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https://www.readbyqxmd.com/read/28432596/exploiting-the-wnt-signaling-pathway-for-clinical-purposes
#1
REVIEW
Mark L Johnson, Robert R Recker
PURPOSE OF REVIEW: The goal of this paper is to evaluate critically the literature published over the past 3 years regarding the Wnt signaling pathway. The Wnt pathway was found to be involved in bone biology in 2001-2002 with the discovery of a (G171V) mutation in the lipoprotein receptor-related protein 5 (LRP5) that resulted in high bone mass and another mutation that completely inactivated Lrp5 function and resulted in osteoporosis pseudoglioma syndrome (OPPG). The molecular biology has been complex, and very interesting...
April 21, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28429560/is-there-a-role-for-newer-biomarkers-in-chronic-kidney-disease-mineral-and-bone-disorder-management
#2
Sven-Jean Tan, Michael Mx Cai
The current management of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) relies largely on clinical judgement and assessment of biochemical parameters including serum calcium, phosphate and intact parathyroid hormone concentrations. In the past two decades, there has been a leap in the understanding of the pathophysiology of CKD-MBD, leading to the discovery of novel biomarkers. The potential utility of these markers in this clinical setting is an area of intense investigation. In the absence of any guidelines aiding the clinician's understanding and application of these markers, we summarise the current available literature surrounding fibroblast growth factor-23, α-Klotho, sclerostin and serum calcification propensity testing and their respective assays in the context of CKD-MBD management...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28428078/kinetic-reconstruction-reveals-time-dependent-effects-of-romosozumab-on-bone-formation-and-osteoblast-function-in-vertebral-cancellous-and-cortical-bone-in-cynomolgus-monkeys
#3
Rogely Waite Boyce, Qing-Tian Niu, Michael S Ominsky
Romosozumab, a humanized monoclonal sclerostin antibody under development for the treatment of osteoporosis, has a unique mechanism of action on bone-increasing bone formation and decreasing bone resorption. The effects on bone formation are transient, eliciting a rapid increase in bone formation that attenuates with continued treatment. Although bone formation attenuates, bone mineral density (BMD) continues to increase. To explore potential tissue-level mechanisms that could contribute to a progressive increase in spine BMD, we used kinetic reconstruction techniques to examine the effects of romosozumab on modeling and remodeling units in vertebral cancellous bone from adult cynomolgus monkeys administered romosozumab for 10 and 28weeks...
April 18, 2017: Bone
https://www.readbyqxmd.com/read/28405928/adynamic-bone-disease-is-a-predominant-bone-pattern-in-early-stages-of-chronic-kidney-disease
#4
REVIEW
Ziad Massy, Tilman Drueke
Chronic kidney disease (CKD) is complicated by disturbances of mineral and bone metabolism which start early in the course of the disease. It has long been assumed that high turnover bone lesions induced by secondary hyperparathyroidism are the predominant type of renal osteodystrophy from the start. However, there is increasing evidence in favor of the view that in early CKD stages low bone turnover is prevailing, with adynamic bone disease being the predominant form. Since serum parathyroid hormone levels increase progressively early on, and the most probable explanation is resistance to the skeletal action of this hormone...
April 12, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28399348/prevalence-and-risk-factors-of-osteoporosisin-postmenopausal-women-with-type-2-diabetes-mellitus
#5
Ivan Raška, Mária Rašková, Vít Zikán, Jan Škrha
OBJECTIVE: Patients with type 2 diabetes (T2DM) are at increased risk of fractures. The aim of this study is to analyze the prevalence and risk factors of osteoporosis and osteoporosis related fractures in postmenopausal women with T2DM. METHODS: A total of 112 postmenopausal women with T2DM and 171 control nondiabetic women received a standardized questionnaire on osteoporosis risk factors, and were evaluated for bone mineral density (BMD, by using a dual energy X-ray absorptiometry), biochemical markers of bone and glucose metabolism, soluble receptor for advanced glycation end products (sRAGE) and its gene polymorphisms (rs1800625 or rs2070600)...
