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https://www.readbyqxmd.com/read/28929919/evaluating-the-efficacy-of-functional-electrical-stimulation-therapy-assisted-walking-after-chronic-motor-incomplete-spinal-cord-injury-effects-on-bone-biomarkers-and-bone-strength
#1
B Catharine Craven, Lora M Giangregorio, S Mohammad Alavinia, Lindsie A Blencowe, Naaz Desai, Sander L Hitzig, Kei Masani, Milos R Popovic
To determine the efficacy of functional electrical stimulation therapy assisted walking (FES-T) compared to a conventional aerobic and resistance training (CONV) with respect to bone biomarkers and lower extremity bone strength outcomes among adults with chronic motor incomplete spinal cord injury (SCI). Design Parallel group randomized controlled trial ( www.clinicaltrials.gov - NCT0020196819). Site Tertiary academic rehabilitation centre in Canada. Methods Adults with chronic (≥18 months) motor incomplete SCI (C2-T12 AIS C-D) were consented and randomized to FES-T or CONV training for 45 minutes thrice-weekly for 4 months...
September 20, 2017: Journal of Spinal Cord Medicine
https://www.readbyqxmd.com/read/28928248/carbonic-anhydrase-iii-protects-osteocytes-from-oxidative-stress
#2
Chao Shi, Yuhei Uda, Christopher Dedic, Ehab Azab, Ningyuan Sun, Amira I Hussein, Christopher A Petty, Keertik Fulzele, Maria C Mitterberger-Vogt, Werner Zwerschke, Renata Pereira, Kunzheng Wang, Paola Divieti Pajevic
Osteocytes are master orchestrators of bone remodeling; they control osteoblast and osteoclast activities both directly via cell-to-cell communication and indirectly via secreted factors, and they are the main postnatal source of sclerostin and RANKL (receptor activator of NF-kB ligand), two regulators of osteoblast and osteoclast function. Despite progress in understanding osteocyte biology and function, much remains to be elucidated. Recently developed osteocytic cell lines-together with new genome editing tools-has allowed a closer look at the biology and molecular makeup of these cells...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28900298/sclerostin-induced-tumor-growth-bone-metastasis-and-osteolysis-in-breast-cancer
#3
Menghai Zhu, Changzhen Liu, Shifei Li, Shudong Zhang, Qi Yao, Qingkun Song
Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Many patients suffer from bone metastasis. Sclerostin, a key regulator of normal bone remodeling, is critically involved in osteolytic bone diseases. However, its role in breast cancer bone metastasis remains unknown. Here, we found that sclerostin was overexpressed in breast cancer tumor tissues and cell lines. Inhibition of sclerostin by antibody (Scl-Ab) significantly reduced migration and invasion of MDA-MB-231 and MCF-7 cells in a time- and dose-dependent manner...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893629/obesity-and-type-2-diabetes-not-a-diet-high-in-fat-sucrose-and-cholesterol-negatively-impacts-bone-outcomes-in-the-hyperphagic-otsuka-long-evans-tokushima-fatty-rat
#4
Laura C Ortinau, Melissa A Linden, Rebecca Dirkes, R Scott Rector, Pamela S Hinton
BACKGROUND: Obesity and type 2 diabetes (T2D) increase fracture risk; however, the association between obesity/T2D may be confounded by consumption of a diet high in fat, sucrose, and cholesterol (HFSC). OBJECTIVE: The study objective was to determine the main and interactive effects of obesity/T2D and a HFSC diet on bone outcomes using hyperphagic Otuska Long Evans Tokushima Fatty (OLETF) rats and normophagic Long Evans Tokushima Otsuka (LETO) controls. METHODS: At 8weeks of age, male OLETF and LETO rats were randomized to either a control (CON, 10 en% from fat as soybean oil) or HFSC (45 en% from fat as soybean oil/lard, 17 en% sucrose, and 1wt%) diet, resulting in four treatment groups...
September 9, 2017: Bone
https://www.readbyqxmd.com/read/28892457/romosozumab-or-alendronate-for-fracture-prevention-in-women-with-osteoporosis
#5
Kenneth G Saag, Jeffrey Petersen, Maria Luisa Brandi, Andrew C Karaplis, Mattias Lorentzon, Thierry Thomas, Judy Maddox, Michelle Fan, Paul D Meisner, Andreas Grauer
Background Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption. Methods We enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture (nonvertebral and symptomatic vertebral fracture) at the time of the primary analysis (after clinical fractures had been confirmed in ≥330 patients)...
