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https://www.readbyqxmd.com/read/28092987/emerging-treatment-approaches-for-myeloma-related-bone-disease
#1
Maria Gavriatopoulou, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos
Multiple myeloma is characterized by the presence of osteolytic lesions that leads to devastating skeletal-related events in the majority of patients. Myeloma bone disease is attributed to increased osteoclastic and suppressed osteoblastic activity. Areas covered: Bisphosphonates remain the main treatment option, however they have limitations on their own. Understanding the pathogenesis of myeloma bone disease may provide a roadmap for new therapeutic approaches. The pathway of RANKRANKLOPG pathway has revealed denosumab, a monoclonal antibody targeting RANKL as a novel emerging therapy for myeloma-related bone disease...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28091892/bariatric-roux-en-y-gastric-bypass-surgery-adipocyte-proteins-involved-in-increased-bone-remodeling-in-humans
#2
Maria Fernanda G Biagioni, Adriana L Mendes, Célia Regina Nogueira, Celso V Leite, Loraine Gollino, Gláucia Mfs Mazeto
PURPOSE: Bariatric surgery has been associated with bone remodeling changes. The action of adipokines on the expression of receptor activator of nuclear factor kappa β ligand (RANKL) and osteoprotegerin (OPG) and on an increase in sclerostin could be related to these changes. MATERIALS AND METHODS: This study aimed to assess the repercussions of weight loss, fat mass (FM), and fat-free mass (FFM) loss and biochemical and hormonal changes on bone remodeling markers after Roux-en-Y gastric bypass (RYGB)...
January 13, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28090669/the-association-between-sclerostin-and-incident-type-2-diabetes-risk-a-cohort-study
#3
Oriana Hoi Yun Yu, Brent Richards, Claudie Berger, Robert G Josse, William D Leslie, David Goltzman, Stephanie M Kaiser, Christopher S Kovacs, K Shawn Davison
OBJECTIVE: To determine whether sclerostin is associated with fasting glucose, insulin levels, insulin resistance or increased risk of incident type 2 diabetes. BACKGROUND: Type 2 diabetic patients have a higher risk of fractures. Recent studies suggest sclerostin, a regulator of osteoblast activity, is associated with diabetes. MATERIALS AND METHODS: Sclerostin levels were obtained from 1,778 individuals with no history of type 2 diabetes participating in the population-based Canadian Multicentre Osteoporosis Study (CaMos) cohort...
January 15, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28081119/sclerostin-promotes-bone-remodeling-in-the-process-of-tooth-movement
#4
Rui Shu, Ding Bai, Tzongjen Sheu, Yao He, Xianrui Yang, Chaoran Xue, Yiruo He, Mengyuan Zhao, Xianglong Han
Tooth movement is a biological process of bone remodeling induced by mechanical force. Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling. However, little is known regarding the role of sclerostin in tooth movement. In this study, models of experimental tooth movement were established in rats and mice. Sclerostin expression was investigated with immunohistochemistry staining, and osteoclastic activity was analyzed with tartrate-resistant acid phosphatase (TRAP) staining. MLO-Y4 osteocyte-like cells underwent uniaxial compression and tension stress or were cultured in hypoxia conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28078875/circulating-srage-in-the-diagnosis-of-osteolytic-bone-metastasis
#5
E Galliera, M G Marazzi, E Vianello, L Drago, A Luzzati, P Bendinelli, P Maroni, L Tacchini, M A Desiderio, M M Corsi Romanelli
Despite the clinical importance of metastasis to the skeleton, the diagnostic tools for early detection and monitoring of bone metastasis lack sensitivity and specificity. We evaluated a promising new serum biomarker, the soluble form of the Receptor of Advanced Glycosylated End-products (sRAGE). sRAGE is involved in the Wnt-signaling pathway, and has been reported to reduce the risk of cancer. We investigated the diagnostic potential of sRAGE to improve the detection and monitoring of bone metastasis. We measured sRAGE in the serum of control healthy subjects, patients with primary tumors and patients with bone metastasis...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28064540/romosozumab-for-the-treatment-of-osteoporosis
#6
Leonardo Bandeira, E Michael Lewiecki, John P Bilezikian
Sclerostin, a glycoprotein produced primarily by osteocytes, blocks the canonical Wnt signaling bone formation pathway. Romosozumab is a humanized monoclonal antibody to sclerostin that binds to sclerostin, permitting the engagement of Wnt ligands with their co-receptors, resulting in an increase in bone formation and bone mineral density (BMD). Clinical studies with romosozumab have shown dramatic improvements in BMD at the spine and hip. Romosozumab is associated with improvement in bone strength through mechanisms that include increases in bone formation and, different from classical osteoanabolic agents, suppression of bone resorption...
