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https://www.readbyqxmd.com/read/28547661/targeting-sclerostin-in-postmenopausal-osteoporosis-focus-on-romosozumab-and-blosozumab
#1
Ian R Reid
Most current treatments for osteoporosis inhibit bone resorption and reduce total fracture numbers by about one-quarter. The identification of the osteocytic protein sclerostin as a potent regulator of bone turnover and bone density has led to the development of a new therapeutic class-agents that inhibit sclerostin activity, resulting in increased bone formation and reduced bone resorption. Romosozumab and blosozumab are monoclonal antibodies that bind to sclerostin, reducing its inhibition of Wnt signaling...
May 25, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28543940/greater-gains-in-spine-and-hip-strength-for-romosozumab-compared-to-teriparatide-in-postmenopausal-women-with-low-bone-mass
#2
T M Keaveny, D B Crittenden, M A Bolognese, H K Genant, K Engelke, B Oliveri, J P Brown, B L Langdahl, C Yan, A Grauer, C Libanati
Romosozumab is a monoclonal antibody that inhibits sclerostin and has been shown to reduce the risk of fractures within 12 months. In a Phase II, randomized, placebo-controlled clinical trial of treatment-naïve postmenopausal women with low bone mass, romosozumab increased BMD at the hip and spine by the dual effect of increasing bone formation and decreasing bone resorption. In a substudy of that trial, which included placebo and teriparatide arms, here we investigated whether those observed increases in BMD also resulted in improvements in estimated strength, as assessed by finite element analysis...
May 25, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28543818/bone-formation-is-coupled-to-resorption-via-suppression-of-sclerostin-expression-by-osteoclasts
#3
Masanori Koide, Yasuhiro Kobayashi, Teruhito Yamashita, Shunsuke Uehara, Midori Nakamura, B Yukihiro Hiraoka, Yuki Ozaki, Tadahiro Iimura, Hisataka Yasuda, Naoyuki Takahashi, Nobuyuki Udagawa
Bone formation is coupled to bone resorption throughout life. However, it is not fully elucidated the coupling mechanisms. Using Tnfrsf11b-deficient (OPG(-/-) ) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/beta-catenin signals were higher in OPG(-/-) and RANKL-transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl-CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures...
May 24, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28540603/positioning-novel-biologicals-in-ckd-mineral-and-bone-disorders
#4
REVIEW
Lida Tartaglione, Marzia Pasquali, Silverio Rotondi, Maria Luisa Muci, Adrian Covic, Sandro Mazzaferro
Renal osteodystrophy (ROD), the histologic bone lesions of chronic kidney disease (CKD), is now included in a wider syndrome with laboratory abnormalities of mineral metabolism and extra-skeletal calcifications or CKD-mineral and bone disorders (CKD-MBD), to highlight the increased burden of mortality. Aging people, frequently identified as early CKD, could suffer from either the classical age-related osteoporosis (OP) or ROD. Distinguishing between these two bone diseases may not be easy without bone biopsy...
May 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28534995/low%C3%A2-level-mechanical-vibration-enhances-osteoblastogenesis-via-a-canonical-wnt-signaling%C3%A2-associated-mechanism
#5
Heqi Gao, Mingming Zhai, Pan Wang, Xuhui Zhang, Jing Cai, Xiaofei Chen, Guanghao Shen, Erping Luo, Da Jing
Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low‑magnitude, high‑frequency whole‑body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive...
May 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28530511/wnt-signaling-related-osteokines-and-transforming-growth-factors-before-and-after-a-single-bout-of-plyometric-exercise-in-child-and-adolescent-females
#6
Jennifer Dekker, Katlynne Nelson, Nigel Kurgan, Bareket Falk, Andrea Josse, Panagiota Klentrou
This study examined resting levels of catabolic and anabolic osteokines related to Wnt signaling and their responses to a single bout of plyometric exercise in child and adolescent females. Fourteen pre-menarcheal girls (10.5 ± 1.8 years old) and 12 post-menarcheal adolescent girls (15.0 ± 1.0 years old) performed a plyometric exercise trial. One resting and three post-exercise blood samples (5 min, 1h, 24h post-exercise) were analysed for sclerostin (SOST), dickkopf-1 (DKK-1), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-β ligand (RANKL) and transforming growth factors (TGF-β1, TGF-β2 and TGF-β3)...
May 22, 2017: Pediatric Exercise Science
https://www.readbyqxmd.com/read/28529816/sclerostin-activity-plays-a-key-role-in-the-negative-effect-of-glucocorticoid-signaling-on-osteoblast-function-in-mice
#7
Eric E Beier, Tzong-Jen Sheu, Emily A Resseguie, Masahiko Takahata, Hani A Awad, Deborah A Cory-Slechta, J Edward Puzas
Stress during prenatal development is correlated with detrimental cognitive and behavioral outcomes in offspring. However, the long-term impact of prenatal stress (PS) and disrupted glucocorticoid signaling on bone mass and strength is not understood. In contrast, the detrimental effect of lead (Pb) on skeletal health is well documented. As stress and Pb act on common biological targets via glucocorticoid signaling pathways and co-occur in the environment, this study first sought to assess the combined effect of stress and Pb on bone quality in association with alterations in glucocorticoid signaling...
