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https://www.readbyqxmd.com/read/28720522/patients-with-non-ambulatory-cerebral-palsy-have-higher-sclerostin-levels-and-lower-bone-mineral-density-than-patients-with-ambulatory-cerebral-palsy
#1
Yoon-Kyum Shin, Young Kwon Yoon, Kyung Bae Chung, Yumie Rhee, Sung-Rae Cho
Bone loss is a serious clinical issue in patients with cerebral palsy (CP). Sclerostin has garnered interest as a key mechanosensor in osteocytes, leading to considerations of the therapeutic utilization of anti-sclerostin medications. This study was undertaken to determine associations among mechanical unloading, sclerostin levels, and bone imbalance in patients with CP. A total of 28 patients with CP participated in this cross-sectional study. The following measurements were taken: anthropometrics, clinical diagnosis of CP subtype and ambulatory status, bone mineral density (BMD) z-scores at the lumbar spine and hip, and blood biochemical markers, including sclerostin, parathyroid hormone (PTH), osteocalcin, C-terminal telopeptide, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, creatinine, calcium, and phosphorus...
July 15, 2017: Bone
https://www.readbyqxmd.com/read/28716553/regional-analysis-of-age-related-local-bone-loss-in-the-spine-of-a-healthy-population-using-3d-voxel-based-modeling
#2
Alexander Valentinitsch, Stefano Trebeschi, Eva Alarcón, Thomas Baum, Johannes Kaesmacher, Claus Zimmer, Cristian Lorenz, Jan S Kirschke
Local variations in bone loss may be of great importance to individually predict osteoporotic fractures but are neglected by current densitometry techniques. The purpose of this study was to evaluate regional variations of normal bone loss at the spine among different age groups using voxel-based morphometry. Non-contrast MDCT scans of 16 patients under the age of 40 (mean age 26years) without spinal pathology were identified as a reference cohort, where each thoracolumbar vertebra was assessed individually...
July 14, 2017: Bone
https://www.readbyqxmd.com/read/28716552/is-heterotopic-ossification-getting-nervous-the-role-of-the-peripheral-nervous-system-in-heterotopic-ossification
#3
Eleanor L Davis, Alan R Davis, Zbigniew Gugala, Elizabeth A Olmsted-Davis
Heterotopic ossification (HO), or de novo bone formation in soft tissue, is often observed following traumatic injury. Recent studies suggest that peripheral nerves may play a key functional role in this process. The results supporting a neurological basis for HO are examined in this article. Evidence supports the fact that BMPs released from bone matrix possess the capacity to induce HO. However, the process cannot be recapitulated using recombinant proteins without extremely high doses suggesting other components are required for this process...
July 14, 2017: Bone
https://www.readbyqxmd.com/read/28716551/application-of-human-induced-pluripotent-stem-cells-to-model-fibrodysplasia-ossificans-progressiva
#4
Emilie Barruet, Edward C Hsiao
Fibrodysplasia ossificans progressiva (FOP) is a genetic condition characterized by massive heterotopic ossification. FOP patients with mutations in the Activin A type I receptor (ACVR1), a bone morphogenetic protein (BMP) receptor. FOP is a progressive and debilitating disease characterized by bone formation flares that often occur after trauma. Since it is often difficult or impossible to obtain large amounts of tissue from human donors due to the risks of inciting more heterotopic bone formation, human induced pluripotent stem cells (hiPSCs) provide an attractive source for establishing in vitro disease models and for applications in drug screening...
July 14, 2017: Bone
https://www.readbyqxmd.com/read/28716550/co-deteriorations-of-anisotropic-extracellular-matrix-arrangement-and-intrinsic-mechanical-property-in-c-src-deficient-osteopetrotic-mouse-femur
#5
Takuya Ishimoto, Bunji Sato, Jee-Wook Lee, Takayoshi Nakano
Osteopetrotic bone shows dissociation between bone mineral density (BMD) and bone strength. In this study, volumetric BMD; preferential orientation of the extracellular matrix (ECM), which is composed of collagen fibers and apatite crystals as bone material quality; and mechanical properties of the src(-/-) osteopetrotic and normal mouse femoral cortical bone were analyzed and compared with each other at a bone tissue level. The degree of preferential orientation of ECM along the femoral long axis was significantly decreased in the src(-/-) mice femur, suggesting deteriorated bone quality...
