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Ronald Y Kwon, Claire J Watson, David Karasik
While genome-wide association studies (GWAS) have revolutionized our understanding of the genetic architecture of skeletal diseases, animal models are required to identify causal mechanisms and to translate underlying biology into new therapies. Despite large-scale knockout mouse phenotyping efforts, the skeletal functions of most genes residing at GWAS-identified loci remain unknown, highlighting a need for complementary model systems to accelerate gene discovery. Over the past several decades, zebrafish (Danio rerio) has emerged as a powerful system for modeling the genetics of human diseases...
February 11, 2019: Bone
Ippei Kanazawa, Ken-Ichiro Tanaka, Ayumu Takeo, Masakazu Notsu, Hitomi Miyake, Toshitsugu Sugimoto
BACKGROUND: Development of assessment tool for fracture risk is an urgent task, because bone mineral density (BMD) is less useful for evaluating fracture risk in type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: In total, 808 T2DM patients were enrolled in this cross-sectional study. To develop a scoring assessment tool using clinical risks for vertebral fracture (VF), we evaluated which variables were associated with VF by logistic regression analysis, and categorized these variables based on cut-off values obtained by using receiver operating characteristic (ROC) curves...
February 11, 2019: Bone
Tove T Borgen, Åshild Bjørnerem, Lene B Solberg, Camilla Andreasen, Cathrine Brunborg, May-Britt Stenbro, Lars M Hübschle, Anne Froholdt, Wender Figved, Ellen M Apalset, Jan-Erik Gjertsen, Trude Basso, Ida Lund, Ann K Hansen, Jens-Meinhard Stutzer, Cecilie Dahl, Tone K Omsland, Lars Nordsletten, Frede Frihagen, Erik F Eriksen
PURPOSE: Norway has among the highest incidence rates of fractures in the world. Vertebral fracture assessment (VFA) and trabecular bone score (TBS) provide information about fracture risk, but their importance have not been studied in Norwegian patients with fragility fractures. The objectives of this study were to examine the clinical characteristics of a cohort of women and men with fragility fractures, their prevalence of vertebral fractures using VFA and prevalence of low TBS, and explore the differences between the sexes and patients with and without vertebral fractures...
February 8, 2019: Bone
LeAnn M Tiede-Lewis, Sarah L Dallas
Osteoporosis is an aging-related disease of reduced bone mass that is particularly prevalent in post-menopausal women, but also affects the aged male population and is associated with increased fracture risk. Osteoporosis is the result of an imbalance whereby bone formation by osteoblasts no longer keeps pace with resorption of bone by osteoclasts. Osteocytes are the most abundant cells in bone and, although previously thought to be quiescent, they are now known to be active, multifunctional cells that play a key role in the maintenance of bone mass by regulating both osteoblast and osteoclast activity...
February 8, 2019: Bone
Jin-Woo Kim, Angenine Marie D Alfafara, Hye-Yeon Kim, Seon-Yeong Kim, Sun-Jong Kim
INTRODUCTION: An acidic environment has been recognized to increase catabolic activities and inhibit osteoblastic deposition, and also exhibited in the pathogenesis of various bone diseases. The aim of the study was to investigate the role of systemic and local pH alteration in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). MATERIAL AND METHODS: Initially, MRONJ was induced in 54 Sprague-Dawley rats via subcutaneous bisphosphonate injections, once a week for 8 weeks...
February 7, 2019: Bone
Geovanna O Pires, Itamar O Vieira, Fabiana R Hernandes, Andre L Teixeira, Ivone B Oliveira, Wagner V Dominguez, Luciene M Dos Reis, Fábio M Montenegro, Rosa M Moysés, Aluizio B Carvalho, Vanda Jorgetti
Secondary hyperparathyroidism is a complication of chronic kidney disease that compromises skeletal integrity. In patients with secondary hyperparathyroidism undergoing parathyroidectomy, parathyroid hormone levels dramatically decrease. The effects of parathyroidectomy on bone tissue are poorly understood, especially regarding the proteins expressed by osteocytes, such as fibroblast growth factor 23, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, sclerostin, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin, which regulate bone turnover...
February 6, 2019: Bone
Maria Almeida, Ryan M Porter
The sirtuin family of NAD+ -dependent protein deacetylases promotes longevity and counteract age-related diseases. One of the major targets of Sirtuins are the FoxO family of transcription factors. FoxOs play a major role in the adaptation of cells to a variety of stressors such as oxidative stress and growth factor deprivation. Studies with murine models of cell-specific loss- or gain-of-function of Sirtuins or FoxOs and with Sirtuin1 stimulators have provided novel insights into the function and signaling of these proteins on the skeleton...
