Clodronate use in yearling, exercising horses on endocrine regulation of bone growth and development
Conrad, Matthew Benjamin
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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 clodronate on endocrine regulation of bone growth, hypothesizing there would be no effect. To test this, 32 Quarter Horses were stratified by age (500 + or - 13 d of age), BW (336 + or - 26 kg), sex (n = 16 males, n = 16 females), and initial bone optical density by aluminum equivalence into four treatment groups for a 168-d trial. The experimental period was divided into two phases mimicking sales preparation (Phase I: d 0-83) and early performance training (Phase II: d 84-168). Investigators were blinded, and all horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW clodronate disodium (OSPHOS®) or saline (placebo) on d 0, 42, 84, and 126. Treatments consisted of control (CON; n = 8), single-dose (1X; n = 8; d 84), two-dose (2X; n = 8; d 0, 84), and four-dose 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. Serum samples were collected every 42 d prior to 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 parameters increased (P < or = 0.01) and growth hormone tended to decrease over time (P = 0.09) following normal growth patterns. A treatment time interaction was observed for PTH (P = 0.05) where 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. Ionized Ca decreased over time (P < 0.01) with no effect on CT concentrations (P > 0.33). These results suggest that while administration of bisphosphonate has no effect on growth morphometrics, its repetitive use alters PTH concentrations after two doses.