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Evaluation of the Effects of Extra-Label Bisphosphonate Use on Markers of Cartilage Metabolism and Inflammation in Juvenile Horses Challenged with Intra-Articular Lipopolysaccharide
Abstract
Perceived chondroprotective and anti-inflammatory benefits of bisphosphonates in the juvenile horse has led to extra-label use despite a lack of supporting data evaluating intra-articular impacts. Thirty-two yearling Quarter Horses were stratified by age (500 ± 13 d), BW (336 ± 26 kg), sex (n = 16 female; n = 16 male) and initial bone optical density into 4 treatment groups for a 140-d trial. The study consisted of two phases: Phase 1 (d 0-84) emulated sales prep and Phase 2 (d 99-140) mimicked early exercise training. Horses were housed individually (3.6 m × 7.3 m) and fed to meet nutritional requirements. Treatments consisted of control (CON; n = 8), single-dose (1X; n = 8; d 84), two-doses (2X; n = 8; d 0, 84), and four-doses (4X; n = 8; d 0, 42, 84, 126). All horses received iso-volumetric intramuscular injections of 1.8mg/kg BW clodronate disodium (OSPHOS®) or saline (placebo) on d 0, 42, 84, and 126. Horses underwent an intra-articular lipopolysaccharide challenge post treatment administration on d 126. Synovial fluid was collected prior to LPS injection (h 0) and at 6, 12, 24, and 336 h post induction. Synovial fluid was analyzed for carboxypropeptide of type II collagen (CPII), collagenase cleavage neopeptide (C2C), and prostaglandin E2 (PGE2) by ELISA. Intra-articular LPS increased CPII, C2C, PGE2 and CPII:C2C (P ≤ 0.01). There tended to be a treatment by hour interaction in CPII (P = 0.06) where CPII was greater in 2X compared to 1X and CON with 4X being intermediate at h 24 post-injection. Likewise, there was a trend for a treatment effect on CPII:C2C (P = 0.06) with 2X and 4X having greater synthesis: degradation than 1X and CON. There was a treatment × h × LPS interaction (P = 0.02) in which 1X, 2X and 4X CD groups had greater synovial PGE2 concentrations at 6 h post-injection in the LPS joint compared to CON. This study indicates that administration of clodronate disodium increases synovial inflammation and tends to increase CPII concentrations in synovial fluid following an acute inflammatory challenge.
Citation
George, James Martin (2023). Evaluation of the Effects of Extra-Label Bisphosphonate Use on Markers of Cartilage Metabolism and Inflammation in Juvenile Horses Challenged with Intra-Articular Lipopolysaccharide. Master's thesis, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /200107.