2017: Bone Research
https://www.readbyqxmd.com/read/28529724/recent-advances-in-the-management-of-osteoporosis
#8
REVIEW
Seiji Fukumoto, Toshio Matsumoto
There has been substantial progress in the management of patients with osteoporosis and the prevention of osteoporotic fractures. Currently available strong anti-resorptive agents are bisphosphonates and an anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody, denosumab. Although bisphosphonates and denosumab both inhibit bone resorption and prevent vertebral and non-vertebral fractures, their mechanisms of action are different. Whereas bisphosphonates' effects on bone mineral density and fracture peak around 3 to 5 years and become plateaued, those of denosumab are maintained for up to 10 years...
2017: F1000Research
https://www.readbyqxmd.com/read/28529307/genetic-deletion-of-sost-or-pharmacological-inhibition-of-sclerostin-prevent-multiple-myeloma-induced-bone-disease-without-affecting-tumor-growth
#9
J Delgado-Calle, J Anderson, M D Cregor, K W Condon, S A Kuhstoss, L I Plotkin, T Bellido, G D Roodman
Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl) levels, an osteocyte-derived inhibitor of Wnt/β-catenin signaling, are elevated in MM patient sera and are increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28526959/adjuvant-tamoxifen-but-not-aromatase-inhibitor-therapy-decreases-serum-levels-of-the-wnt-inhibitor-dickkopf-1-while-not-affecting-sclerostin-in-breast-cancer-patients
#10
Andy Göbel, Jan D Kuhlmann, Theresa Link, Pauline Wimberger, Andrew J Browne, Martina Rauner, Lorenz C Hofbauer, Tilman D Rachner
PURPOSE: Endocrine therapies, including tamoxifen or aromatase inhibitors, are indispensable for the treatment of patients with estrogen receptor (ER)- and/or progesterone-positive breast cancer. Whereas tamoxifen displays partial ER agonistic effects in bone, aromatase inhibitors increase bone resorption and fracture risk. The Wnt inhibitors dickkopf-1 (DKK-1) and sclerostin negatively impact bone formation and are considered targets for the treatment of bone disorders. However, the effect of endocrine therapies on serum DKK-1 and sclerostin levels in patients with primary breast cancer remains elusive...
May 19, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28521873/low-periostin-levels-in-adult-patients-with-langerhans-cell-histiocytosis-are-independently-associated-with-the-disease-activity
#11
Athanasios D Anastasilakis, Stergios A Polyzos, Marina Tsoli, Athanasios Papatheodorou, Panagiotis Kokkoris, Gregory Kaltsas, Evangelos Terpos, Polyzois Makras
PURPOSE: Langerhans cell histiocytosis (LCH) is a rare proliferative disease of cells of the CD1a+/CD207+ myeloid dendritic cell lineage that may infiltrate one or more organs or systems at all ages. We aimed to evaluate periostin and sclerostin serum levels in adult patients with LCH. PROCEDURES: This was a cross-sectional study comparing 38 adult patients with LCH with 38 age- and sex-matched healthy controls. Serum periostin and sclerostin levels were measured to compare between LCH patients and controls as well as between patients with active and non-active disease...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28515094/inhibiting-the-osteocyte-specific-protein-sclerostin-increases-bone-mass-and-fracture-resistance-in-multiple-myeloma
#12
Michelle M McDonald, Michaela R Reagan, Scott E Youlten, Sindhu T Mohanty, Anja Seckinger, Rachael L Terry, Jessica A Pettitt, Marija K Simic, Tegan L Cheng, Alyson Morse, Lawrence M T Le, David Abi-Hanna, Ina Kramer, Carolyne Falank, Heather Fairfield, Irene M Ghobrial, Paul A Baldock, David G Little, Michaela Kneissel, Karin Vanderkerken, J H Duncan Bassett, Graham R Williams, Babatunde O Oyajobi, Dirk Hose, Tri G Phan, Peter I Croucher
Multiple myeloma is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Treatment with bisphosphonates, which inhibit bone resorption, prevents bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28509836/make-no-bones-about-it-rotator-cuff-repair-healing-is-not-just-about-the-tendon-commentary-on-an-article-by-shivam-a-shah-phd-et-al-sclerostin-antibody-treatment-enhances-rotator-cuff-tendon-to-bone-healing-in-an-animal-model
#13
https://www.readbyqxmd.com/read/28509826/sclerostin-antibody-treatment-enhances-rotator-cuff-tendon-to-bone-healing-in-an-animal-model
#14
Shivam A Shah, Ioannis Kormpakis, Necat Havlioglu, Michael S Ominsky, Leesa M Galatz, Stavros Thomopoulos
BACKGROUND: Rotator cuff tears are a common source of pain and disability, and poor healing after repair leads to high retear rates. Bone loss in the humeral head before and after repair has been associated with poor healing. The purpose of the current study was to mitigate bone loss near the repaired cuff and improve healing outcomes. METHODS: Sclerostin antibody (Scl-Ab) treatment, previously shown to increase bone formation and strength in the setting of osteoporosis, was used in the current study to address bone loss and enhance rotator cuff healing in an animal model...
