Bone Abstracts

Background: We identified a family with early onset X-linked osteoporosis and fracturesMethods: We performed whole exome sequencing of the X chromosome in three affected members. After discovering a putative pathogenic variant we performed Sanger sequencing of all exons of this gene in other members of this family and in 95 unrelated men suspected of OI type I without COL1A1/2 mutations. We also genotyped a SNP in this gene (minor allele frequency 0.02) ...

Destruction of the articular cartilage is the major feature of Osteoarthritis (OA). Ageing is the primary risk factor, but how ageing results in OA is still an enigma. In OA, articular chondrocytes degrade their own matrix, while in healthy articular cartilage they preserve it.Transforming growth factor β (TGFβ) is a central regulator of chondrocyte proliferation, differentiation and extracellular matrix production. Deregulation of TGFβ si...

Background: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. It is a variable condition with a range of clinical severity. About 90% of patients with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2 genes, which shows an autosomal dominant pattern (AD) of inheritance. Other genes are associated with the autosomal recessive (AR) ...

Romosozumab is an investigational bone-forming agent that inhibits sclerostin. Recent data demonstrated that it stimulated bone formation, decreased bone resorption, and led to rapid and substantial increases in areal bone mineral density (BMD; McClung, J Bone Miner Res 27 (S1) S8–S9, 2012). In a Phase 1b, randomized, double-blind, placebo-controlled, multiple dose study, we studied the effects of romosozumab administered for 3 months and follow-...

Objectives: Creation of reference curves for areal bone mineral density (aBMD) and bone mineral content (BMC) with consideration of relevant anthropometric variables.Methods: Analysis of the dual-energy X-ray absorptiometry (DXA) data collected as part of the Bone Mineral Density in Childhood Study1, including 2012 boys and girls, 5–22 years old, with a total of 10 525 visits, resulting in aBMD and BMC observations at the lumbar spine, hi...

Background: There is still limited information on changes in growth especially segmental growth and bone mass of glucocorticoid(GC) treated boys with Duchenne Muscular Dystrophy (DMD).Objectives: To evaluate changes in growth and bone mass in GC treated boys with DMD.Methods: Retrospective study of 15 boys with DMD treated with GC, median age 7.6 years (4.1, 15.5) who had repeated DXA scan for clinical monitoring of bone health, me...

Although Vitamin D deficiency is the most common form of rickets worldwide, when there is a failure to respond to cholecalciferol, inborn errors of vitamin D metabolism should be considered. We describe two unrelated individuals who presented with early onset rickets characterised by reduced serum levels of 25(OH)D and 1,25(OH)2D, and a deficient response to Vitamin D2/D3 and calcitriol. Case 1: A Caucasian Australian girl with non-consanguineous parents ...

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Osteocytes differentiate from osteoblasts, are embedded in mineralised matrix and are critical regulators of bone remodelling. In vitro osteocyte models are limited to cell lines in monolayer, which do not represent their 3D environment in vivo. We have shown that osteoblasts in 3D gels differentiate along the osteocytic pathway. Since IGF1 regulates osteoblasts, and is involved in osteocyte response to mechanical loading, we hypothesised that IGF1 modulates ...

Geroderma osteodysplasticum (GO) is a rare autosomal recessive connective tissue disorder characterised by progeria like facies, wrinkled lax skin, joint hypermobility, congenital dislocation of hips and propensity to fragility fractures. In the past 25 years, five patients (three females and two males) diagnosed with GO were referred to our Paediatric metabolic bone service for assessment and management of secondary bone problems. All five children were born to consanguineous...