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https://www.readbyqxmd.com/read/28336490/novel-therapeutic-interventions-for-pseudoachondroplasia
#1
Karen L Posey, Jacqueline T Hecht
Pseudoachondroplasia (PSACH), a severe short-limbed dwarfing condition, is associated with life-long joint pain and early onset osteoarthritis. PSACH is caused by mutations in cartilage oligomeric matrix protein (COMP), a pentameric matricellular protein expressed primarily in cartilage and other musculoskeletal tissues. Mutations in COMP diminish calcium binding and as a result perturb protein folding and export to the extracellular matrix. Mutant COMP is retained in the endoplasmic reticulum (ER) of growth plate chondrocytes resulting in massive intracellular COMP retention...
March 21, 2017: Bone
https://www.readbyqxmd.com/read/28323142/zoledronic-acid-improves-bone-histomorphometry-in-a-murine-model-of-rett-syndrome
#2
Jay R Shapiro, Adele L Boskey, Stephen B Doty, Lyudmila Lukashova, Mary E Blue
Rett syndrome (RTT) is a neurodevelopmental disorder predominately affecting young females, caused by deficiency of the global transcriptional protein methyl CpG binding protein 2 (MeCP2). Osteoblasts express MeCP2 and girls with RTT experience early onset osteoporosis, decreased bone mass and an increased fracture risk. There is no defined treatment for osteoporosis associated with RTT. The present study evaluated the effects of zoledronic acid (ZA), a third generation nitrogen-containing bisphosphonate with primarily anti-osteoclastic activity, in a mouse model of MeCP2 deficiency...
March 18, 2017: Bone
https://www.readbyqxmd.com/read/28323144/tissue-expression-and-source-of-circulating-%C3%AE-klotho
#3
REVIEW
Hannes Olauson, Rik Mencke, Jan-Luuk Hillebrands, Tobias E Larsson
αKlotho (Klotho), a type I transmembrane protein and a coreceptor for Fibroblast growth factor-23, was initially thought to be expressed only in a limited number of tissues, most importantly the kidney, parathyroid gland and choroid plexus. Emerging data may suggest a more ubiquitous Klotho expression pattern which has prompted reevaluation of the restricted Klotho paradigm. Herein we systematically review the evidence for Klotho expression in various tissues and cell types in humans and other mammals, and discuss potential reasons behind existing conflicting data...
March 17, 2017: Bone
https://www.readbyqxmd.com/read/28323146/hypogonadal-men-with-type-2-diabetes-mellitus-have-smaller-bone-size-and-lower-bone-turnover
#4
Georgia Colleluori, Lina Aguirre, Richard Dorin, David Robbins, Dean Blevins, Yoann Barnouin, Rui Chen, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal
INTRODUCTION: Both hypogonadism and type 2 diabetes mellitus (T2D) are associated with increased fracture risk. Emerging data support the negative effect of low testosterone on glucose metabolism, however, there is little information on the bone health of hypogonadal men with diabetes. We evaluated the bone mineral density (BMD), bone geometry and bone turnover of hypogonadal men with T2D compared to hypogonadal men without diabetes. MATERIALS AND METHODS: Cross-sectional study, men 40-74years old, with average morning testosterone (done twice) of<300ng/dl...
March 16, 2017: Bone
https://www.readbyqxmd.com/read/28323145/increased-cortical-porosity-is-associated-with-daily-not-weekly-administration-of-equivalent-doses-of-teriparatide
#5
Roger Zebaze, Ryoko Takao-Kawabata, Yu Peng, Ali Ghasem Zadeh, Kyoko Hirano, Hiroshi Yamane, Aya Takakura, Yukihiro Isogai, Toshinori Ishizuya, Ego Seeman
INTRODUCTION: The pharmacokinetic profile of parathyroid hormone (PTH) determines its effects on bone resorption and formation. When administered intermittently, anabolic effects are favored in comparison with the continuous treatment. Among the intermittent treatment regimens, lower frequency of administration may have a lower effect on bone remodeling. We therefore hypothesized that weekly administration of teriparatide will produce less increase in intracortical remodeling and porosity than reported using daily treatment...