September 11, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28884841/sclerostin-antibody-enhances-bone-formation-in-a-rat-model-of-distraction-osteogenesis
#6
Michelle M McDonald, Alyson Morse, Oliver Birke, Nicole Yc Yu, Kathy Mikulec, Lauren Peacock, Aaron Schindeler, Min Liu, Hua Zhu Ke, David G Little
Neutralizing monoclonal sclerostin antibodies are effective in promoting bone formation at a systemic level and in orthopedic scenarios including closed fracture repair. In this study we examined the effects of sclerostin antibody (Scl-Ab) treatment on regenerate volume, density and strength in a rat model of distraction osteogenesis. Surgical osteotomy was performed on 179 Sprague Dawley rats. After 1 week, rats underwent distraction for 2 weeks, followed by 6 weeks for consolidation. Two treatment groups received biweekly subcutaneous Scl-AbIII (a rodent form of Scl-Ab; 25 mg/kg), either from the start of distraction onwards or restricted to the consolidation phase...
September 8, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28882159/estrogen-attenuates-the-spondyloarthritis-manifestations-of-the-skg-arthritis-model
#7
Hyemin Jeong, Eun-Kyung Bae, Hunnyun Kim, Yeong Hee Eun, In Young Kim, Hyungjin Kim, Jaejoon Lee, Chan Hong Jeon, Eun-Mi Koh, Hoon-Suk Cha
BACKGROUND: Ankylosing spondylitis (AS) is a male-predominant disease, and radiographic evidence of damage is also more severe in males. Estrogen modulates immune-related processes such as T cell differentiation and cytokine production. This study aimed to evaluate the effect of estrogen on the disease activity of spondyloarthritis (SpA). METHODS: The effects of estrogen on the development of arthritis were evaluated by performing ovariectomy and 17β-estradiol (E2) pellet implantation in zymosan-treated SKG mice...
September 7, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28875158/thirty-days-of-spaceflight-does-not-alter-murine-calvariae-structure-despite-increased-sost-expression
#8
Timothy R Macaulay, Jamila H Siamwala, Alan R Hargens, Brandon R Macias
Previously our laboratory documented increases in calvaria bone volume and thickness in mice exposed to 15 days of spaceflight aboard the NASA Shuttle mission STS-131. However, the tissues were not processed for gene expression studies to determine what bone formation pathways might contribute to these structural adaptations. Therefore, this study was designed to investigate both the structural and molecular changes in mice calvariae after a longer duration of spaceflight. The primary purpose was to determine the calvaria bone volume and thickness of mice exposed to 30 days of spaceflight using micro-computed tomography for comparison with our previous findings...
December 2017: Bone Reports
https://www.readbyqxmd.com/read/28872686/weak-bones-in-diabetes-mellitus-an-update-on-pharmaceutical-treatment-options
#9
REVIEW
Daphne P L Lin, Crispin R Dass
OBJECTIVES: Diabetes mellitus is often associated with a number of complications such as nephropathy, neuropathy, retinopathy and foot ulcers. However, weak bone is a diabetic complication that is often overlooked. Although the exact mechanism for weak bones within diabetes mellitus is unclear, studies have shown that the mechanism does differ in both type I (T1DM) and type II diabetes (T2DM). This review, however, investigates the application of mesenchymal stem cells, recombinant human bone morphogenetic protein-2, teriparatide, insulin administration and the effectiveness of a peroxisome proliferator-activated receptor-ϒ modulator, netoglitazone in the context of diabetic weak bones...
September 5, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28860152/proteasome-inhibitor-bortezomib-is-a-novel-therapeutic-agent-for-focal-radiation-induced-osteoporosis
#10
Abhishek Chandra, Luqiang Wang, Tiffany Young, Leilei Zhong, Wei-Ju Tseng, Michael A Levine, Keith Cengel, X Sherry Liu, Yejia Zhang, Robert J Pignolo, Ling Qin
Bone atrophy and its related fragility fractures are frequent, late side effects of radiotherapy in cancer survivors and have a detrimental impact on their quality of life. In another study, we showed that parathyroid hormone 1-34 and anti-sclerostin antibody attenuates radiation-induced bone damage by accelerating DNA repair in osteoblasts. DNA damage responses are partially regulated by the ubiquitin proteasome pathway. In the current study, we examined whether proteasome inhibitors have similar bone-protective effects against radiation damage...
