Bisphosphonates were first synthesized in 1897 by chemists in Germany for industrial applications. Named for the two phosphate groups they contain, bisphosphonates were used to prevent calcium carbonate scaling on machinery and plumbing. It wasn’t until nearly a century later that the chemicals were considered for clinical applications in human medicine based on their effects on bone remodeling.
The continuous breakdown and repair of bone tissue, remodeling helps bone adapt to stresses, becoming stronger and/or repairing damage. “Bone remodeling is why you can break your arm and it heals,” says Kyle Creech, DVM, equine veterinary services manager for Ceva Animal Health, the makers of Tildren. The remodeling processes is a marvel of biology, but it can be explained fairly simply:
Cells called osteoclasts continually roam bone surface, resorbing old or damaged bone. In their wake, different cells known as osteoblasts arrive to lay down new bone. At times of bone stress, such as during extreme physical activity or after a traumatic injury, this process is accelerated, with osteoclasts working faster to tear down the damaged bone. Generally, osteoblasts can keep up the increased pace, laying down new, stronger bone quickly, but the process isn’t instantaneous.
“There can be a lag,” says Jill Stohs, DVM, technical services veterinarian with Dechra Veterinary Products, the makers of Osphos. “In normal bone remodeling, generally it takes about three weeks for osteoclasts to finish their job of removing the damaged and stressed bone. Once the osteoclasts have completed their job, they signal and recruit osteoblasts to the area of removed bone. Osteoblasts may take up to three months to complete their process of adding new bone. By that time, though, the underlying stress has been relieved, so osteoclasts have slowed down their efforts and the osteoblasts can catch up to them.” In cases of navicular syndrome, however, the stress on the navicular bone is continual, meaning osteoclasts are continually working to remove stressed bone tissue and osteoblasts do not have a chance to catch up, and degradation of the bone occurs. This, say Creech and Stohs, is where bisphosphonates can help.
Bisphosphonates restore balance to the bone remodeling process by inhibiting the resorption of bone. Bisphosphonates become attached to calcium in the bone. Then they are ingested by osteoclasts and disrupt the metabolic process of the bone-eating cells, which causes them to die. With fewer osteoclasts at work tearing down bone, the osteoblasts can then keep up with the job of laying down new bone, leading to fewer lesions. “It’s all about re-establishing that balance between the osteoclasts