March 16, 2017: Bone
https://www.readbyqxmd.com/read/28323143/effect-of-age-and-gender-on-serum-periostin-relationship-to-cortical-measures-bone-turnover-and-hormones
#6
Jennifer S Walsh, Fatma Gossiel, Jessica R Scott, Margaret A Paggiosi, Richard Eastell
Periostin is an extracellular matrix protein, and in bone is expressed most highly in the periosteum. It increases bone formation through osteoblast differentiation, cell adhesion, Wnt signalling and collagen cross-linking. We hypothesised that serum periostin would be high at times of life when cortical modeling is active, in early adulthood and in older age, and that it would correlate with cortical bone measures, bone turnover and hormones that regulate cortical modeling. We conducted a cross-sectional observational study of 166 healthy men and women at three skeletal stages; the end of longitudinal growth (16-18years), peak bone mass (30-32years) and older age (over 70years)...
March 16, 2017: Bone
https://www.readbyqxmd.com/read/28286299/importance-of-prompt-antiresorptive-therapy-in-postmenopausal-women-discontinuing-teriparatide-or-denosumab-the-denosumab-and-teriparatide-follow-up-study-data-follow-up
#7
Benjamin Z Leder, Joy N Tsai, Linda A Jiang, Hang Lee
When teriparatide and denosumab are discontinued, bone mineral density (BMD) abruptly decreases. To compare rates of bone loss in postmenopausal women who discontinue denosumab or teriparatide and receive no additional prescription osteoporosis medications to women who discontinue these drugs followed by prompt antiresorptive therapy, we asked women concluding the Denosumab and Teriparatide Administration (DATA) study and its extension, DATA-Switch, to return for BMD measurements 1-2years after study completion...
March 9, 2017: Bone
https://www.readbyqxmd.com/read/28286298/the-effects-of-parathyroid-hormone-peptides-on-the-peripheral-skeleton-of-postmenopausal-women-a-systematic-review
#8
REVIEW
Louis M Metcalf, Terry J Aspray, Eugene V McCloskey
Given current developments in anabolic therapy for bone, we wished to document the effects of the only currently available anabolic therapy, parathyroid hormone (PTH) peptides, on the peripheral skeleton of postmenopausal women. We undertook a systematic review of English articles using MEDLINE, Scopus and the Cochrane Controlled Trials Register (final update 28th March 2016). Additional studies were identified through searches of bibliographies. Studies included those comparing PTH peptides with placebo, with anti-osteoporotic treatments and in combination therapies...
March 9, 2017: Bone
https://www.readbyqxmd.com/read/28286238/the-role-of-the-progressive-ankylosis-protein-ank-in-adipogenic-osteogenic-fate-decision-of-precursor-cells
#9
Takeshi Minashima, Martin Quirno, You Jin Lee, Thorsten Kirsch
The progressive ankylosis protein (ANK) is a transmembrane protein that transports intracellular pyrophosphate (PPi) to the extracellular milieu. In this study we show increased fatty degeneration of the bone marrow of adult ank/ank mice, which lack a functional ANK protein. In addition, isolated bone marrow stromal cells (BMSCs) isolated from ank/ank mice showed a decreased proliferation rate and osteogenic differentiation potential, and an increased adipogenic differentiation potential compared to BMSCs isolated from wild type (WT) littermates...
March 8, 2017: Bone
https://www.readbyqxmd.com/read/28285015/tnf%C3%AE-contributes-to-diabetes-impaired-angiogenesis-in-fracture-healing
#10
Jason C Lim, Kang I Ko, Marcelo Mattos, Miao Fang, Citong Zhang, Daniel Feinberg, Hisham Sindi, Shuai Li, Jazia Alblowi, Rayyan A Kayal, Thomas A Einhorn, Louis Gerstenfeld, Dana Graves
Diabetes increases the likelihood of fracture, interferes with fracture healing and impairs angiogenesis. The latter may be significant due to the critical nature of angiogenesis in fracture healing. Although it is known that diabetes interferes with angiogenesis the mechanisms remain poorly defined. We examined fracture healing in normoglycemic and streptozotocin-induced diabetic mice and quantified the degree of angiogenesis with antibodies to three different vascular markers, CD34, CD31 and Factor VIII. The role of diabetes-enhanced inflammation was investigated by treatment of the TNFα-specific inhibitor, pegsunercept starting 10days after induction of fractures...
