We have made considerable progress in identifying imaging biomarkers, including nuclear scintigraphy, computed tomography, and MRI, as well as fluid biomarkers that we can pick up in the serum. This area is still a work in progress but has got the best potential of predicting catastrophic injury compared to other techniques.

The two biggest breakthroughs in sports medicine, whether it's horse or humans, are arguably arthroscopic surgery and biologic therapies. That's where we are now, as we transition into the Translational Medicine Institute. These are therapies that have minimal side-effects and take us to a newer level. They include proteins, cellular therapies, and stem-cell therapies. We have taken a problem that we treat arthroscopically, and we've been able to raise our success rates significantly with the additional use of bone marrow-derived mesenchymal stem cells.

Continuing this path of discussion, define translational medicine.

Transitional medicine is the use of basic laboratory research, preclinical research in vivo, and clinical examination that leads to patient success, with what we learn in animals often translating into improved medical treatment in humans. The outcome is better diagnosis and better treatment of the patient, whether animal or human.

What do you see as the role of biomedical research and veterinary medicine in the process you just described? Essentially, what is the unique contribution of veterinary medicine in that spectrum of discovery and improved care?

At the present time, you're never going to get a medication or a biologic technique validated and licensed for use in humans until you do good preclinical research in animals. So, pragmatically, you've got to have preclinical work conducted by veterinarians in animals before you can get it into humans. Additionally, many diseases that occur naturally in people also occur naturally in animals. That makes veterinary research and clinical treatment important in advancing human medicine: when we join our efforts and join our discoveries, we find more effective treatments more quickly.

Here, we're interested in musculoskeletal disease and injuries, such as osteoarthritis, cartilage injury, tendon injury. The horse gets these naturally, as does the person. With cancer, the dog is the translational starting point, because they develop so much cancer during the course of their lives, just as humans do.

Veterinary medicine is critical, and it's recognized a lot more, too. In the old days, it was like, “Well, animals are different than people.” You'll still get some pedantic souls who talk like that, but there are lots of parallels.

Did you have an epiphany sometime during your education or your career, when you realized, “This work I'm doing could have far-reaching implications, not only for animal health, but for human health?”

It's been more of an evolution. I learned how to use an arthroscope from a human orthopedic surgeon. After that, we developed the techniques in equine arthroscopic surgery. We got into inflammation and recognizing the importance of synovitis through study in the horse. Now, there's lots of papers in human medicine on the critical nature of primary synovitis and primary subchondral bone disease, something that we've known ever since we started clinically treating horses and have also defined more closely with research. We've always felt that many findings in horses could be extrapolated to humans.

We started working with Dr. Richard Steadman at the Steadman Clinic and Dr. Bill Rodkey at the Steadman Philippon Research Institute in Vail because they wanted us to validate the use of microfracture as a surgical technique to repair damaged areas of articular cartilage of the knee. After that, we had corporations coming to us to test treatments in the horse, and later worked on quite a number of grants from the National Institutes of Health with us doing pivotal preclinical studies in the horse.

What do you think of as a best example of work you've done in the horse that has been applicable to human musculoskeletal disease?

We have worked collaboratively with experts in biomarkers in osteoarthritis. From that, we have developed biomarkers to predict early osteoarthritic change in the horse that also have a fairly good probability of predicting catastrophic fracture, or at least significant musculoskeletal injury, in the horse.

We worked with Dr. Chris Evans, who is arguably the father of gene therapy in human orthopedics, on the interleukin-1 receptor antagonist research. He pointed out that, for the first time, we showed with gene therapy we could get a clinical response close to a cure for osteoarthritis.

Our results with mesenchymal stem cells have been very impressive in the horse. The proof of principle has been accomplished. The optimal use of these cells given the current regulatory standards, including the need to ensure safety, is an evolving challenge. But we've been able to prove the value of these therapies and to stimulate further developmental efforts in human medicine. Our efforts are certainly a small part of the overall human landscape, and people such as Dr. Arnold Caplan at Case Western pioneered the work in bone-marrow-derived mesenchymal stem cells starting over 20 years ago. The advantage of the horse is that we've been able to do clinical studies and get good proof of principle of how they can significantly enhance our ability to treat osteoarthritis, cartilage disease, and tendon injury.

Can you provide a brief introduction to the Translational Medicine Institute?

The Translational Medicine Institute is an evolution from the Orthopaedic Research Center that we started in 1994 and built into a large research program (the largest orthopedic research center in a veterinary school anywhere in the world). The Translational Medicine Institute was a vision by Drs. Dave Frisbie, Chris Kawcak, and me that we sold to John and Leslie Malone. John agreed to be the lead donor. We had to get a matching donation and this was provided by Abigail Kawananakoa. We are going to continue what we have always done for horses but with a larger translational human component. In addition to a $77 million building, we have achieved partnerships with a number of critical programs in human regenerative therapies and sports medicine and one of the principal aims is to be able to not just develop therapies but fast-track them as much as possible into the human patient as well as the equine patient.

Looking forward, what do you see for yourself in the next several years?

I am in transitional retirement, as it is called at Colorado State University. Though I am trying to slow down a bit, it's not going very well at the moment. I have handed over administration to Drs. Frisbie and Kawcak and plan on retirement in another two years. Certainly, I will always have an office and be coming in, but I don't see myself losing any passion for what our program is doing. I want to stay involved with surgery and consultation in the equine industry and doing my bit to keep translating our vision into reality. I am leaving a large group of terrific people to carry on the cause. Other than that, my aim is to rock-climb more, spend more time with my wife, and visit my second home in New Zealand more often.

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Reprinted courtesy of Kentucky Equine Research. Visit ker.com for the latest in equine nutrition and management, and subscribe to Equinews to receive these articles directly.

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AAEP Convention: Standing Arthroscopy Can Be Used On More Than Stifles

When traditional diagnostic tools such as X-ray and ultrasound provide no definitive diagnosis for an equine lameness, a vet may perform an arthroscopy. While this procedure typically requires putting the horse under general anesthesia, a needle arthroscopy can be done while the horse is under standing sedation, Dr. Alvaro Bonilla said at the virtual 2020 American Association of Equine Practitioners Convention and Trade Show.

A safe, reliable procedure, needle arthroscopy is less risky and less costly to the owner; putting a horse under general anesthesia for surgery has its own risks, including recovery. While typically used for diagnostics, a standing arthroscopy can also be used therapeutically for septic joints and small osteochondral fragments, specifically for dorsal fragments of the first phalanx in the fetlock, Alvaro says. However, the procedure does still have limitations.

Previously, needle arthroscopy was used only in the stifle joint; Alvaro reports that now it can be used successfully to evaluate multiple synovial structures, including shoulders, fetlocks, hocks, radiocarpal and middle carpal joints, and carpal sheaths.

When using this diagnostic tool, it's important that the horse is sedated, but not overly so, which could make him unsteady and make the procedure not only difficult, but dangerous. Additionally, the surgical site must be sterile, which can be difficult as debris can fall onto the joint or the horse can urinate. Potential for both complications can be decreased by using blankets and inserting a urinary catheter.

An adjustable, lightweight splint made from stainless steel and aluminum is used during the procedure; to ensure as successful an outcome as possible, horses should be acclimated to wearing the brace before being sedated for the surgery.

The surgical area should be bandaged for four to five days following the procedure; horses that had the procedure for diagnostic reasons can go back to work as soon as the bandages are removed.

Read more at EquiManagement.

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