{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:51:03Z","timestamp":1793317863709,"version":"4.5.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2017,3,29]],"date-time":"2017-03-29T00:00:00Z","timestamp":1490745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100015311","name":"Novartis Institutes for BioMedical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015311","id-type":"DOI","asserted-by":"crossref"}]},{"name":"No\u00eblle L O'Regan"},{"name":"Mereo BioPharma"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>This 21-week, open-label, phase 2a trial aimed to evaluate the pharmacodynamics and safety of multiple, escalating infusions of BPS804, a neutralizing, anti-sclerostin antibody, in adults with moderate osteogenesis imperfecta (OI). Patients received BPS804 (three escalating doses each separated by 2 weeks [5, 10, and 20\u2009mg\/kg]) or no treatment (reference group). The primary efficacy endpoints were mean changes from baseline to day 43 in: procollagen type 1 N-terminal propeptide (P1NP), procollagen type 1 C-terminal propeptide (P1CP), bone-specific alkaline phosphatase (BSAP), osteocalcin (OC), and type 1 collagen cross-linked C-telopeptide (CTX-1). Mean change from baseline to day 141 in lumbar spine areal bone mineral density (aBMD) was also assessed. BPS804 safety and tolerability were assessed every 2 weeks. Overall, 14 adults were enrolled (BPS804 group: n\u2009=\u20099, mean age 30.7 years, mean aBMD Z-score \u20132.6; reference group, n\u2009=\u20095, mean age 27.4 years, mean aBMD Z-score \u20132.2). In the BPS804 group, P1NP, P1CP, BSAP, and OC were increased by 84% (p\u2009&amp;lt;\u20090.001), 53% (p\u2009=\u20090.003), 59% (p\u2009&amp;lt;\u20090.001), and 44% (p\u2009=\u20090.012), respectively, versus baseline (reference: P1NP, +6% [p\u2009=\u20090.651]; P1CP, +5% [p\u2009=\u20090.600]; BSAP, \u201313% [p\u2009=\u20090.582]; OC, \u201319% [p\u2009=\u20090.436]). BPS804 treatment downregulated CTX-1 by 44% from baseline (reference: \u20137%; significance was not tested for this biomarker), and increased aBMD by 4% (p\u2009=\u20090.038; reference group: +1%; p\u2009=\u20090.138). BPS804 was generally well tolerated. There were 32 adverse events reported in nine patients; none was suspected to be treatment-related. There were no treatment-related fractures. BPS804 stimulates bone formation, reduces bone resorption, and increases lumbar spine aBMD in adults with moderate OI. This paves the way for a longer-term, phase 3 trial into the efficacy, safety, and tolerability of BPS804 in patients with OI. \u00a9 2017 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3143","type":"journal-article","created":{"date-parts":[[2017,3,29]],"date-time":"2017-03-29T11:48:15Z","timestamp":1490788095000},"page":"1496-1504","source":"Crossref","is-referenced-by-count":143,"title":["BPS804 Anti-Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6616-3484","authenticated-orcid":false,"given":"Francis H","family":"Glorieux","sequence":"first","affiliation":[{"name":"Research CentreShriners Hospital for Children, and McGill UniversityMontrealQCCanada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Devogelaer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Catholique de LouvainSaint-Luc University HospitalBrusselsBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Durigova","sequence":"additional","affiliation":[{"name":"Research CentreShriners Hospital for Children, and McGill UniversityMontrealQCCanada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Goemaere","sequence":"additional","affiliation":[{"name":"Ghent University HospitalGhentBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hemsley","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical ResearchBaselSwitzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Jakob","sequence":"additional","affiliation":[{"name":"Orthopedic Center for Musculoskeletal ResearchExperimental and Clinical OsteologyOrthopedic DepartmentUniversity of WuerzburgWuerzburgGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Junker","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical ResearchBaselSwitzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Ruckle","sequence":"additional","affiliation":[{"name":"Pacific Pharma GroupTacomaWAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar","family":"Seefried","sequence":"additional","affiliation":[{"name":"Orthopedic Center for Musculoskeletal ResearchExperimental and Clinical OsteologyOrthopedic DepartmentUniversity of WuerzburgWuerzburgGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Winkle","sequence":"additional","affiliation":[{"name":"Anaheim Clinical TrialsAnaheimCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,3,29]]},"reference":[{"key":"2024021014200520700_jbmr3143-bib-0001","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.berh.2007.12.012","article-title":"Osteogenesis imperfecta","volume":"22","author":"Glorieux","year":"2008","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"2024021014200520700_jbmr3143-bib-0002","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1007\/s00198-016-3709-1","article-title":"DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum","volume":"27","author":"Bardai","year":"2016","journal-title":"Osteoporos 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