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Birgit Mentrup, Hermann Girschick, Franz Jakob, Christine Hofmann
Hypophosphatasia (HPP) is a multi-systemic inborn disease with an extraordinary spectrum of severity, ranging from the absence of mineralization to high lethality and it involves different organs including bone, muscle, kidney, lung, gastrointestinal tract and the nervous system. The disease is characterized by low levels of serum alkaline phosphatase, caused by loss-of-function mutations within the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP. Here we present the functional characterization of a gene mutation, detected in intron 7 of the ALPL gene of a boy with infantile HPP in whom routine sequencing of the coding region failed to detect any mutation...
October 21, 2016: Bone
Kenneth Poole, Linda Skingle, Andrew Gee, Thomas Turmezei, Fjola Johannesdottir, Karen Blesic, Collette Rose, Madhavi Vindlacheruvu, Simon Donell, Jan Vaculik, Pavel Dungl, Martin Horak, Jan Stepan, Jonathan Reeve, Graham Treece
BACKGROUND: Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls...
October 21, 2016: Bone
Aimy Sebastian, Gabriela G Loots
Sclerostin is an osteocyte derived negative regulator of bone formation. A highly specific expression pattern and the exclusive bone phenotype have made Sclerostin an attractive target for therapeutic intervention in treating metabolic bone diseases such as osteoporosis and in facilitating fracture repair. Understanding the molecular mechanisms that regulate Sclerostin transcription is of great interest as it may unveil new avenues for therapeutic approaches. Such studies may also elucidate how various signaling pathways intersect to modulate bone metabolism...
October 19, 2016: Bone
Kirby Rickel, Fang Fang, Jianning Tao
Osteosarcoma is the predominant form of bone cancer, affecting mostly adolescents. Recent progress made in molecular genetic studies of osteosarcoma has changed our view on the cause of the disease and ongoing therapeutic approaches for patients. As we draw closer to gaining more complete catalogs of candidate cancer driver genes in common forms of cancer, the landscape of somatic mutations in osteosarcoma is emerging from its first phase. In this review, we summarize recent whole genome and/or whole exome genomic studies, and then put these findings in the context of genetic hallmarks of somatic mutations and mutational processes in human osteosarcoma...
October 16, 2016: Bone
Imranul Alam, Amie K McQueen, Dena Acton, Austin M Reilly, Rita L Gerard-O'Riley, Dana K Oakes, Charishma Kasipathi, Abigail Huffer, Weston B Wright, Michael J Econs
Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic bone disorder due to dysfunctional osteoclast activity. ADO2 is caused by missense mutations in the chloride channel 7 (CLCN7) gene characterized by osteosclerosis with multiple fractures. ADO2 can result in osteomyelitis, visual loss and bone marrow failure. Currently, there is no cure for ADO2, and until recently no appropriate animal model of ADO2 existed to understand better the pathogenesis of this disease and to test new therapies...
October 14, 2016: Bone
Michael J Econs, Glenn W Irwin
No abstract text is available yet for this article.
October 13, 2016: Bone
Pamela S Hinton, Peggy Nigh, John Thyfault
PURPOSE: We previously reported that 12months of resistance training (RT, 2×/wk, N=19) or jump training (JUMP, 3×/wk, N=19) increased whole body and lumbar spine BMD and increased serum bone formation markers relative to resorption in physically active (≥4h/wk) men (mean age: 44±2y; median: 44y) with osteopenia of the hip or spine. The purpose of this secondary analysis was to examine the effects of the RT or JUMP intervention on potential endocrine mediators of the exercise effects on bone, specifically IGF-I, PTH and sclerostin...
October 12, 2016: Bone
Antonius Ljj Bronckers, Donacian M Lyaruu
Supraoptimal intake of fluoride (F) induces structural defects in forming enamel, dentin and bone and increases the risk of bone fractures. Enamel formation is most sensitive to low levels of F and the degree of enamel fluorosis depends on the mouse strain. What molecular mechanism is responsible for these differences in sensitivity is unclear. Maturation ameloblasts transport bicarbonates into enamel in exchange for Cl- to buffer protons released by forming apatites. We proposed that F-enhanced mineral deposition releases excess of protons that will affect mineralization in forming enamel...
October 12, 2016: Bone
Gabriel L Galea, Lance E Lanyon, Joanna S Price
Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss...
October 12, 2016: Bone
R Y van der Velde, C E Wyers, E Teesselink, P P M M Geusens, J P W van den Bergh, F de Vries, C Cooper, N C Harvey, T P van Staa
INTRODUCTION: Given the expected increase in the number of patients with osteoporosis and fragility fractures it is important to have concise information on trends in prescription rates of anti-osteoporosis drugs (AOD). METHODS: We undertook a retrospective observational study using the UK Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2012 in subjects 50years or older, stratified by age, sex, geographic region and ethnicity. Yearly prescription incidence rates of any AOD and of each specific AOD were calculated as the number of patients first prescribed these AODs per 10,000person-years (py)...
October 11, 2016: Bone
Aline G Costa, Serge Cremers, John P Bilezikian
Sclerostin a potent regulator of bone formation, is an antagonist of the Wnt-signaling pathway. The advent of assays to measure circulating sclerostin has enabled research to be performed with the aim to understand the potential role of circulating sclerostin as a pathophysiological marker in a variety of clinical settings. At this time, however, assays to measure circulating sclerostin are still relatively new and have not demonstrated consistent internal agreement in addition to which there are differences between serum and plasma levels...
