{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T19:25:56Z","timestamp":1793820356087,"version":"4.6.1"},"reference-count":61,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"AUVA Austrian Workers' Compensation Board Research Fund"},{"name":"Society for Arthroscopy and Joint Surgery AGA","award":["104"],"award-info":[{"award-number":["104"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Sports Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>A prospective, randomized, placebo-controlled trial showed reduced retears after arthroscopic rotator cuff (RC) repair in patients without osteoporosis by a systemic single-dose of zoledronic acid. Distinct micro-ribonucleic acids (miRNAs) related to inflammation, fibrosis, and tendon-to-bone healing are associated with RC injuries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To investigate the longitudinal effects of a single-dose of zoledronic acid in patients without osteoporosis undergoing arthroscopic RC repair on circulating miRNAs in order to explore the molecular mechanism of this treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design:<\/jats:title>\n                    <jats:p>Controlled laboratory study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Data were collected in the course of a single-center, prospective, randomized, placebo-controlled, triple-blinded (investigator, surgeon, patient) phase II trial. A total of 80 patients underwent arthroscopic RC repair and were intraoperatively randomized to the zoledronic acid group (n = 40) or the control group (n = 40). Circulating plasma miRNAs were assessed preoperatively, 2 days postoperatively, and 3 months postoperatively using small RNA sequencing and reverse transcription quantitative polymerase chain reaction (RT-qPCR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Six miRNAs were selected for validation by RT-qPCR based on small RNA-sequencing analysis. No statistical differences in miRNA plasma levels were observed preoperatively between the 2 study groups. Two days after surgery, plasma levels were significantly lower for miR-140-3p (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .047) in the zoledronic acid group. In the control group, plasma levels were significantly lower for miR-29a-3p (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001), miR-21-5p (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .036), miR-192-5p (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .034), and miR-146a-5p (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) 2 days after surgery. Three months after surgery, miRNA plasma levels of the 2 study groups equalized without any significant differences. Gene target analysis identified collagen type I alpha 1 chain, collagen type III alpha 1 chain, vascular endothelial growth factor, insulin-like growth factor 1, and transforming growth factor-\u03b21 as targets of miRNAs impacted by zoledronic acid.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Longitudinal plasma miRNA expressions suggest a molecular response to zoledronic acid, potentially indicating a reduction of inflammation and fibrosis at the enthesis as well as increased collagen synthesis and vascularization, possibly explaining improved tendon-to-bone healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>Zoledronic acid is a safe and easy-to-apply augmentation technique for patients undergoing arthroscopic RC repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration:<\/jats:title>\n                    <jats:p>NCT05677152 (ClinicalTrials.gov identifier).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03635465261455031","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:47:49Z","timestamp":1781848069000},"page":"2516-2526","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intraoperative Zoledronic Acid for Arthroscopic Rotator Cuff Repair Results in Distinct Circulating Micro-RNA Profiles Indicating Improved Tendon-to-Bone Healing"],"prefix":"10.1177","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0995-5551","authenticated-orcid":false,"given":"Jakob E.","family":"Schanda","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, AUVA Trauma Center 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