May 17, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/28503694/detection-of-early-osteogenic-commitment-in-primary-cells-using-raman-spectroscopy
#15
Stephanie J Smith, Roger Emery, Andrew Pitsillides, Claire E Clarkin, Sumeet Mahajan
Major challenges in the development of novel implant surfaces for artificial joints include osteoblast heterogeneity and the lack of a simple and sensitive in vitro assay to measure early osteogenic responses. Raman spectroscopy is a label-free, non-invasive and non-destructive vibrational fingerprinting optical technique that is increasingly being applied to detect biochemical changes in cells. In this study Raman spectroscopy has been used to obtain bone cell-specific spectral signatures and to identify any changes therein during osteoblast commitment and differentiation of primary cells in culture...
May 15, 2017: Analyst
https://www.readbyqxmd.com/read/28501932/factors-affecting-serum-sclerostin-in-postmenopausal-women
#16
Tomoyuki Kawada
No abstract text is available yet for this article.
May 13, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28493902/circulating-levels-of-sclerostin-but-not-dkk1-associate-with-laboratory-parameters-of-ckd-mbd
#17
Geert J Behets, Liesbeth Viaene, Björn Meijers, Frank Blocki, Vincent M Brandenburg, Anja Verhulst, Patrick C D'Haese, Pieter Evenepoel
INTRODUCTION: Mounting evidence indicates that a disturbed Wnt-β-catenin signaling may be involved in the pathogenesis of chronic kidney disease-mineral and bone and mineral disorder (CKD-MBD). Data on the impact of CKD on circulating levels of the Wnt antagonists sclerostin and Dickkopf related protein 1 (DKK1) and the relationship with laboratory parameters of CKD-MBD are incomplete. METHODS: We analyzed serum sclerostin and DKK1 in 308 patients across the stages of chronic kidney disease (kDOQI stage 1-2 n = 41; CKD stage 3 n = 54; CKD stage 4-5 n = 54; hemodialysis n = 100; peritoneal dialysis n = 59) as well as in 49 healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28492360/resveratrol-inhibits-periodontitis-related-bone-loss-in-rats-submitted-to-cigarette-smoke-inhalation
#18
Fernanda V Ribeiro, Danilo S Pino, Felipe C Franck, Bruno B Benatti, Howard Tenenbaum, Dip Perio, John E Davies, Suzana P Pimentel, Renato C Casarin, Fabiano R Cirano, Marcio Z Casati
BACKGROUND: Alternative therapeutic approaches have been explored in order to modulate the host's response to periodontal disease. The knowledge of new strategies to treat periodontitis is particularly relevant in patients presenting augmented risk to periodontitis, as smokers. The aim of this study was to investigate the impact of Resveratrol (RESV) on the progression of experimental periodontitis (EP) in the presence of cigarette smoke inhalation (CSI). METHODS: Rats were assigned to: CSI+RESV(n=20); CSI+placebo(n=20); Non-CSI(n=20)...
May 11, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28488158/negative-impact-of-high-cumulative-glucocorticoid-dose-on-bone-metabolism-of-patients-with-myasthenia-gravis
#19
Nayara Felicidade Tomaz Braz, Natalia Pessoa Rocha, Érica Leandro Marciano Vieira, Rodrigo Santiago Gomez, Izabela Guimarães Barbosa, Olívio Brito Malheiro, Adriana Maria Kakehasi, Antonio Lucio Teixeira
This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®...
May 9, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28482269/skeletal-growth-and-bone-mineral-acquisition-in-type-1-diabetic-children-abnormalities-of-the-gh-igf-1-axis
#20
REVIEW
Manish Raisingani, Brar Preneet, Brenda Kohn, Shoshana Yakar
Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases diagnosed in childhood. Childhood and adolescent years are also the most important period for growth in height and acquisition of skeletal bone mineral density (BMD). The growth hormone (GH)/insulin like growth factor -1 (IGF-1) axis which regulates growth, is affected by T1DM, with studies showing increased GH and decreased IGF-1 levels in children with T1DM. There is conflicting data as to whether adolescents with TIDM are able to achieve their genetically-determined adult height...
April 28, 2017: Growth Hormone & IGF Research
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