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...

Increasing interest is focusing on the role of the FGF-23/Klotho axis in mediating vascular calcification. However, the underpinning mechanisms have yet to be fully elucidated. Murine VSMCs were cultured in calcifying medium for a 21-day period. FGF-23 mRNA expression was significantly up-regulated by 7 days (1.63-fold; P<0.001), with a concomitant increase in protein expression. mRNA and protein expression of both FGFR1 and Klotho were confirmed. Increased FGF-23...

Short stature and osteoporosis are common in DMD. Disease progression can be slowed by glucocorticoids but these are associated with further growth retardation and skeletal fragility. The defect in growth and skeletal development in children with DMD is probably multifactorial and not solely dependent on glucocorticoid exposure. The muscular dystrophy x-linked (mdx) mouse is the most commonly used animal model of DMD. However, its growth phenotype has not been studied...

Objective: Evaluate the clinical characteristics of all Latin American pediatric patients with Gaucher disease type 1 (GD1) enrolled in the ICGG Gaucher Registry at baseline and investigate long-term outcomes and clinical benefit of prolonged imiglucerase/alglucerase therapy in patients with manifestations of GD1 at baseline.Methods: All Latin American patients with GD1 in the ICGG Gaucher Registry (NCT00358943) who were <18 years of age at the start...

Bone has recently emerged as a novel endocrine organ regulating glucose metabolism. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralisation by generating the mineralisation inhibitor pyrophosphate. In clinical studies increased activity of NPP1 has been found in patients with insulin resistance, and it has been shown to directly inhibit the insulin receptor. We hypothesised that mice lacking NPP1 (Enpp1−/−) would exhibit im...

We used atomic force microscopy (AFM) to study the morphology and development of mineralization-competent matrix vesicles (MVs) secreted by chondrocytes isolated from WT and Phospho1−/− mice in order to validate the role of PHOSPHO1 in MV mineralization. All MVs appeared as flattened globular features either individually dispersed or connected to a mat-like structure. The mat-like structure very closely resembled type-X collagen that has been de...

The quantum leaps in scientific progress have frequently come from technological innovations, which can be referred to as the technology push. In the life-sciences this has been exemplified by the emergence of all kinds of ‘omics’ technologies reflecting the capacity to analyse complete and complex molecular mixtures in a hypothesis-free approach, also known as ‘fishing expeditions’ by more sceptical fellow scientists. Such approaches have been developed fo...

Genetic approaches to bone physiology utilising judicious gain and loss of function models have identified bone as an endocrine organ, being involved in the regulation of energy metabolism and reproduction. Recent advances expand our understanding and identify a new and unconventional role of bone beyond its classical functions. PHOSPHO1 is a bone specific phosphatase with a recognised role in bone mineralisation, but our present studies have now identified a novel role for PH...

Introduction: Perthes disease (PD), idiopathic femoral head avascular necrosis, often results in deformity. The underlying cause is unclear and long-term function is directly related to the roundness of femoral head. Current treatment include mechanical treatments and various surgical procedures, which are therapeutic but can’t prevent collapse. A multicentre, prospective, randomised controlled trial of 12 months zoledronic acid (ZA) in children with PD was conducted. We ...

Metabolic bone disease (MBD) of prematurity is a well-recognized complication of preterm birth. Yet there is limited evidence for the optimal assessment, monitoring, and subsequent bone health management.Retrospective audit of 171 infants born <32 weeks’ gestation between November 2012 and January 2014 at three Monash Health neonatal units (Melbourne, Australia) was undertaken. Infants had mean gestational age (GA) 28.6±2.1 weeks and birth ...