Bone Abstracts

Multiple myeloma (MM) is associated with lytic bone destruction leading to high fracture incidence in the vertebrae. Accurate assessment of fracture risk is required for physicians to determine the necessity for surgery. This risk is currently determined by examining lesion size or number; however, this method does not consider the biomechanical attributes of the bone. Finite element (FE) modelling can simulate mechanical loading on vertebral bodies, and estimate mechanical in...

Aim: Scoliosis is a common skeletal problem affecting 10–30% of patients with neurofibromatosis type 1 (NF1). NF1 patients have been shown to have reduced bone mineral density (BMD) which may play a role in the pathogenesis or progression of scoliosis. Our centre is one of four international centres currently evaluating the efficacy of various spinal imaging techniques and BMD as predictors for scoliosis in NF1. In our cohort we measured the lumbar spine (LS) BMD both by ...

Fibrodysplasia ossificans progressiva (FOP) is a rare debilitating genetic disease characterized by abnormal progressive heterotopic endochondrial ossification of soft tissues. FOP results from mutations in the intracellular domain of the type I BMP receptor ACVR1 (ALK2) the most common of which is R206H. FOP mutations alter the sensitivity of ACVR1 to Activin A from an antagonist to an agonist. We have previously shown that Activin A is necessary and sufficient for driving he...

Background: Peroxisomal Biogenesis Disorders (PBD) is a group of rare metabolic diseases in which peroxisomal function is disrupted. PBD encompasses Zellweger Syndrome Spectrum (ZSS) disorders, which range in severity from classical ZS with severe neurological impairment and markedly reduced life expectancy to Refsum Disease presenting later in childhood. Recent fragility fractures in our ZSS patients in very early childhood prompted case series review.P...

Fanconi anemia (FA) is a rare genetic disease associated with a progressive decline in hematopoietic stem cells leading to bone marrow failure. FA is also characterized by various developmental defects including short stature and skeletal malformations of the upper and lower limbs. Indeed, more than half of children affected with FA have radial-ray abnormalities with a tendency to early osteoporosis and osteopenia. However, the underlying mechanisms leading to bone defects in ...

Background: Hypercalcaemia is a risk following stem cell transplant (SCT) for all types of autosomal recessive osteopetrosis (ARO) due to restored osteoclast differentiation. This can be particularly severe in the osteoclast-poor (OP) form involving the tumour necrosis factor receptor superfamily 11A (TNFRSF11A) gene, encoding RANK. Denosumab, a monoclonal antibody blocking RANK activation, has been described for refractory post-SCT hypercalcaemia in two cases. Our case adds n...

Objectives: X-linked hypophosphatemia (XLH) is a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. This pilot study aims to apply novel imaging techniques to asses the musculoskeletal phenotype of XLH patients by bidirectional axial transmission (BDAT) ultrasound, magnetic resonance spectroscopy (MRS) and high resolution peripheral quantitative computed tomography (HR-pQCT).Methods: BDAT bone ultrasound of the radius and...

FOP is an autosomal dominant disorder characterized by early onset, episodic and progressive ossification of skeletal muscle and associated connective tissue. FOP is driven by mutations in the intracellular domain of ACVR1 (ALK2), the most common of which is R206H. However, rare FOP causing mutations exist throughout the GS and the kinase domain of Acvr1. Several of these mutations result what appears to be a more severe FOP phenotype that includes significant developmental ab...

Maternal vitamin D status has been positively associated with infant bone mass in observational studies. We therefore evaluated whether 1000 IU/day cholecalciferol during pregnancy would lead to greater offspring bone mass at birth, in a UK, multicentre, randomised, double-blind, placebo-controlled trial (MAVIDOS, ISRCTN82927713).At 12 weeks’ gestation, pregnant women with a serum 25-hydroxyvitamin D [25(OH)D] 25-100 nmol/l were randomised to either...

Objectives: Single nucleotide polymorphisms (SNP) in genes related to vitamin D metabolism have been associated with 25-hydroxyvitamin D (25(OH)D) status, but these relationships have not been examined in pregnancy or following antenatal vitamin D supplementation. We assessed whether SNPs in DHCR7 (7-dehydrocholesterol reductase), CYP2R1 (25-hydroxylase), CYP24A1 (24-hydroxylase) and GC (Vitamin D binding protein) were associated with the re...