{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T17:16:44Z","timestamp":1767374204141,"version":"3.37.3"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteogenesis imperfecta (OI) is a genetic bone fragility disorder that features frequent fractures. Bone healing outcomes are contingent on a proper balance between bone formation and resorption, and drugs such as bone morphogenetic proteins (BMPs) and bisphosphonates (BPs) have shown to have utility in modulating fracture repair. While BPs are used for OI to increase BMD and reduce pain and fracture rates, there is little evidence for using BMPs as local agents for fracture healing (alone or with BPs). In this study, we examined wild\u2010type and OI mice (<jats:italic>Col1a2<\/jats:italic><jats:sup><jats:italic>+\/G610C<\/jats:italic><\/jats:sup>) in a murine tibial open fracture model with (i) surgery only\/no treatment, (ii) local BMP\u20102 (10\u2009\u00b5g), or (iii) local BMP\u20102 and postoperative zoledronic acid (ZA; 0.1\u2009mg\/kg total dose). Microcomputed tomography reconstructions of healing fractures indicated BMP\u20102 was less effective in an OI setting, however,\u00a0BMP\u20102\u2009+ZA led to considerable increases in bone volume (+193% WT, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; +154% OI, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and polar moment of inertia (+125% WT, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01; +248% OI, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Tissue histology revealed a thinning of the neocortex of the callus in BMP\u20102 treated OI bone, but considerable retention of woven bone in the healing callus with BMP\u2009+\u2009ZA specimens. These data suggest a cautious approach may be warranted with the sole application of BMP\u20102 in an OI surgical setting as a bone graft substitute. However, this may be overcome by off\u2010label BP\u00a0administration.<\/jats:p>","DOI":"10.1002\/jor.25414","type":"journal-article","created":{"date-parts":[[2022,7,9]],"date-time":"2022-07-09T00:04:06Z","timestamp":1657325046000},"page":"808-814","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Modeling anabolic and antiresorptive therapies for fracture healing in a mouse model of osteogenesis imperfecta"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2267-3671","authenticated-orcid":false,"given":"Alexandra K.","family":"O'Donohue","sequence":"first","affiliation":[{"name":"Bioengineering &amp; Molecular Medicine Laboratory The Children's Hospital at Westmead and the Westmead Institute for Medical Research  Sydney New South Wales Australia"},{"name":"Children's Hospital Westmead Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0631-2975","authenticated-orcid":false,"given":"Aiken","family":"Dao","sequence":"additional","affiliation":[{"name":"Bioengineering &amp; Molecular Medicine Laboratory The Children's Hospital at Westmead and the Westmead Institute for Medical Research  Sydney New South Wales Australia"},{"name":"Children's Hospital Westmead Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin D.","family":"Bobyn","sequence":"additional","affiliation":[{"name":"Bioengineering &amp; Molecular Medicine Laboratory The Children's Hospital at Westmead and the Westmead Institute for Medical Research  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig F.","family":"Munns","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Queensland Children's Hospital  Brisbane Queensland Australia"},{"name":"Child Health Research Centre and Faculty of Medicine The University of Queensland  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G.","family":"Little","sequence":"additional","affiliation":[{"name":"Bioengineering &amp; Molecular Medicine Laboratory The Children's Hospital at Westmead and the Westmead Institute for Medical Research  Sydney New South Wales Australia"},{"name":"Children's Hospital Westmead Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7757-6281","authenticated-orcid":false,"given":"Aaron","family":"Schindeler","sequence":"additional","affiliation":[{"name":"Bioengineering &amp; Molecular Medicine Laboratory The Children's Hospital at Westmead and the Westmead Institute for Medical Research  Sydney New South Wales Australia"},{"name":"Children's Hospital Westmead Clinical School, Faculty of Medicine and Health University of Sydney  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,21]]},"reference":[{"issue":"6","key":"e_1_2_6_2_1","first-page":"259","article-title":"Osteogenesis imperfect: clinical and epidemiological findings in a series of pediatric patients","volume":"76","author":"Cammarata\u2010Scalisi F","year":"2019","journal-title":"Bol Med Hosp Infant 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