Searchable abstracts of presentations at key conferences on calcified tissues
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7th International Conference on Children's Bone Health

Salzburg, Austria
27 Jun 2015 - 30 Jun 2015

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7th International Conference on Children's Bone Health, 27 - 30 June 2015; Salzburg, Austria

ba0004oc1 | (1) | ICCBH2015

Abnormal trabecular micro-architecture and bone mechanical properties in adolescent idiopathic scoliosis: a case–control study with high-resolution peripheral quantitative computed tomography and finite element analysis

Cheuk Ka Yee , Chen Huanxiong , Yu Fiona , Lam Tsz Ping , Lee Simon K M , Ng Bobby K W , Cheng Jack C Y

Adolescent idiopathic scoliosis (AIS) is associated with low bone mineral density (BMD) which has been reported to be an important prognostic factor for curve progression. In addition to BMD, high-resolution peripheral quantitative computed tomography (HR-pQCT) allows measurement of volumetric BMD, bone morphology, trabecular micro-architecture, and evaluation with structure model index (SMI) and finite element analysis (FEA) for mechanical property assessment. The aim of this...

ba0004oc2 | (1) | ICCBH2015

Feature-based recognition of trabecular microstructure using 1.5T magnetic resonance imaging: a new methodology

Dimitri Paul , Lekadir Karim , Hoogendoorn Corne , Armitage Paul , Whitby Elspeth , King David , Frangi Alejandro

Background: Magnetic resonance imaging (MRI) is used clinically to assess bone marrow, muscle and joints. The assessment of cortical and trabecular structure using MRI may provide further insight into the muscle–bone–bone marrow unit. Previous studies using MRI to evaluate microarchitecture are confined to research due to the need for specially adapted coils and navigator software to limit motion artifact. We present a novel statistical method using HRpQCT to determi...

ba0004oc3 | (1) | ICCBH2015

Sedentary time negates the positive influence of moderate-to-vigorous physical activity but not vigorous physical activity on bone strength in adolescent girls

Tan Vina , Macdonald Heather , McKay Heather

We examined the influence of objectively measured moderate-to-vigorous physical activity (MVPA) and vigorous PA (VPA) and sedentary time (SED) on bone strength, structure and density in post-pubertal girls.We had 63 healthy girls (15.3±0.3 years) from the Health Promoting Secondary Schools (HPSS) study with valid accelerometry data and tibia scans. We assessed the left tibia using peripheral quantitative computed tomography (pQCT, XCT 3000, Stratec)...

ba0004oc4 | (1) | ICCBH2015

Increased bone matrix mineralization in treatment-naive children with Crohn's disease

Roschger Paul , Misof Barbara , Klaushofer Klaus , Rauch Frank , Ward Leanne

Background: Crohn’s disease (CD) is an inflammatory bowel disease which affects many organ systems including the skeleton. In children with CD, bone mineral density is frequently low. Bone metabolic abnormalities, including lower biochemical measures of bone turnover (NTX) as well as decreased bone formation indices at the tissue level have been reported. The aim of our study was to gain information on the bone matrix mineralization in CD.Methods: W...

ba0004oc5 | (1) | ICCBH2015

Bivariate analyses of BMD and lean mass in children identifies variants with novel pleiotropic effects across six BMD loci and in the TOM1L2 locus

Medina-Gomez Carolina , Kemp John P , Heppe Denise H M , Tobias Jon H , Hofman Albert , Carola Zillikens M , Uitterlinden Andre G , Jaddoe Vincent W V , Evans David M , Rivadeneira Fernando

Background: Lean and bone mass are heritable traits with high phenotypic correlation (rho=0.44), likely reflecting the underlying mechanical and biochemical interactions between tissues.Aim: Estimate the shared heritability (genetic correlation) of both traits in children and identify genetic determinants displaying pleiotropic effects on lean mass and bone mass accrual.Methods: Participants make part of two prospective po...

