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Bone Reports

Thomas Lind, Roberta Lugano, Ann-Marie Gustafson, Maria Norgård, Arie van Haeringen, Anna Dimberg, Håkan Melhus, Stephen P Robertson, Göran Andersson
Angulated femurs are present prenatally both in CYP26B1 deficient humans with a reduced capacity to degrade retinoic acid (RA, the active metabolite of vitamin A), and mice overexpressing vascular endothelial growth factor a (Vegfa). Since excessive ingestion of vitamin A is known to induce spontaneous fractures and as the Vegfa-induced femur angulation in mice appears to be caused by intrauterine fractures, we analyzed bones from a CYP26B1 deficient human and rats with hypervitaminosis A to further explore Vegfa as a mechanistic link for the effect of vitamin A on bone...
December 2018: Bone Reports
Stacy A Semevolos, Katja F Duesterdieck-Zellmer, Maureen Larson, Marc A Kinsley
Osteochondrosis (OC) is a naturally occurring disease of the articular-epiphyseal cartilage and subchondral bone layers, leading to pain and decreased mobility. The objective of this study was to characterize gene and protein expression of apoptotic markers in chondrocytes surrounding cartilage canals and along the osteochondral junction of osteochondrosis (OC)-affected and normal cartilage, using naturally occurring disease in horses. Paraffin-embedded osteochondral samples (6 OC, 8 normal controls) and cDNA from chondrocytes captured with laser capture microdissection (4 OC, 6 normal controls) were obtained from the lateral trochlear ridge of femoropatellar joints in 14 immature horses (1-6 months of age)...
December 2018: Bone Reports
Kristen B Farrell, Alexander Karpeisky, Douglas H Thamm, Shawn Zinnen
Bones provide essential functions and are sites of unique biochemistry and specialized cells, but can also be sites of disease. The treatment of bone disorders and neoplasia has presented difficulties in the past, and improved delivery of drugs to bone remains an important goal for achieving effective treatments. Drug targeting strategies have improved drug localization to bone by taking advantage of the high mineral concentration unique to the bone hydroxyapatite matrix, as well as tissue-specific cell types...
December 2018: Bone Reports
Takahiro Yamashita, Hiroshi Hagino, Ikuta Hayashi, Masako Hayashibara, Atsushi Tanida, Keita Nagira, Ryohei Fukui, Hideki Nagashima
Objectives: Cathepsin K is expressed by osteoclasts and synovial fibroblasts and degrades key components of bone and cartilage. Inhibition of cathepsin K protease activity may be beneficial for the prevention of bone erosion and cartilage degradation in rheumatoid arthritis (RA). The collagen-induced arthritis (CIA) rat model is well established for studying the pathology and treatment of RA. We investigated the effect of ONO-KK1-300-01, a cathepsin K inhibitor (CKI), on arthritis and bone mineral density (BMD) in rats with CIA...
December 2018: Bone Reports
Takeshi Miyamoto, Akiyoshi Hirayama, Yuiko Sato, Tami Koboyashi, Eri Katsuyama, Hiroya Kanagawa, Atsuhiro Fujie, Mayu Morita, Ryuichi Watanabe, Toshimi Tando, Kana Miyamoto, Takashi Tsuji, Atsushi Funayama, Tomoyoshi Soga, Masaru Tomita, Masaya Nakamura, Morio Matsumoto
Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. Low bone mass and/or pre-existing bone fragility fractures serve as diagnostic criteria in deciding when to start medication for osteoporosis. Although osteoporosis is a metabolic disorder, metabolic markers to predict reduced bone mass are unknown. Here, we show serum metabolomics profiles of women grouped as pre-menopausal with normal bone mineral density (BMD) (normal estrogen and normal BMD; NN), post-menopausal with normal BMD (low estrogen and normal BMD; LN) or post-menopausal with low BMD (low estrogen and low BMD; LL) using comprehensive metabolomics analysis...
December 2018: Bone Reports
Daniel D Bikle, Sophie Patzek, Yongmei Wang
Although the kidney was initially thought to be the sole organ responsible for the production of 1,25(OH)2 D via the enzyme CYP27b1, it is now appreciated that the expression of CYP27b1 in tissues other than the kidney is wide spread. However, the kidney is the major source for circulating 1,25(OH)2 D. Only in certain granulomatous diseases such as sarcoidosis does the extra renal tissue produce sufficient 1,25(OH)2 D to contribute to the circulating levels, generally associated with hypercalcemia, as illustrated by the case report preceding the review...
