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Osteogenesis Imperfecta (OI) is a genetic bone dysplasia characterized by bone deformities and fractures caused by low bone mass and impaired bone quality. OI is a genetically heterogeneous disorder that most commonly arises from dominant mutations in genes encoding type-I collagen (COL1A1 and COL1A2). In addition, OI is recessively inherited with the majority of cases resulting from mutations in prolyl-3-hydroxylation complex members, which includes Cartilage Associated Protein (CRTAP). OI patients are at an increased risk of fracture throughout their lifetimes. However, non-union or delayed healing has been reported in 24% of fractures and 52% of osteotomies. Additionally, re-fractures typically go unreported making the frequency of re-fractures in OI patients unknown. Thus, there is an unmet need to better understand the mechanisms by which OI affects fracture healing. Using an open tibial fracture model, our study demonstrates delayed healing in both Col1a2 and Crtap OI mouse models (dominant and recessive OI, respectively) that is associated with reduced callus size and predicted strength. Callus cartilage distribution and chondrocyte maturation were altered in OI suggesting accelerated cartilage differentiation. Importantly, we determined that healed fractured tibia in female OI mice are biomechanically weaker when compared to the contralateral unfractured bone suggesting that abnormal OI fracture healing OI may prime future re-fracture at the same location. We have previously shown up-regulated TGF-β signaling in OI and we confirm this in the context of fracture healing. Interestingly, treatment of Crtap mice with the anti-TGF-β antibody, 1D11 resulted in further reduced callus size and predicted strength, highlighting the importance of investigating dose response in treatment strategies. These data provide valuable insight into the effect of the extracellular matrix (ECM) on fracture healing, a poorly understood mechanism, and support the need for prevention of primary fractures to decrease incidence of refracture and deformity in OI patients. This article is protected by copyright. All rights reserved.
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Surgical interventions are routinely performed on children with osteogenesis imperfecta (OI) to stabilize long bones, often post fracture. We speculated that a combination of intramedullary reaming an...
Evaluation of the union of osteotomies and fractures in patients with osteogenesis imperfecta (OI) is a critical component of patient care. Studies of the OI patient population have so far used varied...
Retrospective clinical study of individuals with osteogenesis imperfecta (OI).
PTH1-34 (parathyroid hormone 1-34) is the only clinical drug to promote osteogenesis. MSCs (mesenchymal stem cells) have multidirectional differentiation potential and are closely related to fracture ...
The purpose of this review is to outline the current understanding of the molecular mechanisms and natural history of osteogenesis imperfecta, and to describe the development of new treatments for thi...
Alendronate should be considered as an alternative therapy of osteogenesis imperfecta (OI) because it significantly increased areal bone mineral density (BMD) and its Z score, decreased fr...
The purpose of this study is to learn about pregnancy outcomes in osteogenesis imperfecta (OI). Patients enrolled in the Brittle Bone Disorders (BBD) Contact Registry (CR) will be invited ...
To evaluate long-term safety of denosumab in subjects with pediatric osteogenesis imperfecta(OI) completing Study 20130173.
The purpose of this study is to investigate the effect of BPS804 on strength/quality of bone in patients with Type I, III or IV Osteogenesis imperfecta using a special type of CT scanner. ...
Osteogenesis Imperfecta (OI) is a heterogeneous group of rare connective tissue hereditary diseases responsible for fragility and bone deformity. OI is caused by an autosomal dominant muta...
Autosomal dominant COLLAGEN DISEASES resulting from defective biosynthesis of COLLAGEN TYPE I and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV.
The physiological restoration of bone tissue and function after a fracture. It includes BONY CALLUS formation and normal replacement of bone tissue.
An Sp transcription factor that contains three CYS2-HIS2 ZINC FINGERS. It binds to GC RICH SEQUENCES and performs an essential function in regulating gene expression for differentiation of OSTEOBLASTS. Mutations in the SP7 gene are associated with type 12 OSTEOGENESIS IMPERFECTA.
A discoidin domain receptor for FIBRILLAR COLLAGEN and non-fibrillar COLLAGEN TYPE X. It functions in many cellular and developmental processes that include remodeling of the EXTRACELLULAR MATRIX; CELL MIGRATION; CELL DIFFERENTIATION; and CELL PROLIFERATION; as well as OSTEOGENESIS and the maturation of CHONDROCYTES.
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...
Complementary and Alternative Medicine
Alternative medicine are whole medical systems that did not fit with conventional medicine as they have completely different philosophies and ideas on the causes of disease, methods of diagnosis and approaches to treatment. Although often overlapping, co...