Bone Abstracts

Introduction: Osteogenesis imperfecta (OI) is a genetically heterogeneous disorder characterized by bone fragility. OI type V, with autosomal dominant inheritance, is characterized by ossification of the forearm interosseus membrane, radiodense metaphyseal bands, propensity for hyperplastic callus formation, and mesh-like lamellation on bone histology. Type V OI probands are reported to have white sclerae and normal teeth. Recent reports identified the cause of type V OI as a ...

Prof. David Little received his Medical Degree from the University of Sydney where he is Conjoint Professor of Paediatrics and Child Health, specialising in Orthopaedic Surgery. Prof. D Little is Head of Orthopaedic Research and Biotechnology at The Children’s Hospital at Westmead, part of the Sydney Children’s Hospital Network. He has broad clinical interests in Children’s Orthopaedi...

Introduction: Recessive osteogenesis imperfecta (OI) is caused by mutations in genes encoding proteins involved in post-translational interactions with type I collagen. Types VII–IX OI involve defects in the collagen prolyl 3-hydroxylation complex, which modifies α1(I)Pro986. PPIB encodes CyPB, a complex component with PPIase activity and the major isomerase facilitating collagen folding. We investigated the role of CyPB in collagen post-translational modifications a...

Recessive osteogenesis imperfecta (OI) is caused by mutations in genes encoding proteins involved in post-translational interactions with type I collagen. A founder mutation in a new gene responsible for recessive OI has recently been reported in Bedouins from Israel and Saudi Arabia, who have a homozygous deletion of TMEM38B exon 4 and surrounding intronic sequence. TMEM38B encodes TRIC-B, an integral ER membrane monovalent cation channel involved in Ca...

Osteogenesis imperfecta (OI) is a heritable bone dysplasia with collagen-related defects. Dominantly inherited OI is caused by structural defects in type I collagen or IFITM5, while recessive forms are caused by deficiency of proteins that interact with collagen for modification, folding or cross-linking. We have identified the first X-linked form of OI, caused by a defect in regulated intramembrane proteolysis (RIP). One type of RIP involves sequential cleavage of regulatory ...

Objectives: We evaluated the efficacy and safety of intravenous zoledronic acid (IV ZA) in children with glucocorticoid-induced osteoporosis (GIOP) through a randomized, placebo (PBO)-controlled trial.Methods: In this multi-national Phase 3 trial (NCT00799266), children 5–17 years of age with GIOP and low-trauma vertebral fractures (VF) were randomized 1:1 to IV ZA 0.05 mg/kg or IV PBO every six months for one year. Changes in lumbar spine areal bon...

Using a CyPB-null mouse model, we previously demonstrated delayed folding, abnormal post-translational modification and altered crosslinking of type I collagen synthesized by osteoblasts. However, intracellular folding of collagen molecules was further delayed by CsA treatment of CyPB-null cells, suggesting involvement of additional PPIases in collagen folding. Since studies of CyPA functions in osteoblasts have not been reported, we investigated the role of this cytoplasmic P...

Deficiency of Cyclophilin B (CyPB) causes recessively inherited Type IX osteogenesis imperfecta, a moderately severe to lethal bone dysplasia. CyPB, encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that catalyzes the rate-limiting step in collagen folding, and also functions as a component of the collagen prolyl 3-hydroxylation complex. We previously demonstrated in a Ppib−/− mouse model that CyPB PPIase activity r...

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Tibial dysplasia, which leads to fracture and pseudarthrosis, occurs in around 4% of children with NF1, and also in children with no underlying disorder. Pseudarthrosis of the fibular may or may not be present, or as an isolated entity, as can pseudarthrosis in the forearm (rare). Other bone problems faced by individuals with NF1 are scoliosis (20%), pectus excavatum/carinatum (12%), and sphenoid wing dysplasia (7%). Dural ectasia and plexiform neurofibromas can also affect th...