June 2018: Bone Reports
Megan E Mancuso, Joshua E Johnson, Sabahat S Ahmed, Tiffiny A Butler, Karen L Troy
While weight-bearing and resistive exercise modestly increases aBMD, the precise relationship between physical activity and bone microstructure, and strain in humans is not known. Previously, we established a voluntary upper-extremity loading model that assigns a person's target force based on their subject-specific, continuum FE-estimated radius bone strain. Here, our purpose was to quantify the inter-individual variability in radius microstructure and FE-estimated strain explained by site-specific mechanical loading history, and to determine whether variability in strain is captured by aBMD, a clinically relevant measure of bone density and fracture risk...
June 2018: Bone Reports
Jenny E Gunton, Christian M Girgis
Vitamin D is increasingly recognised to play an important role in normal muscle function. Low vitamin D status is associated with an increased risk of falls and proximal weakness. Since vitamin D deficiency is very common, and the signs are non-specific, it is important to maintain a high index of suspicion of vitamin D deficiency in patients with muscle pain and weakness, and it is simple to measure serum 25(OH) vitamin D. Therapy is cheap, safe and effective, but sometimes a larger dose may be needed, and, as shown in our case report, willingness of people to pay for an over the counter medication can be an issue...
June 2018: Bone Reports
Mikkel Bo Brent, Jesper Skovhus Thomsen, Annemarie Brüel
Thrombin is a key component in the coagulation cascade where it converts factor V, VIII, XI, and fibrinogen. In addition to the abundant production of thrombin in the liver, osteoclasts synthesize and secrete thrombin as well. Osteoblasts express thrombin receptors, and it has been reported that thrombin stimulates the expression of RANKL relatively to OPG, resulting in greater osteoclast activation and bone degradation. Pradaxa (dabigatran etexilate, DE) is a new anticoagulant, which has recently been approved for clinical use...
June 2018: Bone Reports
Kornelia Galior, Hemamalini Ketha, Stefan Grebe, Ravinder J Singh
In early 2000's vitamin-D deficiency was shown to be prevalent in several countries including the United States (US). Studies exploring the role of vitamin-D metabolism in diverse disease pathways generated an increased demand for vitamin-D supplementation and an immense public interest in measurement of vitamin-D metabolite levels. In this report, we review the role of vitamin-D metabolism in disease processes, clinical utility of measuring vitamin-D metabolites including 25-hydroxyvitamin-D (25(OH)D), 1,25-dihydroxyvitamin-D and 24,25-dihydroxyvitamin-D and discuss vitamin-D assay methodologies including immunoassays and liquid chromatography mass spectrometry (LC-MS/MS) assays...
June 2018: Bone Reports
Deepak Kumar Khajuria, Maria Raygorodskaya, Eugene Kobyliansky, Yankel Gabet, Sahar Hiram Bab, Chen Shochat, Arkady Torchinsky, David Karasik
The long term skeletal effects of antenatal exposure to teratogen 5-deoxy-2'-cytidine (5-AZA) were studied using two inbred strains, C3H/HeJ (C3H, with inherently stronger bones) and C57Bl/6J (C57, with weaker bones). We previously reported that in-utero exposure to 5-AZA resulted in loss of bone quality in 3- and 6-mo-old C3H offspring. In this study, we further examined whether the long-term effects of an acute teratogenic exposure are still evident in older mice. Bone phenotypes of 12 mo-old mice exposed to a single injection of 5-AZA on day 10 of their mother's pregnancy were evaluated by micro-computed tomography and compared to the untreated controls...
June 2018: Bone Reports
Jenalyn L Yumol, C Brent Wakefield, Sandra M Sacco, Philip J Sullivan, Elena M Comelli, Wendy E Ward
Background: The AIN-93G reference (REF) diet is used to allow the comparison within and between studies of different research groups but its levels of vitamin D (vit D) and calcium (Ca) may be higher than required for healthy bone structure and bone mineral density (BMD). Objective: To determine if lower dietary levels of Ca (3.5, 3 or 2.5 g Ca/kg diet) at 1 of 2 levels of vit D (100 or 400 IU/kg diet) supports similar development of bone structure and BMD compared to AIN-93G reference (REF) diet in female CD-1 mice at 2 and 4 months of age...
June 2018: Bone Reports
Fernando Y Zapata-Cornelio, Zhongmin Jin, David C Barton, Alison C Jones, Ruth K Wilcox
Long bone fractures are common and although treatments are highly effective in most cases, it is challenging to achieve successful repair for groups such as open and periprosthetic fractures. Previous biomechanical studies of fracture repair, including computer and experimental models, have simplified the fracture with a flat geometry or a gap, and there is a need for a more accurate fracture representation to mimic the situation in-vivo . The aims of this study were to develop a methodology for generating repeatable transverse fractures in long bones in-vitro and to characterise the fracture surface using non-invasive computer tomography (CT) methods...