July 14, 2017: Bone
https://www.readbyqxmd.com/read/28712877/bone-mass-microarchitecture-and-strength-are-influenced-by-race-ethnicity-in-young-adult-men-and-women
#6
Kristin L Popp, Julie M Hughes, Adriana Martinez-Betancourt, Matthew Scott, Victoria Turkington, Signe Caksa, Katelyn I Guerriere, Kathryn E Ackerman, Chun Xu, Ginu Unnikrishnan, Jaques Reifman, Mary L Bouxsein
Lower rates of fracture in both Blacks compared to Whites, and men compared to women are not completely explained by differences in bone mineral density (BMD). Prior evidence suggests that more favorable cortical bone microarchitecture may contribute to reduced fracture rates in older Black compared to White women, however it is not known whether these differences are established in young adulthood or develop during aging. Moreover, prior studies using high-resolution pQCT (HR-pQCT) have reported outcomes from a fixed-scan location, which may confound sex- and race/ethnicity-related differences in bone structure...
July 13, 2017: Bone
https://www.readbyqxmd.com/read/28711660/a-novel-deletion-involving-gnas-exon-1-causes-php1a-and-further-refines-the-region-required-for-normal-methylation-at-exon-a-b
#7
Monica Reyes, Anara Karaca, Murat Bastepe, Nese Ersoz Gulcelik, Harald Jüppner
GNAS exons 1-13 encode the biallelically expressed alpha-subunit of the stimulatory G protein (Gαs). Additional transcripts derived from this locus use alternative first exons that undergo parent-specific methylation, thus allowing transcription only from the non-modified allele. Pseudohypoparathyroidism type Ia (PHP1A) is characterized by Albright's Hereditary Osteodystrophy (AHO) and resistance to multiple hormones; this disorder is caused by maternal inactivating mutations involving Gαs exons. In contrast, pseudohypoparathyroidism type Ib (PHP1B) is characterized mostly by resistance to PTH and often mild TSH resistance, usually without AHO features...
July 12, 2017: Bone
https://www.readbyqxmd.com/read/28711659/exercise-initiated-after-the-onset-of-insulin-resistance-improves-trabecular-microarchitecture-and-cortical-bone-biomechanics-of-the-tibia-in-hyperphagic-otsuka-long-evans-tokushima-fatty-rats
#8
Laura C Ortinau, Melissa A Linden, Rebecca K Dirkes, R Scott Rector, Pamela S Hinton
The present study extends our previous findings that exercise, which prevents the onset of insulin resistance and type 2 diabetes (T2D), also prevents the detrimental effects of T2D on whole-bone and tissue-level strength. Our objective was to determine whether exercise improves bone's structural and material properties if insulin resistance is already present in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF rat is hyperphagic due to a loss-of-function mutation in cholecystokinin-1 receptor (CCK-1 receptor), which leads to progressive obesity, insulin resistance and T2D after the majority of skeletal growth is complete...
July 12, 2017: Bone
https://www.readbyqxmd.com/read/28705683/periodontal-ligament-fibroblasts-as-a-cell-model-to-study-osteogenesis-and-osteoclastogenesis-in-fibrodysplasia-ossificans-progressiva
#9
Teun J de Vries, Ton Schoenmaker, Dimitra Micha, Jolanda Hogervorst, Siham Bouskla, Tim Forouzanfar, Gerard Pals, Coen Netelenbos, E Marelise W Eekhoff, Nathalie Bravenboer
Fibrodysplasia Ossificans Progressiva (FOP) is a progressive disease characterized by periods of heterotopic ossification of soft connective tissues, including ligaments. Though progress has been made in recent years in unraveling the underlying mechanism, patient-derived cell models are necessary to test potential treatment options. Periodontal ligament fibroblasts (PLF) from extracted teeth can be used to study deviant bone modeling processes in vitro since these cells are derived from genuine ligaments. They further provide a tool to study the hitherto unknown role of the bone morphogenesis protein receptor type 1 (BMPR-1) Activin A type 1 receptor ACVR1-R206H mutation in osteoclastogenesis...
July 10, 2017: Bone
https://www.readbyqxmd.com/read/28705682/increased-bone-matrix-mineralization-in-treatment-na%C3%A3-ve-children-with-inflammatory-bowel-disease
#10
Barbara M Misof, Paul Roschger, Klaus Klaushofer, Frank Rauch, Jinhui Ma, David R Mack, Leanne M Ward
Inflammatory bowel disease (IBD) affects many organ systems including the skeleton. In children with IBD, bone mineral density (BMD) and bone turnover are frequently low. Disturbances in bone mineralization density distribution (BMDD) are linked to alterations in bone material strength; however, BMDD has not previously been reported in children with chronic inflammatory disorders. The aim of this study was to characterize BMDD based on quantitative backscatter electron imaging in cancellous (Cn.) and cortical (Ct...
