Tildren, the Magical Product against Lameness?!
Sat, 01/10/2009 - 00:00
Hindlegs in the piaffe
Photo © Astrid Appels
by Erin Richards - Republished by permission of The Chronicle of the Horse. Visit www.chronofhorse.com to subscribe.
The signs are familiar and common yet never easy to watch: short,
stubby strides, marked soreness, the head-bobbing lameness. When those
kinds of symptoms are caused by navicular syndrome, treatment options
have been depressingly slim.
But in the early part of this
century, veterinarians with well-connected European colleagues heard
whisperings about, or actually obtained, a new drug that appeared to
work wonders at restoring soundness in horses with bone-related
lamenesses.
From grand prix jumpers with slight changes in their
legs to backyard pleasure horses stricken by navicular, a drug called
Tildren appeared to slow the bone deconstruction process.
Today,
Tildren has become a one-dose ticket to recovery or prevention for many
horses. The problem? In the six years since people started hearing about
the medicine, the U.S. Federal Drug Administration has yet to approve
Tildren for use in this country.
That may change soon, however,
if the results of an intense, nationwide study currently underway and
being funded by the drug’s founder, Ceva Sante Animale in France, go
according to expectations. FDA approval of the drug would open up access
to Tildren for veterinarians and likely decrease the price of the
medicine, making the drug available to a greater number of horses and
owners.
Perhaps because of its international origins, Tildren
still isn’t well known. In France, Ceva is a leading science and
research company that has introduced new drugs and therapies for
everything from cows and poultry to dogs and swine and horses.
But
to obtain Ceva’s Tildren in the United States, licensed veterinarians
are required by law to fill out separate applications for each horse
they think qualifies for the medicine, a process that can take six to
eight weeks from the time a veterinarian diagnoses a horse’s condition
to when he or she has Tildren ready to administer.
An Intravenous Intervention
Upon
arrival, the drug maintains its mystique. At Homestead Equine Hospital
in Pacific, Mo., veterinarian Mark Cassells remembered being a bit
perplexed when he ordered Tildren for the first time. The package was a
little blue box that, when unwrapped, revealed rows of little bottles
and vials and a bunch of French or German directions on how to
administer it.
“None of the instructions are in English,” said
Cassells, who started ordering Tildren for his clients a few years ago
after hearing about the drug at a conference. “There are 20 vials
inside, 10 that contain the drug in a powder form and 10 that contain
the dilutant,” Cassells said. “You mix up one vial of powder and one
vial of dilutant every day to administer intravenously, or you can mix
up the entire thing and administer it in a one-time intravenous dose.”
Most
veterinarians prefer the one-time intravenous dose. Instead of oral
medicine, which gets absorbed more slowly or not at all because it goes
through the digestion system, intravenous Tildren soaks into a horse’s
bones like water seeping into a sponge.
Controlling The DamageThis
is where Tildren goes to work. In a horse with navicular or any other
chronic bone condition—ringbone, for instance, or osteoarthritis of the
hock—Tildren inhibits bone deconstruction by shutting down what are
known as osteoclasts. Osteoclasts, like hungry termites, digest bone,
and Tildren impedes their progress.
More scientifically, Tildren
is a class of substances known as bisphosphonates, which inhibit
osteoclast action and the resorption of bone.
In healthy horses,
bone is constantly being remodeled. This is how animals get stronger;
when the skeletal structure is stressed through training, it responds by
making new bone tissue. Osteoclasts in a healthy horse eat away old
bone to make room for the new and denser bone, which is formed with the
help of osteoblasts. But typically, osteoblasts work much more slowly
than the nibbling osteoclasts.
This is especially important in
horses with navicular syndrome and other chronic bone conditions, where
the bone breakdown process may exceed the bone rebuilding process,
explained veterinarian Rick Mitchell, of Fairfield Equine Associates in
Newtown, Conn.
“By reducing bone breakdown and further
degeneration, the thought is that the drug reduces pain,” Mitchell
explained. “Before Tildren, we didn’t have anything that could do this.”
Tildren
already exists in an oral form that is approved for human use. Known
generically as “tiludronate” or “tiludronate disodium,” the substance
is typically obtained under the brand name Skelid, and it’s used to slow
the weakening of bone that occurs in a condition called Paget’s
disease. Currently, it’s also being tested for treating osteoporosis.
As
for horses, the best ammunition veterinarians and owners had against
chronic bone conditions before Tildren weren’t substances that directly
targeted the bone at all. Drugs such as isoxsuprine and pentoxifiline
are thought to primarily increase circulation in the afflicted areas,
though as Mitchell noted, nobody has rigorously proved isoxsuprine’s
efficacy in randomized and controlled studies.
Tildren hasn’t
replaced those drugs, but it has offered a significantly different way
of attacking the root problem of many chronic bone conditions: bone
breakdown.
In one small study Mitchell and his colleagues
conducted several years ago, the administration of Tildren, combined
with corrective shoeing in horses that showed signs of navicular, had
about an 80 percent soundness success rate after six months.
The
study was fairly small, but Mitchell and other researchers were careful
to make sure the cause of lameness was navicular and not some other
factor. In every case, the administration of Tildren helped more horses
after six months than horses that were administered other types of
therapies without Tildren, for instance, corrective shoeing with bute
and banamine treatment.