February 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28062506/wnt-signaling-pathway-inhibitor-sclerostin-inhibits-angiotensin-ii-induced-aortic-aneurysm-and-atherosclerosis
#7
Smriti Murali Krishna, Sai-Wang Seto, Roby J Jose, Jiaze Li, Susan K Morton, Erik Biros, Yutang Wang, Vianne Nsengiyumva, Jan H N Lindeman, Gabriela G Loots, Catherine M Rush, Jeffrey M Craig, Jonathan Golledge
OBJECTIVE: Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. APPROACH AND RESULTS: SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE(-/-)) mice (SOST(Tg)...
December 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28054585/osseous-differentiation-of-human-fat-tissue-grafts-from-tissue-engineering-to-tissue-differentiation
#8
Maryna Bondarava, Chiara Cattaneo, Bin Ren, Wolfgang E Thasler, Volkmar Jansson, Peter E Müller, Oliver B Betz
Conventional bone tissue engineering approaches require isolation and in vitro propagation of autologous cells, followed by seeding on a variety of scaffolds. Those protracted procedures impede the clinical applications. Here we report the transdifferentiation of human fat tissue fragments retrieved from subcutaneous fat into tissue with bone characteristics in vitro without prior cell isolation and propagation. 3D collagen-I cultures of human fat tissue were cultivated either in growth medium or in osteogenic medium (OM) with or without addition of Bone Morphogenetic Proteins (BMPs) BMP-2, BMP-7 or BMP-9...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28054306/circulating-dickkopf-1-and-sclerostin-in-patients-with-paget-s-disease-of-bone
#9
Luca Idolazzi, Angelo Fassio, Gaia Tripi, Vania Braga, Ombretta Viapiana, Giovanni Adami, Maurizio Rossini, Davide Gatti
Paget disease of bone is a chronic metabolic bone disorder characterized by increased bone resorption and new bone formation. The aim of this study is defining the role of inhibitors of canonical Wnt/b-catenin signaling pathway in patients with Paget disease of bone. Scarce and contrasting results have been reported in literature. We studied 40 patients (15 females and 25 males) with radiological and scintigraphic evidence of Paget disease of bone and 40 healthy subjects matched by age and sex. N-propeptide of type I collagen, C-terminal telopeptide of type I collagen, sclerostin, and Dickkopf-related protein 1 (DKK1) were evaluated by blood samples in our laboratory...
January 5, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28049653/mechanisms-in-endocrinology-diabetes-mellitus-a-state-of-low-bone-turnover-a-systematic-review-and-meta-analysis
#10
REVIEW
Katrine Hygum, Jakob Starup-Linde, Torben Harsløf, Peter Vestergaard, Bente L Langdahl
OBJECTIVE: To investigate the differences in bone turnover between diabetic patients and controls. DESIGN: A systematic review and meta-analysis. METHODS: A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms 'diabetes mellitus' and 'bone turnover', 'sclerostin', 'RANKL', 'osteoprotegerin', 'tartrate-resistant acid' and 'TRAP' were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls...
March 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28030966/systemic-drugs-that-influence-titanium-implant-osseointegration
#11
Dragos Apostu, Ondine Lucaciu, Gheorghe Dan Osvald Lucaciu, Bogdan Crisan, Liana Crisan, Mihaela Baciut, Florin Onisor, Grigore Baciut, Radu Septimiu Câmpian, Simion Bran
Titanium implants are widely used on an increasing number of patients in orthopedic and dental medicine. Despite the good survival rates of these implants, failures that lead to important socio-economic consequences still exist. Recently, research aimed at improving implant fixation, a process called osseointegration, has focused on a new, inovative field: systemic delivery of drugs. Following implant fixation, patients receive systemic drugs that could either impair or enhance osseointegration; these drugs include anabolic and anti-catabolic bone-acting agents in addition to new treatments...
