{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T16:30:19Z","timestamp":1780677019110,"version":"3.54.1"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Osteogenesis imperfecta (OI) is a heterogenous type 1 collagenopathy that results in bone fragility and fractures. There is no standard\u2010of\u2010care treatment to reduce fracture risk for adults with OI. The sialic acid\u2010binding immunoglobulin\u2010like lectin 15 (Siglec 15) immunoreceptor modulates osteoclast development and bone resorption. Prior studies in growing rats demonstrated that Siglec 15 antibodies increased bone mass and improved bone mechanical properties. This study evaluated the safety and efficacy of a Siglec 15 monoclonal antibody, NP159 (NextCure Inc.), in female oim\/oim and wildtype (WT) mice. Mice (n\u2009=\u200920\/group) were treated from 14 to 26 weeks with either NP159 (10\u2009mg\/kg\/dose weekly for 4 weeks, then biweekly for 8 weeks), weekly alendronate (ALN, 0.21\u2009mg\/kg), or weekly saline (equivalent to NP159). Faxitron images (anterior\u2010posterior and medial\u2010lateral) were taken at enrollment and sacrifice to evaluate fracture incidence and healing. Left femurs were analyzed for length, micro\u2010CT parameters, and biomechanical testing. Right tibias were analyzed by Fourier transform infrared spectroscopy. NP159 reduced fracture incidence in oim\/oim, 85% of whom were fracture\u2010free at sacrifice compared to 65% in the ALN group and 55% in the saline group. NP159 treatment enhanced bone strength and structure in oim\/oim, with mineral:matrix and carbonate:phosphate content that normalized towards the WT saline group. Unlike ALN, NP159 had a larger increase in bone stiffness(<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and enhanced both bone microarchitecture and mineralization without altering Bone Mineral Density. Overall, these findings demonstrate the therapeutic value of NP159 in addressing the presently unmet clinical need for safe and efficacious long\u2010term treatments for adults with OI.<\/jats:p>","DOI":"10.1002\/jor.70019","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T05:39:22Z","timestamp":1752903562000},"page":"1776-1786","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Siglec\u201015 Antibody Promotes High Quality Bone Formation in Adult Female Mice With Osteogenesis Imperfecta"],"prefix":"10.1002","volume":"43","author":[{"given":"Ketsia","family":"Seide","sequence":"first","affiliation":[{"name":"Hospital for Special Surgery New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack E.","family":"Mulcrone","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4596-7417","authenticated-orcid":false,"given":"Jonathan","family":"Chacko","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M.","family":"Carter","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Veneziale","sequence":"additional","affiliation":[{"name":"Temple University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Pleshko","sequence":"additional","affiliation":[{"name":"Temple University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Kothari","sequence":"additional","affiliation":[{"name":"NextCure Inc. Beltsville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Langermann","sequence":"additional","affiliation":[{"name":"NextCure Inc. Beltsville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanmugam","family":"Selvam","sequence":"additional","affiliation":[{"name":"NextCure Inc. Beltsville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathleen L.","family":"Raggio","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16051-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.16.2.101"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.81"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36545"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2895"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.49.8.627"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.1.133"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-2023I"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.090712"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37734"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.149"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.190"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X18805759"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay6570"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1989"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0374-x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.07.026"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-021-00161-1"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.11.036"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10825"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","unstructured":"N.Camacho C.Raggio S.Doty et al. Calcified Tissue International2001;69 no.94.","DOI":"10.1007\/s002230010045"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200211000-00010"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00451.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-011-1742-7"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2539"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2006.11.043"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.1922927"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2018.04.009"},{"key":"e_1_2_9_30_1","unstructured":"J.Marino E.Carter M.Baldino A. L.Boskey N. P.Pleshko andC. L.Raggio Preliminary Results: Initiation of Rank\u2010Fc Treatment in Post\u2010Adolescent Oim\/oimOim\/Oim Mice Does Not Reduce Fracture Incidence Poster No. 0545 ORS 2012 Annual Meeting 2012 ORS Annual Meeting 2012."},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.324194"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30654"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.11.036"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocd.2015.06.011"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12018-015-9201-1"},{"key":"e_1_2_9_36_1","first-page":"401","article-title":"Strength Indices From pQCT Imaging Predict up to 85% of Variance in Bone Failure Properties at Tibial Epiphysis and Diaphysis","volume":"8","author":"Kontulainen S. A.","year":"2008","journal-title":"Journal of Musculoskeletal & Neuronal Interactions"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1515\/9781400849505"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1039\/b805661g"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T14:34:16Z","timestamp":1757514856000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.70019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/jor.70019"],"URL":"https:\/\/doi.org\/10.1002\/jor.70019","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]},"assertion":[{"value":"2025-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}