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Sample records for bone mass phenotype

  1. Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high bone mass phenotype due to a mutation in Lrp5

    DEFF Research Database (Denmark)

    Nielsen, Morten Frost; Andersen, Tom E.; Gossiel, F; Hansen, S; Bollerslev, J; Van Hul, W; Eastell, R; Kassem, M; Brixen, K

    2011-01-01

    CONTEXT: Patients with an activation mutation of the Lrp5 gene exhibit high bone mass (HBM). Limited information is available regarding compartment specific changes in bone. The relationship between the phenotype and serum serotonin is not well documented. Objective: to evaluate bone, serotonin and...... bone turnover markers (BTM) in Lrp5-HBM patients. DESIGN: We studied 19 Lrp5-HBM patients (T253I) and 19 age- and sex-matched controls. DXA and HR-pQCT were used to assess BMD and bone structure. Serum serotonin, sclerostin, DKK1 and BTM were evaluated. RESULTS: Z-scores for the forearm, total hip...

  2. Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin

    DEFF Research Database (Denmark)

    Frost, Morten; Andersen, Tom E.; Yadav, Vijay;

    2010-01-01

    The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high......-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex- and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean +/- SEM: 2.16 +/- 0.28 ng....../mL versus 3.51 +/- 0.49 ng/mL, respectively, p < .05). Our data support the hypothesis that circulating serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans. (c) 2010 American Society for Bone and Mineral Research....

  3. Recql4 haploinsufficiency in mice leads to defects in osteoblast progenitors: Implications for low bone mass phenotype

    International Nuclear Information System (INIS)

    The cellular and molecular mechanisms that underlie skeletal abnormalities in defective Recql4-related syndromes are poorly understood. Our objective in this study was to explore the function of Recql4 in osteoblast biology both in vitro and in vivo. Immunohistochemistry on adult mouse bone showed Recql4 protein localization in active osteoblasts around growth plate, but not in fully differentiated osteocytes. Consistent with this finding, Recql4 gene expression was high in proliferating mouse osteoblastic MC3T3.E1 cells and decreased as cells progressively lost their proliferation activity during differentiation. Recql4 overexpression in osteoblastic cells exhibited higher proliferation activity, while its depletion impeded cell growth. In addition, bone marrow stromal cells from male Recql4+/- mice had fewer progenitor cells, including osteoprogenitors, indicated by reduced total fibroblast colony forming units (CFU-f) and alkaline phosphatase-positive CFU-f colonies concomitant with reduced bone mass. These findings provide evidence that Recql4 functions as a regulatory protein during osteoprogenitor proliferation, a critical cellular event during skeleton development

  4. Genetic control of bone mass.

    Science.gov (United States)

    Boudin, Eveline; Fijalkowski, Igor; Hendrickx, Gretl; Van Hul, Wim

    2016-09-01

    Bone mineral density (BMD) is a quantitative traits used as a surrogate phenotype for the diagnosis of osteoporosis, a common metabolic disorder characterized by increased fracture risk as a result of a decreased bone mass and deterioration of the microarchitecture of the bone. Normal variation in BMD is determined by both environmental and genetic factors. According to heritability studies, 50-85% of the variance in BMD is controlled by genetic factors which are mostly polygenic. In contrast to the complex etiology of osteoporosis, there are disorders with deviating BMD values caused by one mutation with a large impact. These mutations can result in monogenic bone disorders with either an extreme high (sclerosteosis, Van Buchem disease, osteopetrosis, high bone mass phenotype) or low BMD (osteogenesis imperfecta, juvenile osteoporosis, primary osteoporosis). Identification of the disease causing genes, increased the knowledge on the regulation of BMD and highlighted important signaling pathways and novel therapeutic targets such as sclerostin, RANKL and cathepsin K. Genetic variation in genes involved in these pathways are often also involved in the regulation of normal variation in BMD and osteoporosis susceptibility. In the last decades, identification of genetic factors regulating BMD has proven to be a challenge. Several approaches have been tested such as linkage studies and candidate and genome wide association studies. Although, throughout the years, technological developments made it possible to study increasing numbers of genetic variants in populations with increasing sample sizes at the same time, only a small fraction of the genetic impact can yet be explained. In order to elucidate the missing heritability, the focus shifted to studying the role of rare variants, copy number variations and epigenetic influences. This review summarizes the genetic cause of different monogenic bone disorders with deviating BMD and the knowledge on genetic factors

  5. Patients With High Bone Mass Phenotype Exhibit Enhanced Osteoblast Differentiation and Inhibition of Adipogenesis of Human Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Qiu, Weimin; Andersen, Tom; Bollerslev, Jens;

    2007-01-01

    ectopic mineralized bone when implanted subcutaneously with hydroxyapatite/tricalcium phosphate in SCID/NOD mice. Conclusions: LRP5 mutations and the level of Wnt signaling determine differentiation fate of hMSCs into osteoblasts or adipocytes. Activation of Wnt signaling can thus provide a novel approach...

  6. Low bone turnover phenotype in Rett syndrome

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    Roende, Gitte; Petersen, Janne; Ravn, Kirstine;

    2014-01-01

    Background:Patients with Rett syndrome (RTT) are at risk of having low bone mass and low-energy fractures.Methods:We characterised bone metabolism by both bone formation and resorption markers in blood in a RTT population of 61 girls and women and 122 well-matched healthy controls. Levels of N...

  7. Low Bone Mass in Thalassemia

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    4 Low Bone Mass in Thalassemia • In addition to a diet rich in calcium and vitamin D, your doctor may recommend taking calcium ... What can be done to treat low bone mass? Following all of the above prevention measures is ...

  8. Bone Mass Measurement: What the Numbers Mean

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    ... supported by your browser. Home Bone Basics Bone Mass Measurement: What the Numbers Mean Publication available in: ... been one or more osteoporotic fractures. Low Bone Mass Versus Osteoporosis The information provided by a BMD ...

  9. Functions of vasopressin and oxytocin in bone mass regulation.

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    Sun, Li; Tamma, Roberto; Yuen, Tony; Colaianni, Graziana; Ji, Yaoting; Cuscito, Concetta; Bailey, Jack; Dhawan, Samarth; Lu, Ping; Calvano, Cosima D; Zhu, Ling-Ling; Zambonin, Carlo G; Di Benedetto, Adriana; Stachnik, Agnes; Liu, Peng; Grano, Maria; Colucci, Silvia; Davies, Terry F; New, Maria I; Zallone, Alberta; Zaidi, Mone

    2016-01-01

    Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr(-/-) mice have osteopenia, and Avpr1α(-/-) mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr(-/-):Avpr1α(-/-) double-mutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avp-stimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α(-/-) cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling. PMID:26699482

  10. Identifying A Molecular Phenotype for Bone Marrow Stromal Cells With In Vivo Bone Forming Capacity

    DEFF Research Database (Denmark)

    Larsen, Kenneth H; Frederiksen, Casper M; Burns, Jorge S;

    2009-01-01

    Abstract The ability of bone marrow stromal cells (BMSCs) to differentiate into osteoblasts is being exploited in cell-based therapy for repair of bone defects. However, the phenotype of ex vivo cultured BMSCs predicting their bone forming capacity is not known. Thus, we employed DNA microarrays...... comparing two human bone marrow stromal cell (hBMSC) populations: one is capable of in vivo heterotopic bone formation (hBMSC-TERT(+Bone)) and the other is not (hBMSC-TERT(-Bone)). Compared to hBMSC-TERT(-Bone), the hBMSC-TERT(+Bone) cells had an increased over-representation of extracellular matrix genes...... (17% versus 5%) and a larger percentage of genes with predicted SP3 transcription factor binding sites in their promoter region (21% versus 8%). On the other hand, hBMSC-TERT(-Bone) cells expressed a larger number of immune-response related genes (26% versus 8%). In order to test for the predictive...

  11. Physical activity increases bone mass during growth

    OpenAIRE

    Karlsson, Magnus K; Nordvist, Anders; Karlsson, Caroline

    2008-01-01

    Background: The incidence of fragility fractures has increased during the last half of the 1900?s. One important determinant of fractures is the bone mineral content (BMC) or bone mineral density (BMD), the amount of mineralised bone. If we could increase peak bone mass (the highest value of BMC reached during life) and/or decrease the age-related bone loss, we could possibly improve the skeletal resistance to fracture. Objective: This review evaluates the importance of exercise as a strategy...

  12. Bone mass and turnover in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Gam, A; Egsmose, C;

    1993-01-01

    Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found in...... lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

  13. Sclerostin Antibody Treatment Improves the Bone Phenotype of Crtap(-/-) Mice, a Model of Recessive Osteogenesis Imperfecta.

    Science.gov (United States)

    Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

    2016-05-01

    Osteogenesis imperfecta (OI) is characterized by low bone mass, poor bone quality, and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin-neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage-associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1-week-old and 6-week-old Crtap(-/-) mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of "pediatric" and "young adult" recessive OI. Vehicle-treated Crtap(-/-) and wild-type (WT) mice served as controls. Compared with control Crtap(-/-) mice, micro-computed tomography (μCT) analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab-treated Crtap(-/-) mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole-bone strength in Crtap(-/-) mice, with more robust effects in the week 6 to 12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6 to 12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen posttranslational modification. © 2015 American Society for Bone and Mineral Research. PMID:26716893

  14. Umbilical cord leptin predicts neonatal bone mass.

    Science.gov (United States)

    Javaid, M K; Godfrey, K M; Taylor, P; Robinson, S M; Crozier, S R; Dennison, E M; Robinson, J S; Breier, B R; Arden, N K; Cooper, C

    2005-05-01

    Evidence is accumulating that the risk of osteoporosis in later life may be determined in part by environmental influences on bone development during intrauterine and early postnatal life. A potential role for fetal leptin in mediating these effects is suggested by animal studies showing that leptin influences prenatal osteoblast growth and development, and that fetal leptin concentrations are altered by changes in maternal nutrition. In a group of term human infants we reported previously that maternal birthweight, smoking, fat mass, and exercise during late pregnancy independently predict neonatal bone mass. To investigate the potential role of leptin in mediating these effects, we now relate leptin concentrations in umbilical venous serum to neonatal bone mass and body composition in 117 infants. There were strong positive associations between umbilical venous leptin concentration and each of whole body bone mineral contents (BMC) (r = 0.42, P < or = 0.001) and estimated volumetric bone density (r = 0.21, P = 0.02); whole body lean mass (r = 0.21, P < or = 0.024); and whole body fat mass (r = 0.60, P < 0.001). The associations with neonatal BMC and fat mass, but not with lean mass, were independent of associations that we have reported previously between cord serum insulin-like growth factor 1 (IGF-1) concentrations and neonatal body composition. Among the maternal determinants of neonatal bone mass, cord leptin explained the relationship with maternal fat stores, but not those with the mother's own birthweight, smoking, or physical activity. We conclude that umbilical venous leptin predicts both the size of the neonatal skeleton and its estimated volumetric mineral density. In addition, among previously documented maternal determinants of neonatal bone mass in healthy pregnancies, maternal fat stores may mediate their effect on fetal bone accrual through variation in fetal leptin concentrations. PMID:15864467

  15. Clinical assessment of bone mass in children

    Directory of Open Access Journals (Sweden)

    L A Sheplyagina

    2005-02-01

    Full Text Available Objective. To give clinical assessment of bone mass main indices in healthy children living in Moscow and Moscow region. Material and methods. 357 healthy children aged 5-16 years (194 male, 163 female were included. Physical development, bone mineral density (BMD by 2-power radiological absorptiometry, bone mineral content (BMC were evaluated. Results. Significant variability of height in children age groups was revealed. 40,2% had disharmonious physical development. BMC and BMD were closely associated with height (r=0,8, p=0,0001 and body mass (r=0,7, p=0,0001. Bone mass indices were proved to be significantly less in children with height and body mass less then 10% percentile. BMD growth rate was less than mineral accumulation rate. Method of body mass clinical assessment in children was elaborated. Conclusion. Application of elaborated tables of conjugated values of anthropometric and densitometric indices allows to decrease of osteopenia overdiagnosis in children and determine causes of insufficient bone mineral content.

  16. Low bone mass in microscopic colitis

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    Lakatos Péter

    2011-05-01

    Full Text Available Abstract Background Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis. Aims The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis. Methods Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively were measured using immunoassays. Results Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm2; p 2; p 2. Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p Conclusions Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.

  17. Rapid-throughput skeletal phenotyping of 100 knockout mice identifies 9 new genes that determine bone strength.

    Directory of Open Access Journals (Sweden)

    J H Duncan Bassett

    Full Text Available Osteoporosis is a common polygenic disease and global healthcare priority but its genetic basis remains largely unknown. We report a high-throughput multi-parameter phenotype screen to identify functionally significant skeletal phenotypes in mice generated by the Wellcome Trust Sanger Institute Mouse Genetics Project and discover novel genes that may be involved in the pathogenesis of osteoporosis. The integrated use of primary phenotype data with quantitative x-ray microradiography, micro-computed tomography, statistical approaches and biomechanical testing in 100 unselected knockout mouse strains identified nine new genetic determinants of bone mass and strength. These nine new genes include five whose deletion results in low bone mass and four whose deletion results in high bone mass. None of the nine genes have been implicated previously in skeletal disorders and detailed analysis of the biomechanical consequences of their deletion revealed a novel functional classification of bone structure and strength. The organ-specific and disease-focused strategy described in this study can be applied to any biological system or tractable polygenic disease, thus providing a general basis to define gene function in a system-specific manner. Application of the approach to diseases affecting other physiological systems will help to realize the full potential of the International Mouse Phenotyping Consortium.

  18. Vitamin B12–dependent taurine synthesis regulates growth and bone mass

    OpenAIRE

    Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S; Velagapudi, Vidya R.; Dougan, Gordon

    2014-01-01

    Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated p...

  19. Peripheral cannabinoid receptor, CB2, regulates bone mass

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    Ofek, Orr; Karsak, Meliha; Leclerc, Nathalie; Fogel, Meirav; Frenkel, Baruch; Wright, Karen; Tam, Joseph; Attar-Namdar, Malka; Kram, Vardit; Shohami, Esther; Mechoulam, Raphael; Zimmer, Andreas; Bab, Itai

    2006-01-01

    The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regulation of liver fibrosis and atherosclerosis. Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered. These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling. The CB2–/– phenotype is also characterized by increased activity of trabecular osteoblasts (bone-forming cells), increased osteoclast (the bone-resorbing cell) number, and a markedly decreased number of diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not have any psychotropic effects enhances endocortical osteoblast number and activity and restrains trabecular osteoclastogenesis, apparently by inhibiting proliferation of osteoclast precursors and receptor activator of NF-κB ligand expression in bone marrow-derived osteoblasts/stromal cells. The same agonist attenuates ovariectomy-induced bone loss and markedly stimulates cortical thickness through the respective suppression of osteoclast number and stimulation of endocortical bone formation. These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries. PMID:16407142

  20. Bone mass and bone metabolic indices in male master rowers.

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    Śliwicka, Ewa; Nowak, Alicja; Zep, Wojciech; Leszczyński, Piotr; Pilaczyńska-Szcześniak, Łucja

    2015-09-01

    The purpose of this study was to assess bone mass and bone metabolic indices in master athletes who regularly perform rowing exercises. The study was performed in 29 men: 14 master rowers and 15 non-athletic, body mass index-matched controls. Dual-energy X-ray absorptiometry measurements of the areal bone mineral density (aBMD) were performed for the total body, regional areas (arms, total forearms, trunk, thoracic spine, pelvis, and legs), lumbar spine (L1-L4), left hip (total hip and femoral neck), and forearm (33 % radius of the dominant and nondominant forearm). Serum concentrations of osteocalcin, collagen type I cross-linked C-telopeptide, visfatin, resistin, insulin, and glucose were determined. Comparative analyses showed significantly lower levels of body fat and higher lean body mass values in the rowers compared to the control group. The rowers also had significantly higher values of total and regional (left arm, trunk, thoracic spine, pelvis, and leg) BMD, as well as higher BMD values for the lumbar spine and the left hip. There were significant differences between the groups with respect to insulin, glucose, and the index of homeostasis model assessment insulin resistance. In conclusion, the systematic training of master rowers has beneficial effects on total and regional BMD and may be recommended for preventing osteoporosis. PMID:25224128

  1. The peak bone mass concept: is it still relevant?

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    Schönau, Eckhard

    2004-08-01

    The peak bone mass concept implies that optimal skeletal development during childhood and adolescence will prevent fractures in late adulthood. This concept is based on the observation that areal bone density increases with growth during childhood, is highest around 20 years of age and declines thereafter. However, it is now clear that strong bones in the youngster do not necessarily lead to a fracture-free old age. In the recent bone densitometric literature, the terms bone mass and bone density are typically used synonymously. In physics, density has been defined as the mass of a body divided by its volume. In clinical practice and science, "bone density" usually has a different meaning-the degree to which a radiation beam is attenuated by a bone, as judged from a two-dimensional projection image (areal bone density). The attenuation of a radiation beam does not only depend on physical density, but also on bone size. A small bone therefore has a lower areal bone density than a larger bone, even if the physical density is the same. Consequently, a low areal bone density value can simply reflect the small size of an otherwise normal bone. At present, bone mass analysis is very useful for epidemiological studies on factors that may have an impact on bone development. There is an ongoing discussion about whether the World Health Organization (WHO) definition of osteoporosis is over-simplistic and requires upgrading to include indices representing the distribution of bone and mineral (bone strength indices). The following suggestions and recommendations outline a new concept: bone mass should not be related to age. There is now more and more evidence that bone mass should be related to bone size or muscle function. Thus analyzed, there is no such entity as a "peak bone mass". Many studies are currently under way to evaluate whether these novel approaches increase sensitivity and specificity of fracture prediction in an individual. Furthermore, the focus of many bone

  2. The myokine irisin increases cortical bone mass

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    Colaianni, Graziana; Cuscito, Concetta; Mongelli, Teresa; Pignataro, Paolo; Buccoliero, Cinzia; Liu, Peng; Lu, Ping; Sartini, Loris; Di Comite, Mariasevera; Mori, Giorgio; Di Benedetto, Adriana; Brunetti, Giacomina; Yuen, Tony; Sun, Li; Reseland, Janne E.; Colucci, Silvia; New, Maria I.; Zaidi, Mone; Cinti, Saverio; Grano, Maria

    2015-01-01

    It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 µg kg−1. We observed significant increases in cortical bone mass and strength, notably in cortical tissue mineral density, periosteal circumference, polar moment of inertia, and bending strength. This anabolic action was mediated primarily through the stimulation of bone formation, but with parallel notable reductions in osteoclast numbers. The trabecular compartment of the same bones was spared, as were vertebrae from the same mice. Higher irisin doses (3,500 µg kg−1 per week) cause browning of adipose tissue; this was not seen with low-dose r-irisin. Expectedly, low-dose r-irisin modulated the skeletal genes, Opn and Sost, but not Ucp1 or Pparγ expression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up-regulated Atf4, Runx2, Osx, Lrp5, β-catenin, Alp, and Col1a1; this is consistent with a direct receptor-mediated action to stimulate osteogenesis. We also noted that, although the irisin precursor Fndc5 was expressed abundantly in skeletal muscle, other sites, such as bone and brain, also expressed Fndc5, albeit at low levels. Furthermore, muscle fibers from r-irisin–injected mice displayed enhanced Fndc5 positivity, and irisin induced Fdnc5 mRNA expression in cultured myoblasts. Our data therefore highlight a previously unknown action of the myokine irisin, which may be the molecular entity responsible for muscle–bone connectivity. PMID:26374841

  3. High fat diet promotes achievement of peak bone mass in young rats

    Energy Technology Data Exchange (ETDEWEB)

    Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna; Pote, Satish T. [National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007 (India); Mittal, Monika; Chattopadhyay, Naibedya [Division of Endocrinology and Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Jankipuram Extension, Sitapur Road, Lucknow 226 031 (India); Wani, Mohan R. [National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007 (India); Bhat, Manoj Kumar, E-mail: manojkbhat@nccs.res.in [National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007 (India)

    2014-12-05

    Highlights: • High fat diet helps in achieving peak bone mass at younger age. • Shifting from high fat to normal diet normalizes obese parameters. • Bone parameters are sustained even after withdrawal of high fat diet. - Abstract: The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.

  4. High fat diet promotes achievement of peak bone mass in young rats

    International Nuclear Information System (INIS)

    Highlights: • High fat diet helps in achieving peak bone mass at younger age. • Shifting from high fat to normal diet normalizes obese parameters. • Bone parameters are sustained even after withdrawal of high fat diet. - Abstract: The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet

  5. Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors

    OpenAIRE

    Danielle E Green; Rubin, Clinton T.

    2014-01-01

    The rising levels of radiation exposure, specifically for medical treatments and accidental exposures, have added great concern for the long term risks of bone fractures. Both the bone marrow and bone architecture are devastated following radiation exposure. Even sub-lethal doses cause a deficit to the bone marrow microenvironment, including a decline in hematopoietic cells, and this deficit occurs in a dose dependent fashion. Certain cell phenotypes though are more susceptible to radiation d...

  6. Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    宋陆茜

    2013-01-01

    Objective To investigate phenotype,cell differentiation and cytogenetic properties of bone marrow(BM) mesenchymal stem cells(MSC)separated from the myelodysplastic syndrome(MDS) patients,and to analyze cytogenetic

  7. Common endocrine control of body weight, reproduction, and bone mass

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Karsenty, Gerard

    2003-01-01

    Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

  8. AMP-activated protein kinase (AMPK) activation regulates in vitro bone formation and bone mass.

    Science.gov (United States)

    Shah, M; Kola, B; Bataveljic, A; Arnett, T R; Viollet, B; Saxon, L; Korbonits, M; Chenu, C

    2010-08-01

    Adenosine 5'-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones. The objective of this study was to determine if AMPK can be activated in osteoblasts by known AMPK modulators and if AMPK activity is involved in osteoblast function in vitro and regulation of bone mass in vivo. ROS 17/2.8 rat osteoblast-like cells were cultured in the presence of AMPK activators (AICAR and metformin), AMPK inhibitor (compound C), the gastric peptide hormone ghrelin and the beta-adrenergic blocker propranolol. AMPK activity was measured in cell lysates by a functional kinase assay and AMPK protein phosphorylation was studied by Western Blotting using an antibody recognizing AMPK Thr-172 residue. We demonstrated that treatment of ROS 17/2.8 cells with AICAR and metformin stimulates Thr-172 phosphorylation of AMPK and dose-dependently increases its activity. In contrast, treatment of ROS 17/2.8 cells with compound C inhibited AMPK phosphorylation. Ghrelin and propranolol dose-dependently increased AMPK phosphorylation and activity. Cell proliferation and alkaline phosphatase activity were not affected by metformin treatment while AICAR significantly inhibited ROS 17/2.8 cell proliferation and alkaline phosphatase activity at high concentrations. To study the effect of AMPK activation on bone formation in vitro, primary osteoblasts obtained from rat calvaria were cultured for 14-17days in the presence of AICAR, metformin and compound C. Formation of 'trabecular-shaped' bone nodules was evaluated following alizarin red staining. We demonstrated that both AICAR and metformin dose-dependently increase trabecular bone nodule formation, while compound C inhibits bone formation. When primary osteoblasts were co-treated with AICAR and compound C, compound C suppressed the stimulatory effect of AICAR on bone nodule formation

  9. The Role of Bone Marrow Cells in the Phenotypic Changes Associated with Diabetic Nephropathy

    OpenAIRE

    Guang Yang; Qingli Cheng; Sheng Liu; Jiahui Zhao

    2015-01-01

    The aim of our study was to investigate the role of bone marrow cells in the phenotypic changes that occur in diabetic nephropathy. Bone marrow cells were obtained from either streptozotocin-induced diabetic or untreated control C3H/He mice and transplanted into control C3H/He mice. Eight weeks after bone marrow cell transplantation, renal morphologic changes and clinical parameters of diabetic nephropathy, including the urine albumin/creatinine ratio and glucose tolerance, were measured in v...

  10. Variation in the MC4R gene is associated with bone phenotypes in elderly Swedish women.

    Directory of Open Access Journals (Sweden)

    Gaurav Garg

    Full Text Available Osteoporosis is characterized by reduced bone mineral density (BMD and increased fracture risk. Fat mass is a determinant of bone strength and both phenotypes have a strong genetic component. In this study, we examined the association between obesity associated polymorphisms (SNPs with body composition, BMD, Ultrasound (QUS, fracture and biomarkers (Homocysteine (Hcy, folate, Vitamin D and Vitamin B12 for obesity and osteoporosis. Five common variants: rs17782313 and rs1770633 (melanocortin 4 receptor (MC4R; rs7566605 (insulin induced gene 2 (INSIG2; rs9939609 and rs1121980 (fat mass and obesity associated (FTO were genotyped in 2 cohorts of Swedish women: PEAK-25 (age 25, n = 1061 and OPRA (age 75, n = 1044. Body mass index (BMI, total body fat and lean mass were strongly positively correlated with QUS and BMD in both cohorts (r(2 = 0.2-0.6. MC4R rs17782313 was associated with QUS in the OPRA cohort and individuals with the minor C-allele had higher values compared to T-allele homozygotes (TT vs. CT vs.100 vs. 103 vs. 103; p = 0.002; (SOS: 1521 vs. 1526 vs. 1524; p = 0.008; (Stiffness index: 69 vs. 73 vs. 74; p = 0.0006 after adjustment for confounders. They also had low folate (18 vs. 17 vs. 16; p = 0.03 and vitamin D (93 vs. 91 vs. 90; p = 0.03 and high Hcy levels (13.7 vs 14.4 vs. 14.5; p = 0.06. Fracture incidence was lower among women with the C-allele, (52% vs. 58%; p = 0.067. Variation in MC4R was not associated with BMD or body composition in either OPRA or PEAK-25. SNPs close to FTO and INSIG2 were not associated with any bone phenotypes in either cohort and FTO SNPs were only associated with body composition in PEAK-25 (p≤0.001. Our results suggest that genetic variation close to MC4R is associated with quantitative ultrasound and risk of fracture.

  11. New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

    International Nuclear Information System (INIS)

    Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr−/−) and wild-type (Ahr+/+) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr+/+ mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr−/− mice displayed a slightly modified bone phenotype as compared with untreated Ahr+/+ mice, while TCDD exposure caused only a few changes in bones of Ahr−/− mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr+/+ mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation results in increased trabecular bone and softer

  12. Neuropeptide Y knockout mice reveal a central role of NPY in the coordination of bone mass to body weight.

    Directory of Open Access Journals (Sweden)

    Paul A Baldock

    Full Text Available Changes in whole body energy levels are closely linked to alterations in body weight and bone mass. Here, we show that hypothalamic signals contribute to the regulation of bone mass in a manner consistent with the central perception of energy status. Mice lacking neuropeptide Y (NPY, a well-known orexigenic factor whose hypothalamic expression is increased in fasting, have significantly increased bone mass in association with enhanced osteoblast activity and elevated expression of bone osteogenic transcription factors, Runx2 and Osterix. In contrast, wild type and NPY knockout (NPY (-/- mice in which NPY is specifically over expressed in the hypothalamus (AAV-NPY+ show a significant reduction in bone mass despite developing an obese phenotype. The AAV-NPY+ induced loss of bone mass is consistent with models known to mimic the central effects of fasting, which also show increased hypothalamic NPY levels. Thus these data indicate that, in addition to well characterized responses to body mass, skeletal tissue also responds to the perception of nutritional status by the hypothalamus independently of body weight. In addition, the reduction in bone mass by AAV NPY+ administration does not completely correct the high bone mass phenotype of NPY (-/- mice, indicating the possibility that peripheral NPY may also be an important regulator of bone mass. Indeed, we demonstrate the expression of NPY specifically in osteoblasts. In conclusion, these data identifies NPY as a critical integrator of bone homeostatic signals; increasing bone mass during times of obesity when hypothalamic NPY expression levels are low and reducing bone formation to conserve energy under 'starving' conditions, when hypothalamic NPY expression levels are high.

  13. Osteoporosis: Peak Bone Mass in Women

    Science.gov (United States)

    ... Bone Health for Lupus Patients Bone Health and Anorexia Nervosa Partner Resources Screening Tests and Immunizations Guidelines for ... calcium. Physical Activity. Girls and boys and young adults who exercise regularly generally achieve greater peak bone ...

  14. Mixed Phenotypic Acute Leukemia Presenting as Mediastinal Mass-2 Cases.

    Science.gov (United States)

    Vardhan, Rig; Kotwal, Jyoti; Ganguli, Prosenjit; Ahmed, Rehan; Sharma, Ajay; Singh, Jasjit

    2016-06-01

    Mixed phenotype acute leukemia symbolizes a very small subset of acute leukemia that simply cannot be allocated as lymphoid or myeloid lineage. The 2008 World Health Organisation classification established stringent standard for diagnosis of mixed phenotype acute leukemia, accentuating myeloperoxidase for myeloid lineage, cytoplasmic CD3 for T lineage and CD19 with other B markers for B lineage obligation. Mixed phenotype leukemia is rare and 3-5 % of acute leukmias of all age groups, is associated with poor outcome with overall survival of 18 months. We wish to present two cases of mixed phenotypic acute leukemia who presented with mediastinal masses, were suspected to be T cell lymphoma/leukemia clinically and radiologically. In one case, tissue diagnosis was given as lymphoma for which treatment was given. These cases show that patients diagnosed as lymphoma on histopathology can be cases of mixed phenotype acute leukemia and varying specific treatment protocols and follow up are required. Awareness of these entities will help in proper diagnosis and treatment. PMID:27408360

  15. Androgen and bone mass in men

    Institute of Scientific and Technical Information of China (English)

    AnnieW.C.Kung

    2003-01-01

    Androgens have multiple actions on the skeleton throughout life. Androgens promote skeletal growth and accumulation of minerals during puberty and adolescence and stimulate osteoblast but suppress osteoclast function,activity and lifespan through complex mechanisms. Also androgens increase periosteal bone apposition, resulting in larger bone size and thicker cortical bone in men. There is convincing evidence to show that aromatization to estrogens was an important pathway for mediating the action of testosterone on bone physiology. Estrogen is probably the dominant sex steroid regulating bone resorption in men, but both testosterone and estrogen are important in maintaining bone formation. ( Asian J Androl 2003 Jun; 5: 148-154)

  16. DXA measurements in rett syndrome reveal small bones with low bone mass

    DEFF Research Database (Denmark)

    Roende, Gitte; Ravn, Kirstine; Fuglsang, Kathrine;

    2011-01-01

    Low bone mass is reported in growth-retarded patients harboring mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene causing Rett syndrome (RTT). We present the first study addressing both bone mineral density (BMD) and bone size in RTT. Our object was to determine whether patients...

  17. The Effect of Estrogen on the Restoration of Bone Mass and Bone Quality in Ovariectomized Rats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To evaluate the effect of estrogen on its ability to restore the bone mass and bone quality in ovariectomized rats by examining the changes of bone morphology and histomorphometry, 3month-old rats were divided randomly into 4 groups: normal control, ovariectomized (OVX), shamoperated (Sham-O) and OVX plus estrogen (OVX+E2). Treatment initiated from the day 8 weeks after operation and continued for 12 weeks. Bone morphology and histomorphometry were examined afterwards. Results showed that comparing to control group, the trabecular bone in OVX appeared thinner and reduced in the amount. The connectivity between trabecula was decreased and the structure disordered. The free-end of trabecula was increased. The cavity of bone marrow enlarged. After treatment with estrogen, above changes improved remarkably by different degree, although did not reach the normal face. The bone histomorphometry results damonstrated that estrogen treatment increased bone mass and the amount of trabecula by 129% and 132% respectively (P<0. 05). The activity of bone resorption decreased significantly and the rate of bone formation increased to 203 %. These results suggest that treatment of ovariectomized rats with estrogen can not only increase bone mass, also improve the bone structure and enhance the property of bone mechanics.

  18. Osteoblast-specific overexpression of amphiregulin leads to transient increase in femoral cancellous bone mass in mice.

    Science.gov (United States)

    Vaidya, Mithila; Lehner, Diana; Handschuh, Stephan; Jay, Freya F; Erben, Reinhold G; Schneider, Marlon R

    2015-12-01

    The epidermal growth factor receptor ligand amphiregulin (AREG) has been implicated in bone physiology and in bone anabolism mediated by intermittent parathyroid hormone treatment. However, the functions of AREG in bone have been only incipiently evaluated in vivo. Here, we generated transgenic mice overexpressing AREG specifically in osteoblasts (Col1-Areg). pQCT analysis of the femoral metaphysis revealed increased trabecular bone mass at 4, 8, and 10weeks of age in Col1-Areg mice compared to control littermates. However, the high bone mass phenotype was transient and disappeared in older animals. Micro-CT analysis of the secondary spongiosa confirmed increased trabecular bone volume and trabecular number in the distal femur of 4-week-old AREG-tg mice compared to control littermates. Furthermore, μ-CT analysis of the primary spongiosa revealed unaltered production of new bone trabeculae in distal femora of Col1-Areg mice. Histomorphometric analysis revealed a reduced number of osteoclasts in 4-week-old Col1-Areg mice, but not at later time points. Cancellous bone formation rate remained unchanged in Col1-Areg mice at all time points. In addition, bone mass and bone turnover in lumbar vertebral bodies were similar in Col1-Areg and control mice at all ages examined. Proliferation and differentiation of osteoblasts isolated from neonatal calvariae did not differ between Col1-Areg and control mice. Taken together, these data suggest that AREG overexpression in osteoblasts induces a transient high bone mass phenotype in the trabecular compartment of the appendicular skeleton by a growth-related, non-cell autonomous mechanism, leading to a positive bone balance with unchanged bone formation and lowered bone resorption. PMID:26103093

  19. The Role of Bone Marrow Cells in the Phenotypic Changes Associated with Diabetic Nephropathy.

    Directory of Open Access Journals (Sweden)

    Guang Yang

    Full Text Available The aim of our study was to investigate the role of bone marrow cells in the phenotypic changes that occur in diabetic nephropathy. Bone marrow cells were obtained from either streptozotocin-induced diabetic or untreated control C3H/He mice and transplanted into control C3H/He mice. Eight weeks after bone marrow cell transplantation, renal morphologic changes and clinical parameters of diabetic nephropathy, including the urine albumin/creatinine ratio and glucose tolerance, were measured in vivo. Expression levels of the genes encoding α1 type IV collagen and transforming growth factor-β1 in the kidney were assayed. Our results demonstrated that glucose tolerance was normal in the recipients of bone marrow transplants from both diabetic and control donors. However, compared with recipients of the control bone marrow transplant, the urinary albumin/creatinine ratio, glomerular size, and the mesangial/glomerular area ratio increased 3.3-fold (p < 0.01, 1.23-fold (p < 0.01, and 2.13-fold (p < 0.001, respectively, in the recipients of the diabetic bone marrow transplant. Expression levels of the genes encoding glomerular α1 type IV collagen and transforming growth factor-β1 were also significantly increased (p < 0.01 in the recipients of the diabetic bone marrow transplant. Our data suggest that bone marrow cells from the STZ-induced diabetic mice can confer a diabetic phenotype to recipient control mice without the presence of hyperglycemia.

  20. Strong effect of SNP rs4988300 of the LRP5 gene on bone phenotype of Caucasian postmenopausal women.

    Science.gov (United States)

    Horváth, Péter; Balla, Bernadett; Kósa, János P; Tóbiás, Bálint; Szili, Balázs; Kirschner, Gyöngyi; Győri, Gabriella; Kató, Karina; Lakatos, Péter; Takács, István

    2016-01-01

    The purpose of this study was to identify relationships between single nucleotide polymorphisms (SNPs) in the genes of the Wnt pathway and bone mineral density (BMD) of postmenopausal women. We chose this pathway due to its importance in bone metabolism that was underlined in several studies. DNA samples of 932 Hungarian postmenopausal women were studied. First, their BMD values at different sites (spine, total hip) were measured, using a Lunar Prodigy DXA scanner. Thereafter, T-score values and the patients' body mass indices (BMIs) were calculated, while information about the fracture history of the sample population was also collected. We genotyped nine SNPs of the following three genes: LRP5, GPR177, and SP7, using a Sequenom MassARRAY Analyzer 4 instrument. The genomic DNA samples used for genotyping were extracted from the buccal mucosa of the subjects. Statistical analyses were carried out using the SPSS 21 and R package. The results of this analysis showed a significant association between SNP rs4988300 of the LRP5 gene and total hip BMD values. We could not reveal any associations between the markers of GPR177, SP7, and bone phenotypes. We found no effect of these genotypes on fracture risk. We could demonstrate a significant gene-gene interaction between two SNPs of LRP5 (rs4988300 and rs634008, p = 0.009) which was lost after Bonferroni correction. We could firmly demonstrate a significant association between rs4988300 of the LRP5 gene and bone density of the hip on the largest homogeneous postmenopausal study group analyzed to date. Our finding corroborates the relationship between LRP5 genotype and bone phenotype in postmenopausal women, however, the complete mechanism of this relationship requires further investigations. PMID:25762437

  1. The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice.

    Science.gov (United States)

    Vinik, Yaron; Shatz-Azoulay, Hadas; Vivanti, Alessia; Hever, Navit; Levy, Yifat; Karmona, Rotem; Brumfeld, Vlad; Baraghithy, Saja; Attar-Lamdar, Malka; Boura-Halfon, Sigalit; Bab, Itai; Zick, Yehiel

    2015-01-01

    Skeletal integrity is maintained by the co-ordinated activity of osteoblasts, the bone-forming cells, and osteoclasts, the bone-resorbing cells. In this study, we show that mice overexpressing galectin-8, a secreted mammalian lectin of the galectins family, exhibit accelerated osteoclasts activity and bone turnover, which culminates in reduced bone mass, similar to cases of postmenopausal osteoporosis and cancerous osteolysis. This phenotype can be attributed to a direct action of galectin-8 on primary cultures of osteoblasts that secrete the osteoclastogenic factor RANKL upon binding of galectin-8. This results in enhanced differentiation into osteoclasts of the bone marrow cells co-cultured with galectin-8-treated osteoblasts. Secretion of RANKL by galectin-8-treated osteoblasts can be attributed to binding of galectin-8 to receptor complexes that positively (uPAR and MRC2) and negatively (LRP1) regulate galectin-8 function. Our findings identify galectins as new players in osteoclastogenesis and bone remodeling, and highlight a potential regulation of bone mass by animal lectins. PMID:25955862

  2. Phenotypic characterization of early events of thymus repopulation in radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    The phenotype of murine thymocytes repopulating the thymus of radiation bone marrow chimeras shortly after irradiation and bone marrow reconstitution was analyzed by immunofluorescence and flow microfluorometry. Thymuses in these chimeras, while essentially devoid of lymphoid cells at day 7, were repopulated by days 10 to 12 after irradiation. It was found that this initial repopulation arose from a radioresistant intrathymic precursor that expanded to an almost complete complement of host-type thymocytes. However, these host-derived thymocytes were unusual in that they were relatively deficient in Lyt 1+2- and peanut agglutinin ''dull'' cells as compared with normal thymocytes. Donor bone-marrow-derived cells first appeared in the irradiated chimeric thymuses between days 12 and 15 after irradiation and bone marrow transfer. By day 19, chimeric thymuses contained more than 98% donor cells. This course was identical for three chimeric combinations, each made across different genetic barriers. In contrast to the cells that populate the fetal thymus during normal ontogeny, the first donor bone-marrow-derived cells that can be detected within the irradiated chimeric thymuses already expressed phenotypically normal adult T cell subpopulations in that they contained significant numbers both of Lyt 1+2- and of Lyt 1+2+ thymocytes. Thus, the Lyt phenotype of donor cells that initially repopulate an adult thymus after irradiation is markedly different from the Lyt phenotype of cells that initially populate the fetal thymus. The differences between adult and fetal thymic development that are observed in radiation bone marrow chimeras may be important in our understanding of T cell differentiation in these animals

  3. A quantification strategy for missing bone mass in case of osteolytic bone lesions

    International Nuclear Information System (INIS)

    Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approach is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean

  4. A quantification strategy for missing bone mass in case of osteolytic bone lesions

    Energy Technology Data Exchange (ETDEWEB)

    Fränzle, Andrea, E-mail: a.fraenzle@dkfz.de; Giske, Kristina [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Bretschi, Maren; Bäuerle, Tobias [Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Hillengass, Jens [Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Bendl, Rolf [Medical Informatics, Heilbronn University, Max-Planck-Strasse 39, 74081 Heilbronn, Germany and Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2013-12-15

    Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approach is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean

  5. New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

    Energy Technology Data Exchange (ETDEWEB)

    Herlin, Maria, E-mail: maria.herlin@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Zioupos, Peter, E-mail: p.zioupos@cranfield.ac.uk [Biomechanics Laboratories, Department of Engineering and Applied Science, Cranfield University, Shrivenham SN6 8LA (United Kingdom); Aula, Antti, E-mail: antti.aula@gmail.com [Department of Medical Physics, Imaging Centre, Tampere University Hospital, Tampere (Finland); Department of Biomedical Engineering, Tampere University of Technology, Tampere (Finland); Risteli, Juha, E-mail: juha.risteli@ppshp.fi [Department of Clinical Chemistry, Oulu University Hospital, Oulu (Finland); Miettinen, Hanna M., E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Jämsä, Timo, E-mail: timo.jamsa@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Diagnostic Radiology, Oulu University Hospital, Oulu (Finland); Tuukkanen, Juha, E-mail: juha.tuukkanen@oulu.fi [Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Korkalainen, Merja, E-mail: merja.korkalainen@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Håkansson, Helen, E-mail: Helen.Hakansson@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Viluksela, Matti, E-mail: matti.viluksela@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Department of Environmental Science, University of Eastern Finland, Kuopio (Finland)

    2013-11-15

    Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup −/−}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup −/−} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup −/−} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation

  6. Diet-induced obesity alters bone remodeling leading to decreased femoral trabecular bone mass in mice.

    Science.gov (United States)

    Cao, Jay J; Sun, Li; Gao, Hongwei

    2010-03-01

    Obesity-derived body mass may be detrimental to bone health through not well-defined mechanisms. In this study we determined changes in bone structure and serum cytokines related to bone metabolism in diet-induced obese mice. Mice fed a high-fat diet (HFD) had higher serum tartrate-resistant acid phosphatase (TRAP) and leptin but lower osteocalcin concentrations than those fed the normal-fat diet. The HFD increased multinucleated TRAP-positive osteoclasts in bone marrow compared to the control diet. Despite being much heavier, mice fed the HFD had lower femoral bone volume, trabecular number, and connectivity density and higher trabecular separation than mice on the control diet. These findings suggest that obesity induced by a HFD increases bone resorption that may blunt any positive effects of increased body weight on bone. PMID:20392249

  7. Calcineurin/NFAT signaling in osteoblasts regulates bone mass.

    Science.gov (United States)

    Winslow, Monte M; Pan, Minggui; Starbuck, Michael; Gallo, Elena M; Deng, Lei; Karsenty, Gerard; Crabtree, Gerald R

    2006-06-01

    Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1(nuc)) in osteoblasts develop high bone mass. NFATc1(nuc) mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1(nuc) mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts. PMID:16740479

  8. Widespread differential maternal and paternal genome effects on fetal bone phenotype at mid-gestation.

    Science.gov (United States)

    Xiang, Ruidong; Lee, Alice M C; Eindorf, Tanja; Javadmanesh, Ali; Ghanipoor-Samami, Mani; Gugger, Madeleine; Fitzsimmons, Carolyn J; Kruk, Zbigniew A; Pitchford, Wayne S; Leviton, Alison J; Thomsen, Dana A; Beckman, Ian; Anderson, Gail I; Burns, Brian M; Rutley, David L; Xian, Cory J; Hiendleder, Stefan

    2014-11-01

    Parent-of-origin-dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1-6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25-hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p

  9. SWIMMING ENHANCES BONE MASS ACQUISITION IN GROWING FEMALE RATS

    Directory of Open Access Journals (Sweden)

    Joanne McVeigh

    2010-12-01

    Full Text Available Growing bones are most responsive to mechanical loading. We investigated bone mass acquisition patterns following a swimming or running exercise intervention of equal duration, in growing rats. We compared changes in bone mineral properties in female Sprague Dawley rats that were divided into three groups: sedentary controls (n = 10, runners (n = 8 and swimmers (n = 11. Runners and swimmers underwent a six week intervention, exercising five days per week, 30min per day. Running rats ran on an inclined treadmill at 0.33 m.s-1, while swimming rats swam in 25oC water. Dual energy X-ray absorptiometry scans measuring bone mineral content (BMC, bone mineral density (BMD and bone area at the femur, lumbar spine and whole body were recorded for all rats before and after the six week intervention. Bone and serum calcium and plasma parathyroid hormone (PTH concentrations were measured at the end of the 6 weeks. Swimming rats had greater BMC and bone area changes at the femur and lumbar spine (p < 0.05 than the running rats and a greater whole body BMC and bone area to that of control rats (p < 0.05. There were no differences in bone gain between running and sedentary control rats. There was no significant difference in serum or bone calcium or PTH concentrations between the groups of rats. A swimming intervention is able to produce greater beneficial effects on the rat skeleton than no exercise at all, suggesting that the strains associated with swimming may engender a unique mechanical load on the bone

  10. The Phenotypic Fate of Bone Marrow-Derived Stem Cells in Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Guowei Feng

    2013-11-01

    Full Text Available Background: Despite increasing attention on the role of bone marrow derived stem cells in repair or rejuvenation of tissues and organs, cellular mechanisms of such cell-based therapy remain poorly understood. Methods: We reconstituted hematopoiesis in recipient C57BL/6J mice by transplanting syngeneic GFP+ bone marrow (BM cells. Subsequently, the recipients received subcutaneous injection of granulocyte-colony stimulating factor (G-CSF and were subjected to acute renal ischemic injury. Flow cytometry and immunostaining were performed at various time points to assess engraftment and phenotype of BM derived stem cells. Results: Administration of G-CSF increased the release of BM derived stem cells into circulation and enhanced the ensuing recruitment of BM derived stem cells into injured kidney. During the second month post injury, migrated BM derived stem cells lost hematopoietic phenotype (CD45 but maintained the expression of other markers (Sca-1, CD133 and CD44, suggesting their potential of transdifferentiation into renal stem cells. Moreover, G-CSF treatment enhanced the phenotypic conversion. Conclusion: Our work depicted a time-course dependent transition of phenotypic characteristics of BM derived stem cells, demonstrated the existence of BM derived stem cells in damaged kidney and revealed the effects of G-CSF on cell transdifferentiation.

  11. Effect of Probiotics Supplementation on Bone Mineral Content and Bone Mass Density

    Directory of Open Access Journals (Sweden)

    Kolsoom Parvaneh

    2014-01-01

    Full Text Available A few studies in animals and a study in humans showed a positive effect of probiotic on bone metabolism and bone mass density. Most of the investigated bacteria were Lactobacillus and Bifidobacterium . The positive results of the probiotics were supported by the high content of dietary calcium and the high amounts of supplemented probiotics. Some of the principal mechanisms include (1 increasing mineral solubility due to production of short chain fatty acids; (2 producing phytase enzyme by bacteria to overcome the effect of mineral depressed by phytate; (3 reducing intestinal inflammation followed by increasing bone mass density; (4 hydrolysing glycoside bond food in the intestines by Lactobacillus and Bifidobacteria. These mechanisms lead to increase bioavailability of the minerals. In conclusion, probiotics showed potential effects on bone metabolism through different mechanisms with outstanding results in the animal model. The results also showed that postmenopausal women who suffered from low bone mass density are potential targets to consume probiotics for increasing mineral bioavailability including calcium and consequently increasing bone mass density.

  12. Maximal strength training improves bone mass in young women

    OpenAIRE

    Carlsen, Trude

    2012-01-01

    Background:  Current exercise guidelines highlight maximising peak bone mass as an important strategy in the prevention of osteoporosis later in life.  Exercise recommendations suggest impact – and weight lifting exercises as effective for improving bone mass in young women.  However,  it  is  still  unclear  which  weight  lifting  intervention,  with  respect  to exercises, intensity, frequency and duration, is the most effective. Objective: The purpose of the study was to investigate the e...

  13. Different titanium surfaces modulate the bone phenotype of SaOS-2 osteoblast-like cells

    Directory of Open Access Journals (Sweden)

    L Postiglione

    2009-06-01

    Full Text Available Commercially pure titanium implants presenting a relatively smooth, machined surface or a roughened endosseous surface show a large percentage of clinical success. Surface properties of dental implants seem to affect bone cells response. Implant topography appears to modulate cell growth and differentiation of osteoblasts affecting the bone healing around the titanium implant. The aim of the present study was to examine the effects of 1cm diameter and 1mm thick titanium disks on cellular morphology, adhesion and bone phenotypic expression of human osteoblast-like cells, SaOS-2. SaOS-2 cells were cultured on commercially 1 cm pure titanium disks with three different surface roughness: smooth (S, sandblasted (SB and titanium plasma sprayed (TPS. Differences in the cellular morphology were found when they were grown on the three different surfaces. An uniform monolayer of cells recovered the S surface, while clusters of multilayered irregularly shaped cells were distributed on the rough SB and TPS surfaces. The adhesion of SaOS-2 cells, as measured after 3h of culture, was not affected by surface roughness. ECM components such as Collagen I (CoI, Fibronectin (FN, Vitronectin (VN and Tenascin (TN were secreted and organized only on the SB and TPS surfaces while they remained into the cytoplasm on the S surfaces. Osteopontin and BSP-II were largely detected on the SB and TPS surfaces, while only minimal production was observed on the S ones. These data show that titanium surface roughness affects bone differentiation of osteoblast like-cells, SaOS-2, indicating that surface properties may be able to modulate the osteoblast phenotype. These observations also suggest that the bone healing response around dental implants can be affected by surface topography.

  14. Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

    Directory of Open Access Journals (Sweden)

    Shriram Nallamshetty

    Full Text Available The effects of retinoids, the structural derivatives of vitamin A (retinol, on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA and its precursor all trans retinaldehyde (Rald, exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1, the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT demonstrated that Aldh1a1-deficient (Aldh1a1(-/- female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/- mice. In serum assays, Aldh1a1(-/- mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/- mesenchymal stem cells (MSCs expressed significantly higher levels of bone morphogenetic protein 2 (BMP2 and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/- mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/- mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.

  15. Bone Mass in Young Adults with down Syndrome

    Science.gov (United States)

    Guijarro, M.; Valero, C.; Paule, B.; Gonzalez-Macias, J.; Riancho, J. A.

    2008-01-01

    Background: Down syndrome (DS) is a frequent cause of intellectual disability. With the increasing life expectancy of these patients, concerns have been raised about the risk of osteoporosis. In fact, several investigators have reported a reduced bone mass in DS. However, the results may be confounded by comorbid diseases, and differences in…

  16. Bone Marrow Transplantation Alters the Tremor Phenotype in the Murine Model of Globoid-Cell Leukodystrophy

    Directory of Open Access Journals (Sweden)

    Adarsh S. Reddy

    2012-01-01

    Full Text Available Tremor is a prominent phenotype of the twitcher mouse, an authentic genetic model of Globoid-Cell Leukodystrophy (GLD, Krabbe’s disease. In the current study, the tremor was quantified using a force-plate actometer designed to accommodate low-weight mice. The actometer records the force oscillations caused by a mouse’s movements, and the rhythmic structure of the force variations can be revealed. Results showed that twitcher mice had significantly increased power across a broad band of higher frequencies compared to wildtype mice. Bone marrow transplantation (BMT, the only available therapy for GLD, worsened the tremor in the twitcher mice and induced a measureable alteration of movement phenotype in the wildtype mice. These data highlight the damaging effects of conditioning radiation and BMT in the neonatal period. The behavioral methodology used herein provides a quantitative approach for assessing the efficacy of potential therapeutic interventions for Krabbe’s disease.

  17. Peak bone mass density among residents of Metro Manila

    International Nuclear Information System (INIS)

    To determine the peak bone mass density among residents of Metro Manila using dual x-ray absorptiometry (DEXA).The design used is cross-sectional study. The study include 23 females and 22 males, with 3 to 4 subjects for each age range of 5. The methods used was bone mass density measurements on the lumbar spine and the femur using dual x-ray absorptiometry (DPXI lunar) were taken. The values were also age-matched and matched with that of a young adult based on programmed Caucasian norm provided by Lunar Co. The values were then scattered against age for each sex. Ten (10) cc of blood was also extracted from the patients, with 5 cc of blood separated for future studies. Patients were also interviewed as to their lifestyle, diet, use of contraceptive pill or hormonal replacement treatment, using a Filipino version of the revised questionnaire on the WHO Study on osteoporosis. The mean bone mass density at the L21.4 level for females was 1.12±0.11 g/cm2 and 0,91±0.11 g/cm2 at the femur. The highest BMD in both the lumbar spine femoral neck measurements among females was achieved between the ages 30-35 years of age with the lowest BMD occurring between 15-20 yrs. old and incidentally in 2 subjects with ages between 40-44. There seems to be little bone loss among beyond the age 35, unlike in the females. Bone mass density among a sample Metro Manila residents was determined using DEXA and the measurements on the lumbar spine and femoral neck. These were age-matched with that of young adult based on Caucasian norm provided by the Lunar Co. Peak bone mass density in the L2L4 level among the females is reached between the ages 30-35 years old, after which there is progressive bone loss with values in the 45-50 years old approximating the values in the 15-19 years old age range. A similar pattern is seen in the measurements taken at the femoral neck. Among males, the peak BMD is reached during the 30-35 years old, but there seems to be no rapid decline or rapid bone loss

  18. Deletion of Estrogen Receptor Beta in Osteoprogenitor Cells Increases Trabecular but Not Cortical Bone Mass in Female Mice.

    Science.gov (United States)

    Nicks, Kristy M; Fujita, Koji; Fraser, Daniel; McGregor, Ulrike; Drake, Matthew T; McGee-Lawrence, Meghan E; Westendorf, Jennifer J; Monroe, David G; Khosla, Sundeep

    2016-03-01

    Although the role of ERα in regulating bone metabolism has been extensively studied, ERβ has been largely dismissed as a relevant modulator of bone mass. Previous studies examining ERβ utilized a germline knockout mouse expressing transcript variants of ERβ and displaying systemic hormonal changes that confounded interpretation of the skeletal phenotype. Thus, we used a conditional ERβ mouse model to achieve deletion of ERβ specifically in early osteoprogenitor cells using the Prx1-Cre driver. We observed marked increases in the trabecular bone volume fraction (of 58% [p development. However, the ratio of colony-forming unit-osteoblasts (CFU-OBs) to CFU-fibroblasts (CFU-Fs) was increased in bone marrow cultures from ERβ(Prx1-CKO) compared with control mice, indicating increased differentiation of osteoblast precursor cells into osteoblasts in ERβ(Prx1-CKO) mice. Detailed quantitative polymerase chain reaction analyses of 128 genes in 16 prespecified pathways revealed significant downregulation of 11 pathways in ERβ(Prx1-CKO) mice. Thus, deletion of ERβ specifically in osteoblast lineage cells, in the absence of all splice variants, increases trabecular bone mass and modulates multiple pathways related to bone metabolism. These findings suggest that pharmacological inhibition of ERβ in bone may provide a novel approach to treat osteoporosis. © 2015 American Society for Bone and Mineral Research. PMID:26418452

  19. ISOLATION AND INDUCTION OF RABBIT BONE MARROW MESENCHYMAL STEM CELLS TO EXPRESS CHONDROCYTIC PHENOTYPE

    Institute of Scientific and Technical Information of China (English)

    尹战海; 刘淼; 王金堂; 曹峻岭; 张璟; 郑钧

    2002-01-01

    Objective To isolate rabbit bone marrow mesenchymal stem cells (MSCs), and observe the inducing effect of growth factors on MSCs to express chondrocytic phenotype. Methods MSCs were seperated from bone marrow of New Zealand rabbit. TGF-β1, IGF-I, Vitamin C and dexamethasone were added into culture medium to induce proliferation and differention of MSCs. Procollagen α1(Ⅱ) mRNA in cells was detected by RT-PCR to observe the chondrogenous effect of inducing factors. ALP in culture medium was detected by automatic biochemical analyser, and lipid droplet in cells was stained by Sudan Ⅲ to clarify whether these factors given had osteogenic and adipogenic potential. Results Expression of articular cartilage specific procollagen α1 (Ⅱ)mRNA was promoted by inducing factors-TGF-β1, IGF-I, Vitamine C and dexamethasone; elevated level of ALP in culture medium and lipid droplet in cells were also detected. Whereas ALP level was decreased and lipid stain were negative in groups without dexamethasone. Conclusion ① Expression of chondrocytic phenotype by MSCs could be induced by the synergistic action of TGF-β1, IGF-I and Vitamine C. ② Dexmathasone had osteogenic and adipogenic potential, it should not be chosen to induce chondrogenic differention of MSCs.

  20. Application of Mass Cytometry (CyTOF) for Functional and Phenotypic Analysis of Natural Killer Cells.

    Science.gov (United States)

    Kay, Alexander W; Strauss-Albee, Dara M; Blish, Catherine A

    2016-01-01

    Mass cytometry is a novel platform for high-dimensional phenotypic and functional analysis of single cells. This system uses elemental metal isotopes conjugated to monoclonal antibodies to evaluate up to 42 parameters simultaneously on individual cells with minimal overlap between channels. The platform can be customized for analysis of both phenotypic and functional markers. Here, we will describe methods to stain, collect, and analyze intracellular functional markers and surface phenotypic markers on natural killer cells. PMID:27177653

  1. Final Report: Bone Mass Inheritance: A Project to Identify the Genetic Regulation of Bone Mass; FINAL

    International Nuclear Information System (INIS)

    This project was designed to find human chromosomal locations that contain genes regulating peak bone density. It is part of a whole genome search for those loci,each responsible for at least 15% of the variation in the peak adult bone density. We accomplished this with a sib pair design, combined with simultaneous examination of extended kindreds. This project gave partial support of the recruitment which has now been completed. The project will extend into 2003. During the remainder of the project, a whole genome scan will be performed from the entire cohort of 2226 persons who have DNA archived, followed by linkage analysis. This project will meet the scientific objective leading eventually to expanded options for treating the condition that leads to bone thinning osteoporosis, and potential fractures in aging populations

  2. Foot Bone in Vivo: Its Center of Mass and Centroid of Shape

    CERN Document Server

    Fan, Yifang; Fan, Yubo; Lin, Zhiyu; Lv, Changsheng

    2010-01-01

    This paper studies foot bone geometrical shape and its mass distribution and establishes an assessment method of bone strength. Using spiral CT scanning, with an accuracy of sub-millimeter, we analyze the data of 384 pieces of foot bones in vivo and investigate the relationship between the bone's external shape and internal structure. This analysis is explored on the bases of the bone's center of mass and its centroid of shape. We observe the phenomenon of superposition of center of mass and centroid of shape fairly precisely, indicating a possible appearance of biomechanical organism. We investigate two aspects of the geometrical shape, (i) distance between compact bone's centroid of shape and that of the bone and (ii) the mean radius of the same density bone issue relative to the bone's centroid of shape. These quantities are used to interpret the influence of different physical exercises imposed on bone strength, thereby contributing to an alternate assessment technique to bone strength.

  3. The effect on bone mass and bone markers of different doses of ibandronate

    DEFF Research Database (Denmark)

    Ravn, Pernille; Clemmesen, B; Riis, B J; Christiansen, C

    1996-01-01

    The present article describes the results from a phase II dose finding study of the effect of ibandronate, a new, third generation bisphosphonate, in postmenopausal osteoporosis. One hundred and eighty postmenopausal, white women, at least 10 years past a natural menopause, with osteopenia defined...... as a bone mineral density (BMD) in the distal forearm at least 1.5 SD below the premenopausal mean, entered and 141 (78%) completed a 12 months randomized, double-blind, placebo-controlled study. The women received 0.25, 0.5, 1.0, 2.5, or 5.0 mg ibandronate daily or placebo. All women received a...... increases bone mass in all skeletal regions in a dose dependent manner with 2.5 mg being the most effective dose. Ibandronate treatment reduces bone turnover to premenopausal levels and is well tolerated....

  4. The Rho-GEF Kalirin regulates bone mass and the function of osteoblasts and osteoclasts

    OpenAIRE

    Huang, Su; Pierre P. Eleniste; Wayakanon, Kornchanok; Mandela, Prashant; Eipper, Betty A.; Mains, Richard E.; Allen, Matthew R; Bruzzaniti, Angela

    2013-01-01

    Bone homeostasis is maintained by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Dysregulation in the activity of the bone cells can lead to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. Kalirin is a novel GTP-exchange factor protein that has been shown to play a role in cytoskeletal remodeling and dendritic spine formation in neurons. We examined Kalirin expression in skeletal tissue and f...

  5. Volleyball and Basketball Enhanced Bone Mass in Prepubescent Boys.

    Science.gov (United States)

    Zouch, Mohamed; Chaari, Hamada; Zribi, Anis; Bouajina, Elyès; Vico, Laurence; Alexandre, Christian; Zaouali, Monia; Ben Nasr, Hela; Masmoudi, Liwa; Tabka, Zouhair

    2016-01-01

    The aim of this study was to examine the effect of volleyball and basketball practice on bone acquisition and to determine which of these 2 high-impact sports is more osteogenic in prepubertal period. We investigated 170 boys (aged 10-12 yr, Tanner stage I): 50 volleyball players (VB), 50 basketball players (BB), and 70 controls. Bone mineral content (BMC, g) and bone area (BA, cm(2)) were measured by dual-energy X-ray absorptiometry at different sites. We found that, both VB and BB have a higher BMC at whole body and most weight-bearing and nonweight-bearing sites than controls, except the BMC in head which was lower in VB and BB than controls. Moreover, only VB exhibited greater BMC in right and left ultra-distal radius than controls. No significant differences were observed between the 3 groups in lumbar spine, femoral neck, and left third D radius BMC. Athletes also exhibited a higher BA in whole body, limbs, lumbar spine, and femoral region than controls. In addition, they have a similar BA in head and left third D radius with controls. The VB exhibited a greater BA in most radius region than controls and a greater femoral neck BA than BB. A significant positive correlation was reported between total lean mass and both BMC and BA in whole body, lumbar spine, total hip, and right whole radius among VB and BB. In summary, we suggest that volleyball and basketball have an osteogenic effect BMC and BA in loaded sites in prepubescent boys. The increased bone mass induced by both volleyball and basketball training in the stressed sites was associated to a decreased skull BMC. Moreover, volleyball practice produces a more sensitive mechanical stress in loaded bones than basketball. This effect seems translated by femoral neck expansion. PMID:26235943

  6. Are levels of bone turnover related to lower bone mass of adolescents previously fed a macrobiotic diet?

    NARCIS (Netherlands)

    Parsons, T.J.; Dusseldorp, van M.; Seibel, M.J.; Staveren, van W.A.

    2001-01-01

    Dutch adolescents who consumed a macrobiotic (vegan-type) diet in early life, demonstrate a lower relative bone mass than their omnivorous counterparts. We investigated whether subjects from the macrobiotic group showed signs of catching up with controls in terms of relative bone mass, reflected by

  7. Peak bone mass density among residents of Metro Manila

    International Nuclear Information System (INIS)

    Study Objectives: To determine the peak bone mass density among residents of Metro Manila using dual energy X-ray absorptiometry and to correlate factors such as age, height, weight, body mass index, total caloric, protein and calcium intake to bone mass density. Design: Cross sectional study Setting: Philippine General Hospital and St Luke's Medical Center, tertiary government and private owned hospitals, respectively. Subjects: Two hundred twenty-eight 228) healthy randomly chosen subjects from amongst hospital companion, aged 15-52 years old, distributed at 25 subjects per group of five per sex. Methods: Bone mass density measurements were done on lumbar spine and femoral neck using dual energy x-ray absorptiometry (Lunar DPXL). Ten (10) cc of blood was extracted on one hundred fourteen (114) patients; 5 cc of which was used for biochemical studies while the rest of the sample was stored for fixture studies. One hundred fourteen (114) patients were then interviewed using the Filipino version of the WHO questionnaire for the Study of Osteoporosis, and their nutritional intake was assessed using a previous day food recall. Results: At present, there are a total of 228 patients recruited. The mean weight and height were 57-43±11.17 kg and 158.16±8.44 cm, respectively, and the mean BMI was 22.99±4.11. The mean daily calcium intake was 501.17±357.79 gms/day (n=64). The mean BMD at the L2-L4 spine for females was 1.14±0.15 gm/cm2 and 1.12±0.21 gm/cm2 for the males. The highest BMD was 1.23±0.20 gm/cm2 in the 35-39 year old age group for the females and 1.26±0.31 gm/cm2 in the 30-34 age group for the males. The mean femoral neck BMD was 0.91±0.12 gm/cm2 for the females and 1.00±0.13 gm/cm2 for the males. The highest femoral neck BMD was 0.931±0.12 gm/cm2 in the 20-24 females and 1.03±0.18 gm/cm2 in the 20-24 age group for the males. Calcium intake and weight was significantly correlated in the lumbar spine. Height and sex was correlated with both the

  8. Dating of some fossil Romanian bones by accelerator mass spectrometry

    International Nuclear Information System (INIS)

    Some fossil bones from Romanian territories have been dated by accelerator mass spectrometry (AMS) using the pelletron system from Lund University. The preparation of samples has been the classical procedure to produce pure graphite from bones specimens, The Paleolithic site from Malu Rosu, near Giurgiu was thoroughly analyzed. Two human fossil skulls from Cioclovina and Baia de Fier of special archaeological importance have been estimated to be of around 30 000 years old, a conclusion with great implications for the history of ancient Romania. By this physical analysis, a long scientific dispute was settled. The two fossil human skulls are the only ones of this age from Romania. One could advance the hypothesis that the skulls belong to a certain type of a branch of Central European Cro-Magon, the classical western type, considering both the chronological and the anthropological features. They constitute eastern limit of the Cro-Magnon man type. (authors)

  9. Spontaneous recovery of bone mass after cure of endogenous hypercortisolism.

    Science.gov (United States)

    Randazzo, Maria Elena; Grossrubatscher, Erika; Dalino Ciaramella, Paolo; Vanzulli, Angelo; Loli, Paola

    2012-06-01

    Patients with Cushing's syndrome (CS) develop osteopenia-osteoporosis. The present study evaluates the recovery of bone mass within 2 years after remission of hypercortisolism and in long term follow up, an issue rarely addressed. Twenty patients (6M, 14F, 3 post-menopausal, 15-64 years old), 15 with Cushing's disease, 2 with ectopic ACTH syndrome, 3 with ACTH-independent CS were studied. BMD, T and Z scores at lumbar spine and proximal femur were assessed by dual-energy X-ray absorptiometry before and 7-33 months after treatment of hypercortisolism. Five patients were treated with bisphosphonates. Four patients had hypogonadism and 4 GH-deficiency. At baseline all patients showed osteopenia/osteoporosis and the spine appeared more damaged than the femur; femur BMD was positively related with body mass index (BMI). No correlations were observed between spine and femur bone parameters and duration of disease or severity of hypercortisolism. Bone parameters did not differ in patients with or without GH or other pituitary deficiencies. After cure of hypercortisolism a significant improvement in spine BMD, Z and T scores and in femur Z and T scores was observed with normalization in 3 patients; there was no significant difference in percent improvement between femur and spine. The increase in bone parameters at spine and femur was independent from values at baseline. The percent increase in spine T and Z scores was positively related with time elapsed since cure. Bisphosphonates did not influence the recovery of bone mineralization. In long term follow up, after a median period of 7 years a further improvement in bone density was observed in 100% of patients at spine and in 9/11 at femur, although 8/11 patients still had femoral and/or vertebral T score in the range of osteopenia/osteoporosis. Spontaneous improvement of osteoporosis after cure of hypercortisolism occurs both at spine and femur, is independent from basal conditions and not affected by bisphosphonates

  10. Do calcium and vitamin D intake influence the effect of cycling on bone mass through adolescence?

    Directory of Open Access Journals (Sweden)

    A. Gómez-Bruton

    2013-08-01

    Full Text Available Introduction: Cycling has been associated with decreased bone mass during adolescence. Calcium (Ca and vitamin D (VitD intake are associated to bone mass and may be important confounders when studying bone mass. Aim: To clarify the effect that Ca and VitD may have on bone mass in adolescent cyclists. Methods: Bone mineral content (BMC and density (BMD of 39 male adolescents (20 cyclists were measured. Ca and VitD intake were also registered. Different ANCOVA analyses were performed in order to evaluate the influence of Ca and VitD on BMC and BMD. Results: Cyclists showed lower values of BMC and BMD than controls at several sites and when adjusting by Ca, Wards triangle BMD appeared also to be lower in cyclists than controls. Conclusion: Nutritional aspects might partially explain differences regarding bone mass in adolescent cyclists and should be taken into account in bone mass analysis as important confounders.

