{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:45:25Z","timestamp":1790919925302,"version":"4.1.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2010,1,27]],"date-time":"2010-01-27T00:00:00Z","timestamp":1264550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Src is a nonreceptor tyrosine kinase thought to be essential for osteoclast function and bone resorption. We investigated the effect of the orally available Src inhibitor saracatinib (AZD0530) on bone turnover in healthy men. The study was part of a randomized, double-blind, placebo-controlled multiple-ascending-dose phase I trial of saracatinib. Fifty-nine healthy men (mean age 34.6 years) were divided into five cohorts; four with 12 subjects and one with 11 subjects, and randomized within each cohort in the ratio 3:1 to receive a single dose of saracatinib or placebo, respectively, followed 7 to 10 days later with daily doses for a further 10 to 14 days. Dosing levels of saracatinib ascended by cohort (60 to 250\u2009mg). Markers of bone turnover were measured predose and 24 and 48\u2009hours after the initial single dose and immediately before and 24 and 48\u2009hours and 10 to 14 days after the final dose. Data from 44 subjects were included in the analysis. There was a dose-dependent decrease in bone resorption markers [serum cross-linked C-telopeptide of type I collagen (sCTX) and urinary cross-linked N-telopeptide of type I collagen normalized to creatinine (uNTX\/Cr)]. At a dose of 250\u2009mg (maximum tolerated dose), sCTX decreased by 88% [95% confidence interval (CI) 84\u201391%] and uNTX\/Cr decreased by 67% (95% CI 53\u201377%) from baseline 24\u2009hours after the final dose. There was no significant effect on bone formation markers. There were no significant adverse events. We conclude that inhibition of Src reduces osteoclastic bone resorption in humans. Saracatinib is a potentially useful treatment for diseases characterized by increased bone resorption, such as metastatic bone disease and osteoporosis. \u00a9 2010 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1359\/jbmr.090830","type":"journal-article","created":{"date-parts":[[2009,9,23]],"date-time":"2009-09-23T15:12:36Z","timestamp":1253718756000},"page":"463-471","source":"Crossref","is-referenced-by-count":92,"title":["Effects of the Src kinase inhibitor saracatinib (AZD0530) on bone turnover in healthy men: A randomized, double-blind, placebo-controlled, multiple-ascending-dose phase I trial"],"prefix":"10.1093","volume":"25","author":[{"given":"Rosemary A","family":"Hannon","sequence":"first","affiliation":[{"name":"Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen","family":"Clack","sequence":"additional","affiliation":[{"name":"AstraZeneca, Alderley Park, 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