Bisphosphonate Pharmacokinetics and Comprehensive Effects on Juvenile Cartilage, Bone Growth and Healing: Implications for Animal Welfare
Principal Investigator: Amy Colbath
DESCRIPTION (provided by applicant):
Bisphosphonates were approved by the FDA for use in adult horses in 2014. Approval was specific for the treatment of navicular syndrome. However, the drugs have been used extensively “off-label” for their perceived pain-relieving effects. Of particular concern is the current “off-label” use in juvenile performance horses. Bisphosphonates interfere with osteoclastic resorption by altering their cellular processes. Osteoclasts are responsible for bone resorption, a critical process in bone remodeling. Juvenile, exercising horses are constantly going through growth and remodeling. Remodeling strengthens the bone in areas of added stress allowing the body to adapt to unique forces. Without the ability to adequately remodel, there may be a risk of traumatic injury or maladaptation. Despite the widespread use of these medications, no studies have provided a detailed evaluation of the effects on bone mass, or bone turnover in the horse. The proposed work provides a comprehensive assessment of bisphosphonates on juvenile, exercising bone by combining an equine study and ovine study. The equine study will provide equine-specific responses to bisphosphonate administration in juvenile horses including serum bone turnover markers, bone healing measurements, and assessment of its analgesic effects. The ovine study conducted at Cornell University will provide a more in depth understanding of the physiological effects on juvenile, exercising animals by allowing antemortem and post-mortem sampling. This study will include serum bone turnover markers and bone biopsies (as will be performed in the equine study) but will be complemented with advanced imaging of weight bearing and non-weightbearing bones, assessment of cartilage health, and biomechanical strength testing. Further, a biorepository of kidney, spleen, liver, adrenal glands, parathyroid gland and synovial fluid will be established for future analysis. Together these studies will provide a comprehensive assessment of the effects of a bisphosphonate, clodronate, on juvenile cartilage, bone growth and bone healing.