July 10, 2017: Bone
https://www.readbyqxmd.com/read/28694163/mice-maintain-predominantly-maternal-g%C3%AE-s-expression-throughout-life-in-brown-fat-tissue-bat-but-not-other-tissues
#11
Olta Tafaj, Steven Hann, Ugur Ayturk, Matthew L Warman, Harald Jüppner
The murine Gnas (human GNAS) locus gives rise to Gαs and different splice variants thereof. The Gαs promoter is not methylated thus allowing biallelic expression in most tissues. In contrast, the alternative first Gnas/GNAS exons and their promoters undergo parent specific methylation, which limits transcription to the non-methylated allele. Pseudohypoparathyroidism type Ia (PHP1A) or type Ib (PHP1B) are caused by heterozygous maternal GNAS mutations suggesting that little or no Gαs is derived in some tissues from the non-mutated paternal GNAS thereby causing hormonal resistance...
July 8, 2017: Bone
https://www.readbyqxmd.com/read/28694162/impaired-bone-strength-estimates-at-the-distal-tibia-and-its-determinants-in-adolescents-with-anorexia-nervosa
#12
Vibha Singhal, Shreya S Tulsiani, Karen Joanie Campoverde, Deborah M Mitchell, Meghan Slattery, Melanie Schorr, Karen K Miller, Miriam A Bredella, Madhusmita Misra, Anne Klibanski
BACKGROUND: Altered bone microarchitecture and higher marrow adipose tissue (MAT) may reduce bone strength. High resolution pQCT (HRpQCT) allows assessment of volumetric BMD (vBMD), and size and microarchitecture parameters of bone, while 1H-magnetic resonance spectroscopy (1H-MRS) allows MAT evaluation. We have reported impaired microarchitecture at the non-weight bearing radius in adolescents with anorexia nervosa (AN) and that these changes may precede aBMD deficits. Data are lacking regarding effects of AN on microarchitecture and strength at the weight-bearing tibia in adolescents and young adults, and the impact of changes in microarchitecture and MAT on strength estimates...
July 7, 2017: Bone
https://www.readbyqxmd.com/read/28689816/a-novel-role-for-dopamine-signaling-in-the-pathogenesis-of-bone-loss-from-the-atypical-antipsychotic-drug-risperidone-in-female-mice
#13
Katherine J Motyl, Megan Beauchemin, Deborah Barlow, Phuong T Le, Kenichi Nagano, Annika Treyball, Anisha Contractor, Roland Baron, Clifford J Rosen, Karen L Houseknecht
Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat schizophrenia, bipolar disorder, and autism, and are prescribed off-label for other mental health issues. AA drugs are associated with severe metabolic side effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data also show that risperidone causes bone loss and increases fracture risk in both men and women. There are several potential mechanisms of bone loss from RIS. One is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism...
July 6, 2017: Bone
https://www.readbyqxmd.com/read/28688892/vascular-ossification-pathology-mechanisms-and-clinical-implications
#14
Michael A Fuery, Lusha Liang, Frederick S Kaplan, Emile R Mohler
In recent years, the mechanisms and clinical significance of vascular calcification have been increasingly investigated. For over a century, however, pathologists have recognized that vascular calcification is a form of heterotopic ossification. In this review, we aim to describe the pathology and molecular processes of vascular ossification, to characterize its clinical significance and treatment options, and to elucidate areas that require further investigation. The molecular mechanisms of vascular ossification involve the activation of regulators including bone morphogenic proteins and chondrogenic transcription factors and the loss of mineralization inhibitors like fetuin-A and pyrophosphate...
July 5, 2017: Bone
https://www.readbyqxmd.com/read/28687496/romosozumab-increases-bone-mineral-density-in-postmenopausal-japanese-women-with-osteoporosis-a-phase-2-study
#15
Hideaki Ishibashi, Daria B Crittenden, Akimitsu Miyauchi, Cesar Libanati, Judy Maddox, Michelle Fan, Li Chen, Andreas Grauer
BACKGROUND: Romosozumab is a monoclonal antibody that inhibits sclerostin and rapidly increases bone mineral density (BMD) through a dual effect on bone by increasing bone formation and decreasing bone resorption, as shown in a global phase 2 study in postmenopausal women with low bone mass. Here, we report the key results of a phase 2, double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of romosozumab in postmenopausal Japanese women with osteoporosis...