August 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28856390/hypogonadal-men-with-higher-body-mass-index-have-higher-bone-density-and-better-bone-quality-but-reduced-muscle-density
#11
Lina E Aguirre, Georgia Colleluori, Richard Dorin, David Robbins, Rui Chen, Bryan Jiang, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal
Although hypogonadism is a risk factor for bone loss and fractures, the different etiopathophysiology and hormonal profile of classical and obesity-induced hypogonadism may lead to differences in musculoskeletal profile. This is a cross-sectional study of hypogonadal men between 40 and 74 years old. Our outcomes include: areal bone mineral density (aBMD) and body composition by dual-energy X-ray absorptiometry; volumetric BMD (vBMD) and soft tissue composition of the tibia by peripheral quantitative computed tomography...
August 30, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28847532/effects-of-reduced-energy-availability-on-bone-metabolism-in-women-and-men
#12
Maria Papageorgiou, Kirsty J Elliott-Sale, Alan Parsons, Johnathan C Y Tang, Julie P Greeves, William D Fraser, Craig Sale
BACKGROUND: The short-term effects of low energy availability (EA) on bone metabolism in physically active women and men are currently unknown. PURPOSE: We evaluated the effects of low EA on bone turnover markers (BTMs) in a cohort of women and a cohort of men, and compared effects between sexes. METHODS: These studies were performed using a randomised, counterbalanced, crossover design. Eleven eumenorrheic women and eleven men completed two 5-day protocols of controlled (CON; 45kcal·kgLBM(-1)·d(-1)) and restricted (RES; 15kcal·kgLBM(-1)·d(-1)) EAs...
August 25, 2017: Bone
https://www.readbyqxmd.com/read/28842678/sost-deficiency-led-to-a-greater-cortical-bone-formation-response-to-mechanical-loading-and-altered-gene-expression
#13
David Pflanz, Annette I Birkhold, Laia Albiol, Tobias Thiele, Catherine Julien, Anne Seliger, Erin Thomson, Ina Kramer, Michaela Kneissel, Georg N Duda, Uwe Kornak, Sara Checa, Bettina M Willie
Bone adaptation optimizes mass and structure, but the mechano-response is already reduced at maturation. Downregulation of sclerostin was believed to be a mandatory step in mechano-adaptation, but in young mice it was shown that load-induced formation can occur independent of sclerostin, a product of the Sost gene. We hypothesized that the bone formation and resorption response to loading is not affected by Sost deficiency, but is age-specific. Our findings indicate that the anabolic response to in vivo tibial loading was reduced at maturation in Sost Knockout (KO) and littermate control (LC) mice...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28836858/investigational-anabolic-agents-for-the-treatment-of-osteoporosis-an-update-on-recent-developments
#14
Anastasia D Dede, Polyzois Makras, Athanasios D Anastasilakis
Teriparatide, a PTH analogue, was the first anabolic agent to be approved for the treatment of osteoporosis in 2002. Abaloparatide was also recently approved by the FDA. The need for other anabolic agents is still unmet. Areas covered: In this review, we discuss target molecules and recent advances in the field of anabolic therapy for osteoporosis. PTH and PTHrP analogues binding to the PTH receptor and different routes of administration of teriparatide to avoid the burden of daily subcutaneous injections are discussed...
August 29, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28811200/globular-adiponectin-reverses-osteo-sarcopenia-and-altered-body-composition-in-ovariectomized-rats
#15
Shyamsundar Pal China, Subhashis Pal, Sourav Chattopadhyay, Konica Porwal, Sapana Kushwaha, Sharmishtha Bhattacharyya, Monika Mittal, Anagha A Gurjar, Tarun Barbhuyan, Abhishek K Singh, Arun K Trivedi, Jiaur R Gayen, Sabyasachi Sanyal, Naibedya Chattopadhyay
Adiponectin regulates various metabolic processes including glucose flux, lipid breakdown and insulin response. We recently reported that adiponectin receptor1 (adipoR1) activation by a small molecule reverses osteopenia in leptin receptor deficient db/db (diabetic) mice. However, the role of adiponectin in bone metabolism under the setting of post-menopausal (estrogen-deficiency) osteopenia and associated metabolic derangements has not been studied. Here, we studied the therapeutic effect of the globular form of adiponectin (gAd), which is predominantly an adipoR1 agonist, in aged ovariectomized (OVX) rats and compared it with standard-of-care anti-osteoporosis drugs...
