Healthy horse bone is constantly metabolizing: Old bone is being resorbed back into the system via osteoclastic activity, while new bone is being reconstructed through osteoblastic activity.
OSTEOBLASTS rebuild bone.
OSTEOCLASTS resorb bone.
There is a fine balance between osteoblastic and osteoclastic activity in the normal horse. The result is the maintenance of healthy, strong bone. This balance is particularly fragile in younger animals.
Several forms of pathology can lead to an imbalance in normal bone metabolism. The rate of osteoclastic resorption of bone can exceed the rate of osteoblastic replacement thereby resulting in weaker, less dense tissue.
Biphosphonates are a class of drug formulated to reestablish normal bone metabolism in pathologic conditions. They have a tremendous affinity for hydroxyappetite (a basic building block of bone). They stick to bone very well and stay in there for a long time, even though they are cleared from the blood stream relatively quickly.
Mechanism of Action
Biphosphonates work by inhibiting osteoclast-mediated bone resorption. This is accomplished by altering the metabolism of osteoclastic cells, thereby resulting in their death. Osteoblastic cells are then able to more effectively improve bone density and strength in an environment absent of osteoclastic activity.
In addition to hindering osteoclastic resorption of bone, biphosphonates may also function to dampen the response of chemical mediators involved in the process of inflammation. Both anti-inflammatory and analgesic (pain-relieving) properties have been suggested, although further research is needed to confirm this argument.
Caution should be exercised when implementing biphosphophonate therapy in horses under 4 years of age, since bone is still growing during this time.
Biphosphonate therapy should not be used in breeding stock (mares and stallions). A fragile metabolism combined with augmented biphosphonate uptake can deleteriously affect normal fetal bone growth and skeletal development.
This form of therapy should not be used in horses with renal (kidney) disease. Biphosphonates are excreted through the urine and can exacerbate associated pathologic conditions. Since non-steroidal anti-inflammatory drugs (NSAIDs) such as Phenylbutazone or Banamine can also be toxic to the kidneys, these medications should not be administered concurrently.
Biphosphonate therapy should also be avoided in cases of Pars Pituitary Intermedia Dysfunction (PPID or Cushings), Equine Metabolic Syndrome (EMS) and Equine Hyperkalemic Periodic Paralysis Disease (HYPP).
Currently Available Forms of Biphosphonates
Biphosphonate therapy for horses first became available in Europe in 2003 in the form of tiludronate (Tildren®). This drug was specifically labeled for the treatment of navicular inflammation, distal tarsitis and fetlock ligament enthesiopathy.
Tiludronate and another biphosphonate, clodronate (OPHOS®), met FDA approval (in the US) in 2014. Both drugs are utilized by The Atlanta Equine Clinic on a regular basis for the treatment of navicular inflammation and high-motion joint disease. This form of therapy has proven to be especially effective in cases in which inadequate bone density is demonstrated during radiographic examination of affected areas.