ba0004oc6 | (1) | ICCBH2015

Early life motor control is positively associated with adolescent bone strength

Ireland Alex , Sayers Adrian , Deere Kevin , Emond Alan , Tobias Jon

Recent evidence supports a strong influence of early life movement on infant bone strength. However, it is not known whether early motor development also influences bone strength in later life. Therefore, we examined relationships between locomotor score (using components of the Denver Developmental Screening Test) at 18 months, and the Avon Longitudinal Study of Parents and Children (ALSPAC) Co-ordination Test (ACT) score at 7 years, and bone outcomes as measured at age 17 ye...

ba0004oc7 | (1) | ICCBH2015

Osteogenesis imperfecta: a pilot trial on treatment with the RANKL-antibody denosumab

Hoyer-Kuhn Heike , Netzer Christian , Hero Barbara , Schoenau Eckhard , Semler Oliver

Osteogenesis imperfecta is a rare disease leading to multiple fractures, skeletal deformities and scoliosis due to a reduced bone mass. Pathological fractures caused by inadequate traumata are the most severe symptom. More than 85% of patients are affected by mutations in COL1A1/A2 impairing quantity and quality of collagen. At present no approved drugs for OI treatment in childhood are available. A single centre prospective pilot study was performed to assess safety and effic...

ba0004oc8 | (1) | ICCBH2015

Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta

Munns Craig , Peacock Lauren , Mikulec Kathy , Kneissel Michaela , Kramer Ina , Cheng Tegan , Schindeler Aaron , Little David

Introduction: Bisphosphonate treatment in children with osteogenesis imperfecta reduces bone catabolism and relies on modelling to form new bone. An anabolic treatment, anti-sclerostin antibody (Anti-SOST Ab), is being investigated in clinical trials. We hypothesized that combined treatment may produce superior outcomes in OI.Methods: Female Col1a2 G610C mice and their wild type littermates (WT) were treated from week 5 to week 9 of life with either sali...

ba0004oc9 | (1) | ICCBH2015

Skeletal manifestations in pediatric WNT1 osteoporosis

Makitie Riikka , Pekkinen Minna , Laine Christine , Makitie Outi

Objectives: We recently identified a heterozygous missense mutation c.652T→G (p. C218G) in WNT1 as the cause of severe primary osteoporosis (Laine et al. New Engl J Med 2013). The mutated WNT1 reduces activation of the canonical WNT1/β-catenin-signaling, resulting in decreased osteoblastic function. The mutation was originally identified in a large Finnish family presenting with dominantly inherited, early-onset osteoporosis, with affected...

ba0004oc10 | (1) | ICCBH2015

Lack of PEDF within the bone matrix is associated with osteoidosis and abnormally high bone mineral content

Fratzl-Zelman Nadja , Schmidt Ingo , Roschger Paul , Roschger Andreas , Reich Adi , Glorieux Francis H. , Wagermaier Wolfgang , Fratzl Peter , Klaushofer Klaus , Marini Joan C. , Rauch Frank

Background and methods: Pigment epithelium-derived factor (PEDF) is a potent antiangiogenic factor, ubiquitously expressed and secreted in human tissues. Hypertrophic cartilage and osteoblasts express PEDF that binds to type I collagen and glycosaminoglycans in the extracellular matrix. Two rare forms of osteogenesis imperfecta (OI) with intact collagen synthesis are associated with PEDF deficiency. Histological observations revealed excessive osteoid formation and prolonged m...

ba0004oc11 | (1) | ICCBH2015

Comparison of RANKL blockade and bisphosphonate anti-resorptive therapies in a growing mouse model of OI: implications of prolonged treatment on bone health

Marino Josephine , Pleshko Nancy , Doty Stephen , Carter Erin , Jepsen Karl , Boskey Adele , Raggio Cathleen

Objective: The purpose of this ongoing study was to determine whether osteogenesis imperfecta (OI) patients entering adulthood should continue with bisphosphonate therapy or would benefit from switching to a RANKL blockade therapy. To address this question, we used a mouse model of type-III OI.Methods: Under IACUC-approval, +/+ and oim/oim mice were treated from 2–26 weeks (n=20/treatment/genotype) with either 1) saline 24 weeks; 2...

