Bone Abstracts

Objectives: The present study aims to evaluate the longitudinal association of fat mass (FM), fat free mass (FFM) with bone stiffness index (BSI) in European children and adolescents over 2 and 6 years follow-up. METHODS: We included children of the IDEFICS/I. Family cohort, who participated in repeated measurements of BSI using calcaneal quantitative ultrasound (QUS), body composition using skinfold thickness, sedentary behaviours (SB) and physical activity (PA) using self-ad...

Objectives: An increased fracture risk is reported in children requiring recurrent courses of glucocorticoids. Reduced bone mineral density (BMD), particularly in the trabecular compartment, has also been demonstrated in a number of childhood diseases treated with glucocorticoids. The differential contribution of glucocorticoids and underlying inflammatory disease to bone demineralisation is poorly understood. Childhood nephrotic syndrome (NS) often follows a relapsing-remitti...

Objectives: Denosumab (Dmab) is a monoclonal antibody targeting RANKL administered by sub-cutaneous injection. Given its convenient mode of administration, our goal was to assess the safety and efficacy of Dmab compared to intravenous zoledronic acid (ZA) in pediatric osteoporosis.Methods: In this one-year pilot study (NCT02632916), children 4–16 years with low-trauma fractures due to osteoporosis were randomized 1:1 to receive ZA 0.025 mg/kg or Dma...

Objectives: Denosumab (Dmab) is a monoclonal antibody targeting RANKL administered by sub-cutaneous injection. Recent reports have raised concern about the ‘rebound phenomenon’ (hypercalcemia and increases in bone turnover markers, BTM) following Dmab in adults, and during treatment in children with osteogenesis imperfecta. The purpose of this report was to explore this phenomenon in children with osteoporosis associated with lower bone turnover.<p class="abstext...

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 ...

Objectives: We sought to identify the disease-causing mutations in two unrelated girls with a clinical diagnosis of osteogenesis imperfecta type IV.Methods: Whole-exome sequencing and cellular studies in skin fibroblasts were conducted.Results: We identified two homozygous variants in SPARC (NM_003118.3; c.497G>A (p.Arg166His) in individual 1; c.787G>A (p.Glu263Lys) in individual 2). Secreted protein, acidic, cyste...

Objectives: Osteogenesis imperfecta (OI) is a bone disease mainly caused by collagen type I mutations and characterized by bone fragility. No definitive cure is available and the search for novel treatments is necessary. The small teleost D. rerio is particularly appealing for drug screening approaches. A zebrafish OI model (Chihuahua) carrying in heterozygosis the G574D substitution in the α1 chain of collagen type I is available. To use this model for ...

Objectives: Osteogenesis Imperfecta (OI) is a heritable brittle bone disease mainly caused by mutation of COL1A1 or COL1A2. Treatment with bisphosphonate is not effective enough in patients with severe OI. 4-phenylbutyric acid (4-PBA) may become a new medicine, which was reported to ameliorate the phenotype of an OI zebrafish model. In the present study, we aimed to analyze the pathology of OI and the effects of 4-PBA on patient-derived fibroblasts and induced pluripotent stem...

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="...