{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:46:07Z","timestamp":1783334767168,"version":"3.54.6"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,5,7]],"date-time":"2023-05-07T00:00:00Z","timestamp":1683417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mutations in the COL1A1 and COL1A2 genes, which encode type I collagen, are present in around 85%\u201390% of osteogenesis imperfecta (OI) patients. Because type I collagen is the principal protein composition of bones, any changes in its gene sequences or synthesis can severely affect bone structure. As a result, skeletal deformity and bone frailty are defining characteristics of OI. Homozygous\n                    <jats:italic>oim\/oim<\/jats:italic>\n                    mice are utilized as models of severe progressive type III OI. Bone adapts to external forces by altering its mass and architecture. Previous attempts to leverage the relationship between muscle and bone involved using a soluble activin receptor type IIB\u2010mFc (sActRIIB\u2010mFc) fusion protein to lower circulating concentrations of activin A and myostatin. These two proteins are part of the TGF\u2010\u03b2 superfamily that regulate muscle and bone function. While this approach resulted in increased muscle masses and enhanced bone properties, adverse effects emerged due to ligand promiscuity, limiting clinical efficacy and obscuring the precise contributions of myostatin and activin A. In this study, we investigated the musculoskeletal and whole\u2010body metabolism effect of treating 5\u2010week\u2010old wildtype (Wt) and\n                    <jats:italic>oim<\/jats:italic>\n                    \/\n                    <jats:italic>oim<\/jats:italic>\n                    mice for 11\u2009weeks with either control antibody (Ctrl\u2010Ab) or monoclonal anti\u2010activin A antibody (ActA\u2010Ab), anti\u2010myostatin antibody (Mstn\u2010Ab), or a combination of ActA\u2010Ab and Mstn\u2010Ab (Combo). We demonstrated that ActA\u2010Ab treatment minimally impacts muscle mass in\n                    <jats:italic>oim<\/jats:italic>\n                    \/\n                    <jats:italic>oim<\/jats:italic>\n                    mice, whereas Mstn\u2010Ab and Combo treatments substantially increased muscle mass and overall lean mass regardless of genotype and sex. Further, while no improvements in cortical bone microarchitecture were observed with all treatments, minimal improvements in trabecular bone microarchitecture were observed with the Combo treatment in\n                    <jats:italic>oim<\/jats:italic>\n                    \/\n                    <jats:italic>oim<\/jats:italic>\n                    mice. Our findings suggest that individual or combinatorial inhibition of myostatin and activin A alone is insufficient to robustly improve femoral biomechanical and microarchitectural properties in severely affected OI mice. \u00a9 2023 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10753","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T02:49:21Z","timestamp":1683514161000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Whole\u2010Body Metabolism and the Musculoskeletal Impacts of Targeting Activin A and Myostatin in Severe Osteogenesis Imperfecta"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-2129","authenticated-orcid":false,"given":"Catherine 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