March 2017: Central European Journal of Public Health
https://www.readbyqxmd.com/read/28397831/microrna-mir-23a-cluster-promotes-osteocyte-differentiation-by-regulating-tgf-%C3%AE-signalling-in-osteoblasts
#6
Huan-Chang Zeng, Yangjin Bae, Brian C Dawson, Yuqing Chen, Terry Bertin, Elda Munivez, Philippe M Campeau, Jianning Tao, Rui Chen, Brendan H Lee
Osteocytes are the terminally differentiated cell type of the osteoblastic lineage and have important functions in skeletal homeostasis. Although the transcriptional regulation of osteoblast differentiation has been well characterized, the factors that regulate differentiation of osteocytes from mature osteoblasts are poorly understood. Here we show that miR-23a∼27a∼24-2 (miR-23a cluster) promotes osteocyte differentiation. Osteoblast-specific miR-23a cluster gain-of-function mice have low bone mass associated with decreased osteoblast but increased osteocyte numbers...
April 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28391431/sclerostin-antibody-increases-callus-size-and-strength-but-does-not-improve-fracture-union-in-a-challenged-open-rat-fracture-model
#7
Alyson Morse, Michelle M McDonald, Aaron Schindeler, Lauren Peacock, Kathy Mikulec, Tegan L Cheng, Min Liu, Hua Zhu Ke, David G Little
Open fractures remain a challenge in orthopedics. Current strategies to intervene are often inadequate, particularly in severe fractures or when treatment is delayed. Sclerostin is a negative regulator of bone growth and sclerostin-neutralizing antibodies (Scl-Ab) can increase bone mass and strength. The application of these antibodies to improve orthopedic repair has shown varied results, and may be dependent on the location and severity of the bony injury. We examined Scl-Ab treatment within an established rat osteotomy model with periosteal stripping analogous to open fracture repair...
April 8, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28390904/normal-bone-density-and-trabecular-bone-score-but-high-serum-sclerostin-in-congenital-generalized-lipodystrophy
#8
Josivan Gomes Lima, Lucia Helena C Nobrega, Natalia Nobrega Lima, Marcel Catão Ferreira Dos Santos, Maria de Fatima P Baracho, Renaud Winzenrieth, Francisco Bandeira, Carolina de O Mendes-Aguiar, Francisco Paulo Freire Neto, Leonardo Capistrano Ferreira, Clifford J Rosen, Selma Maria B Jeronimo
CONTEXT: Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty in storing lipids in adipocytes, low body fat mass, hypoleptinemia, and hyperinsulinemia. Sclerostin is a product of SOST gene that blocks the Wnt/β-catenin pathway, decreasing bone formation and enhancing adipogenesis. There are no data about sclerostin in people with BSCL. OBJECTIVE: We aimed to evaluate serum sclerostin, bone mineral density (BMD), and L1-L4 Trabecular Bone Score (TBS) in BSCL patients, generating new knowledge about potential mechanisms involved in the bone alterations of these patients...
April 5, 2017: Bone
https://www.readbyqxmd.com/read/28388981/application-and-effect-of-mobiletype-bone-health-intervention-in-korean-young-adult-women-with-low-bone-mass-a-randomized-control-trial
#9
Young-Joo Park, Sook-Ja Lee, Nah-Mee Shin, Hyunjeong Shin, Songi Jeon, Jungwoo Lee, Inhae Cho
PURPOSE: This randomized control trial was designed to examine the effect on the self-managing ability for promoting bone health of mobile type-bone health intervention (mobile type-BHI). METHODS: The mobile type-BHI consisted of a mobile application called "Strong bone, Fit body" (SbFb) and group education. A total of 82 college women with low bone mass (Z score < -1) participated. They were assigned randomly to three groups, experimental group I, (n = 28), experimental group II (n = 32), and control group (n = 22)...
