Bisphosphonates are a type of medication that is used to prevent the loss of bone density by inhibiting the activity of osteoclasts- the cells that break down bone tissue. The two main bisphosphonates used in horses are clodronate (OsPhos®) and tiludronate (Tildren®).

These medications are used to treat conditions associated with increased bone turnover, a natural bodily process where old bone cells are resorbed and replaced by new ones. These drugs may also reduce bone pain and inflammation, enhancing quality of life for affected horses.

Currently, bisphosphonates are only approved to treat navicular disease in horses. Veterinarians may prescribe bisphosphonates to treat other conditions, such as arthritis and back pain, at their discretion.

Studies show bisphosphonates are effective at reducing lameness and returning affected horses to their previous levels of performance. Horses receiving bisphosphonates should be closely monitored for any side effects and long-term use should be approached cautiously.

Bisphosphonate Treatment in Horses

Bisphosphonates are a class of drugs originally developed for treating bone fragility disorders such as osteoporosis in humans. Their use has been adapted for horses to treat various musculoskeletal conditions where there’s excessive bone loss or turnover.

There are currently only two bisphosphonates approved by the FDA for use in horses older than four years: tiludronate disodium and clodronate disodium . [1]

Effects on Tissues

The main effect of bisphosphonates is altering normal bone metabolism in favor of maintaining existing bone, rather than building new bone. [1] Bisphosphonates can also reduce bone pain and inflammation through their interactions with bone cells. [1]

Bone Turnover

Bones are constantly in the process of remodeling or turnover, where old bone tissue is resorbed and replaced with new cells. There are two types of bone cell involved in remodeling: osteoclasts and osteoblasts.

  • Osteoblasts regenerate new bone cells
  • Osteoclasts digest old bone cells to make room for the new ones

Bisphosphonate drugs bind to osteoclasts and trigger cell death, which reduces overall numbers of these cells in bone tissue. [1] Decreasing the number of osteoclasts in the tissue slows bone turnover as old bone cells are removed at a significantly slower rate. [1]

This effect on bone remodeling shows promise in treating conditions associated with increased bone resorption, such as repetitive bone stress from exercise. [1] By slowing the rate of bone turnover, these products are expected to slow the progression of painful or performance-limiting conditions, which may prolong a horse’s athletic career and improve quality of life.

Bone Strength

The primary factors influencing bone strength are the degree of mineralization and the integrity of the bone’s architecture. [2] The precise effect of bisphosphonates on bone strength is controversial, as both beneficial and adverse effects have been identified. [2]

By reducing bone turnover, bisphosphonates maintain older bone cells within the tissue. These cells often have higher degrees of mineralization, which increases the stiffness of the bone. [2] Maintaining older bone cells in the tissue also means the collagen (connective tissue) component of bone is older and stiffer compared to new collagen. [2]

Increased stiffness improves bone strength overall, however it reduces the bone’s toughness. Bone toughness refers to the ability of a bone to resist spread of a fracture or crack. [2] This suggests bisphosphonates may increase the amount of pressure required to damage a bone, but may also facilitate catastrophic destruction of the bone if damage does occur. [2]

Bone Pain

The specific mechanism of how bisphosphonates reduce bone pain is unknown, however research suggests osteoclast activity may be a painful stimulus itself. [1] To break down old bone, osteoclasts excrete acidic waste byproducts, which may activate pain sensation in surrounding nerves. [1]

Review of studies from human medicine suggest the efficacy of bisphosphonates in treating arthritis is likely due to pain control rather than altering bone turnover. [3] These studies caution the use of bisphosphonates in athletes, as the pain control properties may allow athletes to continue training and cause additional damage to the joint. [3]

Studies show that horses receiving bisphosphonates have lower lameness scores than untreated horses. [1] Bisphosphonates are effective for pain control in back arthritis, hock arthritis, and navicular syndrome according to equine studies. [3]

The exact dosage, dosing frequency, and route of administration need further research to determine the optimum treatment protocol for specific lameness conditions. [1]

Inflammation

Osteoclasts have a role in bone inflammation by activating inflammatory cells in response to bone injury or disease. [1]

One of the main inflammatory cells activated by osteoclasts are macrophages, the major clean-up cell in the body. [1] Once activated, these cells release proteins that trigger activation of other inflammatory cells, leading to a widespread inflammatory response. [1]

Studies show that bisphosphonates can decrease the release of proteins from activated macrophages, reducing further activation of the inflammatory response. [1]

Joint Protection

There is some evidence to support the use of bisphosphonates as chondroprotectants, which are medications that protect the cartilage from damage. [2] These medications are used to treat arthritis in horses, as they can reduce the progression of disease.