December 28, 2016: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28028632/the-rs3736228-polymorphism-in-the-lrp5-gene-is-associated-with-calcaneal-ultrasound-parameter-but-not-with-body-composition-in-a-cohort-of-young-caucasian-adults
#12
María Correa-Rodríguez, Jacqueline Schmidt-RioValle, Blanca Rueda-Medina
The aim of the present study was to investigate the possible influence of low-density lipoprotein receptor-related protein 5 (LRP5) and sclerostin (SOST) genes as genetic factors contributing to calcaneal quantitative ultrasound (QUS) and body composition variables in a population of young Caucasian adults. The study population comprised a total of 575 individuals (mean age 20.41years; SD 2.36) whose bone mass was assessed through QUS to determine broadband ultrasound attenuation (BUA, dB/MHz). Body composition measurements were performed using a body composition analyser...
December 27, 2016: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28017868/fabrication-of-amorphous-strontium-polyphosphate-microparticles-that-induce-mineralization-of-bone-cells-in-vitro-and-in-vivo
#13
Werner E G Müller, Emad Tolba, Maximilian Ackermann, Meik Neufurth, Shunfeng Wang, Qingling Feng, Heinz C Schröder, Xiaohong Wang
: Here we describe the fabrication process of amorphous strontium-polyphosphate microparticles ("Sr-a-polyP-MP"). The effects of these particles on growth and gene expression were investigated with SaOS-2 cells as well as with human mesenchymal stem cells (MSC) and compared with those particles prepared of amorphous calcium-polyphosphate ("Ca-a-polyP-MP") and of strontium salt. The results revealed a markedly higher stimulation of growth of MSC by "Sr-a-polyP-MP" compared to "Ca-a-polyP-MP" and a significant increase in mineralization of SaOS-2 cells, as well as an enhanced upregulation of the expression of the genes encoding for alkaline phosphatase and the bone morphogenetic protein 2 (BMP-2), likewise performed with SaOS-2 cells...
December 23, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/28017524/active-vitamin-d-treatment-in-ckd-patients-raises-serum-sclerostin-and-this-effect-is-modified-by-circulating-pentosidine-levels
#14
C Torino, P Pizzini, S Cutrupi, G Tripepi, F Mallamaci, R Thadhani, C Zoccali
BACKGROUND AND AIMS: 1,25(OH)2Vitamin D increases the expression of the sclerostin gene. Whether vitamin D receptor activation (VDRA) influences serum sclerostin in CKD and whether compounds interfering with VDRA like Advanced Glycosylation End Products (AGEs) may alter the sclerostin response to VDRA is unknown. METHODS AND RESULTS: Eighty-eight stage G3-4 CKD patients randomly received 2 μg paricalcitol (PCT)/day (n = 44) or placebo (n = 44) for 12 weeks...
November 23, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28000869/advanced-oxidation-protein-products-induce-apoptosis-and-upregulate-sclerostin-and-rankl-expression-in-osteocytic-mlo-y4-cells-via-jnk-p38%C3%A2-mapk-activation
#15
Chaoqun Yu, Dong Huang, Kunyuan Wang, Bochuan Lin, Yuanhang Liu, Songbo Liu, Weichi Wu, Huiru Zhang
Advanced oxidation protein products (AOPPs) are recognized as novel markers of oxidative stress and contribute to various medical conditions, which are associated with secondary osteoporosis. However, little is currently known regarding the role of AOPPs in the development of secondary osteoporosis. As the commander cells of bone remodeling, osteocytes are involved in the pathogenesis of osteoporosis. The present study aimed to determine the cytotoxic mechanisms of AOPPs on osteocytic MLO‑Y4 cells. The results demonstrated that treatment with AOPPs significantly triggered apoptosis of MLO‑Y4 cells, in a dose‑ and time‑dependent manner...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27997588/protective-effects-of-vildagliptin-against-pioglitazone-induced-bone-loss-in-type-2-diabetic-rats
#16
Young Sil Eom, A-Ryeong Gwon, Kyung Min Kwak, Ju-Young Kim, Seung Hee Yu, Sihoon Lee, Yeun Sun Kim, Ie Byung Park, Kwang-Won Kim, Kiyoung Lee, Byung-Joon Kim
Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model...