  11. Jagged1 expression by osteoblast-lineage cells regulates trabecular bone mass and periosteal expansion in mice.

    Science.gov (United States)

    Youngstrom, D W; Dishowitz, M I; Bales, C B; Carr, E; Mutyaba, P L; Kozloff, K M; Shitaye, H; Hankenson, K D; Loomes, K M

    2016-10-01

    Loss-of-function mutations in the Notch ligand, Jagged1 (Jag1), result in multi-system developmental pathologies associated with Alagille syndrome (ALGS). ALGS patients present with skeletal manifestations including hemi-vertebrae, reduced bone mass, increased fracture incidence and poor bone healing. However, it is not known whether the increased fracture risk is due to altered bone homeostasis (primary) or nutritional malabsorption due to chronic liver disease (secondary). To determine the significance of Jag1 loss in bone, we characterized the skeletal phenotype of two Jag1-floxed conditional knockout mouse models: Prx1-Cre;Jag1(f/f) to target osteoprogenitor cells and their progeny, and Col2.3-Cre;Jag1(f/f) to target mid-stage osteoblasts and their progeny. Knockout phenotypes were compared to wild-type (WT) controls using quantitative micro-computed tomography, gene expression profiling and mechanical testing. Expression of Jag1 and the Notch target genes Hes1 and Hey1 was downregulated in all Jag1 knockout mice. Osteoblast differentiation genes were downregulated in whole bone of both groups, but unchanged in Prx1-Cre;Jag1(f/f) cortical bone. Both knockout lines exhibited changes in femoral trabecular morphology including decreased bone volume fraction and increased trabecular spacing, with males presenting a more severe trabecular osteopenic phenotype. Prx1-Cre;Jag1(f/f) mice showed an increase in marrow mesenchymal progenitor cell number and, counterintuitively, developed increased cortical thickness resulting from periosteal expansion, translating to greater mechanical stiffness and strength. Similar alterations in femoral morphology were observed in mice with canonical Notch signaling disrupted using Prx1-Cre-regulatable dominant-negative mastermind like-protein (dnMAML). Taken together, we report that 1) Jag1 negatively regulates the marrow osteochondral progenitor pool, 2) Jag1 is required for normal trabecular bone formation and 3) Notch signaling

  12. 'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

    LENUS (Irish Health Repository)

    Gregson, C L

    2011-04-01

    High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon\\/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg\\/m(2

  13. A clinical study evaluating bone mineral mass in the radius during skeletal growth

    International Nuclear Information System (INIS)

    Using 125-I single photon absorptiometry, bone mineral measurements were performed on 206 healthy Japanese children (2 to 19 years of age). Bone mineral content (BMC), bone width (BW) and BMC/BW values were determined for the radius at distal 1/6 site (metaphysis) and distal 1/3 site (diaphysis). BMC/BW values at both sites correlated well with body height and weight. Bone mass in the diaphysis (distal 1/3 site) increased linearly during the 2-19 years of skeletal growth, but bone mass in the metaphysis (1/6 site) increased steeply during the pubertal period. In children receiving glucocorticoid therapy, bone mass was reduced in proportion to the duration of drug administration. In children under anticonvulsant therapy, the yearly increse in bone mass was significantly low especially in those patients with poor physical activity levels. Bone mineral decrease in the radius occurred in the children with hypopituitalism, hypothyroidism (cretinism), hyperthyroidism and Turner's syndrome. (author)

  14. Association of vitamin D receptor and estrogen receptor-α gene polymorphism with peak bone mass and bone size in Chinese women

    Institute of Scientific and Technical Information of China (English)

    Yue-juan QIN; Zhen-lin ZHANG; Qi-ren HUANG; Jin-wei HE; Yun-qiu HU; Qi ZHOU; Jing-hui LU; Miao LI; Yu-juan LIU

    2004-01-01

    AIM: To investigate if vitamin D receptor (VDR) gene Apa I polymorphism and estrogen receptor-α (ER-α) gene Pvu II, Xba I polymorphisms are related to bone mineral density (BMD), bone mineral content (BMC) and bone size in premenopausal Chinese women. METHODS: The VDR Apa I genotype and ER-α Pvu II, Xba I genotype were determined by PCR-restriction fragment length polymorphism (RFLP) in 493 unrelated healthy women aged 20-40 years of Hah nationality in Shanghai city. BMD (g/cm2), BMC (g), and bone areal size (BAS, cm2) at lumbar spine 1-4 (L1-4) and proximal femur (femoral neck, trochanter and Ward's triangle) were measured by duel-energy X-ray absorptionmetry. RESULTS: All allele frequencies did not deviate from Hardy-Weinberg equilibrium. After phenotypes were adjusted for age, height, and weight, a significant association was found between VDR Apa I genotype and BMC variation at L1-4 and Ward's triangle (P<0.05), but not in BMD or BAS at lumbar spine and proximal femur.ER-α Pvu II, Xba I genotype was not related to BMC, BMD, and BAS at all sites. CONCLUSION: The study suggested that Apa I polymorphism in VDR gene may influence on attainment and maintenance of peak bone mass in premenopausal Chinese women.

  15. Disseminated breast cancer cells acquire a highly malignant and aggressive metastatic phenotype during metastatic latency in the bone.

    Directory of Open Access Journals (Sweden)

    Carolyn G Marsden

    Full Text Available BACKGROUND: Disseminated tumor cells (DTCs in the bone marrow may exist in a dormant state for extended periods of time, maintaining the ability to proliferate upon activation, engraft at new sites, and form detectable metastases. However, understanding of the behavior and biology of dormant breast cancer cells in the bone marrow niche remains limited, as well as their potential involvement in tumor recurrence and metastasis. Therefore, the purpose of this study was to investigate the tumorigenicity and metastatic potential of dormant disseminated breast cancer cells (prior to activation in the bone marrow. METHODOLOGY/PRINCIPAL FINDINGS: Total bone marrow, isolated from mice previously injected with tumorspheres into the mammary fat pad, was injected into the mammary fat pad of NUDE mice. As a negative control, bone marrow isolated from non-injected mice was injected into the mammary fat pad of NUDE mice. The resultant tumors were analyzed by immunohistochemistry for expression of epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were analyzed by H+E staining to detect metastases. The injection of bone marrow isolated from mice previously injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post-injection. However, the injection of bone marrow isolated from non-injected mice did not result in tumor formation in the mammary fat pad. The DTC-derived tumors exhibited accelerated development of metastatic lesions within the lung, liver and kidney. The resultant tumors and the majority of metastatic lesions within the lung and liver exhibited a mesenchymal-like phenotype. CONCLUSIONS/SIGNIFICANCE: Dormant DTCs within the bone marrow are highly malignant upon injection into the mammary fat pad, with the accelerated development of metastatic lesions within the lung, liver and kidney. These results suggest the acquisition of a more aggressive phenotype of DTCs during

  16. Infant dietary patterns and bone mass in childhood: the Generation R Study

    OpenAIRE

    van den Hooven, E. H.; Heppe, D. H. M.; Kiefte-de Jong, J.C.; Medina-Gomez, C; Moll, H.A.; Hofman, A.; Jaddoe, V. W. V.; Rivadeneira, F.; Franco, O. H.

    2015-01-01

    Summary Early life nutrition affects peak bone mass attainment. In this prospective cohort study, children with high adherence to a “dairy and whole grains” pattern in infancy had higher bone mineral density at the age of 6 years. Although the observed effects are small, our study provides insight into mechanisms linking early nutrition to bone acquisition in childhood. Introduction Nutrition in early life may affect peak bone mass attainment. Previous studies on childhood nutrition and skele...

  17. DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Mahmood, Amer;

    2011-01-01

    Delta-like 1/fetal antigen 1 (DLK1/FA-1) is a transmembrane protein belonging to the Notch/Delta family that acts as a membrane-associated or a soluble protein to regulate regeneration of a number of adult tissues. Here we examined the role of DLK1/FA-1 in bone biology using osteoblast-specific Dlk...... the bone marrow by activated T cells. Interestingly, Dlk1(-/-) mice were significantly protected from ovx-induced bone loss compared with wild-type mice. Thus we identified Dlk1 as a novel regulator of bone mass that functions to inhibit bone formation and to stimulate bone resorption. Increasing DLK1...... production by T cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss....

  18. Estrogen receptor-α expression in neuronal cells affects bone mass

    OpenAIRE

    Ohlsson, Claes; Engdahl, Cecilia; Börjesson, Anna E; Sara H Windahl; Studer, Erik; Westberg, Lars; Eriksson, Elias; Koskela, Antti; Tuukkanen, Juha; Krust, Andree; Chambon, Pierre; Carlsten, Hans; Lagerquist, Marie K

    2012-01-01

    It has generally been assumed that bone mass is controlled by endocrine mechanisms and the local bone environment. Recent findings demonstrate that central pathways are involved in the regulation of bone mass. Estrogen is involved in the regulation of bone homeostasis and the CNS is also a target for estrogen actions. The aim of this study was to investigate in vivo the role of central estrogen receptor-α (ERα) expression for bone mass. Nestin-Cre mice were crossed with ERαflox mice to genera...

  19. Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Philip W. Connelly

    2012-01-01

    Full Text Available South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ2=7.72, P=0.02. PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P=0.0001, HDL cholesterol (P=0.009, LDL cholesterol (P=0.02, and diabetes status (P<0.05. Arylesterase activity was only associated with HDL cholesterol (P=0.003. Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients.

  20. AMP-activated protein kinase (AMPK) activation regulates in vitro bone formation and bone mass

    OpenAIRE

    Shah, M; Kola, B; Bataveljic, A.; Arnett, T. R.; Viollet, B.; Saxon, L.; Korbonits, M.; C. Chenu

    2010-01-01

    Adenosine 5′-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones. The objective of this study was to determine if AMPK can be activated in osteoblasts by known AMPK modulators and if AMPK activity is involved in osteoblast function in vitro and regulation of bone mass in vivo. ROS 17/2.8 rat osteoblast-like cells were cult...

  1. Phenotypic characterization of the bone marrow stem cells used in regenerative cellular therapy

    International Nuclear Information System (INIS)

    Regenerative medicine is a novel therapeutic method with broad potential for the treatment of various illnesses, based on the use of bone marrow (BM) stem cells, whose phenotypic characterization is limited. The paper deals with the expression of different cell membrane markers in mononuclear BM cells from 14 patients who underwent autologous cell therapy, obtained by medullary puncture and mobilization to peripheral blood, with the purpose of characterizing the different types of cells present in that heterogeneous cellular population and identifying the adhesion molecules involved in their adhesion. A greater presence was observed of adherent stem cells from the marrow stroma in mononuclear cells obtained directly from the BM; a larger population of CD90+cells in mononuclear cells from CD34-/CD45-peripheral blood with a high expression of molecules CD44 and CD62L, which suggests a greater presence of mesenchymal stem cells (MSC) in mobilized cells from the marrow stroma. The higher levels of CD34+cells in peripheral blood stem cells with a low expression of molecules CD117-and DR-suggests the presence of hematopoietic stem cells, hemangioblasts and progenitor endothelial cells mobilized to peripheral circulation. It was found that mononuclear cells from both the BM and peripheral blood show a high presence of stem cells with expression of adhesion molecule CD44 (MMC marker), probably involved in their migration, settling and differentiation

  2. Exercise improves body fat, lean mass and bone mass in breast cancer survivors

    OpenAIRE

    Irwin, Melinda L; Alvarez-Reeves, Marty; Cadmus, Lisa; Mierzejewski, Eileen; Mayne, Susan T; Yu, Herbert; Chung, Gina G.; Jones, Beth; Knobf, M. Tish; DiPietro, Loretta

    2009-01-01

    Given the negative effects of a breast cancer diagnosis and its treatments on body weight and bone mass, we investigated the effects of a 6-month randomized controlled aerobic exercise intervention vs. usual care on body composition in breast cancer survivors. Secondary aims were to examine the effects stratified by important prognostic and physiologic variables. Seventy-five physically inactive postmenopausal breast cancer survivors were recruited through the Yale-New Haven Hospital Tumor Re...

  3. Bone Mass Density in Normal Iranian Population - Shariati Hospital (1996

    Directory of Open Access Journals (Sweden)

    M Pajoohi

    2002-09-01

    Full Text Available Introduction: The bone mass density (BMD may vary in different countries due to different genetic and environmental factors. This study was performed to determine the BMD of the normal population in Iran. Methods and Materials: Subjects were selected randomly from different works and social classes in Tehran (from the lowest to the highest. For each decade and sexes, 20 normal subjects were selected (140 men and 140 women. BMD was measured with a Hologic 1000 plus machine by dual energy x-ray absorptiometry (DEXA method for the lumber spine (L1, L2, L3, L4, L1-L4 and the femoral neck (neck, trochanter, intertrochanter, ward, total. Data were treated by polynomial approximation (3 rd degree. The obtained curves were compared with the standard Hologic curves for Caucasians. Results: In female the peak bone mass (PBM was 1.019 g/cm² for the lumbar spine and 0.832 for the femoral neck. In male the peak bone mass (PBM was 0.987 g/cm² for the lumbar spine and 0.907 for the femoral neck. The BMD of both lumbar spine and femoral neck were lower than the Hologic standards. For the lumbar spine the mean difference was 6.5 percent (2 to 21 percent, CI=1 for women and 13.8 percent (2 to 36 percent, CI=1.45 for men. In femoral neck the mean difference was 5.4 percent (2 to 16 percent, CI=0.96 for women and 4.6 percent (1 to 14 percent, CI=0.96 for men. Conclusion: The BMD of the lumbar spine and the femoral neck was lower in Iranian compared to the Hologic standards for Caucasians. This was seen in all age groups and in both sexes. It was less pronounced for the PBM in spine was lower in men than woman. The lower BMD of the spine in men was also seen in a cohort of patients with different diseases (inflammatory and non-inflammatory.

  4. Vitamin D levels and bone mass in rheumatoid arthritis.

    Science.gov (United States)

    Brance, María L; Brun, Lucas R; Lioi, Susana; Sánchez, Ariel; Abdala, Marcelo; Oliveri, Beatriz

    2015-03-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease with high prevalence of osteoporosis. Previous evidence indicates an association between vitamin D deficiency and autoimmune diseases. The aim of this study was to evaluate serum 25 hydroxyvitamin D [25(OH)D] levels, bone mineral density (BMD) and disease activity in RA patients living in Argentina. We studied 34 RA women and 41 healthy women as a control group. RA patients had lower 25(OH)D levels (20.4 ± 0.9 ng/ml) than controls (26.3 ± 1.9 ng/ml; p 3.2: 19.5 ± 0.88 ng/ml; DAS-28 ≤3.2: 23.7 ± 2.8 ng/ml (p = 0.047). After 1 year of vitamin D treatment 25(OH)D levels were increased while DAS-28 were decreased (n = 25; p < 0.05). We conclude that patients with RA had lower 25(OH)D levels than the control group. Low levels of 25(OH)D were associated with moderate-high disease activity suggesting the importance of optimal 25(OH)D levels in RA patients. Femoral neck BMD was lower in postM RA patients. No differences in lumbar BMD were found between preM and postM RA patients, suggesting that bone mass evaluation in RA patients should include femoral neck BMD regardless of age. PMID:24980067

  5. Osteoblast-specific Notch2 inactivation causes increased trabecular bone mass at specific sites of the appendicular skeleton.

    Science.gov (United States)

    Yorgan, Timur; Vollersen, Nele; Riedel, Christoph; Jeschke, Anke; Peters, Stephanie; Busse, Bjoern; Amling, Michael; Schinke, Thorsten

    2016-06-01

    Notch signaling is a key pathway controlling various cell fate decisions during embryogenesis and adult life. It is activated by binding of specific ligands to four different Notch receptors that are subsequently cleaved by presenilins to release an intracellular domain that enters the nucleus and activates specific transcription factors. While the skeletal analysis of various mouse models with activated or inactivated Notch signaling has demonstrated a general impact of this pathway on bone remodeling, the more recent identification of NOTCH2 mutations in individuals with Hajdu-Cheney syndrome (HCS) has highlighted its human relevance. Since HCS is primarily characterized by skeletal defects, these latter findings led us to analyze the specific role of Notch2 in skeletal remodeling. After observing Notch2 expression in osteoblasts and osteoclasts, we utilized Runx2-Cre and Lyz2-Cre mice to inactivate Notch2 in cells of the osteoblast or osteoclast lineage, respectively. Whereas Notch2(fl/fl)/Lyz2-Cre mice did not display significant alterations of skeletal growth, bone mass or remodeling, Notch2(fl/fl)/Runx2-Cre mice progressively developed skeletal abnormalities in long bones. More specifically, these mice displayed a striking increase of trabecular bone mass in the proximal femur and the distal tibia at 6 and 12months of age. Whereas undecalcified sectioning of the respective regions did not reveal impaired osteocyte differentiation as a potential trigger for the observed phenotype, ex vivo experiments with bone marrow cells identified an increased osteogenic capacity of Notch2(fl/fl)/Runx2-Cre cultures. Collectively, our findings demonstrate that Notch2 physiologically regulates bone remodeling by inhibiting trabecular bone formation in the appendicular skeleton. Understanding the underlying mechanisms may help to improve diagnosis and therapy of HCS. PMID:27102824

  6. Effects of the environment on bone mass: A human taphonomic study.

    Science.gov (United States)

    Delannoy, Yann; Colard, Thomas; Le Garff, Erwan; Mesli, Vadim; Aubernon, Cindy; Penel, Guillaume; Hedouin, Valéry; Gosset, Didier

    2016-05-01

    An experiment was designed using human ribs placed in different environments to document how moisture and temperature affect the bone mass according to the postmortem interval. The bones were defleshed, weighed and partially buried, with some ribs being left unburied as controls. The ribs were weighed daily, and the mass loss was monitored over a period of 90days. The results showed that significant differences in bone mass loss exist between environments, where the bone mass loss was significantly faster in an environment with low moisture content. This mass loss is thought to be primarily associated with the desiccation of the body and then for a greater part, with the atmospheric moisture content. However, the loss of bone mass can also be explained by early alterations in the organo-mineral matrix which were highlighted by Raman spectroscopy method. PMID:27161926

  7. Genetic Analysis of High Bone Mass Cases from the BARCOS Cohort of Spanish Postmenopausal Women

    Science.gov (United States)

    Urreizti, Roser; Civit, Sergi; Cols, Neus; García-Giralt, Natàlia; Yoskovitz, Guy; Aranguren, Alvaro; Malouf, Jorge; Di Gregorio, Silvana; Río, Luís Del; Güerri, Roberto; Nogués, Xavier; Díez-Pérez, Adolfo; Grinberg, Daniel; Balcells, Susana

    2014-01-01

    The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM. PMID:24736728

  8. Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system.

    Directory of Open Access Journals (Sweden)

    Theodore P Braun

    Full Text Available Signaling via the type 4-melanocortin receptor (MC4R is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO. We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO wild type mice with equivalent fat mass. To examine potential sources of the increased lean mass in MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters increase with age in MC4RKO mice, which likely contributes to increases in lean body mass. We functionally characterized the increased lean mass in MC4RKO mice by examining their capacity for treadmill running. MC4R deficiency results in a decrease in exercise performance. No changes in the ratio of oxidative to glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly reduced heart rate, which may underlie their impaired exercise performance. The reduced exercise capacity we report in the MC4RKO mouse has potential clinical ramifications, as efforts to control body weight in humans with melanocortin deficiency may be ineffective due to poor tolerance for physical activity.

  9. Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature

    OpenAIRE

    D′Amico, L; Patanè, S; Grange, C.; Bussolati, B; Isella, C.; Fontani, L; Godio, L; Cilli, M; D′Amelio, P; Isaia, G; Medico, E; Ferracini, R; Roato, I

    2013-01-01

    Background: Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation. Methods: Primary CD44+CD24− breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/sever...

  10. 42 CFR 410.31 - Bone mass measurement: Conditions for coverage and frequency standards.

    Science.gov (United States)

    2010-10-01

    ... by the FDA under 21 CFR part 807, or approved for marketing by the FDA for this use under 21 CFR part... 42 Public Health 2 2010-10-01 2010-10-01 false Bone mass measurement: Conditions for coverage and... Medical and Other Health Services § 410.31 Bone mass measurement: Conditions for coverage and...

  11. High bone turnover is associated with low bone mass in both pre- and postmenopausal women

    DEFF Research Database (Denmark)

    Ravn, Pernille; Fledelius, C; Rosenquist, C; Overgaard, K; Christiansen, C

    1996-01-01

    In 979 healthy women, aged 30-75 years, bone mass was measured by DXA in the lumbar spine and proximal femur, and by SXA in the distal forearm. Bone turnover was assessed by urinary CrossLaps (CrossLaps ELISA), a new assay which measures type I collagen degradation products in urine and by...... osteocalcin (two-site N-Mid hOsteocalcin ELISA), a new assay which measures the N-terminal-mid fragment (1-43) as well as the intact (1-49) osteocalcin (OCN-Mid) in serum. For comparison data on urinary hydroxyproline (fU Hpr/Cr) and serum, total alkaline phosphatase were included (AP). In premenopausal women...... below 50 years of age, the concentrations of the biochemical markers were stable with age. At menopause CrossLaps and OCN-Mid increased abruptly to a level 60% and 35% above the premenopausal mean values (p < 0.001). Premenopausal women in the highest quartiles, stratified according to the concentration...

  12. GPCR kinase 2 interacting protein 1 (GIT1) regulates osteoclast function and bone mass

    OpenAIRE

    Menon, Prashanthi; Yin, Guoyong; Smolock, Elaine M.; Zuscik, Michael J.; Yan, Chen; Berk, Bradford C.

    2010-01-01

    G-protein coupled receptor (GPCR) kinase 2 interacting protein-1 (GIT1) is a scaffold protein expressed in various cell types including neurons, endothelial and vascular smooth muscle cells. The GIT1 knockout (KO) mouse has a pulmonary phenotype due to impaired endothelial function. Because GIT1 is tyrosine phosphorylated by Src kinase, we anticipated that GIT1 KO should have a bone phenotype similar to Src KO. Microcomputed tomography of the long bones revealed that GIT1 KO mice have a 2.3-f...

  13. Chronic central administration of Ghrelin increases bone mass through a mechanism independent of appetite regulation.

    Directory of Open Access Journals (Sweden)

    Hyung Jin Choi

    Full Text Available Leptin plays a critical role in the central regulation of bone mass. Ghrelin counteracts leptin. In this study, we investigated the effect of chronic intracerebroventricular administration of ghrelin on bone mass in Sprague-Dawley rats (1.5 μg/day for 21 days. Rats were divided into control, ghrelin ad libitum-fed (ghrelin ad lib-fed, and ghrelin pair-fed groups. Ghrelin intracerebroventricular infusion significantly increased body weight in ghrelin ad lib-fed rats but not in ghrelin pair-fed rats, as compared with control rats. Chronic intracerebroventricular ghrelin infusion significantly increased bone mass in the ghrelin pair-fed group compared with control as indicated by increased bone volume percentage, trabecular thickness, trabecular number and volumetric bone mineral density in tibia trabecular bone. There was no significant difference in trabecular bone mass between the control group and the ghrelin ad-lib fed group. Chronic intracerebroventricular ghrelin infusion significantly increased the mineral apposition rate in the ghrelin pair-fed group as compared with control. In conclusion, chronic central administration of ghrelin increases bone mass through a mechanism that is independent of body weight, suggesting that ghrelin may have a bone anabolic effect through the central nervous system.

  14. The Rho-GEF Kalirin regulates bone mass and the function of osteoblasts and osteoclasts.

    Science.gov (United States)

    Huang, Su; Eleniste, Pierre P; Wayakanon, Kornchanok; Mandela, Prashant; Eipper, Betty A; Mains, Richard E; Allen, Matthew R; Bruzzaniti, Angela

    2014-03-01

    Bone homeostasis is maintained by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Dysregulation in the activity of the bone cells can lead to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. Kalirin is a novel GTP-exchange factor protein that has been shown to play a role in cytoskeletal remodeling and dendritic spine formation in neurons. We examined Kalirin expression in skeletal tissue and found that it was expressed in osteoclasts and osteoblasts. Furthermore, micro-CT analyses of the distal femur of global Kalirin knockout (Kal-KO) mice revealed significantly reduced trabecular and cortical bone parameters in Kal-KO mice, compared to WT mice, with significantly reduced bone mass in 8, 14 and 36week-old female Kal-KO mice. Male mice also exhibited a decrease in bone parameters but not to the level seen in female mice. Histomorphometric analyses also revealed decreased bone formation rate in 14week-old female Kal-KO mice, as well as decreased osteoblast number/bone surface and increased osteoclast surface/bone surface. Consistent with our in vivo findings, the bone resorbing activity and differentiation of Kal-KO osteoclasts was increased in vitro. Although alkaline phosphatase activity by Kal-KO osteoblasts was increased in vitro, Kal-KO osteoblasts showed decreased mineralizing activity, as well as decreased secretion of OPG, which was inversely correlated with ERK activity. Taken together, our findings suggest that deletion of Kalirin directly affects osteoclast and osteoblast activity, leading to decreased OPG secretion by osteoblasts which is likely to alter the RANKL/OPG ratio and promote osteoclastogenesis. Therefore, Kalirin may play a role in paracrine and/or endocrine signaling events that control skeletal bone remodeling and the maintenance of bone mass. PMID:24380811

  15. Skeletal development of mice lacking bone sialoprotein (BSP--impairment of long bone growth and progressive establishment of high trabecular bone mass.

    Directory of Open Access Journals (Sweden)

    Wafa Bouleftour

    Full Text Available Adult Ibsp-knockout mice (BSP-/- display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice

  16. Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study.

    Science.gov (United States)

    Schafer, A L; Li, X; Schwartz, A V; Tufts, L S; Wheeler, A L; Grunfeld, C; Stewart, L; Rogers, S J; Carter, J T; Posselt, A M; Black, D M; Shoback, D M

    2015-05-01

    Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean ± SD decline 19.1 ± 6.1 kg or 36.5% ± 10.9%, pEffects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (-7.5%, 95% CI -15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=-0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots. PMID:25603463

  17. FSH and TSH in the Regulation of Bone Mass: The Pituitary/Immune/Bone Axis

    OpenAIRE

    Graziana Colaianni; Concetta Cuscito; Silvia Colucci

    2013-01-01

    Recent evidences have highlighted that the pituitary hormones have profound effects on bone, so that the pituitary-bone axis is now becoming an important issue in the skeletal biology. Here, we discuss the topical evidence about the dysfunction of the pituitary-bone axis that leads to osteoporotic bone loss. We will explore the context of FSH and TSH hormones arguing their direct or indirect role in bone loss. In addition, we will focus on the knowledge that both FSH and TSH have influence on...

  18. The generalized bone phenotype in children with neurofibromatosis 1: a sibling matched case-control study.

    Science.gov (United States)

    Armstrong, Linlea; Jett, Kimberly; Birch, Patricia; Kendler, David L; McKay, Heather; Tsang, Erica; Stevenson, David A; Hanley, David A; Egeli, Deetria; Burrows, Melonie; Friedman, J M

    2013-07-01

    People with neurofibromatosis 1 (NF1) have low bone mineralization, but the natural history and pathogenesis are poorly understood. We performed a sibling-matched case-control study of bone mineral status, morphology, and metabolism. Eighteen children with NF1 without focal bony lesions were compared to unaffected siblings and local population controls. Bone mineral content at the lumbar spine and proximal femur (dual energy X-ray absorptiometry (DXA)) was lower in children with NF1; this difference persisted after adjusting for height and weight. Peripheral quantitative computed tomography (pQCT) of the distal tibia showed that trabecular density was more severely compromised than cortical. Peripheral QCT-derived estimates of bone strength and resistance to bending and stress were poorer among children with NF1 although there was no difference in fracture frequencies. There were no differences in the size or shape of bones after adjusting for height. Differences in markers of bone turnover between cases and controls were in the directions predicted by animal studies, but did not reach statistical significance. Average serum calcium concentration was higher (although within the normal range) in children with NF1; serum 25-OH vitamin D, and PTH levels did not differ significantly between cases and controls. Children with NF1 were less mature (assessed by pubertal stage) than unaffected siblings or population controls. Children with NF1 have a generalized difference of bone metabolism that predominantly affects trabecular bone. Effects of decreased neurofibromin on bone turnover, calcium homeostasis, and pubertal development may contribute to the differences in bone mineral content observed among people with NF1. PMID:23713011

  19. Contribution of the BMI Level or the Body Fat Percentage Level to Bone-Mass

    OpenAIRE

    高畑,陽子; 穴井,孝信

    2011-01-01

    It is unclear which body mass index (BMI) or body fat percentage level has the strongest effect on the bone mass in young women.We examined the data gathered from 233 adolescent girls in a junior high,high school,and university to ascertain the relationship between BMI or body fat percentage and bone mass. The transmission index (TI) of the calcaneus was measured using an ultrasound bone densitometer. The subjects were classified into 3 groups by BMI and body fat percentage se...

  20. Revised Proposal for the Prevention of Low Bone Mass in Patients with Classic Galactosemia

    OpenAIRE

    van Erven, Britt; Römers, Myrna M. M.; Rubio-Gozalbo, M. Estela

    2014-01-01

    Decreased bone mass is frequently encountered in classic galactosemia, an inborn error of galactose metabolism. This decrease is most prominent in adults, but is already seen in prepubertal children with increased risk of osteoporosis and fractures later in life. Therefore, bone health in patients with classic galactosemia is increasingly monitored. Although the pathophysiological mechanism is still not fully understood, several factors could negatively affect bone metabolism in this disease....

  1. Bone mass in schoolchildren in Brazil: the effect of racial miscegenation, pubertal stage, and socioeconomic differences.

    Science.gov (United States)

    Ribeiro, Roberto Regis; Guerra-Junior, Gil; de Azevedo Barros-Filho, Antonio

    2009-01-01

    The purpose of this study was to evaluate bone mass by phalanges ultrasound in healthy white and black schoolchildren in relationship to socioeconomic level, pubertal stage, and body composition. Included were 1,356 healthy schoolchildren aged from 6 to 11 years from different socioeconomic levels and both genders; all were placed into white and black groups. Weight, height, body mass index, fat percentage, fat mass, and lean mass were evaluated by anthropometric methods, and AD-SoS bone quantity and UBPI bone quality were evaluated using a third-generation IGEA phalanges DBM Sonic BP ultrasound. Data were compared using the Mann-Whitney, chi-squared, correlation coefficient, and analyses of multiple linear regression statistical tests with 5% significance. Black schoolchildren predominated in the low socioeconomic levels. Higher values of weight and height for black boys and girls were observed in the lean mass in relation to white children of the same gender and age. An increasing variation in the bone quantity mean was observed from 6 to 11 years of age and with pubertal stage for both genders and skin color. The white schoolchildren presented higher values of bone quantity and quality in relation to the black children. The anthropometric, gender, and socioeconomic level variables explained only 16 and 11% of the variability of bone quantity and quality, respectively. As such, the present study, carried out with healthy black and white Brazilian schoolchildren, demonstrated higher bone mass, as evaluated by ultrasound, in white than in black schoolchildren. PMID:19283337

  2. Dietary Habits, Nutrients and Bone Mass in Spanish Premenopausal Women: The Contribution of Fish to Better Bone Health

    Directory of Open Access Journals (Sweden)

    Julian F. Calderon-Garcia

    2012-12-01

    Full Text Available The moderate consumption of fish is recommended for a healthy diet and is also a feature of the Mediterranean diet. Fish is a major food group in diets throughout the world, and studies show that fish consumption is associated with a lower risk of a number of conditions. Spain has one of the highest annual per capita consumptions of fish worldwide. As fish is a source of high quality protein; n-3 polyunsaturated fatty acids; vitamins, such as A and D; and minerals, such as selenium, calcium, iodine, magnesium, copper and zinc, nutrients that have positive effects on bone characteristics, it has been proposed that its consumption could improve bone health. In this cross-sectional study, we have investigated the relationship between dietary habits and nutrient intake of 151 Spanish premenopausal women and analyzed the association of fish consumption on bone mass measured by quantitative ultrasound of the phalanges. A higher (P < 0.05 bone mass and vitamin D intake (P < 0.05 was observed in the group with a fish intake of 5–7 servings/week. We conclude that increased fish consumption is helpful in maintaining an adequate bone mass in Spanish premenopausal women.

  3. A 21-Week Bone Deposition Promoting Exercise Programme Increases Bone Mass in Young People with Down Syndrome

    Science.gov (United States)

    Gonzalez-Aguero, Alejandro; Vicente-Rodriguez, German; Gomez-Cabello, Alba; Ara, Ignacio; Moreno, Luis A.; Casajus, Jose A.

    2012-01-01

    Aim: To determine whether the bone mass of young people with Down syndrome may increase, following a 21-week conditioning training programme including plyometric jumps. Method: Twenty-eight participants with Down syndrome (13 females, 15 males) aged 10 to 19 years were divided into exercise (DS-E; n = 14; eight females, six males mean age 13y 8mo,…

  4. Calcium- and Phosphorus-Supplemented Diet Increases Bone Mass after Short-Term Exercise and Increases Bone Mass and Structural Strength after Long-Term Exercise in Adult Mice

    OpenAIRE

    Friedman, Michael A.; Bailey, Alyssa M.; Rondon, Matthew J.; McNerny, Erin M.; Sahar, Nadder D.; Kohn, David H.

    2016-01-01

    Exercise has long-lasting benefits to bone health that may help prevent fractures by increasing bone mass, bone strength, and tissue quality. Long-term exercise of 6-12 weeks in rodents increases bone mass and bone strength. However, in growing mice, a short-term exercise program of 3 weeks can limit increases in bone mass and structural strength, compared to non-exercised controls. Short-term exercise can, however, increase tissue strength, suggesting that exercise may create competition for...

  5. Phenotypic analysis of bone marrow lymphocytes from children with acute thrombocytopenic purpura.

    Science.gov (United States)

    Guiziry, Dalai E L; El, Gendy Wessam; Farahat, Nahla; Hassab, Hoda

    2005-01-01

    Hematogones are benign immature B cells that commonly populate the bone marrow of children. Their presence has been noted to interfere with the flow-cytometric analysis of acute lymphoblastic leukemia (ALL), because their immunophenotype is similar to B-precursor cell lymphoblasts. Immune-mediated thrombocytopenia is a clinical condition characterized by increased platelet destruction due to sensitization of platelets by autoantibodies. The aim of this study was to determine the incidence and clinical impact of bone marrow hematogones in cases of acute immune thrombocytopenic purpura (ITP) among children. This was done by immunophenotyping of bone marrow lymphocytes of ITP cases and controls and follow up of cases. This study was done on 25 cases of ITP, 12 females and 13 males, their age ranged from 2 to 13 years. A control group was included in the study, 15 cases of apparently healthy children with matching age and sex taken from among bone marrow donors. Cases and controls were subjected to bone marrow lymphocyte immunophenotyping with flow-cytometry to verify the presence of hematogones. A statistically significant increase in the percentage of hematogones was demonstrated in their bone marrows. An increased percentage of CD10+ lymphocytes was demonstrated; with a mean of 18+/-15.2%, CD19+ with a mean of 27+/-16.3% and CD34+ with a mean of 3.7+/-3.2%. No correlation was found between the percentage of hematogones and peripheral platelet count or bone marrow lymphocytic count. In conclusion, there is an increase in the bone marrow hematogones in ITP cases in comparison to normal controls. This could be the sequence of an immunological response to the cause which determined the disease, or the regeneration of the stem cell compartment following transient damage. PMID:16734134

  6. Human Stromal (Mesenchymal) Stem Cells from Bone Marrow, Adipose Tissue and Skin Exhibit Differences in Molecular Phenotype and Differentiation Potential

    DEFF Research Database (Denmark)

    Al-Nbaheen, May; Vishnubalaji, Radhakrishnan; Ali, Dalia;

    2013-01-01

    Human stromal (mesenchymal) stem cells (hMSCs) are multipotent stem cells with ability to differentiate into mesoderm-type cells e.g. osteoblasts and adipocytes and thus they are being introduced into clinical trials for tissue regeneration. Traditionally, hMSCs have been isolated from bone marrow...... human skin (human adult skin stromal cells, (hASSCs) and human new-born skin stromal cells (hNSSCs)) grew readily in culture and the growth rate was highest in hNSSCs and lowest in hATSCs. Compared with phenotype of hBM-MSC, all cell populations were CD34(-), CD45(-), CD14(-), CD31(-), HLA-DR(-), CD13......, but the number of cells obtained is limited. Here, we compared the MSC-like cell populations, obtained from alternative sources for MSC: adipose tissue and skin, with the standard phenotype of human bone marrow MSC (BM-MSCs). MSC from human adipose tissue (human adipose stromal cells (hATSCs)) and...

  7. Effect of age and disease on bone mass in Japanese patients with schizophrenia

    OpenAIRE

    Sugawara Norio; Yasui-Furukori Norio; Umeda Takashi; Tsuchimine Shoko; Fujii Akira; Sato Yasushi; Saito Manabu; Furukori Hanako; Danjo Kazuma; Matsuzaka Masashi; Takahashi Ippei; Kaneko Sunao

    2012-01-01

    Abstract Background There have been a limited number of studies comparing bone mass between patients with schizophrenia and the general population. The aim of this study was to compare the bone mass of schizophrenia patients with that of healthy subjects in Japan. Methods We recruited patients (n = 362), aged 48.8 ± 15.4 (mean ± SD) years who were diagnosed with schizophrenia or schizoaffective disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV...

  8. Lack of influence of simple premenopausal hysterectomy on bone mass and bone metabolism

    DEFF Research Database (Denmark)

    Ravn, Pernille; Lind, C; Nilas, L

    1995-01-01

    distal forearm by single-energy x-ray absorptiometry. Body composition and bone mineral density in the anteroposterior spine, proximal femur, and total body was measured by dual-energy x-ray absorptiometry. Bone turnover was determined by plasma osteocalcin, serum alkaline phosphatase, and fasting...

  9. Effects of COLIA1 polymorphisms and haplotypes on perimenopausal bone mass, postmenopausal bone loss and fracture risk

    DEFF Research Database (Denmark)

    González-Bofill, N; Husted, L B; Harsløf, T; Tofteng, C L; Abrahamsen, B; Eiken, P; Vestergaard, Peter; Langdahl, B L

    2011-01-01

    total hip by 0.016 +/- 0.007 g/cm(2), 0.015 +/- 0.006 g/cm(2) and 0.017 +/- 0.006 g/cm(2), respectively (p < 0.05-0.005). No association with postmenopausal changes in bone mass and fracture risk and no overall interaction with the effects of hormone therapy could be demonstrated for any of the......One thousand seven hundred seventeen perimenopausal women from the Danish Osteoporosis Prevention Study were genotyped for the -1997G/T, -1663indelT and +1245G/T polymorphisms in the COLIA1 gen. We found that the -1997T allele and a haplotype containing it were associated with reduced bone mineral...... density (BMD) and increased bone turnover at menopause and after 10 years of follow-up. INTRODUCTION: We wanted to investigate whether the -1997G/T, -1663indelT and +1245G/T polymorphisms in the COLIA1 gene are associated with perimenopausal bone mass, early postmenopausal bone loss and interact with...

  10. Caloric restriction leads to high marrow adiposity and low bone mass in growing mice.

    Science.gov (United States)

    Devlin, Maureen J; Cloutier, Alison M; Thomas, Nishina A; Panus, David A; Lotinun, Sutada; Pinz, Ilka; Baron, Roland; Rosen, Clifford J; Bouxsein, Mary L

    2010-09-01

    The effects of caloric restriction (CR) on the skeleton are well studied in adult rodents and include lower cortical bone mass but higher trabecular bone volume. Much less is known about how CR affects bone mass in young, rapidly growing animals. This is an important problem because low caloric intake during skeletal acquisition in humans, as in anorexia nervosa, is associated with low bone mass, increased fracture risk, and osteoporosis in adulthood. To explore this question, we tested the effect of caloric restriction on bone mass and microarchitecture during rapid skeletal growth in young mice. At 3 weeks of age, we weaned male C57Bl/6J mice onto 30% caloric restriction (10% kcal/fat) or normal diet (10% kcal/fat). Outcomes at 6 (n = 4/group) and 12 weeks of age (n = 8/group) included body mass, femur length, serum leptin and insulin-like growth factor 1 (IGF-1) values, whole-body bone mineral density (WBBMD, g/cm(2)), cortical and trabecular bone architecture at the midshaft and distal femur, bone formation and cellularity, and marrow fat measurement. Compared with the normal diet, CR mice had 52% and 88% lower serum leptin and 33% and 39% lower serum IGF-1 at 6 and 12 weeks of age (p < .05 for all). CR mice were smaller, with lower bone mineral density, trabecular, and cortical bone properties. Bone-formation indices were lower, whereas bone-resorption indices were higher (p < .01 for all) in CR versus normal diet mice. Despite having lower percent of body fat, bone marrow adiposity was elevated dramatically in CR versus normal diet mice (p < .05). Thus we conclude that caloric restriction in young, growing mice is associated with impaired skeletal acquisition, low leptin and IGF-1 levels, and high marrow adiposity. These results support the hypothesis that caloric restriction during rapid skeletal growth is deleterious to cortical and trabecular bone mass and architecture, in contrast to potential skeletal benefits of CR in aging animals

  11. Menstrual irregularity and bone mass in premenopausal women: Cross-sectional associations with testosterone and SHBG

    Directory of Open Access Journals (Sweden)

    Otahal Petr

    2010-12-01

    Full Text Available Abstract Background There have been few studies examining the associations between menstrual irregularity, androgens and bone mass in population-based samples of premenopausal women. This study aimed to describe the associations between menstrual pattern, testosterone, sex hormone binding globulin (SHBG and bone mass in a population-based sample of premenopausal women. Methods Cross-sectional study (N = 382, mean age 31.5 years. Menstrual pattern was assessed by questionnaire, bone mass measured by quantitative ultrasound (QUS and androgen status was assessed by levels of serum testosterone, SHBG and the free androgen index (FAI. Results Women with irregular cycles (n = 41, 11% had higher free androgen index (FAI, P = 0.01 and higher QUS measurements including speed of sound (SOS, 1%, P Conclusion Irregular menstrual cycles were associated with higher bone mass in this population-based sample of premenopausal women suggesting menstrual disturbance should continue to be evaluated but may be less harmful for bone mass. The association between menstrual irregularity and bone mass was partially mediated by markers of androgen status especially free testosterone.

  12. Hydrocarbon phenotyping of algal species using pyrolysis-gas chromatography mass spectrometry

    Directory of Open Access Journals (Sweden)

    Kothari Shankar L

    2010-05-01

    Full Text Available Abstract Background Biofuels derived from algae biomass and algae lipids might reduce dependence on fossil fuels. Existing analytical techniques need to facilitate rapid characterization of algal species by phenotyping hydrocarbon-related constituents. Results In this study, we compared the hydrocarbon rich algae Botryococcus braunii against the photoautotrophic model algae Chlamydomonas reinhardtii using pyrolysis-gas chromatography quadrupole mass spectrometry (pyGC-MS. Sequences of up to 48 dried samples can be analyzed using pyGC-MS in an automated manner without any sample preparation. Chromatograms of 30-min run times are sufficient to profile pyrolysis products from C8 to C40 carbon chain length. The freely available software tools AMDIS and SpectConnect enables straightforward data processing. In Botryococcus samples, we identified fatty acids, vitamins, sterols and fatty acid esters and several long chain hydrocarbons. The algae species C. reinhardtii, B. braunii race A and B. braunii race B were readily discriminated using their hydrocarbon phenotypes. Substructure annotation and spectral clustering yielded network graphs of similar components for visual overviews of abundant and minor constituents. Conclusion Pyrolysis-GC-MS facilitates large scale screening of hydrocarbon phenotypes for comparisons of strain differences in algae or impact of altered growth and nutrient conditions.

  13. Establishment of age- and sex-adjusted reference data for hand bone mass and investigation of hand bone loss in patients with rheumatoid arthritis treated in clinical practice

    DEFF Research Database (Denmark)

    Ørnbjerg, Lykke Midtbøll; Østergaard, Mikkel; Jensen, Trine; Hyldstrup, Lars; Bach-Mortensen, Pernille; Bøyesen, Pernille; Thormann, Anja; Tarp, Ulrik; Bøhme, Wolfgang Peter; Lindegaard, Hanne; Poulsen, Uta Engling; Schlemmer, Annette; Graudal, Niels; Rødgaard, Anne; Espesen, Jakob; Kollerup, Gina Birgitte; Glintborg, Bente; Madsen, Ole Rintek; Jensen, Dorte Vendelbo; Hetland, Merete Lund

    2016-01-01

    BACKGROUND: Rheumatoid arthritis is characterised by progressive joint destruction and loss of periarticular bone mass. Hand bone loss (HBL) has therefore been proposed as an outcome measure for treatment efficacy. A definition of increased HBL adjusted for age- and sex-related bone loss is lacking....... In this study, we aimed to: 1) establish reference values for normal hand bone mass (bone mineral density measured by digital x-ray radiogrammetry (DXR-BMD)); and 2) examine whether HBL is normalised in rheumatoid arthritis patients during treatment with tumour necrosis factor alpha inhibitors (TNFI...

  14. Phenotyping of Live Human PBMC using CyTOF™ Mass Cytometry

    Science.gov (United States)

    Leipold, Michael D.; Maecker, Holden T.

    2016-01-01

    Single-cell analysis has become an method of importance in immunology. Fluorescence flow cytometry has been a major player. However, due to issues such as autofluorescence and emission spillover between different fluorophores, alternative techniques are being developed. In recent years, mass cytometry has emerged, wherein antibodies labeled with metal ions are detected by ICP-MS. In order for a cell to be seen, a metal in the mass window must be present; there is no analogous parameter to forward or side scatter. The current mass window selected is approximately AW 103-196, which includes the lanthanides used for most antibody labeling, as well as iridium and rhodium for DNA intercalators. In this protocol, we use a cocktail of antibodies labeled with MAXPAR metal-chelating polymers to surface-stain live PBMC that have been previously cryopreserved. Many of these markers were taken from a standard fluorescence phenotyping panel (Maecker et al., 2012). No intracellular antibodies are used. We use a CyTOF™ (Cytometry by Time-Of-Flight) mass cytometer to acquire the ICP-MS data. Subsequent analysis of the dual count signal data using FlowJo software allows for cell types to be analyzed based on the dual count signal in each mass channel. The percentage of each cell type is determined and reported as a percent of the parent cell type.

  15. Single cell mass cytometry reveals remodeling of human T cell phenotypes by varicella zoster virus.

    Science.gov (United States)

    Sen, Nandini; Mukherjee, Gourab; Arvin, Ann M

    2015-11-15

    The recent application of mass cytometry (CyTOF) to biology provides a 'systems' approach to monitor concurrent changes in multiple host cell factors at the single cell level. We used CyTOF to evaluate T cells infected with varicella zoster virus (VZV) infection, documenting virus-mediated phenotypic and functional changes caused by this T cell tropic human herpesvirus. Here we summarize our findings using two complementary panels of antibodies against surface and intracellular signaling proteins to elucidate the consequences of VZV-mediated perturbations on the surface and in signaling networks of infected T cells. CyTOF data was analyzed by several statistical, analytical and visualization tools including hierarchical clustering, orthogonal scaling, SPADE, viSNE, and SLIDE. Data from the mass cytometry studies demonstrated that VZV infection led to 'remodeling' of the surface architecture of T cells, promoting skin trafficking phenotypes and associated with concomitant activation of T-cell receptor and PI3-kinase pathways. This method offers a novel approach for understanding viral interactions with differentiated host cells important for pathogenesis. PMID:26213183

  16. Molecular, Phenotypic Aspects and Therapeutic Horizons of Rare Genetic Bone Disorders

    Directory of Open Access Journals (Sweden)

    Taha Faruqi

    2014-01-01

    Full Text Available A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.

  17. Bone turnover and metabolism in patients with early multiple sclerosis and prevalent bone mass deficit: a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Stine Marit Moen

    Full Text Available BACKGROUND: Low bone mass is prevalent in ambulatory multiple sclerosis (MS patients even shortly after clinical onset. The mechanism is not known, but could involve shared etiological risk factors between MS and low bone mass such as hypovitaminosis D operating before disease onset, or increased bone loss after disease onset. The aim of this study was to explore the mechanism of the low bone mass in early-stage MS patients. METHODOLOGY/PRINCIPAL FINDINGS: We performed a population-based case-control study comparing bone turnover (cross-linked N-terminal telopeptide of type 1 collagen; NTX, bone alkaline phosphatase; bALP, metabolism (25-hydroxy- and 1, 25-dihydroxyvitamin D, calcium, phosphate, and parathyroid hormone, and relevant lifestyle factors in 99 patients newly diagnosed with clinically isolated syndrome (CIS or MS, and in 159 age, sex, and ethnicity matched controls. After adjustment for possible confounders, there were no significant differences in NTX (mean 3.3; 95% CI -6.9, 13.5; p = 0.519, bALP (mean 1.6; 95% CI -0.2, 3.5; p = 0.081, or in any of the parameters related to bone metabolism in patients compared to controls. The markers of bone turnover and metabolism were not significantly correlated with bone mass density, or associated with the presence of osteoporosis or osteopenia within or between the patient and control groups. Intake of vitamin D and calcium, reported UV exposure, and physical activity did not differ significantly. CONCLUSIONS/SIGNIFICANCE: Bone turnover and metabolism did not differ significantly in CIS and MS patients with prevalent low bone mass compared to controls. These findings indicate that the bone deficit in patients newly diagnosed with MS and CIS is not caused by recent acceleration of bone loss, and are compatible with shared etiological factors between MS and low bone mass.

  18. Determination of peak bone mass density and composition in low income urban residents of metro Manila using isotope techniques

    International Nuclear Information System (INIS)

    The work described in this paper is a continuation of the first phase of the study, which is the determination of the peak bone mass density among residents of Metro Manila using dual energy x-ray absorptiometry. However, it also aims to correlate sex, body mass index, nutritional factors, physical activity and lifestyle to peak bone mass and thus attempts to explain any discrepancies in peak bone mass density to that seen in other countries

  19. Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group

    DEFF Research Database (Denmark)

    Ravn, Pernille; Cizza, G; Bjarnason, N H;

    1999-01-01

    Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n...... = 1609). The 2-year data from the placebo group were used (n = 417). Percentage of body fat, BMI, and body weight were correlated with baseline BMD (r = -0. 13 to -0.43, p < 0.01) and 2-year bone loss (r = -0.14 to -0.19, p < 0.01). Women in the lowest tertiles of percentage of body fat or BMI had up to...... 12% lower BMD at baseline and a more than 2-fold higher 2-year bone loss as compared with women in the highest tertiles (p

  20. Alveolar bone mass in pre- and postmenopausal women with serum calcium as a marker: A comparative study

    Directory of Open Access Journals (Sweden)

    Amitha Ramesh

    2011-01-01

    Conclusion: Postmenopausal women exhibit a reduced alveolar bone mass and lowered levels of serum total calcium with the increasing age. These changes may be useful indicators for low skeletal bone mineral density or osteoporosis.

  1. Risk factors for low bone mass in healthy young adults from North India: studies on BMD and bone turnover markers

    Directory of Open Access Journals (Sweden)

    Anita Fotedar Verma

    2015-04-01

    Full Text Available Background: Despite availability of adequate sunshine, Indian population has the highest prevalence of low bone mass and Bone Mineral Content (BMC. Risk factors for osteoporosis have been extensively studied in the west but poorly investigated in India. We studied BMD and Bone Turnover Markers (BTMs among healthy young adults. Methods: Fifty one healthy young adults (28 Males, 23 Females in the age group of 20-35 years were studied. Morphometric, biochemical parameters and BMD (whole body, spine, hip and wrist were recorded. Anthropometric measurements included height, weight, BMI and Waist/Hip Ratio (WHR. BTMs studied included - serum Bone-Specific Alkaline Phosphatase (sBAP, serum Collagen cross-linked C-Terminal telopeptide (sCTx, serum Osteocalcin (OC and human intact parathyroid hormone (hPTH using standard ELISA kits. Results: Of 51 healthy volunteers 21.57% had normal BMD, 13.73% were frankly osteoporotic and 64.70% were osteopenic. Age, weight and BMI were the best predictors of total BMD and BMC at all sites. sCTX positively correlated with Total Bone Area (TBA, BMD at Hip and Forearm. Using multiple regressions - age, weight, and BMI were significant predictors of BMD in young adults. Percentage body fat had inverse correlation with BMC, BMD and TBA. Weight and height positively correlated with BMD at femoral neck, inter-trochanter and Ward's triangle. Body weight was best predictor of BMD at femoral neck, Ward's triangle, forearm UD, forearm MID and forearm1/3. Conclusion: Majority of healthy young Indians have poor bone health as evidenced by bone markers. [Int J Res Med Sci 2015; 3(4.000: 933-939

  2. Immortalized mouse dental papilla mesenchymal cells preserve odontoblastic phenotype and respond to bone morphogenetic protein 2

    OpenAIRE

    Wang, Feng; Wu, Li-An; Li, Wentong; Yang, Yuan; Guo, Feng; GAO, QINGPING; Chuang, Hui-Hsiu; SHOFF, LISA; Wang, Wei; Chen, Shuo

    2013-01-01

    Odontogenesis is the result of the reciprocal interactions between epithelial–mesenchymal cells leading to terminally differentiated odontoblasts. This process from dental papilla mesenchymal cells to odontoblasts is regulated by a complex signaling pathway. When isolated from the developing tooth germs, odontoblasts quickly lose their potential to maintain the odontoblast-specific phenotype. Therefore, generation of an odontoblast-like cell line would be a good surrogate model for studying t...

  3. Mouse Embryonic Fibroblasts (MEF) Exhibit a Similar but not Identical Phenotype to Bone Marrow Stromal Stem Cells (BMSC)

    DEFF Research Database (Denmark)

    Saeed, Hamid; Taipaleenmäki, Hanna; Aldahmash, Abdullah M; Abdallah, Basem M; Kassem, Moustapha

    2012-01-01

    from E13.5 embryos after removing heads and viscera, followed by plastic adherence. Compared to BMSC, MEF exhibited telomerase activity and improved cell proliferation as assessed by q-PCR based TRAP assay and cell number quantification, respectively. FACS analysis revealed that MEF exhibited surface....../tricalcium phosphate, in immune deficient mice. In conclusion, MEF contain a population of stem cells that behave in ex vivo and in vivo assays, similar but not identical, to BMSC. Due to their enhanced cell growth, they may represent a good alternative for BMSC in studying molecular mechanisms of stem cell commitment......Mouse embryonic fibroblasts have been utilized as a surrogate stem cell model for the postnatal bone marrow-derived stromal stem cells (BMSC) to study mesoderm-type cell differentiation e.g. osteoblasts, adipocytes and chondrocytes. However, no formal characterization of MEF phenotype has been...

  4. Neurospheres induced from bone marrow stromal cells are multipotent for differentiation into neuron, astrocyte, and oligodendrocyte phenotypes

    International Nuclear Information System (INIS)

    Bone marrow stromal cells (MSCs) can be expanded rapidly in vitro and have the potential to be differentiated into neuronal, glial and endodermal cell types. However, induction for differentiation does not always have stable result. We present a new method for efficient induction and acquisition of neural progenitors, neuronal- and glial-like cells from MSCs. We demonstrate that rat MSCs can be induced to neurospheres and most cells are positive for nestin, which is an early marker of neuronal progenitors. In addition, we had success in proliferation of these neurospheres with undifferentiated characteristics and finally we could obtain large numbers of neuronal and glial phenotypes. Many of the cells expressed β-tubulin III when they were cultivated with our method. MSCs can become a valuable cell source as an autograft for clinical application involving regeneration of the central nervous system

  5. Distinct Lysosome Phenotypes Influence Inflammatory Function in Peritoneal and Bone Marrow-Derived Macrophages

    OpenAIRE

    Kassandra Weber; Schilling, Joel D.

    2014-01-01

    Lysosomes play a critical role in the degradation of both extracellular and intracellular material. These dynamic organelles also contribute to nutrient sensing and cell signaling pathways. Macrophages represent a heterogeneous group of phagocytic cells that contribute to tissue homeostasis and inflammation. Recently, there has been a renewed interest in understanding the role of macrophage autophagy and lysosome function in health and disease. Thioglycollate-elicited peritoneal and bone marr...

  6. Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength.

    Science.gov (United States)

    Kamiya, Nobuhiro; Shuxian, Lin; Yamaguchi, Ryosuke; Phipps, Matthew; Aruwajoye, Olumide; Adapala, Naga Suresh; Yuan, Hui; Kim, Harry K W; Feng, Jian Q

    2016-10-01

    Recent studies suggest a critical role of osteocytes in controlling skeletal development and bone remodeling although the molecular mechanism is largely unknown. This study investigated BMP signaling in osteocytes by disrupting Bmpr1a under the Dmp1-promoter. The conditional knockout (cKO) mice displayed a striking osteosclerotic phenotype with increased trabecular bone volume, thickness, number, and mineral density as assessed by X-ray and micro-CT. The bone histomorphometry, H&E, and TRAP staining revealed a dramatic increase in trabecular and cortical bone masses but a sharp reduction in osteoclast number. Moreover, there was an increase in BrdU positive osteocytes (2-5-fold) and osteoid volume (~4-fold) but a decrease in the bone formation rate (~85%) in the cKO bones, indicating a defective mineralization. The SEM analysis revealed poorly formed osteocytes: a sharp increase in cell numbers, a great reduction in cell dendrites, and a remarkable change in the cell distribution pattern. Molecular studies demonstrated a significant decrease in the Sost mRNA levels in bone (>95%), and the SOST protein levels in serum (~85%) and bone matrices. There was a significant increase in the β-catenin (>3-fold) mRNA levels as well as its target genes Tcf1 (>6-fold) and Tcf3 (~2-fold) in the cKO bones. We also showed a significant decrease in the RANKL levels of serum proteins (~65%) and bone mRNA (~57%), and a significant increase in the Opg mRNA levels (>20-fold) together with a significant reduction in the Rankl/Opg ratio (>95%), which are responsible for a sharp reduction in the cKO osteoclasts. The values of mechanical strength were higher in cKO femora (i.e. max force, displacement, and work failure). These results suggest that loss of BMP signaling specifically in osteocytes dramatically increases bone mass presumably through simultaneous inhibition of RANKL and SOST, leading to osteoclast inhibition and Wnt activation together. Finally, a working hypothesis is

  7. Bone Mass and Microarchitecture in CKD Patients with Fracture

    OpenAIRE

    Nickolas, Thomas L.; Stein, Emily; Cohen, Adi; Thomas, Valerie; Staron, Ronald B.; McMahon, Donald J.; Leonard, Mary B.; Shane, Elizabeth

    2010-01-01

    Patients with predialysis chronic kidney disease (CKD) have increased risk for fracture, but the structural mechanisms underlying this increased skeletal fragility are unknown. We measured areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry at the spine, hip, and radius, and we measured volumetric BMD (vBMD), geometry, and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the radius and tibia in patients with CKD: 32 with fracture ...

  8. Adiponectin and peak bone mass in men: a cross-sectional, population-based study

    DEFF Research Database (Denmark)

    Frost, M; Abrahamsen, B; Nielsen, T L;

    2010-01-01

    Adiponectin, a protein classically known to be secreted by adipocytes, is also secreted by bone-forming cells. Results of previous studies have been contradictory as to whether serum adiponectin and bone mineral density (BMD) are associated. The aim of this study was to investigate a possible...... association between serum adiponectin and BMD in young, healthy men at a time of peak bone mass. BMD in the femoral neck, total hip, and lumbar spine were measured in this population-based cross-sectional study of 700 men aged 20-29 years participating in the Odense Androgen Study. Magnetic resonance imaging...... of femoral cortical thickness and bone marrow size was performed in a subsample of 363 participants. The associations between serum adiponectin and various bone measures were investigated by means of regression analyses with adjustment for potential confounding variables. An inverse association was...

  9. Novel Genetic Loci Control Calcium Absorption and Femur Bone Mass as Well as Their Response to Low Calcium Intake in Male BXD Recombinant Inbred Mice.

    Science.gov (United States)

    Reyes Fernandez, Perla C; Replogle, Rebecca A; Wang, Libo; Zhang, Min; Fleet, James C

    2016-05-01

    Low dietary calcium (Ca) intake during growth limits peak bone mass but physiological adaptation can prevent this adverse effect. To assess the genetic control on the physiologic response to dietary Ca restriction (RCR), we conducted a study in 51 BXD lines fed either 0.5% (basal) or 0.25% (low) Ca diets from ages 4 to 12 weeks (n = 8/line/diet). Ca absorption (CaAbs), femur bone mineral density (BMD), and bone mineral content (BMC) were examined. ANCOVA with body size as covariate was used to detect significant line and diet main effects, and line-by-diet interactions. Body size-corrected residuals were used for linkage mapping and to estimate heritability (h(2) ). Loci controlling the phenotypes were identified using composite interval mapping on each diet and for the RCR. h(2) of basal phenotypes (0.37-0.43) and their RCR (0.32-0.38) was moderate. For each phenotype, we identified multiple quantitative trait loci (QTL) on each diet and for the RCR. Several loci affected multiple traits: Chr 1 (88.3-90.6 cM, CaAbs, BMC), Chr 4 (45.8-49.2 cM, CaAbs, BMD, BMC), Chr 8 (28.6-31.6 cM, CaAbs, BMD, RCR), and Chr 15 (13.6-24 cM, BMD, BMC; 32.3-36 cM, CaAbs RCR, BMD). This suggests that gene clusters may regulate interdependent bone-related phenotypes. Using in silico expression QTL (eQTL) mapping and bioinformatic tools, we identified novel candidates for the regulation of bone under Ca stress (Ext1, Deptor), and for the first time, we report genes modulating Ca absorption (Inadl, Sc4mol, Sh3rf1, and Dennd3), and both Ca and bone metabolism (Tceanc2, Tll1, and Aadat). Our data reveal gene-by-diet interactions and the existence of novel relationships between bone and Ca metabolism during growth. © 2015 American Society for Bone and Mineral Research. PMID:26636428

  10. Bone mineral content has stronger association with lean mass than fat mass among Indian urban adolescents

    Directory of Open Access Journals (Sweden)

    Raman K Marwaha

    2015-01-01

    Full Text Available Introduction: There are conflicting reports on the relationship of lean mass (LM and fat mass (FM with bone mineral content (BMC. Given the high prevalence of Vitamin D deficiency in India, we planned the study to evaluate the relationship between LM and FM with BMC in Indian children and adolescents. The objective of the study was to evaluate the relationship of BMC with LM and FM. Materials and Methods: Total and regional BMC, LM, and FM using dual energy X-ray absorptiometry and pubertal staging were assessed in 1403 children and adolescents (boys [B]: 826; girls [G]: 577. BMC index, BMC/LM and BMC/FM ratio, were calculated. Results: The age ranged from 5 to 18 years, with a mean age of 13.2 ± 2.7 years. BMC adjusted for height (BMC index and BMC/height ratio was comparable in both genders. There was no difference in total BMC between genders in the prepubertal group but were higher in more advanced stages of pubertal maturation. The correlation of total as well as regional BMC was stronger for LM (B: Total BMC - 0.880, trunk - 0.715, leg - 0.894, arm - 0.891; G: Total BMC - 0.827, leg - 0.846, arm - 0.815 (all value indicate r2 , P < 0.0001 for all when compared with FM (B: Total BMC - 0.776, trunk - 0.676, leg - 0.772, arm - 0.728; G: Total BMC - 0.781, leg - 0.741, arm - 0.689; all P < 0.0001 except at trunk BMC (LM - 0.682 vs. FM - 0.721; all P < 0.0001, even after controlling for age, height, pubertal stage, and biochemical parameters. Conclusions: BMC had a stronger positive correlation with LM than FM.

