{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T07:18:42Z","timestamp":1773127122115,"version":"3.50.1"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T00:00:00Z","timestamp":1377561600000},"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":[[2014,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>ONO-5334 (Ono Pharmaceutical Co., Ltd., Osaka, Japan) inhibits cathepsin K and has been shown to increase areal bone mineral density (BMD) at the hip and spine in postmenopausal osteoporosis. Quantitative computed tomography (QCT) allows the study of the cortical and trabecular bone separately and provides structural information such as cortical thickness. We investigated the impact of 2 years of cathepsin K inhibition on these different bone compartments with ONO-5334. The clinical study was a randomized, double-blind, placebo, and active controlled parallel group study conducted in 13 centers in six European countries. The original study period of 12 months was extended by another 12 months. A total of 147 subjects (age 55\u201375 years) of the QCT substudy who participated in the extension period were included. Subjects had been randomized into one of five treatment arms: placebo; ONO-5334 50\u2009mg twice per day (BID); ONO-5334 100\u2009mg once daily (QD); ONO-5334 300\u2009mg QD; or alendronate 70\u2009mg once weekly (QW). QCT was obtained to evaluate bone structure at the lumbar spine and proximal femur. After 24 months ONO-5334 showed statistically significant increases versus placebo for integral, trabecular, and cortical BMD at the spine and the hip (for ONO-5334 300\u2009mg QD, BMD increases were 10.5%, 7.1%, and 13.4% for integral, cortical, and trabecular BMD at the spine, respectively, and 6.2%, 3.4%, and 14.6% for integral, cortical, and trabecular total femur BMD, respectively). Changes in cortical and trabecular BMD in the spine and hip were similar for alendronate as for ONO-5334. Integral volume did not demonstrate statistically significant changes under ONO-5334 treatment, thus there was no evidence of periosteal apposition, neither at the spine nor at the femur. Cortical thickness changes were not statistically significant for ONO-5334 in the spine and hip, with exception of a 2.1% increase after month 24 in the intertrochanter for ONO-5334 300\u2009mg QD. Over 2 years ONO-5334 showed a statistically significant and persistent increase of trabecular and integral BMD at the spine and the hip. Cortical BMD also progressively increased but at a lower rate. Changes in bone size and of periosteal apposition were not observed. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2080","type":"journal-article","created":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T13:38:46Z","timestamp":1377610726000},"page":"629-638","source":"Crossref","is-referenced-by-count":40,"title":["The Effect of the Cathepsin K Inhibitor ONO-5334 on Trabecular and Cortical Bone in Postmenopausal Osteoporosis: The OCEAN Study"],"prefix":"10.1093","volume":"29","author":[{"given":"Klaus","family":"Engelke","sequence":"first","affiliation":[{"name":"Institute of Medical PhysicsUniversity of ErlangenGermany"},{"name":"Synarc IncHamburgGermany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Nagase","sequence":"additional","affiliation":[{"name":"Ono Pharma UK LtdLondonUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Fuerst","sequence":"additional","affiliation":[{"name":"Synarc IncSan FranciscoCAUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Small","sequence":"additional","affiliation":[{"name":"Ono Pharma UK LtdLondonUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Kuwayama","sequence":"additional","affiliation":[{"name":"Ono Pharma UK LtdLondonUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Deacon","sequence":"additional","affiliation":[{"name":"Ono Pharma UK LtdLondonUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Eastell","sequence":"additional","affiliation":[{"name":"Department of Human MetabolismUniversity of SheffieldSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry K","family":"Genant","sequence":"additional","affiliation":[{"name":"Department of RadiologyUniversity of CaliforniaSan FranciscoCAUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,8,27]]},"reference":[{"issue":"2","key":"2024020318555551300_jbmr2080-bib-0001","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/jmbi.1994.0083","article-title":"Alignment\/phylogeny of the papain superfamily of cysteine proteases","volume":"246","author":"Berti","year":"1995","journal-title":"J Mol Biol."},{"issue":"5279","key":"2024020318555551300_jbmr2080-bib-0002","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1126\/science.273.5279.1236","article-title":"Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency","volume":"273","author":"Gelb","year":"1996","journal-title":"Science."},{"key":"2024020318555551300_jbmr2080-bib-0003","article-title":"Efficacy of ONO-5334, a cathepsin K inhibitor, on bone mass and strength in ovariectomized cynomolgus monkeys","volume":"25","author":"Yamada","year":"2010","journal-title":"J Bone Miner Res."},{"issue":"3","key":"2024020318555551300_jbmr2080-bib-0004","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1177\/0091270011399080","article-title":"Pharmacodynamic effects on biochemical markers of bone turnover and pharmacokinetics of the cathepsin K inhibitor, ONO-5334, in an ascending multiple-dose, Phase 1 study","volume":"52","author":"Nagase","year":"2012","journal-title":"J Clin Pharmacol."},{"issue":"6","key":"2024020318555551300_jbmr2080-bib-0005","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/jbmr.341","article-title":"Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN study","volume":"26","author":"Eastell","year":"2011","journal-title":"J Bone Miner Res."},{"key":"2024020318555551300_jbmr2080-bib-0006","article-title":"Effect of ONO-5334 on bone mineral density and biochemical markers of bone turnover in postmenopausal osteoporosis: 2-year results from the OCEAN study","volume":"22","author":"Eastell","year":"2013","journal-title":"J Bone Miner Res. 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