English
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 skeletal 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 wit