Clodronate disodium did not impact tuber coxae microarchitecture or bone mineral density in juvenile horses

Abstract

Bisphosphonates, including clodronate disodium (CD), are a class of pharmaceuticals that reduce bone resorption. Despite lack of scientific evidence, anecdotal, extralabel use of CD in young animals occurs, aiming to prevent conditions of bone loss or inflammation during training. The objective of the study was to determine the effects of CD on bone microarchitecture and bone mineral density (BMD) in juvenile horses. The hypotheses were that horses receiving CD would have thicker trabeculae with higher BMD. To test the hypotheses, 32 yearling Quarter 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 4 treatment groups for a 168-d trial. Treatments groups included control (CON; n = 8), single dose of CD (1X; n = 8; d 84), 2 doses of CD (2X; n = 8; d 0, 84), and 4 doses of CD (4X; n = 8; d 0, 42, 84, 126). On d 0, 42, 84, and 126, horses received either 1.8 mg/kg BW CD (OSPHOS®) or isovolumetric saline according to treatment assignments. Horses were housed in individual stalls (3.7 × 7.3 m), fed 1% BW/d concentrate, and allowed ad libitum coastal Bermudagrass hay and water. Horses exercised 5 d/wk in a freestall exerciser using a phase-based progressive workload to mimic sales prep and early training. Biopsies were performed using an oscillating saw to collect samples of the tuber coxa (TC) from each animal on d 84 (left TC only) and d 168 (left, ipsilateral TC; right, contralateral TC). Samples underwent micro-CT (microCT; Quantum GX, PerkinElmer Inc.). Microarchitecture, including bone volume fraction (BV/TV), trabecular separation (TbSp), trabecular thickness (TbTh), trabecular number (TbN), trabecular connectivity density (ConnD), and BMD, were quantified using Dragonfly software (Comet Technologies Canada Inc.). Data were analyzed using PROC MIXED of SAS for the main effect of treatment within each biopsy site. There were no treatment differences for BMD in any TC samples, and there were no treatment effects on bone microarchitecture on d 84 or in the ipsilateral TC on d 168. In the d 168 contralateral TC, there were tendencies in BV/TV (P = 0.09) and TbTh (P = 0.07), where BV/TV was higher in 1X than CON and 4X, and TbTh was higher in 1X than other groups. The tendencies for BV/TV and TbTh were likely driven by one horse in 1X with higher values and are not likely indicative of true population differences. The results led to rejection of the hypotheses, indicating the administered doses of CD had no effect on TC microarchitecture or BMD in juvenile Quarter Horses.