Searchable abstracts of presentations at key conferences on calcified tissues

ba0001oc3.1 | Osteoporosis pathophysiology and genetics | ECTS2013

Heavy cannabis use negatively impacts on bone density: a population based prospective study

Sophocleous Antonia , McKenzie James , Robertson Roy , Ralston Stuart H

The endocannabinoid system has important effects on bone mass and bone turnover. Mice with targeted inactivation of type 1 (CB1) and type 2 (CB2) cannabinoid receptors develop osteoporosis with increasing age raising the possibility that cannabinoid receptor agonists might protect against age-related bone loss. Since cannabis is the most widely used illegal drug and its main psychotropic component -Δ9-tetrahydrocannabinol (THC)- is an agonist at CB1 and CB2 receptors, we ...

ba0001pp383 | Osteoporosis: pathophysiology and epidemiology | ECTS2013

Detection of autoantibodies to osteoprotegerin in patients with rheumatoid arthritis and their association with disease activity

Hauser Barbara , Riches Philip , Gilchrist Tamara , Wilson Jim F , Fraser William D , Ralston Stuart H

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...

ba0003oc1.1 | Phosphate metabolism, fracture repair and osteoarthritis | ECTS2014

Type 2 cannabinoid receptor protects against osteoarthritis in mice

Sophocleous Antonia , Borjesson Anna E , Salter Donald M , Ralston Stuart H

Background: Cannabinoid receptors are expressed in synovial joints but their role in joint disease is unknown. Here we examined the role of the type 2 cannabinoid receptor (CB2) in the pathogenesis of age-related osteoarthritis and osteoarthritis caused by destabilisation of the medial meniscus (DMM) in WT and CB2-deficient mice (Cnr2−/− mice).Methods: The severity of arthritis was graded histologically according to standard techni...

ba0005oc5.3 | Risk factors for fracture, Pagets disease of bone and musle and bone | ECTS2016

Osteoprotegerin autoantibodies are independently associated with low hip bone mineral density and increased fracture risk in patients with ankylosing spondylitis

Hauser Barbara , Zhao Sizheng , Visconti Micaela R , Riches Philip L , Goodson Nicola J , Ralston Stuart H

Osteoporosis and vertebral fractures are recognised complications of ankylosing spondylitis (AS) but the underlying causes are incompletely understood. Osteoprotegerin (OPG) is a decoy receptor for RANK-L and inhibits osteoclastogenesis. We have previously demonstrated that antibodies to OPG (OPG-Ab) are associated with osteoporosis and increased bone turnover in patients with autoimmune diseases. The aim of this study was to determine whether OPG-Abs were detectable in AS pat...

ba0005p241 | Genetics and Epigenetics | ECTS2016

Identification of a novel locus on 2q13 of large effect size which predisposes to clinical vertebral fractures independently of BMD: the GEFOS consortium

Alonso Nerea , The Clinical Vertebral Fracture Consortium Nerea , Uitterlinden Andre , Rivadeneira Fernando , Ralston Stuart H

Vertebral fractures are the most common complication of osteoporosis, but little is known about the genetic determinants of susceptibility. Here we present the results of a genome wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with replication in 667 cases and 2105 controls. A locus tagged by a less frequent variant (rs10190845, A-allele MAF=0.05) was identified on chromosome 2q13 as a strong predictor of clinical verte...

ba0003oc4.4 | Genetics of bone disease | ECTS2014

Variants in RIN3 predispose to Paget's disease of bone

Vallet Maheva , Sophocleous Antonia , Warner Jon , Morris Stewart W , Wilson James F , Albagha Omar ME , Ralston Stuart H

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...

ba0003oc5.2 | Important pathways in bone biology and cancer | ECTS2014

Regulation of bone metastasis by the IKKβ/FoxO3a axis

Marino Silvia , Logan John G. , Sophocleous Antonia , Mollat Patrick , Mognetti Barbara , Ventura Luca , Sims Andrew H. , Rucci Nadia , Ralston Stuart H. , Idris Aymen I.

IκB Kinase β (IKKβ), a key component of NFκB signaling, plays an important role in bone disease and cancer. Genetic and pharmacological inhibition of IKKβ/NFκB signaling increase bone mass and protect against ovariectomy- and inflammation-induced bone loss. Here, we describe a previously unknown role of the IKKβ/FoxO3a axis in bone metastasis associated with breast cancer. We observed that IKKβ expression is prevalent in invasive breast ...