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

Autor: Michael S. Ominsky, Sébastien Lafont, Mickaël Cardinal, Alicia Dessain, Daniel Chappard, Thomas Roels, Guillaume Mabilleau, Daniel Manicourt, Jean-Pierre Devogelaer, Catherine Nyssen-Behets, Patrick Ammann
Přispěvatelé: Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM), Université d'Angers (UA)
Rok vydání: 2019
Předmět:
musculoskeletal diseases
0301 basic medicine
Male
Axial skeleton
[SDV]Life Sciences [q-bio]
Endocrinology
Diabetes and Metabolism
Osteoporosis
030209 endocrinology & metabolism
Lumbar vertebrae
Metaphysis
Bone and Bones
Collagen Type I
03 medical and health sciences
chemistry.chemical_compound
Fractures
Bone
Mice
Random Allocation
0302 clinical medicine
Endocrinology
medicine
Animals
Orthopedics and Sports Medicine
ComputingMilieux_MISCELLANEOUS
Pelvis
Adaptor Proteins
Signal Transducing
Mice
Knockout
Extracellular Matrix Proteins
business.industry
Osteoblast
Anatomy
X-Ray Microtomography
Osteogenesis Imperfecta
musculoskeletal system
medicine.disease
Antibodies
Neutralizing
3. Good health
Disease Models
Animal
medicine.anatomical_structure
Phenotype
chemistry
Osteogenesis imperfecta
Sclerostin
Female
030101 anatomy & morphology
business
Molecular Chaperones
Zdroj: Calcified Tissue International
Calcified Tissue International, Springer Verlag, 2020, 106 (5), pp.494-508. ⟨10.1007/s00223-019-00655-5⟩
ISSN: 1432-0827
0171-967X
DOI: 10.1007/s00223-019-00655-5⟩
Popis: 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.
Databáze: OpenAIRE
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