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There is no cure and treatments focus primarily on mitigation of fractures. Although severe OI can be diagnosed prenatally, physicians lack tools for in utero intervention. Previous studies demonstrate postnatal inhibition of myostatin, a negative regulator of muscle mass, improves bone mass in OI mouse models, with greater skeletal improvements in genetically myostatin-deficient OI mice. Reduced maternal myostatin during pregnancy improved musculoskeletal health in offspring with unaltered myostatin. These findings suggest prenatal inhibition of maternal myostatin can improve bone strength in OI offspring. We hypothesize that targeting muscle-bone crosstalk through pharmacological myostatin inhibition can improve musculoskeletal health in OI offspring and protect from maternal bone loss. We evaluated maternal and fetal safety, metabolic, and musculoskeletal outcomes during pregnancy and lactation in wild-type and OI mice to assess preclinical safety for potential in utero therapy during critical developmental windows. Pregnant and nonpregnant OI mice were subject to anti-myostatin and control antibody therapy during gestation (embryonic days 3.5-E15.5). Maternal and fetal health were evaluated at embryonic day 17.5 and maternal health following lactation. Prenatal maternal anti-myostatin antibody treatment alone was not sufficient to increase maternal muscle and bone mass, and although the placental size was impacted for some, fetal weights, litter size, and maternal metabolic, and musculoskeletal health remained equivalent to control treated dams. Our findings highlight significant and potentially detrimental changes in maternal bone during lactation in an OI mouse model, consistent with pre\/perinatal skeletal findings in non-OI mice and humans.<\/jats:p>","DOI":"10.1210\/endocr\/bqaf080","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T19:56:25Z","timestamp":1746042985000},"source":"Crossref","is-referenced-by-count":1,"title":["Maternal Health and Safety Outcomes of Prenatal Myostatin Inhibition in Osteogenesis Imperfecta Mice"],"prefix":"10.1210","volume":"166","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9326-1661","authenticated-orcid":false,"given":"Tara K","family":"Crawford","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-841X","authenticated-orcid":false,"given":"Brittany N","family":"Lafaver","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6079-6715","authenticated-orcid":false,"given":"Arin K","family":"Oestreich","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["USA"]},{"name":"Center of Regenerative Medicine, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["USA"]},{"name":"Shriners Hospitals for Children , St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca R","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles S","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel M","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith K","family":"Luhmann","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["USA"]},{"name":"Center of Regenerative Medicine, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["USA"]},{"name":"Shriners Hospitals for Children , St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Opoku","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda K","family":"Schulte","sequence":"additional","affiliation":[{"name":"Division of Medicine, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Mastaitis","sequence":"additional","affiliation":[{"name":"Division of Muscle and Metabolic Diseases, Regeneron Pharmaceuticals , Tarrytown, NY 10591 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrienne M","family":"Ohler","sequence":"additional","affiliation":[{"name":"Division of Applied Social Sciences, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura C","family":"Schulz","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of Missouri , Columbia, MO 65211 ,","place":["USA"]},{"name":"Division of Obstetrics Gynecology and Women's Health, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-3783","authenticated-orcid":false,"given":"Charlotte L","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Missouri , Columbia, MO 65211 ,","place":["USA"]},{"name":"Department of Child Health, University of Missouri , Columbia, MO 65211 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"issue":"10028","key":"2026032309025198600_bqaf080-B1","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0140-6736(15)00728-X","article-title":"Osteogenesis 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