August 12, 2017: Bone
https://www.readbyqxmd.com/read/28806419/effects-of-short-term-dry-immersion-on-bone-remodeling-markers-insulin-and-adipokines
#16
Marie-Thérèse Linossier, Liubov E Amirova, Mireille Thomas, Myriam Normand, Marie-Pierre Bareille, Guillemette Gauquelin-Koch, Arnaud Beck, Marie-Claude Costes-Salon, Christine Bonneau, Claude Gharib, Marc-Antoine Custaud, Laurence Vico
BACKGROUND: Dry immersion (DI), a ground-based model of microgravity previously used in Russia, has been recently implemented in France. The aim of this study was to analyze early events in a short-term DI model in which all conditions are met to investigate who is first challenged from osteo- or adipo-kines and to what extent they are associated to insulin-regulating hormones. METHODS: Twelve healthy men were submitted to a 3-day DI. Fasting blood was collected during pre-immersion phase for the determination of the baseline data collection (BDC), daily during DI (DI24h, DI48H and DI72h), then after recovery (R+3h and R+24h)...
2017: PloS One
https://www.readbyqxmd.com/read/28805484/disparate-phospho-smad2-levels-in-advanced-type-2-diabetes-patients-with-diabetic-nephropathy-and-early-experimental-db-db-mouse-model
#17
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28805201/-osteoporosis-and-vascular-calcification-in-rheumatoid-arthritis-the-role-of-osteoprotegerin-and-sclerostin
#18
REVIEW
Magdalena Krajewska-Włodarczyk, Tomasz Stompór
Disorders of bone tissue metabolism and increased frequency of cardiovascular diseases are among the well-known, extra-articular complications of rheumatoid arthritis (ra). The mechanisms leading to local and generalized loss of bone tissue as well as those promoting calcification of vessels are similar. Recently, a great interest has aroused among the studies related to the meaning of the RANKL/RANK/OPG system and the Wnt/β-catenin signaling pathway, as biological links between the bone and vascular systems...
July 21, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28794403/chronological-immunolocalization-of-sclerostin-and-fgf23-in-the-mouse-metaphyseal-trabecular-and-cortical-bone
#19
Atsunaka Sakurai, Tomoka Hasegawa, Ai Kudo, Zhao Shen, Tomoya Nagai, Miki Abe, Taiji Yoshida, Hiromi Hongo, Tomomaya Yamamoto, Tsuneyuki Yamamoto, Kimimitsu Oda, Paulo Henrique Luiz de Freitas, Minqi Li, Hidehiko Sano, Norio Amizuka
To assess the chronological participation of sclerostin and FGF23 in bone metabolism, this study tracked the immunolocalization of sclerostin and FGF23 in the metaphyses of murine long bones from embryonic day 18 (E18) through 1 day after birth, 1 week, 2 weeks, 4 weeks, 8 weeks, and 20 weeks of age. We have selected two regions in the metaphyseal trabeculae for assessing sclerostin and FGF23 localization: close to the chondro-osseous junction, i.e., bone modeling site even in the adult animals, and the trabecular region distant from the growth plate, where bone remodeling takes place...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28782619/differential-responses-of-mechanosensitive-osteocyte-proteins-in-fore-and-hindlimbs-of-hindlimb-unloaded-rats
#20
Corinne E Metzger, Jessica E Brezicha, Jon P Elizondo, S Anand Narayanan, Harry A Hogan, Susan A Bloomfield
Osteocytes are believed to be the primary mechanosensors of bone tissue, signaling to osteoblasts and osteoclasts by releasing specific proteins. Sclerostin, interleukin-6 (IL-6), and insulin-like growth factor-I (IGF-I) are osteocyte proteins that signal to osteoblasts. The primary objective of this study was to determine if osteocyte protein response to mechanical unloading is restricted to the unloaded bone using the hindlimb unloading (HU) rodent model. We also examined tumor necrosis factor-α (TNF-α) due to its interactions with all three osteocyte proteins...
August 3, 2017: Bone
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