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Bisphosphonates, Clodronate (Osphos®) Tiludronate (Tildren®)

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Bone is a dynamic tissue. It is resorbed and deposited in locations depending on mechanical stresses and many other factors. Some chronic equine lameness and pain-causing conditions involve the chronic (and potentially excessive) breakdown of bone. There are two cell types directly involved in this constant process of dissolution and repair of bone. The osteoblast is the cell that deposits and builds bone. The osteoclast dissolves and removes bone.

Bisphosphonates reduce bone breakdown by preventing the bone removing cells (osteoclasts) from resorbing bone. Based on their function then, bisphosphonates should be especially effective in disease states in which bone resorption is an important feature.

Bisphosphonate therapy has two major theoretical advantages to more traditional local therapy. Given systemically (IM or IV depending on particular drug) , a bisphosphonate can treat multiple areas of bone turnover at once. It also targets the process of bone destruction itself rather than providing only symptomatic relief. The medication selectively targets areas of active bone destruction at the time of administration.

It has become clear through use of these drugs that there is a relatively short (several week) period of direct pain relief, unrelated to the main mechanism of interfering with bone resorption. The actual effect on osteoclasts and bone resorption should be visible as reduced lameness at 4-8 weeks and this effect should last up to 6 months.

Two bisphosphonates are currently FDA approved in the USA, for navicular disease only. These drugs are Tildren® (tiludronate) and clodronate, marketed as Osphos®.

Tiludronate is administered to horses by intravenous (IV) infusion. Different protocols exist ranging from a single large dose given over one hour, to smaller doses given over 10 days.

Clodronate is administered by a single 15cc IM injection, usually divided into 3 IM sites. Repeated doses may be given at 3-6 months or if signs of lameness recur.

Bisphophonate therapy can be used alongside traditional treatments (e.g. NSAIDs, steroids, supplements) and supportive therapies (e.g. corrective shoeing, controlled exercise).

YOUR VET’S ROLE

Your vet should make a diagnosis before suggesting the use of these drugs. The drugs should be reserved for cases for which bone resorption is thought to play an active (and undesired) role in the disease process and pain. Your vet also considers the horse’s general health and whether these drugs are a good and safe fit.

While the drugs are FDA approved for use in navicular disease only, they may have benefit in other conditions, used in an extra-label fashion. There are other disease conditions (in which bone resorption plays a role in the disease process and pain) that may benefit from the use of this drug class. Examples are bone spavin (hock arthritis), back pain from intervertebral osteoarthritis (spondylosis), osteochondrosis (OCD) as well as a variety of other conditions. This drug class also may have value in treating chronic osteoarthritis. While cartilage loss is the main hallmark of arthritis, part of the process also involves bone loss and remodeling under the cartilage surface. Inhibition of this bone breakdown may thus slow the progression of joint disease and may provide some direct relief from pain.

Your vet will consider these disease processes and when these drugs might have potential application.

YOUR ROLE

It’s important to be aware of this drug class and to understand its basic mechanism and limitations. It’s also important to be on the lookout for the potential side effects seen right after injection.

Like any treatment for subtle problems, it is very important for you to be as objective as possible when evaluating the treatment’s effectiveness. Try to quantify the degree of lameness before and after administration Keep a record of degree of lameness so that you can better determine the real effect of this treatment on your horse. This way, you can also better recognize when a treated horse is again beginning to show signs and might benefit from another injection. Always communicate with your vet when you have any question about the use of this drug on your horse.

Consider Potential Side Effects & Complications

Horses receiving either of these medications should be monitored for at least 2-6 hours after injection for the short-term side effects.

The IM bisphosphonate (clodronate) is acidic in pH and so the intramuscular injection can be irritating to some horses. They may toss their heads, paw, grind their teeth and curl their lip and show signs of pain following administration. Local swelling at an IM injection site of injection may develop but should resolve within a few days.

Transient colic pain rarely develops after clodronate treatment but typically resolves without treatment, or with 15 minutes of hand walking.

There is at least a possibility that use of bisphosponates could weaken bone and predispose to fracture but this is probably extremely unlikely. This is said to be less likely in horses than in human medication protocols because of some specific drug differences. The human drugs tend to be more potent and long-lasting.

