Bone Abstracts

Communication between osteoblasts and osteoclasts is crucial for bone remodeling. Thrombin and its thrombin receptor (TR; PAR-1) are expressed in osteoclasts and osteoblasts, respectively. To date, the physiological roles of thrombin and TR in bone metabolism have not been elucidated. Therefore, we fully characterized the bone phenotype of mice lacking the thrombin receptor.We performed bone microarchitectural analyses of the femurs of 10–12 week ol...

Transient receptor potential vanilloid channels (TRPVs) have been implicated in Ca2+ homeostasis and bone metabolism. In particular, TRPV4 deficiency was shown to cause sexual dimorphism in bone metabolism and osteoporotic fracture risk. Cortical bone structure was reported to be altered in male TRPV4 knock-out (TRPV4−/−) mice but not in female TRPV−/− mice compared to sex-matched wildtype (TRPV4+/+) animals.To gain knowledge on t...

Background: Fracture incidence rate and growth according to different glucocorticoid (GC) regimen in Duchenne Muscular Dystrophy (DMD) is currently unknown.Objective: To determine the extent of skeletal morbidity and the influence of GC regimen on fracture incidence rate and growth in a contemporary cohort of DMD in the UK.Method: Clinical details of 832 boys with DMD in the North Star database (2006–2015) from 23 centres were...

Introduction: Resistance to thyroid hormone (RTH) is a rare disease, characterized by elevated thyroid hormone and not suppressed TSH concentrations. In 85% of cases it is related to TRβ gene mutations.Objectives: To evaluate biochemical and densitometric features of 14 patients with RTH (RTHG: 7 females (4 children) and seven males (2 children)) in comparison to 24 control subjects (CG, 14 females (8 children) and 10 males (4 children)).<p clas...

Background: Morquio disease was described by the Uruguayan pediatrician Luis Morquio. It’s a congenital disease caused by a deficiency of the N-acetilgalactosamine 6 sulfatase (MPS IV A) or B galactosidase (MPS IV B) and his frequency is 1/100 000 live births Accumulation of mucopolysacharides in tissues results in short stature, skeletal anomalies (vertebral column deformities), loss of hearing, visual anomalies (corneal opacities), cardiac, hepatic and respirat...

Background: Achondroplasia is a genetic disorder wich affects bone growth leading to short stature. It occurs in 1 of every 25 000 live births and it is characteristized by short extremities, hyperlordosis, small hands and macrocephaly, with high forehead and saddle nose. Neurologic complications are due to narrowing of the vertebral foramen. Is transmitted as autosomal dominant and it is due to mutations of the FGFR3 gene witch codifies the fibroblastic receptor of G...

Background: Pseudohypoparathyroidism is characterized by a resistance to parathormone, with variable phenotypical and biochemical manifestations. With genetic disorder caused by heterozygous inactivating mutations in GNAS1, the gene encoding the alpha-chain of G(s), and is associated with short stature, obesity, brachydactyly, and sc ossifications. AHO patients with GNAS1 mutations on maternally inherited alleles also manifest resistance to multiple hormones (e.g. PTH, TSH, LH...

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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...