Searchable abstracts of presentations at key conferences on calcified tissues

ba0005p102 | Cancer and bone: basic, translational and clinical | ECTS2016

Inhibition of mTOR signaling by everolimus has concurrent anti-tumor and bone-protective effects in murine osteolytic cancer models

Browne Andrew , Kubasch Marie Luise , Gobel Andy , Hadji Peyman , Chen David , Rauner Martina , Rachner Tilman , Hofbauer Lorenz

Clinical data suggest that the mTOR inhibitor everolimus may have bone protective effects in addition to its anti-tumor effects in women with ER+/HER2− metastatic breast cancer receiving hormone-ablative therapies. Based on these findings, we tested the hypothesis, whether everolimus exerts concurrent anti-tumor effects while protecting the skeleton in murine models. Thus, we assessed bone metabolism and anti-tumor effects in osteolytic cancer models upon exposure to eve...

ba0005p208 | Cell biology: Osteocytes, mechanobiology | ECTS2016

Transgene expression by Dmp1 promoter fragments occurs in various organs

Saito Hiroaki , Taipaleenmaki Hanna , Al-Jazzar Ahmed , Gasser Andreas , Javaheri Behzad , Scudamore Cheryl , Bellido Teresita , Pitsillides Andrew A , Hesse Eric

Analysis of osteocyte function often uses promoter elements of osteocyte-specific genes i.e. SOST or Dentin-matrix-protein 1 (Dmp1) to overexpress genes or the Cre-recombinase for conditional deletion studies. However, evidence suggests that these promoters may not be osteocyte-specific, which would be critical for subsequent data interpretation. To investigate the selectivity of supposedly osteocyte-specific in vivo models, we crossed the 8kb-Dmp1-Cre mice (i) with A...

ba0005p401 | Osteoporosis: treatment | ECTS2016

Two-fold regional variation in initiation of anti-osteoporosis medication after hip fracture in the UK

Shah Anjali , Prieto-Alhambra Daniel , Hawley Samuel , Delmestri Antonella , Lippett Janet , Cooper Cyrus , Judge Andrew , Javaid Kassim

Objective: Describe UK regional variation in prescription of anti-osteoporosis drug therapy before and after a primary hip fracture during 1999–2013.Materials and Methods: We used primary care data (Clinical Practice Research Datalink) to identify patients with a hip fracture and primary-care prescriptions of any anti-osteoporosis drugs (bisphosphonates, strontium, denosumab, oestrogen therapy, SERMS, teriparatide) prior to primary hip fracture and ...

ba0005p465 | Other diseases of bone and mineral metabolism | ECTS2016

Tracking inflammation in mouse model of fibrodysplasia ossificans progressiva prior to the detection of heterotopic ossification as a potential biomarker

Nannuru Kalyan , Jimenez Johanna , Huang Lily , Wen Xialing , Wang Lili , Xie LiQin , Idone Vincent , Murphy Andrew , Hatsell Sarah , Economides Aris

Fibrodysplasia ossificans progressiva (FOP) is a rare debilitating genetic disease characterized by abnormal progressive heterotopic endochondrial ossification of soft tissues. FOP results from mutations in the intracellular domain of the type I BMP receptor ACVR1 (ALK2) the most common of which is R206H. FOP mutations alter the sensitivity of ACVR1 to Activin A from an antagonist to an agonist. We have previously shown that Activin A is necessary and sufficient for driving he...

ba0001oc1.6 | Osteoporosis epidemiology and long term treatment complications | ECTS2013

Femur geometrical parameters in the pathogenesis of atypical femur fractures

Morin Suzanne N , Godbout Benoit , Wall Michelle , Belzile Etienne L , Michou Laetitia , Ste-Marie Louis-Georges , Karaplis Andrew C , de Guise Jacques A , Brown Jacques P

Background: Atypical femur fractures (AFF) arise in the subtrochanteric and diaphyseal regions. Because of this unique distribution, we hypothesized that patients with AFF demonstrate specific geometrical variations of their femur whereby baseline tensile forces applied to the lateral cortex are higher and might favor the appearance of these rare stress fractures, when exposed to bisphosphonates.Methods: Subjects who sustained AFF, as defined by the ASBM...

ba0001pp448 | Osteoporosis: treatment | ECTS2013

Resolution of effects on bone turnover markers and bone mineral density after discontinuation of long-term bisphosphonate use

Benhamou Claude , De Villiers Tobias , Johnston C Conrad , Langdahl Bente , Saag Kenneth , Denker Andrew , Pong Annpey , McGinnis John P , Rosenberg Elizabeth , Santora Arthur

Relatively little is known about immediate consequences of continuing vs interrupting long-term bisphosphonate treatment. This report describes changes in bone turnover and BMD in a 1-year, dose-finding trial of the calcium-sensing receptor antagonist MK-5442 in postmenopausal, BP-treated women, randomized to continued alendronate 70 mg weekly, switch to placebo, or switch to MK-5442. Recruited women (n=526) had taken alendronate for ≥12 months and an oral BP fo...

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 ...