Effects of clodronate disodium on markers of inflammation and cartilage metabolism 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 without supportive data regarding intra-articular effects on cartilage metabolism and inflammation. Thirty-two yearling Quarter Horses were stratified into 4 treatment groups by age (500 ± 13 d), BW (336 ± 26 kg), sex (n = 16 female; n = 16 male) and initial bone optical density for a 140-d study. The study consisted of two exercise phases: Phase 1 (d 0-84) emulated sales preparation and Phase 2 (d 99-140) mimicked early exercise training. Horses were housed individually (3.6 m × 7.3 m stalls) and fed to meet nutritional requirements. All horses received iso-volumetric intramuscular injections of 1.8 mg/kg BW clodronate disodium (CD) (OSPHOS) or saline (vehicle) on d 0, 42, 84, and 126. Specifically, the treatment groups consisted of the saline control (0×; n = 8), and clodronate injected once (1×; n = 8; d 84), twice (2×; n = 8; d 0, 84), or four times (4×; n = 8; d 0, 42, 84, 126). Horses underwent an intra-articular lipopolysaccharide (LPS) 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 injection. Synovial fluid concentrations of carboxypropeptide of type II collagen (CPII), collagenase cleavage neopeptide (C2C), and prostaglandin E2 (PGE2) were determined by ELISA. Intra-articular LPS increased CPII, C2C, PGE2 and CPII: C2C (P ≤ 0.01). There tended to be a treatment × time interaction in CPII (P = 0.06) where CPII was greatest in 2× with 1× and 0× being the lowest, 4× concentrations were between this range at 24 h post-injection. Likewise, CPII: C2C tended to be influenced by treatment (P = 0.06) with 2× and 4× having greater synthesis: degradation ratio than 1× and 0×. There was a treatment × time × carpus interaction (P = 0.02) in which 1×, 2× and 4× CD groups had greater synovial PGE2 concentrations at 6 h post-injection in the LPS joint compared to 0×. The results of this study indicate that administration of CD increases intra-articular inflammation (PGE2) but does not affect cartilage degradation (C2C) and only tends to increase cartilage synthesis (CPII) according to biomarkers measured. Extra-label bisphosphonate use has occurred in the juvenile horse despite a lack of scientific evidence, due to perceived anti-inflammatory and chondroprotective benefits. The purpose of this study was to evaluate the effects of clodronate disodium (CD) on biomarkers of cartilage metabolism and intra-articular inflammation within the articulating joint of the juvenile horse using an intra-articular inflammatory model. Thirty-two yearling Quarter Horses were treated with either saline, 1-dose, 2-doses or 4-doses of CD for a 140-d study. Carpal circumference and synovial fluid were collected prior to and after initiation of the inflammatory model. Synovial fluid samples were analyzed for biomarkers of cartilage synthesis and degradation as well as intra-articular inflammation. There was no difference between treatments concerning the cartilage degradation biomarker used in this study, and CD only tended to increase cartilage synthesis and carpal circumference after two doses. Treatment by CD did not decrease inflammation, but rather increased inflammation following initiation of the inflammatory challenge. At no point during the sampled timepoints did CD decrease inflammation compared to the control. This initial investigation into the effects of CD on the juvenile articulating joint, laying the groundwork for further investigations into the effects of CD administration in the juvenile synovial joint.
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Publication Date: 2025-11-12 PubMed ID: 41223152PubMed Central: PMC12646851DOI: 10.1093/jas/skaf393Google Scholar: Lookup
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Cite This Article
APA
George JM, Leatherwood JL, Paris BL, Arnold CE, Glass KG, Conrad MB, Martinez RE, Vergara-Hernandez FB, Nielsen BD, Colbath AC, Welsh TH, Bradbery AN.
(2025).
Effects of clodronate disodium on markers of inflammation and cartilage metabolism in juvenile horses challenged with intra-articular lipopolysaccharide.
J Anim Sci, 103, skaf393.
https://doi.org/10.1093/jas/skaf393 Publication
Researcher Affiliations
- Department of Animal Science, Texas A&M University, College Station, TX 77843.
- Department of Animal Science, Tarleton State University, Stephenville, TX 76402.
- Department of Animal Science, Texas A&M University, College Station, TX 77843.
- Department of Animal Science, Tarleton State University, Stephenville, TX 76402.
- Department of Animal Science, Texas A&M University, College Station, TX 77843.
- School of Agricultural Sciences, Sam Houston State University, Huntsville, TX 77341.
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX 77843.
- School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106.
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX 77843.
- Department of Animal and Range Sciences, Montana State University, Bozeman, MT 59717.
- Department of Animal Science, Texas A&M University, College Station, TX 77843.
- Department of Animal Science, Tarleton State University, Stephenville, TX 76402.
- Escuela de Medicina Veterinaria, Facultad de Recursos Naturales y Medicina Veterinaria, Universidad Santo Tomás, Viña del Mar, 2561780, Chile.
- Department of Animal Science, Michigan State University, East Lansing, MI 48824.
- Department of Clinical Sciences, Cornell University, Ithaca, NY 14853.
- Department of Animal Science, Texas A&M University, College Station, TX 77843.
- Department of Animal and Range Sciences, Montana State University, Bozeman, MT 59717.
MeSH Terms
- Animals
- Horses
- Male
- Female
- Lipopolysaccharides / pharmacology
- Lipopolysaccharides / administration & dosage
- Inflammation / veterinary
- Inflammation / chemically induced
- Inflammation / drug therapy
- Horse Diseases / drug therapy
- Horse Diseases / chemically induced
- Clodronic Acid / pharmacology
- Clodronic Acid / administration & dosage
- Clodronic Acid / therapeutic use
- Biomarkers / metabolism
- Injections, Intra-Articular / veterinary
- Bone Density Conservation Agents / pharmacology
- Cartilage / metabolism
- Cartilage / drug effects
- Cartilage, Articular / drug effects
- Cartilage, Articular / metabolism
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