ba0004oc12 | (1) | ICCBH2015

A zebrafish osteogenesis imperfecta model: a new tool to develop novel pharmacological treatments

Gioia Roberta , Tonelli Francesca , Carra Silvia , Cotelli Franco , Bianchi Laura , Gagliardi Assunta , Bini Luca , Biggiogera Marco , Leikin Sergey , Fisher Shannon , Rossi Antonio , Tenni Ruggero , Forlino Antonella

Objectives: Osteogenesis imperfecta (OI) is a bone disease mainly caused by collagen type I mutations and characterized by bone fragility. No definitive cure is available and the search for novel treatments is necessary. The small teleost D. rerio is particularly appealing for drug screening approaches. A zebrafish OI model (Chihuahua) carrying in heterozygosis the G574D substitution in the α1 chain of collagen type I is available. To use this model for ...

ba0004oc13 | (1) | ICCBH2015

Meclozine has a potential effects on short stature and foramen magnum stenosis in transgenic mice with achondroplasia

Matsushita Masaki , Kitoh Hiroshi , Mishima Kenichi , Sugiura Hiroshi , Hasegawa Sachi , Kitamura Akiko , Ishiguro Naoki , Ohno Kinji

ACH (achondroplasia) is one of the most common skeletal dysplasias with severe short stature caused by gain-of-function mutations in the FGFR3 gene. Foramen magnum stenosis is a serious neurological complication of ACH. Downregulation of the FGFR3 signaling is a radical therapeutic strategy for the disease. We previously demonstrated that meclozine, an over-the-counter drug for motion sickness, inhibited elevated FGFR3 signaling in chondrocytic cell lines. In the present study...

ba0004oc14 | (1) | ICCBH2015

Small interfering RNAs as an innovative therapeutic approach for the autosomal dominant osteopetrosis type 2 (ADO2)

Capulli Mattia , Maurizi Antonio , Ventura Luca , Rucci Nadia , Teti Anna

Autosomal dominant osteopetrosis type 2 (ADO2) is a rare genetic disease due to reduced osteoclast function. Clinical manifestations are variable, and in some cases the symptoms, including frequent fractures, osteomyelitis, hematologic and neural failures, are already evident during childhood and worsen with age. In 70% of cases, ADO2 is caused by heterozygous dominant negative mutations of the CLCN7 gene, encoding the Cl−/H+ antiporter type 7. We hypothesized that silen...

ba0004oc15 | (1) | ICCBH2015

Osseous side effects on the growing skeleton exerted by tyrosine kinase inhibitor treatment: data observed in pediatric patients with chronic myeloid leukemia in comparison to a juvenile rat model

Tauer Josephine T , Hofbauer Lorenz C , Erben Reinhold G , Suttorp Meinolf

Background: The tyrosine kinase inhibitor (TKI) imatinib is applied as front-line treatment in adult and pediatric patients with chronic myeloid leukemia (CML) in order to selectively inhibit the causative oncogenic BCR-ABL1 tyrosine kinase. However, TKIs exhibit off-target effects on further kinases involved in the regulation of bone metabolism. As consequence, pediatric patients display longitudinal growth retardation while on imatinib treatment. As CML is a rare disease in ...

ba0004oc16 | (1) | ICCBH2015

Medicarpin, a natural pterocarpan, enhances bone regeneration in cortical bone defect model by activation of notch and Wnt canonical signalling pathway

Dixit Manisha , Raghuvanshi Ashutosh , Goel Atul , Singh Divya

Bone regeneration and fracture healing processes are impaired in post menopausal osteoporosis which is induced by estrogen deficiency. Though agents like BMPs and PTH have been shown to promote bone regeneration but are associated with undesirable side effects. There is a need for new agents that enhance bone regeneration and repair.The aim of this study was to evaluate the bone regenerative capacity of medicarpin in the osteoporotic rat model. Cortical ...

