Bone Abstracts

Background: We identified a family with early onset X-linked osteoporosis and fracturesMethods: We performed whole exome sequencing of the X chromosome in three affected members. After discovering a putative pathogenic variant we performed Sanger sequencing of all exons of this gene in other members of this family and in 95 unrelated men suspected of OI type I without COL1A1/2 mutations. We also genotyped a SNP in this gene (minor allele frequency 0.02) ...

Background: LRP4 gene encodes a member of the LDL receptor gene family, expressed by osteoblasts, which negatively regulates Wnt/β-catenin signalling by potentiating the inhibitory effect of sclerostin on LRP5 signalling. Previously, missense mutations of LRP4 have been described in patients with the phenotype of sclerosteosis, a disease associated with high bone mass and bone overgrowth. Here we investigated the hypothesis the LRP4 mut...

In previous work we identified 63 common variants (MAF>5%) from 56 loci associated with BMD fully comprising non-coding regions of the genome. We hypothesized that genes may harbour both common and rare variants in the protein-coding regions may influence BMD variation. The availability of the ‘exome-chip’ with 235 933 protein-coding variants (non-synonymous, splice sites and stop-altering) provides a feasible way to identify low-frequency variants in exomes....

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...

Although X-linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia leading to a generalized mineralization defect with rickets (and/or osteomalacia), densitometric studies point towards a tendency towards an elevated bone mineral density (BMD). The aim of this cross-sectional in vivo study was to assess bone geometry, volumetric BMD (vBMD), microarchitecture and estimated bone strength using high-resolution peripheral quantitative computed tomograph...

Objective: Although metabolic syndrome is common in gout patients, recent reports that bone mineral density may actually be reduced (and falls common) in this group have led researchers to hypothesise that osteoporotic fracture may be more common in subjects with gout than in healthy controls. We tested this hypothesis in a national Danish registry.Material and Methods: We identified subjects as new users of allopurinol, a proxy for gout, for the years 1...