March 8, 2017: Bone
https://www.readbyqxmd.com/read/28285014/vertebral-fracture-assessment-enhancing-the-diagnosis-prevention-and-treatment-of-osteoporosis
#11
Meltem Zeytinoglu, Rajesh K Jain, Tamara J Vokes
Osteoporosis is a highly prevalent condition, resulting in significant morbidity and mortality. Nevertheless, it is frequently untreated. Vertebral fractures often do not come to clinical attention, yet, their presence is diagnostic of osteoporosis, helps to predict the risk of future fractures, and may alter the choice of pharmacotherapy. The addition of lateral spine imaging technology to the densitometer, for vertebral fracture assessment (VFA), represented a major advancement in the ability to diagnose vertebral fractures and osteoporosis...
March 8, 2017: Bone
https://www.readbyqxmd.com/read/28286239/higher-bone-resorption-excretion-in-south-asian-women-vs-white-caucasians-and-increased-bone-loss-with-higher-seasonal-cycling-of-vitamin-d-results-from-the-d-fines-cohort-study
#12
A L Darling, K H Hart, F Gossiel, F Robertson, J Hunt, T R Hill, S Johnsen, J L Berry, R Eastell, R Vieth, S A Lanham-New
Few data exist on bone turnover in South Asian women and it is not well elucidated as to whether Western dwelling South Asian women have different bone resorption levels to that of women from European ethnic backgrounds. This study assessed bone resorption levels in UK dwelling South Asian and Caucasian women as well as evaluating whether seasonal variation in 25-hydroxyvitamin D [25(OH)D] is associated with bone resorption in either ethnic group. Data for seasonal measures of urinary N-telopeptide of collagen (uNTX) and serum 25(OH)D were analysed from n=373 women (four groups; South Asian postmenopausal n=44, South Asian premenopausal n=50, Caucasian postmenopausal n=144, Caucasian premenopausal n=135) (mean (±SD) age 48 (14) years; age range 18-79years) who participated in the longitudinal D-FINES (Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England) cohort study (2006-2007)...
March 7, 2017: Bone
https://www.readbyqxmd.com/read/28274799/diagnostic-accuracy-of-frax-in-predicting-the-10-year-risk-of-osteoporotic-fractures-using-the-usa-treatment-thresholds-a-systematic-review-and-meta-analysis
#13
Xuezhi Jiang, Morgan Gruner, Florence Trémollieres, Wojciech Pluskiewicz, Elisabeth Sornay-Rendu, Piotr Adamczyk, Peter F Schnatz
OBJECTIVES: The aim of this study was to conduct a systematic review and meta-analysis on the performance of the WHO's Fracture Risk Assessment (FRAX) instrument in predicting 10-year risk of Major Osteoporotic Fractures (MOF) and Hip Fractures (HF), using the USA treatment thresholds, in populations other than their derivation cohorts. DESIGN: EMBASE and MEDLINE database were searched with search engine PubMed and OVID as well as Google Scholar for the English-language literature from July 2008 to July 2016...
March 6, 2017: Bone
https://www.readbyqxmd.com/read/28267633/sclerostin-stimulates-angiogenesis-in-human-endothelial-cells
#14
Angela Oranger, Giacomina Brunetti, Graziana Colaianni, Roberto Tamma, Claudia Carbone, Luciana Lippo, Giorgio Mori, Paolo Pignataro, Nunzio Cirulli, Roberta Zerlotin, Biagio Moretti, Angela Notarnicola, Domenico Ribatti, Maria Grano, Silvia Colucci
Sclerostin, negative regulator of bone formation, has been originally known as an osteocyte product. Recently, it has been also detected in hypertrophic chondrocytes, distinctive cells of avascular cartilage which is invaded by capillaries and then replaced by vascularized bone. Thus, we hypothesized that sclerostin, in addition to its role already known, may exert an angiogenic activity. We first proved that sclerostin increased the proliferation of human umbilical vein endothelial cells (HUVECs), and next, by using the chicken chorioallantoic membrane (CAM) in vivo assay, we demonstrated that it exerts an angiogenic activity similar to that of vascular endothelial growth factor (VEGF)...
March 3, 2017: Bone
https://www.readbyqxmd.com/read/28263916/an-update-on-osteoporosis-pathogenesis-diagnosis-and-treatment
#15
EDITORIAL
Michael McClung, Roland Baron, Mary Bouxsein
No abstract text is available yet for this article.