  11. Effects of hyperthyroidism on bone mass in women of reproductive age

    OpenAIRE

    Ilić Jana; Kovačev Branka; Todorović-Đilas Ljiljana R.

    2004-01-01

    Introduction Hyperthyroidism is one of the most frequent endocrinopathies in women of reproductive age. Consequently, increased risk of osteoporosis may be expected. Material and methods The research has included a group of 30 hyperthyroid women and a control group of 30 healthy women of reproductive age. Age and some clinical characteristics were analyzed, as well as some anthropometric parameters. Bone mass parameters were determined by measuring bone mineral density using ultrasound device...

  12. A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair.

    Science.gov (United States)

    Florio, Monica; Gunasekaran, Kannan; Stolina, Marina; Li, Xiaodong; Liu, Ling; Tipton, Barbara; Salimi-Moosavi, Hossein; Asuncion, Franklin J; Li, Chaoyang; Sun, Banghua; Tan, Hong Lin; Zhang, Li; Han, Chun-Ya; Case, Ryan; Duguay, Amy N; Grisanti, Mario; Stevens, Jennitte; Pretorius, James K; Pacheco, Efrain; Jones, Heidi; Chen, Qing; Soriano, Brian D; Wen, Jie; Heron, Brenda; Jacobsen, Frederick W; Brisan, Emil; Richards, William G; Ke, Hua Zhu; Ominsky, Michael S

    2016-01-01

    Inhibition of the Wnt antagonist sclerostin increases bone mass in patients with osteoporosis and in preclinical animal models. Here we show increased levels of the Wnt antagonist Dickkopf-1 (DKK-1) in animals treated with sclerostin antibody, suggesting a negative feedback mechanism that limits Wnt-driven bone formation. To test our hypothesis that co-inhibition of both factors further increases bone mass, we engineer a first-in-class bispecific antibody with single residue pair mutations in the Fab region to promote efficient and stable cognate light-heavy chain pairing. We demonstrate that dual inhibition of sclerostin and DKK-1 leads to synergistic bone formation in rodents and non-human primates. Furthermore, by targeting distinct facets of fracture healing, the bispecific antibody shows superior bone repair activity compared with monotherapies. This work supports the potential of this agent both for treatment and prevention of fractures and offers a promising therapeutic approach to reduce the burden of low bone mass disorders. PMID:27230681

  13. Decreased osteoclastogenesis, osteoblastogenesis and low bone mass in a mouse model of type 2 diabetes.

    Science.gov (United States)

    Xu, Fei; Dong, Yonghui; Huang, Xin; Li, Mi; Qin, Liang; Ren, Ye; Guo, Fengjing; Chen, Anmin; Huang, Shilong

    2014-10-01

    The effect of type 2 diabetes mellitus (T2DM) on bone is controversial. Therefore, the present study investigated whether T2DM causes osteoporosis and explored the underlying mechanisms involved in this process. The effects of T2DM on bone physiology were analyzed in a mouse model of T2DM; KK/Upj‑Ay/J (KK‑Ay) mice develop diabetes after 8 weeks and exhibit stable diabetes symptoms and signs after 10 weeks when fed a KK‑Ay mouse maintenance fodder. Diabetic mice exhibited hyperglycemia, hyperinsulinemia and increased body and fat pad weight in comparison with C57BL/6 non-diabetic mice. Furthermore, diabetic mice demonstrated low bone weight and bone mineral density in the femur, tibia and fifth lumbar vertebra. Using von Kossa and tartrate-resistant acid phosphatase (TRAP) staining, alkaline phosphatase and TRAP activity analyses and gene profiling it was demonstrated that osteoblastogenesis and osteoclastogenesis were impaired in diabetic mice. To evaluate the bone biomechanics, the ultimate load of the bone was analyzed. It was found that the ultimate load of the tibia in diabetic mice was lower than that in the controls. The results from the present study suggest that bone metabolism is impaired in T2DM, resulting in decreased osteoblastogenesis, osteoclastogenesis and bone mass. PMID:25109926

  14. Rare EN1 Variants and Pediatric Bone Mass.

    Science.gov (United States)

    Mitchell, Jonathan A; Chesi, Alessandra; McCormack, Shana E; Roy, Sani M; Cousminer, Diana L; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Kelly, Andrea; Zemel, Babette S; Grant, Struan Fa

    2016-08-01

    A recent whole-genome sequencing study in search of variation associated with adult areal bone mineral density (aBMD) identified rare variants near EN1, with markedly large effect sizes, and a common variant near SOX6. To understand the developmental effects of these loci, we sought to determine if they were associated with pediatric dual-energy X-ray absorptiometry-derived aBMD and bone mineral content (BMC) and if the associations were modified by sex. Our sample comprised 733 females and 685 males of European ancestry enrolled in the longitudinal Bone Mineral Density in Childhood Study (up to 7 annual study visits). Sex- and age-specific Z-scores, adjusted for height, were calculated for the total hip, femoral neck, spine, and distal radius. Total body less head (TBLH) BMC Z-scores were also calculated. The previously reported single nucleotide polymorphisms (SNPs) near EN1 and SOX6 were derived from our imputed data set. Linear mixed-effects models were used to test associations between each SNP and bone Z-scores, plus interactions with sex were explored. The rare T allele of lead EN1 SNP rs11692564 was associated with higher aBMD Z-score for total hip (beta = 0.62, p = 9.0 × 10(-4) ) and femoral neck (beta = 0.53, p = 0.010). In sex-stratified analyses, this variant was associated with higher bone Z-scores in females only, with the associations being strongest for total hip (sex interaction p = 1.9 × 10(-4) ; beta females = 0.86, p = 6.6 × 10(-6) ) and femoral neck (sex interaction p = 0.016; beta females = 0.73, p = 0.001). The common G allele of SOX6 SNP rs11024028 was associated with higher aBMD Z-score for total hip (beta = 0.12, p = 0.009), femoral neck (beta = 0.13, p = 0.003), and TBLH-BMC (beta = 0.09, p = 0.007); furthermore, this association strengthened in males in the sex-stratified analyses. Our findings reveal that rare genetic variation near EN1 and common variation

  15. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Grubbe, M.-C.; Thomsen, J. S.; Nyengaard, J. R.;

    2014-01-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind......BMD, -13%, P<0.001), trabecular bone volume (BV/TV, -26%, P<0.05), and mid-femoral bone strength (-12%, P<0.05). In addition, BTX reduced rectus femoris muscle mass (-69%, P<0.001) and muscle cell cross sectional area (CSA) (-73%, P<0.001) compared with controls. GH counteracted disuse-induced losses of...... periosteal BFR/BS (2-fold increase vs. BTX, P<0.001), whereas no effect on aBMD, trabecular BV/TV, or bone strength was found. In addition, GH partly prevented loss of muscle mass (+29% vs. BTX, P<0.001), and tended to prevent loss of muscle CSA (+11%, P=0.064). In conclusion, GH mitigates disuse...

  16. Effect of age and disease on bone mass in Japanese patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Sugawara Norio

    2012-02-01

    Full Text Available Abstract Background There have been a limited number of studies comparing bone mass between patients with schizophrenia and the general population. The aim of this study was to compare the bone mass of schizophrenia patients with that of healthy subjects in Japan. Methods We recruited patients (n = 362, aged 48.8 ± 15.4 (mean ± SD years who were diagnosed with schizophrenia or schizoaffective disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV. Bone mass was measured using quantitative ultrasound densitometry of the calcaneus. The osteosono-assessment index (OSI was calculated as a function of the speed of sound and the transmission index. For comparative analysis, OSI data from 832 adults who participated in the Iwaki Health Promotion Project 2009 was used as representative of the general community. Results Mean OSI values among male schizophrenic patients were lower than those in the general population in the case of individuals aged 40 and older. In females, mean OSI values among schizophrenic patients were lower than those in the general community in those aged 60 and older. In an analysis using the general linear model, a significant interaction was observed between subject groups and age in males. Conclusions Older schizophrenic patients exhibit lower bone mass than that observed in the general population. Our data also demonstrate gender and group differences among schizophrenic patients and controls with regard to changes in bone mass associated with aging. These results indicate that intervention programs designed to delay or prevent decreased bone mass in schizophrenic patients might be tailored according to gender.

  17. Changes in Vertebral Bone Marrow Fat and Bone Mass After Gastric Bypass Surgery: A Pilot Study

    OpenAIRE

    Schafer, AL; Li, X; Schwartz, AV; Tufts, LS; Wheeler, AL; Grunfeld, C; Stewart, L; Rogers, SJ; Carter, JT; Posselt, AM; Black, DM; Shoback, DM

    2015-01-01

    Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morb...

  18. Calcium supplementation, bone mineral density and bone mineral content. Predictors of bone mass changes in adolescent mothers during the 6-month postpartum period.

    Science.gov (United States)

    Malpeli, Agustina; Apezteguia, María; Mansur, José L; Armanini, Alicia; Macías Couret, Melisa; Villalobos, Rosa; Kuzminczuk, Marta; Gonzalez, Horacio F

    2012-03-01

    We determined the effect of calcium supplementation on bone mineral density (BMD) and bone mineral content (BMC) and identified predictors of bone mass changes in adolescent mothers 6 months postpartum. A prospective, analytical, clinical study was performed in adolescent mothers (< or = 19 years old; n = 37) from La Plata, Argentina. At 15 days postpartum, mothers were randomly assigned into one of two groups and started with calcium supplementation; one group received dairy products (932 mg Ca; n = 19) and the other calcium citrate tablets (1000 mg calcium/day; n = 18). Weight, height and dietary intake were measured and BMD was determined by DEXA at 15 days (baseline) and 6 months postpartum. BMC, total body BMD and BMD were assessed in lumbar spine, femoral neck, trochanter and total hip. Regression models were used to identify the relationship of total body BMD and BMC with independent variables (calcium supplementation, months of lactation, weight at 6 months, percent weight change, lean mass at 6 months, percent lean mass change, total calcium intake). Results showed that changes in BMD and BMC at the different sites were similar in both groups, and changes in percent body weight and total calcium intake were the main predictive factors. In conclusion, the effect of calcium was similar with either form of supplementation, i.e., dairy products or tablets, and changes in percent body weight and total calcium intake were predictors of total body BMD and BMC changes. PMID:23477205

  19. FTO genotype is associated with phenotypic variability of body mass index

    NARCIS (Netherlands)

    Yang, J.; Loos, R.J.; Powell, J.E.; Medland, S.E.; Speliotes, E.K.; Chasman, D.I.; Rose, L.M.; Thorleifsson, G.; Steinthorsdottir, V.; Magi, R.; Waite, L.; Smith, A.V.; Yerges-Armstrong, L.M.; Monda, K.L.; Hadley, D.; Mahajan, A.; Li, G.; Kapur, K.; Vitart, V.; Huffman, J.E.; Wang, S.R.; Palmer, C.; Esko, T.; Fischer, K.; Zhao, J.H.; Demirkan, A.; Isaacs, A.; Feitosa, M.F.; Luan, J.; Heard-Costa, N.L.; White, C.; Jackson, A.U.; Preuss, M.; Ziegler, A.; Eriksson, J.; Kutalik, Z.; Frau, F.; Nolte, I.M.; Vliet-Ostaptchouk, J.V. van; Hottenga, J.J.; Jacobs, K.B.; Verweij, N.; Goel, A.; Medina-Gomez, C.; Estrada, K.; Bragg-Gresham, J.L.; Sanna, S.; Sidore, C.; Tyrer, J.; Teumer, A.; Prokopenko, I.; Mangino, M.; Lindgren, C.M.; Assimes, T.L.; Shuldiner, A.R.; Hui, J.; Beilby, J.P.; McArdle, W.L.; Hall, P.; Haritunians, T.; Zgaga, L.; Kolcic, I.; Polasek, O.; Zemunik, T.; Oostra, B.A.; Junttila, M.J.; Gronberg, H.; Schreiber, S.; Peters, A.; Hicks, A.A.; Stephens, J.; Foad, N.S.; Laitinen, J.; Pouta, A.; Kaakinen, M.; Willemsen, G.; Vink, J.M.; Wild, S.H.; Navis, G.; Asselbergs, F.W.; Homuth, G.; John, U.; Iribarren, C.; Harris, T.; Launer, L.; Gudnason, V.; O'Connell, J.R.; Boerwinkle, E.; Cadby, G.; Palmer, L.J.; James, A.L.; Musk, A.W.; Ingelsson, E.; Psaty, B.M.; Beckmann, J.S.; Waeber, G.; Vollenweider, P.; Hayward, C.; Wright, A.F.; Rudan, I.; Kiemeney, L.A.L.M.; Vermeulen, S.

    2012-01-01

    There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medici

  20. High bone mass in mice lacking Cx37 because of defective osteoclast differentiation.

    Science.gov (United States)

    Pacheco-Costa, Rafael; Hassan, Iraj; Reginato, Rejane D; Davis, Hannah M; Bruzzaniti, Angela; Allen, Matthew R; Plotkin, Lilian I

    2014-03-21

    Connexin (Cx) proteins are essential for cell differentiation, function, and survival in all tissues with Cx43 being the most studied in bone. We now report that Cx37, another member of the connexin family of proteins, is expressed in osteoclasts, osteoblasts, and osteocytes. Mice with global deletion of Cx37 (Cx37(-/-)) exhibit higher bone mineral density, cancellous bone volume, and mechanical strength compared with wild type littermates. Osteoclast number and surface are significantly lower in bone of Cx37(-/-) mice. In contrast, osteoblast number and surface and bone formation rate in bones from Cx37(-/-) mice are unchanged. Moreover, markers of osteoblast activity ex vivo and in vivo are similar to those of Cx37(+/+) littermates. sRANKL/M-CSF treatment of nonadherent Cx37(-/-) bone marrow cells rendered a 5-fold lower level of osteoclast differentiation compared with Cx37(+/+) cell cultures. Further, Cx37(-/-) osteoclasts are smaller and have fewer nuclei per cell. Expression of RANK, TRAP, cathepsin K, calcitonin receptor, matrix metalloproteinase 9, NFATc1, DC-STAMP, ATP6v0d1, and CD44, markers of osteoclast number, fusion, or activity, is lower in Cx37(-/-) osteoclasts compared with controls. In addition, nonadherent bone marrow cells from Cx37(-/-) mice exhibit higher levels of markers for osteoclast precursors, suggesting altered osteoclast differentiation. The reduction of osteoclast differentiation is associated with activation of Notch signaling. We conclude that Cx37 is required for osteoclast differentiation and fusion, and its absence leads to arrested osteoclast maturation and high bone mass in mice. These findings demonstrate a previously unrecognized role of Cx37 in bone homeostasis that is not compensated for by Cx43 in vivo. PMID:24509854

  1. High Bone Mass in Mice Lacking Cx37 Because of Defective Osteoclast Differentiation*

    Science.gov (United States)

    Pacheco-Costa, Rafael; Hassan, Iraj; Reginato, Rejane D.; Davis, Hannah M.; Bruzzaniti, Angela; Allen, Matthew R.; Plotkin, Lilian I.

    2014-01-01

    Connexin (Cx) proteins are essential for cell differentiation, function, and survival in all tissues with Cx43 being the most studied in bone. We now report that Cx37, another member of the connexin family of proteins, is expressed in osteoclasts, osteoblasts, and osteocytes. Mice with global deletion of Cx37 (Cx37−/−) exhibit higher bone mineral density, cancellous bone volume, and mechanical strength compared with wild type littermates. Osteoclast number and surface are significantly lower in bone of Cx37−/− mice. In contrast, osteoblast number and surface and bone formation rate in bones from Cx37−/− mice are unchanged. Moreover, markers of osteoblast activity ex vivo and in vivo are similar to those of Cx37+/+ littermates. sRANKL/M-CSF treatment of nonadherent Cx37−/− bone marrow cells rendered a 5-fold lower level of osteoclast differentiation compared with Cx37+/+ cell cultures. Further, Cx37−/− osteoclasts are smaller and have fewer nuclei per cell. Expression of RANK, TRAP, cathepsin K, calcitonin receptor, matrix metalloproteinase 9, NFATc1, DC-STAMP, ATP6v0d1, and CD44, markers of osteoclast number, fusion, or activity, is lower in Cx37−/− osteoclasts compared with controls. In addition, nonadherent bone marrow cells from Cx37−/− mice exhibit higher levels of markers for osteoclast precursors, suggesting altered osteoclast differentiation. The reduction of osteoclast differentiation is associated with activation of Notch signaling. We conclude that Cx37 is required for osteoclast differentiation and fusion, and its absence leads to arrested osteoclast maturation and high bone mass in mice. These findings demonstrate a previously unrecognized role of Cx37 in bone homeostasis that is not compensated for by Cx43 in vivo. PMID:24509854

  2. Rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3L exhibit distinct phenotypical and functional characteristics.

    Science.gov (United States)

    N'diaye, Marie; Warnecke, Andreas; Flytzani, Sevasti; Abdelmagid, Nada; Ruhrmann, Sabrina; Olsson, Tomas; Jagodic, Maja; Harris, Robert A; Guerreiro-Cacais, Andre Ortlieb

    2016-03-01

    Dendritic cells are professional APCs that play a central role in the initiation of immune responses. The limited ex vivo availability of dendritic cells inspires the widespread use of bone marrow-derived dendritic cells as an alternative in research. However, the functional characteristics of bone marrow-derived dendritic cells are incompletely understood. Therefore, we compared functional and phenotypic characteristics of rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3 ligand bone marrow-derived dendritic cells. A comparison of surface markers revealed that FLT3 ligand-bone marrow-derived dendritic cells expressed signal regulatory protein α, CD103, and CD4 and baseline levels of MHC class II, CD40, and CD86, which were highly up-regulated upon stimulation. Conversely, GM-CSF/IL-4-bone marrow-derived dendritic cells constitutively expressed signal regulatory protein α, CD11c, and CD11b but only mildly up-regulated MHC class II, CD40, or CD86 following stimulation. Expression of dendritic cell-associated core transcripts was restricted to FLT3 ligand-bone marrow-derived dendritic cells . GM-CSF/IL-4-bone marrow-derived dendritic cells were superior at phagocytosis but were outperformed by FLT3 ligand-bone marrow-derived dendritic cells at antigen presentation and T cell stimulation in vitro. Stimulated GM-CSF/IL-4-bone marrow-derived dendritic cells secreted more TNF, CCL5, CCL20, and NO, whereas FLT3 ligand-bone marrow-derived dendritic cells secreted more IL-6 and IL-12. Finally, whereas GM-CSF/IL-4-bone marrow-derived dendritic cell culture supernatants added to resting T cell cultures promoted forkhead box p3(+) regulatory T cell populations, FLT3 ligand-bone marrow-derived dendritic cell culture supernatants drove Th17 differentiation. We conclude that rat GM-CSF/IL-4-bone marrow-derived dendritic cells and FLT3 ligand-bone marrow-derived dendritic cells are functionally distinct. Our data support the current rationale that FLT3

  3. Bovine lactoferrin improves bone mass and microstructure in ovariectomized rats via OPG/RANKL/RANK pathway

    Institute of Scientific and Technical Information of China (English)

    Jian-ming HOU; Ying XUE; Qing-ming LIN

    2012-01-01

    Aim:Lactoferrin (LF),an 80-kDa iron-binding glycoprotein,is a pleiotropic factor found in colostrum,milk,saliva and epithelial cells of the exocrine glands.The aim of this study was to evaluate the effects of LF on the bones in ovariectomized (Ovx) rats and to identify the pathways that mediate the anabolic action of LF on the bones.Methods:Female Sprague-Dawley rats (6-month-old) underwent ovariectomy,and were treated with different doses of LF (10,100,1000,and 2000 mg·kg-1·d-1,po) or with 7β-estradiol (0.1 mg·kg-1,im,each week) as the positive control.By the end of 6 month-treatments,the bone mass and microstructure in the rats were scanned by micro-computed tomography (micro-CT),and the bone metabolism was evaluated with specific markers,and the mRNA levels of osteoprotegerin (OPG) and the receptor-activator of nuclear factor kB ligand (RANKL) in femur were measured using qRT-PCR.Results:LF treatment dose-dependently elevated the bone volume (BV/TV),trabecular thickness (TbTh) and trabecular number (TbN),and reduced the trabecular separation (TbSp) in Ovx rats.Furthermore,higher doses of LF (1000 and 2000 mg·kg-1·d-1) significantly increased the bone mineral density (BMD) compared with the untreated Ovx rats.The higher doses of LF also significantly increased the serum levels of OC and BALP,and decreased the serum levels of β-CTx and NTX.LF treatment significantly increased the OPG mRNA levels,and suppressed the RANKL mRNA levels,and the RANKL/OPG mRNA ratio in Ovx rats.Conclusion:Oral administration of LF preserves the bone mass and improves the bone microarchitecture.LF enhances bone formation,reduces bone resorption,and decreases bone mass loss,possibly through the regulation of OPG/RANKL/RANK pathway.

  4. Discordant effect of body mass index on bone mineral density and speed of sound

    Directory of Open Access Journals (Sweden)

    Hagag Philippe

    2003-07-01

    Full Text Available Abstract Background Increased BMI may affect the determination of bone mineral density (BMD by dual X-ray absorptiometry (DXA and speed of sound (SOS measured across bones. Preliminary data suggest that axial SOS is less affected by soft tissue. The purpose of this study is to evaluate the effect of body mass index (BMI on BMD and SOS measured along bones. Methods We compared axial BMD determined by DXA with SOS along the phalanx, radius and tibia in 22 overweight (BMI > 27 kg/m2, and 11 lean (BMI = 21 kg/m2 postmenopausal women. Serum bone specific alkaline phosphatase and urinary deoxypyridinoline excretion determined bone turnover. Results Mean femoral neck – but not lumbar spine BMD was higher in the overweight – as compared with the lean group (0.70 ± 0.82, -0.99 ± 0.52, P P Conclusions The high BMI of postmenopausal women may result in spuriously high BMD. SOS measured along bones may be a more appropriate means for evaluating bones of overweight women.

  5. Enzalutamide Reduces the Bone Mass in the Axial But Not the Appendicular Skeleton in Male Mice.

    Science.gov (United States)

    Wu, Jianyao; Movérare-Skrtic, Sofia; Börjesson, Anna E; Lagerquist, Marie K; Sjögren, Klara; Windahl, Sara H; Koskela, Antti; Grahnemo, Louise; Islander, Ulrika; Wilhelmson, Anna S; Tivesten, Åsa; Tuukkanen, Juha; Ohlsson, Claes

    2016-02-01

    Testosterone is a crucial regulator of the skeleton, but the role of the androgen receptor (AR) for the maintenance of the adult male skeleton is unclear. In the present study, the role of the AR for bone metabolism and skeletal growth after sexual maturation was evaluated by means of the drug enzalutamide, which is a new AR antagonist used in the treatment of prostate cancer patients. Nine-week-old male mice were treated with 10, 30, or 100 mg/kg·d of enzalutamide for 21 days or were surgically castrated and were compared with vehicle-treated gonadal intact mice. Although orchidectomy reduced the cortical bone thickness and trabecular bone volume fraction in the appendicular skeleton, these parameters were unaffected by enzalutamide. In contrast, both enzalutamide and orchidectomy reduced the bone mass in the axial skeleton as demonstrated by a reduced lumbar spine areal bone mineral density (P < .001) and trabecular bone volume fraction in L5 vertebrae (P < .001) compared with vehicle-treated gonadal intact mice. A compression test of the L5 vertebrae revealed that the mechanical strength in the axial skeleton was significantly reduced by enzalutamide (maximal load at failure -15.3% ± 3.5%; P < .01). The effects of enzalutamide in the axial skeleton were associated with a high bone turnover. In conclusion, enzalutamide reduces the bone mass in the axial but not the appendicular skeleton in male mice after sexual maturation. We propose that the effect of testosterone on the axial skeleton in male mice is mainly mediated via the AR. PMID:26587782

  6. Bone Marrow Stromal Cells Express Neural Phenotypes in vitro and Migrate in Brain After Transplantation in vivo

    Institute of Scientific and Technical Information of China (English)

    LI-YE YANG; TIAN-HUA HUANG; LIAN MA

    2006-01-01

    Objective To investigate the differentiation of bone marrow stromal cells (BMSC) into neuron-like cells and to explore their potential use for neural transplantation. Methods BMSC from rats and adult humans were cultured in serum-containing media. Salvia miltiorrhiza was used to induce human BMSC (hBMSC) to differentiate. BMSC were identified with immunocytochemistry. Semi-quantitative RT-PCR was used to examine mRNA expression of neurofilamentl (NF1), nestin and neuron-specific enolase (NSE) in rat BMSC (rBMSC). Rat BMSC labelled by Hoschst33258 were transplanted into striatum of rats to trace migration and distribution. Results BMSC expressed NSE, NF1 and nestin mRNA, and NF1 mRNA and expression was increased with induction of Salvia miltiorrhiza. A small number of hBMSC were stained by anti-nestin, anti-GFAP and anti-S100. Salvia miltiorrhiza could induce hBMSC to differentiate into neuron-like cells.Some differentiated neuron-like cells, that expressed NSE, beta-tubulin and NF-200, showed typical neuron morphology, but some neuron-like cells also expressed alpha smooth muscle protein, making their neuron identification complicated. rBMSC could migrate and adapted in the host brains after being transplanted. Conclusion Bone marrow stromal cells could express phenotypes of neurons, and Salvia miltiorrhiza could induce hBMSC to differentiate into neuron-like cells. If BMSC could be converted into neurons instead of mesenchymal derivatives, they would be an abundant and accessible cellular source to treat a variety of neurological diseases.

  7. Visceral fat is more important than peripheral fat for endometrial thickness and bone mass in healthy postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Christiansen, Claus

    2003-01-01

    as double-layer thickness. Body composition was measured by dual energy x-ray absorptiometry, which divides the body into fat mass, lean mass, and bone mass, both for the total body and regional body compartments. An abdominal region was inserted manually. Statistics were Pearson correlations and...... analysis of variance. RESULTS: Endometrial thickness and total body bone mass were correlated, respectively, to body mass index (r = 0.14, P <.01; r = 0.35, P <.001), total body fat mass (r = 0.14, P <.01; r = 0.38, P <.001), abdominal fat mass (r = 0.16, P <.001; r = 0.33, P <.001), peripheral fat mass (r...... = 0.10, P <.05; r = 0.41, P <.001), and abdominal/peripheral fat mass (r = 0.12, P <.01; r = 0.11, P <.01). CONCLUSION: High body mass index and abdominal fat distribution correlate with increased endometrial thickness and bone mass....

  8. Effect of aging on bone mass in adult women

    International Nuclear Information System (INIS)

    Total-body calcium was measured in 40 adult women by total-body neutron activation analysis (TBNAA). Procedures for normalizing the absolute calcium measurements for the parameters of size and age were developed in order to effect a direct comparison of women of age 30 to 78 yr. The normal total-body calcium (TB/sub Ca/) for an individual can be predicted by a formula developed in the present study to within +- 11 percent (1.62 SD) at the 90 percent confidence level. The TB/sub Ca/ loss can be characterized by two components: one with a slower rate, 0.37 percent/yr, and the other with a faster rate, 1.08 percent/yr. The latter, a more rapid postmenopausal loss, started at 50 to 60 yr and was superimposed on the slower rate of loss that started in the fourth decade and continued throughout life. The bone mineral content (BMC) of the radius, measured by the absorptiometric technique, correlated well with the total-body skeletal calcium in this population (r = 0.813, P less than .001). However, for intercomparisons of the BMC values of individuals, normalization of the BMC values for size and age is required, as it is for the TB/sub Ca/ data. Normalization provided by the ratio of BMC to radius width is not adequate for comparative studies

  9. Relative Importance of Lean and Fat Mass on Bone Mineral Density in Iranian Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Jeddi

    2015-07-01

    Full Text Available Background Body weight is made up of lean and fat mass and both are involved in growth and development. Impression of these two components in bone density accrual has been controversial. Objectives The aim of this study was to evaluate the relationship between fat and lean mass and bone density in Iranian children and adolescents. Patients and Methods A cross-sectional study was performed on 472 subjects (235 girls, 237 boys aged 9-18 years old in Fars Province. The participants' weight, height, waist circumference, stage of puberty, and level of physical activity were recorded. Bone Mineral Content (BMC, Bone Mineral Density (BMD, total body fat and lean mass were measured using dual-energy X-ray absorptiometry. Results Results showed that 12.2% of boys and 12.3% of girls were overweight and 5.5% of boys and 4.7% of girls were obese. Obese individuals had greater total body BMD (0.96 ± 0.11 than normal-weight ones (0.86 ± 0.11 (P < 0.001. We found the greatest correlation between total body BMD and total body lean mass (R = 0.78. P < 0.001 and the least correlation with total body fat percentage (R = 0.03, P = 0.44. Total lean mass in more active boys was 38.1 ± 10.9 and in less active boys was 32.3 ± 11.0 (P < 0.001. The results of multiple regression analysis showed that age and total body lean mass were independent factors of BMD in growing children and adolescents. Conclusions These findings suggest that lean mass was the most important predictor of BMD in both genders. Physical activity appears to positively impact on lean mass and needs to be considered in physical education and health-enhancing programs in Iranian school children.

  10. Chronic obstructive pulmonary disease and low bone mass: A case-control study

    Directory of Open Access Journals (Sweden)

    Rakesh K Gupta

    2014-01-01

    Full Text Available Background and Objective: Low bone mass (osteopenia and osteoporosis is one of the effects associated with chronic obstructive pulmonary disease (COPD. There is very little data from Saudi Arabia on COPD and low bone mass. This retrospective study was done to assess the prevalence of osteoporosis and osteopenia in COPD patients attending King Fahd Hospital of the University (KFHU, Alkhobar. Patients and Methods: After obtaining the ethical approval from the research committee, all patients seen between at the King Fahd Hospital of the University between January 2010 and December 2012 were included. The inclusion criteria included a follow up of a minimum 2 years, and the Medical Records should have the details of forced expiratory volume in one second (FEV 1 , blood bone profile and bone biomarkers and dual-energy X-ray absorptiometry (DEXA scan. Patients were labeled as osteopenia if the T score was -<1 to <-2.5 and osteoporosis of <-2.5 as per the WHO definition of osteopenia and osteoporosis. Results: Seventy-three patients were being followed in the clinics and 49 patients satisfied the inclusion criteria. The average age was 60.6 ± 10.47 years; males were 43 and females 6. Three (6.1% were normal and the remaining 46 (93.9% were with low bone mass. Thirty-two (65.3% were osteoporotic and 14 (28.57% were osteopenic. The average duration of COPD was 4.5 ± 6.2 years. Majority (n = 36, 73.4% of patients were in the Global Initiative for COPD (GOLD class II and III. FEV 1 was significantly lower in the patients with low bone mass 1.66 ± 0.60 versus 3.61 ± 0.58 (P < 0.001. Conclusions: Our study shows that over 90% of Saudi Arabian patients with COPD suffer from osteopenia and osteoporosis and unfortunately they remain under-diagnosed and undertreated.

  11. CCL20/CCR6 Signaling Regulates Bone Mass Accrual in Mice.

    Science.gov (United States)

    Doucet, Michele; Jayaraman, Swaathi; Swenson, Emily; Tusing, Brittany; Weber, Kristy L; Kominsky, Scott L

    2016-07-01

    CCL20 is a member of the macrophage inflammatory protein family and is reported to signal monogamously through the receptor CCR6. Although studies have identified the genomic locations of both Ccl20 and Ccr6 as regions important for bone quality, the role of CCL20/CCR6 signaling in regulating bone mass is unknown. By micro-computed tomography (μCT) and histomorphometric analysis, we show that global loss of Ccr6 in mice significantly decreases trabecular bone mass coincident with reduced osteoblast numbers. Notably, CCL20 and CCR6 were co-expressed in osteoblast progenitors and levels increased during osteoblast differentiation, indicating the potential of CCL20/CCR6 signaling to influence osteoblasts through both autocrine and paracrine actions. With respect to autocrine effects, CCR6 was found to act as a functional G protein-coupled receptor in osteoblasts and although its loss did not appear to affect the number or proliferation rate of osteoblast progenitors, differentiation was significantly inhibited as evidenced by delays in osteoblast marker gene expression, alkaline phosphatase activity, and mineralization. In addition, CCL20 promoted osteoblast survival concordant with activation of the PI3K-AKT pathway. Beyond these potential autocrine effects, osteoblast-derived CCL20 stimulated the recruitment of macrophages and T cells, known facilitators of osteoblast differentiation and survival. Finally, we generated mice harboring a global deletion of Ccl20 and found that Ccl20(-/-) mice exhibit a reduction in bone mass similar to that observed in Ccr6(-/-) mice, confirming that this phenomenon is regulated by CCL20 rather than alternate CCR6 ligands. Collectively, these data indicate that CCL20/CCR6 signaling may play an important role in regulating bone mass accrual, potentially by modulating osteoblast maturation, survival, and the recruitment of osteoblast-supporting cells. © 2016 American Society for Bone and Mineral Research. PMID:26890063

  12. Adolescence: How do we increase intestinal calcium absorption to allow for bone mineral mass accumulation?

    Science.gov (United States)

    An increase in calcium absorptive efficiency (fractional absorption of dietary calcium) during adolescence is associated with a rapid increase in total body bone mineral mass (BMM) accumulation. This increase occurs across a range of calcium intakes. It appears to be principally mediated by hormonal...

  13. On one method of fat and protein extraction from bone mass

    International Nuclear Information System (INIS)

    This article describes the actual technological task of the food industry. The problem of the extraction of fat and protein from the bone mass can be solved by different methods. The work offers one of the more effective modes. Results are presented as diagrams. (author)

  14. Local bone mineral mass as a function of dose in radium cases

    International Nuclear Information System (INIS)

    Bone mineral mass at specific sites in the forearms and fingers of females with exposure to radium and mesothorium appears to have no dependence on dose. Data analysis is continuing, so these results should be considered preliminary. Future analyses will include males

  15. Changes in bone mass during low dose corticosteroid treatment in patients with polymyalgia rheumatica

    DEFF Research Database (Denmark)

    Krogsgaard, M R; Thamsborg, G; Lund, B

    1996-01-01

    OBJECTIVE: To compare the long term effects of low dosage prednisolone or deflazacort treatments on bone mass in patients with polymyalgia rheumatica. METHODS: Thirty patients with polymyalgia rheumatica were allocated on a random double blind basis to receive treatment with prednisolone or...

  16. The novel bisphosphonate disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate increases bone mass in post-ovariectomy rats.

    Science.gov (United States)

    Takizawa, Aiko; Chiba, Mirei; Ota, Takeru; Yasuda, Mayumi; Suzuki, Keiko; Kanemitsu, Takuya; Itoh, Takashi; Shinoda, Hisashi; Igarashi, Kaoru

    2016-05-01

    The novel bisphosphonate (BP) disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate (MPMBP) is a non-nitrogen-containing BP with an antioxidant side chain that possesses anti-inflammatory properties. We investigated the systemic effects of this compound on bone loss induced by ovariectomy (OVX) in adult rats. Micro-computed tomography revealed that MPMBP increased bone mass and density in both the metaphysis and diaphysis, and improved the structural properties important for mechanical strength of osteoporotic bone. Sequential bone labeling with tetracycline and calcein indicated that MPMBP decreased longitudinal growth of the primary spongiosa (PS), but stimulated cortical bone formation in the diaphysis. MPMBP increased type I collagen accumulation in the PS, and decreased the number and size of adipocytes in the bone marrow, suggesting inhibition of increased bone marrow adipogenesis induced by OVX. Furthermore, MPMBP reduced the number of bone resorbing cathepsin K-positive osteoclasts induced by OVX. These results suggest that MPMBP could improve bone loss induced by estrogen deficiency. Both stimulation of bone formation and inhibition of bone resorption might play a role in the increase in bone mass and bone density after MPMBP treatment. PMID:27245552

  17. The Relationship of Fat Distribution and Insulin Resistance with Lumbar Spine Bone Mass in Women.

    Directory of Open Access Journals (Sweden)

    Francisco J A de Paula

    Full Text Available Bone marrow harbors a significant amount of body adipose tissue (BMAT. While BMAT might be a source of energy for bone modeling and remodeling, its increment can also represent impairment of osteoblast differentiation. The relationship between BMAT, bone mass and insulin sensitivity is only partially understood and seems to depend on the circumstances. The present study was designed to assess the association of BMAT with bone mineral density in the lumbar spine as well as with visceral adipose tissue, intrahepatic lipids, HOMA-IR, and serum levels of insulin and glucose. This cross-sectional clinical investigation included 31 non-diabetic women, but 11 had a pre-diabetes status. Dual X-ray energy absorptiometry was used to measure bone mineral density and magnetic resonance imaging was used to assess fat deposition in BMAT, visceral adipose tissue and liver. Our results suggest that in non-diabetic, there is an inverse relationship between bone mineral density in lumbar spine and BMAT and a trend persists after adjustment for weight, age, BMI and height. While there is a positive association between visceral adipose tissue and intrahepatic lipids with serum insulin levels, there is no association between BMAT and serum levels of insulin. Conversely, a positive relationship was observed between BMAT and serum glucose levels, whereas this association was not observed with other fat deposits. These relationships did not apply after adjustment for body weight, BMI, height and age. The present study shows that in a group of predominantly non-obese women the association between insulin resistance and BMAT is not an early event, as occurs with visceral adipose tissue and intrahepatic lipids. On the other hand, BMAT has a negative relationship with bone mineral density. Taken together, the results support the view that bone has a complex and non-linear relationship with energy metabolism.

  18. A STUDY TO ASSESS THE BONE MASS IN CHRONIC ALCOHOLIC PATIENT

    Directory of Open Access Journals (Sweden)

    Madharam Bishnoi

    2014-04-01

    Methodology: A cross-sectional study was conducted to assess the alteration in bone mineral density (BMD in alcoholic patients, under the age of 60 year and free of non-modifiable risk factors for osteoporosis. Complete blood examination and laboratory profile was conducted in all the cases. Liver function and bone mass density were also analyzed. Results: Total 30 male patients were studied with an average age of 51 years. Pathological levels of bone mass (in the spinal column and hip were detected in 57% of patients (41% with osteopenia and 16% with osteoporosis, a much higher percentage than that expected in a male population of such an age. Vertebral fractures were observed in six patients (16% and hip fractures in four (11%. Conclusion: The active treatment of the alcoholic patient depends upon the levels of addictive behaviour. The risk of fractures and pathological levels of bone mass in alcoholic cases should be taken into consideration and accordingly comprehensive treatment should be planned. [Natl J Med Res 2014; 4(2.000: 161-164

  19. Transgene silencing of the Hutchinson-Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas resveratrol treatment does not show overall beneficial effects

    DEFF Research Database (Denmark)

    Strandgren, Charlotte; Nasser, Hasina Abdul; McKenna, Tomás;

    2015-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder that is most commonly caused by a de novo point mutation in exon 11 of the LMNA gene, c.1824C>T, which results in an increased production of a truncated form of lamin A known as progerin. In this study, we used a mouse...... alone. However, the reversal of the dental phenotype of overgrown and laterally displaced lower incisors in HGPS mice could be attributed to resveratrol. Our results indicate that the HGPS bone defects were reversible upon suppressed transgenic expression and suggest that treatments targeting aberrant...... progerin splicing give hope to patients who are affected by HGPS.-Strandgren, C., Nasser, H. A., McKenna, T., Koskela, A., Tuukkanen, J., Ohlsson, C., Rozell, B., Eriksson, M. Transgene silencing of the Hutchinson-Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas...

  20. Appendicular bone mass and knee and hand osteoarthritis in Japanese women: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Moji Kazuhiko

    2002-10-01

    Full Text Available Abstract Background It has been reported that there is an inverse association between osteoarthritis (OA and osteoporosis. However, the relationship of bone mass to OA in a Japanese population whose rates of OA are different from Caucasians remains uncertain. Methods We studied the association of appendicular bone mineral density (second metacarpal; mBMD and quantitative bone ultrasound (calcaneus; stiffness index with knee and hand OA among 567 Japanese community-dwelling women. Knee and hand radiographs were scored for OA using Kellgren-Lawrence (K/L scales. In addition, we evaluated the presence of osteophytes and of joint space narrowing. The hand joints were examined at the distal and proximal interphalangeal (DIP, PIP and first metacarpophalangeal/carpometacarpal (MCP/CMC joints. Results After adjusting for age and body mass index (BMI, stiffness index was significantly higher in women with K/L scale, grade 3 at CMC/MCP joint compared with those with no OA. Adjusted means of stiffness index and mBMD were significantly higher in women with definite osteophytes at the CMC/MCP joint compared to those without osteophytes, whereas there were no significant differences for knee, DIP and PIP joints. Stiffness index, but not mBMD, was higher in women with definite joint space narrowing at the CMC/MCP joint compared with those with no joint space narrowing. Conclusions Appendicular bone mass was increased with OA at the CMC/MCP joint, especially among women with osteophytes. Our findings suggest that the association of peripheral bone mass with OA for knee, DIP or PIP may be less clearcut in Japanese women than in other populations.

  1. FTO genotype is associated with phenotypic variability of body mass index

    NARCIS (Netherlands)

    Yang, Jian; Loos, Ruth J. F.; Powell, Joseph E.; Medland, Sarah E.; Speliotes, Elizabeth K.; Chasman, Daniel I.; Rose, Lynda M.; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Maegi, Reedik; Waite, Lindsay; Smith, Albert Vernon; Yerges-Armstrong, Laura M.; Monda, Keri L.; Hadley, David; Mahajan, Anubha; Li, Guo; Kapur, Karen; Vitart, Veronique; Huffman, Jennifer E.; Wang, Sophie R.; Palmer, Cameron; Esko, Toenu; Fischer, Krista; Zhao, Jing Hua; Demirkan, Ayse; Isaacs, Aaron; Feitosa, Mary F.; Luan, Jian'an; Heard-Costa, Nancy L.; White, Charles; Jackson, Anne U.; Preuss, Michael; Ziegler, Andreas; Eriksson, Joel; Kutalik, Zoltan; Frau, Francesca; Nolte, Ilja M.; Van Vliet-Ostaptchouk, Jana V.; Hottenga, Jouke-Jan; Jacobs, Kevin B.; Verweij, Niek; Goel, Anuj; Medina-Gomez, Carolina; Estrada, Karol; Bragg-Gresham, Jennifer Lynn; Sanna, Serena; Sidore, Carlo; Tyrer, Jonathan; Teumer, Alexander; Prokopenko, Inga; Mangino, Massimo; Lindgren, Cecilia M.; Assimes, Themistocles L.; Shuldiner, Alan R.; Hui, Jennie; Beilby, John P.; McArdle, Wendy L.; Hall, Per; Haritunians, Talin; Zgaga, Lina; Kolcic, Ivana; Polasek, Ozren; Zemunik, Tatijana; Oostra, Ben A.; Junttila, M. Juhani; Groenberg, Henrik; Schreiber, Stefan; Peters, Annette; Hicks, Andrew A.; Stephens, Jonathan; Foad, Nicola S.; Laitinen, Jaana; Pouta, Anneli; Kaakinen, Marika; Willemsen, Gonneke; Vink, Jacqueline M.; Wild, Sarah H.; Navis, Gerjan; Asselbergs, Folkert W.; Homuth, Georg; John, Ulrich; Iribarren, Carlos; Harris, Tamara; Launer, Lenore; Gudnason, Vilmundur; O'Connell, Jeffrey R.; Boerwinkle, Eric; Cadby, Gemma; Palmer, Lyle J.; James, Alan L.; Musk, Arthur W.; Ingelsson, Erik; Psaty, Bruce M.; Beckmann, Jacques S.; Waeber, Gerard; Vollenweider, Peter; Hayward, Caroline; Wright, Alan F.; Rudan, Igor; Groop, Leif C.; Metspalu, Andres; Khaw, Kay Tee; van Duijn, Cornelia M.; Borecki, Ingrid B.; Province, Michael A.; Wareham, Nicholas J.; Tardif, Jean-Claude; Huikuri, Heikki V.; Cupples, L. Adrienne; Atwood, Larry D.; Fox, Caroline S.; Boehnke, Michael; Collins, Francis S.; Mohlke, Karen L.; Erdmann, Jeanette; Schunkert, Heribert; Hengstenberg, Christian; Stark, Klaus; Lorentzon, Mattias; Ohlsson, Claes; Cusi, Daniele; Staessen, Jan A.; Van der Klauw, Melanie M.; Pramstaller, Peter P.; Kathiresan, Sekar; Jolley, Jennifer D.; Ripatti, Samuli; Jarvelin, Marjo-Riitta; de Geus, Eco J. C.; Boomsma, Dorret I.; Penninx, Brenda; Wilson, James F.; Campbell, Harry; Chanock, Stephen J.; van der Harst, Pim; Hamsten, Anders; Watkins, Hugh; Hofman, Albert; Witteman, Jacqueline C.; Zillikens, M. Carola; Uitterlinden, Andre G.; Rivadeneira, Fernando; Zillikens, M. Carola; Kiemeney, Lambertus A.; Vermeulen, Sita H.; Abecasis, Goncalo R.; Schlessinger, David; Schipf, Sabine; Stumvoll, Michael; Toenjes, Anke; Spector, Tim D.; North, Kari E.; Lettre, Guillaume; McCarthy, Mark I.; Berndt, Sonja I.; Heath, Andrew C.; Madden, Pamela A. F.; Nyholt, Dale R.; Montgomery, Grant W.; Martin, Nicholas G.; McKnight, Barbara; Strachan, David P.; Hill, William G.; Snieder, Harold; Ridker, Paul M.; Thorsteinsdottir, Unnur; Stefansson, Kari; Frayling, Timothy M.; Hirschhorn, Joel N.; Goddard, Michael E.; Visscher, Peter M.

    2012-01-01

    There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human m

  2. A myostatin inhibitor (propeptide-Fc) increases muscle mass and muscle fiber size in aged mice but does not increase bone density or bone strength.

    Science.gov (United States)

    Arounleut, Phonepasong; Bialek, Peter; Liang, Li-Fang; Upadhyay, Sunil; Fulzele, Sadanand; Johnson, Maribeth; Elsalanty, Mohammed; Isales, Carlos M; Hamrick, Mark W

    2013-09-01

    Loss of muscle and bone mass with age are significant contributors to falls and fractures among the elderly. Myostatin deficiency is associated with increased muscle mass in mice, dogs, cows, sheep and humans, and mice lacking myostatin have been observed to show increased bone density in the limb, spine, and jaw. Transgenic overexpression of myostatin propeptide, which binds to and inhibits the active myostatin ligand, also increases muscle mass and bone density in mice. We therefore sought to test the hypothesis that in vivo inhibition of myostatin using an injectable myostatin propeptide (GDF8 propeptide-Fc) would increase both muscle mass and bone density in aged (24 mo) mice. Male mice were injected weekly (20 mg/kg body weight) with recombinant myostatin propeptide-Fc (PRO) or vehicle (VEH; saline) for four weeks. There was no difference in body weight between the two groups at the end of the treatment period, but PRO treatment significantly increased mass of the tibialis anterior muscle (+ 7%) and increased muscle fiber diameter of the extensor digitorum longus (+ 16%) and soleus (+ 6%) muscles compared to VEH treatment. Bone volume relative to total volume (BV/TV) of the femur calculated by microCT did not differ significantly between PRO- and VEH-treated mice, and ultimate force (Fu), stiffness (S), toughness (U) measured from three-point bending tests also did not differ significantly between groups. Histomorphometric assays also revealed no differences in bone formation or resorption in response to PRO treatment. These data suggest that while developmental perturbation of myostatin signaling through either gene knockout or transgenic inhibition may alter both muscle and bone mass in mice, pharmacological inhibition of myostatin in aged mice has a more pronounced effect on skeletal muscle than on bone. PMID:23832079

  3. Association of Body Weight and Body Mass Index with Bone Mineral Density in Women and Men from Kosovo

    OpenAIRE

    Rexhepi, Sylejman; Bahtiri, Elton; Rexhepi, Mjellma; Sahatciu-Meka, Vjollca; Rexhepi, Blerta

    2015-01-01

    Background and objective: Body weight and body mass index (BMI) are considered potentially modifiable determinants of bone mass. Therefore, the aim of this study was to explore the association between body weight and body mass index (BMI) with total hip and lumbar spine bone mineral density (BMD). Methods: This cross-sectional study included a population of 100 women and 32 men from Kosovo into three BMI groups. All the study subjects underwent dual-energy X-ray absorptiometry (DXA) measureme...

  4. In Situ Characterizing Membrane Lipid Phenotype of Human Lung Cancer Cell Lines Using Mass Spectrometry Profiling

    Science.gov (United States)

    He, Manwen; Guo, Shuai; Ren, Junling; Li, Zhili

    2016-01-01

    Abnormal lipid metabolisms are closely associated with cancers. In this study, mass spectrometry was employed to in situ investigate the associations of membrane lipid phenotypes of six human lung cancer cell lines (i.e., A549, H1650, H1975 from adenocarcinoma, H157 and H1703 from squamous cell carcinomas, and H460 from a large cell carcinoma) with cancer cell types and finally total 230 lipids were detected. Based these 230 lipids, partial least-square discriminant analysis indicated that fifteen lipids (i.e., PE 18:0_18:1, PI 18:0_20:4, SM 42:2, PE 16:0_20:4, PE 36:2, PC 36:2, SM 34:1, PA 38:3,C18:0, C22:4, PA 34:2, C20:5, C20:2, C18:2, and CerP 36:2) with variable importance in the projection (VIP) value of > 1.0 could be used to differentiate six cancer cell lines with the Predicted Residual Sum of Square (PRESS) score of 0.1974. Positive correlation between polyunsaturated fatty acids (i.e., C20:4, C22:4, C22:5, and C22:6) and polyunsaturated phospholipids (PE 16:0_20:4, PE 38:4, and PI 18:0_20:4) was observed in lung adenocarcinoma cells, especially for H1975 cells. Three adenocarcinoma cell lines (i.e., A549, H1650, and H1975) could be differentiated from other lung cancer cell lines based on the expression of C18:1, C20:1, C20:2, C20:5, and C22:6.

  5. Hypoestrogenism in young women and its influence on bone mass density.

    Science.gov (United States)

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Genazzani, Andrea Riccardo

    2010-09-01

    One of the most important hormonal factors responsible for bone health is estradiol. Genetic factors, adequacy of hormonal functioning, nutrition and physical activity may be the markers of bone status and development in young women. During adolescence, women reach peak bone acquisition and develop a skeletal mass. This process is largely regulated by endocrine factors mainly such as adequate levels of gonadal, adrenal and pituitary hormones. The crucial role played by estradiol and its impact on bones are very multiple. Estradiol induces growth factors' activation, receptor activator of nuclear factor kappa B ligand (RANKL) production inhibition and is mainly referred to antiresorptive activity. Clinical situations leading to hypoestrogenism has been linked to decreased bone mineral density leading to osteopenia and osteoporosis. This status both in fertile and perimenopausal women can increase the risk of pathological fractures. Such conditions as hypothalamic-pituitary insufficiency (functional hypothalamic amenorrhea, anorexia nervosa, Kallmann syndrome, hyperprolactinemia), ovarian failure (gonadal dysgenesis, premature ovarian failure) and iatrogenic treatment (surgery, chemotherapy, radiotherapy) can cause hypoestrogenism. The treatment of osteopenia and osteoporosis caused by hypoestrogenism is very essential and multidirectional. The crucial role of the therapy is the achievement of proper serum estradiol concentration and eliminate the causes of hypoestrogenism. PMID:20504098

  6. Effects of Obesity on Bone Mass and Quality in Ovariectomized Female Zucker Rats

    Directory of Open Access Journals (Sweden)

    Rafaela G. Feresin

    2014-01-01

    Full Text Available Obesity and osteoporosis are two chronic conditions that have been increasing in prevalence. Despite prior data supporting the positive relationship between body weight and bone mineral density (BMD, recent findings show excess body weight to be detrimental to bone mass, strength, and quality. To evaluate whether obesity would further exacerbate the effects of ovariectomy on bone, we examined the tibiae and fourth lumbar (L4 vertebrae from leptin receptor-deficient female (Leprfa/fa Zucker rats and their heterozygous lean controls (Leprfa/+ that were either sham-operated or ovariectomized (Ovx. BMD of L4 vertebra was measured using dual-energy X-ray absorptiometry, and microcomputed tomography was used to assess the microstructural properties of the tibiae. Ovariectomy significantly (P<0.001 decreased the BMD of L4 vertebrae in lean and obese Zucker rats. Lower trabecular number and greater trabecular separation (P<0.001 were also observed in the tibiae of lean- and obese-Ovx rats when compared to sham rats. However, only the obese-Ovx rats had lower trabecular thickness (Tb.Th (P<0.005 than the other groups. These findings demonstrated that ovarian hormone deficiency adversely affected bone mass and quality in lean and obese rats while obesity only affected Tb.Th in Ovx-female Zucker rats.

  7. Waist Circumference: A Key Determinant of Bone Mass in University Students

    OpenAIRE

    Rapheeporn KHWANCHUEA; Sasithorn THANAPOP; Samuhasaneeto, Suchittra; Suree CHARTWAINGAM; Sirirak MUKEM

    2013-01-01

    This study aimed to assess bone mineral density (BMD) status, and to explore association between lifestyle behaviors, body mass index (BMI), waist circumference (WC) and BMD status of 217 students (55 males and 162 females) aged between 17 - 23 years studying at Walailak University. The BMD was measured at distal-third radius, and confirmed at mid-shaft tibia by Quantitative ultrasound analysis. BMI and WC were recorded to assess obesity, and lifestyle behaviors were evaluated using a questio...

  8. Relationship of Weight and Body Mass Index with Bone Mineral Density in Adult Men from Kosovo

    OpenAIRE

    Hoxha, Rexhep; Islami, Hilmi; Qorraj-Bytyqi, Hasime; Thaçi, Shpetim; Bahtiri, Elton

    2014-01-01

    Background and objective: Body weight and body mass index (BMI) are considered strong predictors of osteoporotic fractures, though optimal BMI levels remain unsettled. There are several studies conducted on women about the relationship between BMI and bone mineral density (BMD), and just a few so far on men. Therefore, the objective of current study was to analyze the relationship between weight and BMI and BMD measured in lumbar spine (L1-L4), femur neck and total hip in 64 men from Kosovo. ...

  9. Bone

    International Nuclear Information System (INIS)

    Bone scanning provides information on the extent of primary bone tumors, on possible metastatic disease, on the presence of osteomyelitis prior to observation of roentgenographic changes so that earlier therapy is possible, on the presence of collagen diseases, on the presence of fractures not disclosed by x-ray films, and on the evaluation of aseptic necrosis. However, the total effect and contribution of bone scanning to the diagnosis, treatment, and ultimate prognosis of pediatric skeletal diseases is, as yet, unknown. (auth)

  10. CCAAT/enhancer binding protein β-deficiency enhances type 1 diabetic bone phenotype by increasing marrow adiposity and bone resorption

    OpenAIRE

    Motyl, Katherine J.; Raetz, Michelle; Tekalur, Srinivasan Arjun; Schwartz, Richard C.; McCabe, Laura R.

    2011-01-01

    Bone loss in type 1 diabetes is accompanied by increased marrow fat, which could directly reduce osteoblast activity or result from altered bone marrow mesenchymal cell lineage selection (adipocyte vs. osteoblast). CCAAT/enhancer binding protein beta (C/EBPβ) is an important regulator of both adipocyte and osteoblast differentiation. C/EBPβ-null mice have delayed bone formation and defective lipid accumulation in brown adipose tissue. To examine the balance of C/EBPβ functions in the diabetic...

  11. Effects of a 6-month football intervention program on bone mass and physical fitness in overweight children

    DEFF Research Database (Denmark)

    Seabra, André; Serra, Hugo; Seabra, Ana;

    2016-01-01

    Introduction: Physical activity is an important medium for improving bone mass and physical fitness of children, and as such is often emphasized in intervention programs with overweight/obesity children. Only few studies have examined the impact of a specific team sport intervention on the bone...

  12. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.

    Science.gov (United States)

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D'mello, Anil P

    2016-04-01

    The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure. PMID:26763577

  13. Dietary Restriction-Induced Alterations in Bone Phenotype: Effects of Lifelong Versus Short-Term Caloric Restriction on Femoral and Vertebral Bone in C57BL/6 Mice.

    Science.gov (United States)

    Behrendt, Ann-Kathrin; Kuhla, Angela; Osterberg, Anja; Polley, Christian; Herlyn, Philipp; Fischer, Dagmar-Christiane; Scotland, Maike; Wree, Andreas; Histing, Tina; Menger, Michael D; Müller-Hilke, Brigitte; Mittlmeier, Thomas; Vollmar, Brigitte

    2016-04-01

    Caloric restriction (CR) is a well-described dietary intervention that delays the onset of aging-associated biochemical and physiological changes, thereby extending the life span of rodents. The influence of CR on metabolism, strength, and morphology of bone has been controversially discussed in literature. Thus, the present study evaluated whether lifelong CR versus short-term late-onset dietary intervention differentially affects the development of senile osteoporosis in C57BL/6 mice. Two different dietary regimens with 40% food restriction were performed: lifelong CR starting in 4-week-old mice was maintained for 4, 20, or 74 weeks. In contrast, short-term late-onset CR lasting a period of 12 weeks was commenced at 48 or 68 weeks of age. Control mice were fed ad libitum (AL). Bone specimens were assessed using microcomputed tomography (μCT, femur and lumbar vertebral body) and biomechanical testing (femur). Adverse effects of CR, including reduced cortical bone mineral density (Ct.BMD) and thickness (Ct.Th), were detected to some extent in senile mice (68+12w) but in particular in cortical bone of young growing mice (4+4w), associated with reduced femoral failure force (F). However, we observed a profound capacity of bone to compensate these deleterious changes of minor nutrition with increasing age presumably via reorganization of trabecular bone. Especially in lumbar vertebrae, lifelong CR lasting 20 or 74 weeks had beneficial effects on trabecular bone mineral density (Tb.BMD), bone volume fraction (BV/TV), and trabecular number (Tb.N). In parallel, lifelong CR groups showed reduced structure model index values compared to age-matched controls indicating a transformation of vertebral trabecular bone microarchitecture toward a platelike geometry. This effect was not visible in senile mice after short-term 12-week CR. In summary, CR has differential effects on cortical and trabecular bone dependent on bone localization and starting age. Our study underlines

  14. Peak bone mass density among residents of metro Manila: A preliminary report

    International Nuclear Information System (INIS)

    Study Objective: To determine the peak bone mass density among residents of Metro Manila using dual X-ray absorptiometry (DEXA). Design: Cross-sectional study. Setting: Philippine General Hospital, a university based tertiary care hospital, and St. Luke's Medical Center, a private tertiary care center. Subjects: Forty five (45) healthy subjects aged 15-50 years old, all current residents of Metro Manila, were randomly chosen from among hospital companions were included in the study. There were 23 females and 22 males, with 3 to 4 subjects for each age range of 5. Methods: Bone mass density measurements on the lumbar spine and the femur using dual X-ray absorptiometry (DPXL Lunar) were taken. The values were also age-matched and matched with that of a young adult based on programmed Caucasian norm provided by Lunar Co. The values were then scattered against age for each sex. Ten (10) cc of blood was also extracted from the patients, with the 5 cc of blood separated for future studies. Parathormone assay and biochemistry examinations were also done. Patents were also interviewed as to their lifestyle, diet, use of contraceptive pill or hormonal replacement treatment, using a Filipino version of the revised questionnaire on the WHO Study on Osteoporosis. Dietary content was estimated using a previous day food recall. Results: The mean weight and height for females were 59.48±16.34 kg and 153.52±5.09 cm respectively, and for males, 58.14±10.06 kg and 162.52±6.75 cm respectively. The mean bone mass density at the L2L4 level for females was 1.12±0.11 g/cm2 and 0.91±0.11 g/cm2 at the femur. The highest BMD in both the lumbar spine femoral neck measurements among females was achieved among those aged 30-35 years of age with the lowest BMD occurring between 15-19 and 45-50 years of age in the lumbar spine among female subjects. The highest BMD at the lumbar spine and the femoral neck among males was achieved between the ages 30-35 years of age with the lowest IND

  15. Effect of daily lithium chloride administration on bone mass and strength in growing broiler chickens.

    Science.gov (United States)

    Harvey, B M; Eschbach, M; Glynn, E A; Kotha, S; Darre, M; Adams, D J; Ramanathan, R; Mancini, R; Govoni, K E

    2015-02-01

    The objective was to determine the effects of oral lithium chloride supplementation on bone strength and mass in broiler chickens. Ninety-six broilers were assigned to 1 of 2 treatment groups (lithium chloride or control; n=48/treatment). Beginning at 1 or 3 wk of age, chickens were administered lithium chloride (20 mg/kg body weight) or water daily by oral gavage. At 6 wk of age, chickens were euthanized and bone and muscle samples were collected. A 24 h lithium chloride (20 mg/kg body weight) challenge determined that serum lithium chloride increased within 2 h and cleared the system within 24 h, demonstrating the effective delivery of lithium chloride. Treatment did not influence body weight (P≥0.20) or feed intake (P≥0.81), demonstrating that lithium chloride did not negatively affect broiler growth. To determine bone strength, 3-point bending was performed on the femora and tibiae obtained from control and lithium chloride-treated birds in the 1 wk group. Lithium chloride-treated birds had a 22% reduction in stiffness compared with control in the femora (P=0.02) without a corresponding reduction in elastic modulus. No differences were observed in yield or ultimate load and in the corresponding calculations of stresses (P≥0.26). The toughness of tibiae was not altered in lithium chloride compared with control (P=0.11). Bone length and micro-CT imaging were performed on the tibiae of control and lithium chloride groups. No differences (P≥0.52) in bone length, cortical or trabecular bone volume, trabecular thickness, number, or spacing were observed. Lithium chloride treatment did not affect pectoralis muscle color or lipid oxidation (P>0.05). In conclusion, lithium chloride treatment in broilers did not negatively affect growth or meat quality. A reduction in bone stiffness of the femur with lithium chloride treatment was observed, however unlike the mouse model, the dosages of lithium chloride used in the current study did not result in anabolic effects

  16. Mesenchymal stromal cells from bone marrow treated with bovine tendon extract acquire the phenotype of mature tenocytes

    OpenAIRE

    Lívia Maria Mendonça Augusto; Diego Pinheiro Aguiar; Danielle Cabral Bonfim; Amanda dos Santos Cavalcanti; Priscila Ladeira Casado; Maria Eugênia Leite Duarte

    2016-01-01

    ABSTRACT OBJECTIVE: This study evaluated in vitro differentiation of mesenchymal stromal cells isolated from bone marrow, in tenocytes after treatment with bovine tendon extract. METHODS: Bovine tendons were used for preparation of the extract and were stored at -80 °C. Mesenchymal stromal cells from the bone marrow of three donors were used for cytotoxicity tests by means of MTT and cell differentiation by means of qPCR. RESULTS: The data showed that mesenchymal stromal cells from bone...

  17. Influence of androgens on bone mass in young women with sickle cell anemia

    International Nuclear Information System (INIS)

    The objective was to evaluate the relationship between the gender hormonal levels and bone mineral density in premenopausal women suffering with sickle cell disease. Method was a cross-sectional study including consecutive female adult patients with sickle cell anemia attending the outpatient hematology/orthopedic clinics, or admitted to King Fahd University Hospital, Al-Khobar, Saudi Arabia, between August 2006 and June 2007. Patient's age was documented and body mass index was calculated. Blood was drawn for complete blood picture, biochemistry and hormonal profile including total estradiol E2 and total testosterone Te. Bone mineral density BMD was measured for all patients using dual energy x-ray absorptiometry scan at the hip and lumbar spine. We analyzed the data of 51 patients with an average age of 26+/-3.1 years. Patients were divided into two groups group A and group B. Group A had normal BMD and group B with low BMD. Thirty-one (60.8%) were in group A and 20 (39.2%) were in group B. The E-2 level was not statistically different between the 2 groups, while Te level was significantly lower in women with low BMD 38+/-11.8 versus 22.3+/-11.7 ng/dl, p<0.001. Our study indicates that in menopausal female patients with sickle cell anemia, testosterone may play a role in the preservation of bone mass. (author)

  18. Vitamin D and estrogen receptor-alpha genotype and indices of bone mass and bone turnover in Danish girls

    DEFF Research Database (Denmark)

    Cusack, S.; Mølgaard, C.; Michaelsen, K. F.;

    2006-01-01

    environmental factors. VDR genotypes had no effect on bone turnover markers. XX and PP ER alpha genotypes were associated (P <0.05) with reduced levels of urinary pyridinium cross-links, whereas serum osteocalcin was similar among genotypes. These findings suggest that the rate of bone resorption was influenced...... (VDR) (FokI, TaqI) and estrogen receptor-alpha (ER alpha) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH)D, and...

  19. High prevalence of low bone mass and associated factors in Korean HIV-positive male patients undergoing antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Pyoeng Gyun Choe

    2014-01-01

    Full Text Available Introduction: Low bone mass is prevalent in HIV-positive patients. However, compared to Western countries, less is known about HIV-associated osteopenia in Asian populations. Methods: We performed a cross-sectional survey in Seoul National University Hospital from December 2011 to May 2012. We measured bone mineral density using central dual energy X-ray absorptiometry, with consent, in male HIV-positive patients, aged 40 years and older. Diagnosis of low bone mass was made using International Society for Clinical Densitometry Z-score criteria in the 40–49 years age group and World Health Organization T-score criteria in the >50-year age group. The data were compared with those of a community-based cohort in Korea. Results: Eighty-four HIV-positive male patients were included in this study. Median age was 49 (interquartile range [IQR], 45–56 years, and median body mass index (BMI was 22.6 (IQR, 20.9–24.4. Viral suppression was achieved in 75 (89.3% patients and median duration of antiretroviral therapy was 71 (IQR, 36–120 months. The overall prevalence of low bone mass was 16.7% in the 40–49 years age group and 54.8% in the>50 years age group. Our cohort had significantly lower bone mass at the femur neck and total hip than HIV-negative Koreans in the 40–49 years age group. Low bone mass was significantly associated with low BMI, and a high level of serum carboxy-terminal collagen crosslinks, but was not associated with antiretroviral regimen or duration of antiretroviral therapy. Conclusions: Low bone mass is prevalent in Korean HIV-positive males undergoing antiretroviral therapy, and may be associated with increased bone resorption.

