{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:40:46Z","timestamp":1790775646676,"version":"4.1.0"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,8,31]],"date-time":"2013-08-31T00:00:00Z","timestamp":1377907200000},"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":[[2014,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Two clinical studies were conducted to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses (intravenous [iv] and subcutaneous [sc]) of blosozumab in postmenopausal women, including prior\/current bisphosphonate (BP) users. In these phase 1, randomized, subject- and investigator-blind, placebo-controlled studies, subjects received escalating doses of blosozumab: single iv doses up to 750\u2009mg, single sc doses of 150\u2009mg, multiple iv doses up to 750\u2009mg every 2 weeks (Q2W) for 8 weeks, multiple sc doses up to 270\u2009mg Q2W for 8 weeks, or placebo. Six subjects were randomized to each dose in the single-dose study (12 to placebo) and up to 12 subjects to each arm in the multiple-dose study. Blosozumab was well tolerated with no safety concerns identified after single or multiple administrations up to 750\u2009mg. Dose-dependent responses were observed in sclerostin, N-terminal propeptide of procollagen type 1, bone-specific alkaline phosphatase, osteocalcin, C-terminal fragment of type 1 collagen, and bone mineral density (BMD) after single and multiple (up to 5) administrations of blosozumab. There was up to a 3.41% (p\u2009=\u20090.002) and up to a 7.71% (p\u2009&amp;lt;\u20090.001) change from baseline in lumbar spine BMD at day 85 after single or multiple administrations of blosozumab, respectively. Prior BP use did not appear to have a clear impact on the effects of single doses of blosozumab when considering bone biomarker and BMD responses. Antibodies to blosozumab were detected by a screening assay, but no patterns with regard to dose or route of administration and no clear impact on blosozumab exposure or PD responses were identified. In summary, blosozumab was well tolerated and exhibited anabolic effects on bone. These findings support further investigation of blosozumab as a potential anabolic therapy for osteoporosis. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2092","type":"journal-article","created":{"date-parts":[[2013,8,31]],"date-time":"2013-08-31T11:46:37Z","timestamp":1377949597000},"page":"935-943","source":"Crossref","is-referenced-by-count":160,"title":["Single- and Multiple-Dose Randomized Studies of Blosozumab, a Monoclonal Antibody Against Sclerostin, in Healthy Postmenopausal Women"],"prefix":"10.1093","volume":"29","author":[{"given":"Juliet","family":"McColm","sequence":"first","affiliation":[{"name":"Eli Lilly and CompanyWindleshamUnited Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leijun","family":"Hu","sequence":"additional","affiliation":[{"name":"Eli Lilly and CompanyIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Womack","sequence":"additional","affiliation":[{"name":"Eli Lilly and CompanyIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Cai","family":"Tang","sequence":"additional","affiliation":[{"name":"Eli Lilly and CompanySingaporeRepublic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan Y","family":"Chiang","sequence":"additional","affiliation":[{"name":"Eli Lilly and CompanyIndianapolisINUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,31]]},"reference":[{"key":"2024020318551476700_jbmr2092-bib-0001","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1096\/fj.05-4221fje","article-title":"Sclerostin is a delayed secreted product of osteocytes that inhibits bone 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by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats","volume":"12","author":"Li","year":"2010","journal-title":"J Bone Miner Res."},{"key":"2024020318551476700_jbmr2092-bib-0008","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1002\/jbmr.14","article-title":"Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength","volume":"5","author":"Ominsky","year":"2010","journal-title":"J Bone Miner Res."},{"key":"2024020318551476700_jbmr2092-bib-0009","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/jbmr.173","article-title":"Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody","volume":"1","author":"Padhi","year":"2011","journal-title":"J Bone Miner Res."},{"key":"2024020318551476700_jbmr2092-bib-0010","article-title":"Blosozumab, a humanized monoclonal antibody, and a chimeric rodent monoclonal antibody against sclerostin robustly increase bone formation activity in intact monkeys and ovariectomized rats","author":"Ma","year":"2012","journal-title":"J Bone Miner Res."},{"key":"2024020318551476700_jbmr2092-bib-0011","first-page":"455","article-title":"Clinical role of bisphosphonate therapy","volume":"4","author":"Hampson","year":"2012","journal-title":"Int J Womens Health."},{"key":"2024020318551476700_jbmr2092-bib-0012","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1210\/jc.2007-0711","article-title":"Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis","volume":"3","author":"Boonen","year":"2008","journal-title":"J Clin Endocrinol Metab."}],"container-title":["Journal of Bone and Mineral 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