ba0004oc17 | (1) | ICCBH2015

Inhibition of TGFβ signalling delays ossification in patients with fibrodysplasia ossificans progressiva

Micha Dimitra , Voermans Elise , Huib van Essen , Drukker Jesse , Netelenbos Coen , Eekhoff Marelise , Bravenboer Nathalie

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder characterized by progressive heterotopic ossification. FOP patients only present great toe malformations at birth. However, as they grow older they develop soft tissue lumps as a result of flare-ups causing the irreversible replacement of skeletal muscle tissue with bone tissue leading to cumulative physical immobility. Classical FOP patients possess a mutation (c.617G>A; R206H) in the activin recept...

ba0004oc18 | (1) | ICCBH2015

Improvement in bone manifestations and respiratory status in infants and young children with HPP treated with asfotase alfa: an update on the ENB-010-10 trial

Hofmann Christine , Rockman-Greenberg Cheryl , Harmatz Paul , Moseley Scott , Odrljin Tatjana , Liese Johannes

Objectives: Hypophosphatasia (HPP) is a rare metabolic disease caused by loss-of-function mutation(s) in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). HPP in infants is characterized by poor skeletal mineralization, respiratory compromise, and a high risk of mortality. We previously reported improved mineralization and respiratory function in 15 patients enrolled in this second study of asfotase alfa, a bone-targeted recombinant human TNSALP, in infants a...

ba0004oc19 | (1) | ICCBH2015

The VINE study: vitamin D in newborns: a randomized controlled trial comparing daily and bolus supplementation in breastfed infants of vitamin D deficient mothers

Huynh Julie , Lu Thao , Liew Danny , Doery James , Tudball Ronald , Jona Madeleine , Bhamjee Roisin , Rodda Christine

Objective: There is no published data to demonstrate the efficacy and safety of a single bolus dose vitamin D in breastfed infants of vitamin D deficient mothers. We evaluated the efficacy and safety of this alternative approach in newborn infants <4 months of age.Method: This single centre study was conducted from Aug 2013 to May 2014. Of 307 pregnant women diagnosed with vitamin D deficiency (25OHD<50 nmol/l) 70 were recruited. Their newborn in...

ba0004oc20 | (1) | ICCBH2015

The effect of calcium supplementation on adolescent bone growth in pre-pubertal Gambian females: a 12-year follow-up study

Ward Kate , Cole Tim , Laskey Ann , Ceesay Mustapha , Mendy Michael , Prentice Ann

In rural Gambian prepubertal children with low calcium intakes (mean 300 mg/day) we reported positive effects, sustained for at least a year (y), on bone mineral content (BMC) after 12 months supplementation with calcium carbonate to international levels1,2. The group was followed up regularly until the end of height growth, and supplementation did not affect height growth in the girls3. Our aim was to determine whether the supplementation altered the tim...

ba0004oc21 | (1) | ICCBH2015

Maternal vitamin D deficiency alters later skeletal responsiveness to mechanical loading in a model system

Borg Stephanie , Buckley Harriet , Nicholson Kirsty , Skerry Tim , Bishop Nick

Fractures in children are common; prospective cohort studies suggest narrower bones predispose to fracture. Early life events can influence later growth and development. Observational studies suggest children born to mothers with lower vitamin D levels during pregnancy have narrower bones. We investigated the effects of maternal vitamin D deficiency on offspring’s bones’ response to mechanical loading in a model system.C57BL/6 female mice (...

ba0004oc22 | (1) | ICCBH2015

Extra vitamin D from food fortification and bone fractures in adolescents: results from the D-tect study

Handel Mina Nicole , Raymond Kyle , Cooper Cyrus , Heitmann Berit Lilienthal , Abrahamsen Bo

Background: Improving the general population’s vitamin D status through food fortification is part of an ongoing international debate. Vitamin D status during pregnancy may influence the long-term bone health of the offspring; yet conflicting results have been reported and none of the studies have examined paediatric fracture as outcome.Method: The influence of extra vitamin D exposure during prenatal life and risk of fracture during adolescence was...