Searchable abstracts of presentations at key conferences on calcified tissues

ba0005ht5 | (1) | ECTS2016

Superior Gains in Bone Mineral Density (BMD) and Estimated Strength at the Hip for Romosozumab Compared With Teriparatide (TPTD) in Women With Postmenopausal Osteoporosis Transitioning From Bisphosphonate Therapy: Results of the Phase 3 Open-label STRUCTURE Study

Langdahl B , Libanati C , Crittenden D B , Bolognese M A , Brown J P , Daizadeh N S , Dokoupilova E , Engelke K , Finkelstein J S , Genant H K , Goemaere S , Hyldstrup L , Jodar-Gimeno E , Keaveny T M , Kendler D , Lakatos P , Maddox J , Malouf J , Massari F E , Molina J F

STRUCTURE was a phase 3, open-label study evaluating the effect of romosozumab or TPTD for 12 months in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy (NCT01796301). This study enrolled women with postmenopausal osteoporosis who had taken an oral bisphosphonate for ≥3 years prior to screening and alendronate in the year prior to screening; had a BMD T-score ≤−2.5 at the total hip (TH), lumbar spine (LS), or femoral neck (FN);...

ba0005p234 | Genetics and Epigenetics | ECTS2016

SNP regulation of miRNA expression and its association with osteoporosis

De-Ugarte Laura , Caro-Molina Enrique , Rodriguez-Sanz Maria , Garcia-Perez M A , Olmos J M , Sosa-Henriquez Manuel , Perez-Cano Ramon , Gomez-Alonso Carlos , Del Rio Luis , Mateo-Agudo Jesus , Navarro-Casado Laura , Gonzalez-Macias Jesus , Del Pino-Montes Javier , Munoz-Torres Manuel , Diaz-Curiel Manuel , Malouf Jorge , Perez-Catrillon J L , Nogues Xavier , Garcia-Giralt Natalia , Diez-Perez Adolfo

Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotype variability. The aim of this study was to identify osteoporosis-related SNPs by affecting the expression levels of mature microRNAs.The first approach was to perform an association analysis of putative functional SNPs located in pri-miRNA sequences of bone-related microRNAs with the lumbar spine and femoral neck (FN) bone mineral den...

ba0005oc4.1 | Catabolism and metabolism | ECTS2016

A small molecule inhibitor of TRAF6 dependent signaling reduces osteoclastogenesis and prevents ovariectomy induced bone loss

Marino Silvia , Bishop Ryan , Bendle Gavin , Nicolaes Gerry , Lutgens Esther , Idris Aymen

Tumour necrosis factor receptor-associated factor 6 (TRAF6) plays a key role in osteoclastogenesis through the regulation of RANK/CD40 TRAF6-mediated signaling. Mice deficient in TRAF6 exhibit high bone mass and were protected against inflammation-induced bone loss. Here we describe the effects of a small-molecule 6877002 that has been shown to prevent the binding of TRAF6 to its domain on RANK/CD40 receptor on osteoclast formation in vitro and in vivo and on...

ba0005p32 | Bone biomechanics and quality | ECTS2016

Characterization of bone using ultrasonic waves and structural borne acoustic waves

Aygun Haydar , Barlow Chris , Yule Lawrence

An orthogonally-anisotropic Biot-Johnson-Allard (BJA) model in which the dependences of tortuosity on porosity and angle are determined empirically from acoustic measurements on bone replicas has been developed. Phase velocities and attenuations of the fast and slow waves versus frequency, porosity and angle of propagation have been predicted by using BJA model. The attenuation of the fast wave is below 0.5 Np/m throughout the frequency and propagation angle range. The attenua...

ba0006oc9 | (1) | ICCBH2017

Calcium carbonate supplementation of pregnant rural Gambian mothers alters offspring IGF-1 at age 7.5 years in a sex-dependent manner

Prentice Ann , Nigdikar Shailja , Moore Sophie

Objective: We have observed sex-specific effects of pregnancy calcium carbonate supplementation in 8–12 year old Gambian children, indicating slower growth after infancy in girls born to calcium-supplemented mothers but faster in boys.1,2 IGF-1 is a key driver of growth and is responsive to calcium supplementation.3 The aim of this study was to determine whether the pregnancy supplement had resulted in sex-specific effects on mid-childhood IGF1 of th...

ba0003oc4.1 | Genetics of bone disease | ECTS2014

PLS3 mutations in X-linked osteoporosis with fractures

Zillikens M Carola , van Dijk Fleur S , Micha Dimitra , Riessland Markus , Marcelis Carlo LM , de-Die Smulders Christine E , Milbradt Janine , Franken Anton A , Harsevoort Arjan J , Lichtenbelt Klaske D , van de Peppel J , Pruijs Hans E , Rubio-Gozalbo M Estela , Zwertbroek Rolf , Moutaouakil Youssef , Egthuijsen Jaqueline , van der Eerden B , Hammerschmidt Matthias , Bijman Renate , Semeins Cor M , Bakker Astrid D , Everts Vincent , Klein-Nulend Jenneke , Campos-Obando Natalia , Hofman Albert , te Meerman Gerard J , van Leeuwen JP , Verkerk Annemieke JMH , Uitterlinden Andre G , Maugeri Alessandra , Sistermans Erik A , Waisfisz Quinten , Meijers-Heijboer Hanne , Wirth Brunhilde , Simon Marleen EH , Pals Gerard

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) ...

ba0001pp282 | Genetics | ECTS2013

Phenotypic dissection of bone mineral density facilitates the identification of skeletal site specificity on the genetic regulation of bone

Kemp John P , Medina-Gomez Carolina , Estrada Karol , Heppe Denise , Zillikens Carola , Timpson Nicholas , Pourcain Beate , Ring Susan , Hofman Albert , Jaddoe Vincent V W , Smith George Davey , Uitterlinden Andre G , Tobias Jonathan H , Rivadeneira Fernando , Evans David M

Heritability of bone mineral density (BMD) varies at skeletal sites, possibly reflecting different relative contributions of environmental and genetic influences. To quantify shared genetic influences across different sites, we estimated the genetic correlation of BMD at the upper limb (UL), lower limb (LL), and skull (S) obtained from whole body DXA scans, using bivariate genome-wide complex trait analysis (GCTA). The study (n=9395) combined data from the Avon Longit...

ba0003pp69 | Bone development/growth and fracture repair | ECTS2014

Enhancement of fracture repair by upregulation of the innate immune response

Santo Ana Isabel Espirito , Chan James K , Glass Graeme E , Ersek Adel , Freidin Andrew , Williams Garry A , Gowers Kate , Jeffery Rosemary , Otto William R , Poulsom Richard , Feldmann Marc , Rankin Sara M , Horwood Nicole J , Nanchahal Jagdeep

Osteoporotic fractures are very common and represent an enormous unmet medical need. Our group has previously reported that addition of rTNF to the fracture site promotes fracture healing in C57/BL6 mice (Glass et al. PNAS 2011). Using a murine fracture model of endochondral healing, we observed that local addition of rTNF only accelerates fracture repair if administered within the first 24 h following injury. The optimal therapeutic dose is 1 ng. TNF is firs...