March 2, 2017: Bone
https://www.readbyqxmd.com/read/28238808/hypophosphatasia-an-overview-for-2017
#16
Michael P Whyte
Hypophosphatasia (HPP) is the inborn-error-of-metabolism that features low serum alkaline phosphatase (ALP) activity (hypophosphatasemia) caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of ALP (TNSALP). Autosomal recessive or autosomal dominant inheritance from among >300 TNSALP (ALPL) mutations largely explains HPP's remarkably broad-ranging severity. TNSALP is a cell-surface homodimeric phosphohydrolase richly expressed in the skeleton, liver, kidney, and developing teeth...
February 24, 2017: Bone
https://www.readbyqxmd.com/read/28254468/pharmacologically-targeting-beta-catenin-for-nf1-associated-deficiencies-in-fracture-repair
#17
Gurpreet S Baht, Puviindran Nadesan, David Silkstone, Benjamin A Alman
Patients with Neurofibromatosis type 1 display delayed fracture healing and the increased deposition of fibrous tissue at the fracture site. Severe cases can lead to non-union and even congenital pseudarthrosis. Neurofibromatosis type 1 is caused by a mutation in the NF1 gene and mice lacking the Nf1 gene show a fracture repair phenotype similar to that seen in patients. Tissue from the fracture site of patients with Neurofibromatosis type 1 and from mice deficient in the Nf1 gene both show elevated levels of β-catenin protein and activation of β-catenin mediated signaling...
February 22, 2017: Bone
https://www.readbyqxmd.com/read/28254467/the-influence-of-%C3%AE-actinin-3-deficiency-on-bone-remodelling-markers-in-young-men
#18
Itamar Levinger, Xu Yan, David Bishop, Peter J Houweling, Ioannis Papadimitriou, Fiona Munson, Elizabeth Byrnes, Daniele Vicari, Tara C Brennan-Speranza, Nir Eynon
There is a large individual variation in the bone remodelling markers (BRMs) osteocalcin (OC), procollagen 1 N-terminal propeptide (P1NP) and β-isomerized C-terminal telopeptide (β-CTx), as well as undercarboxylated osteocalcin (ucOC), at rest and in response to exercise. α-actinin-3 (ACTN3), a sarcomeric protein, is expressed in skeletal muscle and osteoblasts and may influence BRM levels and the cross-talk between muscle and bone. We tested the levels of serum BRMs in α-actinin-3 deficient humans (ACTN3 XX) at baseline, and following a single bout of exercise...
February 22, 2017: Bone
https://www.readbyqxmd.com/read/28254466/impaired-rib-bone-mass-and-quality-in-end-stage-cystic-fibrosis-patients
#19
Geneviève Mailhot, Natalie Dion, Delphine Farlay, Sébastien Rizzo, Nathalie J Bureau, Valérie Jomphe, Safiétou Sankhe, Georges Boivin, Larry C Lands, Pasquale Ferraro, Louis-Georges Ste-Marie
BACKGROUND: Advancements in research and clinical care have considerably extended the life expectancy of cystic fibrosis (CF) patients. However, with this extended survival come comorbidities. One of the leading co-morbidities is CF-related bone disease (CFBD), which progresses with disease severity and places patients at high risk for fractures, particularly of the ribs and vertebrae. Evidence that CF patients with vertebral fractures had higher bone mineral density (BMD) than the nonfracture group led us to postulate that bone quality is impaired in these patients...
February 22, 2017: Bone
https://www.readbyqxmd.com/read/28249797/parathyroid-hormone-s-enhancement-of-bones-osteogenic-response-to-loading-is-affected-by-ageing-in-a-dose-and-time-dependent-manner
#20
Lee B Meakin, Henry Todd, Peter J Delisser, Gabriel L Galea, Alaa Moustafa, Lance E Lanyon, Sara H Windahl, Joanna S Price
Decreased effectiveness of bones' adaptive response to mechanical loading contributes to age-related bone loss. In young mice, intermittent administration of parathyroid hormone (iPTH) at 20-80μg/kg/day interacts synergistically with artificially applied loading to increase bone mass. Here we report investigations on the effect of different doses and duration of iPTH treatment on mice whose osteogenic response to artificial loading is impaired by age. One group of aged, 19-month-old female C57BL/6 mice was given 0, 25, 50 or 100μg/kg/day iPTH for 4weeks...
February 22, 2017: Bone
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