2016: PloS One
https://www.readbyqxmd.com/read/27981516/physical-activity-and-hypocaloric-diet-recovers-osteoblasts-homeostasis-in-women-affected-by-abdominal-obesity
#17
Viviana M Bimonte, Simona Fittipaldi, Chiara Marocco, Gian Pietro Emerenziani, Rachele Fornari, Laura Guidetti, Eleonora Poggiogalle, Emanuele Nicolai, Luigi Di Luigi, Lorenzo M Donini, Carlo Baldari, Andrea Lenzi, Emanuela A Greco, Silvia Migliaccio
Obesity is a multifactorial disease linked to metabolic chronic disorders such as diabetes, and hypertension. Also, it has recently been associated with skeletal alterations and low bone mineral density. We previously demonstrated that exposure of osteoblasts to sera of sedentary subjects affected by obesity alters cell homeostasis in vitro, leading to disruption of intracellular differentiation pathways and cellular activity. Thus, the purpose of the present study has been to evaluate whether sera of sedentary obese women, subjected to physical activity and hypocaloric diet, could recover osteoblast homeostasis in vitro as compared to the sera of same patients before intervention protocol...
December 16, 2016: Endocrine
https://www.readbyqxmd.com/read/27981392/histological-evidence-that-metformin-reverses-the-adverse-effects-of-diabetes-on-orthodontic-tooth-movement-in-rats
#18
Jing Sun, Juan Du, Wei Feng, Boyao Lu, Hongrui Liu, Jie Guo, Norio Amizuka, Minqi Li
This study evaluated the effects of metformin on orthodontic tooth movement in a rat model of type 2 diabetes mellitus. Rats were fed a high-fat diet for 4 weeks to induce fat accumulation and insulin resistance, and then injected with a low dose of streptozotocin (35 mg/kg) intraperitoneally to induce type 2 diabetes. An orthodontic appliance was placed in normoglycemic, type 2 diabetes, and type 2 diabetes with metformin-administrated rats. After 14 days, type 2 diabetes rats exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphatase-positive osteoclasts, stronger cathepsin K expression, and weaker alkaline phosphatase immunostaining than normoglycemic rats...
December 15, 2016: Journal of Molecular Histology
https://www.readbyqxmd.com/read/27966788/notch-signaling-participates-in-tgf-%C3%AE-induced-sost-expression-under-intermittent-compressive-stress
#19
Jeeranan Manokawinchoke, Piyamas Sumrejkanchanakij, Prasit Pavasant, Thanaphum Osathanon
Notch signaling is regulated by mechanical stimuli in various cell types. It has previously been reported that intermittent compressive stimuli enhanced sclerostin (SOST) expression in human periodontal ligament cells (hPDLs) by regulating transforming growth factor-β (TGF-β) expression. The aim of the present study was to determine the involvement of Notch signaling in the TGF-β induced SOST expression in hPDLs. Cells were treated with intermittent compressive stress in a computer-controlled apparatus for 24 h...
December 14, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27965160/hormonal-and-systemic-regulation-of-sclerostin
#20
Matthew T Drake, Sundeep Khosla
The Wnt/β-catenin signaling pathway plays an essential role in osteoblast biology. Sclerostin is a soluble antagonist of Wnt/β-catenin signaling secreted primarily by osteocytes. Current evidence indicates that sclerostin likely functions as a local/paracrine regulator of bone metabolism rather than as an endocrine hormone. Nonetheless, circulating sclerostin levels in humans often reflect changes in the bone microenvironment, although there may be exceptions to this observation. Using existing assays, circulating sclerostin levels have been shown to be altered in response to both hormonal stimuli and across a variety of normal physiological and pathophysiological conditions...
December 10, 2016: Bone
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