As veterinarians, we are frequently asked about products to treat chronic conditions, subtle lameness or lameness that has not responded to other therapies. One of the most exciting products to come along in the last few years is Tildren. It is a medication that has allowed us to offer a novel therapy for some of the most chronic causes of lameness that are often unresponsive to other therapies.
How does it work?
Tildren, or Tiludronate for all you pharmacology buffs, is a non-nitrogen containing bisphosphonate. The bisphosphonates are a class of drug that work at the cellular level to slow down or prevent bone loss. Bone is constantly changing and remodeling based on the forces applied to it. Osteoclasts are specialized bone cells which resorb bone, while osteoblasts are bone cells which serve to lay down new bone, a process known as mineralization. Tildren is thought to regulate bone remodeling by reducing the activity of osteoclasts while increasing osteoblastic activity. Bone loss is reduced, resulting in the maintenance of or increase in bone density and strength. Tildren was first used in human medicine for treating diseases that cause bone loss such as osteoporosis and Paget’s disease. Other bisphosphonate drugs include Fosamax, Boniva, Actonel and Reclast. In horses, Tildren has been studied for treatment of navicular disease, osteoarthritis and lesions of the thoracolumbar vertebral column.
Navicular disease, or caudal heel pain, is seen most often as a low-grade front end lameness of both front feet. The discomfort can be caused by changes to the bones as well as the soft tissues within the hoof. The cause of navicular disease is still not well understood, and each individual horse may suffer from differing pathologies. Often, the navicular bone itself is affected when it undergoes excessive bone degeneration or proliferation. These changes can weaken the bone, causing pain in the back of the foot. A drug that affects the cells that mediate bone resorption and proliferation like Tildren can therefore be helpful. Clinical trials have shown that Tildren is effective in treating navicular disease when given at a total dose of 1 milligram per kilogram of body weight broken up into 10 daily intravenous injections. A recent research study showed that 100 percent of horses suffering from acute navicular disease (affected by the disease for six months or less) responded to Tildren treatment, whereas only 60 percent of horses that had chronic disease (affected by the disease for greater than six months) responded, and that of the horses with more acute navicular disease, 75 percent returned to normal work within six months. Therefore it’s very important that Tildren be given earlier rather than later in the disease process. Although there was clear success in horses treated with Tildren in this study, it’s important to keep in mind that not all horses diagnosed with navicular disease have disease of only the navicular bone. Therefore, Tildren, which treats bony lesions, may not help every horse with navicular syndrome.
Osteoarthritis is ubiquitous across every equine discipline and can affect horses of all ages. Clinical signs are variable but can include lameness, stiffness, decreased range of motion and decreased performance. It is a degenerative condition that occurs in joints and can be caused by trauma, joint instability, malformation or increased forces placed upon the joint. The arthritis process often leads to destruction of the cartilage that cushions the bone, leading to inflammation and joint pain. The body attempts to stabilize the inflamed joint by laying down new bone. This is where Tildren is thought to be helpful, as it inhibits the activity of osteoclasts. Tildren is also purported to have anti-inflammatory effects, so it potentially quiets the inflammation of the affected joints. Tildren has been used most commonly to treat osteoarthritis of the hocks and thoracolumbar vertebral column.
Thoracolumbar pain can manifest itself in the horse through poor performance, an unwillingness to jump, behavior abnormalities (bucking, rearing) or non-specific lameness. Typically the diagnosis is made by how the horse looks clinically in combination with x-rays, ultrasound or nuclear scintigraphy (bone scan). Traditionally, treatment has been aimed at relieving pain through local injections of corticosteroids or other anti-inflammatories. Tildren is one of the first medications given intravenously that has shown to be effective in treating thoracolumbar lesions. Osteoarthritis has been found to be the primary cause of thoracolumbar pain; therefore, Tildren should be effective in preventing the bone remodeling that often leads to pain. A recent study showed that 80 percent of horses treated intravenously with Tildren showed reduced signs of back pain within 60 days.
How is it administered?
Tildren is usually administered through an intravenous catheter over 30 minutes. Besides systemic intravenous dosing, Tildren can also be given via regional limb perfusion. This procedure is used when it is desirable to concentrate the medication to a specific area. The procedure is done with the horse standing under heavy sedation. A tourniquet is placed above and below the site where drug concentration is wanted and helps prevent migration of the drug outside the area of interest. A catheter is then inserted into a vessel and the medication is injected. The tourniquets are usually left in place for 20–30 minutes. Regional limb perfusion allows for higher local concentrations of Tildren compared to those that can be achieved through systemic dosing and can therefore reduce the amount used. Formal research has not yet been performed on this route of administration of Tildren; however, many practitioners have cited success with this technique.
In general, Tildren is very safe and well-tolerated; however, it should not be administered to horses younger than three years old or to pregnant mares. There are a small percentage of horses that may experience mild colic, sweating or muscle fasciculations.
Although Tildren has been used for many years in the United States, the U.S. Food and Drug Administration (FDA) has not approved it for use in this country. Currently, Tildren can only be imported from Europe and used off-label in the United States. Due to the increasing amount of positive research results, veterinarians in the United States are pushing for FDA approval. More research is needed to validate its use, not only when given systemically but also when given via regional limb perfusion. However, if your horse has one of the conditions mentioned above that you believe might benefit from Tildren therapy, talk with your veterinarian.
UPDATE: The FDA has approved the use of Tildren in the U.S. as of December, 2014. Tildren is available for veterinarians to purchase through national distribution channels. If you think your horse could benefit from the use of Tildren, discuss the options with your vet.