It’s still possible, said Mitchell, that
it was simply their selection of cases that produced the positive
results and not the drug itself. But, the results they got in that study
matched the results obtained by Jean-Marie Denoix, a veterinarian in
France, one of the earliest researchers to test the drug and one of the
most well-known experts in the field.
“I think we have good
information that Tildren works, but we don’t have solid proof yet,”
Mitchell said. “What we do know is that if it works as well as we think
it does, then the earlier a horse with bony changes gets treated with
it, the better.”
More Rigorous StudyThe
most rigorous and widespread Tildren study to date is currently being
carried out in about nine locations across the United States. Mitchell’s
clinic is one of the test sites, as is the Wisconsin Equine Clinic and
Hospital in Oconomowoc, about 35 minutes west of Milwaukee.
Ceva
is paying for the study, with the explicit goal of proving efficacy and
getting an FDA permit to treat navicular bone disease with the drug.
At
Wisconsin Equine, veterinarian Doug Langer has so far had 23 horses
that have been accepted into the study. He expected the 200 horses
needed across the country to be accepted before the end of 2008.
The
only problem, he said, is that only a small percentage of horses they
test actually qualify to be a part of the study—between 20 and 25
percent. With more thorough imaging, Langer said they sometimes discover
that potential test subjects have more going on inside their bodies
than just changes to the navicular bone.
For control purposes,
the horses accepted must only show changes to their navicular bone and
no other ligament, tendon or bone injuries.
“I don’t think the company paying for the study expected they would have to be paying for so many MRIs,” Langer said.
Once
the test subjects are identified, the horses either receive Tildren or
an intravenous placebo. The veterinarians then follow the test subjects
for two months and document any changes.
If, at the end of the
two months, it turns out that the horse received the placebo, then the
owner is allowed to have their horse receive the real drug, if they so
choose.
On the East Coast, Mitchell said that getting horses into
the study has been a bit slow because some owners don’t want to disrupt
their show schedule; others are leery of being involved in a study
where for two months their horse may only be receiving a placebo.
“The
other problem is that sometimes it’s hard for us, too, to identify just
navicular bone edema,” Mitchell said. “There’s a potential for owners
to not get the drug, and that makes some of them reluctant to
participate.”
But
the point of a rigorous study, Mitchell said, is to prove efficacy.
Once you can prove efficacy and safety, everything else tends to fall in
line and the drug will be made available in the United States.
In Wisconsin, Langer said his experiences with the drug so far have been, “quite remarkable.”
“Back
in May, I had a horse with navicular that was [grade] three out of five
lame,” Langer said. “Severe navicular. It wasn’t even a candidate for
nerving. It was given one treatment of Tildren, and I didn’t evaluate it
again until four months later. At that time, it was completely sound.”
Langer added: “If we can help even half of the horses with that kind of affliction, then it’s a step in the right direction.”
Not PerfectTildren
is not a cure-all, and there are still some drawbacks. The drug targets
bone and, specifically, the processes that affect bone degeneration. So
that means it won’t ease any lamenesses caused by tendon, ligament or
muscle injuries. Also, it’s not intended for use on horses that are
still growing, or mares that are pregnant or lactating.
Occasionally,
some horses get a bit colicky after the administration of the IV fluid
with the Tildren solution. Also, Tildren cannot be used while a horse is
in competition as there are some withdrawal times.
Then there’s
the issue of price. At $1,000 to $1,100 per dose (one time or 10
intravenous shots over 10 days), Tildren isn’t a cheap medication.
However, that price is likely to decrease once the FDA approves the drug
and it becomes warehoused in the United States.
To keep extra
doses of Tildren on hand right now, many veterinarians are compelled to
engage in a bit of sleight of hand with the FDA, usually by
re-submitting the names of horses who have already received the drug to
keep new doses coming over from Europe. This keeps the veterinarians
from having to go through the laborious process of filling out all new
paperwork for a new horse that needs the drug and making the owner wait
six weeks or so until the medicine comes through in that horse’s name.
Some veterinarians combine Tildren with additional therapies such as shockwave therapy to get the best results.
Kathy
Frame, from Oconomowoc, Wisc., said that her 16-year-old grand prix
show jumper had a bit of a hitch in his hind end, which she treated with
Tildren and then shockwave therapy. Frame said the horse was never
lame, he just seemed a bit off.
“We
won a grand prix the week I did the shockwave, so it’s a little hard to
tell if it was the Tildren I did before or the other therapy,” Frame
said.
Kyle Dewar, also from Oconomowoc (and engaged to Frame),
said he once used Tildren on one of his older horses. The horse had
ringbone, Dewer said, and he administered Tildren after getting the drug
from a friend in Europe.
“It eased his arthritic changes,” Dewer said of his older jumper.
Now, Dewar said, he uses it on some warmbloods that he imports from Europe.
“If
I notice a little something on an X-ray in Europe, I know I could use
some Tildren on it,” Dewar said. “They may have an enlarged vascular
channel in their foot or slight navicular changes, and Tildren seems to
improve the bone density and clear those right up.”
As a rule,
people won’t see immediate effects from Tildren. It takes time to work,
and the maximum benefit will be seen in about two months.
“By no means is this a magic cure,” said Langer at Wisconsin Equine, “but it has helped a lot of horses.”
Source:
The Chronicle of the Horse
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