Exercising sheep as a preclinical model for musculoskeletal research

To establish an orthopedic, preclinical, ovine model of controlled exercise using an equine walker. 20 Dorset-Polypay sheep. Sheep underwent 11 weeks of exercise, 4 days per week. Exercise duration and intensity increased until sheep performed 25 minutes at 1.3 m/s and 5 min at 2.0 m/s. Physical/lameness examinations were conducted every 14 days. Blood was collected every 28 days for analysis of serum bone biomarkers (SBB): bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), carboxy-telopeptide of type I collagen cross-links (CTX-I), tartrate-resistant acid phosphatase 5b (TRAP5b), and receptor activator of nuclear factor-kβ ligand (RANKL). Sheep adapted easily to group exercise. Animals grew taller (P = .006) but had a 4% weight loss (P = .003). RANKL was reduced on days 28 and 84 compared to day 56 (P < .05), CTX-1 was reduced on days 28 and 84 compared to days 0 and 56 (P < .05), and TRAP5b was greater on day 28 compared to day 0 (P = .009). BALP and PINP did not change. The described preclinical model of exercising sheep has distinct advantages including ease of handling, an established lameness scale, commercially available ovine SBB assays, and the ability to alter footing characteristics and complete circular exercise. Decreasing CTX-I and RANKL with no change in BALP and PINP suggests reduced bone resorption over the study period. Future studies may include a sedentary group or utilize adult animals to alleviate any influence of growth on SBB.