Bone Abstracts

Objectives: Asfotase alfa (AA), an enzyme replacement therapy, is the only approved treatment for pediatric-onset hypophosphatasia (HPP). We evaluated the safety profile of AA from the clinical trial program spanning pediatric and adult patients.Methods: Safety data were pooled from 4 open-label, multicenter studies in children aged ≤3 years (study 002/003 [NCT00744042/NCT01205152]; n=11) and ≤5 years (study 010-10 [NCT01176266]; <em...

Objectives: Cross-sectional studies show that exercise may have positive effects on bone outcomes in youth. However, there is no evidence from longitudinal studies, which type of sports can induce improvements in bone acquisition in adolescent athletes. Therefore, this study aimed to investigate the longitudinal differences in bone acquisition and bone metabolism between adolescent males participating in osteogenic (football) and non-osteogenic (swimming, cycling) sports compa...

Objectives: Osteogenesis imperfecta (OI) is a heritable disorder characterized by bone deformity and skeletal fragility. Cartilage associated protein (CRTAP), proline 3-Hydroxylase 1 (P3H1) and Cyclophylin B (PPIB) are components of the endoplasmic reticulum (ER)-resident complex involved in the 3-hydroxylation of specific proline residues in collagen type I α chains. Mutations in these proteins are responsible for recessive OI type VII, VIII and IX, respectively. Murine ...

Objectives: The Brtl mouse, a unique model for the autosomal dominant forms of osteogenesis imperfecta was used to prove the feasibility of a lentiviral-shRNA-based strategy to improve collagen quality by targeting the mutant Col1a1 allele at the point mutation responsible for the causative substitution Gly349Cys. The ability to specifically suppress the mutant allele should convert the moderate Brtl outcome to the mild one caused by quantitative defect.<p class="...

Dominant osteogenesis imperfecta (OI) is a bone disease mainly caused by collagen type I mutations and characterized by bone fragility and growth delay. Nowadays no definitive cure is available. A zebrafish OI model (Chihuahua) carrying an heterozygous G574D substitution in the α1 chain of collagen type I was generated by ENU mutagenesis and is available in our laboratory. Control (WT) and mutant (Chi+/−) fish growth was followed up from day 1 post fertilization to ...

Bone tissue homeostasis requires the coordinated activity of osteoblasts, the bone forming cells, of osteoclasts, the bone resorbing cells, and of osteocytes, generally referred as the bone mechano-sensors. In this contest, osteoblasts are the mesenchymal cells secreting the extracellular matrix components on which hydroxyapatite crystals are then deposited. The most abundant protein of this organic matrix is type I collagen, a heterotrimeric secretory protein, synthesized as ...

Objective: FOP is a rare, severely disabling disease characterized by episodic flare-ups and accumulation of heterotopic ossification (HO) leading to restricted movement, physical disability, and early death. Data from two Phase 2 interventional studies and one natural history study (NHS) were used to evaluate whether palovarotene could reduce HO following an FOP flare-up.Methods: HO volume at the flare-up site was determined by CT at baseline and 12 wee...

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...

Introduction: Administration of antibodies that neutralize sclerostin has been demonstrated to increase bone mass. We report the key findings of a Phase 2 study of the human sclerostin antibody, blosozumab (bmab).Methods: Study GSDB was a randomized, parallel-design, double-blind placebo-controlled study, designed to assess the dose–response relationship of bmab in postmenopausal women with low bone mineral density (BMD; lumbar spine (LS) T...

see PP282....