Searchable abstracts of presentations at key conferences on calcified tissues

ba0001pp203 | Cell biology: osteoblasts and bone formation | ECTS2013

Connectivity Map-based discovery of novel compounds that induce osteoblast differentiation

Brum A M , van de Peppel J , van Kerkwijk A , Janssen M , Schreuders-Koedam M , Strini T , Eijken M , van Leeuwen J P T M , van der Eerden B C J

Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. Little is currently known about what specific factors stimulate osteoblast differentiation from human mesenchymal stem cells (hMSCs). Therefore, the aim for this project is to determine novel factors and mechanisms involved in human bone production which can be targeted to treat osteoporosis, using gene expression profiling and bioinformati...

ba0002oc11 | Biology | ICCBH2013

Connectivity map-based discovery of novel compounds that induce osteoblast differentiation

Brum A M , de Peppel J van , van Kerkwijk A , Janssen M , Schreuders-Koedam M , Strini T , Eijken M , van Leeuwen J P T M , van der Eerden B C J

Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. Little is currently known about what specific factors stimulate osteoblast differentiation from human mesenchymal stem cells (hMSCs). Therefore, the aim for this project is to determine novel factors and mechanisms involved in human bone production which can be targeted to treat osteoporosis, using gene expression profiling and bioinformati...

ba0005oc1.4 | Clinical trials and osteoporosis treatment | ECTS2016

Relationship between total hip (TH) BMD T-score and incidence of nonvertebral fracture (NVFX) with up to 10 years of Denosumab (Dmab) treatment

Ferrari S , Adami S , Brown J P , Cosman F , Czerwiński E , de Gregorio L H , Malouf J , Reginster J-Y , Daizadeh N S , Wang A , Wagman R B , Lewiecki E M

The relationship between BMD T-score and FX risk has not been established in patients receiving osteoporosis therapy. In the FREEDOM Extension study, continuous DMAb therapy for up to 10 years increased BMD levels with no therapeutic plateau at lumbar spine or TH [Bone et al, ASBMR 2015]. Such improvements would only be meaningful if associated with FX reductions. We investigated the relationship between TH BMD T-score and NVFX in women who received DMAb during FREEDOM and tho...

ba0001oc3.5 | Osteoporosis pathophysiology and genetics | ECTS2013

Genome-wide association identifies a new susceptibility locus at 4q35 associated with clinical vertebral fractures in post-menopausal women: the GEFOS-GENOMOS consortium

Alonso N , Estrada K , Herrera L , Kabir D , Olmos J M , Sanudo C , Riancho J A , Oei L , Medina-Gomez M C , Stenkjaer L , Bjerre L , Langdahl B , Brown M A , Duncan E L , Sims M , Kaptoge S , Reeve J , Lewis J , Prince R , Reppe S , Olstad O K , Gautvik K M , Garcia-Giralt N , Nogues X , Mencej-Bedrac S , Marc J , del Pino J , Gonzalez-Sarmiento R , Wolstein O , Eisman J , Feenstra B , Melbye M , Albagha O M E , WTCCC , Davies G , Starr J , Deary I , Quintela I , Fernandez C , Carracedo A , Lucas G , Elosua R , Uitterlinden A G , Rivadeneira F , Ralston S H

Vertebral fractures (VF) defined by morphometric analysis of spine radiographs are the most common complication of osteoporosis. Those that come to medical attention, with symptoms such as back pain and kyphosis are termed clinical vertebral fractures (CVF) and account for significant morbidity and mortality. Although much progress was made in identifying loci for bone mineral density, the genetic determinants of CVF remain unclear. Here we present the initial results from a g...

ba0001pp167 | Cell biology: osteoblasts and bone formation | ECTS2013

Adipogenesis occurs at the expense of osteoblast differentiation in primary osteoblasts deficient in protease-activated receptor 2

Kularathna Pamuditha , Pagel Charles N , Hooper John D , Mackie Eleanor J

The G protein-coupled receptor, protease-activated receptor 2 (PAR2), is expressed by osteoblasts and required for normal skeletal growth and repair. Prostate cancer (PCa) cells commonly secrete proteolytic activators of PAR2 (including matriptase and kallikrein-related peptidase 4) and frequently form osteogenic metastases in bone. This study was undertaken to investigate the hypothesis that PAR2 activators released by PCa cells modulate osteo...

ba0001pp228 | Cell biology: osteoclasts and bone resorption | ECTS2013

Bisphosphonates differently affect jaw and long-bone marrow cells

Vermeer Jenny A F , Jansen Ineke D C , Renders Greetje A P , de Vries Teun J , Everts Vincent

Bisphosphonates (BPs) such as zoledronic acid (ZA) are widely used to treat bone diseases. The use of BPs can lead to osteonecrosis of the jaw (ONJ), but it is not clear why in particular the jaw bone is affected. Previously, it was shown that osteoclasts derived from different bone sites have different properties. We hypothesize that BPs have distinct effects on bone-site specific osteoclasts or precursors. To investigate this, female C57BL/6J mice were injected intraperitone...

ba0001pp280 | Genetics | ECTS2013

Association between dentinogenesis imperfecta and mutations in COLIA1 and COLIA2 genes

Andersson Kristofer , Dahllof Goran , Astrom Eva , Rubin C-J , Kindmark A , Lindahl Katarina , Ljunggren Osten , Malmgren Barbro

Introduction: Dentinogenesis imperfecta (DI) is a common dental aberration in patients with osteogenesis imperfecta (OI). Mutations that cause abnormal collagen chains will cause more serious types of OI and it has been claimed that DI should be a marker for qualitative defected collagen. It has also been supposed that normal development of teeth may be more dependent on normal α2(I) than normal α1(I) chains which are encoded by COLIA2 and COLIA1 ge...

ba0001pp433 | Osteoporosis: treatment | ECTS2013

Denosumab is associated with progressive improvements in hip cortical mass and thickness

Poole K , Treece G , Gee A , Brown J P , McClung M R , Wang A , Libanati C

Denosumab (DMAb) significantly improves bone strength at the hip, estimated by FEA from QCT scans, from baseline (B/L) and vs placebo (Pbo) (Keaveny ASBMR 2010). We determined the extent and distribution of mass and thickness changes at the proximal femur, a key skeletal site for fracture risk, using a novel cortical bone mapping technique on the same serial QCT scans. A FREEDOM substudy included 80 women who underwent hip QCT scanning at B/L and months 12, 24 and 36 during DM...