  20. Phenotypic and functional properties of murine thymocytes. II. Quantitation of host- and donor-derived cytolytic T lymphocyte precursors in regenerating radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Thymocytes from radiation bone marrow chimeras, in which donor bone marrow and irradiated recipient differed at the Thy-1 locus, were stained by indirect immunofluorescence with monoclonal anti-Thy-1 antibodies and analyzed by flow microfluorometry (FMF). Kinetic studies indicated an early appearance of host-derived (CBA, Thy-1.2+) thymocytes, which reaches maximum number of 10 to 20 x 106 cells at 12 to 16 days after bone marrow reconstitution. Donor-derived (AKR, Thy-1.1+) cells were not detectable until 10 to 12 days after reconstitution; subsequently, they increased exponentially in number until 28 days, when they accounted for essentially all cells in the thymus (50 x 106). Concomitant with the appearance and disappearance of host-derived cells was a change in their Thy-1 surface phenotype. In particular, the proportion of host cells having a ''mature'' phenotype (weakly Thy-1.2 staining) increased progressively with time after irradiation. Functional studies using a sensitive mixed leukocyte microculture system to quantitate cytolytic T lymphocyte precursors (CTL-P) were also carried out in regenerating chimeric thymuses. Initially, the regenerating thymus contained few CTL-P, but by 4 wk after reconstitution, frequencies similar to control adult thymuses were obtained. Analysis of the CTL-P content of host and donor-derived subpopulations, separated either by appropriate anti-Thy-1 antibody plus complement or by direct cell sorting, indicated that both host- and donor-derived cells contained appreciable numbers of CTL-P. Furthermore, increases in CTL-P frequency of both host and donor subpopulations correlated with changes in their surface Thy-1 phenotype

  1. Normative Data for Bone Mass in Healthy Term Infants from Birth to 1 Year of Age

    Directory of Open Access Journals (Sweden)

    Sina Gallo

    2012-01-01

    Full Text Available For over 2 decades, dual-energy X-ray absorptiometry (DXA has been the gold standard for estimating bone mineral density (BMD and facture risk in adults. More recently DXA has been used to evaluate BMD in pediatrics. However, BMD is usually assessed against reference data for which none currently exists in infancy. A prospective study was conducted to assess bone mass of term infants (37 to 42 weeks of gestation, weight appropriate for gestational age, and born to healthy mothers. The group consisted of 33 boys and 26 girls recruited from the Winnipeg Health Sciences Center (Manitoba, Canada. Whole body (WB as well as regional sites of the lumbar spine (LS 1–4 and femur was measured using DXA (QDR 4500A, Hologic Inc. providing bone mineral content (BMC for all sites and BMD for spine. During the year, WB BMC increased by 200% (76.0±14.2 versus 227.0±29.7 g, spine BMC by 130% (2.35±0.42 versus 5.37±1.02 g, and femur BMC by 190% (2.94±0.54 versus 8.50±1.84 g. Spine BMD increased by 14% (0.266±0.044 versus 0.304±0.044 g/cm2 during the year. This data, representing the accretion of bone mass during the first year of life, is based on a representative sample of infants and will aid in the interpretation of diagnostic DXA scans by researchers and health professionals.

  2. Split-hand/foot malformation with long-bone deficiency and BHLHA9 duplication: two cases and expansion of the phenotype to radial agenesis.

    Science.gov (United States)

    Petit, Florence; Andrieux, Joris; Demeer, Bénédicte; Collet, Louis-Michel; Copin, Henri; Boudry-Labis, Elise; Escande, Fabienne; Manouvrier-Hanu, Sylvie; Mathieu-Dramard, Michèle

    2013-02-01

    Split-hand/foot malformation (SHFM) with long-bone deficiency (SHFLD, MIM#119100) is a rare condition characterised by SHFM associated with long-bone malformation usually involving the tibia. Previous published data reported several unrelated patients with 17p13.3 duplication and SHFLD. Recently, BHLHA9 has been proposed to be the major candidate gene responsible for this limb malformation. Here we report two new patients affected with ectrodactyly harbouring a 17p13.3 duplication detected by array-CGH. Both duplications contain 3 genes including BHLHA9 and are inherited from an unaffected parent. One of the patients presents a complete radial agenesis, expanding the phenotype of SHFLD3. PMID:23202277

  3. Cognitive function in relation with bone mass and nutrition: cross-sectional association in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Brownbill Rhonda A

    2004-05-01

    Full Text Available Abstract Background It has been suggested that bone loss and cognitive decline are co-occurring conditions, possibly due to their relationship with estrogen. Cognitive decline has been associated with various nutritional deficiencies as well. The purpose of this study was to determine if cognitive function is related to bone mineral density of various skeletal sites as well as to various dietary components. Methods Cross-sectional study with 97 healthy, Caucasian, postmenopausal women (59.4–85.0 years enrolled in a larger longitudinal study, investigating the effects of sodium on bone mass. The subjects were divided into two groups based on cognition scores. Group 1 represented lower and Group 2 higher scores on cognitive function. Bone mineral density from the whole body, lumbar spine, femur and forearm were measured with the Lunar DPX-MD instrument. Anthropometry was measured by standard methods. Cognition was assessed using the Mini Mental State Examination. Cumulative (over 2 years dietary intake from 3-day records was analyzed by Food Processor® (ESHA Research, Salem, OR and cumulative physical activity was assessed using Allied Dunbar National Fitness Survey for older adults. Results Subjects' cognition scores ranged from 22–30 (normal, 27–30, indicating all subjects had either mild or no cognitive impairment. Multiple Analysis of Covariance adjusted for age, height, weight, physical activity, alcohol, calcium, sodium and energy intake, showed a statistically significant association between cognition and bone mineral density of all measurable sites (η2 = 0.21, P 2 = 0.07, P = 0.050. Group 2 did have a significantly higher potassium intake (P = 0.023. In multiple regression, saturated fat had a significant negative relationship with cognitive function. Conclusions It appears mild degree of cognitive impairment may be a marker for lower bone mineral density as well as for a diet lower in carbohydrate and potassium intake, and higher

  4. Transgene silencing of the Hutchinson-Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas resveratrol treatment does not show overall beneficial effects.

    Science.gov (United States)

    Strandgren, Charlotte; Nasser, Hasina Abdul; McKenna, Tomás; Koskela, Antti; Tuukkanen, Juha; Ohlsson, Claes; Rozell, Björn; Eriksson, Maria

    2015-08-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder that is most commonly caused by a de novo point mutation in exon 11 of the LMNA gene, c.1824C>T, which results in an increased production of a truncated form of lamin A known as progerin. In this study, we used a mouse model to study the possibility of recovering from HGPS bone disease upon silencing of the HGPS mutation, and the potential benefits from treatment with resveratrol. We show that complete silencing of the transgenic expression of progerin normalized bone morphology and mineralization already after 7 weeks. The improvements included lower frequencies of rib fractures and callus formation, an increased number of osteocytes in remodeled bone, and normalized dentinogenesis. The beneficial effects from resveratrol treatment were less significant and to a large extent similar to mice treated with sucrose alone. However, the reversal of the dental phenotype of overgrown and laterally displaced lower incisors in HGPS mice could be attributed to resveratrol. Our results indicate that the HGPS bone defects were reversible upon suppressed transgenic expression and suggest that treatments targeting aberrant progerin splicing give hope to patients who are affected by HGPS. PMID:25877214

  5. The cannabinoid receptor type 2 (CNR2) gene is associated with hand bone strength phenotypes in an ethnically homogeneous family sample.

    Science.gov (United States)

    Karsak, Meliha; Malkin, Ida; Toliat, Mohammad R; Kubisch, Christian; Nürnberg, Peter; Zimmer, Andreas; Livshits, Gregory

    2009-11-01

    Genetic variants within the CNR2 gene encoding the cannabinoid receptor CB2 have been shown to be associated with osteoporosis and low bone mineral density (BMD) in case-control studies. We now examined the association of polymorphisms in CNR2 with hand bone strength in an ethnically homogeneous healthy family sample of European origin (Chuvashians) living in Russia. We show that non-synonymous CNR2 SNPs are significantly associated with radiographic hand BMD and breaking bending resistance index (BBRI) by two different transmission disequilibrium tests. For both tests highly significant p values (ranging from 0.007 to 0.008 for hand BMD, and from 0.001 to 0.003 for BBRI) were also obtained with additional SNPs at the CNR2 locus. The associations remained significant after correction for multiple testing. In conclusion, in addition to the association of CNR2 polymorphisms with low BMD at selected clinically relevant skeletal sites, we now report their significant association with hand bone strength phenotypes using a family-based study design implying an even broader impact of genetic variation at the CNR2 locus on bone structure and function. PMID:19565271

  6. Sedentary behaviours and its association with bone mass in adolescents: the HELENA cross-sectional study

    Directory of Open Access Journals (Sweden)

    Gracia-Marco Luis

    2012-11-01

    Full Text Available Abstract Background We aimed to examine whether time spent on different sedentary behaviours is associated with bone mineral content (BMC in adolescents, after controlling for relevant confounders such as lean mass and objectively measured physical activity (PA, and if so, whether extra-curricular participation in osteogenic sports could have a role in this association. Methods Participants were 359 Spanish adolescents (12.5-17.5 yr, 178 boys, from the HELENA-CSS (2006–07. Relationships of sedentary behaviours with bone variables were analysed by linear regression. The prevalence of low BMC (at least 1SD below the mean and time spent on sedentary behaviours according to extracurricular sport participation was analysed by Chi-square tests. Results In boys, the use of internet for non-study was negatively associated with whole body BMC after adjustment for lean mass and moderate to vigorous PA (MVPA. In girls, the time spent studying was negatively associated with femoral neck BMC. Additional adjustment for lean mass slightly reduced the negative association between time spent studying and femoral neck BMC. The additional adjustment for MVPA did not change the results at this site. The percentage of girls having low femoral neck BMC was significantly smaller in those participating in osteogenic sports (≥ 3 h/week than in the rest, independently of the cut-off selected for the time spent studying. Conclusions The use of internet for non-study (in boys and the time spent studying (in girls are negatively associated with whole body and femoral neck BMC, respectively. In addition, at least 3 h/week of extra-curricular osteogenic sports may help to counteract the negative association of time spent studying on bone health in girls.

  7. Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma

    OpenAIRE

    Hansmann, Leo; Blum, Lisa; Ju, Chia-Hsin; Liedtke, Michaela; Robinson, William H; Davis, Mark M.

    2015-01-01

    It would be very beneficial if the status of cancers could be determined from a blood specimen. However, peripheral blood leukocytes are very heterogeneous between individuals and thus high resolution technologies are likely required. We used cytometry by time-of-flight (CyTOF) and next generation sequencing to ask whether a plasma cell cancer (multiple myeloma) and related pre-cancerous states had any consistent effect on the peripheral blood mononuclear cell phenotypes of patients. Analysis...

  8. Trabecular bone mineral density measured by quantitative CT of the lumbar spine in children and adolescents: reference values and peak bone mass

    International Nuclear Information System (INIS)

    Purpose: The aim of this study was to assess bone density values in the trabecular substance of the lumbar vertebral column in children and young adults in Germany from infancy to the age of peak bone mass. Materials and Methods: We performed quantiative computed tomography (QCT) on the first lumbar vertebra in 28 children and adolescents without diseases that may influence bone metabolism (15 boys, 13 girls, mean ages 11 and 8 years, respectively). We also measured 17 healthy young adults (9 men, 8 women, mean ages 20 and 21 years). We used a Somatom Balance Scanner (Siemens, Erlangen) and the Siemens Osteo software. Scan parameters: Slice thickness 1 cm, 80 kV, 81 or 114 mAs. We measured the trabecular bone density and the area and height of the vertebra and calculated the volume and content of calcium hydroxyapatite (Ca-HA) in the trabecular substance of the first lumbar vertebra. Results: Prepubertal boys had a mean bone density of 148.5 (median [med] 150.1, standard deviation [SD] 15.4) mg/Ca-HA per ml bone, and prepubertal girls had a mean density of 149.5 (med 150.8, SD 23.5) mg/ml. We did not observe a difference between prepubertal boys and girls. After puberty there was a significant difference (p<0.001) between males and females: Mean density (male) 158.0, med 162.5, SD 24.0 mg/ml, mean density (female) 191.2, med 191.3, SD 17.7 mg/ml. The Ca-HA content in the trabecular bone of the first lumbar vertebra was 1.1 (med 1.1, SD 0.5) g for prepubertal boys and 1.1 (0.9, 0.4) g for prepubertal girls. For post-pubertal males, the mean Ca-HA content was 3.5 g, med 3.5 SD 0.5 g, and for post-pubertal females, the mean content was 2.8, med 2.7, SD 0.4 g. Conclusion: The normal trabecular bone mineral density is 150 mg/ml with a standard deviation of 20 mg/ml independent of age or gender until the beginning of puberty. Peak bone mass (bone mineral content) in the trabecular substance of the lumbar vertebral column is higher in males than in females, and peak bone

  9. Mesenchymal stromal cells from bone marrow treated with bovine tendon extract acquire the phenotype of mature tenocytes☆

    Science.gov (United States)

    Augusto, Lívia Maria Mendonça; Aguiar, Diego Pinheiro; Bonfim, Danielle Cabral; dos Santos Cavalcanti, Amanda; Casado, Priscila Ladeira; Duarte, Maria Eugênia Leite

    2016-01-01

    Objective This study evaluated in vitro differentiation of mesenchymal stromal cells isolated from bone marrow, in tenocytes after treatment with bovine tendon extract. Methods Bovine tendons were used for preparation of the extract and were stored at −80 °C. Mesenchymal stromal cells from the bone marrow of three donors were used for cytotoxicity tests by means of MTT and cell differentiation by means of qPCR. Results The data showed that mesenchymal stromal cells from bone marrow treated for up to 21 days in the presence of bovine tendon extract diluted at diminishing concentrations (1:10, 1:50 and 1:250) promoted activation of biglycan, collagen type I and fibromodulin expression. Conclusion Our results show that bovine tendon extract is capable of promoting differentiation of bone marrow stromal cells in tenocytes. PMID:26962503

  10. Soccer increases bone mass in prepubescent boys during growth: a 3-yr longitudinal study.

    Science.gov (United States)

    Zouch, Mohamed; Zribi, Anis; Alexandre, Christian; Chaari, Hamada; Frere, Delphine; Tabka, Zouhair; Vico, Laurence

    2015-01-01

    The aim of this study was to examine the effect of 3-yr soccer practice on bone acquisition in prepubescent boys. We investigated 65 boys (aged 10-13 yr, Tanner stage I) at baseline, among which only 40 boys (Tanner stages II and III) have continued the 3-yr follow-up: 23 soccer players (F) completed 2-5 h of training plus 1 competition game per week and 17 controls (C). Bone mineral density (BMD, g/cm(2)) and bone mineral content (BMC, g) were measured by dual-energy X-ray absorptiometry at different sites. At baseline, BMD was higher in soccer players than in controls in the whole body and legs. In contrast, there was nonsignificant difference BMD in head, femoral neck, arms, and BMC in all measured sites between groups. At 3-yr follow-up, soccer players were found to have higher BMD and BMC at all sites than controls, except for head BMD and BMC and arms BMC in which the difference was nonsignificant between groups. During the 3-yr follow-up, the soccer players were found to gain significantly more in lumbar spine (31.2% ± 2.9% vs 23.9% ± 2.1%; p < 0.05), femoral neck (24.1% ± 1.8% vs 11.4% ± 1.9%; p < 0.001), whole body (16.5% ± 1.4% vs 11.8% ± 1.5%; p < 0.05), and nondominant arm BMD (18.2% ± 1.4% vs 13.6% ± 1.7%; p < 0.05) as well as lumbar spine (62.5% ± 20.1% vs 39.5% ± 20.1%; p < 0.001), femoral neck, (37.7% ± 14.2% vs 28.9% ± 12.8%; p < 0.05) and nondominant arm BMC (68.6% ± 22.9% vs 50.1% ± 22.4%; p < 0.05) than controls. In contrast, soccer players have less %BMD and %BMC changes in the head than controls. A nonsignificant difference was found in legs, dominant arm, head %BMD and %BMC changes, and whole-body %BMC changes between groups. In summary, we suggest that soccer has an osteogenic effect BMD and BMC in loaded sites in pubertal soccer players. The increased bone mass induced by soccer training in the stressed sites was associated to a decreased skull bone mass after 3 yr of follow-up. PMID:25592396

  11. Disseminated Breast Cancer Cells Acquire a Highly Malignant and Aggressive Metastatic Phenotype during Metastatic Latency in the Bone

    OpenAIRE

    Marsden, Carolyn G; Wright, Mary Jo; Carrier, Latonya; Moroz, Krzysztof; Rowan, Brian G.

    2012-01-01

    Background Disseminated tumor cells (DTCs) in the bone marrow may exist in a dormant state for extended periods of time, maintaining the ability to proliferate upon activation, engraft at new sites, and form detectable metastases. However, understanding of the behavior and biology of dormant breast cancer cells in the bone marrow niche remains limited, as well as their potential involvement in tumor recurrence and metastasis. Therefore, the purpose of this study was to investigate the tumorig...

  12. A primary phosphorus-deficient skeletal phenotype in juvenile Atlantic salmon Salmo salar: the uncoupling of bone formation and mineralization.

    Science.gov (United States)

    Witten, P E; Owen, M A G; Fontanillas, R; Soenens, M; McGurk, C; Obach, A

    2016-02-01

    To understand the effect of low dietary phosphorus (P) intake on the vertebral column of Atlantic salmon Salmo salar, a primary P deficiency was induced in post-smolts. The dietary P provision was reduced by 50% for a period of 10 weeks under controlled conditions. The animal's skeleton was subsequently analysed by radiology, histological examination, histochemical detection of minerals in bones and scales and chemical mineral analysis. This is the first account of how a primary P deficiency affects the skeleton in S. salar at the cellular and at the micro-anatomical level. Animals that received the P-deficient diet displayed known signs of P deficiency including reduced growth and soft, pliable opercula. Bone and scale mineral content decreased by c. 50%. On radiographs, vertebral bodies appear small, undersized and with enlarged intervertebral spaces. Contrary to the X-ray-based diagnosis, the histological examination revealed that vertebral bodies had a regular size and regular internal bone structures; intervertebral spaces were not enlarged. Bone matrix formation was continuous and uninterrupted, albeit without traces of mineralization. Likewise, scale growth continues with regular annuli formation, but new scale matrix remains without minerals. The 10 week long experiment generated a homogeneous osteomalacia of vertebral bodies without apparent induction of skeletal malformations. The experiment shows that bone formation and bone mineralization are, to a large degree, independent processes in the fish examined. Therefore, a deficit in mineralization must not be the only cause of the alterations of the vertebral bone structure observed in farmed S. salar. It is discussed how the observed uncoupling of bone formation and mineralization helps to better diagnose, understand and prevent P deficiency-related malformations in farmed S. salar. PMID:26707938

  13. Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia

    Directory of Open Access Journals (Sweden)

    Fujiwara S

    2014-11-01

    Full Text Available Saeko Fujiwara,1 Etsuro Hamaya,2 Masayo Sato,2 Peita Graham-Clarke,3 Jennifer A Flynn,2 Russel Burge41Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan; 2Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan; 3Global Health Outcomes, Eli Lilly Australia, Sydney, NSW, Australia; 4Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USAPurpose: To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia.Materials and methods: Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood–lipid profile; occurrence of adverse events; and change in quality of life or pain. Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis.Results: Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications, but not the hip region (eight publications, a low incidence of vertebral fracture (three publications, decreases in markers of bone turnover (eleven publications, improved hip structural geometry (two publications, improved blood–lipid profiles (five publications, a low incidence of hot flushes

  14. Visualizing fossilization using laser ablation-inductively coupled plasma-mass spectrometry maps of trace elements in Late Cretaceous bones

    Science.gov (United States)

    Koenig, A.E.; Rogers, R.R.; Trueman, C.N.

    2009-01-01

    Elemental maps generated by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) provide a previously unavailable high-resolution visualization of the complex physicochemical conditions operating within individual bones during the early stages of diagenesis and fossilization. A selection of LA-ICP-MS maps of bones collected from the Late Cretaceous of Montana (United States) and Madagascar graphically illustrate diverse paths to recrystallization, and reveal unique insights into geochemical aspects of taphonomic history. Some bones show distinct gradients in concentrations of rare earth elements and uranium, with highest concentrations at external bone margins. Others exhibit more intricate patterns of trace element uptake related to bone histology and its control on the flow paths of pore waters. Patterns of element uptake as revealed by LA-ICP-MS maps can be used to guide sampling strategies, and call into question previous studies that hinge upon localized bulk samples of fossilized bone tissue. LA-ICP-MS maps also allow for comparison of recrystallization rates among fossil bones, and afford a novel approach to identifying bones or regions of bones potentially suitable for extracting intact biogeochemical signals. ?? 2009 Geological Society of America.

  15. Disentangling the body weight-bone mineral density association among breast cancer survivors: an examination of the independent roles of lean mass and fat mass

    OpenAIRE

    George, Stephanie M; McTiernan, Anne; Villaseñor, Adriana; Alfano, Catherine M.; Irwin, Melinda L.; Neuhouser, Marian L.; Baumgartner, Richard N.; Baumgartner, Kathy B.; Bernstein, Leslie; Smith, Ashley W.; Ballard-Barbash, Rachel

    2013-01-01

    Abstract Background Bone mineral density (BMD) and lean mass (LM) may both decrease in breast cancer survivors, thereby increasing risk of falls and fractures. Research is needed to determine whether lean mass (LM) and fat mass (FM) independently relate to BMD in this patient group. Methods The Health, Eating, Activity, and Lifestyle Study participants included 599 women, ages 29–87 years, diagnosed...

  16. The relationship between bioactive components in breast milk and bone mass in infants

    Science.gov (United States)

    Casazza, Krista; Hanks, Lynae J; Fields, David A

    2014-01-01

    Human breast milk (HBM) contains numerous bioactive components, recently shown to be associated with growth and body composition in breastfed offspring. Reciprocity in adipogenic and osteogenic pathways suggests bone mass may also be influenced by these components. The association between bioactive components found in HBM and bone mineral content (BMC), to our knowledge, is unknown. The purpose of this proof-of-principle study was to evaluate the association between specific bioactive components in HBM in exclusively breastfed infants and skeletal health in the first 6 months of life and examine potential gender differences in these associations. Thirty-five mother–infant dyads were followed from 1 to 6 months. The contents of a single breast expression were used for analyses of bioactive components (insulin, glucose, leptin, interleukin-6 and tumor necrosis factor-α (TNFα), whereas BMC was evaluated by dual-energy X-ray absorptiometry. In the total sample, there was a positive association between TNFα and BMC at 1 (P=0.004) and 6 months (P=0.007). When stratified by sex, females exhibited a positive association between BMC and glucose and an inverse relationship between BMC and TNF-α at 1 month with TNF-α strengthening (P=0.006) at 6 months. In males, at 6 months a positive relationship between BMC and HBM glucose and an inverse relationship with HBM leptin were observed with no associations observed at 1 month. Although preliminary, the associations between bioactive components in HBM highlight the importance HBM has on bone accretion. It is critically important to identify factors in HBM that contribute to optimal bone health. PMID:25328673

  17. Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis.

    Science.gov (United States)

    Pejoski, David; Tchitchek, Nicolas; Rodriguez Pozo, André; Elhmouzi-Younes, Jamila; Yousfi-Bogniaho, Rahima; Rogez-Kreuz, Christine; Clayette, Pascal; Dereuddre-Bosquet, Nathalie; Lévy, Yves; Cosma, Antonio; Le Grand, Roger; Beignon, Anne-Sophie

    2016-06-01

    Broadening our understanding of the abundance and phenotype of B cell subsets that are induced or perturbed by exogenous Ags will improve the vaccine evaluation process. Mass cytometry (CyTOF) is being used to increase the number of markers that can be investigated in single cells, and therefore characterize cell phenotype at an unprecedented level. We designed a panel of CyTOF Abs to compare the B cell response in cynomolgus macaques at baseline, and 8 and 28 d after the second homologous immunization with modified vaccinia virus Ankara. The spanning-tree progression analysis of density-normalized events (SPADE) algorithm was used to identify clusters of CD20(+) B cells. Our data revealed the phenotypic complexity and diversity of circulating B cells at steady-state and significant vaccine-induced changes in the proportions of some B cell clusters. All SPADE clusters, including those altered quantitatively by vaccination, were characterized phenotypically and compared using double hierarchical clustering. Vaccine-altered clusters composed of previously described subsets including CD27(hi)CD21(lo) activated memory and CD27(+)CD21(+) resting memory B cells, and subphenotypes with novel patterns of marker coexpression. The expansion, followed by the contraction, of a single memory B cell SPADE cluster was positively correlated with serum anti-vaccine Ab titers. Similar results were generated by a different algorithm, automatic classification of cellular expression by nonlinear stochastic embedding. In conclusion, we present an in-depth characterization of B cell subphenotypes and proportions, before and after vaccination, using a two-step clustering analysis of CyTOF data, which is suitable for longitudinal studies and B cell subsets and biomarkers discovery. PMID:27183591

  18. Bone marrow fat.

    Science.gov (United States)

    Hardouin, Pierre; Pansini, Vittorio; Cortet, Bernard

    2014-07-01

    Bone marrow fat (BMF) results from an accumulation of fat cells within the bone marrow. Fat is not a simple filling tissue but is now considered as an actor within bone microenvironment. BMF is not comparable to other fat depots, as in subcutaneous or visceral tissues. Recent studies on bone marrow adipocytes have shown that they do not appear only as storage cells, but also as cells secreting adipokines, like leptin and adiponectin. Moreover bone marrow adipocytes share the same precursor with osteoblasts, the mesenchymal stem cell. It is now well established that high BMF is associated with weak bone mass in osteoporosis, especially during aging and anorexia nervosa. But numerous questions remain discussed: what is the precise phenotype of bone marrow adipocytes? What is the real function of BMF, and how does bone marrow adipocyte act on its environment? Is the increase of BMF during osteoporosis responsible for bone loss? Is BMF involved in other diseases? How to measure BMF in humans? A better understanding of BMF could allow to obtain new diagnostic tools for osteoporosis management, and could open major therapeutic perspectives. PMID:24703396

  19. Dose estimates for patients receiving radiation from various instruments used for measuring bone mass and density

    International Nuclear Information System (INIS)

    The patient dose from in vivo measurement of bone mass and density was estimated by a phantom method. The measurement methods studied were microdensitometry (MD method), single photon absorptiometry (SPA), dual energy X ray absorptiometry (DEXA), quantitative computed tomography (QCT) and conventional X-ray photography (X-P) for vertebrae, all of which have been used for mass screening or clinical examination of osteoporosis. The organ absorbed doses from the QCT and X ray photography were several mSv and these values were one to two orders of magnitude higher than those from the DEXA method. The effective dose and entrance skin dose from the QCT and X ray photography were one to two orders of magnitude higher than the DEXA, which were μSv and some ten μSv, respectively. The application of X-P and QCT for a young population should be carefully judged. (author)

  20. Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men

    NARCIS (Netherlands)

    Bravenboer, N; Holzmann, PJ; ter Maaten, JC; Stuurman, LM; Roos, JC; Lips, P

    2005-01-01

    Long-term GH treatment in GH-deficient men resulted in a continuous increase in bone turnover as shown by histomorphometry. BMD continuously increased in all regions of interest, but more in the regions with predominantly cortical bone. Introduction: Adults with growth hormone (GH) deficiency have r

  1. Bone mineral density, body mass index and cigarette smoking among Iranian women: implications for prevention

    Directory of Open Access Journals (Sweden)

    Nguyen Nguyen D

    2005-06-01

    Full Text Available Abstract Background While risk factors of osteoporosis in Western populations have been extensively documented, such a profile has not been well studied in Caucasians of non-European origin. This study was designed to estimate the modifiable distribution and determinants of bone mineral density (BMD among Iranian women in Australia. Methods Ninety women aged 35 years and older completed a questionnaire on socio-demographic and lifestyle factors. BMD was measured at the lumbar spine (LS and femoral neck (FN using DXA (GE Lunar, WI, USA, and was expressed in g/cm2 as well as T-score. Results In multiple regression analysis, advancing age, lower body mass index (BMI, and smoking were independently associated with LS and FN BMD, with the 3 factors collectively accounting for 30% and 38% variance of LS and FN BMD, respectively. LS and FN BMD in smokers was 8% lower than that in non-smokers. Further analysis of interaction between BMI and smoking revealed that the effect of smoking was only observed in the obese group (p = 0.029 for LSBMD and p = 0.007 for FNBMD, but not in the overweight and normal groups. Using T-scores from two bone sites the prevalence of osteoporosis (T-scores ≤ -2.5 was 3.8% and 26.3% in pre-and post-menopausal women, respectively. Among current smokers, the prevalence was higher (31.3% than that among ex-smokers (28.6% and non-smokers (7.5%. Conclusion These data, for the first time, indicate that apart from advancing age and lower body mass index, cigarette smoking is an important modifiable determinant of bone mineral density in these Caucasians of non-European origin.

  2. Clinical and hormonal variables related to bone mass loss in anorexia nervosa patients.

    Science.gov (United States)

    Fernández-Soto, María Luisa; González-Jiménez, Amalia; Chamorro-Fernández, Marta; Leyva-Martínez, Socorro

    2013-01-01

    A better understanding of the prognostic factors of low bone mass in anorexia nervosa (AN) and development of effective therapeutic strategies is critical. In order to determine which clinical, biochemical, and/or hormonal parameters could be related to bone mineral density (BMD), 47 female AN patients were classified according to the WHO osteoporosis criteria at lumbar spine (LS). This was a cross-sectional study of 16 AN women with osteoporosis criteria and 31without. Control group was 25 healthy, normal-weight, age-matched women. We assessed BMD using dual-energy X-ray absorptiometry at the LS and body composition. We measured serum fasting cortisol, estradiol, insulin-like growth factor-1 (IGF-1), leptin, sex hormone-binding globulin, albumin and retinol binding protein levels. The prevalence of osteoporosis was 34% and osteopenia 19% at the LS. The AN group with osteoporosis had lower IGF-1 and estradiol levels (both posteoporosis. The BMD and T-score at LS was inversely related to the duration of amenorrhea (posteoporosis. A low BMD is a consequence of hormonal alterations which include hypoestrogenism, hypoleptinemia, hypercortisolism, and decreases in IGF-1 levels, as well as a low BMI and fat mass. PMID:23601428

  3. Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma

    Science.gov (United States)

    Hansmann, Leo; Blum, Lisa; Ju, Chia-Hsin; Liedtke, Michaela; Robinson, William H.; Davis, Mark M.

    2015-01-01

    It would be very beneficial if the status of cancers could be determined from a blood specimen. However, peripheral blood leukocytes are very heterogeneous between individuals and thus high resolution technologies are likely required. We used cytometry by time-of-flight (CyTOF) and next generation sequencing to ask whether a plasma cell cancer (multiple myeloma) and related pre-cancerous states had any consistent effect on the peripheral blood mononuclear cell phenotypes of patients. Analysis of peripheral blood samples from 13 cancer patients, 9 pre-cancer patients, and 9 healthy individuals revealed significant differences in the frequencies of the T, B, and natural killer cell compartments. Most strikingly, we identified a novel B-cell population that normally accounts for 4.0±0.7% (mean±SD) of total B cells and is up to 13-fold expanded in multiple myeloma patients with active disease. This population expressed markers previously associated with both memory (CD27+) and naïve (CD24loCD38+) phenotypes. Single-cell immunoglobulin gene sequencing showed polyclonality, indicating that these cells are not precursors to the myeloma, and somatic mutations, a characteristic of memory cells. SYK, ERK, and p38 phosphorylation responses, and the fact that most of these cells expressed isotypes other than IgM or IgD, confirmed the memory character of this population, defining it as a novel type of memory B cells. PMID:25711758

  4. Phenotyping of Live Human PBMC using CyTOF™ Mass Cytometry

    OpenAIRE

    Leipold, Michael D.; Maecker, Holden T.

    2015-01-01

    Single-cell analysis has become an method of importance in immunology. Fluorescence flow cytometry has been a major player. However, due to issues such as autofluorescence and emission spillover between different fluorophores, alternative techniques are being developed. In recent years, mass cytometry has emerged, wherein antibodies labeled with metal ions are detected by ICP-MS. In order for a cell to be seen, a metal in the mass window must be present; there is no analogous parameter to for...

  5. Activation of Natural Killer Cells in Patients with Chronic Bone and Joint Infection due to Staphylococci Expressing or Not the Small Colony Variant Phenotype

    Directory of Open Access Journals (Sweden)

    Sébastien Viel

    2014-01-01

    Full Text Available Chronic bone and joint infections (BJI are devastating diseases. Relapses are frequently observed, as some pathogens, especially staphylococci, can persist intracellularly by expressing a particular phenotype called small colony variant (SCV. As natural killer (NK cells are lymphocytes specialized in the killing of host cells infected by intracellular pathogens, we studied NK cells of patients with chronic BJI due to staphylococci expressing or not SCVs (10 patients in both groups. Controls were patients infected with other bacteria without detectable expression of SCVs, and healthy volunteers. NK cell phenotype was evaluated from PBMCs by flow cytometry. Degranulation capacity was evaluated after stimulation with K562 cells in vitro. We found that NK cells were activated in terms of CD69 expression, loss of CD16 and perforin, in all infected patients in comparison with healthy volunteers, independently of the SCV phenotype. Peripheral NK cells in patients with chronic BJI display signs of recent activation and degranulation in vivo in response to CD16-mediated signals, regardless of the type of bacteria involved. This could involve a universal capacity of isolates responsible for chronic BJI to produce undetectable SCVs in vivo, which might be a target of future intervention.

  6. Interferon-γ and Tumor Necrosis Factor-α Polarize Bone Marrow Stromal Cells Uniformly to a Th1 Phenotype.

    Science.gov (United States)

    Jin, Ping; Zhao, Yuanlong; Liu, Hui; Chen, Jinguo; Ren, Jiaqiang; Jin, Jianjian; Bedognetti, Davide; Liu, Shutong; Wang, Ena; Marincola, Francesco; Stroncek, David

    2016-01-01

    Activated T cells polarize mesenchymal stromal cells (MSCs) to a proinflammatory Th1 phenotype which likely has an important role in amplifying the immune response in the tumor microenvironment. We investigated the role of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), two factors produced by activated T cells, in MSC polarization. Gene expression and culture supernatant analysis showed that TNF-α and IFN-γ stimulated MSCs expressed distinct sets of proinflammatory factors. The combination of IFN-γ and TNF-α was synergistic and induced a transcriptome most similar to that found in MSCs stimulated with activated T cells and similar to that found in the inflamed tumor microenvironment; a Th1 phenotype with the expression of the immunosuppressive factors IL-4, IL-10, CD274/PD-L1 and indoleamine 2,3 dioxygenase (IDO). Single cell qRT-PCR analysis showed that the combination of IFN-γ and TNF-α polarized uniformly to this phenotype. The combination of IFN-γ and TNF-α results in the synergist uniform polarization of MSCs toward a primarily Th1 phenotype. The stimulation of MSCs by IFN-γ and TNF-α released from activated tumor infiltrating T cells is likely responsible for the production of many factors that characterize the tumor microenvironment. PMID:27211104

  7. Cluster analysis of bone microarchitecture from high resolution peripheral quantitative computed tomography demonstrates two separate phenotypes associated with high fracture risk in men and women.

    Science.gov (United States)

    Edwards, M H; Robinson, D E; Ward, K A; Javaid, M K; Walker-Bone, K; Cooper, C; Dennison, E M

    2016-07-01

    Osteoporosis is a major healthcare problem which is conventionally assessed by dual energy X-ray absorptiometry (DXA). New technologies such as high resolution peripheral quantitative computed tomography (HRpQCT) also predict fracture risk. HRpQCT measures a number of bone characteristics that may inform specific patterns of bone deficits. We used cluster analysis to define different bone phenotypes and their relationships to fracture prevalence and areal bone mineral density (BMD). 177 men and 159 women, in whom fracture history was determined by self-report and vertebral fracture assessment, underwent HRpQCT of the distal radius and femoral neck DXA. Five clusters were derived with two clusters associated with elevated fracture risk. "Cluster 1" contained 26 women (50.0% fractured) and 30 men (50.0% fractured) with a lower mean cortical thickness and cortical volumetric BMD, and in men only, a mean total and trabecular area more than the sex-specific cohort mean. "Cluster 2" contained 20 women (50.0% fractured) and 14 men (35.7% fractured) with a lower mean trabecular density and trabecular number than the sex-specific cohort mean. Logistic regression showed fracture rates in these clusters to be significantly higher than the lowest fracture risk cluster [5] (pfemoral neck areal BMD was significantly lower than cluster 5 in women in cluster 1 and 2 (p<0.001 for both), and in men, in cluster 2 (p<0.001) but not 1 (p=0.220). In conclusion, this study demonstrates two distinct high risk clusters in both men and women which may differ in etiology and response to treatment. As cluster 1 in men does not have low areal BMD, these men may not be identified as high risk by conventional DXA alone. PMID:27130873

  8. Reduced Bone and Body Mass in Young Male Rats Exposed to Lead

    Directory of Open Access Journals (Sweden)

    Fellipe Augusto Tocchini de Figueiredo

    2014-01-01

    Full Text Available The aim of this study was to see whether there would be differences in whole blood versus tibia lead concentrations over time in growing rats prenatally. Lead was given in the drinking water at 30 mg/L from the time the dams were pregnant until offspring was 28- or 60-day-old. Concentrations of lead were measured in whole blood and in tibia after 28 (28D and 60 days (60D in control (C and in lead-exposed animals (Pb. Lead measurements were made by GF-AAS. There was no significant difference (P>0.05 in the concentration of whole blood lead between Pb-28D (8.0±1.1 μg/dL and Pb-60D (7.2±0.89 μg/dL, while both significantly varied (P<0.01 from controls (0.2 μg/dL. Bone lead concentrations significantly varied between the Pb-28D (8.02±1.12 μg/g and the Pb-60D (43.3±13.26 μg/g lead-exposed groups (P<0.01, while those exposed groups were also significantly higher (P<0.0001 than the 28D and 60D control groups (Pb < 1 μg/g. The Pb-60D group showed a 25% decrease in tibia mass as compared to the respective control. The five times higher amount of lead found in the bone of older animals (Pb-60D versus Pb-28D, which reinforces the importance of using bone lead as an exposure biomarker.

  9. Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.

    Science.gov (United States)

    Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Li, Feijiang; Xu, Qiaoling; Xie, Kangning; Tang, Chi; Liu, Juan; Guo, Wei; Wu, Xiaoming; Jiang, Maogang; Luo, Erping

    2014-10-01

    A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, β-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities

  10. Differential diagnosis between chronic otitis media with and without cholesteatoma by temporal bone CT: focus on bone change and mass effect

    International Nuclear Information System (INIS)

    %, 9%) were more common in COM with cholesteatoma (p-value less than 0.05). Soft tissue in Prussak's space (58%, 72%), retraction of the tympanic membrane (19%, 9%), and tympanosclerosis (8%, 10%) were not however, important findings (p-value greater than 0.05). Bone erosion or destruction was seen in COM without cholesteatoma, but expansile bone erosion or destruction with mass effect suggested COM with cholesteatoma. These findings of temporal bone CT in COM demonstrate the existence and extent of combined cholesteatoma, and are therefore valuable. (author)

  11. Consumption of different sources of omega-3 polyunsaturated fatty acids by growing female rats affects long bone mass and microarchitecture.

    Science.gov (United States)

    Lukas, Robin; Gigliotti, Joseph C; Smith, Brenda J; Altman, Stephanie; Tou, Janet C

    2011-09-01

    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) consumption has been reported to improve bone health. However, sources of ω-3 PUFAs differ in the type of fatty acids and structural form. The study objective was to determine the effect of various ω-3 PUFAs sources on bone during growth. Young (age 28d) female Sprague-Dawley rats were randomly assigned (n=10/group) to a high fat 12% (wt) diet consisting of either corn oil (CO) or ω-3 PUFA rich, flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) for 8 weeks. Bone mass was assessed by dual-energy X-ray absorptiometry (DXA) and bone microarchitecture by micro-computed tomography (μCT). Bone turnover markers were measured by enzyme immunoassay. Lipid peroxidation was measured by calorimetric assays. Results showed that rats fed TO, rich in docosahexaenoic acid (DHA, 22:6ω-3) had higher (P<0.009) tibial bone mineral density (BMD) and bone mineral content (BMC) and lower (P=0.05) lipid peroxidation compared to the CO-fed rats. Reduced lipid peroxidation was associated with increased tibial BMD (r2=0.08, P=0.02) and BMC (r2=0.71, P=0.01). On the other hand, rats fed FO or MO, rich in alpha-linolenic acid (ALA, 18:3ω-3), improved bone microarchitecture compared to rats fed CO or SO. Serum osteocalcin was higher (P=0.03) in rats fed FO compared to rats fed SO. Serum osteocalcin was associated with improved trabecular bone microarchitecture. The animal study results suggest consuming a variety of ω-3 PUFA sources to promote bone health during the growth stage. PMID:21672645

  12. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations.

    Science.gov (United States)

    Weaver, C M; Gordon, C M; Janz, K F; Kalkwarf, H J; Lappe, J M; Lewis, R; O'Karma, M; Wallace, T C; Zemel, B S

    2016-04-01

    Lifestyle choices influence 20-40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. Lifestyle Factor Grade Macronutrients  Fat D  Protein C Micronutrients  Calcium A  Vitamin D B  Micronutrients other than calcium and vitamin D D Food Patterns  Dairy B  Fiber C  Fruits and vegetables C  Detriment of cola and

  13. Determination of peak bone mass density and composition in low-income urban residents of metro Manila using isotope techniques

    International Nuclear Information System (INIS)

    Filipinos are predisposed to osteoporosis because of inadequate calcium in their diet early on in life, confounded by malnutrition, susceptibility to infectious diseases and their generally small body frame. And yet the problem of osteoporosis has not been properly addressed. The incidence of osteoporosis is not known since oftentimes it is established only once complications have set in. It is believed that osteoporosis poses a public health concern but its extent is not realized at present because of lack of local epidemiological data. This study aims to determine the bone mass density as a function of age among 210 screened and healthy volunteers coming from urban poor communities of Metro Manila over a 3-year period. A LUNAR DPX-L bone densitometry for dual X-ray photon absorptiometry will be used, with measurements taken on the spine and femur. It also aims to correlate factors such as nutritional intake, physical activity, lifestyle, sex and body mass index with that of bone mass density. Blood and urine samples will be obtained for biochemistry and hormonal radioimmunoassay examination. Statistical analysis will be done to com are differences within the group and to determine rate of bone loss as a function of age and sex. Plans for future research include the determination of trace element content in cortical bone and tooth samples from healthy living subjects. (author)

  14. Pb distribution in bones from the Franklin expedition: synchrotron X-ray fluorescence and laser ablation/mass spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Ronald Richard; Naftel, Steven; Macfie, Sheila; Jones, Keith; Nelson, Andrew [The University of Western Ontario, London, ON (Canada)

    2013-04-15

    Synchrotron micro-X-ray Fluorescence has been used to map the metal distribution in selected bone fragments representative of remains associated with the Franklin expedition. In addition, laser ablation mass spectroscopy using a 25 {mu}m diameter circular spot was employed to compare the Pb isotope distributions in small regions within the bone fragments. The X-ray Fluorescence mapping shows Pb to be widely distributed in the bone while the Pb isotope ratios obtained by laser ablation within small areas representative of bone with different Pb exchange rates do not show statistically significant differences. These results are inconsistent with the hypothesis that faulty solder seals in tinned meat were the principle source of Pb in the remains of the expedition personnel. (orig.)

  15. Niacin and olive oil promote skewing to the M2 phenotype in bone marrow-derived macrophages of mice with metabolic syndrome.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Naranjo, Maria C; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G; Bermudez, Beatriz

    2016-05-18

    Metabolic syndrome (MetS) is associated with obesity, dyslipemia, type 2 diabetes and chronic low-grade inflammation. The aim of this study was to determine the role of high-fat low-cholesterol diets (HFLCDs) rich in SFAs (HFLCD-SFAs), MUFAs (HFLCD-MUFAs) or MUFAs plus omega-3 long-chain PUFAs (HFLCD-PUFAs) on polarisation and inflammatory potential in bone marrow-derived macrophages (BMDMs) from niacin (NA)-treated Lep(ob/ob)LDLR(-/-) mice. Animals fed with HFLCD-SFAs had increased weight and serum triglycerides, and their BMDMs accumulated triglycerides over the animals fed with HFLCD-MUFAs or -PUFAs. Furthermore, BMDMs from animals fed with HFLCD-SFAs were polarised towards the M1 phenotype with functional competence to produce pro-inflammatory cytokines, whereas BMDMs from animals fed with HFLCD-MUFAs or -PUFAs were skewed to the anti-inflammatory M2 phenotype. These findings open opportunities for developing novel nutritional strategies with olive oil as the most important dietary source of MUFAs (notably oleic acid) to prevent development and progression of metabolic complications in the NA-treated MetS. PMID:27116638

  16. Effect of chronic undernutrition on body mass and mechanical bone quality under normoxic and altitude hypoxic conditions.

    Science.gov (United States)

    Lezon, Christian; Bozzini, Clarisa; Agûero Romero, Alan; Pinto, Patricia; Champin, Graciela; Alippi, Rosa M; Boyer, Patricia; Bozzini, Carlos E

    2016-05-01

    Both undernutrition and hypoxia exert a negative influence on both growth pattern and bone mechanical properties in developing rats. The present study explored the effects of chronic food restriction on both variables in growing rats exposed to simulated high-altitude hypoxia. Male rats (n 80) aged 28 d were divided into normoxic (Nx) and hypoxic (Hx) groups. Hx rats were exposed to hypobaric air (380 mmHg) in decompression chambers. At T0, Nx and Hx rats were subdivided into four equal subgroups: normoxic control and hypoxic controls, and normoxic growth-restricted and hypoxic growth-restricted received 80 % of the amount of food consumed freely by their respective controls for a 4-week period. Half of these animals were studied at the end of this period (T4). The remaining rats in each group continued under the same environmental conditions, but food was offered ad libitum to explore the type of catch-up growth during 8 weeks. Structural bone properties (strength and stiffness) were evaluated in the right femur midshaft by the mechanical three-point bending test; geometric properties (length, cross-sectional area, cortical mass, bending cross-sectional moment of inertia) and intrinsic properties of the bone tissue (elastic modulus) were measured or derived from appropriate equations. Bone mineralisation was assessed by ash measurement of the left femur. These data indicate that the growth-retarded effects of diminished food intake, induced either by food restriction or hypoxia-related inhibition of appetite, generated the formation of corresponding smaller bones in which subnormal structural and geometric properties were observed. However, they seemed to be appropriate to the body mass of the animals and suggest, therefore, that the bones were not osteopenic. When food restriction was imposed in Hx rats, the combined effects of both variables were additive, inducing a further reduction of bone mass and bone load-carrying capacity. In all cases, the mechanical

  17. Bone Mass and Turnover in Women with Epilepsy on Antiepileptic Drug Monotherapy

    OpenAIRE

    Pack, Alison M.; Morrell, Martha J.; Marcus, Robert; Holloway, Leah; Flaster, Edith; Doñe, Silvia; Randall, Alison; Seale, Cairn; Shane, Elizabeth

    2005-01-01

    Antiepileptic drugs, particularly cytochrome P450 enzyme inducers, are associated with disorders of bone metabolism. We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine). Subjects completed exercise and nutrition questionnaires and bone mineral density studies. Serum was analyzed for indices of bone metabolism including calcium, 25-hydroxyvitamin D, parathyroid hormone, insulin growth factor I, insulin bin...

  18. Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments

    Directory of Open Access Journals (Sweden)

    Sanna Maria

    2006-02-01

    Full Text Available Abstract Background It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential. Results In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC. Cells were treated with: (1 TPA, forskolin, IBMX, FGF-1 or (2 retinoic acid and 2-mercaptoethanol (BME. Treatment (1 induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1 compared with treatment (2. In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments. Conclusion Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage.

  19. Strategies for the chemical analysis of highly porous bone scaffolds using secondary ion mass spectrometry

    International Nuclear Information System (INIS)

    Understanding the distribution of critical elements (e.g. silicon and calcium) within silica-based bone scaffolds synthesized by different methods is central to the optimization of these materials. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has been used to determine this information due to its very high surface sensitivity and its ability to map all the elements and compounds in the periodic table with high spatial resolution. The SIMS image data can also be combined with depth profiles to construct three-dimensional chemical maps. However, the scaffolds have interconnected pore networks, which are very challenging structures for the SIMS technique. To overcome this problem two experimental methodologies have been developed. The first method involved the use of the focused ion beam technique to obtain clear images of the regions of interest and subsequently mark them by introducing fiducial marks; the samples were then analysed using the ToF-SIMS technique to yield the chemical analyses of the regions of interest. The second method involved impregnating the pores using a suitable reagent so that a flat surface could be achieved, and this was followed by secondary ion mapping and 3D chemical imaging with ToF-SIMS. The samples used in this work were sol–gel 70S30C foam and electrospun fibres and calcium-containing silica/gelatin hybrid scaffolds. The results demonstrate the feasibility of both these experimental methodologies and indicate that these methods can provide an opportunity to compare various artificial bone scaffolds, which will be of help in improving scaffold synthesis and processing routes. The techniques are also transferable to many other types of porous material. (paper)

  20. Current socio-economic measures, and not those measured during infancy, affect bone mass in poor urban South african children.

    Science.gov (United States)

    Norris, Shane A; Sheppard, Zoë A; Griffiths, Paula L; Cameron, Noël; Pettifor, John M

    2008-09-01

    Understanding the impact of socio-economic status (SES) on physical development in children is important, especially in developing countries where considerable inequalities persist. This is the first study to examine the association between SES on bone development at the whole body, femoral neck, and lumbar spine in black children living in Soweto and Johannesburg, South Africa. Linear regression models were used to study associations between SES during infancy and current SES, anthropometric, and DXA-derived bone mass in 9/10-yr-old children (n = 309). Findings suggest that current SES measures, rather than SES during infancy, are stronger predictors of current whole body bone area (BA) and whole body BMC after adjusting for body size, pubertal development, physical activity, habitual dietary calcium intake, and body composition. SES had no significant effect on either hip or spine bone mass. Caregiver's marital/cohabiting status (indicator of social support) and whether there was a television in the home (indicator of greater income) at age 9/10 yr were the most important socio-economic determinants of whole body BA and BMC. SES has a significant independent effect on whole body BMC through its impact on BA. This suggests that poverty alleviation policies in South Africa could have a positive effect on bone health. PMID:18442310

  1. Dinosaur bone beds and mass mortality: Implications for the K-T extinction

    Science.gov (United States)

    Carpenter, Kenneth

    1988-01-01

    Mass accumulations of fossilized large terrestrial vertebrate skeletons (bone beds: BB) provide a test for K-T catastrophic extinction hypotheses. The two major factors contributing to BB formation are mode of death and sedimentation rate. Catastrophic mass mortality (CMM) is the sudden death of numerous individuals where species, age, health, gender, or social ranking offer no survivorship advantage. Noncatastrophic mass mortality (NCMM) occurs over time and is strongly influenced by species, age, or gender. In addition to cause of death, sedimentation rate is also important in BB formation. Models of BBs can be made. The CMM drops all individuals in their tracks, therefore, the BB should reflect the living population with respect to species, age, or gender. The NCMM results in monospecific BBs skewed in the direction of the less fit, usually the very young or very old, or towards a specific gender. The NCMM and AM BBs may become more similar the more spread out over time NCMM deaths occur because carcasses are widely scattered requiring hydraulic accumulation, and the greater time allows for more disarticulation and weathering. The CMM and NCMM BB appear to be dominated by social animals. Applying this and the characteristics of mortality patterns to the uppermost Cretaceous Hell Creek Formation indicates that only NCMM and AM BB occur. Furthermore, NCMM BB are rare in the upper third of the Hell Creek. Near the K-T boundary, only AM BB are known. The absence of CMM and NCMM BB appears to be real reflecting a decrease in population levels of some dinosaurs prior to the K-T event. The absence of CMM suggests that the K-T event did not lead to an instantaneous extinction of dinosaurs. Nor was there a protracted die-off due to an asteroid impact winter, because no NCMM BB are known at or near the K-T boundary.

  2. Characterization of lung infection-induced TCRγδ T cell phenotypes by CyTOF mass cytometry.

    Science.gov (United States)

    Wanke-Jellinek, Lorenz; Keegan, Joshua W; Dolan, James W; Lederer, James A

    2016-03-01

    T cell receptor γδ cells are known to be the primary effector T cells involved in the response to bacterial infections, yet their phenotypic characteristics are not as well established as other T cell subsets. In this study, we used cytometry by time-of-flight mass cytometry to better characterize the phenotypic response of T cell receptor γδ cells to Streptococcus pneumoniae lung infection. Mice were infected, and cells from lung washouts, spleen, and lymph nodes were stained to detect cell-surface, intracellular, and signaling markers. We observed that infection caused a significant increase in T cell receptor γδ cells, which expressed high interferon-γ and interleukin-17A levels. Profiling T cell receptor γδ cells by cytometry by time-of-flight revealed that activated γδ T cells uniquely coexpressed cell-surface Gr-1, cluster of differentiation 14, and cluster of differentiation 274 (programmed death-ligand 1). Further classification of Gr-1 expression patterns on T cell receptor γδ cells demonstrated that Gr-1(+) T cell receptor γδ cells were the primary source of interferon-γ, whereas Gr-1(-) cells mostly expressed interleukin-17A. Gr-1(+) T cell receptor γδ cells also showed higher ζ-chain-associated protein kinase 70, p38, and 4eBP1 signaling in response to infection as compared with Gr-1(-) T cell receptor γδ cells. Taken together, Gr-1 expression patterns on γδ T cells in the lung provide a robust marker to differentiate interferon-γ- and interleukin-17A-producing subsets involved in the early immune response to bacterial pneumonia. PMID:26428679

  3. Control of bone resorption by semaphorin 4D is dependent on ovarian function.

    Directory of Open Access Journals (Sweden)

    Romain Dacquin

    Full Text Available Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that the immune semaphorin 4D (Sema4D is a novel factor controlling bone resorption. Sema4D-deficient primary osteoclasts showed impaired spreading, adhesion, migration and resorption due to altered ß3 integrin sub-unit downstream signaling. In apparent accordance with these in vitro results, Sema4D deletion in sexually mature female mice led to a high bone mass phenotype due to defective bone resorption by osteoclasts. Mutant males, however, displayed normal bone mass and the female osteopetrotic phenotype was only detected at the onset of sexual maturity, indicating that, in vivo, this intrinsic osteoclast defect might be overcome in these mice. Using bone marrow cross transplantation, we confirmed that Sema4D controls bone resorption through an indirect mechanism. In addition, we show that Sema4D -/- mice were less fertile than their WT littermates. A decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian follicles can explain this attenuated fertility. Interestingly, ovariectomy abrogated the bone resorption phenotype in Sema4D -/- mice, providing the evidence that the observed high bone mass phenotype is strictly dependent on ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an indirect regulator of bone resorption, which acts via its effect on reproductive function.

  4. Effects of Habitual Physical Activity and Fitness on Tibial Cortical Bone Mass, Structure and Mass Distribution in Pre-pubertal Boys and Girls: The Look Study.

    Science.gov (United States)

    Duckham, Rachel L; Rantalainen, Timo; Ducher, Gaele; Hill, Briony; Telford, Richard D; Telford, Rohan M; Daly, Robin M

    2016-07-01

    Targeted weight-bearing activities during the pre-pubertal years can improve cortical bone mass, structure and distribution, but less is known about the influence of habitual physical activity (PA) and fitness. This study examined the effects of contrasting habitual PA and fitness levels on cortical bone density, geometry and mass distribution in pre-pubertal children. Boys (n = 241) and girls (n = 245) aged 7-9 years had a pQCT scan to measure tibial mid-shaft total, cortical and medullary area, cortical thickness, density, polar strength strain index (SSIpolar) and the mass/density distribution through the bone cortex (radial distribution divided into endo-, mid- and pericortical regions) and around the centre of mass (polar distribution). Four contrasting PA and fitness groups (inactive-unfit, inactive-fit, active-unfit, active-fit) were generated based on daily step counts (pedometer, 7-days) and fitness levels (20-m shuttle test and vertical jump) for boys and girls separately. Active-fit boys had 7.3-7.7 % greater cortical area and thickness compared to inactive-unfit boys (P fitness categories in girls, but active-fit girls had 6.1 % (P fit girls, which was likely due to their 6.7 % (P fit girls. Higher levels of habitual PA-fitness were associated with small regional-specific gains in 66 % tibial cortical bone mass in pre-pubertal children, particularly boys. PMID:26983726

  5. Modeling the effect of levothyroxine therapy on bone mass density in postmenopausal women: a different approach leads to new inference

    Directory of Open Access Journals (Sweden)

    Tavangar Seyed

    2007-06-01

    Full Text Available Abstract Background The diagnosis, treatment and prevention of osteoporosis is a national health emergency. Osteoporosis quietly progresses without symptoms until late stage complications occur. Older patients are more commonly at risk of fractures due to osteoporosis. The fracture risk increases when suppressive doses of levothyroxine are administered especially in postmenopausal women. The question is; "When should bone mass density be tested in postmenopausal women after the initiation of suppressive levothyroxine therapy?". Standard guidelines for the prevention of osteoporosis suggest that follow-up be done in 1 to 2 years. We were interested in predicting the level of bone mass density in postmenopausal women after the initiation of suppressive levothyroxine therapy with a novel approach. Methods The study used data from the literature on the influence of exogenous thyroid hormones on bone mass density. Four cubic polynomial equations were obtained by curve fitting for Ward's triangle, trochanter, spine and femoral neck. The behaviors of the models were investigated by statistical and mathematical analyses. Results There are four points of inflexion on the graphs of the first derivatives of the equations with respect to time at about 6, 5, 7 and 5 months. In other words, there is a maximum speed of bone loss around the 6th month after the start of suppressive L-thyroxine therapy in post-menopausal women. Conclusion It seems reasonable to check bone mass density at the 6th month of therapy. More research is needed to explain the cause and to confirm the clinical application of this phenomenon for osteoporosis, but such an approach can be used as a guide to future experimentation. The investigation of change over time may lead to more sophisticated decision making in a wide variety of clinical problems.

  6. The Ca, Cl, Mg, Na, and P mass fractions in benign and malignant giant cell tumors of bone investigated by neutron activation analysis

    International Nuclear Information System (INIS)

    The Ca, Cl, Mg, Na, and P content and Ca/P, Ca/Mg, Ca/Na, Cl/Ca, and Cl/Na ratios in samples of intact bone, benign and malignant giant cell tumor (GCT) of bone were investigated by neutron activation analysis with high resolution spectrometry of short-lived radionuclides. It was found that in GCT tissue the mass fractions of Cl and Na are higher and the mass fraction of Ca and P are lower than in normal bone tissues. Moreover, it was shown that higher Cl/Na mass fraction ratios as well as lower Ca/Cl, Ca/Mg, and Ca/Na mass fraction ratios are typical of the GCT tissue compared to intact bone. Finally, we propose to use the estimation of such parameters as the Cl mass fraction and the Ca/Cl mass fraction ratio as an additional test for differential diagnosis between benign and malignant GCT. (author)

  7. Palaeoecological and morphofunctional interpretation of bone mass increase: an example in Late Cretaceous shallow marine squamates.

    Science.gov (United States)

    Houssaye, Alexandra

    2013-02-01

    Bone mass increase (BMI; i.e. osteosclerosis with possible additional pachyostosis) is characteristically displayed by many Late Cretaceous squamates that adapted to shallow marine environments-plesiopelvic mosasauroids, stem-ophidians and pachyophiids. A combined morphological and microanatomical analysis of vertebrae and, to a lesser extent, ribs of these fossil squamates provides new data about the distribution and variability of this osseous specialization in these taxa. Classical thin sections and third generation synchrotron microtomography and laminography were used for the microanatomical analysis. Following the explanation of the likely involvement of this specialization in the control of buoyancy, body trim and Carrier's constraint, new palaeoecological inferences and new hypotheses about the locomotor abilities and life environment of these organisms are produced. The taxa displaying BMI are considered to have undertaken long dives, hovering slowly and maintaining a horizontal trim, in shallow and protected water environments. Conversely, marine stem-ophidians deprived of this specialization are regarded as slow surface swimmers able to live in more open marine environments. This study highlights the importance of microanatomical data for palaeoecological studies. It also discusses the significance of the use of this specialization as a character in phylogenetic studies. PMID:22943660

  8. 7,12-Dimethylbenz(a)anthracene-induced genotoxicity on bone marrow cells from mice phenotypically selected for low acute inflammatory response.

    Science.gov (United States)

    Katz, Iana Suly Santos; Albuquerque, Layra Lucy; Suppa, Alessandra Paes; da Silva, Graziela Batista; Jensen, José Ricardo; Borrego, Andrea; Massa, Solange; Starobinas, Nancy; Cabrera, Wafa Hanna Koury; De Franco, Marcelo; Borelli, Primavera; Ibañez, Olga Martinez; Ribeiro, Orlando Garcia

    2016-01-01

    Exposure to polycyclic aromatic hydrocarbon (PAH) environmental contaminants has been associated with the development of mutations and cancer. 7,12-Dimethylbenz(a)anthracene ( DMBA), a genotoxic agent, reacts with DNA directly, inducing p53-dependent cytotoxicity resulting in cell death by apoptosis or giving rise to cancer. DMBA metabolism largely depends on activation of the aryl hydrocarbon receptor (AhR). Mice phenotypically selected for high (AIRmax) or low (AIRmin) acute inflammatory response present a complete segregation of Ahr alleles endowed with low (Ahr(d)) or high (Ahr(b1)) affinity to PAHs, respectively. To evaluate the role of AhR genetic polymorphism on the bone marrow susceptibility to DMBA, AIRmax and AIRmin mice were treated with a single intraperitoneal injection of DMBA (50mg/kg b.w.) in olive oil. Bone marrow cells (BMCs) were phenotyped by both flow cytometry and cytoslide preparations. Despite a significant decrease in total cell count in BM from AIRmin mice, there was an increase of blast cells and immature neutrophils at 1 and 50 days after DMBA treatment, probably due to a cell-cycle blockade at the G1/S transition leading to immature stage cell production. A panel of proteins related to cell cycle regulation was evaluated in immature BM cells (Lin(-)) by Western Blot, and DNA damage and repair were measured using an alkaline version of the Comet assay. In Lin(-) cells isolated from AIRmin mice, high levels were found in both p53 and p21 protein contents in contrast with the low levels of CDK4 and Ciclin D1. Evaluation of DNA repair in DMBA-treated BMCs, indicated long-lasting genotoxicity and cytotoxicity in BMC from AIRmin mice and a blockade of cell cycle progression. On the other hand, AIRmax mice have a high capacity of DNA damage repair and protection. These mechanisms can be associated with the differential susceptibility to the toxic and carcinogenic effects of DMBA observed in these mice. PMID:26687588

  9. Factors associated with low bone mass in the hemodialysis patients – a cross-sectional correlation study

    Directory of Open Access Journals (Sweden)

    Huang Guey-Shiun

    2009-06-01

    Full Text Available Abstract Background Low bone mass is common in end-stage renal disease patients, especially those undergoing hemodialysis. It can lead to serious bone health problems such as fragility fractures. The purpose of this study is to investigate the risk factors of low bone mass in the hemodialysis patients. Methods Sixty-three subjects on hemodialysis for at least 6 months were recruited from a single center for this cross-sectional study. We collected data by questionnaire survey and medical records review. All subjects underwent a bone mineral density (BMD assay with dual-energy x-ray absorptiometry at the lumbar spine and right hip. Data were statistically analyzed by means of descriptive analysis, independent t test and one way analysis of variance for continuous variables, Pearson product-moment correlation to explore the correlated factors of BMD, and stepwise multiple linear regression to identify the predictors of low bone mass. Results Using WHO criteria as a cutoff point, fifty-one subjects (81% had a T-score lower than -1, of them 8 subjects (13% had osteoporosis with the femoral neck most commonly affected. Regarding risk factors, age, serum alkaline phosphatase (ALP level, and intact parathyroid hormone (iPTH level had significant negative correlations with the femoral neck and lumbar spine BMD. On the other hand, serum albumin level, effective exercise time, and body weight (BW had significant positive correlations with the femoral neck and lumbar spine BMD. Age, effective exercise time, and serum albumin level significantly predicted the femoral neck BMD (R2 × 0.25, whereas BW and the ALP level significantly predicted the lumbar spine BMD (R2 × 0.20. Conclusion This study showed that advanced age, low BW, low serum albumin level, and high ALP and iPTH levels were associated with a low bone mass in the hemodialysis patients. We suggest that regular monitoring of the femoral neck BMD, maintaining an adequate serum albumin level and BW

  10. Selective Determinants of Low Bone Mineral Mass in Adult Women with Anorexia Nervosa

    OpenAIRE

    Andrea Trombetti; Laura Richert; François R. Herrmann; Thierry Chevalley; Jean-Daniel Graf; René Rizzoli

    2013-01-01

    We investigated the relative effect of amenorrhea and insulin-like growth factor-I (sIGF-I) levels on cancellous and cortical bone density and size. We investigated 66 adult women with anorexia nervosa. Lumbar spine and proximal femur bone mineral density was measured by DXA. We calculated bone mineral apparent density. Structural geometry of the spine and the hip was determined from DXA images. Weight and BMI, but not height, as well as bone mineral content and density, but not area and geom...

  11. Lean Mass and Body Fat Percentage Are Contradictory Predictors of Bone Mineral Density in Pre-Menopausal Pacific Island Women.

