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

AbstractIn 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), incre ased 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 abso lute increase in cortical and trabecular bone mass was higher in Scl-Ab WT than in Scl-Ab oim/oim. The effects ...
Source: Calcified Tissue International - Category: Orthopaedics Source Type: research

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ConclusionsNovel disease-causing variants were identified in 29%, and a higher proportion of non-collagen defects was seen. Obtaining a precise diagnosis of OI in underrepresented populations allows expanding our understanding of its molecular landscape, potentially leading to improved personalized care in the future.
Source: Osteoporosis International - Category: Orthopaedics Source Type: research
This article is protected by copyright. All rights reserved.
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research
Abstract Danio rerio (zebrafish) is an elective model organism for the study of vertebrate development because of its high degree of homology with human genes and organs, including bone. Zebrafish embryos, because of the optical clarity, small size, and fast development, can be easily used in large-scale mutagenesis experiments to isolate mutants with developmental skeletal defects and in high-throughput screenings to find new chemical compounds for the ability to revert the pathological phenotype. On the other hand, the adult zebrafish represents another powerful resource for pathogenic and therapeutic studies ab...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Authors: Barik A, Chakravorty N Abstract Titanium implants are considered the gold standard of treatment for dental and orthopedic applications. Biocompatibility, low elasticity, and corrosion resistance are some of the key properties of these metallic implants. Nonetheless, a long-term clinical failure of implants may occur due to inadequate osseointegration. Poor osseointegration induces mobility, inflammation, increased bone resorption, and osteolysis; hence, it may result in painful revision surgeries. Topographical modifications, improvement in hydrophilicity, and the development of controlled-release drug-loa...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
ABSTRACTSclerostin antibody (Scl ‐Ab) is an anabolic bone agent that has been shown to increase bone mass in clinical trials of adult diseases of low bone mass, such as osteoporosis and osteogenesis imperfecta (OI). Its use to decrease bone fragility in pediatric OI has shown efficacy in several growing mouse models, suggesting t ranslational potential to pediatric disorders of low bone mass. However, the effects of pharmacologic inhibition of sclerostin during periods of rapid growth and development have not yet been described with respect to the cranium, where lifelong deficiency of functioning sclerostin leads to patt...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research
ConclusionWe identified pathogenic mutations in 81% of our Japanese patients with OI. Most mutations were located onCOL1A1 andCOL1A2. This study revealed that glycine substitutions onCOL1A1 resulted in the severe phenotype among Japanese patients with OI.
Source: Osteoporosis International - Category: Orthopaedics Source Type: research
Conclusions: AP is a common finding in OI patients (54%). Among hips of OI patients that met criteria for AP in early radiographs, 42% (20/48) demonstrated greater CE angles in their latest radiographs. Similar changes were observed in OI patients who did not initially meet criteria for diagnosis for AP. However, CE angle measurements between the 2 groups did not significantly differ (P=0.71). In terms of Kohler line crossing, patients that met criteria for AP in early radiographs had significantly greater change per year than those that did not have AP criteria (P
Source: Journal of Pediatric Orthopaedics - Category: Orthopaedics Tags: Hip Source Type: research
ConclusionAccess to genetic testing in OI is increasing as advances in genetic technologies decreases cost; a clinical diagnostic pathway needs to be implemented for managing variants identified by such testing.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
AbstractPurpose of ReviewTo review the differential diagnosis of low bone mineral density (BMD).Recent FindingsOsteoporosis is the most common cause of low BMD in adults; however, non-osteoporotic causes of low BMD should be considered in the differential diagnosis of patients with low BMD. Mild osteogenesis imperfecta, osteomalacia, and mineral and bone disorder of chronic kidney disease as well as several other rare diseases can be characterized by low BMD.SummaryThis review summarizes the differential diagnosis of low BMD. It is important to differentiate osteoporosis from other causes of low BMD since treatment regimen...
Source: Current Osteoporosis Reports - Category: Orthopaedics Source Type: research
This article is protected by copyright. All rights reserved.
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research
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