by: Christy West, Digital Editor/Producer August 01 2010, Article # 16761
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The laminitis mystery is far from solved, but researchers continue to discover new clues about its causes,
treatment, and prevention.
Laminitis, an often devastating hoof disease that can strike horses of any breed without warning, is a major
issue for horse owners and veterinarians alike. In the recent American Horse Publications (AHP) Equine
Industry Survey, nearly 50% of the 11,000-plus owners surveyed listed it as a health issue of concern. And
in last year's AAEP (American Association of Equine Practitioners) Equine Research study, 63% of the
responding veterinarians listed it as a health condition in need of more research, making it the No. 1 health
problem listed on the survey.
Some of the best minds in equine veterinary medicine have targeted this disease, and the pieces are starting
to fall into place. Here we'll visit studies described by James Orsini, DVM, Dipl. ACVS, Penn Vet
Laminitis Institute director; and Amy Rucker, DVM, of Midwest Equine in Columbia, Mo., who both
presented at the Fifth International Equine Conference on Laminitis and Diseases of the Foot (Nov. 6-8,
Laminitis is an inflammation of the laminae--interlocking leaflike tissues attaching the hoof to the coffin
bone. It can strike any number of feet on any horse due to a variety of triggers, from high-carbohydrate
diets in sensitive horses to colic to retained placenta to mechanical overload. Severity ranges from mild and
curable to severe and incurable (resulting in euthanasia).
Enzymes and the Laminitis Process
A major focus in laminitis research has been enzymes (which catalyze or stimulate chemical reactions in
the body) that get out of balance in early stages of the disease. It's been theorized that if these enzymes
could be controlled medically, laminitis could be prevented or minimized. Previous work has often focused
on enzymes called matrix metalloproteinases (MMPs), which have a role in hoof growth but become
overactive in laminitis. However, more recent work has found that another enzyme, an aggrecanase termed
ADAMTS-4, spikes much earlier in the laminitic disease process than MMPs (first reported by Orsini and
colleagues at Penn in 2005).
Christopher Pollitt, BVSc, PhD, director of the Australian Equine Laminitis Research Unit and research
director of the Penn Vet Laminitis Institute, wrote that these findings "are causing us to rethink the early
events that culminate in clinical signs of laminitis." Another researcher, Samuel Black, PhD, professor of
Veterinary and Animal Sciences at the University of Massachusetts, discussed similar ADAMTS-4
findings, lending support to this line of research.
Black also reported that certain molecules that help joint cartilage resist compressive forces (the
proteoglycans: aggrecan and versican) have recently been found in the laminae, suggesting a similar role
there. Thus, increased activity of the ADAMTS-4 enzyme that breaks down these molecules "may
contribute to the loss of lamellar function in laminitis," he noted.
Hormones and Laminitis
Overweight horses are at higher risk for laminitis, often due to insulin resistance (a reduction in sensitivity
to insulin that -decreases the ability of glucose to be transported into the body's cells from the bloodstream).
Nicholas Frank, DVM, PhD, Dipl. ACVIM, associate professor of Large Animal Medicine at the
University of Tennessee, noted insulin resistance can "lower the threshold" for laminitis in affected horses.
He also noted small management changes, such as introducing a new batch of hay or feed with higher
levels of nonstructural carbohydrates (NSC), stress increases, or exercise reduction, can push these horses
over the edge. Frank reported that even healthy horses hospitalized for two weeks had increased insulin
resistance, suggesting that stress and possibly exercise reduction can contribute to insulin resistance.
"We haven't had any studies to support this in the past," noted Orsini.
Nutrition and Pasture Management
Horses with high body condition scores (7-9, fleshy to extremely fat; see
www.TheHorse.com/pdf/nutrition/bcs.pdf for more on body condition scores), hyperinsulinemia (high
levels of insulin in the bloodstream of 32mU/L or more), and cresty necks "are the ones you should look at
very carefully, as these are good predictive criteria for laminitis development under certain conditions,"
said Orsini. This research was presented by Ray Geor, MVSc, PhD, Dipl. ACVIM, professor and
chairperson of the Department of Large Animal Clinical Sciences at Michigan State University.
For these at-risk horses, Geor recommended reducing digestible energy in the diet, keeping NSC levels in
grass hay at 10% or less (see "Analyzing Forages" at www.TheHorse.com/6172), removing grain from the
diet, feeding hay at 1.5% of the horse's body weight per day or less, eliminating pasture grass access until
the horse is no longer overweight, and increasing exercise to improve insulin sensitivity.
"Prevention is still the best course of (laminitis) treatment," stated Orsini.
In another presentation a researcher reported that regional weather conditions are more important than grass
type or even overall season when it comes to NSC content in pastures. Kathryn Watts, BS, of Rocky
Mountain Research and Consulting, reported that when comparing established, matched stands of several
grass species in Colorado and Utah throughout the year, the samples from cooler, sunnier Colorado were
always higher in NSC by up to 8%. Cool temperatures (below 40°F at night), sunny weather, drought
stress, fall rains/cool temperatures (increased growth), and frost stress can all increase NSC concentrations,
"She has also told us that it may be safer to turn an at-risk horse out on winter pasture after snow covers the
ground and leaches out some of the sugars from the grass," recalled Rucker.