Studies show that bisphosphonates can inhibit the enzymes and inflammatory products that destroy cartilage cells in cases of arthritis. [2] One canine study showed cartilage loss and the progression of arthritis were reduced in dogs receiving bisphosphonates after a cranial cruciate ligament tear. [2]

Clinical Usage in Horses

The two bisphosphonate products available for horses are specifically designed to treat navicular disease. [1] Bisphosphonates may be prescribed at the discretion of the treating veterinarian for pain management in other cases of bone and joint disease. [1]

Bisphosphonates have poor absorption from the digestive tract, so all bisphosphonate products are formulated for injection. [1] The dosage and dosing schedule depend on the product used and the disease being treated. [1]

Navicular Disease

Both tiludronate and clodronate are FDA-approved for treating symptoms of navicular disease in horses. [1] Navicular disease is a common cause of lameness resulting from pain or inflammation in the navicular bone or its surrounding structures. [2]

Studies suggest navicular disease is caused by abnormal forces on the navicular bone leading to bone degeneration, pain, and lameness. [2]

The administration route for tiludronate is intravenous infusion over a period of 90 minutes. [4] Clodronate administration involves a series of three intramuscular injections in three separate areas on the horse’s body. [5]

Both medications can be repeated at 3-6 month intervals if signs of lameness recur. [4] It can take up to 2 months to see improvement in lameness after administration of these medications. [4]

Scientific Evidence

There are several studies supporting the use of bisphosphonates in reducing lameness in horses with navicular disease. [1]

Studies on clodronate show that around 65% of horses have a positive response to treatment by 180 days after administration. [1] Many horses improve at least one lameness grade within 90 days of treatment, with 48% of horses becoming sound. [1][6]

Another study showed similar results with 74% of horses showing lameness improvement after clodronate treatment. [7]

Tiludronate-treated horses show improved weight bearing on lame limbs compared to control horses. [1] Another study showed treated horses returned to previous levels of activity within 2-6 months of treatment. [2]

Response to bisphosphonate treatment is variable depending on the horse and the study. Studies suggest horses with active bone pain show the most improvement after bisphosphonate administration. [1]

Other Uses

Bisphosphonates are often prescribed at the discretion of the treating veterinarian to treat conditions other than navicular disease. [3]

Common off-label uses of bisphosphonates include treatment for: [1][3][8]

Overall, there is limited scientific evidence to support the use of bisphosphonates in treating conditions outside of navicular disease. [1] Most studies investigating other uses of bisphosphonates focus on arthritis.

One study in horses with spinal arthritis showed improved range of motion in the back 60 days after bisphosphonate administration. [9] 77% of owners in the study reported a positive response in their horse’s symptoms after treatment. [9]

Other studies show reduced lameness and pain scores after treatment in horses with hock and fetlock arthritis. [1][10]

One study also reported fewer osteophytes (bone proliferations) surrounding hock joints in horses treated with bisphosphonates. [10] Osteophytes are a common indicator of arthritis on X-rays. Researchers identified similar findings in human medicine, along with reports of improved function and reduced stiffness. [6]

The presumed effect of bisphosphonates in these studies is as a pain control agent, rather than treating the arthritis itself. [3][11][12]

One study examining a large group of horses receiving bisphosphonates for both navicular disease and other conditions showed 72% of horses treated returned to performance within 6 months of administration. [8] These findings suggest bisphosphonates may be effective in treating other disorders beyond navicular disease. [8]

Side Effects

Approximately 30-45% of horses develop symptoms of colic within 4 hours of bisphosphonate administration. [4] Signs include: [4][5]

  • Pawing
  • Pacing
  • Restlessness
  • Rolling
  • Biting at the flanks
  • Kicking at the abdomen
  • Muscle tremors

Symptoms typically resolve without treatment, however some horses may require additional veterinary care. [4]

Some horses develop additional side effects anywhere from 4 to 24 hours after administration, such as: [4][5]

  • Reduced appetite
  • Stiff or sore neck or soreness at the injection site
  • Fever
  • Increased urination

Kidney Problems

Rarely, bisphosphonates can cause sudden onset kidney failure in horses. [4][5] For this reason, other drugs that may compromise kidney health should not be given to horses receiving bisphosphonate treatment. [4][5]

Medications to avoid include, but are not limited to: [4][5]

Many veterinarians recommend bloodwork prior to bisphosphonate administration to ensure there is no pre-existing evidence of kidney disease. [1]

Long-Term Effects

Some research suggests bisphosphonate use may increase the risk of bone fractures in horses. [3]

In other species, including humans, long-term use of bisphosphonates increases the risk of osteonecrosis (death of bone tissue) of the jaw. [3] In humans, bisphosphonate use also increases the risk of femur fractures. [3]

Although a direct association between bisphosphonates and fractures in horses has not been studied, evidence from other species suggests that bisphosphonates should be used cautiously in horses. [3]