February 6, 2019: Bone
Maria Sode Rønne, Malene Heidemann, Louise Lylloff, Anders J Schou, Jakob Tarp, Anna Bugge, Jens Ole Laursen, Niklas Rye Jørgensen, Steffen Husby, Niels Wedderkopp, Christian Mølgaard
PURPOSE: Insulin resistance may exert a negative influence on bone mass in childhood and adolescence. The objective was to assess the association between insulin resistance and total body less head (TBLH) bone mineral content (BMC) and to investigate whether body composition, physical activity or osteocalcin levels may influence this association. METHODS: A longitudinal study with follow-up over >6 years was performed and included 562 apparently healthy participants with a mean age of 9...
February 6, 2019: Bone
Eijiro Sakamoto, Jun-Ichi Kido, Ryosuke Takagi, Yuji Inagaki, Koji Naruishi, Toshihiko Nagata, Hiromichi Yumoto
Sclerostin is a secreted glycoprotein that is mainly expressed in osteocytes, exerts negative effects on bone formation, and is present at elevated levels in diabetes mellitus (DM). Periodontitis is an infectious disease caused by periodontopathic bacteria, a complication of DM, and sometimes associated with severe inflammation and alveolar bone resorption. Advanced glycation end-products (AGEs) are a major pathogen in DM complications and adversely influence periodontitis in DM patients. In the present study, the effects of AGE2 and Porphyromonas gingivalis lipopolysaccharide (P-LPS) on the expression of sclerostin in mouse osteocyte-like cells (MLO-Y4-A2 cells) and its function in osteoblast differentiation were investigated...
February 5, 2019: Bone
Thomas J O'Leary, Robert M Gifford, Rebecca L Double, Rebecca M Reynolds, David R Woods, Sophie L Wardle, Julie P Greeves
PURPOSE: To investigate the skeletal effects of the first all-female trans-Antarctic traverse. METHODS: Six women (mean ± SD, age 32 ± 3 years, height 1.72 ± 0.07 m, body mass 72.8 ± 4.0 kg) hauled 80 kg sledges over 1700 km in 61 days from coast-to-coast across the Antarctic. Whole-body areal bone mineral density (aBMD) (dual-energy X-ray absorptiometry) and tibial volumetric BMD (vBMD), geometry, microarchitecture and estimated mechanical properties (high-resolution peripheral quantitative computed tomography) were assessed 39 days before (pre-expedition) and 15 days after the expedition (post-expedition)...
February 5, 2019: Bone
Vanessa D Sherk, Clifford J Rosen
Osteocytes are the most prevalent cell in the skeleton and are the master regulator of bone remodeling. Despite the understanding that osteocytes have a multiyear lifespan, and some factors induce apoptosis in osteocytes, much less is understood about the induction and consequences of osteocyte senescence. Filling these gaps in knowledge will provide novel approaches to slowing age-related bone loss and preventing fragility fractures. The purpose of this review is to examine the roles of senescence and apoptosis in osteocytes in age-related bone loss...
February 5, 2019: Bone
Sung-Hee Yoon, Marc Grynpas, Jane Mitchell
Duchenne Muscular Dystrophy (DMD) is a progressive muscle disorder caused by genetic mutations of the dystrophin encoding gene. In the absence of functional dystrophin, DMD patients suffer from muscle inflammation and wasting, as well as compromised bone health with increased risk of fracture. The use of high dose glucocorticoids (GC) as the standard therapy also contributes to bone fragility. This study examined the effects of intermittent, daily administered parathyroid hormone (iPTH), an approved bone anabolic therapy, on growing bone and dystrophic muscle in the presence and absence of prednisone treatment using the Mdx mouse model of DMD...
February 1, 2019: Bone
Diana L Cousminer, Shana E McCormack, Jonathan A Mitchell, Alessandra Chesi, Joseph M Kindler, Andrea Kelly, Benjamin F Voight, Heidi J Kalkwarf, Joan M Lappe, John A Shepherd, Sharon E Oberfield, Vicente Gilsanz, Babette S Zemel, Struan F A Grant
Over the past two decades, a low frequency variant (rs1800012) within the first intron of the type I collagen alpha 1 (COLIA1) gene has been implicated in lower areal BMD (aBMD) and increased risk of osteoporotic fracture. This association is particularly strong in postmenopausal women, in whom net bone loss arises in the context of high bone turnover. High bone turnover also accompanies childhood linear growth; however, the role of rs1800012 in this stage of net bone accretion is less well understood. Thus, we assessed the association between rs1800012 and aBMD and bone mineral content (BMC) Z-scores for the 1/3 distal radius, lumbar spine, total hip, and femoral neck total body less head in the Bone Mineral Density in Childhood Study, a mixed-longitudinal cohort of children and adolescents (total n = 804 girls and 771 boys; n = 19 girls and 22 boys with the TT genotype)...