    Science.gov (United States)

    Casale, Maria; von Hurst, Pamela R; Beck, Kathryn L; Shultz, Sarah; Kruger, Marlena C; O'Brien, Wendy; Conlon, Cathryn A; Kruger, Rozanne

    2016-01-01

    Anecdotally, it is suggested that Pacific Island women have good bone mineral density (BMD) compared to other ethnicities; however, little evidence for this or for associated factors exists. This study aimed to explore associations between predictors of bone mineral density (BMD, g/cm²), in pre-menopausal Pacific Island women. Healthy pre-menopausal Pacific Island women (age 16-45 years) were recruited as part of the larger EXPLORE Study. Total body BMD and body composition were assessed using Dual X-ray Absorptiometry and air-displacement plethysmography (n = 83). A food frequency questionnaire (n = 56) and current bone-specific physical activity questionnaire (n = 59) were completed. Variables expected to be associated with BMD were applied to a hierarchical multiple regression analysis. Due to missing data, physical activity and dietary intake factors were considered only in simple correlations. Mean BMD was 1.1 ± 0.08 g/cm². Bone-free, fat-free lean mass (LMO, 52.4 ± 6.9 kg) and age were positively associated with BMD, and percent body fat (38.4 ± 7.6) was inversely associated with BMD, explaining 37.7% of total variance. Lean mass was the strongest predictor of BMD, while many established contributors to bone health (calcium, physical activity, protein, and vitamin C) were not associated with BMD in this population, partly due to difficulty retrieving dietary data. This highlights the importance of physical activity and protein intake during any weight loss interventions to in order to minimise the loss of muscle mass, whilst maximizing loss of adipose tissue. PMID:27483314

  12. Body composition and bone mineral mass in normal and obese female population using dual X-ray absorptiometry

    International Nuclear Information System (INIS)

    It has been observed that a greater percentage of body fat is associated with augmented bone mineral mass. Objective: The goal of this work was to assess the relationship between bone mineral density (BMD in g/cm2) and content (BMC in g) and soft tissue components, fat and lean mass (in g) in whole body of adult female population in Chile. Method: We studied 185 volunteers, asymptomatic, excluding those using estrogens, regular medication, tobacco (>10 cigarettes/day), excessive alcohol intake or with prior oophorectomy. They were separated in 111 pre and 74 post menopausal and according to body mass index (BMI) they were 37 women > 30 kg/m2 and 148 2. A Lunar Dual X-Ray absorptiometer was used to determine whole BMD and BMC. Results: Post menopausal women were older and smaller [p:0.0001], with higher body mass index [p:0.0007] and with lower BMD and BMC and higher fat mass than the pre menopausal group; In the whole group, women with BMI ≥ 30 (obese) were compared with normal weight observing no difference in BMD. The fat mass incremented significantly with age. Obese women > 50 years presented greater BMC than the non-obese. The percentage of fat corresponded to 48% in the obese group and to 39% in the non-obese [p<0.0001]. Conclusion: Fat mass somehow protect bone mineral loss in older normal population, probably associated to multifactorial causes including extra ovaric estrogen production. Postmenopausal women presented lower mineral content than premenopausal, as it was expected

  13. Determinants of bone mass and bone size in a large cohort of physically active young adult men

    Directory of Open Access Journals (Sweden)

    Garrett P

    2006-02-01

    Full Text Available Abstract The determinants of bone mineral density (BMD at multiple sites were examined in a fit college population. Subjects were 755 males (mean age = 18.7 years entering the United States Military Academy. A questionnaire assessed exercise frequency and milk, caffeine, and alcohol consumption and tobacco use. Academy staff measured height, weight, and fitness. Calcaneal BMD was measured by peripheral dual-energy x-ray absorptiometry (pDXA. Peripheral-quantitative computed tomography (pQCT was used to measure tibial mineral content, circumference and cortical thickness. Spine and hip BMD were measured by DXA in a subset (n = 159. Mean BMD at all sites was approximately one standard deviation above young normal (p

  14. Infant dietary patterns and bone mass in childhood: the Generation R Study

    NARCIS (Netherlands)

    E.H. van den Hooven (Edith); D.H.M. Heppe (Denise); J.C. Kiefte-de Jong (Jessica); M.C. Medina-Gomez (Carolina); H.A. Moll (Henriëtte); A. Hofman (Albert); V.W.V. Jaddoe (Vincent); F. Rivadeneira Ramirez (Fernando); O.H. Franco (Oscar)

    2015-01-01

    textabstractConclusions: An infant dietary pattern characterized by high intakes of dairy and cheese, whole grains, and eggs is positively associated with bone development in childhood. Further research is needed to investigate the consequences for bone health in later life.Results: Higher adherence

  15. Osteoporosis: Modern Paradigms for Last Century's Bones.

    Science.gov (United States)

    Kruger, Marlena C; Wolber, Frances M

    2016-01-01

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a "brittle bone" disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture. PMID:27322315

  16. Adiponectin and peak bone mass in men: a cross-sectional, population-based study

    DEFF Research Database (Denmark)

    Nielsen, Morten Frost; Abrahamsen, B; Nielsen, T L;

    2010-01-01

    Adiponectin, a protein classically known to be secreted by adipocytes, is also secreted by bone-forming cells. Results of previous studies have been contradictory as to whether serum adiponectin and bone mineral density (BMD) are associated. The aim of this study was to investigate a possible...... of femoral cortical thickness and bone marrow size was performed in a subsample of 363 participants. The associations between serum adiponectin and various bone measures were investigated by means of regression analyses with adjustment for potential confounding variables. An inverse association was...... found between serum adiponectin and total hip BMD and a direct between adiponectin and femoral bone marrow size (r = -0.092; P = 0.036 and r = 0.164; P = 0.003, respectively). Femoral muscle size may, at least in part, explain the association between adiponectin and total hip BMD. Serum adiponectin was...

  17. The Effects of Hypergravity and Adrenalectomy on Bone Mineral Content, Urine Calcium and Body Mass in Rats

    Science.gov (United States)

    Lau, A.; Ramirez, J.; Melson, E.; Moran, M.; Baer, L.; Arnaud, S.; Wade, C.; Girten, B.; Dalton, Bonnie (Technical Monitor)

    2001-01-01

    The effects of 14 days of increased gravitational load, and the absence of adrenal stress hormones on total body bone mineral content (BMC) were examined in male Sprague-Dawley rats. Centrifugation at 2 Gs (2G) was used to increase the gravitational load, and bilateral adrenalectomy (ADX) was used to eliminate the production of adrenal stress hormones. Stationary groups at 1 G (1G) and sham operated (SHAM) animals served as controls. Thirty rats (n=6 or 8) made up the four experimental groups (1G SHAM, 1G ADX, 2G SHAM and 2G ADX). BMC was assessed by dual energy x-ray absorptiometry (DXA) which was performed to determine the total body bone mineral content, and also through bone ashing of the left femur and the left humerus. Activity was determined through biotelemetry, also body mass and food intake were measured. Multi-factorial analysis of variance (MANCOVA) and Newman Keuls post hoc tests were used to analyze significant effects (p is less than 0.05) for the primary variables. Results from both DXA and the ashed femur indicated that BMC decreased significantly with increased G for both the SHAM and ADX groups. The BMC determined by DXA for the 1G ADX group was also significantly lower than the 1G SHAM group, however the 2G SHAM and 2G ADX groups were not significantly different. However, the bone ashing results showed the femur differed significantly only between the rates of centrifugation and not between the ADX and SHAM. The humerus showed no significant difference between any of the groups. There was a significant decrease in body mass with increased G and there was no ADX effect on body mass. When DXA BMC was normalized for body mass changes, there were no significant group differences. However, with bone ashing, the femur BMC/BW still showed significant difference between rates of centrifugation, with the 2G group being lower. Activity level decreased with body mass, and food intake data showed there was significant hypophagia during the first few days of

  18. The Relationship of Age, Body Mass Index, and Individual Habit to Bone Mineral Density in Adults

    International Nuclear Information System (INIS)

    We studied the change of bone mineral density (BMD) by age, body mass index (BMI), coffee, carbonated drink, alcohol, smoking, and exercise in adults who checked in health center. The number of study subjects was total 268 persons (women of 136 persons and men of 132 persons). The BMD was determined in lumbar spine and femoral neck by dual energy x-ray absorptiometry. And we got some results as below : 1. In women, mean body height was , mean body weight was 155.8±6.0 cm, and mean BMI was 56.8±7.9 kg. In men, mean body height was 169.1±6.0 cm, mean body weight was 69.0±9.5 kg, and mean BMI was 24.1±2.7 kg/m2. 2. BMD decreased as age increased, and the age was the most determinant factor for BMD (p<0.01). Women's BMD decreased rapidly in the groups aged ≥50s, while men's BMD decreased gradually with age. In addition, for both sex, lower BMD was measured in lumbar spine than in femoral neck. 3. BMD increased in high BMI, and BMD with BMI increased distinctly in the group aged 50s. But their relationship was not significant. 4. In view of the distribution by three BMD categories, women's BMD was mostly normal in the groups aged ≥40s but the rate of osteopenia and osteoporosis was similar in the group aged 50s, and the rate of osteoporosis was the highest in the groups aged 60s and 70s. Men's BMD was mostly normal through all groups except the group aged 70s. 5. Coffee and carbonated drink were not influenced in BMD. But alcohol-drinking group showed higher BMD than non-drinking group, and alcohol was statistically significant determinant for BMD (p<0.05). Smoking and exercise were not statistically significant determinant of BMD.

  19. Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

    Science.gov (United States)

    Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2016-09-01

    Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. PMID:27297606

  20. Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid Chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies.

    Science.gov (United States)

    Gray, Nicola; Adesina-Georgiadis, Kyrillos; Chekmeneva, Elena; Plumb, Robert S; Wilson, Ian D; Nicholson, Jeremy K

    2016-06-01

    A rapid gradient microbore ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) method has been developed to provide a high-throughput analytical platform for the metabolic phenotyping of urine from large sample cohorts. The rapid microbore metabolic profiling (RAMMP) approach was based on scaling a conventional reversed-phase UPLC-MS method for urinary profiling from 2.1 mm × 100 mm columns to 1 mm × 50 mm columns, increasing the linear velocity of the solvent, and decreasing the gradient time to provide an analysis time of 2.5 min/sample. Comparison showed that conventional UPLC-MS and rapid gradient approaches provided peak capacities of 150 and 50, respectively, with the conventional method detecting approximately 19 000 features compared to the ∼6 000 found using the rapid gradient method. Similar levels of repeatability were seen for both methods. Despite the reduced peak capacity and the reduction in ions detected, the RAMMP method was able to achieve similar levels of group discrimination as conventional UPLC-MS when applied to rat urine samples obtained from investigative studies on the effects of acute 2-bromophenol and chronic acetaminophen administration. When compared to a direct infusion MS method of similar analysis time the RAMMP method provided superior selectivity. The RAMMP approach provides a robust and sensitive method that is well suited to high-throughput metabonomic analysis of complex mixtures such as urine combined with a 5-fold reduction in analysis time compared with the conventional UPLC-MS method. PMID:27116471

  1. Physical activity and bone mineral accrual in boys with different body mass parameters during puberty: a longitudinal study.

    Directory of Open Access Journals (Sweden)

    Donvina Vaitkeviciute

    Full Text Available The aim of our longitudinal study was to investigate the relationships between physical activity and bone mass in boys with different body mass status during the years surrounding pubertal growth spurt. Two hundred and six boys entering puberty took part in this study. The subjects were divided into underweight (BMI 26.02 groups at baseline according to age related categories. Whole-body DXA scans were performed at baseline, after 12 and 24 months to assess body composition (lean body mass, fat mass, and total body (TB, lumbar spine (LS and femoral neck (FN bone mineral density (BMD parameters. Physical activity was measured by 7-day accelerometry. For longitudinal analysis, multilevel fixed effects regression models were constructed. Biological age, height and lean body mass had an effect for explanation of TB BMD, FN BMD and LS BMD. Moderate to vigorous physical activity (MVPA, vigorous physical activity (VPA and sedentary time (SED had the significant effect only on FN BMD. Being an underweight boy at the baseline indicated greater chance (p<0.01 to have lower TB BMD in the future (2 years at follow up development, compared to normal weight (estimates = -0.038, overweight (estimates = -0.061 and obese boys (estimates = -0.106.

  2. Anorexia Nervosa and Bone

    OpenAIRE

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure and reduced bone strength, all of which contribute to increased fracture risk., Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising addition concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, hormonal alterations secondary to nutritional factors...

  3. No important influence of limited steroid exposure on bone mass during the first year after renal transplantation: a prospective, randomized, multicenter study.

    NARCIS (Netherlands)

    Meulen, C.G. ter; Riemsdijk, I.C. van; Hene, R.J.; Christiaans, M.H.; Borm, G.F.; Corstens, F.H.M.; Gelder, T. van; Hilbrands, L.B.; Weimar, W.; Hoitsma, A.J.

    2004-01-01

    BACKGROUND: Steroid-related bone loss is a recognized complication after renal transplantation. In a prospective, randomized, multicenter study we compared the influence of a steroid-free immunosuppressive regimen with a regimen with limited steroid exposure on the changes in bone mass after renal t

  4. Immunocytochemical Phenotyping of Disseminated Tumor Cells in Bone Marrow by uPA Receptor and CK18: Investigation of Sensitivity and Specificity of an Immunogold/Alkaline Phosphatase Double Staining Protocol

    OpenAIRE

    Allgayer, Heike; Heiss, Markus Maria; Riesenberg, Rainer; Babic, Rudolf; Jauch, Karl Walter; Schildberg, Friedrich Wilhelm

    1997-01-01

    Phenotyping of cytokeratin (CK) 18-positive cells in bone marrow is gaining increasing importance for future prognostic screening of carcinoma patients. Urokinase-type plasminogen activator receptor (uPA-R) is one example of a potential aggressive marker for those cells. However, a valid and reliable double staining method is needed. Using monoclonal antibodies against uPA-R and CK18, we modified an immunogold/alkaline phosphatase double staining protocol. UPA-R/CK18-positive tumor cell contr...

  5. Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

    Institute of Scientific and Technical Information of China (English)

    Douglas J DiGirolamo; Vandana Singhal; Xiaoli Chang; Se-Jin Lee; Emily L Germain-Lee

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.

  6. Bone microenvironment-mediated resistance of cancer cells to bisphosphonates and impact on bone osteocytes/stem cells.

    Science.gov (United States)

    Alasmari, Abeer; Lin, Shih-Chun; Dibart, Serge; Salih, Erdjan

    2016-08-01

    Anti-resorptive bisphosphonates (BPs) have been clinically used to prevent cancer-bone metastasis and cancer-induced bone pathologies despite the fact that the phenotypic response of the cancer-bone interactions to BP exposure is "uncharted territory". This study offers unique insights into the interplay between cancer stem cells and osteocytes/osteoblasts and mesenchymal stem cells using a three-dimensional (3D) live cancer-bone interactive model. We provide extraordinary cryptic details of the biological events that occur as a result of alendronate (ALN) treatment using 3D live cancer-bone model systems under specific bone remodeling stages. While cancer cells are susceptible to BP treatment in the absence of bone, they are totally unaffected in the presence of bone. Cancer cells colonize live bone irrespective of whether the bone is committed to bone resorption or formation and hence, cancer-bone metastasis/interactions are though to be "independent of bone remodeling stages". In our 3D live bone model systems, ALN inhibited bone resorption at the osteoclast differentiation level through effects of mineral-bound ALN on osteocytes and osteoblasts. The mineral-bound ALN rendered bone incapable of osteoblast differentiation, while cancer cells colonize the bone with striking morphological adaptations which led to a conclusion that a direct anti-cancer effect of BPs in a "live or in vivo" bone microenvironment is implausible. The above studies were complemented with mass spectrometric analysis of the media from cancer-bone organ cultures in the absence and presence of ALN. The mineral-bound ALN impacts the bone organs by limiting transformation of mesenchymal stem cells to osteoblasts and leads to diminished endosteal cell population and degenerated osteocytes within the mineralized bone matrix. PMID:27155840

  7. Irisin and FNDC5: effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women

    OpenAIRE

    Ellefsen, Stian; Vikmoen, Olav; Slettaløkken, Gunnar; Whist, Jon Elling; Nygård, Håvard; Hollan, Ivana; Rauk, Irene; Vegge, Geir; Strand, Tor A.; Raastad, Truls; Rønnestad, Bent

    2014-01-01

    Purpose: To investigate the effects of strength training on abundances of irisin-related biomarkers in skeletal muscle and blood of untrained young women, and their associations with body mass composition, muscle phenotype and levels of thyroid hormones. Methods: Eighteen untrained women performed 12 weeks of progressive whole-body heavy strength training, with measurement of strength, body composition, expression of irisin-related genes (FNDC5 and PGC1α) in two different skeletal muscles,...

  8. Aortic calcification and femoral bone density are independently associated with left ventricular mass in patients with chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Colin D Chue

    Full Text Available BACKGROUND: Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a cross-sectional observational study. METHODOLOGY AND PRINCIPAL FINDINGS: A total of 120 patients were recruited (54% male, mean age 55 ± 14 years, mean glomerular filtration rate 50 ± 13 ml/min/1.73 m(2. Abdominal aortic calcification was assessed using lateral lumbar spine radiography and was present in 48%. Mean femoral Z-score measured using dual energy x-ray absorptiometry was 0.60 ± 1.06. Cardiovascular magnetic resonance imaging was used to determine left ventricular mass. One patient had left ventricular hypertrophy. Subjects with aortic calcification had higher left ventricular mass compared to those without (56 ± 16 vs. 48 ± 12 g/m(2, P = 0.002, as did patients with femoral Z-scores below zero (56 ± 15 vs. 49 ± 13 g/m(2, P = 0.01. In univariate analysis presence of aortic calcification correlated with left ventricular mass (r = 0.32, P = 0.001; mean femoral Z-score inversely correlated with left ventricular mass (r = -0.28, P = 0.004. In a multivariate regression model that included presence of aortic calcification, mean femoral Z-score, gender and 24-hour systolic blood pressure, 46% of the variability in left ventricular mass was explained (P<0.001. CONCLUSIONS: In patients with stage 3 non-diabetic chronic kidney disease, lower mean femoral Z-score and presence of aortic calcification are independently associated with increased left ventricular mass. Further research exploring the pathophysiology that underlies these relationships is warranted.

  9. Clinical significance of HLA-DR+, CD19+, CD10+ immature B-cell phenotype and CD34+ cell detection in bone marrow lymphocytes from children affected with immune thrombocytopenic purpura.

    Science.gov (United States)

    Callea, V; Comis, M; Iaria, G; Sculli, G; Morabito, F; Lombardo, V T

    1997-01-01

    In children with immune thrombocytopenic purpura (ITP), bone marrow lymphocytes can express the common acute lymphoblastic leukemia antigen (CALLA) pattern with no evidence of leukemia or lymphoma. Bone marrow lymphocytes from 23 children and 20 adults affected with ITP were studied to determine the incidence and the clinical impact of lymphocytes with the immature B-cell phenotype and CD34+ cell expression. In this investigation we identified a group consisting of 52% of the children who showed the immature B phenotype, while the remaining 48%, similarly to adult ITP displayed an increase of T-cell antigens. CD34 was positive in 53% of children, but it was present in only half of the patients with the immature B phenotype and it was always absent in adults. IgH genes disclosed a germline configuration in all six patients in the immature B phenotype group. No difference was found in the two groups of children in terms of age, presentation of the disease or final outcome. Finally, no patient in either children's group has developed an acute lymphoproliferative disorder. PMID:9299867

  10. Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease

    OpenAIRE

    Suva, Larry J.; Hartman, Eric; Dilley, Joshua D.; Russell, Susan; Akel, Nisreen S.; Skinner, Robert A.; Hogue, William R.; Budde, Ulrich; Varughese, Kottayil I.; Kanaji, Taisuke; Ware, Jerry

    2008-01-01

    The platelet glycoprotein Ib-IX receptor binds surface-bound von Willebrand factor and supports platelet adhesion to damaged vascular surfaces. A limited number of mutations within the glycoprotein Ib-IX complex have been described that permit a structurally altered receptor to interact with soluble von Willebrand factor, and this is the molecular basis of platelet-type von Willebrand disease. We have developed and characterized a mouse model of platelet-type von Willebrand disease (G233V) an...

  11. Association between body mass index and mortality for colorectal cancer survivors: overall and by tumor molecular phenotype

    Science.gov (United States)

    Campbell, Peter T.; Newton, Christina C.; Newcomb, Polly A.; Phipps, Amanda I.; Ahnen, Dennis J.; Baron, John A.; Buchanan, Daniel D.; Casey, Graham; Cleary, Sean P.; Cotterchio, Michelle; Farris, Alton B.; Figueiredo, Jane C.; Gallinger, Steven; Green, Roger C.; Haile, Robert W.; Hopper, John L.; Jenkins, Mark A.; Le Marchand, Loïc; Makar, Karen W.; McLaughlin, John R.; Potter, John D.; Renehan, Andrew G.; Sinicrope, Frank A.; Thibodeau, Stephen N.; Ulrich, Cornelia M.; Win, Aung Ko; Lindor, Noralane M.; Limburg, Paul J.

    2015-01-01

    Background Microsatellite instability (MSI) and BRAF-mutation status are associated with colorectal cancer survival whereas the role of body mass index (BMI) is less clear. We evaluated the association between BMI and colorectal cancer survival, overall and by strata of MSI, BRAF-mutation, sex, and other factors. Methods This study included 5,615 men and women diagnosed with invasive colorectal cancer who were followed for mortality (maximum: 14.7 years; mean: 5.9 years). Pre-diagnosis BMI was derived from self-reported weight approximately 1-year before diagnosis and height. Tumor MSI and BRAF-mutation status were available for 4,131 and 4,414 persons, respectively. Multivariable hazard ratios (HR) and 95% confidence intervals (CIs) were estimated from delayed-entry Cox proportional hazards models. Results In multivariable models, high pre-diagnosis BMI was associated with higher risk of all-cause mortality in both sexes (per 5-kg/m2, HR = 1.10; 95% CI = 1.06 to 1.15), with similar associations stratified by sex (p-interaction: 0.41), colon vs rectum (p-interaction: 0.86), MSI status (p-interaction: 0.84), and BRAF-mutation status (p-interaction: 0.28). In joint models, with MS-stable/MSI-low and normal BMI as the reference group, risk of death was higher for MS-stable/MSI-low and obese BMI (HR: 1.32; p-value: 0.0002), not statistically significantly lower for MSI-high and normal BMI (HR: 0.86; p-value: 0.29), and approximately the same for MSI-high and obese BMI (HR: 1.00; p-value: 0.98). Conclusions High pre-diagnosis BMI was associated with increased mortality; this association was consistent across participant subgroups, including strata of tumor molecular phenotype. Impact High BMI may attenuate the survival benefit otherwise observed with MSI-high tumors. PMID:26038390

  12. Associations of Bone Mineral Density with Lean Mass, Fat Mass, and Dietary Patterns in Postmenopausal Chinese Women: A 2-Year Prospective Study.

    Directory of Open Access Journals (Sweden)

    Yongjie Chen

    Full Text Available To assess factors associated with bone mineral density (BMD in postmenopausal women in a longitudinal study, and to examine the relative contribution of lean mass, fat mass, dietary patterns, and years since menopause to BMD.Two hundred and eighty-two postmenopausal women were randomly selected from Hongqi Community Health Center, in Harbin City, China. All participants were followed up from 2009 to 2011. Dietary data were collected using a Food Frequency Questionnaire. BMD of the left hip, the lumbar spine, and the total body, and the body composition were measured by dual-energy X-ray absorptiometry at baseline and follow-up.Lean mass and fat mass were positively associated with BMD of the spine, hip, and the total body at both baseline and follow-up. The association between fat mass and BMD at the spine at baseline (P = 0.210 and at the spine (P = 0.116 and hip (P = 0.073 in the second year was not statistically significant when height was adjusted. Six dietary patterns were identified but only cereal grains-fruits pattern (P = 0.001 in the spine, P = 0.037 in hip and milk-root vegetables pattern (P = 0.010 in hip were associated with BMD of the spine and hip. The linear mixed model of follow-up data showed that lean mass, years since menopause, and age of menophania were the significant determinants of BMD of all sites. Moreover, lean mass was the best determinant of BMD (VIP = 1.936.Lean mass, years since menopause, age of menophania and dietary patterns are the important determinants of BMD of the spine, hip, and the total body. Lean mass is the best determinant of BMD.

  13. Peripheral bone mass is not affected by winter vitamin D deficiency in children and young adults from Ushuaia.

    Science.gov (United States)

    Oliveri, M B; Wittich, A; Mautalen, C; Chaperon, A; Kizlansky, A

    2000-09-01

    Low vitamin D levels in elderly people are associated with reduced bone mass, secondary hyperparathyroidism, and increased fracture risk. Its effect on the growing skeleton is not well known. The aim of this study was to evaluate the possible influence of chronic winter vitamin D deficiency and higher winter parathyroid hormone (PTH) levels on bone mass in prepubertal children and young adults. The study was carried out in male and female Caucasian subjects. A total of 163 prepubertal children (X age +/- 1 SD: 8.9 +/- 0.7 years) and 234 young adults (22.9 +/- 3.6 years) who had never received vitamin D supplementation were recruited from two areas in Argentina: (1)Ushuaia (55 degrees South latitude), where the population is known to have low winter 25OHD levels and higher levels of PTH in winter than in summer, and (2)Buenos Aires (34 degrees S), where ultraviolet (UV) radiation and vitamin D nutritional status in the population are adequate all year round. Bone mineral content (BMC) and bone mineral density (BMD) of the ultradistal and distal radius were measured in the young adults. Only distal radius measurements were taken in the children. Similar results were obtained in age-sex matched groups from both areas. The only results showing significant difference corresponded to comparison among the Ushuaian women: those whose calcium (Ca) intake was below 800 mg/day presented lower BMD and BMC values than those whose Ca intake was above that level (0.469 +/- 0.046 versus 0.498 +/- 0.041 g/cm(2), P Ushuaia and Buenos Aires in spite of the previously documented difference between both areas regarding UV radiation and winter vitamin D status. BMD of axial skeletal areas as well the concomitant effect of a low Ca diet and vitamin D deficiency on the growing skeleton should be studied further. PMID:10954776

  14. In vivo assessment of forearm bone mass and ulnar bending stiffness in healthy men

    Science.gov (United States)

    Myburgh, K. H.; Zhou, L. J.; Steele, C. R.; Arnaud, S.; Marcus, R.

    1992-01-01

    The cross-sectional bending stiffness EI of the ulna was measured in vivo by mechanical resistance tissue analysis (MRTA) in 90 men aged 19-89 years. MRTA measures the impedance response of low-frequency vibrations to determine EI, which is a reflection of elastic modulus E and moment of inertia I for the whole ulna. EI was compared to conventional estimates of bone mineral content (BMC), bone width (BW), and BMC/BW, which were all measured by single-photon absorptiometry. Results obtained from the nondominant ulna indicate that BW increases (r = 0.27, p = 0.01) and ulnar BMC/BW decreases (r = -0.31, p < or = 0.005) with age. Neither BMC nor EI declined with age. The single best predictor of EI was BW (r2 = 0.47, p = 0.0001), and further small but significant contributions were made by BMC (r2 = 0.53, p = 0.0001) and grip strength (r2 = 0.55, p = 0.0001). These results suggest that the resistance of older men to forearm fracture is related to age-associated changes in the moment of inertia achieved by redistributing bone mineral farther from the bending axis. We conclude that the in vivo assessment of bone geometry offers important insights to the comprehensive evaluation of bone strength.

  15. Selective Determinants of Low Bone Mineral Mass in Adult Women with Anorexia Nervosa

    Science.gov (United States)

    Trombetti, Andrea; Richert, Laura; Herrmann, François R.; Chevalley, Thierry; Graf, Jean-Daniel; Rizzoli, René

    2013-01-01

    We investigated the relative effect of amenorrhea and insulin-like growth factor-I (sIGF-I) levels on cancellous and cortical bone density and size. We investigated 66 adult women with anorexia nervosa. Lumbar spine and proximal femur bone mineral density was measured by DXA. We calculated bone mineral apparent density. Structural geometry of the spine and the hip was determined from DXA images. Weight and BMI, but not height, as well as bone mineral content and density, but not area and geometry parameters, were lower in patients with anorexia nervosa as compared with the control group. Amenorrhea, disease duration, and sIGF-I were significantly associated with lumbar spine and proximal femur BMD. In a multiple regression model, we found that sIGF-I was the only significant independent predictor of proximal femur BMD, while duration of amenorrhea was the only factor associated with lumbar spine BMD. Finally, femoral neck bone mineral apparent density, but not hip geometry variables, was correlated with sIGF-I. In anorexia nervosa, spine BMD was related to hypogonadism, whereas sIGF-I predicted proximal femur BMD. The site-specific effect of sIGF-I could be related to reduced volumetric BMD rather than to modified hip geometry. PMID:23634145

  16. Selective determinants of low bone mineral mass in adult women with anorexia nervosa.

    Science.gov (United States)

    Trombetti, Andrea; Richert, Laura; Herrmann, François R; Chevalley, Thierry; Graf, Jean-Daniel; Rizzoli, René

    2013-01-01

    We investigated the relative effect of amenorrhea and insulin-like growth factor-I (sIGF-I) levels on cancellous and cortical bone density and size. We investigated 66 adult women with anorexia nervosa. Lumbar spine and proximal femur bone mineral density was measured by DXA. We calculated bone mineral apparent density. Structural geometry of the spine and the hip was determined from DXA images. Weight and BMI, but not height, as well as bone mineral content and density, but not area and geometry parameters, were lower in patients with anorexia nervosa as compared with the control group. Amenorrhea, disease duration, and sIGF-I were significantly associated with lumbar spine and proximal femur BMD. In a multiple regression model, we found that sIGF-I was the only significant independent predictor of proximal femur BMD, while duration of amenorrhea was the only factor associated with lumbar spine BMD. Finally, femoral neck bone mineral apparent density, but not hip geometry variables, was correlated with sIGF-I. In anorexia nervosa, spine BMD was related to hypogonadism, whereas sIGF-I predicted proximal femur BMD. The site-specific effect of sIGF-I could be related to reduced volumetric BMD rather than to modified hip geometry. PMID:23634145

  17. Dlk1/FA1 is a novel endocrine regulator of bone and fat mass and its serum level is modulated by growth hormone

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ding, Ming; Jensen, Charlotte H;

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. Fetal antigen 1 (FA1) is the soluble form of dlk1 (delta-like 1), which is a member of the Notch-Delta family. We previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1 mice) using the hydrodynamic-based gene transfer procedure. We found that increased serum FA1 levels led to a significant reduction in total body weight, fat...... level was reduced by 40% during GH treatment. In conclusion, our data identify the FA1 as a novel endocrine factor regulating bone mass and fat mass in vivo, and its serum levels are regulated by GH. FA1 thus provides a novel class of developmental molecules that regulate physiological functions of the...

  18. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-03-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  19. Streptozotocin, Type I Diabetes Severity and Bone

    Directory of Open Access Journals (Sweden)

    Motyl Katherine

    2009-01-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  20. Calcium and vitamin D requirements for optimal bone mass during adolescence

    Science.gov (United States)

    There remains very strong interest in the calcium and vitamin D requirements of adolescents related to bone health. The Institute of Medicine (IOM) released new dietary guidelines in late 2010 for these nutrients. These guidelines were primarily based on literature published in 2009 and earlier and ...

  1. Changes in biochemical markers and bone mass after withdrawal of ibandronate treatment

    DEFF Research Database (Denmark)

    Ravn, Pernille; Christensen, J O; Baumann, M; Clemmesen, B

    1998-01-01

    quartiles with less reduced concentrations (p < 0.01). During the withdrawal period, uCL and alkaline phosphatase (AP) returned to baseline values 12 months after discontinuation of treatment in all groups, whereas OC(N-MID) and bone-specific AP were still reduced 10%-25% in the groups previously treated...

  2. A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass

    Institute of Scientific and Technical Information of China (English)

    Shawn; LEVY

    2010-01-01

    Osteoporosis is a highly heritable common bone disease leading to fractures that severely impair the life quality of patients.Wrist fractures caused by osteoporosis are largely due to the scarcity of wrist bone mass.Here we report the results of a genome-wide association study (GWAS) of wrist bone mineral density (BMD).We examined ~500000 SNP markers in 1000 unrelated homogeneous Caucasian subjects and found a novel allelic association with wrist BMD at rs11023787 in the SOX6 (SRY (sex determining region Y)-box 6) gene (P=9.00×10-5).Subjects carrying the C allele of rs11023787 in SOX6 had significantly higher mean wrist BMD values than those with the T allele (0.485:0.462 g cm-2 for C allele vs.T allele carriers).For validation,we performed SOX6 association for BMD in an independent Chinese sample and found that SNP rs11023787 was significantly associated with wrist BMD in the Chinese sample (P=6.41×10-3).Meta-analyses of the GWAS scan and the replication studies yielded P-values of 5.20×10-6 for rs11023787.Results of this study,together with the functional relevance of SOX6 in cartilage formation,support the SOX6 gene as an important gene for BMD variation.

  3. Dlk1/FA1 Is a Novel Endocrine Regulator of Bone and Fat Mass and Its Serum Level Is Modulated By Growth Hormone

    DEFF Research Database (Denmark)

    Abdallah, B.M.; Ding, M.; Jensen, C.H.;

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. FA1 (fetal antigen 1) is the soluble form of dlk1 (delta like 1), which is a member of the Notch-Delta family. We have previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1-mice) using the hydrodynamic-based gene transfer procedure (HGTP). We found that increased serum FA1 levels led to a significant reduction in total body weight......, fat mass and bone mass in a dose-dependent manner. Reduced bone mass in FA1-mice was associated with the inhibition of mineral apposition rate and bone formation rates by 58% and 72% respectively. Since FA1 is co-localized with growth hormone (GH) in the pituitary gland, we explored the possible...

  4. G(–2548A leptin gene polymorphism in obese subjects is associated with serum leptin concentration and bone mass

    Directory of Open Access Journals (Sweden)

    Edward Franek

    2010-05-01

    Full Text Available INTRODUCTION: Clinical studies have shown either positive or in some other cases negative correlations between leptinemia and bone mineral density (BMD or bone mineral content (BMC. OBJECTIVES: The aim of the present study was to assess whether these discrepancies might be associated with the effect of G(–2548A leptin or A326G and A668G leptin receptor gene polymorphisms on serum leptin concentrations or BMD and BMC. PATIENTS AND METHODS: The study included 72 obese patients (39 women and 33 men, aged 46 ±8.8 years; body mass index [BMI] >30 kg/m2. In all subjects, serum creatinine, glucose, lipids, leptin, and insulin were determined. Total fat mass (TFM, BMC, and BMD were assessed using dual energy X‑ray absorptiometry (Lunar DPX-L. RESULTS: No significant correlations were observed between body mass composition parameters (TFM, lean mass, BMC or BMD in relation to genotypes. A positive correlation was found between serum leptin concentration and BMI. An inverse association was observed between leptin concentrations and BMC. Multiple regression analysis showed independent correlations of leptinemia with sex (P <0.001, TFM (P <0.000 001, BMC (P = 0.0001, and the presence of (–2548A allele of the leptin gene (P <0.05. These parameters together accounted for 83% of variability in serum leptin concentrations. CONCLUSIONS: In obese patients, serum leptin concentration shows an independent inverse correlation with BMD and male sex, but positively with TFM and the presence of –2548A allele of leptin gene. These parameters are responsible for 83% of leptin concentration variability. No correlations between the examined polymorphisms and BMC or BMD were found.

  5. Relationship between Body Mass Composition, Bone Mineral Density, Skin Fibrosis and 25(OH Vitamin D Serum Levels in Systemic Sclerosis.

    Directory of Open Access Journals (Sweden)

    Addolorata Corrado

    Full Text Available A reduced bone mineral density (BMD is observed in several rheumatic autoimmune diseases, including Systemic Sclerosis (SSc; nevertheless, data concerning the possible determinants of bone loss in this disease are not fully investigated. The aim of this study is to evaluate the relationship between BMD, body mass composition, skin sclerosis and serum Vitamin D levels in two subsets of SSc patients. 64 post-menopausal SSc patients, classified as limited cutaneous (lcSSc or diffuse cutaneous (dcSSc SSc, were studied. As control, 35 healthy post-menopausal women were recruited. Clinical parameters were evaluated, including the extent of skin involvement. BMD at lumbar spine, hip, femoral neck and body mass composition were determined by dual-energy X-ray absorptiometry. Serum calcium, phosphorus, alkaline phosphatase, urine pyridinium cross-links, intact parathyroid hormone and 25-hydroxyvitamin D (25OHD were measured. BMD at spine, femoral neck and total hip was significantly lower in SSc patients compared to controls. In dcSSc subset, BMD at spine, femoral neck and total hip was significantly lower compared to lcSSc. No differences in both fat and lean mass were found in the three study groups even if patients with dcSSc showed a slightly lower total body mass compared to healthy controls. Total mineral content was significantly reduced in dSSc compared to both healthy subjects and lcSSc group. Hypovitaminosis D was observed both in healthy post-menopausal women and in SSc patients, but 25OHD levels were significantly lower in dcSSc compared to lcSSc and inversely correlated with the extent of skin thickness. These results support the hypothesis that the extent of skin involvement in SSc patients could be an important factor in determining low circulating levels of 25OHD, which in turn could play a significant role in the reduction of BMD and total mineral content.

  6. Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry

    OpenAIRE

    Dolan, A; Arden, N.; Grahame, R.; Spector, T

    1998-01-01

    OBJECTIVE—Ehlers Danlos syndrome (EDS) is an inherited disorder of connective tissue characterised by hyperextensible skin, joint laxity, and easy bruising. There are phenotypic similarities with osteogenesis imperfecta, but in EDS a tendency to fracture or altered bone mass has not previously been considered to be a cardinal feature.
METHOD—This case-control design study investigates whether 23 patients with EDS had differences in fracture rates, bone mass, and calcaneal ultrasound parameter...

  7. Evaluation of cortical bone mass, thickness and density by z-scores in osteopenic conditions and in relation to menopause and estrogen treatment

    International Nuclear Information System (INIS)

    Z-scores express, differences from normals in standard deviation units, and are particularly useful for comparison of changes where normal values are age- and sex-dependent. We determined z-scores for bone mineral mass, cortical thickness, and bone mineral density in the radius in various conditions and diseases in both sexes. In the males, z-scores were calculated for age, but in the females z-scores for menopausal status (years postmenopausal exclusive of years on estrogen treatment) were found to be more appropriate. With few exceptions, changes in a disease were of a similar order in both sexes. For bone minerals mass few mean z-scores were significantly increased, but diseases with significantly decreased mean z-scores were numerous. The usefulness of z-scores in diagnosis and study of metabolic bone disease is discussed. (orig.)

  8. Alterations in Muscle Mass and Contractile Phenotype in Response to Unloading Models: Role of Transcriptional/Pretranslational Mechanisms

    Directory of Open Access Journals (Sweden)

    Kenneth M Baldwin

    2013-10-01

    Full Text Available Skeletal muscle is the largest organ system in mammalian organisms providing postural control and movement patterns of varying intensity. Through evolution, skeletal muscle fibers have evolved into three phenotype clusters defined as a muscle unit which consists of all muscle fibers innervated by a single motoneuron linking varying numbers of fibers of similar phenotype. This fundamental organization of the motor unit reflects the fact that there is a remarkable interdependence of gene regulation between the motoneurons and the muscle mainly via activity-dependent mechanisms. These fiber types can be classified via the primary type of myosin heavy chain (MHC gene expressed in the motor unit. Four MHC gene encoded proteins have been identified in striated muscle: slow type I MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic contraction speed of the myofiber with the type I generating the slowest and IIb the fastest contractile speed. Over the last ~35 years, a large body of knowledge suggests that altered loading state cause both fiber atrophy/wasting and a slow to fast shift in the contractile phenotype in the target muscle(s. Hence, this review will examine findings from three different animal models of unloading: 1 space flight (SF, i.e., microgravity; 2 hindlimb suspension (HS, a procedure that chronically eliminates weight bearing of the lower limbs; and 3 spinal cord isolation (SI, a surgical procedure that eliminates neural activation of the motoneurons and associated muscles while maintaining neurotrophic motoneuron-muscle connectivity. The collective findings demonstrate: 1 all three models show a similar pattern of fiber atrophy with differences mainly in the magnitude and kinetics of alteration; 2 transcriptional/pretranslational processes play a major role in both the atrophy process and phenotype shifts; and 3 signaling pathways impacting these alterations appear to be similar in each of the models

  9. Alterations of Mass Density and 3D Osteocyte Lacunar Properties in Bisphosphonate-Related Osteonecrotic Human Jaw Bone, a Synchrotron µCT Study

    Science.gov (United States)

    Hesse, Bernhard; Langer, Max; Varga, Peter; Pacureanu, Alexandra; Dong, Pei; Schrof, Susanne; Männicke, Nils; Suhonen, Heikki; Olivier, Cecile; Maurer, Peter; Kazakia, Galateia J.

    2014-01-01

    Osteonecrosis of the jaw, in association with bisphosphonates (BRONJ) used for treating osteoporosis or cancer, is a severe and most often irreversible side effect whose underlying pathophysiological mechanisms remain largely unknown. Osteocytes are involved in bone remodeling and mineralization where they orchestrate the delicate equilibrium between osteoclast and osteoblast activity and through the active process called osteocytic osteolysis. Here, we hypothesized that (i) changes of the mineralized tissue matrix play a substantial role in the pathogenesis of BRONJ, and (ii) the osteocyte lacunar morphology is altered in BRONJ. Synchrotron µCT with phase contrast is an appropriate tool for assessing both the 3D morphology of the osteocyte lacunae and the bone matrix mass density. Here, we used this technique to investigate the mass density distribution and 3D osteocyte lacunar properties at the sub-micrometer scale in human bone samples from the jaw, femur and tibia. First, we compared healthy human jaw bone to human tibia and femur in order to assess the specific differences and address potential explanations of why the jaw bone is exclusively targeted by the necrosis as a side effect of BP treatment. Second, we investigated the differences between BRONJ and control jaw bone samples to detect potential differences which could aid an improved understanding of the course of BRONJ. We found that the apparent mass density of jaw bone was significantly smaller compared to that of tibia, consistent with a higher bone turnover in the jaw bone. The variance of the lacunar volume distribution was significantly different depending on the anatomical site. The comparison between BRONJ and control jaw specimens revealed no significant increase in mineralization after BP. We found a significant decrease in osteocyte-lacunar density in the BRONJ group compared to the control jaw. Interestingly, the osteocyte-lacunar volume distribution was not altered after BP treatment. PMID

  10. Osteoblast-targeted overexpression of TAZ increases bone mass in vivo.

    Directory of Open Access Journals (Sweden)

    Jae-Yeon Yang

    Full Text Available Osteoblasts are derived from mesenchymal progenitors. Differentiation to osteoblasts and adipocytes is reciprocally regulated. Transcriptional coactivator with a PDZ-binding motif (TAZ is a transcriptional coactivator that induces differentiation of mesenchymal cells into osteoblasts while blocking differentiation into adipocytes. To investigate the role of TAZ on bone metabolism in vivo, we generated transgenic mice that overexpress TAZ under the control of the procollagen type 1 promoter (Col1-TAZ. Whole body bone mineral density (BMD of 6- to 19-week-old Col-TAZ mice was 4% to 7% higher than that of their wild-type (WT littermates, whereas no difference was noticed in Col.1-TAZ female mice. Microcomputed tomography analyses of proximal tibiae at 16 weeks of age demonstrated a significant increase in trabecular bone volume (26.7% and trabecular number (26.6% with a reciprocal decrease in trabecular spacing (14.2% in Col1-TAZ mice compared with their WT littermates. In addition, dynamic histomorphometric analysis of the lumbar spine revealed increased mineral apposition rate (42.8% and the serum P1NP level was also significantly increased (53% in Col.1-TAZ mice. When primary calvaria cells were cultured in osteogenic medium, alkaline phosphatase (ALP activity was significantly increased and adipogenesis was significantly suppressed in Col1-TAZ mice compared with their WT littermates. Quantitative real-time polymerase chain reaction analyses showed that expression of collagen type 1, bone sialoprotein, osteocalcin, ALP, osterix, and Runx2 was significantly increased in calvaria cells from Col1-TAZ mice compared to their WT littermates. In vitro, TAZ enhanced Runx2-mediated transcriptional activity while suppressing the peroxisome proliferator-activated receptor gamma signaling pathway. TAZ also enhanced transcriptional activity from 3TP-Lux, which reflects transforming growth factor-beta (TGF-β-mediated signaling. In addition, TAZ enhanced TGF

  11. Comparison of the Bruker MALDI-TOF Mass Spectrometry System and Conventional Phenotypic Methods for Identification of Gram-Positive Rods

    OpenAIRE

    Barberis, Claudia; Almuzara, Marisa; Join-Lambert, Olivier; Ramírez, María Soledad; Famiglietti, Angela; Vay, Carlos

    2014-01-01

    In recent years, MALDI-TOF Mass Spectrometry (MS) method has emerged as a promising and a reliable tool for bacteria identification. In this study we compared Bruker MALDI-TOF MS and conventional phenotypic methods to identify a collection of 333 Gram-positive clinical isolates comprising 22 genera and 60 species. 16S rRNA sequencing was the reference molecular technique, and rpoB gene sequecing was used as a secondary gene target when 16Sr RNA did not allow species identification of Coryneba...

  12. Metabolic profiling of plant extracts using direct-injection electrospray ionization mass spectrometry allows for high-throughput phenotypic characterization according to genetic and environmental effects.

    Science.gov (United States)

    García-Flores, Martín; Juárez-Colunga, Sheila; García-Casarrubias, Adrián; Trachsel, Samuel; Winkler, Robert; Tiessen, Axel

    2015-01-28

    In comparison to the exponential increase of genotyping methods, phenotyping strategies are lagging behind in agricultural sciences. Genetic improvement depends upon the abundance of quantitative phenotypic data and the statistical partitioning of variance into environmental, genetic, and random effects. A metabolic phenotyping strategy was adapted to increase sample throughput while saving reagents, reducing cost, and simplifying data analysis. The chemical profiles of stem extracts from maize plants grown under low nitrogen (LN) or control trial (CT) were analyzed using optimized protocols for direct-injection electrospray ionization mass spectrometry (DIESI-MS). Specific ions significantly decreased or increased because of environmental (LN versus CT) or genotypic effects. Biochemical profiling with DIESI-MS had a superior cost-benefit compared to other standard analytical technologies (e.g., ultraviolet, near-infrared reflectance spectroscopy, high-performance liquid chromatography, and gas chromatography with flame ionization detection) routinely used for plant breeding. The method can be successfully applied in maize, strawberry, coffee, and other crop species. PMID:25588121

  13. Decreased Nocturnal Oxytocin Levels in Anorexia Nervosa Are Associated with Low Bone Mineral Density and Fat Mass

    Science.gov (United States)

    Lawson, Elizabeth A.; Donoho, Daniel A.; Blum, Justine I.; Meenaghan, Erinne M.; Misra, Madhusmita; Herzog, David B.; Sluss, Patrick M.; Miller, Karen K.; Klibanski, Anne

    2013-01-01

    Objective Anorexia nervosa is characterized by self-induced starvation and associated with severe bone and fat loss. Oxytocin is a peptide hormone involved in appetite and energy homeostasis. Recent data show that oxytocin has an anabolic effect on bone and stimulates osteoblast function. There is limited information about oxytocin levels or its relationship to decreased bone mineral density (BMD) in anorexia nervosa. Our objective was to investigate the relationship between oxytocin levels, BMD and body composition in women with anorexia nervosa. Method We studied 36 women, mean age 27.6±1.3 years: 17 with anorexia nervosa (AN) and 19 healthy controls (HC) in a cross-sectional study. Oxytocin levels were determined from pooled serum samples obtained every 20 minutes from 8pm to 8am. Fasting leptin levels were measured. BMD at the anterior-posterior (AP) and lateral spine and hip, and body composition were assessed by dual energy X-ray absorptiometry. Results Mean oxytocin levels (14.3±1.5 vs. 31.8±5.1 pg/mL, p=0.003), leptin levels (2.7±0.5 vs. 11.4±1.1 ng/mL, p<0.0001), BMD (AP spine: 0.83±0.02 vs. 1.04±0.03; lateral spine: 0.63±0.02 vs. 0.81±0.02; total hip: 0.79±0.03 vs. 0.97±0.03 g/cm2, <0.0001), and fat mass (8.8±0.6 vs. 19.7±0.9 kg, p<0.0001) were lower in AN vs. HC. Oxytocin levels were associated with BMD at the AP (r=0.40, p=0.02) and lateral (r=0.36, p=0.04) spine, fat mass (r=0.42, p=0.01), and leptin levels (r=0.55, p=0.001). Conclusion Overnight secretion of oxytocin in AN is decreased compared with healthy women. Low oxytocin levels are associated with decreased BMD and body fat and may contribute to anorexia nervosa-induced bone loss. PMID:21903023

  14. Global variations in peak bone mass as studied by dual-energy X-ray absorptiometry

    International Nuclear Information System (INIS)

    In 1994, the International Atomic Energy Agency (IAEA) initiated a 5-year Co-ordinated Research Project (CRP) to determine geographical and racial differences in peak bone mineral density (BMD) in men and women aged 15-49 years. Distinct global differences in BMD were demonstrated at the hip and spine in both men and women approximating to one population standard deviation between populations with the highest and lowest BMD. These differences persist following adjustments for age, sex and body size. Such information is valuable in understanding the reasons for global differences in fracture rate and predicting future trends in fracture incidence. (author)

  15. 5-Azacytidine-induced protein 2 (AZI2) regulates bone mass by fine-tuning osteoclast survival.

    Science.gov (United States)

    Maruyama, Kenta; Fukasaka, Masahiro; Uematsu, Satoshi; Takeuchi, Osamu; Kondo, Takeshi; Saitoh, Tatsuya; Martino, Mikaël M; Akira, Shizuo

    2015-04-10

    5-Azacytidine-induced protein 2 (AZI2) is a TNF receptor (TNFR)-associated factor family member-associated NF-κB activator-binding kinase 1-binding protein that regulates the production of IFNs. A previous in vitro study showed that AZI2 is involved in dendritic cell differentiation. However, the roles of AZI2 in immunity and its pleiotropic functions are unknown in vivo. Here we report that AZI2 knock-out mice exhibit normal dendritic cell differentiation in vivo. However, we found that adult AZI2 knock-out mice have severe osteoporosis due to increased osteoclast longevity. We revealed that the higher longevity of AZI2-deficient osteoclasts is due to an augmented activation of proto-oncogene tyrosine-protein kinase Src (c-Src), which is a critical player in osteoclast survival. We found that AZI2 inhibits c-Src activity by regulating the activation of heat shock protein 90 (Hsp90), a chaperone involved in c-Src dephosphorylation. Furthermore, we demonstrated that AZI2 indirectly inhibits c-Src by interacting with the Hsp90 co-chaperone Cdc37. Strikingly, administration of a c-Src inhibitor markedly prevented bone loss in AZI2 knock-out mice. Together, these findings indicate that AZI2 regulates bone mass by fine-tuning osteoclast survival. PMID:25691576

  16. 5-Azacytidine-induced Protein 2 (AZI2) Regulates Bone Mass by Fine-tuning Osteoclast Survival*

    Science.gov (United States)

    Maruyama, Kenta; Fukasaka, Masahiro; Uematsu, Satoshi; Takeuchi, Osamu; Kondo, Takeshi; Saitoh, Tatsuya; Martino, Mikaël M.; Akira, Shizuo

    2015-01-01

    5-Azacytidine-induced protein 2 (AZI2) is a TNF receptor (TNFR)-associated factor family member-associated NF-κB activator-binding kinase 1-binding protein that regulates the production of IFNs. A previous in vitro study showed that AZI2 is involved in dendritic cell differentiation. However, the roles of AZI2 in immunity and its pleiotropic functions are unknown in vivo. Here we report that AZI2 knock-out mice exhibit normal dendritic cell differentiation in vivo. However, we found that adult AZI2 knock-out mice have severe osteoporosis due to increased osteoclast longevity. We revealed that the higher longevity of AZI2-deficient osteoclasts is due to an augmented activation of proto-oncogene tyrosine-protein kinase Src (c-Src), which is a critical player in osteoclast survival. We found that AZI2 inhibits c-Src activity by regulating the activation of heat shock protein 90 (Hsp90), a chaperone involved in c-Src dephosphorylation. Furthermore, we demonstrated that AZI2 indirectly inhibits c-Src by interacting with the Hsp90 co-chaperone Cdc37. Strikingly, administration of a c-Src inhibitor markedly prevented bone loss in AZI2 knock-out mice. Together, these findings indicate that AZI2 regulates bone mass by fine-tuning osteoclast survival. PMID:25691576

  17. Liver-derived IGF-I regulates cortical bone mass but is dispensable for the osteogenic response to mechanical loading in female mice.

    Science.gov (United States)

    Svensson, Johan; Windahl, Sara H; Saxon, Leanne; Sjögren, Klara; Koskela, Antti; Tuukkanen, Juha; Ohlsson, Claes

    2016-07-01

    Low circulating IGF-I is associated with increased fracture risk. Conditional depletion of IGF-I produced in osteoblasts or osteocytes inhibits the bone anabolic effect of mechanical loading. Here, we determined the role of endocrine IGF-I for the osteogenic response to mechanical loading in young adult and old female mice with adult, liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice, serum IGF-I reduced by ≈70%) and control mice. The right tibia was subjected to short periods of axial cyclic compressive loading three times/wk for 2 wk, and measurements were performed using microcomputed tomography and mechanical testing by three-point bending. In the nonloaded left tibia, the LI-IGF-I(-/-) mice had lower cortical bone area and increased cortical porosity, resulting in reduced bone mechanical strength compared with the controls. Mechanical loading induced a similar response in LI-IGF-I(-/-) and control mice in terms of cortical bone area and trabecular bone volume fraction. In fact, mechanical loading produced a more marked increase in cortical bone mechanical strength, which was associated with a less marked increase in cortical porosity, in the LI-IGF-I(-/-) mice compared with the control mice. In conclusion, liver-derived IGF-I regulates cortical bone mass, cortical porosity, and mechanical strength under normal (nonloaded) conditions. However, despite an ∼70% reduction in circulating IGF-I, the osteogenic response to mechanical loading was not attenuated in the LI-IGF-I(-/-) mice. PMID:27221117

  18. Two to three years of hormone replacement treatment in healthy women have long-term preventive effects on bone mass and osteoporotic fractures: the PERF study

    DEFF Research Database (Denmark)

    Bagger, Yu Z; Tankó, László B; Alexandersen, Peter; Hansen, Henrik Bo; Møllgaard, Anette; Ravn, Pernille; Qvist, Per; Kanis, John A; Christiansen, Claus

    2004-01-01

    density (BMD) at the spine (L1-L4) and bone mineral content (BMC) in the forearm were measured at baseline, the end of the trials, and follow-up. At follow-up, we assessed the radiological presence of vertebral fracture and collected information on the new incidence of nonvertebral fractures. Compared...... determine whether administration of HRT for 2-3 years in the early postmenopausal years provides long-term benefits, such as prevention of bone loss and osteoporotic fractures, we studied a group of 347 healthy postmenopausal women with normal bone mass who had earlier completed one of four placebo...... was accompanied by a significantly reduced risk of all osteoporotic fractures as compared with the placebo group [OR = 0.48 (95% CI, 0.26-0.88)]. 'Fast losers' on placebo had more than a 4-fold higher risk of fractures than had the women on limited HRT with a normal rate of bone loss after withdrawal...

  19. A novel mouse model of human breast cancer stem-like cells with high CD44+CD24-/lower phenotype metastasis to human bone

    Institute of Scientific and Technical Information of China (English)

    LING Li-jun; WANG Feng; WANG Shui; LIU Xiao-an; SHEN En-chao; DING Qiang; LU Chao; XU Jian; CAO Qin-hong; ZHU Hai-qing

    2008-01-01

    Background A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.Methods Human breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1x105, 1x106 human breast cancer stem-like cells, and 1x106 parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1x106 MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR). Results Our results demonstrated that cells in implanted human bones of group B, which received 1x106 cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P=0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest. Conclusions In the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.

  20. Three-dimensional geometric analysis of felid limb bone allometry.

    Directory of Open Access Journals (Sweden)

    Michael Doube

    Full Text Available BACKGROUND: Studies of bone allometry typically use simple measurements taken in a small number of locations per bone; often the midshaft diameter or joint surface area is compared to body mass or bone length. However, bones must fulfil multiple roles simultaneously with minimum cost to the animal while meeting the structural requirements imposed by behaviour and locomotion, and not exceeding its capacity for adaptation and repair. We use entire bone volumes from the forelimbs and hindlimbs of Felidae (cats to investigate regional complexities in bone allometry. METHOD/PRINCIPAL FINDINGS: Computed tomographic (CT images (16435 slices in 116 stacks were made of 9 limb bones from each of 13 individuals of 9 feline species ranging in size from domestic cat (Felis catus to tiger (Panthera tigris. Eleven geometric parameters were calculated for every CT slice and scaling exponents calculated at 5% increments along the entire length of each bone. Three-dimensional moments of inertia were calculated for each bone volume, and spherical radii were measured in the glenoid cavity, humeral head and femoral head. Allometry of the midshaft, moments of inertia and joint radii were determined. Allometry was highly variable and related to local bone function, with joint surfaces and muscle attachment sites generally showing stronger positive allometry than the midshaft. CONCLUSIONS/SIGNIFICANCE: Examining whole bones revealed that bone allometry is strongly affected by regional variations in bone function, presumably through mechanical effects on bone modelling. Bone's phenotypic plasticity may be an advantage during rapid evolutionary divergence by allowing exploitation of the full size range that a morphotype can occupy. Felids show bone allometry rather than postural change across their size range, unlike similar-sized animals.

  1. Sequential treatment with basic fibroblast growth factor and parathyroid hormone restores lost cancellous bone mass and strength in the proximal tibia of aged ovariectomized rats

    DEFF Research Database (Denmark)

    Wronski, T.J.; Ratkus, A.M.; Thomsen, Jesper Skovhus; Vulcan, Q.; Mosekilde, Lis

    2001-01-01

    This study was designed to determine whether sequential treatment with basic fibroblast growth factor (bFGF) and parathyroid hormone (PTH) can restore lost cancellous bone mass and strength at a severely osteopenic skeletal site in aged ovariectomized (OVX) rats. Female Sprague-Dawley rats were s...

  2. Comparison of the Bruker MALDI-TOF mass spectrometry system and conventional phenotypic methods for identification of Gram-positive rods.

    Directory of Open Access Journals (Sweden)

    Claudia Barberis

    Full Text Available In recent years, MALDI-TOF Mass Spectrometry (MS method has emerged as a promising and a reliable tool for bacteria identification. In this study we compared Bruker MALDI-TOF MS and conventional phenotypic methods to identify a collection of 333 Gram-positive clinical isolates comprising 22 genera and 60 species. 16S rRNA sequencing was the reference molecular technique, and rpoB gene sequecing was used as a secondary gene target when 16Sr RNA did not allow species identification of Corynebacterium spp. We also investigate if score cut-offs values of ≥ 1,5 and ≥ 1,7 were accurate for genus and species-level identification using the Bruker system. Identification at species level was obtained for 92,49% of Gram-positive rods by MALDI-TOF MS compared to 85,89% by phenotypic method. Our data validates the score ≥ 1,5 for genus level and ≥ 1,7 for species-level identification in a large and diverse collection of Gram-positive rods. The present study has proved the accuracy of MALDI-TOF MS as an identification method in Gram-positive rods compared to currently used methods in routine laboratories.

  3. Osteoporosis or Low Bone Mass at the Femur Neck or Lumbar Spine in Older Adults: United States, 2005-2008

    Science.gov (United States)

    ... HW, Dunn WL, Calvo MS, et al. Updated data on proximal femur bone mineral levels of U.S. adults. Osteoporos Int 8:468–89. 1998. Kelly TJ. Bone mineral density reference databases for American men and women. J Bone Miner Res 5 (Suppl1):S249. 1990. Centers for Disease ...

  4. 9-Demethoxy-medicarpin promotes peak bone mass achievement and has bone conserving effect in ovariectomized mice: Positively regulates osteoblast functions and suppresses osteoclastogenesis.

    Science.gov (United States)

    Goel, Atul; Raghuvanshi, Ashutosh; Kumar, Amit; Gautam, Abnish; Srivastava, Kamini; Kureel, Jyoti; Singh, Divya

    2015-08-15

    We report a new bone anabolic and anti-catabolic pterocarpan 9-demethoxy-medicarpin (DMM) for the management of postmenopausal osteoporosis. DMM promoted osteoblast functions via activation of P38MAPK/BMP-2 pathway and suppressed osteoclastogenesis in bone marrow cells (BMCs). In calvarial osteoblasts, DMM blocked nuclear factor kappaB (NFκB) signaling and inhibited the mRNA levels of pro-inflammatory cytokines. DMM treatment led to increased OPG (osteoprotegrin) and decreased transcript levels of TRAP (tartarate resistant acid phosphatase), RANK (receptor activator of NFκB) and RANKL (RANK ligand) in osteoblast-osteoclast co-cultures. Immature female SD rats administered with DMM exhibited increased bone mineral density, bone biomechanical strength, new bone formation and cortical bone parameters. Ovx mice administered with DMM led to significant restoration of trabecular microarchitecture and had reduced formation of osteoclasts and increased formation of osteoprogenitor cells in BMCs. DMM exhibited no uterine estrogenicity. Overall, these results demonstrate the therapeutic potential of DMM for the management of postmenopausal osteoporosis. PMID:25957087

  5. Osteoporosis: Modern Paradigms for Last Century’s Bones

    Science.gov (United States)

    Kruger, Marlena C.; Wolber, Frances M.

    2016-01-01

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a “brittle bone” disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture. PMID:27322315

  6. Osteoporosis: Modern Paradigms for Last Century’s Bones

    Directory of Open Access Journals (Sweden)

    Marlena C. Kruger

    2016-06-01

    Full Text Available The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a “brittle bone” disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture.

  7. Dating of two Paleolithic human fossil bones from Romania by accelerator mass spectrometry

    CERN Document Server

    Olariu, A; Faarinen, M P; Hellborg, R; Persson, P; Skog, G; Stenström, K; Alexandrescu, Emilian; Faarinen, Mikko; Hellborg, Ragnar; Olariu, Agata; Persson, Per; Skog, Goran; Stenstrom, Kristina

    2003-01-01

    In this study we have dated two human fossil remains found in Romania, by the method of radiocarbon using the technique of the accelerator mass spectrometry. The human fossil remains from Woman's cave, Baia deFier, have been dated to the age 30150 $\\pm$ 800 years BP, and the skull from the Cioclovina cave has been dated to the age 29000 $\\pm$ 700 years BP. These are the most ancient dated till now human fossil remains from Romania, possibly belonging to the upper Paleolithic, the Aurignacian period.

  8. Generation of mesenchymal stromal cells in the presence of platelet lysate: a phenotypic and functional comparison of umbilical cord blood- and bone marrow-derived progenitors

    OpenAIRE

    Avanzini, Maria Antonietta; Bernardo, Maria Ester; Cometa, Angela Maria; Perotti, Cesare; Zaffaroni, Nadia; Novara, Francesca; Visai, Livia; Moretta, Antonia; Del Fante, Claudia; Villa, Raffaella; Ball, Lynne M.; Fibbe, Willem E; Maccario, Rita; Locatelli, Franco

    2009-01-01

    Umbilical cord blood is an attractive source of stem cells for several cell-based therapies. In this paper, it is shown that umbilical cord blood-derived mesenchymal stroma cells, cultured in the presence of platelet lysate, have an increased proliferative potential but comparable immunomodulatory functions relative to their bone marrow-derived counterparts.

  9. Loss of Gsα in the Postnatal Skeleton Leads to Low Bone Mass and a Blunted Response to Anabolic Parathyroid Hormone Therapy.

    Science.gov (United States)

    Sinha, Partha; Aarnisalo, Piia; Chubb, Rhiannon; Poulton, Ingrid J; Guo, Jun; Nachtrab, Gregory; Kimura, Takaharu; Swami, Srilatha; Saeed, Hamid; Chen, Min; Weinstein, Lee S; Schipani, Ernestina; Sims, Natalie A; Kronenberg, Henry M; Wu, Joy Y

    2016-01-22

    Parathyroid hormone (PTH) is an important regulator of osteoblast function and is the only anabolic therapy currently approved for treatment of osteoporosis. The PTH receptor (PTH1R) is a G protein-coupled receptor that signals via multiple G proteins including Gsα. Mice expressing a constitutively active mutant PTH1R exhibited a dramatic increase in trabecular bone that was dependent upon expression of Gsα in the osteoblast lineage. Postnatal removal of Gsα in the osteoblast lineage (P-Gsα(OsxKO) mice) yielded markedly reduced trabecular and cortical bone mass. Treatment with anabolic PTH(1-34) (80 μg/kg/day) for 4 weeks failed to increase trabecular bone volume or cortical thickness in male and female P-Gsα(OsxKO) mice. Surprisingly, in both male and female mice, PTH administration significantly increased osteoblast numbers and bone formation rate in both control and P-Gsα(OsxKO) mice. In mice that express a mutated PTH1R that activates adenylyl cyclase and protein kinase A (PKA) via Gsα but not phospholipase C via Gq/11 (D/D mice), PTH significantly enhanced bone formation, indicating that phospholipase C activation is not required for increased bone turnover in response to PTH. Therefore, although the anabolic effect of intermittent PTH treatment on trabecular bone volume is blunted by deletion of Gsα in osteoblasts, PTH can stimulate osteoblast differentiation and bone formation. Together these findings suggest that alternative signaling pathways beyond Gsα and Gq/11 act downstream of PTH on osteoblast differentiation. PMID:26598522

  10. Amino acid delta13C analysis of hair proteins and bone collagen using liquid chromatography/isotope ratio mass spectrometry: paleodietary implications from intra-individual comparisons

    DEFF Research Database (Denmark)

    Raghavan, Maanasa; McCullagh, James S O; Lynnerup, Niels;

    2010-01-01

    We report a novel method for the chromatographic separation and measurement of stable carbon isotope ratios (delta(13)C) of individual amino acids in hair proteins and bone collagen using the LC-IsoLink system, which interfaces liquid chromatography (LC) with isotope ratio mass spectrometry (IRMS......). This paper provides baseline separation of 15 and 13 of the 18 amino acids in bone collagen and hair proteins, respectively. We also describe an approach to analysing small hair samples for compound-specific analysis of segmental hair sections. The LC/IRMS method is applied in a historical context by...

