Clodronate disodium reduced TRAP5b independent of affecting other systemic biomarkers of bone resorption or formation in yearling, exercising Quarter Horses

Clodronate disodium (CD), a bisphosphonate, modulates bone metabolism. Though extra-label use in juvenile horses is anecdotally reported, impacts on skeletal development are unknown. The objective was to determine the effects of CD on systemic markers of bone turnover in yearling horses undergoing exercise, hypothesizing that biomarkers of bone resorption would decrease while biomarkers of bone formation would not change, and that repeat CD treatments would have greater effect. To test this, 32 yearling Quarter Horses were used in a 168-d trial. Horses were stratified by age (500 ± 13 d), BW (336 ± 26 kg), sex (n = 16 geldings; n = 16 fillies), and initial bone optical density and randomly allocated to one of four treatment groups receiving either 1.8 mg/kg BW CD (Osphos) or isovolumetric saline (placebo). Investigators were blinded to treatments that included control (CON; n = 8), single-dose CD (1X; n = 8; d84), two-doses CD (2X; n = 8; d0 and 84), and four-doses CD (4X; n = 8; d0, 42, 84, and 126). Horses were housed individually in stalls and fed to meet nutrient requirements. Horses exercised 5 d/wk using a free stall exerciser in a phase-based progressive workload; Phase I (d0-84) simulated sales preparation and Phase II (d85-168) mimicked an early training program. Blood was collected on d0, 42, 84, 126, and 168 before treatment injections, when applicable. Serum was analyzed for receptor activator of nuclear factor κB ligand (RANKL), tartrate resistant acid phosphatase 5 b (TRAP5b), c-terminal crosslinks of type I collagen (CTX-1), bone-specific alkaline phosphatase (BAP) and procollagen type I n-terminal propeptide (PINP) via commercial ELISA or EIA. Data were analyzed using PROC MIXED of SAS with a baseline covariate for BAP. A treatment×time interaction was noted for osteoclastic TRAP5b (P = 0.03), decreasing in 4X from d0 to 126 and returning to baseline at d168, and decreasing in 2X to d84 whereas in CON and 1X it increased or remained the same over time. Serum CTX-1, a type I collagen degradation marker, increased over time (P < 0.01) in all treatments. Osteoblastic BAP increased (P < 0.01) from d42 to 84 and remained elevated until d168. There was no change in PINP (P = 0.35) or osteoclast differentiation signal RANKL (P≥0.24). The results indicate that CD administration in horses undergoing low-intensity exercise reduces a serum biomarker of osteoclast number and activity without affecting serum biomarkers of bone formation or resorption.