Bone Abstracts

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...

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...

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)...

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...

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...

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...

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...

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...

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...

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...

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...

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 ...

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...

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...

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 ...

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 ...

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...

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...

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...

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...

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 (...

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...