Studies in horses show that bisphosphonates can persist in the body for up to three years after a single administration, so further research into the effect of long-term bisphosphonate exposure in horses is necessary. [3]

Risks in Young Horses

These medications are sometimes used to treat bone conditions in young racehorses due to their pain control effects. [3] However, many experts advocate against the use of bisphosphonates in young, growing horses. [3]

Osteoclasts are particularly active in young horses, as the demand for bone remodeling is highest during times of growth and development. [3] Studies in young rabbits show use of bisphosphonates reduces the length of bones due to impaired osteoclast activity. [3]

Additionally, studies show bisphosphonates can alter the bones’ normal adaptations to increasing exercise. [3] As exercise levels increase, osteoclasts activate to adjust the bone’s structure and strength to better compensate for the new activity demands. [3]

One study showed use of bisphosphonates in young horses reduced indicators of bone turnover to levels similar to unexercised horses. [13] Therefore, altering the activity of osteoclasts by using bisphosphonates during this period may result in reduced bone strength. [3]

Use in Competition

Some competitive organizations restrict the use of bisphosphonates in performance horses. [1] Restrictions range from controlled use prior to performance to banning horses that receive bisphosphonate treatment permanently. [1]

It’s important for horse owners to familiarize themselves with their performance organization’s policies on bisphosphonates. If banned by your competitive association, consult with your veterinarian to determine whether other treatment options are available for your horse.

Organizations with restriction or control policies on bisphosphonate use include but are not limited to: [1]

  • Fédération Equestre Internationale (FEI)
  • Equestrian Canada
  • United States Equestrian Federation
  • California Horse Racing Board
  • British Horse Racing Authority

Summary

Bisphosphonates are a class of drug that affect the body’s natural bone remodeling processes to promote maintenance of old bone tissue and reduce the growth rate of new bone.

  • The main bisphosphonates used in horses are clodronate (OsPhos®) and tiludronate (Tildren®)
  • Veterinarians use bisphosphonates to treat navicular disease and other bone-related conditions in horses
  • Bisphosphonates are effective in reducing lameness associated with certain musculoskeletal conditions and returning horses to previous levels of performance
  • Bisphosphonates can cause side effects and may increase the risk of serious bone injuries long-term

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References

  1. Yocom, A. et al. Review of the Mechanism of Action and Use of Bisphosphonates in Horses. Journal of Equine Veterinary Science. 2023. doi: 10.1016/j.jevs.2023.104503.
  2. Soto, S. A. and Chiappe Barbará, A. Bisphosphonates: Pharmacology and Clinical Approach to Their Use in Equine Osteoarticular Diseases. Journal of Equine Veterinary Science. 2014. doi: 10.1016/j.jevs.2014.01.009.
  3. Vergara-Hernandez, F. B. et al. Is the Use of Bisphosphonates Putting Horses at Risk? An Osteoclast Perspective. Animals. 2022. doi: 10.3390/ani12131722.
  4. Tiludronate, Plumb’s Veterinary Drugs.
  5. Clodronate, Plumb’s Veterinary Drugs.
  6. Markell, R. et al. What Do We Know About Clodronate Now? A Medical and Veterinary Perspective. Journal of Equine Veterinary Science. 2020. doi: 10.1016/j.jevs.2019.102874.
  7. Frevel, M. et al. Multi-Centre Field Trial to Evaluate the Effectiveness of Clodronic Acid for Navicular Syndrome. Equine Veterinary Journal. 2014. doi: 10.1111/evj.12323_10.
  8. Tischmacher, A. et al. Retrospective Analysis of the Use of Tiludronate in Equine Practice: Safety on 1804 Horses, Efficacy on 343 Horses. Journal of Equine Veterinary Science. 2022. doi: 10.1016/j.jevs.2022.104007.
  9. Coudry, V. et al. Efficacy of Tiludronate in the Treatment of Horses with Signs of Pain Associated with Osteoarthritic Lesions of the Thoracolumbar Vertebral Column. American Journal of Veterinary Research. 2007. doi: 10.2460/ajvr.68.3.329.
  10. Gough, M. R. et al. Tiludronate Infusion in the Treatment of Bone Spavin: A Double Blind Placebo-Controlled Trial. Equine Veterinary Journal. 2010. doi: 10.1111/j.2042-3306.2010.00120.x.
  11. Suva, L. J. et al. Bisphosphonates in Veterinary Medicine: The New Horizon for Use. Bone. 2021. doi: 10.1016/j.bone.2020.115711.
  12. Mitchell, A. et al. Bisphosphonate Use in the Horse: What Is Good and What Is Not?. BMC Veterinary Research. 2019. doi: 10.1186/s12917-019-1966-x.
  13. McLellan, J. Science-in-Brief: Bisphosphonate Use in the Racehorse: Safe or Unsafe?. Equine Veterinary Journal. 2017. doi: 10.1111/evj.12682.