October 11, 2016: Bone
Antoon H van Lierop, Natasha M Appelman-Dijkstra, Socrates E Papapoulos
Sclerosteosis and van Buchem disease are two rare bone sclerosing dysplasia caused by genetic defects in the synthesis of sclerostin. In this article we review the demographic, clinical, biochemical, radiological, and histological characteristics of patients with sclerosteosis and van Buchem disease that led to a better understanding of the role of sclerostin in bone metabolism in humans and we discuss the relevance of these findings for the development of new therapeutics for the treatment of patients with osteoporosis...
October 11, 2016: Bone
Jesus Delgado-Calle, Amy Y Sato, Teresita Bellido
After discovering that lack of Sost/sclerostin expression is the cause of the high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive animal experimentation and clinical studies demonstrated that sclerostin plays a critical role in bone homeostasis and that its deficiency or pharmacological neutralization increases bone formation. Dysregulation of sclerostin expression also underlies the pathophysiology of skeletal disorders characterized by loss of bone mass as well as the damaging effects of some cancers in bone...
October 11, 2016: Bone
Kristin L Popp, William McDermott, Julie M Hughes, Stephanie A Baxter, Steven D Stovitz, Moira A Petit
PURPOSE: To determine differences in bone geometry, estimates of bone strength, muscle size and bone strength relative to load, in women runners with and without a history of stress fracture. METHODS: We recruited 32 competitive distance runners aged 18-35, with (SFX, n=16) or without (NSFX, n=16) a history of stress fracture for this case-control study. Peripheral quantitative computed tomography (pQCT) was used to assess volumetric bone mineral density (vBMD, mg/mm(3)), total (ToA) and cortical (CtA) bone areas (mm(2)), and estimated compressive bone strength (bone strength index; BSI, mg/mm(4)) at the distal tibia...
October 10, 2016: Bone
Daniel G Whitney, Harshvardhan Singh, Freeman Miller, Mary F Barbe, Jill M Slade, Ryan T Pohlig, Christopher M Modlesky
INTRODUCTION: Nonambulatory children with severe cerebral palsy (CP) have underdeveloped bone architecture, low bone strength and a high degree of fat infiltration in the lower extremity musculature. The present study aims to determine if such a profile exists in ambulatory children with mild CP and if excess fat infiltration extends into the bone marrow. MATERIALS AND METHODS: Ambulatory children with mild spastic CP and typically developing children (4 to 11years; 12/group) were tested...
October 9, 2016: Bone
K Pernelle, L Imbert, C Bosser, J-C Auregan, M Cruel, A Ogier, P Jurdic, T Hoc
Human cortical bone permanently remodels itself resulting in a haversian microstructure with heterogeneous mechanical and mineral properties. Remodeling is carried out by a subtle equilibrium between bone formation by osteoblasts and bone degradation by osteoclasts. The mechanisms regulating osteoclast activity were studied using easy access supports whose homogeneous microstructures differ from human bone microstructure. In the current study, we show that human osteoclasts resorb human cortical bone non-randomly with respect to this specific human bone microstructural heterogeneity...
October 8, 2016: Bone
Satoru Otsuru, Kathleen M Overholt, Timothy S Olson, Ted J Hofmann, Adam J Guess, Victoria M Velazquez, Takashi Kaito, Massimo Dominici, Edwin M Horwitz
Despite years of extensive investigation, the cellular origin of heterotopic ossification (HO) has not been fully elucidated. We have previously shown that circulating bone marrow-derived osteoblast progenitor cells, characterized by the immunophenotype CD45-/CD44+/CXCR4+, contributed to the formation of heterotopic bone induced by bone morphogenetic protein (BMP)-2. In contrast, other reports have demonstrated the contribution of CD45+ hematopoietic derived cells to HO. Therefore, in this study, we developed a novel triple transgenic mouse strain that allows us to visualize CD45+ cells with red fluorescence and mature osteoblasts with green fluorescence...
October 7, 2016: Bone
Ilkka Vuorimies, Heidi Arponen, Helena Valta, Outi Tiesalo, Marja Ekholm, Helena Ranta, Marjut Evälahti, Outi Mäkitie, Janna Waltimo-Sirén
Bisphosphonates have established their role as medical therapy for pediatric osteogenesis imperfecta (OI) patients. Since bisphosphonates have also been shown to delay tooth development in animal models, we aimed to assess whether the medication has a similar effect on children with OI. In this cross-sectional study, bisphosphonate-treated OI patients of whom dental panoramic tomograph was taken between 3 and 16years of age formed the study group. The patients, 22 in total, had been treated with pamidronate, zoledronic acid or risedronate for at least one year before the radiography...
October 7, 2016: Bone
Christian Faul
Fibroblast growth factors (FGF) are mitogenic signal mediators that induce cell proliferation and survival. Although cardiac myocytes are post-mitotic, they have been shown to be able to respond to local and circulating FGFs. While precise molecular mechanisms are not well characterized, some FGF family members have been shown to induce cardiac remodeling under physiologic conditions by mediating hypertrophic growth in cardiac myocytes and by promoting angiogenesis, both events leading to increased cardiac function and output...
October 7, 2016: Bone
J Jakob Schwiedrzik, Mohammad J Mirzaali, Suwanwadee Thaiwichai, James P Best, Johann Michler, Philippe K Zysset, Uwe Wolfram
No abstract text is available yet for this article.
October 3, 2016: Bone
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