{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:12:27Z","timestamp":1788772347561,"version":"build-2803163510"},"reference-count":224,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Total joint arthroplasty is a surgical procedure with rising global incidence. Although a strong postoperative inflammatory response is necessary for tissue repair following primary arthroplasty, it may prove to be harmful if excessive or prolonged. This could compromise osseointegration, increase pain, and delay the detection of periprosthetic joint infection. This narrative review examines the principal inflammatory pathways activated by primary arthroplasty. Damage-associated molecular patterns produced by injury and cell death, such as High Mobility Group Box 1 Protein, cell-free DNA, extracellular ATP, histones, and heat shock proteins, trigger innate immune activation following surgical trauma. These mediators use inflammasome pathways and pattern recognition receptors to intensify inflammatory signaling. The acute-phase trajectory, characterized by increases in C-reactive protein and erythrocyte sedimentation rate, alongside the role of interleukin-6 as a precursor factor, is examined together with synovial markers to facilitate the differentiation between septic and aseptic inflammation. Cytokine signaling cascades (JAK-STAT, NF-\u03baB, MAPK) and the RANK\/RANKL\/OPG axis at the bone-immune interface are also considered. This manuscript highlights relevant inflammatory pathways, clinically significant biomarkers, and pathway-guided management strategies to provide an overview of the current research on the biological mechanisms underlying perioperative inflammation in primary arthroplasty. No inflammatory biomarker has yet been validated as a predictor of aseptic loosening.<\/jats:p>","DOI":"10.3390\/medicina62091713","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Key Inflammatory Pathways, Biomarkers, and Targeted Management Strategies in Primary Total Joint Arthroplasty: A Narrative Review"],"prefix":"10.3390","volume":"62","author":[{"given":"Adelina-Elena","family":"Moise","sequence":"first","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"\u201cFoisor\u201d Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai Emanuel","family":"Gherghe","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"\u201cFoisor\u201d Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3442-1139","authenticated-orcid":false,"given":"Alex-Gabriel","family":"Grigore","sequence":"additional","affiliation":[{"name":"\u201cFoisor\u201d Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3270-1488","authenticated-orcid":false,"given":"Iosif-Aliodor","family":"Timofticiuc","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matei","family":"Todor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Balaban","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5595-1135","authenticated-orcid":false,"given":"Constantin-Adrian","family":"Andrei","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"\u201cFoisor\u201d Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-1684","authenticated-orcid":false,"given":"Serban","family":"Dragosloveanu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"\u201cFoisor\u201d Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4530-7965","authenticated-orcid":false,"given":"Constantin","family":"Caruntu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Dermatology, \u201cProf. N.C. Paulescu\u201d National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7676-6393","authenticated-orcid":false,"given":"Cristian","family":"Scheau","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"\u201cFoisor\u201d Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.joca.2017.03.008","article-title":"Inflammation and post-operative recovery in patients undergoing total knee arthroplasty-secondary analysis of a randomized controlled trial","volume":"25","author":"Langkilde","year":"2017","journal-title":"Osteoarthr. 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