  11. Heterogeneous Stock Rat: A Unique Animal Model for Mapping Genes Influencing Bone Fragility

    OpenAIRE

    Alam, Imranul; Koller, Daniel L; Sun, Qiwei; Roeder, Ryan K.; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla

    2011-01-01

    Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in 4 inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which ...

  12. EFFECTS OF WHOLE-BODY VIBRATION TRAINING ON BONE-FREE LEAN BODY MASS AND MUSCLE STRENGTH IN YOUNG ADULTS

    Directory of Open Access Journals (Sweden)

    Yusuke Osawa

    2011-03-01

    Full Text Available Resistance training with whole-body vibration (WBV is becoming increasingly popular as an alternative to conventional resistance training or as supplementary training. Despite its growing popularity, the specific effects of WBV training on muscle morphology, strength, and endurance are not well understood, particularly in young adults. The aim of this study was to determine the effects of WBV training on bone-free lean body mass (BFLBM, and maximal muscle strength and endurance in healthy, untrained, young individuals. Eighteen healthy men and women (21-39 years were randomly assigned to either a body-weight exercise with WBV (VT group or a control exercise group without WBV (CON. Participants performed eight exercises per 40- min session on a vibration platform (VT group, frequency = 30-40 Hz; amplitude = 2 mm twice weekly for 12 weeks. Anthropometry, total and regional BFLBM (trunks, legs, and arms measured by dual- energy X-ray absorptiometry, and muscle strength and endurance measured by maximal isometric lumbar extension strength, maximal isokinetic knee extension and flexion strength, and the number of sit- ups performed were recorded and compared. Two-way repeated-measures ANOVA revealed no significant changes between the groups in any of the measured variables. We conclude that 12 weeks of body weight vibration exercise compared to body weight exercise alone does not provide meaningful changes to BFLBM or muscle performance in healthy young adults.

  13. Age- and sex-related changes in bone mass measured by neutron activation

    International Nuclear Information System (INIS)

    Total-body calcium (TBCa) measurements have been employed in two basic types of studies. In the first type, serial measurements made on an individual patient are used to trace the time variation in body calcium. In the second type of study, the absolute total body calcium of an individual is determined and compared to a standard or predicted value in order to determine the deficit or excess of calcium. Generally, the standards are derived from data obtained from normal populations and grouped by the parameters of age and sex (mean value denoted TBCa/sub m/). In the study reported in this paper, the clinical usefulness of predicted calcium (TBCa/sub p/) is evaluated. The predicted value (TBCa/sub p/) for an individual is obtained with an algorithm utilizing values of sex and age, height and lean body mass (as derived from 40K measurement). The latter two components characterize skeletal size and body habitus, respectively. For the study, 133 white women and 71 white men ranging in age from 20 to 80 years were selected from a larger population. Individuals with evidence of metabolic calcium disorders or osteoporosis were excluded. Additionally, the women and men selected were first judged to have total body potassium levels in the normal range. For each age decade, the variance of TBCa values of these individuals, when expressed in terms of TBCa/sub p/, was significantly less than when expressed in terms of TBCa/sub m/. Thus, erroneous conclusions based on Ca deficit in osteoporosis could be drawn for individuals whose height and body size differ markedly from the average, as the variation of their TBCa values often exceeds the variation in the age and sex cohort. Data on a group of osteoporotic women were compared with the normal skeletal baseline values both in terms of the TBCa and the TBCa/sub p/ values

  14. Age- and sex-related changes in bone mass measured by neutron activation

    Energy Technology Data Exchange (ETDEWEB)

    Cohn, S.H.; Aloia, J.F.; Vaswani, A.N.; Zanzi, I.; Vartsky, D.; Ellis, K.J.

    1981-01-01

    Total-body calcium (TBCa) measurements have been employed in two basic types of studies. In the first type, serial measurements made on an individual patient are used to trace the time variation in body calcium. In the second type of study, the absolute total body calcium of an individual is determined and compared to a standard or predicted value in order to determine the deficit or excess of calcium. Generally, the standards are derived from data obtained from normal populations and grouped by the parameters of age and sex (mean value denoted TBCa/sub m/). In the study reported in this paper, the clinical usefulness of predicted calcium (TBCa/sub p/) is evaluated. The predicted value (TBCa/sub p/) for an individual is obtained with an algorithm utilizing values of sex and age, height and lean body mass (as derived from /sup 40/K measurement). The latter two components characterize skeletal size and body habitus, respectively. For the study, 133 white women and 71 white men ranging in age from 20 to 80 years were selected from a larger population. Individuals with evidence of metabolic calcium disorders or osteoporosis were excluded. Additionally, the women and men selected were first judged to have total body potassium levels in the normal range. For each age decade, the variance of TBCa values of these individuals, when expressed in terms of TBCa/sub p/, was significantly less than when expressed in terms of TBCa/sub m/. Thus, erroneous conclusions based on Ca deficit in osteoporosis could be drawn for individuals whose height and body size differ markedly from the average, as the variation of their TBCa values often exceeds the variation in the age and sex cohort. Data on a group of osteoporotic women were compared with the normal skeletal baseline values both in terms of the TBCa and the TBCa/sub p/ values.

  15. Circadian Clock Regulates Bone Resorption in Mice.

    Science.gov (United States)

    Xu, Cheng; Ochi, Hiroki; Fukuda, Toru; Sato, Shingo; Sunamura, Satoko; Takarada, Takeshi; Hinoi, Eiichi; Okawa, Atsushi; Takeda, Shu

    2016-07-01

    The circadian clock controls many behavioral and physiological processes beyond daily rhythms. Circadian dysfunction increases the risk of cancer, obesity, and cardiovascular and metabolic diseases. Although clinical studies have shown that bone resorption is controlled by circadian rhythm, as indicated by diurnal variations in bone resorption, the molecular mechanism of circadian clock-dependent bone resorption remains unknown. To clarify the role of circadian rhythm in bone resorption, aryl hydrocarbon receptor nuclear translocator-like (Bmal1), a prototype circadian gene, was knocked out specifically in osteoclasts. Osteoclast-specific Bmal1-knockout mice showed a high bone mass phenotype due to reduced osteoclast differentiation. A cell-based assay revealed that BMAL1 upregulated nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (Nfatc1) transcription through its binding to an E-box element located on the Nfatc1 promoter in cooperation with circadian locomotor output cycles kaput (CLOCK), a heterodimer partner of BMAL1. Moreover, steroid receptor coactivator (SRC) family members were shown to interact with and upregulate BMAL1:CLOCK transcriptional activity. Collectively, these data suggest that bone resorption is controlled by osteoclastic BMAL1 through interactions with the SRC family and binding to the Nfatc1 promoter. © 2016 American Society for Bone and Mineral Research. PMID:26841172

  16. Bone Metabolism in Anorexia Nervosa

    OpenAIRE

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in ...

  17. Bone Metabolism in Adolescents with Anorexia Nervosa

    OpenAIRE

    Misra, Madhusmita; Klibanski, Anne

    2011-01-01

    Adolescents with anorexia nervosa (AN) are at risk for low bone mass at multiple sites, associated with decreased bone turnover. Bone microarchitecture is also affected, with a decrease in bone trabecular volume and trabecular thickness, and an increase in trabecular separation. The adolescent years are typically the time when marked increases occur in bone mass accrual towards the attainment of peak bone mass, an important determinant of bone health and fracture risk in later life. AN often ...

  18. Anorexia nervosa and bone.

    Science.gov (United States)

    Misra, Madhusmita; Klibanski, Anne

    2014-06-01

    Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure, and reduced bone strength, all of which contribute to increased fracture risk. Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising additional concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, and hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiological estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age, given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN. PMID:24898127

  19. Anorexia Nervosa and Bone

    Science.gov (United States)

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure and reduced bone strength, all of which contribute to increased fracture risk., Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising addition concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiologic estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN. PMID:24898127

  20. Associations between hypothalamic-pituitary-adrenal axis function and peak bone mass at 20years of age in a birth cohort.

    Science.gov (United States)

    Zhu, Kun; Henley, David; Pennell, Craig; Herbison, Carly E; Mountain, Jenny; Lye, Stephen; Walsh, John P

    2016-04-01

    In older adults, high-normal circulating cortisol levels are associated with lower bone mass, but relationships between hypothalamic-pituitary-adrenal axis function and peak bone mass in young adults have not been examined. We studied 411 male and 390 female participants in the Western Australia Pregnancy Cohort (Raine) Study. At 18years of age, participants underwent a Trier Social Stress Test (TSST) with measurement of plasma and salivary cortisol at baseline and at multiple time points after stress. Cortisol responses were classified as anticipatory responder (significant fall in cortisol during the test), reactive responder (significant increase) or non-responder. At 20years, total body bone mineral content (BMC) and density (BMD) were measured by DXA. In males, after adjustment for weight, height (for BMC and bone area only), alcohol and smoking, there was a significant inverse relationship between both plasma and salivary cortisol measured at baseline in the TSST and each of BMC and BMD, such that each additional 10% of salivary cortisol was associated with reductions of 6.9g (95% CI -11.7, -2.2) in BMC, and 1.8mg/cm(2) (95% CI -3.3, -0.4) in BMD. Males classified as anticipatory responders in the TSST had 3.2% lower BMC (adjusted mean±SE: 3131±28 vs. 3233±18g, P=0.006) and 2.5% lower BMD (1108±9 vs. 1136±6mg/cm(2), P=0.022) than reactive responders. In females, there were no significant relationships between baseline cortisol or TSST responses and BMC or BMD in covariate-adjusted analyses. We conclude that in young males (but not females), higher circulating cortisol at the baseline of the stress test and an anticipatory responder pattern on the TSST are associated with lower total body bone mass. PMID:26802258

  1. Exploring correlation between bone metabolism markers and densitometric traits in extended families from Spain.

    Science.gov (United States)

    Athanasiadis, Georgios; Arranz, Laura; Ziyatdinov, Andrey; Brunel, Helena; Camacho, Mercedes; Malouf, Jorge; Sosa, Nerea Hernandez-de; Vila, Luis; Casademont, Jordi; Soria, Jose Manuel

    2016-09-01

    Osteoporosis is a common multifactorial disorder characterized by low bone mass and reduced bone strength that may cause fragility fractures. In recent years, there have been substantial advancements in the biochemical monitoring of bone metabolism through the measurement of bone turnover markers. Currently, good knowledge of the genetics of such markers has become an indispensable part of osteoporosis research. In this study, we used the Genetic Analysis of Osteoporosis Project to study the genetics of the plasma levels of 12 markers related to bone metabolism and osteoporosis. Plasma phenotypes were determined through biochemical assays and log-transformed values were used together with a set of covariates to model genetic and environmental contributions to phenotypic variation, thus estimating the heritability of each trait. In addition, we studied correlations between the 12 markers and a wide variety of previously described densitometric traits. All of the 12 bone metabolism markers showed significant heritability, ranging from 0.194 for osteocalcin to 0.516 for sclerostin after correcting for covariate effects. Strong genetic correlations were observed between osteocalcin and several bone mineral densitometric traits, a finding with potentially useful diagnostic applications. In addition, suggestive genetic correlations with densitometric traits were observed for leptin and sclerostin. Overall, the few strong and several suggestive genetic correlations point out the existence of a complex underlying genetic architecture for bone metabolism plasma phenotypes and provide a strong motivation for pursuing novel whole-genome gene-mapping strategies. PMID:27241279

  2. Impaired bone remodeling and its correction by combination therapy in a mouse model of mucopolysaccharidosis-I.

    Science.gov (United States)

    Kuehn, Sonja C; Koehne, Till; Cornils, Kerstin; Markmann, Sandra; Riedel, Christoph; Pestka, Jan M; Schweizer, Michaela; Baldauf, Christina; Yorgan, Timur A; Krause, Matthias; Keller, Johannes; Neven, Mona; Breyer, Sandra; Stuecker, Ralf; Muschol, Nicole; Busse, Bjoern; Braulke, Thomas; Fehse, Boris; Amling, Michael; Schinke, Thorsten

    2015-12-15

    Mucopolysaccharidosis-I (MPS-I) is a lysosomal storage disease (LSD) caused by inactivating mutations of IDUA, encoding the glycosaminoglycan-degrading enzyme α-l-iduronidase. Although MPS-I is associated with skeletal abnormalities, the impact of IDUA deficiency on bone remodeling is poorly defined. Here we report that Idua-deficient mice progressively develop a high bone mass phenotype with pathological lysosomal storage in cells of the osteoblast lineage. Histomorphometric quantification identified shortening of bone-forming units and reduced osteoclast numbers per bone surface. This phenotype was not transferable into wild-type mice by bone marrow transplantation (BMT). In contrast, the high bone mass phenotype of Idua-deficient mice was prevented by BMT from wild-type donors. At the cellular level, BMT did not only normalize defects of Idua-deficient osteoblasts and osteocytes but additionally caused increased osteoclastogenesis. Based on clinical observations in an individual with MPS-I, previously subjected to BMT and enzyme replacement therapy (ERT), we treated Idua-deficient mice accordingly and found that combining both treatments normalized all histomorphometric parameters of bone remodeling. Our results demonstrate that BMT and ERT profoundly affect skeletal remodeling of Idua-deficient mice, thereby suggesting that individuals with MPS-I should be monitored for their bone remodeling status, before and after treatment, to avoid long-term skeletal complications. PMID:26427607

  3. Bone mass density estimation: Archimede’s principle versus automatic X-ray histogram and edge detection technique in ovariectomized rats treated with germinated brown rice bioactives

    Directory of Open Access Journals (Sweden)

    Muhammad SI

    2013-10-01

    Full Text Available Sani Ismaila Muhammad,1,2 Ismail Maznah,1,3 Rozi Binti Mahmud,4 Maher Faik Esmaile,5 Zuki Abu Bakar Zakaria6 1Laboratory of Molecular Biomedicine, Institute of Bioscience, 2Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria; 3Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, 4Department of Radiology, Faculty of Medicine and Health Sciences, 5Department of Electrical and Electronic Engineering, Faculty of Engineering, 6Department of Pre-clinical Studies, Faculty of Veterinary Medicine, University Putra Malaysia, Selangor, Malaysia Background: Bone mass density is an important parameter used in the estimation of the severity and depth of lesions in osteoporosis. Estimation of bone density using existing methods in experimental models has its advantages as well as drawbacks. Materials and methods: In this study, the X-ray histogram edge detection technique was used to estimate the bone mass density in ovariectomized rats treated orally with germinated brown rice (GBR bioactives, and the results were compared with estimated results obtained using Archimede’s principle. New bone cell proliferation was assessed by histology and immunohistochemical reaction using polyclonal nuclear antigen. Additionally, serum alkaline phosphatase activity, serum and bone calcium and zinc concentrations were detected using a chemistry analyzer and atomic absorption spectroscopy. Rats were divided into groups of six as follows: sham (nonovariectomized, nontreated; ovariectomized, nontreated; and ovariectomized and treated with estrogen, or Remifemin®, GBR-phenolics, acylated steryl glucosides, gamma oryzanol, and gamma amino-butyric acid extracted from GBR at different doses. Results: Our results indicate a significant increase in alkaline phosphatase activity, serum and bone calcium, and zinc and ash content in the treated groups compared with the ovariectomized

  4. Effects of long term treatment with high doses of odanacatib on bone mass, bone strength, and remodeling/modeling in newly ovariectomized monkeys.

    Science.gov (United States)

    Duong, L T; Pickarski, M; Cusick, T; Chen, C M; Zhuo, Y; Scott, K; Samadfam, R; Smith, S Y; Pennypacker, B L

    2016-07-01

    The objectives here were to evaluate the effects of odanacatib (ODN) at doses exceeding the clinical exposure on biomechanical properties of lumbar vertebrae (LV), hip and central femur (CF), and compare ODN to alendronate (ALN) on bone remodeling/modeling in ovariectomized (OVX) monkeys. Ten days post-surgery, animals were treated with vehicle (VEH), ODN-L (2mg/kg/day, p.o.), ODN-H (8/4mg/kg/day), or ALN (30μg/kg/week, s.c.) for 20months. An intact group was also included. ODN-L provided systemic exposures of 1.8-fold of clinical exposure. ODN-H started at 20-fold for 5.5months, and then reduced to 7.8-fold of clinical exposure, compared to ALN at approximated clinical exposure. From cross sectional analyses, LV density and peak load in ODN at both doses or ALN were not different from VEH or Intact. However, cortical thickness of femoral neck (FN) and CF in ODN were higher (21-34%, p<0.05) than VEH, due to smaller endocortical (Ec) perimeter of FN (10-11%; p<0.05) and CF (9-12%; ODN-L, p<0.05), and larger CF periosteal (Ps) perimeter (2-12%; ODN-H, p<0.001) versus VEH. ODN groups also showed slightly higher cortical porosity and Ps non-lamellar bone in CF. ODN-H treatment resulted in higher CF peak load (p<0.05) versus VEH. For all bone sites analyzed, a positive, linear relationship (r(2)=0.46-0.69, p<0.0001) of peak load to density or structural parameters was demonstrated. No treatment-related differences in the derived intrinsic strength properties were evidenced as compared between groups. ALN reduced all remodeling surfaces without affecting Ps modeling. Trabecular and intracortical remodeling were reduced in ODN groups, similar to ALN. Ec mineralizing surface in ODN-H trended to be lower than VEH by month 20, but Ec bone formation indices in ODN groups generally were not different from VEH. Ps modeling in ODN groups was significantly higher than other treatment groups. This study overall demonstrated the bone safety profile of ODN and its unique mechanism

  5. β3-adrenergic receptor gene, body mass index, bone mineral density and fracture risk in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES)

    OpenAIRE

    Center Jacqueline R; Eisman John A; Morrison Nigel A; Nguyen Nguyen D; Wang Claire Y; Nguyen Tuan V

    2006-01-01

    Abstract Background Recent studies have suggested that the Arg allele of β3-adrenergic receptor (ADRB3) gene is associated with body mass index (BMI), which is an important predictor of bone mineral density (BMD) and fracture risk. However, whether the ADRB3 gene polymorphism is associated with fracture risk has not been investigated. The aim of study was to examine the inter-relationships between ADRB3 gene polymorphisms, BMI, BMD and fracture risk in elderly Caucasians. Methods Genotypes of...

  6. Association between Β3-Adrenergic receptor (ADRB3) gene polymorphism with body mass index and bone mineral density in Turkish postmenopausal women

    OpenAIRE

    Turgay İşbir2, Ayşe Can1, Özlem Kurt-Şirin1, Hülya Yılmaz-Aydoğan2 Mehmet Uyar3, Mehmet Fatih Seyhan2,

    2016-01-01

    Abstract: Previous studies have suggested that β3-adrenergic receptor (ADRB3) gene is associated with body mass index (BMI), which is an important predictor of bone mineral density (BMD). However, little is known concerning the effect of the ADRB3 gene on BMD. The present study investigated the relationship between ADRB3 Trp64Arg polymorphism, BMI and BMD in Turkish postmenopausal women. 133 postmenopausal women (81 osteoporotic and 52 healthy control) were recruited. For the detection of ADR...

  7. Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency? A systematic literature analysis

    DEFF Research Database (Denmark)

    Klefter, O.; Feldt-Rasmussen, U.

    2009-01-01

    OBJECTIVE: Adult patients with GH deficiency (GHD) are characterized by a reduced muscle mass, but also reduced bone mineral density (BMD) and content (BMC), which have been ascribed to GHD per se. The aim of this study was to investigate if changes in BMD/BMC in adult GHD patients could be due to...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...

  8. Effects of whole-body vibration training on physical function, bone and muscle mass in adolescents and young adults with cerebral palsy

    Science.gov (United States)

    Gusso, Silmara; Munns, Craig F; Colle, Patrícia; Derraik, José G B; Biggs, Janene B; Cutfield, Wayne S; Hofman, Paul L

    2016-01-01

    We performed a clinical trial on the effects of whole-body vibration training (WBVT) on muscle function and bone health of adolescents and young adults with cerebral palsy. Forty participants (11.3–20.8 years) with mild to moderate cerebral palsy (GMFCS II–III) underwent 20-week WBVT on a vibration plate for 9 minutes/day 4 times/week at 20 Hz (without controls). Assessments included 6-minute walk test, whole-body DXA, lower leg pQCT scans, and muscle function (force plate). Twenty weeks of WBVT were associated with increased lean mass in the total body (+770 g; p = 0.0003), trunk (+410 g; p = 0.004), and lower limbs (+240 g; p = 0.012). Bone mineral content increased in total body (+48 g; p = 0.0001), lumbar spine (+2.7 g; p = 0.0003), and lower limbs (+13 g; p < 0.0001). Similarly, bone mineral density increased in total body (+0.008 g/cm2; p = 0.013), lumbar spine (+0.014 g/cm2; p = 0.003), and lower limbs (+0.023 g/cm2; p < 0.0001). Participants reduced the time taken to perform the chair test, and improved the distance walked in the 6-minute walk test by 11% and 35% for those with GMFCS II and III, respectively. WBVT was associated with increases in muscle mass and bone mass and density, and improved mobility of adolescents and young adults with cerebral palsy. PMID:26936535

  9. Effects of a Specialist-Led, School Physical Education Program on Bone Mass, Structure, and Strength in Primary School Children: A 4-Year Cluster Randomized Controlled Trial.

    Science.gov (United States)

    Daly, Robin M; Ducher, Gaele; Hill, Briony; Telford, Rohan M; Eser, Prisca; Naughton, Geraldine; Seibel, Markus J; Telford, Richard D

    2016-02-01

    This 4-year cluster randomized controlled trial of 365 boys and 362 girls (mean age 8.1 ± 0.3 years) from grade 2 in 29 primary schools investigated the effects of a specialist-taught physical education (PE) program on bone strength and body composition. All children received 150 min/week of common practice (CP) PE from general classroom teachers but in 13 schools 100 min/week of CP PE was replaced by specialized-led PE (SPE) by teachers who emphasized more vigorous exercise/games combined with static and dynamic postural activities involving muscle strength. Outcome measures assessed in grades 2, 4, and 6 included: total body bone mineral content (BMC), lean mass (LM), and fat mass (FM) by DXA, and radius and tibia (4% and 66% sites) bone structure, volumetric density and strength, and muscle cross-sectional area (CSA) by pQCT. After 4-years, gains in total body BMC, FM, and muscle CSA were similar between the groups in both sexes, but girls in the SPE group experienced a greater gain in total body LM (mean 1.0 kg; 95% CI, 0.2 to 1.9 kg). Compared to CP, girls in the SPE group also had greater gains in cortical area (CoA) and cortical thickness (CoTh) at the mid-tibia (CoA, 5.0% [95% CI, 0.2% to 1.9%]; CoTh, 7.5% [95% CI, 2.4% to 12.6%]) and mid-radius (CoA, 9.3% [95% CI, 3.5% to 15.1%]; CoTh, 14.4% [95% CI, 6.1% to 22.7%]), whereas SPE boys had a 5.2% (95% CI, 0.4% to 10.0%) greater gain in mid-tibia CoTh. These benefits were due to reduced endocortical expansion. There were no significant benefits of SPE on total bone area, cortical density or bone strength at the mid-shaft sites, nor any appreciable effects at the distal skeletal sites. This study indicates that a specialist-led school-based PE program improves cortical bone structure, due to reduced endocortical expansion. This finding challenges the notion that periosteal apposition is the predominant response of bone to loading during the prepubertal and early-pubertal period. PMID:26260216

  10. Parathyroid Hormone Induces Bone Cell Motility and Loss of Mature Osteocyte Phenotype through L-Calcium Channel Dependent and Independent Mechanisms.

    Directory of Open Access Journals (Sweden)

    Matthew Prideaux

    results show that PTH induces loss of the mature osteocyte phenotype and promotes the motility of these cells. These two effects are mediated through different mechanisms. The loss of phenotype effect is independent and the cell motility effect is dependent on calcium signaling.

  11. Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios

    DEFF Research Database (Denmark)

    Jørgensen, Henrik L; Kusk, Philip; Madsen, Bente Elmfelt; Fenger, Mogens; Lauritzen, Jes B

    2004-01-01

    The purpose of this study is to investigate the association of serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter with peripheral measures of bone mass and with odds ratios for wrist and hip fracture in a case-control study of postmenopausal Danish women. The study included...... 66 women with lower forearm fracture, 41 women with hip fracture, and 206 age-matched controls. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel as well as bone mineral density (BMD) measured by DXA at the distal forearm. S-OPG was measured by ELISA. The A...... the controls. Patients with a combination of the highest quartile of S-OPG and presence of the G allele ( n = 23) had a significantly elevated fracture odds ratio, 4.0 (95% CI, 1.7-9.9). A significant negative association between S-OPG with peripheral measures of bone mass and with increased fracture...

  12. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  13. Bone Grafts

    Science.gov (United States)

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some ...

  14. Difference in canal encroachment by the fusion mass between anterior cervical discectomy and fusion with bone autograft and anterior plating, and stand-alone cage.

    Science.gov (United States)

    Lee, Soo Eon; Chung, Chun Kee; Kim, Chi Heon

    2016-07-01

    We conducted a prospective randomized study comparing stand-alone cage and bone autograft and plate implants in anterior cervical discectomy and fusion (www.clinicaltrials.gov, NCT01011569). Our interim analysis showed autologous bone graft with plating was superior to a stand-alone cage for segmental lordosis. During this analysis, we noted a difference in canal encroachment by the fusion mass between the two fusion groups. A narrow cervical spinal canal is an important factor in the development of cervical spondylotic myelopathy, therefore this unexpected potential risk of spinal cord compression necessitated another interim analysis to investigate whether there was a difference in canal encroachment by the fusion mass between the two groups. Patients had a minimum 1year of follow-up. The Neck Disability Index, neck and arm pain Visual Analog Scales and lateral radiographs, including bone fusion patterns, were evaluated. Twenty-seven (16 males, 11 females, mean age 54.8years) and 31 (24 males, seven females, mean age 54.5years) patients were in the cage and plate group, respectively. Both groups improved after surgery. Fusion began at 2.6months and 1.3months and finished at 6.7months and 4.0months in 24 (88.9%) and 28 (90.3%) patients in the cage and plate group, respectively. Encroachment into the spinal canal by the fusion mass was significantly different between the fusion types, occuring in 21 (77.8%) patients in the cage group versus six (19.4%) in the plate group (p=0.003). There was a high incidence of spinal canal encroachment by the fusion mass in the stand-alone cage group, possibly limiting use in narrow spinal canals. PMID:27234609

  15. The importance and relevance of peak bone mass in the prevalence of osteoporosis Importancia y relevancia de la masa ósea máxima en la prevalencia de osteoporosis

    OpenAIRE

    Jean-Philippe Bonjour; Thierry Chevalley; Serge Ferrari; René Rizzoli

    2009-01-01

    Bone mass and strength achieved at the end of the growth period, simply designated as "Peak Bone Mass (PBM)", plays an essential role in the risk of osteoporotic fractures occurring in adulthood. It is considered that an increase of PBM by one standard deviation would reduce the fracture risk by 50%. As estimated from twin studies, genetics is the major determinant of PBM, accounting for about 60 to 80% of its variance. During pubertal maturation, the size of the bone increases whereas the vo...

  16. Sequential treatment with basic fibroblast growth factor and PTH is more efficacious than treatment with PTH alone for increasing vertebral bone mass and strength in osteopenic ovariectomized rats

    DEFF Research Database (Denmark)

    Iwaniec, U.T.; Mosekilde, Li.; Mitova-Caneva, N.G.;

    2002-01-01

    the jugular veins of all rats, and vehicle or bFGF at a dose of 250 microg/kg was injected daily for 14 d. Three groups of rats were killed at the end of bFGF treatment. The remaining rats were continued on their respective antiresorptive therapy and injected sc with vehicle or synthetic human PTH-(1...... estrogen and risedronate did not suppress the anabolic response of bone to bFGF and PTH. In fact, a trend for an even greater increase in cancellous bone mass and node to terminus ratio was observed in OVX rats treated with risedronate, bFGF, and PTH. These findings indicate that sequential treatment with...

  17. Protein-containing nutrient supplementation following strength training enhances the effect on muscle mass, strength, and bone formation in postmenopausal women

    DEFF Research Database (Denmark)

    Holm, Lars; Olesen, Jens L; Matsumoto, Keitaro;

    2008-01-01

    We evaluated the response of various muscle and bone adaptation parameters with 24 wk of strength training in healthy, early postmenopausal women when a nutrient supplement (protein, carbohydrate, calcium, and vitamin D) or a placebo supplement (a minimum of energy) was ingested immediately...... following each training session. At inclusion, each woman was randomly and double-blindedly assigned to a nutrient group or a placebo (control) group. Muscle hypertrophy was evaluated from biopsies, MRI, and dual-energy X-ray absorptiometry (DEXA) scans, and muscle strength was determined in a dynamometer...... nutrient supplementation results in superior improvements in muscle mass, muscle strength, femoral neck BMD, and bone formation during 24 wk of strength training. The observed differences following such a short intervention emphasize the significance of postexercise nutrient supply on musculoskeletal...

  18. The relationship between obesity phenotypes and the changes of bone mineral density and vitamin D receptor in type 2 diabetes mellitus patients%2型糖尿病患者肥胖表型和骨量变化与维生素D受体的关系

    Institute of Scientific and Technical Information of China (English)

    李进; 金美娟; 黄璟; 徐静; 徐执政

    2016-01-01

    Objective To investigate the correlation between vitamin D receptor gene and bone mass and obesity phenotypes in patients with type 2 diabetes mellitus.Methods 318 patients with type 2 diabetes were chosen as diabetes group,and 50 healthy people were selected as healthy control group.Vitamin D receptor gene Apa Ⅰ type was detected in the two groups.Height,weight and body mass index(BMI)biochemical index,fat content(FM),lean tissue content(LM)and bone mineral density were detected in patients with type 2 diabetes mellitus.The relationship between vitamin D receptor gene(Apa Ⅰ)polymorphism and BMD and obesity phenotypes in type 2 diabetes was analyzed.Results The VDR gene distribution between the diabetes group and healthy control group showed no signif-icant difference(Z =0.561,P >0.05).The vitamin D receptor genotype in the diabetes group included AA 31 cases (9.7%),Aa type 108 cases(34.0%),aa type 179 cases(56.3%),while the vitamin D receptor genotype in the healthy control group comprised AA 7 cases(9.3%),Aa type 29 cases(38.7%),aa type 39 cases(52.0%).The percentage of AA in both groups was significantly less than that of Aa and aa(χ2 diabetic group =4.127,3.976,all P <0.05;χ2 healthy control group =5.129,4.213,all P <0.05).Proportion of normal bone mass and average bone density in AA,Aa,aa type decreased(χ2 =15.552,P <0.05;F =5.127,P <0.05),the genotype AA was not detec-ted in osteoporosis group.BMI and FM were the highest in AA,which were significantly higher than those of Aa,aa (F =4.319,4.263,all P <0.05).Conclusion Vitamin D receptor gene Apa Ⅰ type polymorphism is related with BMD and obesity in type 2 diabetes mellitus,and it has predictive value on bone mass changes.The increase of BMI and FMmay be beneficial to bone mineral density.%目的:探讨2型糖尿病患者维生素 D 受体(VDR)基因与骨量、肥胖表型的相关关系。方法选择2型糖尿病患者318例为糖尿病组,50例健康查体者为健康对照

  19. Eating disorders and bone.

    Science.gov (United States)

    Tomlinson, Dale; Morgan, Sarah L

    2013-01-01

    Low bone mineral density (BMD) is a frequent and often-overlooked consequence of eating disorders, in particular anorexia nervosa and eating disorders associated with the female athlete triad. The causes of low BMD are multifactorial and include low peak bone mass accrual, accelerated bone resorption, and changes in bone microarchitecture. Early diagnosis and interventions focused on nutritional rehabilitation and weight gain reduce the risk of further BMD deficits and fractures. PMID:24094471

  20. 十一酸睾酮对骨质疏松老年男性骨量及骨代谢的影响%Influence of Testosterone Undecanoate on Bone Mass and Bone Metabolism in Elderly Male Patients with Osteoporosis

    Institute of Scientific and Technical Information of China (English)

    吴小明; 吴凯; 申广浩; 汤池

    2015-01-01

    目的:观察十一酸睾酮对骨质疏松老年男性患者骨量及骨代谢的影响。方法选择2013年1月至2014年12月收治的骨质疏松症患者100例,随机分为对照组和观察组,各50例。两组均给予钙剂、维生素D、降钙素等促进骨化抑制骨吸收的药物治疗,观察组加用十一酸睾酮。两组患者均以4周为1个疗程,治疗3个疗程。结果观察组总有效率为98.00%,高于对照组的86.00%( P﹤0.05)。治疗前,两组患者腰椎正位、股骨颈的骨密度(BMD)、各项骨代谢指标无明显差异( P﹥0.05);治疗后,两组患者BMD、各项骨代谢指标均显著改善,且观察组改善情况显著优于对照组( P﹤0.05)。两组患者不良反应均较轻,差异无统计学意义( P﹥0.05)。结论十一酸睾酮对骨质疏松老年男性患者具有治疗作用,临床疗效显著,减轻疼痛,可影响患者骨量及骨代谢,且无明显不良反应发生,值得临床推广。%Objective To observe the influence of testosterone undecanoate on bone mass and bone metabolism in elderly male patients with osteoporosis. Methods 100 cases of osteoporosis patients admitted to the hospital from January 2013 to December 2014 were ran-domly divided into the control group and the observation group, 50 cases in each group. The two groups were treated with calcium, vita-min D, calcitonin to promote ossification and inhibit bone absorption, and the observation group was added with testosterone unde-canoate. 4 weeks was 1 course of treatment and the two groups were treated for 3 courses. Results The total effective rate of the ob-servation group was 98. 00%, which was higher than 86. 00% in the control group ( P ﹤ 0. 05 ) . The lumbar spine and femoral neck BMD of the two groups had no significant difference before treatment, after treatment( P ﹥ 0. 05), the BMD of the two groups signifi-cantly improved, and the improvement of the observation group

  1. The Microenvironment Matters: Estrogen Deficiency Fuels Cancer Bone Metastases

    OpenAIRE

    Wright, Laura E; Guise, Theresa A.

    2014-01-01

    Factors released during osteoclastic bone resorption enhance disseminated breast cancer cell progression by stimulating invasiveness, growth and a bone-resorptive phenotype in cancer cells. Post-menopausal bone loss may accelerate progression of breast cancer growth in bone, explaining the anti-cancer benefit of the bone-specific anti-resorptive agent zoledronic acid in the post-menopausal setting.

  2. Bone mineral density and changes in bone metabolism in patients with obstructive sleep apnea syndrome.

    Science.gov (United States)

    Terzi, Rabia; Yılmaz, Zahide

    2016-07-01

    The aim of this study was to evaluate the differences between patients with obstructive sleep apnea syndrome (OSAS) and phenotypically similar subjects without OSAS in terms of bone mineral density (BMD) and bone turnover markers. The study was conducted on 30 males diagnosed with OSAS and 20 healthy males. All subjects underwent polysomnographic testing. Calcium, phosphorus parathyroid hormone, thyroid stimulating hormone, bone-specific alkaline phosphatase, 25-hydroxyvitamin D3, osteocalcin, and beta-CrossLaps (β-CTx) were measured. BMD in the lumbar spine (L1-L4) and femoral neck was measured by dual energy X-ray absorptiometry. There was no statistically significant difference between the two groups in terms of demographic data with the exception of bone mass index and waist circumference. (p < 0.05). Analyses showed significantly lower BMD measurements in the femoral neck and T-scores in the femoral neck in patients diagnosed with OSAS. Serum β-CTx levels were found to be statistically significantly higher in the OSAS group (p = 0.017). In multivariate assessments performed for apnea/hypopnea index values, mean saturation O2 levels were found to be significantly associated with osteocalcin levels and neck BMD. OSAS patients might represent a risk group with respect to loss of BMD and bone resorption. It is important to evaluate bone loss in these patients. Further studies should be carried out on larger study populations to evaluate the effects of chronic hypoxia on BMD in detail. PMID:26204846

  3. Bone mass after long-term euthyroidism in former hyperthyroid women treated with (131)I influence of menopausal status.

    Science.gov (United States)

    Serraclara, A; Jódar, E; Sarabia, F; Hawkins, F

    2001-01-01

    The objective of this study was to assess bone mineral density (BMD) and bone markers in former hyperthyroid females after long-term euthyroidism (>4 yr) following (131)I therapy, as well as the potential influence of the timing of menopause. Twenty-six females ages 57 +/- 8 yr previously diagnosed with hyperthyroidism and treated with (131)I who were euthyroid for a minimum of the last 4 yr (10 +/- 5 yr) were studied. Eighteen patients (69%) were on levothyroxine (LT(4)) replacement therapy for 9 +/- 4 yr. BMD (g/cm(2) and Z-score) was measured by dual X-ray absorptiometry in the lumbar spine, femoral neck, and Ward's triangle. BMD (Z-score) was lower than the normal reference values for the Spanish population in all sites (lumbar spine: -0.65 +/- 1.13; femoral neck: -0.47 +/- 0.95; Ward's triangle: -0.37 +/- 0.88). No differences were found between BMD values according to the etiology of the hyperthyroidism or current LT(4) therapy. Current postmenopausal patients (n = 21) showed lower BMD than current premenopausal patients in the lumbar spine and femoral neck (p menopausal status when hyperthyroidism was diagnosed. Former hyperthyroid patients after long-term euthyroidism following (131)I therapy showed reduced BMD at the lumbar spine and proximal femur. Menopausal women showed a greater reduction in bone density. The menopausal status at the time of diagnosis did not seem to have long-term effects in bone density; nevertheless, an early therapeutic intervention in premenopause is suggested to reduce bone loss. PMID:11740067

  4. Stability Performance of Inductively Coupled Plasma Mass Spectrometry-Phenotyped Kernel Minerals Concentration and Grain Yield in Maize in Different Agro-Climatic Zones.

    Directory of Open Access Journals (Sweden)

    Mallana Gowdra Mallikarjuna

    Full Text Available Deficiency of iron and zinc causes micronutrient malnutrition or hidden hunger, which severely affects ~25% of global population. Genetic biofortification of maize has emerged as cost effective and sustainable approach in addressing malnourishment of iron and zinc deficiency. Therefore, understanding the genetic variation and stability of kernel micronutrients and grain yield of the maize inbreds is a prerequisite in breeding micronutrient-rich high yielding hybrids to alleviate micronutrient malnutrition. We report here, the genetic variability and stability of the kernel micronutrients concentration and grain yield in a set of 50 maize inbred panel selected from the national and the international centres that were raised at six different maize growing regions of India. Phenotyping of kernels using inductively coupled plasma mass spectrometry (ICP-MS revealed considerable variability for kernel minerals concentration (iron: 18.88 to 47.65 mg kg(-1; zinc: 5.41 to 30.85 mg kg(-1; manganese: 3.30 to 17.73 mg kg(-1; copper: 0.53 to 5.48 mg kg(-1 and grain yield (826.6 to 5413 kg ha(-1. Significant positive correlation was observed between kernel iron and zinc within (r = 0.37 to r = 0.52, p < 0.05 and across locations (r = 0.44, p < 0.01. Variance components of the additive main effects and multiplicative interactions (AMMI model showed significant genotype and genotype × environment interaction for kernel minerals concentration and grain yield. Most of the variation was contributed by genotype main effect for kernel iron (39.6%, manganese (41.34% and copper (41.12%, and environment main effects for both kernel zinc (40.5% and grain yield (37.0%. Genotype main effect plus genotype-by-environment interaction (GGE biplot identified several mega environments for kernel minerals and grain yield. Comparison of stability parameters revealed AMMI stability value (ASV as the better representative of the AMMI stability parameters. Dynamic stability

  5. Small Animal Bone Biomechanics

    OpenAIRE

    Vashishth, Deepak

    2008-01-01

    Animal models, in particular mice, offer the possibility of naturally achieving or genetically engineering a skeletal phenotype associated with disease and conducting destructive fracture tests on bone to determine the resulting change in bone’s mechanical properties. Several recent developments, including nano- and micro- indentation testing, microtensile and microcompressive testing, and bending tests on notched whole bone specimens, offer the possibility to mechanically probe small animal ...

  6. Bone Biopsy

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging guidance ... limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided procedure ...

  7. Dietary patterns in Canadian men and women ages 25 and older: relationship to demographics, body mass index, and bone mineral density

    Directory of Open Access Journals (Sweden)

    Towheed Tanveer

    2010-01-01

    Full Text Available Abstract Background Previous research has shown that underlying dietary patterns are related to the risk of many different adverse health outcomes, but the relationship of these underlying patterns to skeletal fragility is not well understood. The objective of the study was to determine whether dietary patterns in men (ages 25-49, 50+ and women (pre-menopause, post-menopause are related to femoral neck bone mineral density (BMD independently of other lifestyle variables, and whether this relationship is mediated by body mass index. Methods We performed an analysis of 1928 men and 4611 women participants in the Canadian Multicentre Osteoporosis Study, a randomly selected population-based longitudinal cohort. We determined dietary patterns based on the self-administered food frequency questionnaires in year 2 of the study (1997-99. Our primary outcome was BMD as measured by dual x-ray absorptiometry in year 5 of the study (2000-02. Results We identified two underlying dietary patterns using factor analysis and then derived factor scores. The first factor (nutrient dense was most strongly associated with intake of fruits, vegetables, and whole grains. The second factor (energy dense was most strongly associated with intake of soft drinks, potato chips and French fries, certain meats (hamburger, hot dog, lunch meat, bacon, and sausage, and certain desserts (doughnuts, chocolate, ice cream. The energy dense factor was associated with higher body mass index independent of other demographic and lifestyle factors, and body mass index was a strong independent predictor of BMD. Surprisingly, we did not find a similar positive association between diet and BMD. In fact, when adjusted for body mass index, each standard deviation increase in the energy dense score was associated with a BMD decrease of 0.009 (95% CI: 0.002, 0.016 g/cm2 for men 50+ years old and 0.004 (95% CI: 0.000, 0.008 g/cm2 for postmenopausal women. In contrast, for men 25-49 years old

  8. Functional microimaging. A hierarchical investigation of bone failure behavior

    International Nuclear Information System (INIS)

    Biomechanical testing is the gold standard to determine bone competence, and has been used extensively. Direct mechanical testing provides detailed information on overall bone mechanical and material properties, but fails in revealing local properties such as local deformations and strains and does not permit quantification of fracture progression. Therefore, we incorporated several imaging methods in our mechanical setups to get a better insight into bone deformation and failure characteristics on various levels of structural organization. Our aim was to develop an integrative approach for hierarchical investigation of bone, working at different scales of resolution ranging from the whole bone to its ultrastructure. Inbred strains of mice make useful models to study bone properties. In this study, we concentrated on C57BL/6 (B6) and in C3H/He (C3H) mice, two strains known for their differences in bone phenotype. At the macroscopic level, we used high-resolution and high-speed cameras which allowed to visualize global failure behavior and fracture initiation with high temporal resolution. This image data proved especially important when dealing with small bones such as murine femora. At the microscopic level, bone microstructure, i.e. trabecular architecture and cortical porosity, are known to influence bone strength and failure mechanisms significantly. For this reason, we developed an image-guided failure assessment technique, also referred to as functional microimaging, allowing direct time-lapsed three-dimensional visualization and computation of local displacements and strains for better quantification of fracture initiation and progression. While the resolution of conventional desktop micro-computed tomography is typically around a few micrometers, computer tomography systems based on highly brilliant synchrotron radiation X-ray sources permit to explore the sub-micrometer world. This allowed, for the first time, to uncover fully nondestructively the 3D

  9. The bone mass density in men aged over 50 and its relation to the concentration of free and total testosterone in the blood serum

    International Nuclear Information System (INIS)

    As the mean length of life increases, osteoporosis affects a growing number of men and women, thus becoming an important medical and socioeconomic problem in many countries. Pathogenesis and the prevalence of the osteoporosis in women are well established, however, in men, they are still controversial. In this study, the bone mass density (BMD) of the lumbar spine was determined in 100 healthy men age 50-83, using quantitative computed tomography (QCT). Also, the total serum and free testosterone was measured. The mean BMD was 123.1I39.3 mg/cm3, and the values below a fracture threshold were noted in 39% of subjects. The mean concentration of total and free serum testosterone was 4.3I1.7 ng/ml and 6.2I3.7 pg/ml, respectively. There was a significant (p3, respectively). There was no correlation found between total testosterone and BMD. Results indicate that reduced bone mass density in males over 50 is as frequent as recently reported in females. Moreover, sex hormones seem to be related to osteoporosis development in men as well. (author)

  10. ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats

    DEFF Research Database (Denmark)

    Neerup, Trine Skovlund Ryge; Stahlhut, Martin; Petersen, Jørgen S; Daugaard, Jens Rejnhold; Jensen, Jens-Erik B; Peng, Zhiqi; Morko, Jukka; Thorkildsen, Christian

    2011-01-01

    Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac₅c¹, Aib³, Leu⁸, Gln¹⁰, Har¹¹, Ala¹², Trp...

  11. BONE MASS, RATES OF OSTEOPOROTIC FRACTURES, AND PREVENTION OF FRACTURES: ARE THERE DIFFERENCES BETWEEN CHINA AND WESTERN COUNTRIES?

    Institute of Scientific and Technical Information of China (English)

    葛秦生; StevenRCummings; 涂苓; 陈孝署; 赵熙和; 俞卫

    1994-01-01

    Fractures are one of the most common causes of disability in older women.The quantity and density of bone decrease with age.Most types of fractures increase as bone density declines.But most of the knowledge about causes and prevention of fractures comes from studies performed in Western countries.Asian women appear to have similar or slightly lower bone density that may be a result of their smaller size.The appear to have a lower risk of hip fracture than Whites.which may be a result of their shorter hip axis.The risks of other types of fractures in Chinese women is less well defined and reasons for differences in the rates of osteoporotic fractures between China and Western countries remain to be expolored.A study is underway in Beijing to describe the risks and potential causes of fractures among older women in urban China.Randomized trials in Western countries have demonstrated that calcium and vitamin D,estrogen,calcitonin,or bisphosphonates can reduce the rate of fractures.Increased intake of calcium and vitamin D may be the most effective approach to preventing fractures in China,but this should be tested be tested in a randomized trial.

  12. Anorexia nervosa and bone metabolism.

    Science.gov (United States)

    Fazeli, Pouneh K; Klibanski, Anne

    2014-09-01

    Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation with a lifetime prevalence of 2.2% in women. The most common medical co-morbidity in women with AN is bone loss, with over 85% of women having bone mineral density values more than one standard deviation below an age comparable mean. The low bone mass in AN is due to multiple hormonal adaptations to under nutrition, including hypothalamic amenorrhea and growth hormone resistance. Importantly, this low bone mass is also associated with a seven-fold increased risk of fracture. Therefore, strategies to effectively prevent bone loss and increase bone mass are critical. We will review hormonal adaptations that contribute to bone loss in this population as well as promising new therapies that may increase bone mass and reduce fracture risk in AN. PMID:24882734

  13. Anorexia nervosa and bone metabolism

    Science.gov (United States)

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation with a lifetime prevalence of 2.2% in women. The most common medical co-morbidity in women with AN is bone loss, with over 85% of women having bone mineral density values more than one standard deviation below an age comparable mean. The low bone mass in AN is due to multiple hormonal adaptations to under nutrition, including hypothalamic amenorrhea and growth hormone resistance. Importantly, this low bone mass is also associated with a seven-fold increased risk of fracture. Therefore, strategies to effectively prevent bone loss and increase low bone mass are critical. We will review hormonal adaptations that contribute to bone loss in this population as well as promising new therapies that may increase bone mass and reduce fracture risk in AN. PMID:24882734

  14. A high proportion of bone marrow T cells with regulatory phenotype (CD4+CD25hiFoxP3+) in Ewing sarcoma patients is associated with metastatic disease.

    Science.gov (United States)

    Brinkrolf, Peter; Landmeier, Silke; Altvater, Bianca; Chen, Christiane; Pscherer, Sibylle; Rosemann, Annegret; Ranft, Andreas; Dirksen, Uta; Juergens, Heribert; Rossig, Claudia

    2009-08-15

    Immunosuppressive CD4+CD25(hi)FoxP3+ T cells (T(reg) cells) have been found at increased densities within the tumor microenvironment in many malignancies and interfere with protective antitumor immune responses. Osseous Ewing sarcomas (ESs) are thought to derive from a bone marrow (BM) mesenchymal cell of origin, and microscopic marrow involvement defines a subpopulation of patients at a high risk of relapse. We hypothesized that BM-resident T cells may contribute to a permissive milieu for immune escape of ESs. Using 6-color-flow cytometry, we investigated the pattern of immune cell subset distribution including NK cells, gammadelta T cells, central and effector memory CD8+ and CD4+ T cells as well as T cells with regulatory phenotype (T(reg) cells) in BM obtained at diagnosis from 45 primary or relapsed ES patients treated within standardized protocols. Although patients at relapse had an inverted CD4:CD8 T-cell ratio, neither CD8+ effector/memory T-cell subsets nor T(reg) cells significantly differed from patients at diagnosis. No significant associations of innate and effector/memory T-cell subpopulations with known risk factors were found, including age, gender, tumor site, primary metastases and histological tumor response. By contrast, T(reg) cells were found at significantly higher frequencies in patients with primary metastatic disease compared with localized ESs (5.0 vs. 3.3%, p = 0.01). Thus, increased BM T(reg) cells in patients with metastasized ES may reflect an immune escape mechanism that contributes to the development of metastatic disease. Immunotherapeutic strategies will have to adequately consider the regulatory milieu within areas of Ewing tumor-immune interactions. PMID:19480009

  15. The value of calcaneal bone mass measurement using a dual X-ray laser calscan device in risk screening for osteoporosis

    Directory of Open Access Journals (Sweden)

    Gulseren Kayalar

    2009-01-01

    Full Text Available OBJECTIVE: To evaluate how bone mineral density in the calcaneus measured by a dual energy X-ray laser (DXL correlates with bone mineral density in the spine and hip in Turkish women over 40 years of age and to determine whether calcaneal dual energy X-ray laser variables are associated with clinical risk factors to the same extent as axial bone mineral density measurements obtained using dual energy x-ray absorbtiometry (DXA. MATERIALS AND METHODS: A total of 2,884 Turkish women, aged 40-90 years, living in Ankara were randomly selected. Calcaneal bone mineral density was evaluated using a dual energy X-ray laser Calscan device. Subjects exhibiting a calcaneal dual energy X-ray laser T- score <-2.5 received a referral for DXA of the spine and hip. Besides dual energy X-ray laser measurements, all subjects were questioned about their medical history and the most relevant risk factors for osteoporosis. RESULTS: Using a T-score threshold of -2.5, which is recommended by the World Health Organization (WHO, dual energy X-ray laser calcaneal measurements showed that 13% of the subjects had osteoporosis, while another 56% had osteopenia. The mean calcaneal dual energy X-ray laser T-score of postmenopausal subjects who were smokers with a positive history of fracture, hormone replacement therapy (HRT, covered dressing style, lower educational level, no regular exercise habits, and low tea consumption was significantly lower than that obtained for the other group (p<0.05. A significant correlation was observed between the calcaneal dual energy X-ray laser T-score and age (r=-0.465, p=0.001, body mass index (BMI (r=0.223, p=0.001, number of live births (r=-0.229, p=0.001, breast feeding time (r=-0.064, p=0.001, and age at menarche (r=-0.050, p=0.008. The correlations between calcaneal DXL and DXA T-scores (r=0.340, p=0.001 and calcaneal DXL and DXA Z-scores (r=0.360, p=0.001 at the spine, and calcaneal DXL and DXA T- scores (r=0.28, p=0.001 and calcaneal

  16. Energy deficiency, menstrual disturbances and low bone mass: What do Australian exercising females know about the female athlete triad?

    Science.gov (United States)

    Kyriazis, Stephanie M; Kukuljan, Sonja; Turner, Anne I; van der Pligt, Paige; Ducher, Gaele

    2012-02-15

    PURPOSE: Prevention of the female athlete triad is essential to protect female athletes' health. The aim of this study was to investigate the knowledge, attitudes and behaviours of regularly exercising adult females towards eating patterns, menstrual cycles and bone health. METHODS: A total of 191 female exercisers, aged 18-40 y, engaging in ≥2 hr/wk of strenuous activity, completed a survey. After excluding 11 surveys (due to incomplete answers), the 180 participants were categorised into lean-build sports (n=82; running/athletics, triathlon, swimming, cycling, dancing, rowing), non lean-build sports (n=94; basketball, netball, soccer, hockey, volleyball, tennis, trampoline, squash, Australian football) or gym/fitness activities (n=4). RESULTS: Mean (±SD) training volume was 9.0±5.5 hr/wk, with participants competing from local up to international level. Only 10% of respondents could name the 3 components of the female athlete triad. Regardless of the reported history of stress fracture, 45% of the respondents did not think that amenorrhoea (absence of menses for ≥ three months) could affect bone health, and 22% of those involved in lean-build sports would do nothing if experiencing amenorrhoea (vs. 3.2% in non lean-build sports, p=0.005). Lean-build sports, history of amenorrhoea and history of stress fracture were all significantly associated with not taking action in the presence of amenorrhoea (all p<0.005). CONCLUSIONS: Few active Australian women are aware of the detrimental effects of menstrual dysfunction on bone health. Education programs are needed to prevent the female athlete triad and ensure appropriate actions are taken by athletes when experiencing amenorrhoea. PMID:22349258

  17. Hormonal Relationships to Bone Mass in Elderly Spanish Men as Influenced by Dietary Calcium and Vitamin D

    OpenAIRE

    Jose M Moran; Luis Gonzalez Lopez-Arza; Jesus M. Lavado-Garcia; Maria Pedrera-Canal; Purificacion Rey-Sanchez; Rodriguez-Velasco, Francisco J.; Pilar Fernandez; Juan D. Pedrera-Zamorano

    2013-01-01

    We aim to evaluate whether calcium and vitamin D intake is associated with 25-hydroxyvitamin D (25-OH-Vitamin D3) and parathyroid hormone (PTH) serum concentrations or is associated with either the phalangeal dual energy X-ray absorptiometry (pDXA) or the quantitative bone ultrasound (QUS) in independent elderly men. Serum PTH and 25-OH-Vitamin D3 were measured in 195 healthy elderly men (mean age: 73.31 ± 5.10 year). Food intake was quantified using a dietetic scale. Participants with 25-...

  18. Preventing and Treating Brittle Bones and Osteoporosis | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... Javascript on. Feature: Osteoporosis Preventing and Treating Brittle Bones and Osteoporosis Past Issues / Winter 2011 Table of ... at high risk due to low bone mass. Bone and Bone Loss Bone is living, growing tissue. ...

  19. Urinary cadmium excretion is correlated with calcaneal bone mass i Japanese women living in an urban area

    International Nuclear Information System (INIS)

    Nine hundred eight women aged 40-88 years living in a non-Cd-polluted area in Japan were analyzed for urinary cadmium (Cd) N-acetyl-β-D-glucosaminidase (NAG) activity, β2-microglobuli (B2MG) concentration, and for the stiffness index (STIFF) of calcaneal bone using an ultrasound method. The urinary Cd in the subjects, with a mean an range of 2.87 and 0.25-11.4 μg/g creatinine, respectively, showed significant correlation with NAG but not with B2MG. STIFF was significantly inversely correlated with urinary Cd, and the association remaine significant after adjusting for age, body weight, and menstrual status suggesting a significant effect of Cd on the bone loss in these subject without signs of Cd-induced kidney damage. A two-fold increase in urinary C was accompanied by a decrease in STIFF corresponding to a 1.7-year rise in age. These results emphasize the need for reassessment of the significance of Cd exposure in the general Japanese population

  20. Distribution Principle of Bone Tissue

    CERN Document Server

    Fan, Yifang; Fan, Yubo; Xu, Zongxiang; Li, Zhiyu

    2009-01-01

    Using the analytic and experimental techniques we present an exploratory study of the mass distribution features of the high coincidence of centre of mass of heterogeneous bone tissue in vivo and its centroid of geometry position. A geometric concept of the average distribution radius of bone issue is proposed and functional relation of this geometric distribution feature between the partition density and its relative tissue average distribution radius is observed. Based upon the mass distribution feature, our results suggest a relative distance assessment index between the center of mass of cortical bone and the bone center of mass and establish a bone strength equation. Analysing the data of human foot in vivo, we notice that the mass and geometric distribution laws have expanded the connotation of Wolff's law, which implies a leap towards the quantitative description of bone strength. We finally conclude that this will not only make a positive contribution to help assess osteoporosis, but will also provide...

  1. Age-Related Changes in Bone Mass in the Senescence-Accelerated Mouse (SAM): SAM-R/3 and SAM-P/6 as New Murine Models for Senile Osteoporosis

    OpenAIRE

    Matsushita, Mutsumi; Tsuboyama, Tadao; Kasai, Ryuichi; Okumura, Hideo; Yamamuro, Takao; HIGUCHI, Keiichi; Higuchi, Kayoko; Kohno, Atsuko; Yonezu, Tomonori; Utani, Atsushi; Umezawa, Makiko; TAKEDA, Toshio

    1986-01-01

    Age-related changes of the femoral bone mass in several strains of the senescence-accelerated mouse (SAM) were investigated. Microdensitometrically, all strains exhibited essentially the same patterns of age changes, that is, bone mass corrected by the diameter of the shaft reached the peak value when the mice were 4 or 5 months of age and then fell linearly with age up to over 20 months of age. Two strains, SAM-R/3 and SAM-P/6, which originated from the same ancestry on pedigree, had a signi...

  2. Decreased Bone Mineral Density in Patients Submitted to Kidney Transplantation Is Related to Age, Body Mass Index, Time on Dialysis, and Hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Miguel Madeira

    2014-01-01

    Full Text Available Background. Renal transplantation (Tx influences bone mineral density (BMD by several mechanisms. The main objective of this study was to correlate BMD and risk factors associated with bone loss in patients submitted to kidney Tx. Methods. We evaluated 88 individuals after renal Tx (median time = 31.5 months since Tx. All of them sustained glomerular filtration rate ≥60 mL/min/1.73 m2. BMD was measured by dual-energy X-ray absorptiometry (DXA, Prodigy-GE. Calcium, phosphate, albumin, creatinine, and intact parathormone (PTH were measured at the same time. All statistical tests were two-sided and P value less than 0.05 were accepted as significant for all analyses in this study. Results. Serum PTH was raised in 42% patients, but corrected calcium was normal in 83 patients. No fragility fracture was reported, but the overall prevalence of osteoporosis was 27.6% and lower than expected BMD (Z-score ≤ −2.0 SD was observed in 28.4%. Patients with lower than expected BMD had higher PTH levels. Conclusions. Older age, lower body mass index (BMI, longer time on dialysis, and elevated PTH levels were identified as the main factors associated with lower BMD.

  3. Bone Grafts

    Science.gov (United States)

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  4. Bone metabolism in anorexia nervosa.

    Science.gov (United States)

    Fazeli, Pouneh K; Klibanski, Anne

    2014-03-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed, chronic nutritional deprivation and distorted body image. AN is associated with a number of medical comorbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  5. Bone Metabolism in Anorexia Nervosa

    Science.gov (United States)

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  6. Increasing weight-bearing physical activity and calcium-rich foods to promote bone mass gains among 9–11 year old girls: outcomes of the Cal-Girls study

    Directory of Open Access Journals (Sweden)

    Hannan Peter

    2005-07-01

    Full Text Available Abstract Background A two-year, community-based, group-randomized trial to promote bone mass gains among 9–11 year-old girls through increased intake of calcium-rich foods and weight-bearing physical activity was evaluated. Methods Following baseline data collection, 30 5th-grade Girl Scout troops were randomized to a two-year behavioral intervention program or to a no-treatment control group. Evaluations were conducted at baseline, one year, and two years. Measures included bone mineral content, density, and area (measured by DXA, dietary calcium intake (24-hour recall, and weight-bearing physical activity (physical activity checklist interview. Mixed-model regression was used to evaluate treatment-related changes in bone mineral content (g for the total body, lumbar spine (L1-L4, proximal femur, one-third distal radius, and femoral neck. Changes in eating and physical activity behavioral outcomes were examined. Results Although the intervention was implemented with high fidelity, no significant intervention effects were observed for total bone mineral content or any specific bone sites. Significant intervention effects were observed for increases in dietary calcium. No significant intervention effects were observed for increases in weight-bearing physical activity. Conclusion Future research needs to identify the optimal dosage of weight-bearing physical activity and calcium-rich dietary behavior change required to maximize bone mass gains in pre-adolescent and adolescent girls.

  7. Physiologically-based pharmacokinetic modeling of tamoxifen and its metabolites in women of different CYP2D6 phenotypes provides new insight into the tamoxifen mass balance

    Directory of Open Access Journals (Sweden)

    Kristin eDickschen

    2012-05-01

    Full Text Available Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of estrogen receptor positive (ER+ mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6. It is widely accepted that CYP2D6 poor metabolizers (PM exert a pronounced decrease in endoxifen steady-state plasma concentrations compared to CYP2D6 extensive metabolizers (EM. Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved.In this context, physiologically-based pharmacokinetic (PBPK-modeling provides a useful tool to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy.It has long been thought that only a minor percentage of endoxifen is formed via 4-hydroxytamoxifen. However, the current investigation supports very recently published data that postulates a contribution of 4-hydroxytamoxifen above 20 % to total endoxifen formation. The developed PBPK-model describes tamoxifen PK in rats and humans. Moreover, tamoxifen metabolism in dependence of CYP2D6 phenotype in populations of European female individuals is well described, thus providing a good basis to further investigate the linkage of PK, mode of action, and treatment outcome in dependence of factors such as phenotype, ethnicity or co-treatment with CYP2D6 inhibitors.

  8. Bone Metabolism in Adolescents with Anorexia Nervosa

    Science.gov (United States)

    Misra, Madhusmita; Klibanski, Anne

    2013-01-01

    Adolescents with anorexia nervosa (AN) are at risk for low bone mass at multiple sites, associated with decreased bone turnover. Bone microarchitecture is also affected, with a decrease in bone trabecular volume and trabecular thickness, and an increase in trabecular separation. The adolescent years are typically the time when marked increases occur in bone mass accrual towards the attainment of peak bone mass, an important determinant of bone health and fracture risk in later life. AN often begins in the adolescent years, and decreased rates of bone mass accrual at this critical time are therefore also concerning for deficits in peak bone mass. Factors contributing to low bone density and decreased rates of bone accrual include alterations in body composition such as low BMI and lean body mass, and hormonal alterations such as hypogonadism, a nutritionally acquired resistance to growth hormone and low levels of IGF-1, relative hypercortisolemia, low levels of leptin, and increased adiponectin (for fat mass) and peptide YY. Therapeutic strategies include optimizing weight and menstrual recovery, and adequate calcium and vitamin D replacement. Oral estrogen-progesterone combination pills are not effective in increasing bone density in adolescents with AN. RhIGF-1 increases levels of bone formation markers in the short-term, while long-term effects remain to be determined. Bisphosphonates act by decreasing bone resorption, and are not optimal for use in adolescents with AN, in whom the primary defect is low bone formation. PMID:21301203

  9. Mechanisms inducing low bone density in Duchenne muscular dystrophy in mice and humans.

    Science.gov (United States)

    Rufo, Anna; Del Fattore, Andrea; Capulli, Mattia; Carvello, Francesco; De Pasquale, Loredana; Ferrari, Serge; Pierroz, Dominique; Morandi, Lucia; De Simone, Michele; Rucci, Nadia; Bertini, Enrico; Bianchi, Maria Luisa; De Benedetti, Fabrizio; Teti, Anna

    2011-08-01

    Patients affected by Duchenne muscular dystrophy (DMD) and dystrophic MDX mice were investigated in this study for their bone phenotype and systemic regulators of bone turnover. Micro-computed tomographic (µCT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild-type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro-osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL-6) was increased compared with wild-type mice. Likewise, DMD patients showed low bone mineral density (BMD) Z-scores and high bone-resorption marker and serum IL-6. Human primary osteoblasts from healthy donors incubated with 10% sera from DMD patients showed decreased nodule mineralization. Many osteogenic genes were downregulated in these cultures, including osterix and osteocalcin, by a mechanism blunted by an IL-6-neutralizing antibody. In contrast, the mRNAs of osteoclastogenic cytokines IL6, IL11, inhibin-βA, and TGFβ2 were increased, although only IL-6 was found to be high in the circulation. Consistently, enhancement of osteoclastogenesis was noted in cultures of circulating mononuclear precursors from DMD patients or from healthy donors cultured in the presence of DMD sera or IL-6. Circulating IL-6 also played a dominant role in osteoclast formation because ex vivo wild-type calvarial bones cultured with 10% sera of MDX mice showed increase osteoclast and bone-resorption parameters that were dampen by treatment with an IL-6 antibody. These results point to IL-6 as an important mediator of bone loss in DMD and suggest that targeted anti-IL-6 therapy may have a positive impact on the bone phenotype in these patients. PMID:21509823

  10. Biochemical markers of bone turnover

    International Nuclear Information System (INIS)

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays

  11. Blood and Bones: The Influence of the Mass Media on Australian Primary School Children's Understandings of Genes and DNA

    Science.gov (United States)

    Donovan, Jenny; Venville, Grady

    2012-06-01

    Previous research showed that primary school children held several misconceptions about genetics of concern for their future lives. Included were beliefs that genes and DNA are separate substances, with genes causing family resemblance and DNA identifying suspects at crime scenes. Responses to this work `blamed' the mass media for these misunderstandings. This study aimed to determine whether that blame had any foundation by examining the media habits and conceptions about genes and DNA of Australian children. With little prior research considering the influence of entertainment mass media on children's academically relevant knowledge, this was an exploratory study with a mixed modes design. Data were collected by detailed media questionnaires and face-to-face interviews with 62 children aged 10-12 years, and subjected to content and thematic analysis. Specific mass media examples children reported using were examined for genetics content. Results indicate 5 h/day of media use, mostly television including crime shows, and that children perceived television to be their main source of information about genetics. Most children (89 %) knew DNA, 60 % knew genes, and more was known about uses of DNA outside the body such as crime solving or resolving family relationships than about its biological nature and function. Half believed DNA is only in blood and body parts used for forensics. These concepts paralleled the themes emerging from the media examples. The results indicate that the mass media is a pervasive teacher of children, and that fundamental concepts could be introduced earlier in schools to establish scientific concepts before misconceptions arise.

