{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:18:10Z","timestamp":1779333490424,"version":"3.51.4"},"reference-count":41,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2009\u00b1\u200913 d), BW (336\u2009\u00b1\u200926\u2009kg), sex (n\u2009=\u200916 female; n\u2009=\u200916 male) and initial bone optical density for a 140-d study. The study consisted of two exercise phases: Phase 1 (d 0\u201384) emulated sales preparation and Phase 2 (d 99\u2013140) mimicked early exercise training. Horses were housed individually (3.6\u2009m\u2009\u00d7\u20097.3\u2009m stalls) and fed to meet nutritional requirements. All horses received iso-volumetric intramuscular injections of 1.8\u2009mg\/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\u00d7; n\u2009=\u20098), and clodronate injected once (1\u00d7; n\u2009=\u20098; d 84), twice (2\u00d7; n\u2009=\u20098; d 0, 84), or four times (4\u00d7; n\u2009=\u20098; 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\u2009h 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\u2009\u2264\u20090.01). There tended to be a treatment \u00d7 time interaction in CPII (P\u2009=\u20090.06) where CPII was greatest in 2\u00d7 with 1\u00d7 and 0\u00d7 being the lowest, 4\u00d7 concentrations were between this range at 24\u2009h post-injection. Likewise, CPII: C2C tended to be influenced by treatment (P\u2009=\u20090.06) with 2\u00d7 and 4\u00d7 having greater synthesis: degradation ratio than 1\u00d7 and 0\u00d7. There was a treatment \u00d7 time \u00d7 carpus interaction (P\u2009=\u20090.02) in which 1\u00d7, 2\u00d7 and 4\u00d7 CD groups had greater synovial PGE2 concentrations at 6\u2009h post-injection in the LPS joint compared to 0\u00d7. 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.<\/jats:p>","DOI":"10.1093\/jas\/skaf393","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T13:00:48Z","timestamp":1762952448000},"source":"Crossref","is-referenced-by-count":1,"title":["Effects of clodronate disodium on markers of inflammation and cartilage metabolism in juvenile horses challenged with intra-articular lipopolysaccharide"],"prefix":"10.1093","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1233-3045","authenticated-orcid":false,"given":"James M","family":"George","sequence":"first","affiliation":[{"name":"Department of Animal Science, Texas A&M University , College Station, TX 77843"},{"name":"Department of Animal Science, Tarleton State University , Stephenville, TX 76402"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L","family":"Leatherwood","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Texas A&M University , College Station, TX 77843"},{"name":"Department of Animal Science, Tarleton State University , Stephenville, TX 76402"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-3857","authenticated-orcid":false,"given":"Brittany L","family":"Paris","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Texas A&M University , College Station, TX 77843"},{"name":"School of Agricultural Sciences, Sam Houston State University , Huntsville, TX 77341"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn E","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Large Animal Clinical Sciences, Texas A&M University , College Station, TX 77843"},{"name":"School of Veterinary Medicine, Texas Tech University , Amarillo, TX 79106"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kati G","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Large Animal Clinical Sciences, Texas A&M University , College Station, TX 77843"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew B","family":"Conrad","sequence":"additional","affiliation":[{"name":"Department of Animal and Range Sciences, Montana State University , Bozeman, MT 59717"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael E","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Texas A&M University , College Station, TX 77843"},{"name":"Department of Animal Science, Tarleton State University , Stephenville, TX 76402"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando B","family":"Vergara-Hernandez","sequence":"additional","affiliation":[{"name":"Escuela de Medicina Veterinaria, Facultad de Recursos Naturales y Medicina Veterinaria, Universidad Santo Tom\u00e1s , Vi\u00f1a del Mar , 2561780,","place":["Chile"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-5731","authenticated-orcid":false,"given":"Brian D","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Michigan State University , East Lansing, MI 48824"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimee C","family":"Colbath","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Cornell University , Ithaca, NY 14853"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas H","family":"Welsh","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Texas A&M University , College Station, TX 77843"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda N","family":"Bradbery","sequence":"additional","affiliation":[{"name":"Department of Animal and Range Sciences, Montana State University , Bozeman, MT 59717"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"issue":"31","key":"2025112522415256500_skaf393-B1","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1111\/j.2042-3306.1999.tb05323.x","article-title":"Conclusions regarding the influence of exercise on the development of the equine musculoskeletal system with special reference to osteochondrosis","volume":"31","author":"Barneveld","year":"1999","journal-title":"Equine Vet. 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