March 2017: Asian Nursing Research
https://www.readbyqxmd.com/read/28388723/high-sclerostin-and-dickkopf-1-dkk-1-serum-levels-in-children-and-adolescents-with-type-1-diabetes-mellitus
#10
Maria Felicia Faienza, Annamaria Ventura, Maurizio Delvecchio, Anna Fusillo, Laura Piacente, Gabriella Aceto, Graziana Colaianni, Silvia Colucci, Luciano Cavallo, Maria Grano, Giacomina Brunetti
Context: Childhood type 1 diabetes mellitus (T1DM) is associated with decreased bone mass. Sclerostin and dickkopf-1 (DKK-1) are Wnt inhibitors that regulate bone formation. Objective: To evaluate sclerostin and DKK-1 levels in T1DM children and to analyze the influence of glycemic control on bone health. Design and setting: Cross-sectional study conducted at a clinical research center. Participants: One hundred and six T1DM subjects (12...
April 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28382551/high-doses-of-vitamin-c-plus-e-reduce-strength-training-induced-improvements-in-areal-bone-mineral-density-in-elderly-men
#11
Astrid Kamilla Stunes, Unni Syversen, Sveinung Berntsen, Gøran Paulsen, Tonje H Stea, Ken J Hetlelid, Hilde Lohne-Seiler, Mats Peder Mosti, Thomas Bjørnsen, Truls Raastad, Glenn Haugeberg
PURPOSE: Resistance training is beneficial for maintaining bone mass. We aimed to investigate the skeletal effects of high doses of antioxidants [vitamin C + E (α-tocopherol)] supplementation during 12-week supervised strength training in healthy, elderly men METHODS: Design: double-blinded randomized placebo-controlled study. Participants followed a supervised, undulating periodic exercise program with weekly adjusted load: 3 sessions/week and 3-15 repetitions maximum (RM) sets/exercise...
April 5, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28381451/mechanisms-in-endocrinology-genetic-regulation-of-bone-formation-from-monogenic-to-complex-bone-disorders
#12
Eveline Boudin, Wim Van Hul
Throughout life, bone is continuously remodelled to be able to fulfil its multiple functions. The importance of strictly regulating the bone remodelling process, which is defined by the sequential actions of osteoclasts and osteoblasts, is shown by a variety of disorders with abnormalities in bone mass and strength. The best known and most common example of such a disorder is osteoporosis which is marked by a decreased bone mass and strength that consequently results in an increased fracture risk. As osteoporosis is a serious health problem, a large amount of studies focusses on elucidating the aetiology of the disease as well as on the identification of novel therapeutic targets for the treatment of osteoporotic patients...
April 5, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28379384/osteocyte-protein-expression-is-altered-in-low-turnover-osteoporosis-caused-by-mutations-in-wnt1-and-pls3
#13
Katherine Wesseling-Perry, Riikka E Mäkitie, Ville-Valtteri Välimäki, Tero Laine, Christine M Laine, Matti J Välimäki, Renata C Pereira, Outi Mäkitie
Context: Osteocytes express proteins that regulate bone remodeling and mineralization as well as osteoblast and adipocyte differentiation. Objective: To evaluate the relationship between osteocyte-specific protein expression and bone histology in patients with monogenic osteoporosis due to WNT1 or PLS3 mutations. Design and Setting: Cross-sectional cohort study at a University Hospital. Participants: 6 patients (4 males, age range 14-72 years) with a heterozygous WNT1 mutation and 5 patients (4 males, age 9-70 years) with a hetero-/hemizygous PLS3 mutation...
April 3, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28374174/serum-sclerostin-increases-after-acute-physical-activity
#14
Marie-Eva Pickering, Marie Simon, Elisabeth Sornay-Rendu, Karim Chikh, Marie-Christine Carlier, Anne-Lise Raby, Pawel Szulc, Cyrille B Confavreux
Physical activity has a major impact on bone density and on osteoporosis prevention. Sclerostin is produced by osteocytes and inhibits bone formation. The impact of exercise on sclerostin secretion has not been studied so far. This pilot study aimed to explore circulating sclerostin levels immediately after acute exercise. Healthy young women practicing physical activity less than 120 min per week were enrolled. The exercise was a 45-min, low-speed, treadmill running test. Blood samples were taken at rest before exercise and within 5 min after the end of exercise...
