Assistant Professor of Large Animal Orthopedic Surgery Cornell University Ithaca, New York
Clodronate disodium (CLO) is used in juvenile, exercising horses. Serious adverse effects on bone modeling and remodeling may result from CLO use. The objective of the study was to determine the effects of CLO administration on bone modeling and remodeling in juvenile animals under forced exercise. We hypothesized CLO would decrease bone turnover, resulting in decreased bone growth, serum bone biomarkers, bone density (BD), and maximal force to failure. Forty juvenile sheep (n=10/group): Control group; 0.6 mg/kg CLO IM at 0d; 0.6 mg/kg CLO IM at 84d; 0.6 mg/kg CLO IM at 0d and 84d. Sheep were exercised 4 days/week. Outcome measures included physical examination (PE) and lameness examination (LE) every 14 days. Serum was harvested every 28 days for bone (CTX-I, PINP, BALP, TRAP5b, RANKL) and cartilage (CTX-II) turnover markers until euthanasia at 164d. Computed tomography (CT) was used to evaluate BD. The fused metacarpus (MC3/4) and fourth lumbar vertebrae (L4) underwent biomechanical testing (BMT). Sheep weight, height, serum bone/cartilage markers, BD, and BMT results did not differ between groups. All groups had a significant increase in serum BALP (P=0.008), and a decrease in CTX-1 (P=0.03) and RANKL (P=0.03) from baseline. Continued growth and initiation of exercise resulted in evidence of bone formation and resorption, but CLO had no measurable effect. Study limitations include the study duration and the absence of a sedentary control group. This study did not detect adverse effects of clodronate disodium in this juvenile, exercising sheep model.