  12. Bone health in eating disorders.

    Science.gov (United States)

    Zuckerman-Levin, N; Hochberg, Z; Latzer, Y

    2014-03-01

    Eating disorders (EDs) put adolescents and young adults at risk for impaired bone health. Low bone mineral density (BMD) with ED is caused by failure to accrue peak bone mass in adolescence and bone loss in young adulthood. Although ED patients diagnosed with bone loss may be asymptomatic, some suffer bone pains and have increased incidence of fractures. Adolescents with ED are prone to increased prevalence of stress fractures, kyphoscoliosis and height loss. The clinical picture of the various EDs involves endocrinopathies that contribute to impaired bone health. Anorexia nervosa (AN) is characterized by low bone turnover, with relatively higher osteoclastic (bone resorptive) than osteoblastic (bone formation) activity. Bone loss in AN occurs in both the trabecular and cortical bones, although the former is more vulnerable. Bone loss in AN has been shown to be influenced by malnutrition and low weight, reduced fat mass, oestrogen and androgen deficiency, glucocorticoid excess, impaired growth hormone-insulin-like growth factor 1 axis, and more. Bone loss in AN may not be completely reversible despite recovery from the illness. Treatment modalities involving hormonal therapies have limited effectiveness, whereas increased caloric intake, weight gain and resumption of menses are essential to improved BMD. PMID:24165231

  13. Reduced systemic bone mineral density associated with a rare case of tooth and nail syndrome

    International Nuclear Information System (INIS)

    Purpose: This is the first report of a rare genetic tooth and nail syndrome (TNS) diagnosed in a 14-year-old Caucasian girl with a complete absence of the permanent dentition and, additionally, reduced total and lumbar spine bone mineral density (BMD). This coincidence suggests a new clinical manifestation of the disorder in which genetic factors and/or shared mechanisms may be responsible for the deterioration of the stomatognathic system, anodontia, nail phenotype and osteopenia. Low bone mass appears to be a new component of the syndrome. There is a rationale for bone densitometry scans assuming that patients with TNS may have an increased risk of osteopenia. Reduced BMD and, possibly, impaired bone quality and strength may produce difficulties or even exclude such patients from future treatment with dental implants. (authors)

  14. Hormonal Relationships to Bone Mass in Elderly Spanish Men as Influenced by Dietary Calcium and Vitamin D

    Directory of Open Access Journals (Sweden)

    Jose M. Moran

    2013-12-01

    Full Text Available We aim to evaluate whether calcium and vitamin D intake is associated with 25-hydroxyvitamin D (25-OH-Vitamin D3 and parathyroid hormone (PTH serum concentrations or is associated with either the phalangeal dual energy X-ray absorptiometry (pDXA or the quantitative bone ultrasound (QUS in independent elderly men. Serum PTH and 25-OH-Vitamin D3 were measured in 195 healthy elderly men (mean age: 73.31 ± 5.10 year. Food intake was quantified using a dietetic scale. Participants with 25-OH-Vitamin D3 levels ≥ 30 ng/mL (75 nmol/L and a calcium intake of 800–1200 mg/day exhibited the lowest PTH levels (41.49 ± 16.72 ng/mL. The highest PTH levels (75.60 ± 14.16 ng/mL were observed in the <30 ng/mL group 25-OH-Vitamin D3 with a calcium intake >1200 mg/day. No significant differences in the serum PTH levels based on the serum 25-OH-Vitamin D3 levels were observed among participants with a calcium intake of 800–1200 mg/day. Serum PTH was inversely correlated with serum 25-OH-Vitamin D3 in the entire patient sample (r = −0.288, p = 0.019. No differences in any of the three densitometry techniques were observed between any of the age groups in the 800–1200 mg/day and >1200 mg/day calcium intake groups. PTH levels correlate negatively with serum 25-OH-Vitamin D3 levels, and neither calcium nor vitamin D intake exert a strong influence on either of the two parameters.

  15. Hormonal relationships to bone mass in elderly Spanish men as influenced by dietary calcium and vitamin D.

    Science.gov (United States)

    Moran, Jose M; Lopez-Arza, Luis Gonzalez; Lavado-Garcia, Jesus M; Pedrera-Canal, Maria; Rey-Sanchez, Purificacion; Rodriguez-Velasco, Francisco J; Fernandez, Pilar; Pedrera-Zamorano, Juan D

    2013-12-01

    We aim to evaluate whether calcium and vitamin D intake is associated with 25-hydroxyvitamin D (25-OH-Vitamin D3) and parathyroid hormone (PTH) serum concentrations or is associated with either the phalangeal dual energy X-ray absorptiometry (pDXA) or the quantitative bone ultrasound (QUS) in independent elderly men. Serum PTH and 25-OH-Vitamin D3 were measured in 195 healthy elderly men (mean age: 73.31 ± 5.10 year). Food intake was quantified using a dietetic scale. Participants with 25-OH-Vitamin D3 levels ≥ 30 ng/mL (75 nmol/L) and a calcium intake of 800-1200 mg/day exhibited the lowest PTH levels (41.49 ± 16.72 ng/mL). The highest PTH levels (75.60 ± 14.16 ng/mL) were observed in the ng/mL group 25-OH-Vitamin D3 with a calcium intake >1200 mg/day. No significant differences in the serum PTH levels based on the serum 25-OH-Vitamin D3 levels were observed among participants with a calcium intake of 800-1200 mg/day. Serum PTH was inversely correlated with serum 25-OH-Vitamin D3 in the entire patient sample (r = -0.288, p = 0.019). No differences in any of the three densitometry techniques were observed between any of the age groups in the 800-1200 mg/day and >1200 mg/day calcium intake groups. PTH levels correlate negatively with serum 25-OH-Vitamin D3 levels, and neither calcium nor vitamin D intake exert a strong influence on either of the two parameters. PMID:24304609

  16. GENETIC MARKERS OF LOW BONE MINERAL DENSITY IN PATIENTS WITH CYSTIC FIBROSIS.

    Directory of Open Access Journals (Sweden)

    Tatjana Jakovska

    2015-03-01

    Full Text Available Introduction: failure to maintain bone mass density is a major problem in patients with cystic fibrosis (CF. CF is due to mutations in the CFTR gene and other genes may contribute to modifying the disease. Genetic and environmental factors may play a role in determining the variability of bone mass. Aim of the study: to analyse the association between polymorphic variants of genes considered to be risk factors of bone metabolism disturbances and decreased bone mineral density (BMD in children and adults with CF in R. Macedonia. Materials and methods: the study included 80 clinically stable CF patients (age range 5-36y, who regularly attended the CF center at the Pediatric Clinic in Skopje, Macedonia. Three candidate genes likely associated with BMD variability were studied: the vitamin D receptor (VDR gene, the estrogen receptor alpha (ESR1 and the type I alpha I collagen (COLIA1 gene. A complete bone and CF evaluation was obtained for all patients: 55 had normal BMD (group 1, 17 were osteopenic (group 2 and 8 were osteoporotic (group 3. Results: Low bone mineral density (Z score < -1SD was found in 31.25% patients and in 10% of them BMD was below -2SD. Patients with low BMD had worse BMI, FEV1 and more severe symptoms of CF. No significant correlation was found between COLIA1 and VDR polymorphisms and BMD. Conclusion: There was no evidence that the genes under study may modulate bone phenotype in CF.

  17. Determination of osteocalcin in meat and bone meal of bovine and porcine origin using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry and high-resolution hybrid mass spectrometry

    International Nuclear Information System (INIS)

    A method has been developed for determining the origin of meat and bone meal (MBM) by detecting species-specific osteocalcin (OC) using matrix-assisted laser desorption ionization/time-of-flight (MALDI/TOF) and high-resolution hybrid mass spectrometry (HR-Q/TOF MS). The analysis is based on the detection of typical species-specific OC and its tryptic peptide fragments which differ in mass due to differences in the amino-acid sequences between species. After dissolving the MBM samples in EDTA buffer, purification after ultrafiltration was performed using two methods: solid-phase extraction using Zip-Tip C18 or size exclusion coupled with reverse-phase chromatography. Fractions containing partially purified intact OC were analyzed using LC-Q/TOF and MALDI/TOF mass spectrometry. Species-specific OC was detected at the typical protonated and doubly protonated molecular ions. Furthermore, typical porcine- and bovine-derived tryptic fragments from MBM were detected after enzymatic digestion. In order to determine the underlying amino-acid sequences and to confirm the assignment to OC-derived peptides, MS/MS analysis was carried out. In conclusion, we were able to detect OC in bovine and porcine MBM with high sensitivity and the MS-based method described here by which total OC mass and marker peptides of digested OC are recorded can be used as an alternative approach to detect genus-specific differences in MBM and can be applied as a confirmatory method to mainly immunological osteocalcin screening methods.

  18. Determination of osteocalcin in meat and bone meal of bovine and porcine origin using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry and high-resolution hybrid mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Balizs, Gabor, E-mail: gabor.balizs@bfr.bund.de [Federal Institute for Risk Assessment, Thielallee 88-92, D-14195 Berlin (Germany); Weise, Christoph [Freie Universitaet Berlin, Institute for Chemistry and Biochemistry, Thielallee 63, D-14195 Berlin (Germany); Rozycki, Christel; Opialla, Tobias; Sawada, Stefanie; Zagon, Jutta; Lampen, Alfonso [Federal Institute for Risk Assessment, Thielallee 88-92, D-14195 Berlin (Germany)

    2011-05-05

    A method has been developed for determining the origin of meat and bone meal (MBM) by detecting species-specific osteocalcin (OC) using matrix-assisted laser desorption ionization/time-of-flight (MALDI/TOF) and high-resolution hybrid mass spectrometry (HR-Q/TOF MS). The analysis is based on the detection of typical species-specific OC and its tryptic peptide fragments which differ in mass due to differences in the amino-acid sequences between species. After dissolving the MBM samples in EDTA buffer, purification after ultrafiltration was performed using two methods: solid-phase extraction using Zip-Tip C{sub 18} or size exclusion coupled with reverse-phase chromatography. Fractions containing partially purified intact OC were analyzed using LC-Q/TOF and MALDI/TOF mass spectrometry. Species-specific OC was detected at the typical protonated and doubly protonated molecular ions. Furthermore, typical porcine- and bovine-derived tryptic fragments from MBM were detected after enzymatic digestion. In order to determine the underlying amino-acid sequences and to confirm the assignment to OC-derived peptides, MS/MS analysis was carried out. In conclusion, we were able to detect OC in bovine and porcine MBM with high sensitivity and the MS-based method described here by which total OC mass and marker peptides of digested OC are recorded can be used as an alternative approach to detect genus-specific differences in MBM and can be applied as a confirmatory method to mainly immunological osteocalcin screening methods.

  19. Bone Density in Cerebral Palsy

    OpenAIRE

    Houlihan, Christine Murray; Stevenson, Richard D.

    2009-01-01

    Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture.1 Osteoporosis remains a major health problem worldwide, costing an estimated $13.8 billion in health care each year in the United States. Despite advances in treating osteoporosis in the elderly, no cure exists. Osteoporosis has its roots in childhood. Accrual of bone mass occurs throughout childhood and early adulthood, and peak bone mass is a key determinant...

  20. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  1. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another part of the body is more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 ...

  2. Bone Diseases

    Science.gov (United States)

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  3. Aging and bone. X-ray bone densitometry

    International Nuclear Information System (INIS)

    Bone mass at all ages of the individuals is the integration of genetic factors, nutrition, physical exercise, hormonal environments, and other factors influencing the bone. It is also a measurable risk factor for osteoporosis which may subsequently cause bone fractures. Thus measuring bone mass is required to predict the probability of developing bone fractures subsequent to osteoporosis, and to diagnose osteoporosis, and to manage the osteoporosis patient. This paper discusses bone mineral measurements according to their characteristics and clinical application. Methodology for measuring bone mass has rapidly progressed during the past 15 years, which covers photodensitometry, photon absorptiometry (single energy X-ray absorptiometry and dual energy X-ray absorptiometry), quantitative CT, and ultrasound. These techniques have allowed noninvasive measurement of bone mineral density in any site of the skeleton with high accuracy and precision, although a single use of the technique cannot satisfy the complete clinical requirements. Thus the most appropriate method for measuring bone mineral density is important to monitor bone mass change and according to the specific site. (N.K.)

  4. Versatile lipid profiling by liquid chromatography–high resolution mass spectrometry using all ion fragmentation and polarity switching. Preliminary application for serum samples phenotyping related to canine mammary cancer

    International Nuclear Information System (INIS)

    Graphical abstract: -- Highlights: •Lipidomics, high resolution mass spectrometry, polarity switching, serum, canine mammary cancer. -- Abstract: Lipids represent an extended class of substances characterized by such high variety and complexity that makes their unified analyses by liquid chromatography coupled to either high resolution or tandem mass spectrometry (LC–HRMS or LC–MS/MS) a real challenge. In the present study, a new versatile methodology associating ultra high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC–HRMS/MS) have been developed for a comprehensive analysis of lipids. The use of polarity switching and “all ion fragmentation” (AIF) have been two action levels particularly exploited to finally permit the detection and identification of a multi-class and multi-analyte extended range of lipids in a single run. For identification purposes, both higher energy collision dissociation (HCD) and in-source CID (collision induced dissociation) fragmentation were evaluated in order to obtain information about the precursor and product ions in the same spectra. This approach provides both class-specific and lipid-specific fragments, enhancing lipid identification. Finally, the developed method was applied for differential phenotyping of serum samples collected from pet dogs developing spontaneous malignant mammary tumors and health controls. A biological signature associated with the presence of cancer was then successfully revealed from this lipidome analysis, which required to be further investigated and confirmed at larger scale

  5. Versatile lipid profiling by liquid chromatography–high resolution mass spectrometry using all ion fragmentation and polarity switching. Preliminary application for serum samples phenotyping related to canine mammary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gallart-Ayala, H., E-mail: laberca@oniris-nantes.fr [LUNAM, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes Atlantique (Oniris), USC 1329 INRA Laboratoire d’Etude des résidus et Contaminants dans les Aliments (LABERCA), Site de la Chantrerie – CS50707, 44307 Nantes cedex 3 (France); Courant, F.; Severe, S.; Antignac, J.-P. [LUNAM, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes Atlantique (Oniris), USC 1329 INRA Laboratoire d’Etude des résidus et Contaminants dans les Aliments (LABERCA), Site de la Chantrerie – CS50707, 44307 Nantes cedex 3 (France); Morio, F.; Abadie, J. [LUNAM, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes Atlantique (Oniris), Cancers Animaux, Modèles pour la Recherche en Oncologie Comparée (AMaROC), Site de la Chantrerie–CS50707, 44307 Nantes cedex 3 (France); Le Bizec, B. [LUNAM, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes Atlantique (Oniris), USC 1329 INRA Laboratoire d’Etude des résidus et Contaminants dans les Aliments (LABERCA), Site de la Chantrerie – CS50707, 44307 Nantes cedex 3 (France)

    2013-09-24

    Graphical abstract: -- Highlights: •Lipidomics, high resolution mass spectrometry, polarity switching, serum, canine mammary cancer. -- Abstract: Lipids represent an extended class of substances characterized by such high variety and complexity that makes their unified analyses by liquid chromatography coupled to either high resolution or tandem mass spectrometry (LC–HRMS or LC–MS/MS) a real challenge. In the present study, a new versatile methodology associating ultra high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC–HRMS/MS) have been developed for a comprehensive analysis of lipids. The use of polarity switching and “all ion fragmentation” (AIF) have been two action levels particularly exploited to finally permit the detection and identification of a multi-class and multi-analyte extended range of lipids in a single run. For identification purposes, both higher energy collision dissociation (HCD) and in-source CID (collision induced dissociation) fragmentation were evaluated in order to obtain information about the precursor and product ions in the same spectra. This approach provides both class-specific and lipid-specific fragments, enhancing lipid identification. Finally, the developed method was applied for differential phenotyping of serum samples collected from pet dogs developing spontaneous malignant mammary tumors and health controls. A biological signature associated with the presence of cancer was then successfully revealed from this lipidome analysis, which required to be further investigated and confirmed at larger scale.

  6. Association between VDR ApaI Polymorphism and Hip Bone Mineral Density Can Be Modified by Body Mass Index: A Study on Postmenopausal Chinese Women

    Institute of Scientific and Technical Information of China (English)

    Hong XU; Dong-Hai XIONG; Fu-Hua XU; Yuan-Yuan ZHANG; Shu-Feng LEI; Hong-Wen DENG

    2005-01-01

    Osteoporosis is a major public health problem for old people. Genetic factors are considered to be major contributors to the pathogenesis of postmenopausal osteoporosis. The vitamin D receptor (VDR)gene is a prominent candidate gene for the regulation of postmenopausal bone mass; however, despite extensive studies, controversy remains regarding its association with postmenopausal body mineral density (BMD)variation. In this study, a total of 260 healthy postmenopausal Chinese women were genotyped at the VDR ApaI locus using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Raw hip BMD was significantly associated with VDR ApaI polymorphism with and without adjusting for age(P=0.015 and 0.040, respectively). This genetic effect can explain 3.32% of hip BMD variation. However,the significant association vanished after correcting for both age and body mass index (BMI) (P=0.169). In addition, we observed a significant association between VDR ApaI polymorphism with unadjusted BMI(P=0.042) or BMI adjusted for age (P=0.049). The raw hip BMD was also found to be significantly correlated with BMI (r=0.517, P=0.0001), with BMI explaining 26.35% of the variation of hip BMD. All of these facts prompt us to conclude that the significant association between the VDR ApaI genotype and hip BMD may be modified by BMI in postmenopausal Chinese women. Our findings may partially explain the earlier inconsistent association results concerning the VDR gene and BMD, and highlight the importance of incorporating covariates such as BMI into osteoporosis association studies.

  7. Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study

    DEFF Research Database (Denmark)

    Ravn, Pernille; Hosking, D; Thompson, D; Cizza, G; Wasnich, R D; McClung, M; Yates, A J; Bjarnason, N H; Christiansen, C

    1999-01-01

    To establish whether biochemical markers could be used to monitor alendronate (ALN) treatment and predict long-term response in bone mass, we used results from an ongoing, randomized trial of ALN treatment for prevention of postmenopausal osteoporosis (n = 1202). In women treated with ALN (5 mg...... a 4- to 5-fold greater increase at month 24 in BMD in the tertiles, with the greatest decrease at month 6 in NTX or OC. In women treated with ALN (5 mg) who had a change at month 24 in spine BMD of at least 0%, 86% (NTX) and 79% (OC) had a decrease at month 6 of at least 40% (NTX) or 20% (OC......) (sensitivity). The corresponding specificities were 48% (NTX) and 53% (OC). In conclusion, change at month 6 in NTX and OC, in groups of women treated with ALN, indicated the numeric long-term response in BMD within these groups. In individual women, a decrease at month 6, in NTX or OC below the cut...

  8. Relationship between Weight, Body Mass Index, and Bone Mineral Density in Men Referred for Dual-Energy X-Ray Absorptiometry Scan in Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Salamat

    2013-01-01

    Full Text Available Objective. Although several studies have investigated the association between body mass index (BMI and bone mineral density (BMD, the results are inconsistent. The aim of this study was to further investigate the relation between BMI, weight and BMD in an Iranian men population. Methods. A total of 230 men 50-79 years old were examined. All men underwent a standard BMD scans of hip (total hip, femoral neck, trochanter, and femoral shaft and lumbar vertebrae (L2-L4 using a Dual-Energy X-ray Absorptiometry (DXA scan and examination of body size. Participants were categorised in two BMI group: normal weight <25.0 kg/m2 and overweight and obese, BMI ≥ 25 kg/m2. Results. Compared to men with BMI ≥ 25, the age-adjusted odds ratio of osteopenia was 2.2 (95% CI 0.85, 5.93 and for osteoporosis was 4.4 (1.51, 12.87 for men with BMI < 25. It was noted that BMI and weight was associated with a high BMD, compatible with a diagnosis of osteoporosis. Conclusions. These data indicate that both BMI and weight are associated with BMD of hip and vertebrae and overweight and obesity decreased the risk for osteoporosis. The results of this study highlight the need for osteoporosis prevention strategies in elderly men as well as postmenopausal women.

  9. Identification of Proteins and Peptide Biomarkers for Detecting Banned Processed Animal Proteins (PAPs) in Meat and Bone Meal by Mass Spectrometry.

    Science.gov (United States)

    Marbaix, Hélène; Budinger, Dimitri; Dieu, Marc; Fumière, Olivier; Gillard, Nathalie; Delahaut, Philippe; Mauro, Sergio; Raes, Martine

    2016-03-23

    The outbreak of bovine spongiform encephalopathy (BSE) in the United Kingdom in 1986, with processed animal proteins (PAPs) as the main vector of the disease, has led to their prohibition in feed. The progressive release of the feed ban required the development of new analytical methods to determine the exact origin of PAPs from meat and bone meal. We set up a promising MS-based method to determine the species and the source (legal or not) present in PAPs: a TCA-acetone protein extraction followed by a cleanup step, an in-solution tryptic digestion of 5 h (with a 1:20 protein/trypsin ratio), and mass spectrometry analyses, first without any a priori, with a Q-TOF, followed by a targeted triple-quadrupole analysis. Using this procedure, we were able to overcome some of the major limitations of the official methods to analyze PAPs, detecting and identifying prohibited animal products in feedstuffs by the monitoring of peptides specific for cows, pigs, and sheep in PAPs. PMID:26943838

  10. Massa óssea e composição corporal em estudantes universitários Bone mass and body composition in college students

    Directory of Open Access Journals (Sweden)

    Cristina Reuter

    2012-06-01

    : PE male students showed a higher amount of lean body mass (79.5 ± 5.9 vs. 75.1 ± 5.3; p = 0.03 and a lower amount of body fat (16.7 ± 6.1 vs. 21.6 ± 5.6; p = 0.02 and PE female students showed a higher amount of lean body mass (68.2 ± 5.5 vs. 65.3 ± 5.5; p = 0.05. The BMD of the neck of femur (NOF, total femur (TF, and total body (TB was higher in PE students of both genders. PE students practiced more physical activities than MED students. Low bone mass (LBM was more frequent in MED students (34.9% vs. 4.7%; p = 0.001, provided that the risk of a MED student to show LBM was nine times higher for lumbar spine (LS, five times for NOF, eight times for TF, and seven times for TB. CONCLUSION: BC and BMD were different among the students; MED students have shown a higher risk of having LBM, and PE students practiced more physical activities.

  11. The normal bone scan

    International Nuclear Information System (INIS)

    This paper discusses applications of the bone scan. It is the most frequently performed nuclear medicine investigation, the commonest indication being the detection of occult metastases, for which purpose the entire skeleton should be imaged. For other purposes it is often adequate to examine only part of the skeleton. The amount of isotope taken up at any site depends primarily on the local rate of bone turnover rather than on bone mass. The scintigraphic appearance therefore does not necessarily correlate with the radiographic one; however, as there is a relationship between the rate at which bone is replaced and the quantity of bone which is present at any point, the two appearances are not entirely unrelated. Recognition of abnormality is based on a detailed knowledge of normal scintigraphic appearances

  12. Aged-Related Changes in Body Composition and Association between Body Composition with Bone Mass Density by Body Mass Index in Chinese Han Men over 50-year-old.

    Directory of Open Access Journals (Sweden)

    Ying Jiang

    Full Text Available Aging, body composition, and body mass index (BMI are important factors in bone mineral density (BMD. Although several studies have investigated the various parameters and factors that differentially influence BMD, the results have been inconsistent. Thus, the primary goal of the present study was to further characterize the relationships of aging, body composition parameters, and BMI with BMD in Chinese Han males older than 50 years.The present study was a retrospective analysis of the body composition, BMI, and BMD of 358 Chinese male outpatients between 50 and 89 years of age that were recruited from our hospital between 2009 and 2011. Qualified subjects were stratified according to age and BMI as follows: 50-59 (n = 35, 60-69 (n = 123, 70-79 (n = 93, and 80-89 (n = 107 years of age and low weight (BMI: < 20 kg/m2; n = 21, medium weight (20 ≤ BMI < 24 kg/m2; n = 118, overweight (24 ≤ BMI < 28 kg/m2; n = 178, and obese (BMI ≥ 28 kg/m2; n = 41. Dual-energy X-ray absorptiometry (DEXA was used to assess bone mineral content (BMC, lean mass (LM, fat mass (FM, fat-free mass (FFM, lumbar spine (L1-L4 BMD, femoral neck BMD, and total hip BMD. Additionally, the FM index (FMI; FM/height2, LM index (LMI; LM/height2, FFM index (FFMI; [BMC+LM]/height2, percentage of BMC (%BMC; BMC/[BMC+FM+LM] × 100%, percentage of FM (%FM; FM/[BMC+FM+LM] × 100%, and percentage of LM (%LM; LM/(BMC+FM+LM × 100% were calculated. Osteopenia or osteoporosis was identified using the criteria and T-score of the World Health Organization.Although there were no significant differences in BMI among the age groups, there was a significant decline in height and weight according to age (p < 0.0001 and p = 0.0002, respectively. The LMI and FFMI also declined with age (both p < 0.0001 whereas the FMI exhibited a significant increase that peaked in the 80-89-years group (p = 0.0145. Although the absolute values of BMC and LM declined with age (p = 0.0031 and p < 0

  13. Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study

    DEFF Research Database (Denmark)

    Jensen, L B; Vestergaard, P; Hermann, A P; Gram, J; Eiken, Pia Agnete; Abrahamsen, Bo; Brot, C; Kolthoff, Niels-Ulrik; Sørensen, O H; Beck-Nielsen, H; Nielsen, S Pors; Charles, P; Mosekilde, Leif

    2003-01-01

    menopause. Fat gain protects against bone loss in untreated women but not in HRT-treated women. The data suggest that women's attitudes to HRT are more positive if they have low body weight, but there is no evidence that the conclusions in this study are skewed by selection bias....... in women randomized to HRT (1.94 +/- 4.86 kg) than in women randomized to no HRT (2.57 +/- 4.63, p = 0.046). A similar pattern was seen in the group receiving HRT or not by their own choice. The smaller weight gain in women on HRT was almost entirely caused by a lesser gain in fat. The main...... determinant of the weight gain was a decline in physical fitness. Women opting for HRT had a significantly lower body weight at inclusion than the other participants, but the results in the self-selected part of the study followed the pattern found in the randomized part. The change in fat mass was the...

  14. Long-term changes in bone mass after partial gastrectomy in a well-defined population and its relation to tobacco and alcohol consumption

    DEFF Research Database (Denmark)

    Krogsgaard, M R; Frølich, A; Lund, B

    1995-01-01

    the daily alcohol consumption or cumulative tobacco consumption and bone mineral content in each group. Gastrectomized women smoked much more than control women, and smoking may be a determinant factor for the bone loss, as it is in healthy persons. Operated patients had a lower intake of milk...

  15. Canalicular network morphology is the major determinant of the spatial distribution of mass density in human bone tissue: evidence by means of synchrotron radiation phase-contrast nano-CT.

    Science.gov (United States)

    Hesse, Bernhard; Varga, Peter; Langer, Max; Pacureanu, Alexandra; Schrof, Susanne; Männicke, Nils; Suhonen, Heikki; Maurer, Peter; Cloetens, Peter; Peyrin, Francoise; Raum, Kay

    2015-02-01

    In bone remodeling, maturation of the newly formed osteonal tissue is associated with a rapid primary increase followed by a slower secondary increase of mineralization. This requires supply and precipitation of mineral into the bone matrix. Mineral delivery can occur only from the extracellular fluid via interfaces such as the Haversian system and the osteocyte pore network. We hypothesized that in mineralization, mineral exchange is achieved by the diffusion of mineral from the lacunar-canalicular network (LCN) to the bone matrix, resulting in a gradual change in tissue mineralization with respect to the distance from the pore-matrix interface. We expected to observe alterations in the mass density distribution with tissue age. We further hypothesized that mineral exchange occurs not only at the lacunar but also at the canalicular boundaries. The aim of this study was, therefore, to investigate the spatial distribution of mass density in the perilacunar and pericanalicular bone matrix and to explore how these densities are influenced by tissue aging. This is achieved by analyzing human jawbone specimens originating from four healthy donors and four treated with high-dosage bisphosphonate using synchrotron radiation phase-contrast nano-CT with a 50-nm voxel size. Our results provide the first experimental evidence that mass density in the direct vicinity of both lacunae (p < 0.001) and canaliculi (p < 0.001) is different from the mean matrix mass density, resulting in gradients with respect to the distance from both pore-matrix interfaces, which diminish with increasing tissue age. Though limited by the sample size, these findings support our hypotheses. Moreover, the density gradients are more pronounced around the lacunae than around the canaliculi, which are explained by geometrical considerations in the LCN morphology. In addition, we speculate that mineral exchange occurs at all interfaces of the LCN, not only in mineralization but also in mineral

  16. Odanacatib in postmenopausal women with low bone mineral density: a review of current clinical evidence

    OpenAIRE

    Zerbini, Cristiano A. F.; McClung, Michael R.

    2013-01-01

    Human bones are in a continuous process of remodeling that ensures renovation and maintenance of the skeletal mass. Bone remodeling has two phases that are normally coupled and balanced: bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. An increase in bone resorption over bone formation results in a progressive loss of bone mass and impairment of bone microarchitecture leading to osteoporosis and its associated fractures. Recent advances in the understanding ...

  17. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  18. Parental contribution and growth hormone gene polymorphism associated with growth phenotypes of red sea bream Pagrus major in mass production: A case study

    Directory of Open Access Journals (Sweden)

    Eitaro Sawayama

    2015-11-01

    Full Text Available Red sea bream is one of the most important aquaculture fish species in Japan. To improve the productivity of this fish during seed production, improved growth traits and reduced size variation are needed. In this study, we assessed parental contribution of fast- and slow-growing individuals observed in two different rearing phases in a mass production lot: (1 50 dph reared in a tank and (2 200 dph reared in a net cage. We also assessed GH gene (pmaGH polymorphisms based on a previously developed minisatellite DNA marker. Specific broodstock individuals were significantly associated with fast- or slow-growing individuals at 50 dph and 200 dph. Significant differences in pmaGH minisatellite allele frequencies were observed between fast- and slow-growing groups at 50 dph in the frequency of two alleles (pmaGH-740 and pmaGH-900, respectively. Combining the results of DNA parentage analysis and pmaGH minisatellite allele analysis, one dam and two sires, possessing pmaGH-740, were significantly associated with the slow-growing groups. These results suggest that the minisatellite marker of pmaGH could be a useful tool for growth selection of this fish species.

  19. Bone Biochemistry on the International Space Station

    Science.gov (United States)

    Smith, Scott M.; Heer, Martina; Zwart, Sara R.

    2016-01-01

    Bone biochemical measures provide valuable insight into the nature and time course of microgravity effects on bone during space flight, where imaging technology cannot be employed. Increased bone resorption is a hallmark of space flight, while markers of bone formation are typically unchanged or decreased. Recent studies (after the deployment to ISS of the advanced resistive exercise device, ARED), have documented that astronauts with good nutritional intake (e.g., maintenance of body mass), good vitamin D status, and exercise maintained bone mineral density. These data are encouraging, but crewmembers exercising on the ARED do have alterations in bone biochemistry, specifically, bone resorption is still increased above preflight levels, but bone formation is also significantly increased. While this bone remodeling raises questions about the strength of the resulting bone, however documents beneficial effects of nutrition and exercise in counteracting bone loss of space flight.

  20. The effects of cinacalcet treatment on bone mineral metabolism, anemia parameters, left ventricular mass index and parathyroid gland volume in hemodialysis patients with severe secondary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Dilek Torun

    2016-01-01

    Full Text Available The aim of this study was to investigate the effects of cinacalcet therapy on anemia parameters, bone mineral metabolism, left ventricular mass index (LVMI and parathyroid gland volume in hemodialysis (HD patients with secondary hyperparathyroidism. Twenty-five HD patients (M/F: 11/14, mean age: 45.2 ± 17.9 years, mean HD duration: 96.4 ± 32.7 months were included in this prospective pilot study. The indication to start calcimimetic therapy was persistent serum levels of parathyroid hormone (PTH >1000 pg/mL, refractory to intravenous (i.v. vitamin D and phosphate-binding therapy. The initial and one-year results of adjusted serum calcium (Ca +2 , phosphate (P, Ca × P product, PTH, hemoglobin (Hb and ferritin levels, transferrin saturation index (TSAT, median weekly erythropoietin (EPO dose, LVMI, and parathyroid volume by parathyroid ultrasonography were determined. There were no differences between pre- and post-treatment levels of serum Ca +2 (P = 0.853, P (P = 0.447, Ca × P product (P = 0.587, PTH (P = 0.273, ferritin (P = 0.153 and TSAT (P = 0.104. After 1 year of calcimimetic therapy, the Hb levels were significantly higher than the initial levels (P = 0.048. The weekly dose of EPO decreased with no statistical significance. The dose of cinacalcet was increased from 32.4 ± 12.0 to 60.0 ± 24.4 mg/day (P = 0.01. There were no differences between the pre- and post-treatment results regarding weekly vitamin D dose, parenteral iron dose, LVMI and parathyroid volume. The results of our study suggest that cinacalcet therapy might have an additional benefit in the control anemia in HD patients.

  1. Assessment risk of osteoporosis in Chinese people: relationship among body mass index, serum lipid profiles, blood glucose, and bone mineral density

    Science.gov (United States)

    Cui, Rongtao; Zhou, Lin; Li, Zuohong; Li, Qing; Qi, Zhiming; Zhang, Junyong

    2016-01-01

    Objective The aim of our study was to investigate the relationship among age, sex, body mass index (BMI), serum lipid profiles, blood glucose (BG), and bone mineral density (BMD), making an assessment of the risk of osteoporosis. Materials and methods A total of 1,035 male and 3,953 female healthy volunteers (aged 41–95 years) were recruited by an open invitation. The basic information, including age, sex, height, weight, waistline, hipline, menstrual cycle, and medical history, were collected by a questionnaire survey and physical examination. Serum lipid profiles, BG, postprandial blood glucose, and glycosylated hemoglobin were obtained after 12 hours fasting. BMD in lumbar spine was measured by dual-energy X-ray absorptiometry scanning. Results The age-adjusted BMD in females was significantly lower than in males. With aging, greater differences of BMD distribution exist in elderly females than in males (P7.0 mmol/L was lower than in people with BG of ≤7.0 mmol/L (P<0.001). People with serum high-density lipoprotein cholesterol levels of ≥1.56 mmol/L had a greater prevalence of osteoporosis compared with high-density lipoprotein cholesterol ≤1.55 mmol/L. Logistic regression with odds ratios showed that no association was found among total cholesterol, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin, postprandial blood glucose and BMD. Conclusion The present study further confirmed that factors such as age, sex, weight, BMI, high-density lipoprotein cholesterol, and diabetes are significant predictors of osteoporosis in the Chinese people. PMID:27445467

  2. β3-adrenergic receptor gene, body mass index, bone mineral density and fracture risk in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES

    Directory of Open Access Journals (Sweden)

    Center Jacqueline R

    2006-07-01

    Full Text Available Abstract Background Recent studies have suggested that the Arg allele of β3-adrenergic receptor (ADRB3 gene is associated with body mass index (BMI, which is an important predictor of bone mineral density (BMD and fracture risk. However, whether the ADRB3 gene polymorphism is associated with fracture risk has not been investigated. The aim of study was to examine the inter-relationships between ADRB3 gene polymorphisms, BMI, BMD and fracture risk in elderly Caucasians. Methods Genotypes of the ADRB3 gene were determined in 265 men and 446 women aged 60+ in 1989 at entry into the study, whose BMD were measured by DXA (GE Lunar, WI USA at baseline. During the follow-up period (between 1989 and 2004, fractures were ascertained by reviewing radiography reports and personal interviews. Results The allelic frequencies of the Trp and the Arg alleles were 0.925 and 0.075 respectively, and the relative frequencies of genotypes Trp/Trp, Trp/Arg and Arg/Arg 0.857, 0.138 and 0.006 respectively. There was no significant association between BMI and ADRB3 genotypes (p = 0.10 in women and p = 0.68 in men. There was also no significant association between ADRB3 genotypes and lumbar spine or femoral neck BMD in either men and women. Furthermore, there were no significant association between ADRB3 genotypes and fracture risk in both women and men, either before or after adjusting for and, BMD and BMI. Conclusion The present data suggested that in Caucasian population the contribution of ADRB3 genotypes to the prediction of BMI, BMD and fracture risk is limited.

  3. Overexpression of H1 Calponin in Osteoblast Lineage Cells Leads to a Decrease in Bone Mass by Disrupting Osteoblast Function and Promoting Osteoclast Formation

    OpenAIRE

    Su, Nan; Chen, Maomao; Chen, Siyu; Li, Can; Xie, Yangli; Zhu, Ying; Zhang, Yaozong; Zhao, Ling; He, Qifen; Du, Xiaolan; Chen, Di; Chen, Lin

    2013-01-01

    H1 calponin (CNN1) is known as a smooth muscle-specific, actin-binding protein which regulates smooth muscle contractive activity. Although previous studies have shown that CNN1 has effect on bone, the mechanism is not well defined. To investigate the role of CNN1 in maintaining bone homeostasis, we generated transgenic mice overexpressing Cnn1 under the control of the osteoblast-specific 3.6-kb Col1a1 promoter. Col1a1-Cnn1 transgenic mice showed delayed bone formation at embryonic stage and ...

  4. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  5. Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells.

    Science.gov (United States)

    Schulze, Jochen; Bickert, Thomas; Beil, F Timo; Zaiss, Mario M; Albers, Joachim; Wintges, Kristofer; Streichert, Thomas; Klaetschke, Kristin; Keller, Johannes; Hissnauer, Tim-Nicolas; Spiro, Alexander S; Gessner, Andre; Schett, Georg; Amling, Michael; McKenzie, Andrew N J; Horst, Andrea Kristina; Schinke, Thorsten

    2011-04-01

    Since the hematopoetic system is located within the bone marrow, it is not surprising that recent evidence has demonstrated the existence of molecular interactions between bone and immune cells. While interleukin 1 (IL-1) and IL-18, two cytokines of the IL-1 family, have been shown to regulate differentiation and activity of bone cells, the role of IL-33, another IL-1 family member, has not been addressed yet. Since we observed that the expression of IL-33 increases during osteoblast differentiation, we analyzed its possible influence on bone formation and observed that IL-33 did not affect matrix mineralization but enhanced the expression of Tnfsf11, the gene encoding RANKL. This finding led us to analyze the skeletal phenotype of Il1rl1-deficient mice, which lack the IL-33 receptor ST2. Unexpectedly, these mice displayed normal bone formation but increased bone resorption, thereby resulting in low trabecular bone mass. Since this finding suggested a negative influence of IL-33 on osteoclastogenesis, we next analyzed osteoclast differentiation from bone marrow precursor cells and observed that IL-33 completely abolished the generation of TRACP(+) multinucleated osteoclasts, even in the presence of RANKL and macrophage colony-stimulating factor (M-CSF). Although our molecular studies revealed that IL-33 treatment of bone marrow cells caused a shift toward other hematopoetic lineages, we further observed a direct negative influence of IL-33 on the osteoclastogenic differentiation of RAW264.7 macrophages, where IL-33 repressed the expression of Nfatc1, which encodes one of the key transciption factors of osteoclast differentiation. Taken together, these findings have uncovered a previously unknown function of IL-33 as an inhibitor of bone resorption. PMID:20939024

  6. Anorexia nervosa and bone metabolism

    OpenAIRE

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation with a lifetime prevalence of 2.2% in women. The most common medical co-morbidity in women with AN is bone loss, with over 85% of women having bone mineral density values more than one standard deviation below an age comparable mean. The low bone mass in AN is due to multiple hormonal adaptations to under nutrition, including hypothalamic amenorrhea and growth hormone resistance. Importa...

  7. Bone scanning in osteoporosis

    International Nuclear Information System (INIS)

    This paper reports on bone scanning in osteoporosis a diagnosis of osteoporosis most often follows fracture, and clearly this should be confirmed by x-ray. The bone scan therefore does not have an important role to play in the initial diagnosis of osteoporosis. While the exact mechanism by which the 99mTc-labeled diphosphonates localize in the skeleton is not fully understood, it is believed that they adsorb onto bone surfaces most probably via the calcium of hydroxyapatite crystals. Because the major factors that affect adsorption are osteoblastic activity and to a lesser extent skeletal vascularity, it is apparent that a bone scan image presents a functional display of skeletal metabolic activity. However, osteoporosis is a disorder in which gradual change in bone mass may occur over many years and, in keeping with this minor imbalance in skeletal metabolism, the bone scan appearances are usually normal. However, the scan images may appear of poor quality because of relatively low bone uptake of tracer with, on occasion, a washed-out pattern of activity in the axial and appendicular bone. It has been suggested that such a pattern occurs in severe or end-stage osteoporosis caused by markedly reduced osteoblastic activity. If kyphosis is observed on the bone scan or if there appears to be loss of spinal height with proximity of ribs to each other or increased closeness of rib cage to pelvis, then appearances suggest vertebral collapse and would be in keeping with a diagnosis of osteoporosis. Such evidence is, however, indirect and in practice a bone scan is an extremely unreliable means of diagnosing osteoporosis

  8. The More Efficacious Acupoints of Zusanli and Sanyinjiao Than That of Non-acupoints on Bone Mass in Osteopenic Ovariectomized Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To clarify whether the acupoints of Zusanli (ST36) and Sanyinjiao (SP6) have specific actions other than non-acupoints to bone. Methods: Forty Sprague-Dawley female rats were divided into five groups: Sham operated (sham) group; Ovariectomized (OVX, model) group; non-acupuncture group; OVX, needling on Zusanli and Sanyinjiao (Acp-A) group; OVX, needling on the reverse sides of Zusanli and Sanyinjiao (Acp-B) group; OVX, periostineal stimulation on the same height as points of Zusanli and Sanyinjiao (Acp-C) group. The experiment was continued for 23 weeks and then all animals were sacrificied.Results: OVX had a significantly higher body weight and lower bone mineral density (BMD) on the lumbar vertebrae, total femora and tibiae than sham rats, however, Acp-A showed a higher BMD compared with the other OVX groups. On the other hand, bone weights, bone strength and bone morphometry such as trabecular volume, trabecular separation, labeled width and bone formation rate also showed the same improvements in Acp-A as compared to the other OVX rats. Conclusion: The stimulation on Zusanli and Sanyinjiao specifically prevented the development of osteopenic rats compared with non-acupoints.

  9. A Root-Based Combination Supplement Containing Pueraria lobata and Rehmannia glutinosa and Exercise Preserve Bone Mass in Ovariectomized Rats Fed a High-Fat Diet.

    Science.gov (United States)

    Ok, Hyang Mok; Gebreamanuel, Meron Regu; Oh, Sang A; Jeon, Hyejin; Lee, Won Jun; Kwon, Oran

    2015-12-01

    The aim of this study was to evaluate the effects of a supplement containing Pueraria lobata/Rehmannia glutinosa (PR) root extracts on bone turnover in ovariectomized (OVX) rats (a model for postmenopausal osteoporosis). Female Sprague-Dawley rats (8 weeks old) were randomized into eight groups: sham-operated rats with low-fat control diet + vehicle, OVX rats with low-fat control diet + vehicle, OVX rats with high-fat diet (HFD) + vehicle, OVX rats with HFD + vehicle + exercise, OVX rats with HFD + PR (400 mg/kg body weight/day p.o.), OVX rats with HFD + PR + exercise, OVX rats with HFD + 17β-estradiol (0.5 mg/kg body weight/day p.o.), OVX rats with HFD + 17β-estradiol + exercise. Bone microarchitecture, bone turnover markers (e.g., plasma alkaline phosphatase and osteocalcin), expressions of osteogenic and resorptive gene markers in the bone were measured. Eight weeks of PR and/or aerobic exercise improved cortical microarchitecture of the femur and decreased markers of bone turnover and expression of skeletal osteoclastogenic genes in the femur. PR supplementation combined with exercise preserved bone loss induced by estrogen deficiency and should be investigated further as an alternative to hormone replacement therapy for preventing osteoporosis in postmenopausal women. PMID:26319677

  10. Use of cabbage leaves (Brassica oleracea var. acephala) in the stabilization of bone mass after menopause Uso do suco das folhas da couve (Brassica oleracea var acephala), na estabilização da massa óssea pós-menopausa

    OpenAIRE

    João V. Pereira; Hosana B. Santos; Maria F. Agra; Diego N. Guedes; João Modesto-Filho

    2006-01-01

    This work evaluates the use of cabbage leaves, Brassica oleracea var acephala (Cruciferae family) to stabilize bone mass in 13 menopausal women. The mature leaves were used after removal of the midrib and petiole and taken as a juice and given to the patient once a day for 24 months. Densitometric exams were performed every six months. The measurement points were the Trocanter and Ward's triangle. According to the results found, the use of cabbage leaf juice results in bone mass stabilization...

  11. Phenotypic heterogeneity of Streptococcus mutans in dentin.

    Science.gov (United States)

    Rupf, S; Hannig, M; Breitung, K; Schellenberger, W; Eschrich, K; Remmerbach, T; Kneist, S

    2008-12-01

    Information concerning phenotypic heterogeneity of Streptococcus mutans in carious dentin is sparse. Matrix-assisted laser-desorption/ionization-time-of-flight mass-spectrometry (MALDI-TOF-MS) facilitates the phenotypic differentiation of bacteria to the subspecies level. To verify a supposed influence of restorative treatment on the phenotypic heterogeneity of S. mutans, we isolated and compared a total of 222 S. mutans strains from dentin samples of 21 human deciduous molars during caries excavation (T(1)) and 8 wks (T(2)) after removal of the temporary restoration. Phenotypic heterogeneity was determined by MALDI-TOF-MS and hierarchical clustering. Thirty-six distinct S. mutans phenotypes could be identified. Although indistinguishable phenotypes were found in the same teeth at T(1) and T(2), as well as in different teeth of individual participants, the phenotypic heterogeneity increased significantly, from 1.4 phenotypes per S. mutans-positive dentin sample at T(1) to 2.2 phenotypes at T(2). We attribute this to an adaptation of S. mutans to the modified environment under the restoration following caries excavation. PMID:19029088

  12. Myostatin (GDF-8) as a Key Factor Linking Muscle Mass and Skeletal Form

    OpenAIRE

    Elkasrawy, Moataz N.; Hamrick, Mark W.

    2010-01-01

    Myostatin (GDF-8) is a member of the transforming growth factor-beta (TGF-β) superfamily that is highly expressed in skeletal muscle, and myostatin loss-of-function leads to doubling of skeletal muscle mass. Myostatin-deficient mice have been used as a model for studying muscle-bone interactions, and here we review the skeletal phenotype associated with altered myostatin signaling. It is now known that myostatin is a key regulator of mesenchymal stem cell proliferation and differentiation, an...

  13. Bone tumor

    Science.gov (United States)

    ... physical exam. Tests that may be done include: Alkaline phosphatase blood level Bone biopsy Bone scan Chest x- ... also affect the results of the following tests: Alkaline phosphatase isoenzyme Blood calcium level Parathyroid hormone Blood phosphorus ...

  14. Potential bone-inducing activity in vitro of recombinant human bone morphogenetic protein-7 from a CHO expression system

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-yan; SHI Wei-wei; WANG Hao; LI Bo-hua; YANG Yang; TAN Min; XUE Jing-ya; GUO Ya-jun

    2005-01-01

    Objective: To express the recombinant human bone morphogenetic protein-7 (rhBMP-7) in Chinese hamster ovary(CHO) cells, and to establish the in vitro biological activity assay of rhBMP-7.Methods: Human BMP-7 cDNA was subcloned into p114 mammalian expression vector and transfected to CHO cells by using the Lipofectamine2000 transfection method. CHO cell supernatants were harvested and analyzed to identify the molecule mass of secreted rhBMP-7 and examine its biological activity in vitro to stimulate the synthesis of alkaline phophatase(ALP), a characteristic of osteoblast phenotypes. Results:rhBMP-7 was produced stably in CHO cells, as a processed mature disulfide-linked homodimer, with an apparent molecular mass of 36 000. Examination of the rhBMP-7 biological activity showed that rhBMP-7 specifically stimulated the production of ALP(4-fold increase at 100 ng of rhBMP-7/ml). Conclusion: The rhBMP-7 from CHO expression system has significant biological activity in induction of osteoblast phenotype, which demonstrates rhBMP-7 has the potential bone regeneration activity.

  15. The NK1R-/- mouse phenotype suggests that small body size, with a sex- and diet-dependent excess in body mass and fat, are physical biomarkers for a human endophenotype with vulnerability to attention deficit hyperactivity disorder.

    Science.gov (United States)

    Pillidge, Katharine; Heal, David J; Stanford, S Clare

    2016-09-01

    The abnormal behaviour of NK1R-/- mice (locomotor hyperactivity, inattentiveness and impulsivity in the 5-Choice Serial Reaction-Time Test) is arguably analogous to that of patients with attention deficit hyperactivity disorder (ADHD). Evidence suggests that small body size and increased body weight are risk factors for ADHD. Here, we compared the body size, body mass and body composition of male and female NK1R-/- mice and their wildtypes that had been fed either standard laboratory chow or a high-fat (45%: 'Western') diet. Male NK1R-/- mice from both cohorts were approximately 7% shorter than wildtypes. A similar trend was evident in females. Male NK1R-/- mice fed the normal diet weighed less than wildtypes but the 'body mass index' ('mBMI': weight (mg)/length (cm)(2)) of female NK1R-/- mice was higher than wildtypes. When given the high-fat diet, the mBMI of both male and female NK1R-/- mice was higher than wildtypes. There were no consistent genotype or sex differences in protein, ash or water content of mice from the two cohorts. However, the fat content of male NK1R-/- mice on the Western diet was considerably (35%) higher than wildtypes and resembled that of females from both genotypes. We conclude that a lack of functional NK1R is associated with small body size but increases vulnerability to an increase in mBMI and fat content, especially in males. This phenotype could also be evident in ADHD patients with polymorphism(s) of the TACR1 gene (the human equivalent of Nk1r). PMID:27462087

  16. A T Cell View of the Bone Marrow

    Science.gov (United States)

    Bonomo, Adriana; Monteiro, Ana Carolina; Gonçalves-Silva, Triciana; Cordeiro-Spinetti, Eric; Galvani, Rômulo Gonçalves; Balduino, Alex

    2016-01-01

    The majority of T cells present in the bone marrow (BM) represent an activated/memory phenotype and most of these, if not all, are circulating T cells. Their lodging in the BM keeps them activated, turning the BM microenvironment into a “memory reservoir.” This article will focus on how T cell activation in the BM results in both direct and indirect effects on the hematopoiesis. The hematopoietic stem cell niche will be presented, with its main components and organization, along with the role played by T lymphocytes in basal and pathologic conditions and their effect on the bone remodeling process. Also discussed herein will be how “normal” bone mass peak is achieved only in the presence of an intact adaptive immune system, with T and B cells playing critical roles in this process. Our main hypothesis is that the partnership between T cells and cells of the BM microenvironment orchestrates numerous processes regulating immunity, hematopoiesis, and bone remodeling. PMID:27242791

  17. The importance and relevance of peak bone mass in the prevalence of osteoporosis Importancia y relevancia de la masa ósea máxima en la prevalencia de osteoporosis

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Bonjour

    2009-01-01

    Full Text Available Bone mass and strength achieved at the end of the growth period, simply designated as "Peak Bone Mass (PBM", plays an essential role in the risk of osteoporotic fractures occurring in adulthood. It is considered that an increase of PBM by one standard deviation would reduce the fracture risk by 50%. As estimated from twin studies, genetics is the major determinant of PBM, accounting for about 60 to 80% of its variance. During pubertal maturation, the size of the bone increases whereas the volumetric bone mineral density remains constant in both genders. At the end of puberty, the sex difference is essentially due to a greater bone size in male than female subjects. This is achieved by larger periosteal deposition in boys, thus conferring at PBM a better resistance to mechanical forces in men than in women. Sex hormones and the IGF-1 system are implicated in the bone sexual dimorphism occurring during pubertal maturation. The genetically determined trajectory of bone mass development can be modulated to a certain extent by modifiable environmental factors, particularly physical activity, calcium and protein intakes. Prepuberty appears to be an opportune time to modify environmental factors that impinge on bone mineral mass acquisition.La masa y fortaleza ósea conseguida al final del periodo de crecimiento, designada simplemente como masa ósea máxima (MOM, constituye un factor crítico en cuanto al riesgo de fracturas osteoporóticas en la edad adulta. Se considera que un aumento de MOM de una desviación estándar reduciría el riesgo de fracturas en 50 por ciento. Los estudios en gemelos han mostrado que la genética es el principal determinante de MOM, siendo responsable de 60 a 80% de su variación. Durante la maduración puberal el tamaño de los huesos aumenta mientras que su densidad mineral volumétrica permanece constante en ambos géneros. Al final de la pubertad la diferenciación sexual se debe básicamente al mayor tamaño de los

  18. Mechanical Loading Synergistically Increases Trabecular Bone Volume and Improves Mechanical Properties in the Mouse when BMP Signaling Is Specifically Ablated in Osteoblasts.

    Directory of Open Access Journals (Sweden)

    Ayaka Iura

    Full Text Available Bone homeostasis is affected by several factors, particularly mechanical loading and growth factor signaling pathways. There is overwhelming evidence to validate the importance of these signaling pathways, however, whether these signals work synergistically or independently to contribute to proper bone maintenance is poorly understood. Weight-bearing exercise increases mechanical load on the skeletal system and can improves bone quality. We previously reported that conditional knockout (cKO of Bmpr1a, which encodes one of the type 1 receptors for Bone Morphogenetic Proteins (BMPs, in an osteoblast-specific manner increased trabecular bone mass by suppressing osteoclastogenesis. The cKO bones also showed increased cortical porosity, which is expected to impair bone mechanical properties. Here, we evaluated the impact of weight-bearing exercise on the cKO bone phenotype to understand interactions between mechanical loading and BMP signaling through BMPR1A. Male mice with disruption of Bmpr1a induced at 9 weeks of age, exercised 5 days per week on a motor-driven treadmill from 11 to 16 weeks of age. Trabecular bone volume in cKO tibia was further increased by exercise, whereas exercise did not affect the trabecular bone in the control genotype group. This finding was supported by decreased levels of osteoclasts in the cKO tibiae. The cortical porosity in the cKO bones showed a marginally significant decrease with exercise and approached normal levels. Exercise increased ductility and toughness in the cKO bones. Taken together, reduction in BMPR1A signaling may sensitize osteoblasts for mechanical loading to improve bone mechanical properties.

  19. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

    Science.gov (United States)

    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

    2015-01-01

    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  20. Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis - the effect of sex, Kellgren-Lawrence (KL score, Body Mass Index (BMI, oral salmon calcitonin (sCT treatment and diurnal variation

    Directory of Open Access Journals (Sweden)

    Henriksen K

    2010-06-01

    Full Text Available Abstract Background Osteoarthritis (OA involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL score, Body Mass Index (BMI, oral salmon calcitonin (sCT treatment and diurnal variation. Methods This study was a 2-week, double-blind, double-dummy, randomized study including 37 postmenopausal women and 36 men, aged 57-75 years, with painful knee OA, and a KL-score of I - III. Subjects were allocated to one of three treatment arms: 0.6 mg or 0.8 mg oral sCT, or placebo given twice-daily for 14 days. Correlations between gender, KL score, or BMI and the bone resorption marker, serum C-terminal telopeptide of collagen type I (CTX-I, or the cartilage degradation marker, urine C-terminal telopeptide of collagen type II (CTX-II were investigated. Results At baseline, biomarkers indicated women with OA experienced higher bone and cartilage degradation than men. CTX-I levels were significantly higher, and CTX-II levels only marginally higher, in women than in men (p = 0.04 and p = 0.06, respectively. Increasing KL score was not correlated with bone resorption, but was significantly associated with the cartilage degradation CTX-II marker in both men and women (p = 0.007. BMI was significantly and negatively correlated to the bone resorption marker CTX-I, r = -0.40 (p = 0.002, but showed only a borderline positive correlation to CTX-II, r = 0.25 (p = 0.12. Before morning treatments on days 1 and 14, no correlation was seen between CTX-I and CTX-II in either the sCT or placebo group. However, oral sCT and food intake induced a clear correlation between these bone and cartilage degradation markers. Four hours after the first sCT dose on treatment days 1 and 14, a significant correlation (r = 0.71, p p = 0.02, but not on day 14. Conclusion Bone resorption was higher in

  1. The two faces of serotonin in bone biology

    OpenAIRE

    Ducy, Patricia; Karsenty, Gerard

    2010-01-01

    The serotonin molecule has some remarkable properties. It is synthesized by two different genes at two different sites, and, surprisingly, plays antagonistic functions on bone mass accrual at these two sites. When produced peripherally, serotonin acts as a hormone to inhibit bone formation. In contrast, when produced in the brain, serotonin acts as a neurotransmitter to exert a positive and dominant effect on bone mass accrual by enhancing bone formation and limiting bone resorption. The effe...

  2. Cortical thinning of clavicle bone in renal stone male patients

    International Nuclear Information System (INIS)

    Radiogrametry of the clavicle is the oldest direct method of bone mass measurement. It has offered a better understanding of the in-vivo changes of cortical bone mass during life which accounts for 80% of the skeleton. This study is aimed to find out the effect of bone resorption (bone thinning) on the formation of renal calculi, particularly clavicle bone resorption using radiogrametry method

  3. Human Osteoblast Differentiation and Bone Formation: Growth Factors, Hormones and Regulatory Networks

    OpenAIRE

    Eijken, Marco

    2007-01-01

    textabstractOsteoporosis is the most common bone disease and is characterized by low bone mass, micro architectural deterioration and decreased bone quality resulting in increased risk of fractures. Osteoblasts, the bone forming cells, play a crucial role in the regulation of bone mass and bone quality. Osteoblasts are of mesenchymal origin and undergo a complex differentiation process regulated by many endocrine and autocrine factors. In order to develop novel bone anabolic drugs, more knowl...

  4. Osteoporosis and adynamic bone in chronic kidney disease

    OpenAIRE

    Cannata, J.B. (Jorge); Rodríguez, Minerva; Gómez, Carlos

    2013-01-01

    Among the chronic kidney disease–mineral bone disease (CKD-MBD) disorders, osteoporosis and adynamic bone are highly prevalent, and they have been consistently associated with low bone mass, bone fractures, vascular calcifications and greater mortality in general and CKD populations. Despite the fact that osteoporosis and adynamic bone have similar clinical outcomes, they have different pathogeneses and clinical management. In osteoporosis, there is a lack of balance between bone format...

  5. Adynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix.

    Science.gov (United States)

    Ng, Adeline H; Omelon, Sidney; Variola, Fabio; Allo, Bedilu; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2016-02-01

    Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long-term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2.3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X-ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age-related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover. PMID:26332924

  6. Ethnic Differences in Bone Health

    Directory of Open Access Journals (Sweden)

    Ayse eZengin

    2015-03-01

    Full Text Available There are differences in bone health between ethnic groups in both men and in women. Variations in body size and composition are likely to contribute to reported differences. Most studies report ethnic differences in areal bone mineral density (aBMD which do not consistently parallel ethnic patterns in fracture rates. This suggests that other parameters beside aBMD should be considered when determining fracture risk between and within populations, including other aspects of bone strength: bone structure and microarchitecture as well muscle strength (mass, force generation, anatomy and fat mass. We review what is known about differences in bone-densitometry derived outcomes between ethnic groups and the extent to which they account for the differences in fracture risk. Studies are included that were published primarily between 1994 – 2014. A ‘one size fits all approach’ should not be used to understand better ethnic differences in fracture risk.

  7. Protein-containing nutrient supplementation following strength training enhances the effect on muscle mass, strength, and bone formation in postmenopausal women

    DEFF Research Database (Denmark)

    Holm, Lars; Olesen, J.L.; Matsumoto, K.;

    2008-01-01

    We evaluated the response of various muscle and bone adaptation parameters with 24 wk of strength training in healthy, early postmenopausal women when a nutrient supplement (protein, carbohydrate, calcium, and vitamin D) or a placebo supplement (a minimum of energy) was ingested immediately follo...

  8. Gravity, calcium, and bone - Update, 1989

    Science.gov (United States)

    Arnaud, Sara B.; Morey-Holton, Emily

    1990-01-01

    Recent results obtained on skeletal adaptation, calcium metabolism, and bone browth during short-term flights and ground simulated-microgravity experiments are presented. Results demonstrate that two principal components of calcium metabolism respond within days to changes in body position and to weightlessness: the calcium endocrine system and bone characteristics. Furthermore, results of recent studies imply that bone biomechanics are more severely affected by spaceflight exposures than is the bone mass.

  9. 北京老年妇女膳食钙摄入水平与骨量关系%The association between calcium intake bone mass in Beijing older women

    Institute of Scientific and Technical Information of China (English)

    陶黎; 王翠侠; 刘颖; 左娇蕾; 张倩

    2011-01-01

    Objective To observe the association between dietary calcium intake and bone mass in Beijing old postmenopausal women.Methods A total of 445 community-dwelling elderly women over 60 years(60 to 86 years old) were selected randomly from 17 communities of 6 blocks in 3 districts in Beijing.Their dietary intake were collected by food frequency questionnaires,and bone mineral density(BMD) at lumber spine,hips,and total body were measured by DXA( Norland XR-46,America).Results The bone mass and the rate of osteoporosis varied in different position, with highest at trochanter as 19.4%.The BMD at hips and trochanter in subjects with dietary calcium intake more than 1000 mg/d were 3.4% and 4.9% higher than those in subjects with lower calcium intake ( P < 0.05 ); their prevalence of osteoporosis at trochanter decreased to 12.7% ( P < 0.05 ) ,with more normal bone mass at this position.No significant effect of calcium intake were observed on bone mass of total body or lumber spine.Conclusion Dietary calcium intake has different effect on variance position.More dietary calcium intake would benefit bone mass at hips.%目的 研究老年妇女在不同膳食钙摄入水平下骨密度变化情况.方法 从北京市3个城区6个街道17个社区中随机选取60岁以上(60~86岁)的老年妇女445人作为研究对象.采用食物频率表调查过去一年的膳食摄入,用双能X线吸收仪(DXA)测定其全身、股骨和腰椎骨密度.结果 我国健康老年妇女不同部位的骨量、骨质疏松的发生率均不同,大转子发生骨质疏松的比例最高,达到19.4%.膳食钙摄人大于1000mg/d的研究对象的髋骨BMD和大转子BMD分别比钙摄入量小于1000mg/d的人高3.4%和4.9%(P<0.05);而大转子BMD诊断为骨质疏松的比例显著下降到12.7%(P<0.05),为"骨量正常"的比例显著增加.未观察到不同膳食钙摄入水平对全身和腰椎骨量的显著影响.结论 膳食钙摄入对不同部分的效果不同,

  10. Bone nutrients for vegetarians.

    Science.gov (United States)

    Mangels, Ann Reed

    2014-07-01

    The process of bone mineralization and resorption is complex and is affected by numerous factors, including dietary constituents. Although some dietary factors involved in bone health, such as calcium and vitamin D, are typically associated with dairy products, plant-based sources of these nutrients also supply other key nutrients involved in bone maintenance. Some research suggests that vegetarian diets, especially vegan diets, are associated with lower bone mineral density (BMD), but this does not appear to be clinically significant. Vegan diets are not associated with an increased fracture risk if calcium intake is adequate. Dietary factors in plant-based diets that support the development and maintenance of bone mass include calcium, vitamin D, protein, potassium, and soy isoflavones. Other factors present in plant-based diets such as oxalic acid and phytic acid can potentially interfere with absorption and retention of calcium and thereby have a negative effect on BMD. Impaired vitamin B-12 status also negatively affects BMD. The role of protein in calcium balance is multifaceted. Overall, calcium and protein intakes in accord with Dietary Reference Intakes are recommended for vegetarians, including vegans. Fortified foods are often helpful in meeting recommendations for calcium and vitamin D. Plant-based diets can provide adequate amounts of key nutrients for bone health. PMID:24898231

  11. [Abnormality in bone metabolism after burn].

    Science.gov (United States)

    Gong, X; Xie, W G

    2016-08-20

    Burn causes bone metabolic abnormality in most cases, including the changes in osteoblasts and osteoclasts, bone mass loss, and bone absorption, which results in decreased bone mineral density. These changes are sustainable for many years after burn and even cause growth retardation in burned children. The mechanisms of bone metabolic abnormality after burn include the increasing glucocorticoids due to stress response, a variety of cytokines and inflammatory medium due to inflammatory response, vitamin D deficiency, hypoparathyroidism, and bone loss due to long-term lying in bed. This article reviews the pathogenesis and regularity of bone metabolic abnormality after burn, the relationship between bone metabolic abnormality and burn area/depth, and the treatment of bone metabolic abnormality, etc. and discusses the research directions in the future. PMID:27562160

  12. [Bone diseases].

