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Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse

Osteogenesis imperfecta (OI), which is most often due to a collagen type 1 gene mutation, is characterized by low bone density and bone fragility. In OI patients, gender-related differences were reported, but data in the literature are not convergent. We previously observed that sclerostin antibody...

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Autores principales: Cardinal, Mickaël, Chretien, Antoine, Roels, Thomas, Lafont, Sébastien, Ominsky, Michael S., Devogelaer, Jean-Pierre, Manicourt, Daniel H., Behets, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383339/
https://www.ncbi.nlm.nih.gov/pubmed/34447412
http://dx.doi.org/10.3389/fgene.2021.705505
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author Cardinal, Mickaël
Chretien, Antoine
Roels, Thomas
Lafont, Sébastien
Ominsky, Michael S.
Devogelaer, Jean-Pierre
Manicourt, Daniel H.
Behets, Catherine
author_facet Cardinal, Mickaël
Chretien, Antoine
Roels, Thomas
Lafont, Sébastien
Ominsky, Michael S.
Devogelaer, Jean-Pierre
Manicourt, Daniel H.
Behets, Catherine
author_sort Cardinal, Mickaël
collection PubMed
description Osteogenesis imperfecta (OI), which is most often due to a collagen type 1 gene mutation, is characterized by low bone density and bone fragility. In OI patients, gender-related differences were reported, but data in the literature are not convergent. We previously observed that sclerostin antibody (Scl-Ab), which stimulates osteoblast Wnt pathway via sclerostin inactivation, improved spine and long-bone parameters and biomechanical strength in female oim/oim mice, a validated model of human type 3 OI. Here, we wanted to highlight the effect of Scl-Ab on male oim/oim bones in order to identify a possible distinct therapeutic effect from that observed in females. According to the same protocol as our previous study with female mice, male wild-type (Wt) and oim/oim mice received vehicle or Scl-Ab from 5 to 14 weeks of age. Clinimetric and quantitative bone parameters were studied using X-rays, peripheral quantitative computed tomography, microradiography, and dynamic histomorphometry and compared to those of females. Contrary to Wt mice, male oim/oim had significantly lower weight, snout–sacrum length, and bone mineral content than females at 5 weeks. No significant difference in these clinimetric parameters was observed at 14 weeks, whereas male oim showed significantly more long-bone fractures than females. Scl-Ab improved bone mineral density and bone volume/total volume ratio (BV/TV) of vertebral body in Wt and oim/oim, without significant difference between male and female at 14 weeks. Male vehicle oim/oim had a significantly lower cortical thickness (Ct.Th) and BV/TV of tibial diaphysis than female and showed a higher number of fractures at 14 weeks. Scl-Ab increased midshaft periosteal apposition rate in such a way that tibial Ct.Th of male oim/oim was not significantly different from the female one at 14 weeks. The number of fractures was lower in male than female oim/oim after 14 weeks of Scl-Ab treatment, but this difference was not significant. Nevertheless, Scl-Ab–treated oim/oim male and female mice remained smaller than the Wt ones. In conclusion, our results highlighted differences between male and female oim/oim at 4 and 14 weeks of age, as well as some male-specific response of cortical bone to Scl-Ab. These gender-related particularities of oim/oim should be considered when testing experimental treatments.
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spelling pubmed-83833392021-08-25 Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse Cardinal, Mickaël Chretien, Antoine Roels, Thomas Lafont, Sébastien Ominsky, Michael S. Devogelaer, Jean-Pierre Manicourt, Daniel H. Behets, Catherine Front Genet Genetics Osteogenesis imperfecta (OI), which is most often due to a collagen type 1 gene mutation, is characterized by low bone density and bone fragility. In OI patients, gender-related differences were reported, but data in the literature are not convergent. We previously observed that sclerostin antibody (Scl-Ab), which stimulates osteoblast Wnt pathway via sclerostin inactivation, improved spine and long-bone parameters and biomechanical strength in female oim/oim mice, a validated model of human type 3 OI. Here, we wanted to highlight the effect of Scl-Ab on male oim/oim bones in order to identify a possible distinct therapeutic effect from that observed in females. According to the same protocol as our previous study with female mice, male wild-type (Wt) and oim/oim mice received vehicle or Scl-Ab from 5 to 14 weeks of age. Clinimetric and quantitative bone parameters were studied using X-rays, peripheral quantitative computed tomography, microradiography, and dynamic histomorphometry and compared to those of females. Contrary to Wt mice, male oim/oim had significantly lower weight, snout–sacrum length, and bone mineral content than females at 5 weeks. No significant difference in these clinimetric parameters was observed at 14 weeks, whereas male oim showed significantly more long-bone fractures than females. Scl-Ab improved bone mineral density and bone volume/total volume ratio (BV/TV) of vertebral body in Wt and oim/oim, without significant difference between male and female at 14 weeks. Male vehicle oim/oim had a significantly lower cortical thickness (Ct.Th) and BV/TV of tibial diaphysis than female and showed a higher number of fractures at 14 weeks. Scl-Ab increased midshaft periosteal apposition rate in such a way that tibial Ct.Th of male oim/oim was not significantly different from the female one at 14 weeks. The number of fractures was lower in male than female oim/oim after 14 weeks of Scl-Ab treatment, but this difference was not significant. Nevertheless, Scl-Ab–treated oim/oim male and female mice remained smaller than the Wt ones. In conclusion, our results highlighted differences between male and female oim/oim at 4 and 14 weeks of age, as well as some male-specific response of cortical bone to Scl-Ab. These gender-related particularities of oim/oim should be considered when testing experimental treatments. Frontiers Media S.A. 2021-08-10 /pmc/articles/PMC8383339/ /pubmed/34447412 http://dx.doi.org/10.3389/fgene.2021.705505 Text en Copyright © 2021 Cardinal, Chretien, Roels, Lafont, Ominsky, Devogelaer, Manicourt and Behets. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Cardinal, Mickaël
Chretien, Antoine
Roels, Thomas
Lafont, Sébastien
Ominsky, Michael S.
Devogelaer, Jean-Pierre
Manicourt, Daniel H.
Behets, Catherine
Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse
title Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse
title_full Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse
title_fullStr Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse
title_full_unstemmed Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse
title_short Gender-Related Impact of Sclerostin Antibody on Bone in the Osteogenesis Imperfecta Mouse
title_sort gender-related impact of sclerostin antibody on bone in the osteogenesis imperfecta mouse
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383339/
https://www.ncbi.nlm.nih.gov/pubmed/34447412
http://dx.doi.org/10.3389/fgene.2021.705505
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