Searchable abstracts of presentations at key conferences on calcified tissues

ba0001pp137 | Cancer and bone: basic, translational and clinical | ECTS2013

Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma

Lamoureux Francois , Baud'huin Marc , Ory Benjamin , Gleave Martin , Heymann Dominique , Redini Francoise

Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, zoledronic acid triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), whi...

ba0001pp139 | Cancer and bone: basic, translational and clinical | ECTS2013

New PI3Kα-specific inhibitor, BYL719: therapeutic interest in osteosarcoma

Gobin Berengere , Baud'huin Marc , Charrier Celine , Hervouet Soizic , Lezot Frederic , Blanchard Frederic , Heymann Dominique

It has been established that disturbances of intracellular signaling pathways strongly contribute to the oncologic process. Indeed, phosphatidylinositol-3-kinase (PI3K) became a key target in cancer therapy, due to its high frequency of mutation and/or gain of function of its catalytic subunits in cancer cells. In this context, we investigated the in vitro and in vivo effects of a new PI3Kα inhibitor, BYL719 (Novartis Pharma), on bone cells and its thera...

ba0001pp170 | Cell biology: osteoblasts and bone formation | ECTS2013

Calcium transport and phosphomonohydrolase activity by proteoliposomes harboring annexin V and alkaline phosphatase

Bolean Mayte , Simao Ana Maria , Kiffer-Moreira Tina , Hoylaerts Marc , Millan Jose Luis , Ciancaglini Pietro

The biomineralization process is initiated inside matrix vesicles (MVs), with phosphate and calcium ions crystallizing as hydroxyapatite. This process is accomplished by the activities of several proteins, such as annexins (e.g. AnxV) that mediates Ca2+ influx into MVs and tissue-nonspecific alkaline phosphatase (TNAP), a phosphomonohydrolase that uses ATP and PPi as substrates. Dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS...

ba0001pp318 | Osteoporosis: evaluation and imaging | ECTS2013

Binding kinetics of fluorescent bisphosphonates as a tool for monitoring bone dynamics in vivo

Tower Robert , Campbell Graeme , Muller Marc , Will Olga , Grundmann Frederieka , Schem Christian , Gluer Claus , Tiwari Sanjay

Bone resorption and deposition occur in a tightly regulated fashion reflecting the coupled activities of osteoclasts and osteoblasts. Several pathological conditions perturb this balance between bone synthesis and resorption, including osteoporosis and skeletal metastases. The uncoupling of remodeling activities contributes to disseminated tumor cells homing to the bone and to tumor growth in bone. Therefore, a reliable marker of bone remodeling would be useful to provide a st...

ba0001pp339 | Osteoporosis: evaluation and imaging | ECTS2013

What is the performance in vertebral fracture discrimination by bone mineral density, micro-architecture estimation, and FRAX in stand-alone, combined or adjusted approaches: the OsteoLaus Study

Lamy Olivier , Krieg Marc-Antoine , Stoll Delphine , Aubry-Rozier Berengere , Metzger Marie , Hans Didier

The aim of the study is to compare the performance of FRAX vs TBS adjusted FRAX using Leslie B et al.1 method to better identify women at high fracture risk. The OsteoLaus cohort (1500 women 50–80 years living in Lausanne, CH) started in 2010. CRF for OP, FRAX, spine and hip BMD, VFA by DXA and TBS were recorded. Sensitivity and specificity in regard to vertebral fracture grade 2 and 3 has been calculated. Net reclassification improvement (NRI) had als...

ba0002p48 | (1) | ICCBH2013

Pubertal induction with testosterone of a boy with bilateral anorchia guided by the development of his monozygotic twin brother

Van Caenegem Eva , Vandewalle Sara , Taes Youri , Kaufman Jean-Marc , Craen Margarita , Guy T'Sjoen

Introduction: We describe a monozygotic twin pair, of which one boy was diagnosed with anorchia. Both were followed-up till age 17.Case report: At birth, in one twin 46 XY boy (A), testes were not palpable while his brother (B) was unaffected. Stimulation with human chorionic gonadotrophin (hCG) and orchidopexia were unsuccessful at age 3. A second hCG-stimulation test was performed at age 8, where serum testosterone response failed to increase. No testi...

ba0002p96 | (1) | ICCBH2013

Cross-sectional associations of sex steroids with bone maturation, bone mineral density and bone geometry in boys

Vandewalle Sara , Taes Youri , Fiers Tom , Toye Kaatje , Roggen Inge , Kaufman Jean-Marc , De Schepper Jean

Background: Although both testosterone and estrogens are considered essential for normal bone growth, epiphyseal maturation and bone mass accrual during adolescence, only very few data concerning the changes of estrogens, bone maturation, bone mineral density (BMD) and bone geometry in healthy boys at different pubertal stages have been published.Objectives: This study aimed to analyze the relationship between sex steroids and more especially estrogens a...

ba0003pp111 | Cell biology: osteoblasts and bone formation | ECTS2014

Osteopontin as a novel substrate for proprotein convertase 5/6 (PCSK5) in bone

Hoac Betty , Susan-Resiga Delia , Essalmani Rachid , Marcinkiweicz Edwidge , Barros Nilana , Seidah Nabil , McKee Marc

Proprotein convertase PC5/6 (Pcsk5) is expressed in mouse bone and Pcsk5 epiblast-specific conditional knockout mice have a bone phenotype displaying small size, delayed ossification and additional thoracic segments and ribs. Some features are attributed to growth and developmental factor 11 (GDF11) – a known substrate for PC5/6 – while the delayed mineralization has yet to be explained. Osteopontin (OPN) is a bone matrix protein with roles in miner...

ba0003pp225 | Osteoporosis: evaluation and imaging | ECTS2014

Utilizing bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate changes in long bone and vertebra bone metabolism using in vivo fluorescent molecular tomography

Tower Robert J , Muller Marc , Will Olga , Tiwari Sanjay , Gluer Claus C , Campbell Graeme M

Bone resorption and formation occur in a tightly regulated fashion reflecting the coupled activities of osteoclasts and osteoblasts. Several pathological conditions perturb this balance, including osteoporosis and skeletal metastases. In the case of metastases, the uncoupling of resorption and formation activities contributes to disseminated tumor cells homing to the bone and to tumor growth within the bone in highly localized regions. Therefore, a site-specific marker of bone...