April 3, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28370407/bps804-anti-sclerostin-antibody-in-adults-with-moderate-osteogenesis-imperfecta-results-of-a-randomized-phase-2a-trial
#15
Francis H Glorieux, Jean-Pierre Devogelaer, Michaela Durigova, Stefan Goemaere, Sarah Hemsley, Franz Jakob, Uwe Junker, Jon Ruckle, Lothar Seefried, Peter J Winkle
TRIAL DESIGN: This 21-week, open-label, phase 2a trial aimed to evaluate the pharmacodynamics and safety of multiple, escalating infusions of BPS804, a neutralizing, anti-sclerostin antibody, in adults with moderate osteogenesis imperfecta (OI). METHODS: Patients received BPS804 (three escalating doses each separated by 2 weeks [5, 10 and 20 mg/kg]) or no treatment (reference group). The primary efficacy endpoints were mean changes from baseline to day 43 in: procollagen type 1 N-terminal propeptide (P1NP), procollagen type 1 C-terminal propeptide (P1CP), bone-specific alkaline phosphatase (BSAP), osteocalcin (OC) and type 1 collagen cross-linked C-telopeptide (CTX-1)...
March 29, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28370281/new-insights-into-the-local-and-systemic-functions-of-sclerostin-regulation-of-quiescent-bone-lining-cells-and-beige-adipogenesis-in-peripheral-fat-depots
#16
Jesus Delgado-Calle, Teresita Bellido
No abstract text is available yet for this article.
March 29, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28365850/acute-bone-changes-after-lower-limb-amputation-resulting-from-traumatic-injury
#17
D A Bemben, V D Sherk, W J J Ertl, M G Bemben
Bone health is critical for lower limb amputees, affecting their ability to use a prosthesis and their risk of osteoporosis. We found large losses in hip bone mineral density (BMD) and in amputated bone strength in the first year of prosthesis use, suggesting a need for load bearing interventions early post-amputation. INTRODUCTION: Large deficits in hip areal BMD (aBMD) and residual limb volumetric BMD (vBMD) occur after lower limb amputation; however, the time course of these bone quality changes is unknown...
April 1, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28364259/the-effects-of-sclerostin-antibody-plus-parathyroid-hormone-1-34-on-bone-formation-in-ovariectomized-rats
#18
Jian Wu, Xian-Hua Cai, Xing-Xing Qin, Yan-Xi Liu
Previous studies have demonstrated the effects of sclerostin antibody (Scl-Ab) and parathyroid hormone (1-34, PTH) on healing in osteoporosis; however, reports about the combined effects of Scl-Ab plus PTH on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with Scl-Ab and PTH on osteoporosis healing in ovariectomized (OVX) rats. After bilateral ovariectomy, 12 weeks were allowed to pass for the establishment of standard conditions for osteoporosis in animal models...
March 31, 2017: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/28363954/estrogen-deficiency-attenuates-fluid-flow-induced-ca-2-i-oscillations-and-mechanoresponsiveness-of-mlo-y4-osteocytes
#19
Vishwa Deepak, Pushpalata Kayastha, Laoise M McNamara
It has been proposed that estrogen regulates the mechanosensitivity of osteocytes; however, the effects of estrogen deficiency that arises during postmenopausal osteoporosis on mechanical stimulation-induced calcium signaling in osteocytes remains elusive. Here, we pretreated MLO-Y4 osteocytes with 10 nM E2 for 2, 3 and 5 d, then simulated postmenopausal conditions either by withdrawing estrogen (EW) from culture medium, or by inhibiting the estrogen receptor by using fulvestrant and estrogen (FE; ICI 182,780) in vitro We investigated [Ca(2+)]i oscillations and mechanobiologic responses of osteocytes (EW and FE) that were exposed to oscillatory fluid flow (OFF; 1 Pa, 0...
March 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28341377/lrp5-from-bedside-to-bench-to-bone
#20
Bart O Williams
A role for Low-density lipoprotein related receptor 5 (LRP5) in human bone was first established by the identification of genetic alterations that led to dramatic changes in human bone mass. Shortly thereafter, mutations that altered the function of the Sclerostin (SOST) gene were also associated with altered human bone mass. Subsequent studies of LRP5 and Sclerostin have provided important insights into the mechanisms by which these proteins regulate skeletal homeostasis. Sclerostin normally binds to LRP5 and the related LRP6 protein and prevents their activation by Wnt ligands...
March 21, 2017: Bone
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