Bone Abstracts

RANKL induced osteoclastogenesis is mediated by several transcription factors such as NF-κB, AP-1 and Nfatc1. We have found that also cysteine proteinases are involved in the signaling pathway downstream RANK. Thus, cystatin C, Z-RLVG-CHN2 (the sequence of which is based upon one of the enzyme inhibitory domains in cystatin C) and the fungal molecule E-64 – inhibit RANKL induced mouse and human osteoclast formation in vitro (Strålberg et ...

The aims of this study were to establish the prevalence of the high bone mass (HBM) phenotype in a cohort of Spanish postmenapausal women (BARCOS); to determine whether any of the HBM cases carry LRP5 or DKK1 mutations; to test the hypothesis of an inverse correlation between the number of common variant risk alleles and HBM; and to characterize the expression of osteoblast-specific and Wnt pathway genes in primary osteoblast RNA samples from two HBM cases.</...

The aim of the study is to compare the performance of FRAX vs TBS adjusted FRAX using Leslie B et al.1 method to better identify women at high fracture risk. The OsteoLaus cohort (1500 women 50–80 years living in Lausanne, CH) started in 2010. CRF for OP, FRAX, spine and hip BMD, VFA by DXA and TBS were recorded. Sensitivity and specificity in regard to vertebral fracture grade 2 and 3 has been calculated. Net reclassification improvement (NRI) had als...

Introduction: Osteoporosis and fragility fractures are recognized complications of rheumatoid arthritis (RA). Previously Riches et al. described a patient with celiac disease and severe osteoporosis in whom neutralizing antibodies to osteoprotegerin (OPG) were present. The aim of this study was to determine if OPG autoantibodies were present in patients with RA and other rheumatic diseases and to relate these to clinical features.Methods: We dev...

Brittle bones have been reported in children, adolescents and adults with cystic fibrosis (CF), independently of sex; this has been termed CF-related bone disease. In CF patients with the F508del mutation in the (Cftr) gene, vertebral fractures and the subsequent dorsal kyphosis decrease pulmonary function, thus accelerating the course of the disease. Mice with the homozygous F508del mutation in CFTR develop a severe osteopenic phenotype early on, in both sexes (Le He...

Muscle size and function are closely correlated with skeletal development. Examining the relationship between muscle and bone is thus of central interest in clinical bone research. Surprisingly, however, there is little information on how to evaluate the functional muscle-bone relationship in clinical studies. Many past studies on muscle–bone interaction seem to have analyzed muscle and bone measures that were convenient to collect but did not evaluate a specific model of...

Objective: Idiopathic hypercalciuria (IH) is defined as excessive 24 h urinary calcium excretion (>4 mg/kg per 24 h), that persists after correction of dietary imbalances in the absence of secondary causes. Recent studies with DXA in children with IH provide evidence of decreased areal BMD. We used peripheral quantitative computed tomography (pQCT) of the tibia, to test the hypothesis that IH results in decreases of volumetric (mg/cm3) BMD of the trabecular and/...

Background: Osteogenesis Imperfecta is commonly due to dominant mutations in type I collagen genes, COL1A1 and COL1A2. Recessive forms, which are rarer, are caused instead by mutations in various genes coding for proteins involved in collagen post-translational modifications, folding and secretion. A novel disease locus, SERPINF1, coding for pigment-epithelium-derived-factor (PEDF), a likely key factor in bone deposition and remodelling, has been fou...

Fractures are very common and affect 2% of the population per annum. Fragility fractures represent the greatest unmet need and are associated with high rates of morbidity and mortality. Currently, there is no approved therapy for enhancing healing of fragility fractures. We previously reported that upregulation of the early inflammatory response following skeletal injury can promote fracture repair (Glass et al PNAS 2011). Inflammation represents the earliest response followin...

Background: Paget’s disease of Bone (PDB) has a strong genetic component and a candidate locus for the disease has been identified on chromosome 14q32, tagged by rs10498635 located within RIN3 (Albagha et al, Nat Genet 2011). RIN3 encodes a protein that acts as a guanine nucleotide exchange factor for Rab5b and Rab31. Here we investigated the candidacy of RIN3 as a predisposing gene for PDB.Methods: We studied expression of RIN3 by quantita...