June 2018: Bone Reports
Mohammad W Aref, Elizabeth A Swallow, Neal X Chen, Sharon M Moe, Matthew R Allen
Patients with chronic kidney disease (CKD) are at an alarming risk of cardiovascular disease and fracture-associated mortality. CKD has been shown to have negative effects on vascular reactivity and organ perfusion. Although alterations in bone blood flow are linked to dysregulation of bone remodeling and mass in multiple conditions, changes to skeletal perfusion in the setting of CKD have not been explored. The goal of this study was to establish the effect of CKD on skeletal perfusion in a rat model of CKD...
June 2018: Bone Reports
M J Devlin, A Robbins, M N Cosman, C A Moursi, A M Cloutier, L Louis, M Van Vliet, C Conlon, M L Bouxsein
The effects of obesity on bone metabolism are complex, and may be mediated by consumption of a high fat diet and/or by obesity-induced metabolic dysregulation. To test the hypothesis that both high fat (HF) diet and diet-induced metabolic disease independently decrease skeletal acquisition, we compared effects of HF diet on bone mass and microarchitecture in two mouse strains: diet-induced obesity (DIO)-susceptible C57BL/6J (B6) and DIO-resistant FVB/NJ (FVB). At 3 wks of age we weaned 120 female FVB and B6 mice onto normal (N, 10% Kcal/fat) or HF diet (45% Kcal/fat) and euthanized them at 6, 12 and 20 weeks of age (N = 10/grp)...
June 2018: Bone Reports
Kiyotaka Okada, Naoyuki Kawao, Kohei Tatsumi, Masayoshi Ishida, Yoshimasa Takafuji, Shinzi Kurashimo, Katsumi Okumoto, Kotaro Kojima, Osamu Matsuo, Hiroshi Kaji
We previously revealed that stromal cell-derived factor-1 (SDF-1) is involved in the changes in the number of bone marrow stem cells during the bone repair process in mice. Moreover, we reported that plasminogen (Plg) deficiency delays bone repair and the accumulation of macrophages at the site of bone damage in mice. We investigated the roles of Plg in the changes in bone marrow stem cells during bone repair. We analyzed the numbers of hematopoietic stem cells (HSC) and mesenchymal stem cells (MSCs) within bone marrow from Plg-deficient and wild-type mice after a femoral bone injury using flow cytometric analysis...
June 2018: Bone Reports
Sarah L West, Chamith S Rajapakse, Tammy Rayner, Rhiannon Miller, Michelle A Slinger, Greg D Wells
Bone imaging is currently the best non-invasive way to assess changes to bone associated with aging or chronic disease. However, common imaging techniques such as dual energy x-ray absorptiometry are associated with limitations. Magnetic resonance imaging (MRI) is a radiation-free technique that can measure bone microarchitecture. However, published MRI bone assessment protocols use specialized MRI coils and sequences and therefore have limited transferability across institutions. We developed a protocol on a Siemens 3 Tesla MRI machine, using a commercially available coil (Siemens 15 CH knee coil), and manufacturer supplied sequences to acquire images at the tibia...
June 2018: Bone Reports
T C Hausherr, K Nuss, E Thein, S Krähenbühl, L A Applegate, D P Pioletti
Several approaches to combine bone substitutes with biomolecules, cells or mechanical loading have been explored as an alternative to the limitation and risk-related bone auto- and allo-grafts. In particular, human bone progenitor cells seeded in porous poly(L-lactic acid)/tricalcium phosphate scaffolds have shown promising results. Furthermore, the application of mechanical loading has long been known to be a key player in the regulation of bone architecture and mechanical properties. Several in vivo studies have pointed out the importance of its temporal offset...
June 2018: Bone Reports
Luuk J J Scheres, Fleur S van Dijk, Arjan J Harsevoort, Atty T H van Dijk, Anne Marieke Dommisse, Guus J M Janus, Anton A M Franken
An expert center for adults with Osteogenesis Imperfecta (OI) has been founded at the Isala Hospital in Zwolle, the Netherlands to achieve optimal care for adults with OI. Clinical data such as patient history, Dual Energy X-ray Absorptiometry measurements and laboratory findings are collected with patient consent. This study provides an overview of clinical characteristics of the patients who visited the clinic during its first 5 years, a total of 151 patients. In this study, we focus on bisphosphonate use and bone density measurements at time of presentation at the expert center...
June 2018: Bone Reports
Meena Balasubramanian, Rebecca Jones, Elizabeth Milne, Charlotte Marshall, Paul Arundel, Kath Smith, Nicholas J Bishop
Objectives: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; intelligence is reported to be normal. However, a minority of children seen also show symptomology consistent with an 'Autism Spectrum Disorder'. A joint genetics and psychology research study was undertaken to identify these patients using 'Gold Standard' research tools: Autism Diagnostic Inventory Revised (ADI-R); Autism Diagnostic Observation Schedule (ADOS) and undertake genetic analyses in them...
June 2018: Bone Reports
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