{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:03:21Z","timestamp":1786986201333,"version":"build-2736575974"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is a prevalent cause of chronic pain and impaired mobility in dogs. Grapiprant, an EP4 prostaglandin receptor antagonist, represents a novel therapeutic option with a favorable safety profile compared to traditional NSAIDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      To evaluate the clinical efficacy of grapiprant in dogs with naturally occurring OA and to investigate systemic metabolomic changes using proton nuclear magnetic resonance (\n                      <jats:sup>1<\/jats:sup>\n                      H-NMR) spectroscopy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-six dogs with mild to moderate OA were enrolled in a prospective off\u2013on\u2013off study (30\u202fdays pre-treatment, 60\u202fdays grapiprant treatment at 2\u202fmg\/kg, 30\u202fdays post-treatment). Outcomes included owner questionnaires (LOAD, CBPI), pressure-sensitive walkway gait analysis (GLS), orthopedic evaluation, and plasma metabolomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Grapiprant significantly reduced LOAD scores at T30 and T60 compared with baseline (*\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05), with partial regression at Tpost. GLS improved significantly at T60 (**\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). Metabolomic analysis (both unsupervised and supervised methods) highlighted a clear discrimination between pre-and post-treatment plasma samples, revealing a statistically significant decrease in lactate, N-acetyl glycoproteins and formate in pretreatments samples and, on the contrary a significantly increase in citrate (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Grapiprant improved mobility and pain control in dogs with OA and induced metabolomic shifts consistent with reduced inflammation and improved energy metabolism. This is the first study to integrate clinical outcomes with metabolomics in canine OA, supporting the translational value of metabolic biomarkers for monitoring therapeutic response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1811478","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:50:06Z","timestamp":1781535006000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of clinical effects and plasma metabolomic profiles after the administration of grapiprant in dogs affected by osteoarthritis: a prospective, off\u2013on\u2013off, clinical study"],"prefix":"10.3389","volume":"13","author":[{"given":"Claudia","family":"Piemontese","sequence":"first","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Roberta","family":"Girelli","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento","place":["Lecce, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Stabile","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Lacitignola","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Fraccascia","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Crovace","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Paolo","family":"Fanizzi","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies, University of Salento","place":["Lecce, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Staffieri","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/S0195-5616(97)50076-3","article-title":"Osteoarthritis. 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