Kidney disease is possible when using drugs of this class. In most cases, other drugs that compromise kidney function (NSAIDS like bute or Banamine) should NOT be used around the time of drug administration and should not be used to treat mild side effects of these drugs.

Consider Reasons Not To Use This Treatment

Adequate safety studies have not been performed in young, growing animals under 4 years of age, or in pregnant or lactating mares. For that reason, it should generally not be used in these horses. Tiludronate should not be used in a horse younger than 2 years old or horses or in horses with evidence of kidney disease. NSAIDS (bute, flunixin (Banamine), firocoxib, etc) should not be used along with bisphosponates. These drugs may predispose a horse to kidney problems with administration of a bisphosponate. In most cases, a bisphosphonate should NOT be used without a diagnosis. A bisphosphonate probably has little or no value and may cause harm when used to "prevent disease". There is almost never a reason to give a bisphosphonate more frequently than the recommended frequency. Because of the intricate interplay between bone resorption and deposition in natural fracture repair, this drug class should not be given to a horse within 4-6 weeks of fracture.

Is It working? Timeframe for effect

Maximum effect is seen 6-8 weeks after treatment, and the effect can last for up to 6 months. You should see reduced lameness during this period. Sometimes you will see significant improvement in lameness within 7-14 days after administration. This is likely due to a transient pain-relieving effect seen with these drugs. This very early response may not be an indication of the long-term effectiveness of the medication (it may be independent of the main, bone modifying effects). In the case of navicular syndrome, bisphosphonates can show less effect when the disease has been long standing, but they still may be helpful.

Questions To Ask My Vet

  • What makes you think a bisphosphonate is a good choice for my horse's problem?
  • What is your opinion of the studies that show beneficial use of this medication?
  • What has been your experience with this medication?
  • What signs should I look for after treatment indicating that this medication has helped?
  • How frequently do you expect my horse to need to be retreated?
  • How do we know when to re-dose?
  • How concerned are you about potential side effects or complications?

Helpful terms & topics in HSVGWritten, Reviewed or Shared by Experts in Equine Health

Dechra Veterinary Products
Osphos®
(clodronate injection)
OSPHOS is an injectable bisphosphonate solution for the control of clinical signs associated with navicular syndrome in horses four years and older. Lameness in 74.7% of horses improved by at least one grade 56 days after treatment. Mild transient colic was only seen following 9.0% of treatments. Osphos is the only FDA approved intramuscular bisphosphonate injection for the control of the clinical signs associated with navicular syndrome in horses. (Prescription Only)
Ceva Animal Health Inc. Tildren®, (tildronate disodium)
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Author: Coauthored by Doug Thal DVM DABVP & Susan Shaffer DVM

RELATED REFERENCES

Denoix JM, Thibaud D, Riccio B. Tiludronate as a new therapeutic agent in the treatment of navicular disease: a double-blind placebo controlled clinical trial. Equine Vet J 2003;35(4):407-13.Allen AK, Johns S, et al. How to Diagnose & Treat Back Pain in the Horse. AAEP Proceedings 2010;56:384-88.Fortier et al. Systemic Therapies for Joint Disease in Horses. Cited in Oral Joint Supplement Topic, 2005.Gough MR, Thibaud D, Smith RK. Tiludronate infusion in the treatment of bone spavin: a double blind placebo-controlled trial. Equine Vet J 2010;42(5):381-87.Coudry V1, Thibaud D, Riccio B, Audigi? F, Didierlaurent D, Denoix JM
Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column.
Am J Vet Res. 2007 Mar;68(3):329-37.
Gough MR1, Thibaud D, Smith RK. Tiludronate infusion in the treatment of bone spavin: a double blind placebo-controlled trial.
Equine Vet J. 2010 Jul;42(5):381-7. doi: 10.1111/j.2042-3306.2010.00120.x.


Pers. Communication- Dr Joseph Manning, Dechra Tech Services Veterinarian. Coudry V, Thibaud D, Riccio B, et al. Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column. Am J Vet Res 2007;68(3):329-37.

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