January 31, 2019: Bone
Hongbo Dong, Junting Liu, Yinkun Yan, Dongqing Hou, Xiaoyuan Zhao, Hong Cheng, Shengxu Li, Wei Chen, Jie Mi
Body mass plays a crucial role in the bone growth and development, but few studies have examined the association of long-term cumulative impact and trajectory patterns of childhood body mass index (BMI) with adult bone mass, and the mediation effect of adult BMI and body composition on these associations. A total of 397 Chinese adults (54.4%) who had been examined for BMI 4-8 times during childhood (6-19 years) and bone mass in adulthood (29-37 years), were included for analysis. Adult bone mineral content (BMC), areal bone mineral density (aBMD) and body composition were assessed via dual-energy x-ray absorptiometry...
January 30, 2019: Bone
Valeria F Caparbo, Pedro Furlam, Carla G S Saad, Jackeline C Alvarenga, Berengère Aubry-Rozier, Didier Hans, Artur J de Brum-Fernandes, Rosa M R Pereira
OBJECTIVES: To compare bone quality using the trabecular bone score (TBS) and bone microarchitecture in the distal tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) in ankylosing spondylitis (AS) patients and healthy controls (HC). METHODS: Areal bone mineral density (aBMD) and TBS (TBS iNsight software) were evaluated using DXA (Hologic, QDR 4500); while volumetric bone mineral density (vBMD) and bone microarchitecture were analyzed in the distal tibia using HR-pQCT (Scanco) in 73 male patients with AS and 52 age-matched HC...
January 29, 2019: Bone
Gregorio Valdez
The musculoskeletal system includes skeletal muscles, bones and innervating axons from neurons in the central and peripheral nervous system. Together, they form the largest structure in the body. They also initiate and coordinate locomotion, provide structural stability, and contribute to metabolism and homeostasis. Because of these functions, much effort has been devoted to ascertaining the impact of acute and chronic stress, such as disease, injury and aging, on the musculoskeletal system. This review will examine the role of the nervous system in the deleterious changes that accrue in skeletal muscles and bones during the progression of neurologic diseases and with advancing age...
January 26, 2019: Bone
Meena Balasubramanian, Aline Verschueren, Simon Kleevens, Ilse Luyckx, Melanie Perik, Schaida Schirwani, Geert Mortier, Hiroko Morisaki, Inez Rodrigus, Lut Van Laer, Aline Verstraeten, Bart Loeys
Osteogenesis imperfecta (OI) is the commonest form of heritable bone fragility. It is mainly characterized by fractures, hearing loss and dentinogenesis imperfecta. OI patients are at increased risk of cardiovascular disease of variable severity. Aortic aneurysm/dissection is one of the rarer but potentially serious cardiovascular complications of OI. So far, only six patients with aortic dissection and OI have been reported. As such, present OI diagnostic guidelines do not recommend systematic screening of patients for aortopathy...
January 23, 2019: Bone
Cong Zhang, Zhen Zhao, Yue Sun, Lijun Xu, Ruizhi JiaJue, Lijia Cui, Qianqian Pang, Yan Jiang, Mei Li, Ou Wang, Xiaodong He, Shuli He, Min Nie, Xiaoping Xing, Xunwu Meng, Xueying Zhou, Lina Yan, Jared M Kaplan, Karl L Insogna, Weibo Xia
X-linked Hypophosphatemia (XLH) is caused by loss of function mutations in the PHEX gene. Given the recent availability of a new therapy for XLH, a retrospective analysis of the most recent 261 Chinese patients with XLH evaluated at Peking Union Medical College Hospital was conducted. Clinical, biochemical, radiographic studies, as well as genetic analyses, including Sanger sequencing for point mutations and Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large deletions/duplications were employed...
January 22, 2019: Bone
Yuki Yamaguchi, Hiroyuki Kanzaki, Yutaka Miyamoto, Kanako Itohiya, Sari Fukaya, Yuuta Katsumata, Yoshiki Nakamura
INTRODUCTION: The purpose of this study was to examine growth-promoting effects of myo-inositol nutritional supplementation on the mandible in experimental animals. METHODS: Mice were fed on diets that contained various concentration of myo-inositol for 3 to 12 weeks. The length of the mandible, maxilla, and femur were measured on μCT images. The mandible and tibia were examined histologically and immunohistochemically. The effects of myo-inositol on cell proliferation and chondrocytic differentiation were examined using ATDC5 cells...
January 22, 2019: Bone
Olja Grgic, Kuan Chung, Enisa Shevroja, Katerina Trajanoska, Andre G Uitterlinden, Eppo B Wolvius, Fernando Rivadeneira, Carolina Medina-Gomez
Fracture rate in childhood is increasing and its consequences may affect health and developmental processes and cause school absence and restricted activity days. There are scarce epidemiologic studies regarding fractures in children. The aim of this study was to evaluate if pediatric fractures show disparities across sexes and ethnic groups. This study was conducted based on data from 3632 participants of the Generation R Study. Prevalent fractures were assessed using a questionnaire at a mean age of 9.7 years...
January 21, 2019: Bone
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