Bone Abstracts

Osteoporosis pseudoglioma syndrome (OPPGS) is a rare autosomal recessive disorder characterised by congenital or juvenile-onset blindness, severe juvenile-onset osteoporosis, and skeletal fragility. OPPGS is caused by loss-of-function mutations in the LRP5 gene, a member of the LDL receptor family. It activates the canonical Wnt/β-catenin pathway, regulating osteoblastic bone formation. We investigated a 40-year-old Caucasian male presenting with congenital blind...

Genetic skeletal diseases (GSDs) are an extremely diverse and complex group of rare genetic diseases that primarily affect the development and homeostasis of the osseous skeleton. There are more than 450 unique and well-characterised phenotypes that range in severity from relatively mild to severe and lethal forms. Although individually rare, as a group of related genetic diseases, GSDs have an overall prevalence of at least 1/4000 child. Qualitative defects in cartilage struc...

Biographical DetailsMichael D Briggs obtained his PhD at the MRC Clinical Research Centre, Harrow, studying the genetic basis of osteogenesis imperfecta. He undertook postdoctoral work at UCLA identifying the genetic basis of chondrodysplasias. In 1996 Mike moved to Manchester as an AR-UK Fellow to continue studying disease mechanisms in chondrodysplasia. In 2004 he was awarded a Wellcome...

Zoledronic acid (AZ), is considered first-line treatment for Paget’s disease (PD) of bone. The most common adverse event is flu-like syndrome, described between 10 and 50% of patients. Nowadays, there is not known exactly the molecular basis of this syndrome yet. Statins play an important role in the mevalonate pathway, blocking the production of proinflammatory cytokines secreted by T cells γ/δ.Objectives: Characterization and in...

Objective: The aim of this study is to compare the bone health index (BHI) for healthy Swiss children born in 1955 with healthy Swiss children born a generation later.Method: BHI is derived from the cortical thickness in the three middle metacarpals. It is determined with the BoneXpert medical device, which automatically analyses a standard bone age hand radiograph. The measurement result is independent of the sharpness of the image. The image data are f...

Background: LRP4 gene encodes a member of the LDL receptor gene family, expressed by osteoblasts, which negatively regulates Wnt/β-catenin signalling by potentiating the inhibitory effect of sclerostin on LRP5 signalling. Previously, missense mutations of LRP4 have been described in patients with the phenotype of sclerosteosis, a disease associated with high bone mass and bone overgrowth. Here we investigated the hypothesis the LRP4 mut...

Muscle and loading force application alters bone structure and increases bone mineral density (BMD), particularly during growth. However, bone microarchitectural texture, as assessed by the trabecular bone score (TBS), changes during growth is unknown. We hypothesized that TBS would be positively correlated with growth and higher in growing girls participating in regular physical exercise.68 girls (mean age 12±0.3 years; BMI 18±2.8 kg/m2</...

Osteosarcoma is a heterogeneous tumor from the mesenchymal lineage, and is the most common form of primary bone cancer. Normally, lesions contain undifferentiated cancer stem cells (CSCs) that support uncontrolled growth/proliferation, and pre-osteoblasts that form excessive amounts of immature bone. CSCs are characterized by high expression of the transcriptional regulators Sox2 and yes-associated protein (YAP) that are essential for tumorigenicity. YAP is restrained by the H...

Objective: The BoneXpert method for automated bone age determination from hand X-rays also determines the cortical thickness T and the bone width W in the three middle metacarpals. From these, the method derives the cortical area A=π W T (1 – T/W), the metacarpal index MCI =A/(WW) and the Bone Health Index. Recently, the method has been extended down to new-borns, and the aim of this study is to report reference curves for these bone measures.M...

Introduction: Parathyroid hormone (PTH) measurement is of use in i) differential diagnosis of hypercalcaemia and ii) patients with renal impairment at risk of bone disease. PTH immunoassays are complicated by cross-reactivity with truncated (inactive) variant forms, which accumulate in patients with renal impairment. PTH assay variability is a critical governance issue in renal medicine, suggesting an MS-based reference method is required.Aim: To develop...