Sclerostin-Antibody Treatment Decreases Fracture Rates in Axial Skeleton and Improves the Skeletal Phenotype in Growing oim/oim Mice.

Autor:	Cardinal, Mickaël, Dessain, Alicia, Roels, Thomas, Lafont, Sébastien, Ominsky, Michael S., Devogelaer, Jean-Pierre, Chappard, Daniel, Mabilleau, Guillaume, Ammann, Patrick, Nyssen-Behets, Catherine, Manicourt, Daniel H.
Předmět:	SKELETON TREATMENT of fractures COMPACT bone BONE density BONES STATURE SACRUM OSTEOBLASTS THERAPEUTIC use of immunoglobulins BONE fracture prevention BIOLOGICAL models PROTEINS COLLAGEN RESEARCH OSTEOGENESIS imperfecta MOLECULAR chaperones ANIMAL experimentation RESEARCH methodology MEDICAL cooperation EVALUATION research COMPARATIVE studies COMPUTED tomography STATISTICAL sampling CARRIER proteins PHENOTYPES MICE CHEMICAL inhibitors
Zdroj:	Calcified Tissue International; May2020, Vol. 106 Issue 5, p494-508, 15p
Abstrakt:	In osteogenesis imperfecta (OI), vertebrae brittleness causes thorax deformations and leads to cardiopulmonary failure. As sclerostin-neutralizing antibodies increase bone mass and strength in animal models of osteoporosis, their administration in two murine models of severe OI enhanced the strength of vertebrae in growing female Crtap-/- mice but not in growing male Col1a1Jrt/+ mice. However, these two studies ignored the impact of antibodies on spine growth, fracture rates, and compressive mechanical properties. Here, we conducted a randomized controlled trial in oim/oim mice, an established model of human severe OI type III due to a mutation in Col1a2. Five-week-old female WT and oim/oim mice received either PBS or sclerostin antibody (Scl-Ab) for 9 weeks. Analyses included radiography, histomorphometry, pQCT, microcomputed tomography, and biomechanical testing. Though it did not modify vertebral axial growth, Scl-Ab treatment markedly reduced the fracture prevalence in the pelvis and caudal vertebrae, enhanced osteoblast activity (L4), increased cervico-sacral spine BMD, and improved the lumbosacral spine bone cross-sectional area. Scl-Ab did not impact vertebral height and body size but enhanced the cortical thickness and trabecular bone volume significantly in the two Scl-Ab groups. At lumbar vertebrae and tibial metaphysis, the absolute increase in cortical and trabecular bone mass was higher in Scl-Ab WT than in Scl-Ab oim/oim. The effects on trabecular bone mass were mainly due to changes in trabecular number at vertebrae and in trabecular thickness at metaphyses. Additionally, Scl-Ab did not restore a standard trabecular network, but improved bone compressive ultimate load with more robust effects at vertebrae than at metaphysis. Overall, Scl-Ab treatment may be beneficial for reducing vertebral fractures and spine deformities in patients with severe OI. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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