2 Effects of extra-label bisphosphonate use on growth parameters and endocrine biomarkers of bone health in juvenile horses

Abstract

Extra-label bisphosphonate use in juvenile horses is widespread despite limited scientific understanding of biological and welfare impacts on skeletally immature, exercising horses. The objective of this study was to determine the effects of bisphosphonate (clodronate disodium; CD) on endocrine regulation of bone growth, hypothesizing there would be no effect. To test this, 32 Quarter Horses were stratified by age (500 ± 13 d of age), BW (336 ± 26 kg), sex (n = 16 males, n = 16 females), and initial bone optical density by aluminum equivalence into 4 treatment groups for a 168-d trial. The experimental period was divided into 2 phases mimicking sales preparation (Phase I: d 0–83) and early performance training (Phase II: d 84–168). Horses were housed in individual stalls (3.6 m × 7.3 m) and fed diets formulated to meet nutrient requirements. Investigators were blinded, and all horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW CD (OSPHOS®) or saline (placebo) on d 0, 42, 84, and 126. Treatments consisted of control (CON; n = 8), single-dose CD (1X; n = 8; d 84), 2-dose CD (2X; n = 8; d 0, 84), and 4-dose CD groups (4X;n = 8; d 0, 42, 84, 126). Physical measurements including BW, wither height (WH), hip height (HH), body length (BL), and heart girth (HG) circumference were recorded every 42 d from d 0. Likewise, serum samples were collected every 42 d before treatment administration to quantify growth hormone (GH), calcitonin (CT), parathyroid hormone (PTH), and ionized calcium. Data were analyzed using PROC MIXED of SAS. All physical growth measurements increased over time (P ≤ 0.01) but were not affected by treatment (P ≥ 0.62). Similarly, there was no effect of treatment (P = 0.44) for GH, but concentrations tended to decrease over time as growth rate slowed (P = 0.09). A treatment ´ time interaction was observed for PTH (P = 0.05) where concentrations increased following 2 clodronate doses. Specifically, concentrations increased on d 84 in 4X and on d 126 in 2X following the second administration of clodronate while 1X and CON remained unchanged. There was no effect of treatment (P = 0.98), time (P = 0.33), nor treatment × time interaction (P = 0.61) for CT despite the increase in PTH. Ionized calcium concentrations decreased over time (P < 0.01) with no effect of treatment (P = 0.26) or treatment × time interaction (P = 0.32). These results suggest that while administration of bisphosphonate has no effect on growth morphometrics, its repetitive use alters PTH concentrations after 2 doses.