Searchable abstracts of presentations at key conferences on calcified tissues

ba0001oc3.4 | Osteoporosis pathophysiology and genetics | ECTS2013

Cortical exceeds trabecular bone loss before menopause but net bone loss is modest because periosteal apposition occurs

Bjornerem Ashild , Wang Xiaofang , Ghasem-Zadeh Ali , Bui Minh , Hopper John , Zebaze Roger , Seeman Ego

Introduction: Bone mineral density decreases before menopause and is held to be due to trabecular, not cortical, bone loss. Yet neither a negative bone balance, nor accelerated remodelling occurs before 45 years of age. We hypothesized that bone loss will first appear after 45 years and will be cortical (as 80% of bone is cortical).Methods/design: Images of distal tibia acquired using high-resolution peripheral quantitative computed tomography (Scanco Me...

ba0001pp29 | Arthritis and other joint diseases: translational and clinical | ECTS2013

A deletion mutation of the gene P58IPK, the cellular inhibitor of PKR and PERK, results in a degenerative joint phenotype in mice

Gilbert Sophie , Nowell Mari , Bonnet Cleo , Ladiges Warren , Morton John , Duance Vic , Mason Debbie

Objective: The protein kinases, PKR, and PERK have been implicated in pro-inflammatory cytokine-mediated cartilage degradation in vitro and endoplasmic reticulum stress-induced arthritis respectively. The objective of this study was to establish whether loss of P58IPK, an inhibitor of PKR and PERK, results in a degenerative joint phenotype in vivo.Methods: Sections of knee joints from P58IPK-null and wild-type mice...

ba0001pp92 | Bone development/growth and fracture repair | ECTS2013

Identifying scoliosis in population-based cohorts: development and validation of a novel method based on total body dual energy X-ray absorptiometry scans

Taylor Hilary , Harding Ian , Hutchinson John , Nelson Ian , Blom Ashley , Tobias Jon , Clark Emma

Background: Scoliosis is lateral curvature of the spine ≥10°, as measured on standing spinal radiographs. There are no published studies that have investigated determinants of scoliosis using a prospective cohort design, making the establishment of cause and effect difficult. Several large population-based cohorts exist throughout the world with a wide range of data already collected, and while spinal imaging with radiographs is not generally collected in these coho...

ba0001pp93 | Bone development/growth and fracture repair | ECTS2013

Smaller bones at aged 10 predicts scoliosis at aged 15: results from a population-based birth cohort

Taylor Hilary , Blom Ashley , Harding Ian , Hutchinson John , Nelson Ian , Tobias Jon , Clark Emma

Background: Scoliosis is lateral curvature of the spine, and adolescent idiopathic scoliosis (AIS) accounts for the majority of cases of scoliosis. One potential determinant of scoliosis that is of great interest is bone size and density. However, there are no published studies that have investigated determinants of scoliosis using a prospective cohort design making the establishment of cause and effect difficult.Methods: This study was based on the Avon...

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...

ba0002op11 | (1) | ICCBH2013

Artistic gymnasts display micro-architectural advantages over trampolining and tumbling gymnasts: a high resolution peripheral quantitative computed tomography study

Burt Lauren A , Stanger Scott P , Schipilow John D , Boyd Steven K

Participation in high impact sports during growth increases bone quality. Gymnasts have previously displayed increased bone mass and strength at both the upper and lower limbs compared with controls. However, it is not yet understood how bone microarchitecture is affected by gymnastics participation, and if this differs based on gymnastics discipline. Therefore, the objective of this study was to investigate the influence of gymnastics discipline on bone microarchitecture in a...

ba0002p132 | (1) | ICCBH2013

Studies on bone and osteoclasts in patients with Shwachman Diamond syndrome

Helfrich Miep , Mellis David , Coxon Fraser , Greenhorn John , Kuijpers Taco , Crockett Julie

Shwachman Diamond syndrome (SDS; MIM 260400) is a monogenic, autosomal recessive, pancreatic condition often accompanied by low bone mass and fracture. In SDS, as in cystic fibrosis, a low bone mass may be secondary to poor nutrition or chronic low-grade infection, but it has also been suggested there may be a primary bone phenotype. Paradoxically, recent studies in cell lines and in a mouse knockout for the SBDS gene, have suggested changes in important osteoclast gr...

ba0003ht3 | (1) | ECTS2014

Consistent, marked and rapid increases in hip and spine BMD with the PTHrP1-34 analog, abaloparatide (BA058), compared to placebo and teriparatide

Yates John , Alexandersen Peter , Krogsaa Annesofie , Nedergaard Bettina , Clarkin Marcie , Hattersley Gary , Karsdal Morten , Christiansen Claus

Background: Treatments that result in greater increases in bone mass of normal quality by increasing bone formation rather than decreasing resorption are needed. Abaloparatide is a synthetic analog of PTHrP1-34 that has shown strong efficacy to increase bone mass and bone strength in animals. We conducted two phase 2 placebo-controlled studies both of which included abaloparatide 80 μg sc daily (ABL) in postmenopausal women with osteoporosis. Study 1 also inclu...

ba0003lb1 | (1) | ECTS2014

Endochrondral ossification, mesenchymal stem cell and Wnt pathway specific loci predict differential skeletal effects in high bone mass

Gregson Celia , Kemp John , Marshall Mhairi , Smith George Davey , Brown Matthew , Duncan Emma , Tobias Jon

Extreme high bone mass (HBM) may be monogenic (e.g. LRP5 mutations) or polygenic, due to variants in the same genes determining bone mineral density (BMD) as found in the general population. We aimed to determine how variation in established BMD loci, in different functional pathways, explains the HBM phenotype.241 unexplained HBM cases (lumbar spine(LS)1+total hip(TH) Z-scores≥+4.4) were recruited from 15 UK centres, by screening...