July 4, 2017: Bone
https://www.readbyqxmd.com/read/28684193/treatment-with-neridronate-in-children-and-adolescents-with-osteogenesis-imperfecta-data-from-open-label-not-controlled-three-year-italian-study
#16
L Idolazzi, A Fassio, O Viapiana, M Rossini, G Adami, F Bertoldo, F Antoniazzi, D Gatti
INTRODUCTION: The present study assessed the long-term efficacy and safety of intravenous (i.v.) neridronate in children and adolescents affected by osteogenesis imperfecta (OI). METHODS: 55 young patients (mean age 12.6±3.9years) affected by OI were included in the study. Neridronate was administered by i.v. infusion at a dose of 2mg/kg (maximum dose of 100mg) at intervals of three-months for three years. Dual X-ray absorptiometry of the lumbar spine, hip and ultradistal and proximal radius were evaluated every 6months...
July 3, 2017: Bone
https://www.readbyqxmd.com/read/28684192/involvement-of-sphingosine-kinase-sphingosine-1-phosphate-metabolic-pathway-in-spondyloarthritis
#17
Carole Bougault, Alaeddine El Jamal, Anne Briolay, Saida Mebarek, Marie-Astrid Boutet, Thomas Garraud, Benoit Le Goff, Fréderic Blanchard, David Magne, Leyre Brizuela
Spondyloarthritis (SpA) is a relatively common chronic inflammatory joint disorder, with a prevalence of about 0.2-0.5% worldwide. The primary target of the pathological process is the enthesis, where tendons and ligaments attach to underlying bone. These insertion sites are hotspots of bone formation (enthesophytes), which can lead to ankylosis. Unfortunately, the mechanisms causing the onset and progression of entheseal ossification remain largely unknown. Sphingosine 1-phosphate (S1P), a lipid generated after sphingosine phosphorylation by sphingosine kinases 1 and 2 (SK1/2), plays important roles in cell proliferation, differentiation and survival...
July 3, 2017: Bone
https://www.readbyqxmd.com/read/28676440/severe-bone-loss-and-multiple-fractures-in-scn8a-related-epileptic-encephalopathy
#18
Tim Rolvien, Sebastian Butscheidt, Anke Jeschke, Axel Neu, Jonas Denecke, Christian Kubisch, Miriam H Meisler, Klaus Pueschel, Florian Barvencik, Timur Yorgan, Ralf Oheim, Thorsten Schinke, Michael Amling
Mutations in the SCN8A gene encoding the neuronal voltage-gated sodium channel Nav1.6 are known to be associated with epileptic encephalopathy type 13. We identified a novel de novo SCN8A mutation (p.Phe360Ala, c.1078_1079delTTinsGC, Exon 9) in a 6-year-old girl with epileptic encephalopathy accompanied by severe juvenile osteoporosis and multiple skeletal fractures, similar to three previous case reports. Skeletal assessment using dual energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) and serum analyses revealed a combined trabecular and cortical bone loss syndrome with elevated bone resorption...
July 1, 2017: Bone
https://www.readbyqxmd.com/read/28676439/the-effect-of-stress-fracture-interventions-in-a-single-elite-infantry-training-unit-1983-2015
#19
Charles Milgrom, Aharon S Finestone
Stress fractures can be seen as an undesired byproduct of demanding physical training. The threshold value of stress that places an individual bone at high risk for stress fracture has not been identified. In a prospective study of stress fractures in 1983, a 31% incidence was found during demanding Israeli infantry basic training by bone scan criteria. Within a subgroup of these recruits, an elite infantry unit was found to have a 40% incidence. Since then and until 2015, eight additional induction companies of the same elite infantry unit were prospectively monitored for stress fractures during their basic training...
July 1, 2017: Bone
https://www.readbyqxmd.com/read/28676438/parathyroid-hormone-inhibits-notch-signaling-in-osteoblasts-and-osteocytes
#20
Stefano Zanotti, Ernesto Canalis
Parathyroid hormone (PTH) and Notch receptors regulate bone formation by governing the function of osteoblastic cells. To determine whether PTH interacts with Notch signaling as a way to control osteoblast function, we tested the effects of PTH on Notch activity in osteoblast- and osteocyte-enriched cultures. Notch signaling was activated in osteoblast-enriched cells from wild-type C57BL/6J mice following exposure to the Notch ligand Delta-like (Dll)1 or by the transient transfection of the Notch intracellular domain (NICD), the transcriptionally active fragment of Notch1...
July 1, 2017: Bone
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