Lastly in the nutrition area, Pollitt reported that the laminae appear to depend more on anaerobic (without
oxygen) energy metabolism. Thus, they consume a good deal of glucose; Pollitt discussed using an open-
centered (cannulated) screw through the hoof wall to help deliver glucose and medications directly to the
Pentoxifylline Susan Eades, DVM, PhD, Dipl. ACVIM, a professor of Veterinary Clinical Sciences at
Louisiana State University, reported that of the medications doxycycline, oxytetracycline, pentoxifylline,
and flunixin meglumine, pentoxifylline was the most potent inhibitor of MMP production. She also noted
that in a small study, horses given pentoxifylline every 12 hours after dosing with excessive carbohydrate
(to induce laminitis) were one to two grades less lame than controls, and in some cases they did not become
lame at all.
Pain medications Tony Yaksh, PhD, vice chair of Anesthesiology at the University of California, San
Diego, discussed the possibility that the pain of laminitis might represent not only the pain of the disease,
but also hypersensitized nerve pain termed neuropathic pain. Normally associated with "complex pain
states" such as those in arthritis, osteosarcoma, and diabetes, this neuropathic pain does not always respond
completely to pain medications directed toward other mechanisms of pain.
"He challenged us to think about whether we should be treating for both types of pain, not just one or the
other," recalled Orsini.
Investigating inflammatory processes is another major focus in laminitis research. James Belknap, DVM,
PhD, Dipl. ACVS, a professor of Veterinary Clinical Sciences at The Ohio State University, discussed
several ongoing projects in this area with the following findings:
The two main laminitis models used for study, which include the carbohydrate overload model mentioned above and a model whereby researchers use black walnut extract to induce laminitis, both cause inflammation in the laminae. However, the times at which the inflammation arises, and the particular inflammatory mediators that the researchers see, vary between the models.
While oxidant stress (damage from free radicals) does occur with laminitis, it appears to be controlled and, thus, not a significant cause of structural failure.
Although white blood cells were thought only to be present in the laminae when laminar damage occurred, Belknap reported they also have been found in normal laminae. The number of white blood cells of different types does increase in the laminae with laminitis, but to different degrees depending on the model.
Since certain white blood cells in large amounts could contribute to laminar damage, inhibiting them could help reduce laminitis severity. Belknap reported that nonspecific cyclo-oxygenase (COX) inhibitors might be indicated for initial laminitis treatment, and COX-2 inhibitors might be better for long-term use in chronic cases. Anti-inflammatory drugs such as corticosteroids inhibit white blood cell activity and might also be worth considering, but until this use for them is studied, sticking to non-steroidal anti-inflammatory medications such as phenylbutazone (Bute),
flunixin meglumine (Banamine), and firocoxib (Equioxx), as prescribed by your veterinarian, is best.
Researchers are also studying highly targeted medications that inhibit specific inflammatory enzymes and receptors.
Rucker presented a "diagnostic multimedia" approach that included taking a detailed history, conducting a
physical exam, radiography, digital venography, and MRI when available to determine the degree of
damage and develop an effective treatment plan.
"As our understanding of the soft tissue pathology in laminitic horses improves, enhanced use of traditional
technology and adaptation of newer technology offers the opportunity to detect the changes and implement
appropriate treatment much earlier in the disease process when treatment response is optimum," she noted.
"You have to have mechanical collapse of the foot (to some degree) even before you can see measurement
changes on a radiograph, but you can see major changes earlier on venograms and MRI imaging." (More
information on imaging protocols: Clinical and Radiographic Examination of the Equine Foot,
Tenotomy Cutting the deep digital flexor tendon to remove its pull on the diseased laminae is often a last
resort, but some practitioners have found it to be very effective when used early. Scott Morrison, DVM, of
Rood & Riddle Equine Hospital in Lexington, Ky., discussed a 245-horse retrospective study of tenotomy
cases and reported success rates (pasture soundness at minimum) as high as 93%, depending on the case.
Sinkers (the coffin bone sinks straight down in the hoof capsule without its tip rotating down toward the
sole) had the lowest success rate at 18%.
"Deep digital flexor tenotomy accompanied by realignment shoeing improves the outcome in horses with
chronic laminitis that are unresponsive to shoeing alone," said Morrison.
Cold therapy Cryotherapy was shown to prevent laminitis in high-risk cases years ago, but today there's
still no commercial system in widespread use due to technical challenges. At the conference, Andrew van
Eps, BVSc, PhD, MACVSc, Dipl. ACVIM, senior lecturer in Equine Medicine at the University of
Queensland, discussed a study using a system in which a membrane stays in contact with the lower leg and
foot while coolant constantly circulates over it. He reported that this type of system was effective at
keeping the foot near the target temperature of 5°C (41°F).
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