    Science.gov (United States)

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

    Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw. PMID:26946704

  13. Development of a method based on inductively coupled plasma-dynamic reaction cell-mass spectrometry for the simultaneous determination of phosphorus, calcium and strontium in bone and dental tissue

    Energy Technology Data Exchange (ETDEWEB)

    De Muynck, David [Ghent University, Department of Analytical Chemistry, Krijgslaan 281-S12, BE-9000 Ghent (Belgium)], E-mail: David.DeMuynck@UGent.be; Vanhaecke, Frank [Ghent University, Department of Analytical Chemistry, Krijgslaan 281-S12, BE-9000 Ghent (Belgium)], E-mail: Frank.Vanhaecke@UGent.be

    2009-05-15

    A method, based on the use of a quadrupole-based inductively coupled plasma-mass spectrometry instrument equipped with a quadrupole-based collision/reaction cell (dynamic reaction cell, DRC), was developed for the simultaneous determination of phosphorus, calcium and strontium in bone and dental (enamel and dentine) tissue. The use of NH{sub 3}, introduced at a gas flow rate of 0.8 mL min{sup -1} in the dynamic reaction cell, combined with a rejection parameter q (RPq) setting of 0.65, allows interference-free determination of calcium via its low-abundant isotopes {sup 42}Ca, {sup 43}Ca and {sup 44}Ca, and of strontium via its isotopes {sup 86}Sr and {sup 88}Sr that are freed from overlap due to the occurrence of ArCa{sup +} and/or Ca{sub 2}{sup +} ions. Also the determination of phosphorus ({sup 31}P, mono-isotopic) was shown to be achievable using the same dynamic reaction cell operating conditions. The bone certified reference materials NIST SRM 1400 Bone Ash and NIST SRM 1486 Bone Meal were used for validation of the measurement protocol that was shown capable of providing accurate and reproducible results. Detection limits of P, Ca and Sr in dental tissue digests were established as 3 {mu}g L{sup -1} for P, 2 {mu}g L{sup -1} for Ca and 0.2 {mu}g L{sup -1} for Sr. This method can be used to simultaneously (i) evaluate the impact of diagenesis on the elemental and isotopic composition of buried skeletal tissue via its Ca/P ratio and (ii) determine its Sr concentration. The measurement protocol was demonstrated as fit-for-purpose by the analysis of a set of teeth of archaeological interest for their Ca/P ratio and Sr concentration.

  14. Development of a method based on inductively coupled plasma-dynamic reaction cell-mass spectrometry for the simultaneous determination of phosphorus, calcium and strontium in bone and dental tissue

    Science.gov (United States)

    De Muynck, David; Vanhaecke, Frank

    2009-05-01

    A method, based on the use of a quadrupole-based inductively coupled plasma-mass spectrometry instrument equipped with a quadrupole-based collision/reaction cell (dynamic reaction cell, DRC), was developed for the simultaneous determination of phosphorus, calcium and strontium in bone and dental (enamel and dentine) tissue. The use of NH 3, introduced at a gas flow rate of 0.8 mL min - 1 in the dynamic reaction cell, combined with a rejection parameter q (RPq) setting of 0.65, allows interference-free determination of calcium via its low-abundant isotopes 42Ca, 43Ca and 44Ca, and of strontium via its isotopes 86Sr and 88Sr that are freed from overlap due to the occurrence of ArCa + and/or Ca 2+ ions. Also the determination of phosphorus ( 31P, mono-isotopic) was shown to be achievable using the same dynamic reaction cell operating conditions. The bone certified reference materials NIST SRM 1400 Bone Ash and NIST SRM 1486 Bone Meal were used for validation of the measurement protocol that was shown capable of providing accurate and reproducible results. Detection limits of P, Ca and Sr in dental tissue digests were established as 3 µg L - 1 for P, 2 µg L - 1 for Ca and 0.2 µg L - 1 for Sr. This method can be used to simultaneously (i) evaluate the impact of diagenesis on the elemental and isotopic composition of buried skeletal tissue via its Ca/P ratio and (ii) determine its Sr concentration. The measurement protocol was demonstrated as fit-for-purpose by the analysis of a set of teeth of archaeological interest for their Ca/P ratio and Sr concentration.

  15. Development of a method based on inductively coupled plasma-dynamic reaction cell-mass spectrometry for the simultaneous determination of phosphorus, calcium and strontium in bone and dental tissue

    International Nuclear Information System (INIS)

    A method, based on the use of a quadrupole-based inductively coupled plasma-mass spectrometry instrument equipped with a quadrupole-based collision/reaction cell (dynamic reaction cell, DRC), was developed for the simultaneous determination of phosphorus, calcium and strontium in bone and dental (enamel and dentine) tissue. The use of NH3, introduced at a gas flow rate of 0.8 mL min-1 in the dynamic reaction cell, combined with a rejection parameter q (RPq) setting of 0.65, allows interference-free determination of calcium via its low-abundant isotopes 42Ca, 43Ca and 44Ca, and of strontium via its isotopes 86Sr and 88Sr that are freed from overlap due to the occurrence of ArCa+ and/or Ca2+ ions. Also the determination of phosphorus (31P, mono-isotopic) was shown to be achievable using the same dynamic reaction cell operating conditions. The bone certified reference materials NIST SRM 1400 Bone Ash and NIST SRM 1486 Bone Meal were used for validation of the measurement protocol that was shown capable of providing accurate and reproducible results. Detection limits of P, Ca and Sr in dental tissue digests were established as 3 μg L-1 for P, 2 μg L-1 for Ca and 0.2 μg L-1 for Sr. This method can be used to simultaneously (i) evaluate the impact of diagenesis on the elemental and isotopic composition of buried skeletal tissue via its Ca/P ratio and (ii) determine its Sr concentration. The measurement protocol was demonstrated as fit-for-purpose by the analysis of a set of teeth of archaeological interest for their Ca/P ratio and Sr concentration.

  16. Cycling and bone health: a systematic review

    OpenAIRE

    Olmedillas Hugo; González-Agüero Alejandro; Moreno Luis A; Casajus José A; Vicente-Rodríguez Germán

    2012-01-01

    Abstract Background Cycling is considered to be a highly beneficial sport for significantly enhancing cardiovascular fitness in individuals, yet studies show little or no corresponding improvements in bone mass. Methods A scientific literature search on studies discussing bone mass and bone metabolism in cyclists was performed to collect all relevant published material up to April 2012. Descriptive, cross-sectional, longitudinal and interventional studies were all reviewed. Inclusion criteria...

  17. Relation of grip strength, bone mineral density and body mass index in postmenopausal women%绝经后女性握力和体重指数与骨密度的相关研究

    Institute of Scientific and Technical Information of China (English)

    吕波

    2014-01-01

    Objective To study the positive association between hand grip strength and bone mineral density in postmenopausal women.We conducted a screening program for osteoporosis in a large cohort of postmenopausal women to investigate the relation among hand grip strength,other nutritional parameters and bone density.Methods This investigation involved 973 volunteers from March 2012 to March 2013 at Tianjin Hongqiao Hospital.Bone mineral density,hand grip strength measurement,body mass index and T score were analyzed.Results Univariate analysis showed that hand grip strength measurement,body mass index and T score were correlated (Pearson correlation coefficient were 0.201,0.115,P =0.001,0.009) ; age and T score were negatively correlated(Pearson correlation coefficient were-0.358,P =0.001).Incidence of osteoporosis was 19.7% (192/973).Conclusion Both body mass index and handgrip strength are strongly correlated to bone mineral density.%目的 探讨绝经后女性握力和体重指数与骨密度之间的相关性.方法 收集2012年3月至2013年3月在天津市红桥医院检查治疗973名女性志愿者,所有志愿者均接受足跟部骨密度测量(T指数)、握力测试和体重指数测量并进行相关性分析.结果 在单变量分析中,握力和体重指数与T指数相关(Pearson相关系数分别为0.201、0.115,P=0.001、0.009),年龄与T指数呈负相关(Pearson相关系数为-0.358,P=0.001).骨质疏松发病率18.7%(182/973).有骨质疏松和无骨质疏松绝经年龄、握力比较[绝经年龄(48±6)岁比(49±5)岁,P=0.020;握力(23±6)kg比(24±6) kg,P=0.001].结论 体重指数和握力二者均与骨密度密切相关,二者可作为预示骨疾病的关键因子.

  18. Interferon Gamma, but not Calcitriol Improves the Osteopetrotic Phenotypes in ADO2 Mice.

    Science.gov (United States)

    Alam, Imranul; Gray, Amie K; Acton, Dena; Gerard-O'Riley, Rita L; Reilly, Austin M; Econs, Michael J

    2015-11-01

    ADO2 is a heritable osteosclerotic disorder that usually results from heterozygous missense dominant negative mutations in the chloride channel 7 gene (CLCN7). ADO2 is characterized by a wide range of features and severity, including multiple fractures, impaired vision due to secondary bony overgrowth and/or the lack of the optical canal enlargement with growth, and osteonecrosis/osteomyelitis. The disease is presently incurable, although anecdotal evidence suggests that calcitriol and interferon gamma-1b (IFN-G) may have some beneficial effects. To identify the role of these drugs for the treatment of ADO2, we utilized a knock-in (G213R mutation in Clcn7) ADO2 mouse model that resembles the human disease. Six-week-old ADO2 heterozygous mice were administered vehicle (PBS) or calcitriol or IFN-G 5 times per week for 8 weeks. We determined bone phenotypes using DXA and μCT, and analyzed serum biochemistry and bone resorption markers. ADO2 mice treated with all doses of IFN-G significantly (pTV gain in both male and female compared to the vehicle group. In contrast, mice treated with low and medium doses of calcitriol showed a trend of higher aBMD and BV/TV whereas high dose calcitriol significantly (p<0.05) increased bone mass compared to the vehicle group. The calcium and phosphorus levels did not differ between vehicle and IFN-G or calcitriol treated mice; however, we detected significantly (p<0.05) elevated levels of CTX/TRAP5b ratio in IFN-G treated mice. Our findings indicate that while IFN-G at all doses substantially improved the osteopetrotic phenotypes in ADO2 heterozygous mice, calcitriol treatment at any dose did not improve the phenotype and at high dose further increased bone mass. Thus, use of high dose calcitriol therapy in ADO2 patients merits serious reconsideration. Importantly, our data support the prospect of a clinical trial of IFN-G in ADO2 patients. PMID:25943708

  19. Talking Bones.

    Science.gov (United States)

    Johnson, Jaclyn; Kassing, Sharon

    2002-01-01

    Describes cooperation with the Saint Louis Zoo to provide opportunities for elementary school students to learn about bones, how animals move, what they eat, and how much they grow. Uses biofacts which include bones, skulls, and other parts to make the laboratory a hands-on experience for students. (YDS)

  20. Bone Markers

    Science.gov (United States)

    ... bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker for bone resorption. It is ... resorption include: N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx)) – a peptide fragment from the amino terminal ...

  1. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone....... The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry...... is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year...

  2. Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

    Science.gov (United States)

    Halloran, B.; Weider, T.; Morey-Holton, E.

    1999-01-01

    The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

  3. Pathophysiology of bone loss in the female athlete.

    Science.gov (United States)

    Lambrinoudaki, Irene; Papadimitriou, Dimitra

    2010-09-01

    Low bone mass is frequent among female athletes. The "female athlete triad" is a term that describes the interaction among energy availability, menstrual function, and bone metabolism that may lead to amenorrhea and osteopenia or osteoporosis. The main pathophysiologic mechanisms that lead to low bone mass in female athletes are low energy availability and functional hypothalamic amenorrhea. Increased energy expenditure and/or decreased energy intake, as well as the presence of eating disorders, are associated with low bone mass. In addition, menstrual dysfunction is quite common, especially among athletes competing in sports favoring leanness, and also associates with low bone mass. Screening for bone loss in female athletes should take place in the presence of amenorrhea or body mass index <18 kg/m(2) . Management of low bone mass aims to restore normal energy availability and nutritional habits. Hormone replacement therapy has no effect in abnormally underweight patients unless normal eating behaviors are restored. PMID:20840252

  4. CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

    DEFF Research Database (Denmark)

    Tormin, Ariane; Li, Ou; Brune, Jan Claas;

    2011-01-01

    Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of prim...

  5. Nmp4/CIZ suppresses the response of bone to anabolic parathyroid hormone by regulating both osteoblasts and osteoclasts.

    Science.gov (United States)

    Childress, Paul; Philip, Binu K; Robling, Alexander G; Bruzzaniti, Angela; Kacena, Melissa A; Bivi, Nicoletta; Plotkin, Lilian I; Heller, Aaron; Bidwell, Joseph P

    2011-07-01

    How parathyroid hormone (PTH) increases bone mass is unclear, but understanding this phenomenon is significant to the improvement of osteoporosis therapy. Nmp4/CIZ is a nucleocytoplasmic shuttling transcriptional repressor that suppresses PTH-induced osteoblast gene expression and hormone-stimulated gains in murine femoral trabecular bone. To further characterize Nmp4/CIZ suppression of hormone-mediated bone growth, we treated 10-week-old Nmp4-knockout (KO) and wild-type (WT) mice with intermittent human PTH(1-34) at 30 μg/kg daily or vehicle, 7 days/week, for 2, 3, or 7 weeks. Null mice treated with hormone (7 weeks) gained more vertebral and tibial cancellous bone than WT animals, paralleling the exaggerated response in the femur. Interestingly, Nmp4/CIZ suppression of this hormone-stimulated bone formation was not apparent during the first 2 weeks of treatment. Consistent with the null mice enhanced PTH-stimulated addition of trabecular bone, these animals exhibited an augmented hormone-induced increase in serum osteocalcin 3 weeks into treatment. Unexpectedly, the Nmp4-KO mice displayed an osteoclast phenotype. Serum C-terminal telopeptide, a marker for bone resorption, was elevated in the null mice, irrespective of treatment. Nmp4-KO bone marrow cultures produced more osteoclasts, which exhibited elevated resorbing activity, compared to WT cultures. The expression of several genes critical to the development of both osteoblasts and osteoclasts was elevated in Nmp4-KO mice at 2 weeks, but not 3 weeks, of hormone exposure. We propose that Nmp4/CIZ dampens PTH-induced improvement of trabecular bone throughout the skeleton by transiently suppressing hormone-stimulated increases in the expression of proteins key to the required enhanced activity and number of both osteoblasts and osteoclasts. PMID:21607813

  6. Estrogen-mimicking isoflavone genistein prevents bone loss in a rat model of obstructive sleep apnea-hypopnea syndrome

    OpenAIRE

    Song, Lige; Liang, Xiao; Zhou, Yun

    2014-01-01

    Objective: Intermittent hypoxia was introduced to mimic obstructive sleep apnea-hypopnea syndrome (OSAHS) in rats. Then, bone mass, bone strength and bone turnover were evaluated, and the influence of genistein on bone mass reduction was investigated in these rats. Methods: OSAHS animal model was established via chronic intermittent hypoxia, and genistein (2.5 mg/kg/day) was used to treat OSAHS rats. The bone mineral density (BMD), bone Histomorphometric indicators, bone biomechanics and expr...

  7. Fibrillin microfibrils in bone physiology.

    Science.gov (United States)

    Smaldone, Silvia; Ramirez, Francesco

    2016-01-01

    The severe skeletal abnormalities associated with Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCA) underscore the notion that fibrillin assemblies (microfibrils and elastic fibers) play a critical role in bone formation and function in spite of representing a low abundance component of skeletal matrices. Studies of MFS and CCA mice have correlated the skeletal phenotypes of these mutant animals with distinct pathophysiological mechanisms that reflect the contextual contribution of fibrillin-1 and -2 scaffolds to TGFβ and BMP signaling during bone patterning, growth and metabolism. Illustrative examples include the unique role of fibrillin-2 in regulating BMP-dependent limb patterning and the distinct impact of the two fibrillin proteins on the commitment and differentiation of marrow mesenchymal stem cells. Collectively, these findings have important implication for our understanding of the pathophysiological mechanisms that drive age- and injury-related processes of bone degeneration. PMID:26408953

  8. Bone Tumor

    Science.gov (United States)

    ... the knee in either the femur (thigh) or tibia (shinbone). Other common locations include the hip and ... bone that is weakened by a tumor to fracture, or break. This may be severely painful. Occasionally, ...

  9. Your Bones

    Science.gov (United States)

    ... a fall! If you play sports like football, soccer, lacrosse, or ice hockey, always wear all the ... to strengthen your bones is through exercise like running, jumping, dancing, and playing sports. Take these steps ...

  10. Bone health in anorexia nervosa

    Science.gov (United States)

    Misra, Madhusmita; Klibanski, Anne

    2013-01-01

    Purpose of review Anorexia nervosa is associated with low bone mineral density (BMD), concerning for an increased risk of fractures, and decreased bone accrual in adolescents, concerning for suboptimal peak bone mass. This review discusses causes of impaired bone health in anorexia nervosa and potential therapeutic strategies. Recent findings Low BMD in anorexia nervosa is consequent to decreased lean mass, hypogonadism, low insulin-like growth factor-1 (IGF-1), relative hypercortisolemia and alterations in hormones impacted by energy availability. Weight gain causes some improvement in bone accrual, but not to the extent observed in controls, and vitamin D supplementation does not increase BMD. Oral estrogen is not effective in increasing BMD, likely from IGF-1 suppressive effects. In contrast, transdermal estrogen replacement is effective in increasing bone accrual in adolescents with anorexia nervosa, although not to the extent seen in controls. Recombinant human IGF-1 increases bone formation in adolescents, and with oral estrogen increases BMD in adults with anorexia nervosa. Bisphosphonates increase BMD in adults, but not in adolescents, and should be used cautiously given their long half-life. Summary Further investigation is necessary to explore therapies for low BMD in anorexia nervosa. Weight gain is to be encouraged. Transdermal estrogen in adolescents, and bisphosphonates in adults, have a potential therapeutic role. PMID:21897220

  11. An adaptation model for trabecular bone at different mechanical levels

    OpenAIRE

    Lv Linwei; Gao Jiazi; Zhu Dong; Gong He; Zhang Xizheng

    2010-01-01

    Abstract Background Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of b...

  12. High-fat Diet Causes Bone Loss in Young Mice by Promoting Osteoclastogenesis through Alteration of the Bone Marrow Environment

    OpenAIRE

    Shu, Lei; Beier, Eric; Sheu, Tzong; Zhang, Hengwei; Zuscik, Michael; Puzas, J. Edward; Boyce, F. Brendan; Mooney, A. Robert; Xing, Lianping

    2015-01-01

    Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks...

  13. Optimizing Bone Health in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Jason L. Buckner

    2015-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA, as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

  14. Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Zaher, Walid; Larsen, Kenneth H;

    2015-01-01

    by bioluminescence imaging (BLI). In order to identify the molecular phenotype associated with enhanced migration, we carried out comparative DNA microarray analysis of gene expression of hBMSC-derived high bone forming (HBF) clones versus low bone forming (LBF) clones. RESULTS: HBF clones were exhibited higher ex...

  15. The response of bone to unloading

    Science.gov (United States)

    Bikle, D. D.; Halloran, B. P.

    1999-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with

  16. Bone marrow origin of Ia molecules purified from epidermal cells

    International Nuclear Information System (INIS)

    Using radiation bone marrow chimeras, we have shown that Ia molecules purified from epidermal cell preparations of the mouse reflect the Ia phenotype of the bone marrow donor. This result strongly suggests that Ia molecules are synthesized by a bone-marrow-derived cell in the epidermis. Furthermore, results of peptide map analysis of immunoprecipitated biosynthetically labeled Ia suggest that the Ia molecules found in skin are identical to those found on B lymphocytes. These results support biochemical as well as serologic identity

  17. Validación de cuestionarios para el estudio de hábitos alimentarios y masa ósea Validation of questionnaires for the study of food habits and bone mass

    Directory of Open Access Journals (Sweden)

    A. Rivas

    2009-10-01

    Full Text Available Antecedentes: La pérdida de masa y densidad de los huesos esta influenciada por factores nutricionales, actuando sobre el pico de masa ósea, la pérdida ósea relacionada con la edad y la fortaleza muscular. El objetivo del presente estudio es validar un cuestionario de frecuencia de consumo de alimentos aplicado a la estimación de la relación entre los hábitos alimentarios y la densidad mineral ósea de una población adulta sana. Métodos: Los resultados obtenidos mediante el cuestionario de frecuencia de consumo de alimentos se compararon con los de recordatorios de 24 horas. Las medidas de la densidad mineral ósea se realizaron mediante densitometría de calcáneo. Resultados: Se demuestra la validez del cuestionario al obtener coeficientes de correlación de Spearman entre 0,014 y 0,467. Asimismo el test de Bland-Altman muestra que no existe variación entre los dos métodos para las variables analizadas. El análisis de correlación muestra que la densidad mineral ósea está asociada significativamente al consumo de vitamina D, vitamina A, vitamina B12, folato, tiamina y hierro. El consumo de lípidos totales no fue asociado con la densidad mineral ósea, sin embargo la ingesta de ácidos grasos monoinsaturados, EPA y DHA y colesterol muestra una correlación estadísticamente significativa. Conclusión: El cuestionario estima el consumo de energía y nutrientes con adecuada validez. Su aplicación nos ha permitido deducir la importancia de una dieta rica en vitaminas del grupo B, vitamina D, calcio, hierro y ácidos grasos monoinsaturados y n-3 en la salud ósea.Background: The loss of bone mass and density is influenced by nutritional factors that act on the bone mass peak, age-related bone loss and muscle strength. The objective of the present study was to validate a food frequency questionnaire applied to estimate the relationship between food habits and bone mineral density (BMD in a healthy adult population. Methods: The

  18. Bone densitometer

    International Nuclear Information System (INIS)

    In an x-ray bone densitometer, special calibration techniques are employed to accommodate variations. In one aspect, a bone-like calibration material is interposed and the system determines the calibration data from rays passing only through flesh. In another aspect, a rotating device carries the calibration material through the beam. The specific densitometer shown uses an x-ray tube operated at two different voltages to generate a pencil beam, the energy levels of the x-ray photons being a function of the voltage applied. An integrating detector is timed to integrate the detected signal of the patient-attenuated beam over each pulse, the signals are converted to digital values and a digital computer converts the set of values produced by the raster scan into a representation of the bone density of the patient. Multiple reference detectors with differing absorbers are used by the system to continuously correct for variation in voltage and current of the x-ray tube. Calibration is accomplished by the digital computer on the basis of passing the pencil beam through known bone-representing substance as the densitometer scans portions of the patient having bone and adjacent portions having only flesh. A set of detected signals affected by the calibration substance in regions having only flesh is compared by the computer with a set of detected signals unaffected by the calibration material

  19. In Vivo Over-expression of Circulating Dlk1/Pref-1 Protein Using Hydrodynamic-based Gene Transfer Leads to Lower Bone mass With Marked Effects on Trabecular Bone Micro-architecture

    DEFF Research Database (Denmark)

    Ding, Ming

    Dlk1/Pref-1 (delta like1/preadipocte factor-1) is an imprinted gene encoding a transmembrane protein that belongs to EGF-like repeats protein family. We have recently identified Dlk1/Pref-1 as negative regulator for differentiation of human mesenchymal stem cells into osteoblasts and adipocytes...... (Abdallah BM, et. al., JBMR, May,19(5):841-852, 2004). To further investigate the in vivo effect of Dlk1/Pref-1 on bone, we generated mice expressing high serum levels of FA1 (biological soluble form of Dlk1) using the hydrodynamic-based gene transfer procedure. Full length of mouse Pref-1 cDNA was...... subcloned under human ubiquitin promoter and rapidly injected via tail vein into BALB/cA male mice (16 weeks old, n =15) every 2 weeks over a period of 2 months. DNA, mRNA analysis, immunohistology and ELISA for FA1 were assayed to identify the expression of the transgene. Bone mass and structure were...

  20. Blood and Bones: The Influence of the Mass Media on Australian Primary School Children's Understandings of Genes and DNA

    Science.gov (United States)

    Donovan, Jenny; Venville, Grady

    2014-01-01

    Previous research showed that primary school children held several misconceptions about genetics of concern for their future lives. Included were beliefs that genes and DNA are separate substances, with genes causing family resemblance and DNA identifying suspects at crime scenes. Responses to this work "blamed" the mass media for these…

  1. Short Anabolic Peptides for Bone Growth.

    Science.gov (United States)

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth. PMID:27297498

  2. Vibrational spectroscopy in biomedical science: bone

    Science.gov (United States)

    Gamsjäger, Sonja; Zoehrer, R.; Roschger, P.; Fratzl, P.; Klaushofer, K.; Mendelsohn, R.; Paschalis, E. P.

    2009-02-01

    Fourier transform infrared imaging (FTIR) and Raman Microspectroscopy are powerful tools for characterizing the distribution of different chemical moieties in heterogeneous materials. FTIR and Raman measurements have been adapted to assess the maturity of the mineral and the quality of the organic component (collagen and non-collagenous proteins) of the mineralized tissue in bone. Unique to the FTIRI analysis is the capability to provide the spatial distribution of two of the major collagen cross-links (pyridinoline, and dehydro-dihydroxylysinonorleucine) and through the study of normal and diseased bone, relate them to bone strength. These FTIR parameters have been validated based on analysis of model compounds. It is widely accepted that bone strength is determined by bone mass and bone quality. The latter is a multifactorial term encompassing the material and structural properties of bone, and one important aspect of the bone material properties is the organic matrix. The bone material properties can be defined by parameters of mineral and collagen, as determined by FTIR and Raman analysis. Considerably less attention has been directed at collagen, although there are several publications in the literature reporting altered collagen properties associated with fragile bone, in both animals and humans. Since bone is a heterogeneous tissue due to the remodeling process, microscopic areas may be carefully selected based on quantitative Backscattered Electron Imaging or histological staining, thus ensuring comparison of areas with similar metabolic activity and mineral content. In conclusion, FTIRI and Raman vibrational spectroscopy are proving to be powerful tools in bone-related medical research.

  3. Mutations in FAM20C Are Associated with Lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), Highlighting a Crucial Molecule in Bone Development

    OpenAIRE

    Simpson, M. A. ; Hsu, R. ; Keir, L. S. ; Hao, J. ; Sivapalan, G. ; Ernst, L. M. ; Zackai, E. H. ; Al-Gazali, L. I. ; Hulskamp, G. ; Kingston, H. M. ; Prescott, T. E. ; Ion, A. ; Patton, M. A. ; Murday, V. ; George, A. 

    2007-01-01

    The generation and homeostasis of bone tissue throughout development and maturity is controlled by the carefully balanced processes of bone formation and resorption. Disruption of this balance can give rise to a broad range of skeletal pathologies. Lethal osteosclerotic bone dysplasia (or, Raine syndrome) is an autosomal recessive disorder characterized by generalized osteosclerosis with periosteal bone formation and a distinctive facial phenotype. Affected individuals survive only days or we...

  4. Gravity, Calcium, And Bone: Update, 1989

    Science.gov (United States)

    Arnaud, Sara B.; Morey-Holton, Emily

    1992-01-01

    Report reviews short-term flight and ground-based experiments on effects of 1 g and 0 g on skeletal adaptation, calcium metabolism, and growth processes. Results indicate two principal components of calcium metabolism-calcium endocrine system and bone - respond within days to changes in orientation of body in gravitation and to weightlessness. Effects of spaceflight or bed rest on biomechanics of bones more severe than on total body bone mass.

  5. Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats.

    Science.gov (United States)

    Gasser, Jürg A; Hulter, Henry N; Imboden, Peter; Krapf, Reto

    2014-03-01

    Chronic metabolic acidosis (CMA) might result in a decrease in vivo in bone mass based on its reported in vitro inhibition of bone mineralization, bone formation, or stimulation of bone resorption, but such data, in the absence of other disorders, have not been reported. CMA also results in negative nitrogen balance, which might decrease skeletal muscle mass. This study analyzed the net in vivo effects of CMA's cellular and physicochemical processes on bone turnover, trabecular and cortical bone density, and bone microarchitecture using both peripheral quantitative computed tomography and μCT. CMA induced by NH4Cl administration (15 mEq/kg body wt/day) in intact and ovariectomized (OVX) rats resulted in stable CMA (mean Δ[HCO3(-)]p = 10 mmol/l). CMA decreased plasma osteocalcin and increased TRAP5b in intact and OVX animals. CMA decreased total volumetric bone mineral density (vBMD) after 6 and 10 wk (week 10: intact normal +2.1 ± 0.9% vs. intact acidosis -3.6 ± 1.2%, P effect attributable to a decrease in cortical thickness and, thus, cortical bone mass (no significant effect on cancellous vBMD, week 10) attributed to an increase in endosteal bone resorption (nominally increased endosteal circumference). Trabecular bone volume (BV/TV) decreased significantly in both CMA groups at 6 and 10 wk, associated with a decrease in trabecular number. CMA significantly decreased muscle cross-sectional area in the proximal hindlimb at 6 and 10 wk. In conclusion, chronic metabolic acidosis induces a large decrease in cortical bone mass (a prime determinant of bone fragility) in intact and OVX rats and impairs bone microarchitecture characterized by a decrease in trabecular number. PMID:24352505

  6. Bone lesion biopsy

    Science.gov (United States)

    Bone biopsy; Biopsy - bone ... needle is gently pushed and twisted into the bone. Once the sample is obtained, the needle is ... sample is sent to a lab for examination. Bone biopsy may also be done under general anesthesia ...

  7. What Is Bone?

    Science.gov (United States)

    ... by your browser. Home Bone Basics What Is Bone? Publication available in: PDF (57 KB) Related Resources ... Men, and Osteoporosis Osteoporosis Prevention For Your Information Bone Remodeling Throughout life, bone is constantly renewed through ...

  8. Calcium and bones

    Science.gov (United States)

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  9. Facts about Broken Bones

    Science.gov (United States)

    ... White House Lunch Recipes The Facts About Broken Bones KidsHealth > For Kids > The Facts About Broken Bones ... through the skin . continue What Happens When a Bone Breaks? It hurts to break a bone! It's ...

  10. Bone biopsy (image)

    Science.gov (United States)

    A bone biopsy is performed by making a small incision into the skin. A biopsy needle retrieves a sample of bone and it ... examination. The most common reasons for bone lesion biopsy are to distinguish between benign and malignant bone ...

  11. Bone lesion biopsy

    Science.gov (United States)

    Bone biopsy; Biopsy - bone ... is sent to a lab for examination. Bone biopsy may also be done under general anesthesia to ... remove the bone can be done if the biopsy exam shows that there is an abnormal growth ...

  12. The temporal response of bone to unloading

    Science.gov (United States)

    Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

    1984-01-01

    Rats were suspended by their tails with the forelimbs bearing the weight load to simulate the weightlessness of space flight. Growth in bone mass ceased by 1 week in the hindlimbs and lumbar vertebrae in growing rats, while growth in the forelimbs and cervical vertebrae remained unaffected. The effects of selective skeletal unloading on bone formation during 2 weeks of suspension was investigated using radio iostope incorporation (with Ca-45 and H-3 proline) and histomorphometry (with tetracycline labeling). The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. This model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed in the accretion of bone mass, which then resumes at a normal rate by 14 days, despite continued skeletal unloading. This cycle of inhibition and resumption of bone formation has profound implication for understanding bone dynamics durng space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

  13. Massa óssea em crianças e adolescentes que vivem com vírus da imunodeficiência humana Bone mass in children and adolescents infected with human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Luiz R. A. de Lima

    2013-02-01

    Nutrition Examination Survey IV (NHANES IV. METHOD: The study included 48 children and adolescents (7 to 17 years old infected with HIV through vertical transmission. BMC and BMD were measured by dual energy absorptiometry X-ray, by calculating z-scores based on data from NHANES IV. The information on clinical and laboratory parameters of infection by HIV was obtained from medical records. Physical activity, calcium intake, and skeletal maturation were also assessed. Descriptive and inferential statistical procedures were used, with levels of significance set at 5%. RESULTS: Seropositive patients presented lower values compared to data from NHANES IV in all z-scores of bone mass (mean = -0.52 to -1.22, SD = 0.91 and 0.84, respectively. Based on the subtotal z-BMD, there was a prevalence of 16.7% of children and adolescents with low bone mass for age. Individuals using protease inhibitors presented a lower total z-BMD when compared to the group that did not use (-1.31 vs. -0.79, p = 0.02. There were no bone mass differences in relation to physical activity and calcium intake. CONCLUSIONS: In the present sample children and adolescents living with HIV have low bone mass for age, and the use of protease inhibitors appears to be related to such decreases.

  14. How to exhaust your bone marrow

    DEFF Research Database (Denmark)

    Salomo, Louise; Salomo, Morten; Andersen, Steven A W;

    2013-01-01

    at work and in his spare time, and kept a very thorough training and weight diary. Owing to a high intake of energy and protein drinks he tried to optimise his physical performance and kept a normal body mass index  at 23.7. A bone marrow biopsy showed gelatinous bone marrow transformation, normally...

  15. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  16. Phenotypic Resistance to Antibiotics

    Directory of Open Access Journals (Sweden)

    Jose L. Martinez

    2013-04-01

    Full Text Available The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

  17. Handheld FRET-Aptamer Sensor for Bone Markers Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Astronauts lose significant bone mass during lengthy spaceflights. Although, no effective treatments or prophylactics have yet been defined, it is important to...

  18. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

    Henriksen, K; Leeming, Diana Julie; Byrjalsen, I;

    2007-01-01

    We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of...... aged bones....

  19. Selenoprotein P is the essential selenium transporter for bones.

    Science.gov (United States)

    Pietschmann, Nicole; Rijntjes, Eddy; Hoeg, Antonia; Stoedter, Mette; Schweizer, Ulrich; Seemann, Petra; Schomburg, Lutz

    2014-05-01

    Selenium (Se) plays an important role in bone physiology as best reflected by Kashin-Beck disease, an endemic Se-dependent osteoarthritis. Bone development is delayed in children with mutations in SECIS binding protein 2 (SBP2), a central factor for selenoprotein biosynthesis. Circulating selenoprotein P (SePP) is positively associated with bone turnover in humans, yet its function for bone homeostasis is not known. We have analysed murine models of altered Se metabolism. Most of the known selenoprotein genes and factors needed for selenoprotein biosynthesis are expressed in bones. Bone Se is not associated with the mineral but exclusively with the organic matrix. Genetic ablation of Sepp-expression causes a drastic decline in serum (25-fold) but only a mild reduction in bone (2.5-fold) Se concentrations. Cell-specific expression of a SePP transgene in hepatocytes efficiently restores bone Se levels in Sepp-knockout mice. Of the two known SePP receptors, Lrp8 was detected in bones while Lrp2 was absent. Interestingly, Lrp8 mRNA concentrations were strongly increased in bones of Sepp-knockout mice likely in order to counteract the developing Se deficiency. Our data highlight SePP as the essential Se transporter to bones, and suggest a novel feedback mechanism for preferential uptake of Se in Se-deprived bones, thereby contributing to our understanding of hepatic osteodystrophy and the consistent bone phenotype observed in subjects with inherited selenoprotein biosynthesis mutations. PMID:24626785

  20. Effect of a program of short bouts of exercise on bone health in adolescents involved in different sports: the PRO-BONE study protocol

    OpenAIRE

    Vlachopoulos, Dimitris; Barker, Alan R; Williams, Craig A.; Karen M. Knapp; Metcalf, Brad S.; Gracia-Marco, Luis

    2015-01-01

    Background Osteoporosis is a skeletal disease associated with high morbidity, mortality and increased economic costs. Early prevention during adolescence appears to be one of the most beneficial practices. Exercise is an effective approach for developing bone mass during puberty, but some sports may have a positive or negative impact on bone mass accrual. Plyometric jump training has been suggested as a type of exercise that can augment bone, but its effects on adolescent bone mass have not b...

  1. Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station.

    Directory of Open Access Journals (Sweden)

    Naoto Shiba

    Full Text Available Musculoskeletal atrophy is one of the major problems of extended periods of exposure to weightlessness such as on the International Space Station (ISS. We developed the Hybrid Training System (HTS to maintain an astronaut's musculoskeletal system using an electrically stimulated antagonist to resist the volitional contraction of the agonist instead of gravity. The present study assessed the system's orbital operation capability and utility, as well as its preventative effect on an astronaut's musculoskeletal atrophy.HTS was attached to the non-dominant arm of an astronaut staying on the ISS, and his dominant arm without HTS was established as the control (CTR. 10 sets of 10 reciprocal elbow curls were one training session, and 12 total sessions of training (3 times per week for 4 weeks were performed. Pre and post flight ground based evaluations were performed by Biodex (muscle performance, MRI (muscle volume, and DXA (BMD, lean [muscle] mass, fat mass. Pre and post training inflight evaluations were performed by a hand held dynamometer (muscle force and a measuring tape (upper arm circumference.The experiment was completed on schedule, and HTS functioned well without problems. Isokinetic elbow extension torque (Nm changed -19.4% in HTS, and -21.7% in CTR. Isokinetic elbow flexion torque changed -23.7% in HTS, and there was no change in CTR. Total Work (Joule of elbow extension changed -8.3% in HTS, and +0.3% in CTR. For elbow flexion it changed -23.3% in HTS and -32.6% in CTR. Average Power (Watts of elbow extension changed +22.1% in HTS and -8.0% in CTR. For elbow flexion it changed -6.5% in HTS and -4.8% in CTR. Triceps muscle volume according to MRI changed +11.7% and that of biceps was +2.1% using HTS, however -0.1% and -0.4% respectively for CTR. BMD changed +4.6% in the HTS arm and -1.2% for CTR. Lean (muscle mass of the arm changed only +10.6% in HTS. Fat mass changed -12.6% in HTS and -6.4% in CTR.These results showed the orbital

  2. Influence of Gastrectomy on Cortical and Cancellous Bones in Rats

    Directory of Open Access Journals (Sweden)

    Jun Iwamoto

    2013-01-01

    Full Text Available The aim of the present study was to examine the influence of gastrectomy (GX on cortical and cancellous bones in rats. Twenty male Sprague-Dawley rats were randomized into the two groups of 10 animals each: a sham operation (control group and a GX group. Seven weeks after surgery, the bone mineral content and density (BMC and BMD, resp. and the mechanical strength of the femur were determined, and bone histomorphometric analyses were performed on the tibia. GX induced decreases in the BMC, BMD, ultimate force, work to failure, and stiffness of the femoral distal metaphysis and the BMC, BMD, and ultimate force of the femoral diaphysis. GX induced a decrease in cancellous bone mass, characterized by an increased osteoid thickness, osteoid surface, osteoid volume, and bone formation. GX also induced a decrease in cortical bone mass, characterized by increased endocortical bone resorption. The GX induced reductions in the bone mass and strength parameters were greater in cancellous bone than in cortical bone. The present study showed that the response of bone formation, resorption, and osteoid parameters to GX and the degree of GX-induced osteopenia and the deterioration of bone strength appeared to differ between cortical and cancellous bones in rats.

  3. Physiology and molecular characterization of metabolism related mouse models for bone disease

    OpenAIRE

    Chi, Shen

    2015-01-01

    Bone disorders are commonly associated with various metabolic diseases. Two ENU- induced mutant mouse lines were analyzed to explore the relationship between bone and metabolic phenotypes. SATB2 was proven to regulate bone development. In addition, a previously unknown role of the gene in energy metabolism was uncovered. Only a minor influence on bone homeostasis and energy metabolism could be attributed to the T720A mutation of DLL1.

  4. Lipid metabolism disorders and bone dysfunction-interrelated and mutually regulated (Review)

    OpenAIRE

    Tian, Li; Yu, Xijie

    2015-01-01

    The association between lipid and bone metabolism has become an increasing focus of interest in recent years, and accumulating evidence has shown that atherosclerosis (AS) and osteoporosis (OP), a disorder of bone metabolism, frequently co-exist. Fat and bone are known to share a common progenitor cell: Multipotent mesenchymal stem cells (MSC) in the bone marrow (BM), which are able to differentiate into various cell phenotypes, including osteoblasts, adipocytes and chondrocytes. Laboratory-b...

  5. Phenotypic Switching in Fungi

    OpenAIRE

    Jain, Neena; Hasan, Fahmi; Fries, Bettina C.

    2008-01-01

    Over the past three decades new fungal diseases have emerged that now constitute a major threat, especially for patients with chronic diseases and/or underlying immune defi ciencies. Despite the epidemiologic data, the emergence of stable drug-resistant or hyper-virulent fungal strains in human disease has not been demonstrated as seen in emerging viral and bacterial infections. Fungi are eukaryotic microbes that capitalize on a sophisticated built-in ability to generate phenotypic variabilit...

  6. Postmenopausal bone loss and the risk of osteoporosis.

    Science.gov (United States)

    Christiansen, C

    1994-01-01

    The two most important risk factors for long-term skeletal health are the peak bone mass and the subsequent rate of bone loss. The rate of bone loss after skeletal maturity is determined by both genetic factors and environmental factors. Furthermore, all factors that impair estrogen production will increase bone loss. The present risk of developing osteoporosis and fractures may be assessed by bone mass measurements in the total skeleton, or in local parts of the skeleton such as the spine, hip and forearm, by single-photon/X-ray absorptiometry (SPA or SXA), dual-photon/energy X-ray absorptiometry (DPA or DXA), or quantitative computed tomography (QCT). Furthermore, the rate of bone loss in postmenopausal women may be assessed by means of a number of biochemical markers. The fútúre risk of developing osteoporosis may thus be determined by combining the values for bone mineral content and bone loss. PMID:8081059

  7. Understanding the local actions of lipids in bone physiology.

    Science.gov (United States)

    During, Alexandrine; Penel, Guillaume; Hardouin, Pierre

    2015-07-01

    The adult skeleton is a metabolically active organ system that undergoes continuous remodeling to remove old and/or stressed bone (resorption) and replace it with new bone (formation) in order to maintain a constant bone mass and preserve bone strength from micro-damage accumulation. In that remodeling process, cellular balances--adipocytogenesis/osteoblastogenesis and osteoblastogenesis/osteoclastogenesis--are critical and tightly controlled by many factors, including lipids as discussed in the present review. Interest in the bone lipid area has increased as a result of in vivo evidences indicating a reciprocal relationship between bone mass and marrow adiposity. Lipids in bones are usually assumed to be present only in the bone marrow. However, the mineralized bone tissue itself also contains small amounts of lipids which might play an important role in bone physiology. Fatty acids, cholesterol, phospholipids and several endogenous metabolites (i.e., prostaglandins, oxysterols) have been purported to act on bone cell survival and functions, the bone mineralization process, and critical signaling pathways. Thus, they can be regarded as regulatory molecules important in bone health. Recently, several specific lipids derived from membrane phospholipids (i.e., sphingosine-1-phosphate, lysophosphatidic acid and different fatty acid amides) have emerged as important mediators in bone physiology and the number of such molecules will probably increase in the near future. The present paper reviews the current knowledge about: (1°) bone lipid composition in both bone marrow and mineralized tissue compartments, and (2°) local actions of lipids on bone physiology in relation to their metabolism. Understanding the roles of lipids in bone is essential to knowing how an imbalance in their signaling pathways might contribute to bone pathologies, such as osteoporosis. PMID:26118851

  8. A new concept of the pattern of structural changes with bone loss by histomorphometric analysis using bone slabs.

    Science.gov (United States)

    Hoshino, K; Naguro, T; Iino, A

    1999-01-01

    We examined naked bone slabs (1.2 mm thick) from iliac bone biopsied cores obtained from 33 women aged 33-89 years. The number, size, and shape of the pores in the bone slabs were analyzed. The results revealed that the % bone area (the percentage area occupied by bone in the slab) was linearly correlated with age and other parameters, such as the size of pores, irregularity of pores, and pore distance, but was not correlated to the number of pores. We found a second-degree polynomial relationship between the % bone area and the number of pores. Based on three parameters--% bone area, number of pores, and size of pores--cluster analysis was performed and the specimens divided into three groups. The group with sufficient bone mass showed few small round pores, and the group with severe bone loss revealed a few large pores that were caved in. The characteristics of these groups represented the relationship between bone mass and structural change. The remaining group with moderate bone loss was divided into two subgroups, one with an increased number of pores without expansion and one with expanded pores without an increase in number. We presumed that the variations between the groups were caused by differences between fine and rough structures in the trabeculae caused during the process of bone loss. We concluded that this analysis of bone slabs allowed the pattern of trabecular structural change that occurred with bone loss to be determined easily and visually. PMID:10757677

  9. Bone Quality: The Mechanical Effects of Microarchitecture and Matrix Properties

    OpenAIRE

    Day, Judd

    2005-01-01

    textabstractIn this body of work we have examined some of the current concepts pertaining to the relation between bone mass, bone quality and the mechanical properties of bone. In our first series of studies we used a model of human osteoarthritis to investigate the implications of changes in the effective tissue modulus. Having established that the material properties of the trabecular bone were altered in the earliest stages of osteoarthritis, we then investigated a possible cause, namely th...

  10. Osteoporosis: Modern Paradigms for Last Century’s Bones

    OpenAIRE

    Kruger, Marlena C.; Wolber, Frances M.

    2016-01-01

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a “brittle bone” disease that occurs in post-menopausal, thin, Caucasian women wi...

  11. 肥胖男童骨矿物质含量及瘦体重的研究%Research of Bone Mineral Content and Lean Mass in Male Obese Children.

    Institute of Scientific and Technical Information of China (English)

    姜梅; 黄玉春; 华天懿; 赵淑霞

    2001-01-01

    【目的】了解以体脂含量增加为特点的肥胖儿童骨矿物质含量、骨密度及瘦体重有何变化。【方法】应用体块指数(BMI)诊断的肥胖组及对年龄、身高进行一一配对的正常组儿童各17例,年龄7~13岁,测定其骨矿物质含量(BMC)、骨密度(BMD)及瘦体重(LM),观察二组间的差异,再用体脂含量百分比(F%)来重新诊断这34名儿童,观察肥胖组与对照组间上述指标的差异,并应用多因素分析肥胖与骨矿物质含量之间的关系。【结果】应用BMI为诊断标准时肥胖组与对照组间的BMC、BMD、LM有显著差异。改用F%为诊断标准后,肥胖儿童与正常儿童间的BMC、BMD差别消失,LM之间的差别也减小,多因素分析结果:体脂含量、肥胖与BMC无关。【结论】若以体脂含量增加来定义肥胖儿童,其骨矿物质含量、骨密度与正常儿童相比无差别,瘦体重差别也不大,单纯体脂含量的增加并不能引起骨矿物质含量的改变。%【Objective】 To assess and compare bone mineral content(BMC), bone mineral density(BMD)and lean mass(LM) in normal children and obese children who have excessive fat.  【Methods】 In a case control study,17 male obese children aged 7~13,diagnosed by body mass index(BMI)were recruited,17 healthy male children mached for age and height were enrolled as control.Total body BMC,total body BMD and total LM were measured by dual X-ray absorptiometry. The results were compared between the two groups. Then, obesity were rediagnosed by body fat percent(F%) in these 34 children, comparation was done again. Multiple-linear-regression analysis was used to access the influence of age, height, body composition variables and obesity on the dependent variable BMC. 【Results】 When BMI was used to diagnose obesity, there was significant differences in BMC,BMD and LM between two groups. However, when F% was used to assess obesity, no

  12. Osedax borings in fossil marine bird bones

    Science.gov (United States)

    Kiel, Steffen; Kahl, Wolf-Achim; Goedert, James L.

    2011-01-01

    The bone-eating marine annelid Osedax consumes mainly whale bones on the deep-sea floor, but recent colonization experiments with cow bones and molecular age estimates suggesting a possible Cretaceous origin of Osedax indicate that this worm might be able grow on a wider range of substrates. The suggested Cretaceous origin was thought to imply that Osedax could colonize marine reptile or fish bones, but there is currently no evidence that Osedax consumes bones other than those of mammals. We provide the first evidence that Osedax was, and most likely still is, able to consume non-mammalian bones, namely bird bones. Borings resembling those produced by living Osedax were found in bones of early Oligocene marine flightless diving birds (family Plotopteridae). The species that produced these boreholes had a branching filiform root that grew to a length of at least 3 mm, and lived in densities of up to 40 individuals per square centimeter. The inclusion of bird bones into the diet of Osedax has interesting implications for the recent suggestion of a Cretaceous origin of this worm because marine birds have existed continuously since the Cretaceous. Bird bones could have enabled this worm to survive times in the Earth's history when large marine vertebrates other than fish were rare, specifically after the disappearance of large marine reptiles at the end-Cretaceous mass extinction event and before the rise of whales in the Eocene.

  13. Bone changes in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Alcoholism has been associated with growth impairment,osteomalacia, delayed fracture healing, and asepticnecrosis (primarily necrosis of the femoral head), butthe main alterations observed in the bones of alcoholicpatients are osteoporosis and an increased risk offractures. Decreased bone mass is a hallmark of osteoporosis,and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanolmay affect both mechanisms. It is generally acceptedthat ethanol decreases bone synthesis, and most authorshave reported decreased osteocalcin levels (a "marker" ofbone synthesis), but some controversy exists regardingthe effect of alcohol on bone breakdown, and, indeed,disparate results have been reported for telopeptideand other biochemical markers of bone resorption.In addition to the direct effect of ethanol, systemicalterations such as malnutrition, malabsorption, liverdisease, increased levels of proinflammatory cytokines,alcoholic myopathy and neuropathy, low testosteronelevels, and an increased risk of trauma, play contributoryroles. The treatment of alcoholic bone disease should beaimed towards increasing bone formation and decreasingbone degradation. In this sense, vitamin D and calciumsupplementation, together with biphosphonates areessential, but alcohol abstinence and nutritional improvementare equally important. In this review we study thepathogenesis of bone changes in alcoholic liver diseaseand discuss potential therapies.

  14. Reduced vertebral bone density in hypercalciuric nephrolithiasis

    Science.gov (United States)

    Pietschmann, F.; Breslau, N. A.; Pak, C. Y.

    1992-01-01

    Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.

  15. Gaucher Disease: The Metabolic Defect, Pathophysiology, Phenotypes And Natural History

    OpenAIRE

    Baris, Hagit N; Cohen, Ian J.; Mistry, Pramod K

    2014-01-01

    Gaucher disease (GD), a prototype lysosomal storage disorder, results from inherited deficiency of lysosomal glucocerebrosidase due to biallelic mutations in GBA. The result is widespread accumulation of macrophages engorged with predominantly lysosomal glucocerebroside. A complex multisystem phenotype arises involving the liver, spleen, bone marrow and occasionally the lungs in type 1 Gaucher disease; in neuronopathic fulminant type 2 and chronic type 3 disease there is in addition progressi...

  16. Effects of obesity on bone metabolism

    Directory of Open Access Journals (Sweden)

    Cao Jay J

    2011-06-01

    Full Text Available Abstract Obesity is traditionally viewed to be beneficial to bone health because of well-established positive effect of mechanical loading conferred by body weight on bone formation, despite being a risk factor for many other chronic health disorders. Although body mass has a positive effect on bone formation, whether the mass derived from an obesity condition or excessive fat accumulation is beneficial to bone remains controversial. The underline pathophysiological relationship between obesity and bone is complex and continues to be an active research area. Recent data from epidemiological and animal studies strongly support that fat accumulation is detrimental to bone mass. To our knowledge, obesity possibly affects bone metabolism through several mechanisms. Because both adipocytes and osteoblasts are derived from a common multipotential mesenchymal stem cell, obesity may increase adipocyte differentiation and fat accumulation while decrease osteoblast differentiation and bone formation. Obesity is associated with chronic inflammation. The increased circulating and tissue proinflammatory cytokines in obesity may promote osteoclast activity and bone resorption through modifying the receptor activator of NF-κB (RANK/RANK ligand/osteoprotegerin pathway. Furthermore, the excessive secretion of leptin and/or decreased production of adiponectin by adipocytes in obesity may either directly affect bone formation or indirectly affect bone resorption through up-regulated proinflammatory cytokine production. Finally, high-fat intake may interfere with intestinal calcium absorption and therefore decrease calcium availability for bone formation. Unraveling the relationship between fat and bone metabolism at molecular level may help us to develop therapeutic agents to prevent or treat both obesity and osteoporosis. Obesity, defined as having a body mass index ≥ 30 kg/m2, is a condition in which excessive body fat accumulates to a degree that adversely

  17. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is currently defined as a common preventable and treatable disease that is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious...... particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association with...

  18. Macrophages: Their Emerging Roles in Bone.

    Science.gov (United States)

    Sinder, Benjamin P; Pettit, Allison R; McCauley, Laurie K

    2015-12-01

    Macrophages are present in nearly all tissues and are critical for development, homeostasis, and regeneration. Resident tissue macrophages of bone, termed osteal macrophages, are recently classified myeloid cells that are distinct from osteoclasts. Osteal macrophages are located immediately adjacent to osteoblasts, regulate bone formation, and play diverse roles in skeletal homeostasis. Genetic or pharmacological modulation of macrophages in vivo results in significant bone phenotypes, and these phenotypes depend on which macrophage subsets are altered. Macrophages are also key mediators of osseous wound healing and fracture repair, with distinct roles at various stages of the repair process. A central function of macrophages is their phagocytic ability. Each day, billions of cells die in the body and efferocytosis (phagocytosis of apoptotic cells) is a critical process in both clearing dead cells and recruitment of replacement progenitor cells to maintain homeostasis. Recent data suggest a role for efferocytosis in bone biology and these new mechanisms are outlined. Finally, although macrophages have an established role in primary tumors, emerging evidence suggests that macrophages in bone support cancers which preferentially metastasize to the skeleton. Collectively, this developing area of osteoimmunology raises new questions and promises to provide novel insights into pathophysiologic conditions as well as therapeutic and regenerative approaches vital for skeletal health. PMID:26531055

  19. Current status of physical activities among preschool children and relationship of activity type with bone mass%学龄前儿童体力活动状况调查及其与骨量的回归分析

    Institute of Scientific and Technical Information of China (English)

    张琚; 吴方银; 曾果; 张丽; 曾乔颖

    2013-01-01

    Objective To investigate physical activities of preschool children by gender and to explore the effects of activity type on bone indexes.Methods During 2009 and 2010,397 preschool children of 3-5 years old were randomly selected from 4 kindergartens in Chengdu Province of China.Ultrasound bone analyzer was used to assess children's bone mass.A physical activity questionnaire was completed by parents to evaluate physical activities at leisure time.Student's t test and least square regression were used for data analysis.Results Concerning activity types,boys spent more leisure time on running and Wushu than girls did (t values were 1.94 and 2.84,respectively ; both P < 0.05).However,girls spent more time on dancing (0.78 h),jumping rope (0.08 h) and manual labour (0.22 h) each day (t values were-9.50,-3.43 and-1.92,respectively; all P < 0.05).The weekly total exercise time and energy consumption per unit of body weight of girls vs.boys were 7.29 vs.6.51 h and 127.57 vs.113.85 kJ (t values were 2.63 and 2.04,respectively ; both P < 0.05).About per day time on sleeping and per week time on watching television,there were no significant difference between boys and girls (t =0.180,0.520;P >0.05).But boys spent more time on electronic game and computer than girls (t =0.760,2.510;P < 0.05).The normalized correlation coefficient for bone mass and moderate physical activities or jumping was 0.184 and 0.275,respectively (both P < 0.05).Conclusions Our data suggest that preschool children's bone volume may be positively correlated with moderate physical activities and jumping activities.Introducing some moderate physical activities or activity appliance,toys and playing fields as well as increasing professional training might be helpful.%目的 调查学龄前儿童体力活动状况及其性别差异,探索各种不同运动类型对骨骼健康指标的影响.方法 于2009至2010年期间在成都市不同城区采用典型抽样方法抽取4所

  20. Effect of Polycaprolactone Scaffold Permeability on Bone Regeneration In Vivo

    OpenAIRE

    Mitsak, Anna G.; Kemppainen, Jessica M.; Harris, Matthew T.; Hollister, Scott J

    2011-01-01

    Successful bone tissue engineering depends on the scaffold's ability to allow nutrient diffusion to and waste removal from the regeneration site, as well as provide an appropriate mechanical environment. Since bone is highly vascularized, scaffolds that provide greater mass transport may support increased bone regeneration. Permeability encompasses the salient features of three-dimensional porous scaffold architecture effects on scaffold mass transport. We hypothesized that higher permeabilit...

  1. Comprehensive characterisation of hypertensive heart disease left ventricular phenotypes

    OpenAIRE

    Rodrigues, Jonathan C. L.; Amadu, Antonio Matteo; Dastidar, Amardeep Ghosh; Szantho, Gergley V; Lyen, Stephen M.; Godsave, Cattleya; Ratcliffe, Laura E K; Burchell, Amy E; Hart, Emma C.; Hamilton, Mark C K; Nightingale, Angus K; Paton, Julian F. R.; Manghat, Nathan E; Bucciarelli-Ducci, Chiara

    2016-01-01

    OBJECTIVE: Myocardial intracellular/extracellular structure and aortic function were assessed among hypertensive left ventricular (LV) phenotypes using cardiovascular magnetic resonance (CMR).METHODS: An observational study from consecutive tertiary hypertension clinic patients referred for CMR (1.5 T) was performed. Four LV phenotypes were defined: (1) normal with normal indexed LV mass (LVM) and LVM to volume ratio (M/V), (2) concentric remodelling with normal LVM but elevated M/V, (3) conc...

  2. Bone marrow biopsy

    Science.gov (United States)

    Biopsy - bone marrow ... A bone marrow biopsy may be done in the health care provider's office or in a hospital. The sample may be taken from the pelvic or breast bone. Sometimes, other areas are used. Marrow is removed ...

  3. Bone marrow aspiration

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003658.htm Bone marrow aspiration To use the sharing features on this page, please enable JavaScript. Bone marrow is the soft tissue inside bones that helps ...

  4. Murine fertilized ovum, blastomere and morula cells lacking SP phenotype

    Institute of Scientific and Technical Information of China (English)

    XU; YiXin; HE; ZhiYing; ZHU; HaiYing; CHEN; XueSong; LI; JianXiu; ZHANG; HongXia; PAN; XingHua

    2007-01-01

    In the field of stem cell research, SP (side population) phenotype is used to define the property that cells maintain a high efflux capability for some fluorescent dye, such as Hoechst 33342. Recently, many researches proposed that SP phenotype is a phenotype shared by some stem cells and some progenitor cells, and that SP phenotype is regarded as a candidate purification marker for stem cells. In this research, murine fertilized ova (including conjugate and single nucleus fertilized ova), 2-cell stage and 8-cell stage blastomeres, morulas and blastocysts were isolated and directly stained by Hoechst 33342 dye. The results show that fertilized ovum, blastomere and morula cells do not demonstrate any ability to efflux the dye. However, the inner cell mass (ICM) cells of blastocyst exhibit SP phenotype, which is consistent with the result of embryonic stem cells (ESCs) in vitro. These results indicate that the SP phenotype of ICM-derived ESCs is an intrinsic property and independent of the culture condition in vitro, and that SP phenotype is one of the characteristics of at least some pluripotent stem cells, but is not shared by totipotent stem cells. In addition, the result that the SP phenotype of ICM cells disappeared when the inhibitor verapamil was added into medium implies that the SP phenotype is directly associated with ABCG2. These results suggest that not all the stem cells demonstrate SP phenotype, and that SP phenotype might act as a purification marker for partial stem cells such as some pluripotent embryonic stem cells and multipotent adult stem cells, but not for all stem cells exampled by the totipotent stem cells in the very early stage of mouse embryos.

  5. Bone strength: more than just bone density.

    Science.gov (United States)

    Ott, Susan M

    2016-01-01

    The following bone density measurements have limited utility in determining bone strength because they do not include bone quality: microarchitecture, mineralization, ability to repair damage, collagen structure, crystal size, or marrow composition. Patients with kidney disease have poor bone quality. Newman et al. now describe beneficial effects with raloxifene in an animal model of progressive kidney disease. These biomechanical measurements will be important in the development of medications to decrease fractures in patients. PMID:26759040

  6. Osteoblasts in Bone Physiology—Mini Review

    Directory of Open Access Journals (Sweden)

    Orit Rosenberg

    2012-04-01

    Full Text Available Bone structural integrity and shape are maintained by removal of old matrix by osteoclasts and in-situ synthesis of new bone by osteoblasts. These cells comprise the basic multicellular unit (BMU. Bone mass maintenance is determined by the net anabolic activity of the BMU, when the matrix elaboration of the osteoblasts equals or exceeds the bone resorption by the osteoclasts. The normal function of the BMU causes a continuous remodeling process of the bone, with deposition of bony matrix (osteoid along the vectors of the generated force by gravity and attached muscle activity. The osteoblasts are derived from mesenchymal stem cells (MSCs. Circulating hormones and locally produced cytokines and growth factors modulate the replication and differentiation of osteoclast and osteoblast progenitors. The appropriate number of the osteoblasts in the BMU is determined by the differentiation of the precursor bone-marrow stem cells into mature osteoblasts, their proliferation with subsequent maturation into metabolically active osteocytes, and osteoblast degradation by apoptosis. Thus, the two crucial points to target when planning to control the osteoblast population are the processes of cell proliferation and apoptosis, which are regulated by cellular hedgehog and Wnt pathways that involve humoral and mechanical stimulations. Osteoblasts regulate both bone matrix synthesis and mineralization directly by their own synthetic activities, and bone resorption indirectly by its paracrinic effects on osteoclasts. The overall synthetic and regulatory activities of osteoblasts govern bone tissue integrity and shape.

  7. Bone growth and turnover in progesterone receptor knockout mice.

    Energy Technology Data Exchange (ETDEWEB)

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jaime C.; Waters, Katrina M.; Lydon, John P.; O' Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-05-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

  8. Bone development

    DEFF Research Database (Denmark)

    Tatara, M.R.; Tygesen, Malin Plumhoff; Sawa-Wojtanowicz, B.;

    2007-01-01

    The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram...... at 146 days of life and five left and right ribs (fourth to eighth) were removed for analysis. The influence of AKG on skeletal system development was evaluated in relation to both geometrical and mechanical properties, as well as quantitative computed tomography (QCT). No significant differences between...... has a long-term effect on skeletal development when given early in neonatal life, and that changes in rib properties serve to improve chest mechanics and functioning in young animals. Moreover, neonatal administration of AKG may be considered as an effective factor enhancing proper development...

  9. Characterization of murine macrophages from bone marrow, spleen and peritoneum

    OpenAIRE

    Wang Changqi; Yu Xiao; Cao Qi; Wang Ya; Zheng Guoping; Tan Thian Kui; Zhao Hong; Zhao Ye; Wang Yiping; Harris David CH

    2013-01-01

    Abstract Background Macrophages have heterogeneous phenotypes and complex functions within both innate and adaptive immune responses. To date, most experimental studies have been performed on macrophages derived from bone marrow, spleen and peritoneum. However, differences among macrophages from these particular sources remain unclear. In this study, the features of murine macrophages from bone marrow, spleen and peritoneum were compared. Results We found that peritoneal macrophages (PMs) app...

  10. Leptin regulates bone formation via the sympathetic nervous system

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

    2002-01-01

    We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

  11. Exercise, lifestyle, and your bones

    Science.gov (United States)

    Osteoporosis - exercise; Low bone density - exercise ... Osteoporosis is a disease that causes bones to become brittle and more likely to fracture (break). With osteoporosis, the bones lose density. Bone density is the amount of bone ...

  12. Hyperhomocysteinemia decreases bone blood flow

    Directory of Open Access Journals (Sweden)

    Neetu Tyagi

    2011-01-01

    Full Text Available Neetu Tyagi*, Thomas P Vacek*, John T Fleming, Jonathan C Vacek, Suresh C TyagiDepartment of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA *These authors have equal authorshipAbstract: Elevated plasma levels of homocysteine (Hcy, known as hyperhomocysteinemia (HHcy, are associated with osteoporosis. A decrease in bone blood flow is a potential cause of compromised bone mechanical properties. Therefore, we hypothesized that HHcy decreases bone blood flow and biomechanical properties. To test this hypothesis, male Sprague–Dawley rats were treated with Hcy (0.67 g/L in drinking water for 8 weeks. Age-matched rats served as controls. At the end of the treatment period, the rats were anesthetized. Blood samples were collected from experimental or control rats. Biochemical turnover markers (body weight, Hcy, vitamin B12, and folate were measured. Systolic blood pressure was measured from the right carotid artery. Tibia blood flow was measured by laser Doppler flow probe. The results indicated that Hcy levels were significantly higher in the Hcy-treated group than in control rats, whereas vitamin B12 levels were lower in the Hcy-treated group compared with control rats. There was no significant difference in folate concentration and blood pressure in Hcy-treated versus control rats. The tibial blood flow index of the control group was significantly higher (0.78 ± 0.09 flow unit compared with the Hcy-treated group (0.51 ± 0.09. The tibial mass was 1.1 ± 0.1 g in the control group and 0.9 ± 0.1 in the Hcy-treated group. The tibia bone density was unchanged in Hcy-treated rats. These results suggest that Hcy causes a reduction in bone blood flow, which contributes to compromised bone biomechanical properties.Keywords: homocysteine, tibia, bone density

  13. IL-6 Contributes to the Defective Osteogenesis of Bone Marrow Stromal Cells from the Vertebral Body of the Glucocorticoid-Induced Osteoporotic Mouse

    Science.gov (United States)

    Zhang, Yuan-yuan; Yang, Hui-lin

    2016-01-01

    Osteoporosis is one of the most prevalent skeletal system diseases. It is characterized by a decrease in bone mass and microarchitectural changes in bone tissue that lead to an attenuation of bone resistance and susceptibility to fracture. Vertebral fracture is by far the most prevalent osteoporotic fracture. In the musculoskeletal system, osteoblasts, originated from bone marrow stromal cells (BMSC), are responsible for osteoid synthesis and mineralization. In osteoporosis, BMSC osteogenic differentiation is defective. However, to date, what leads to the defective BMSC osteogenesis in osteoporosis remains an open question. In the current study, we made attempts to answer this question. A mouse model of glucocorticoid-induced osteoporosis (GIO) was established and BMSC were isolated from vertebral body. The impairment of osteogenesis was observed in BMSC of osteoporotic vertebral body. The expression profiles of thirty-six factors, which play important roles in bone metabolisms, were compared through antibody array between normal and osteoporotic BMSC. Significantly higher secretion level of IL-6 was observed in osteoporotic BMSCs compared with normal control. We provided evidences that IL-6 over-secretion impaired osteogenesis of osteoporotic BMSC. Further, it was observed that β-catenin activity was inhibited in response to IL-6 over-secretion. More importantly, in vivo administration of IL-6 neutralizing antibody was found to be helpful to rescue the osteoporotic phenotype of mouse vertebral body. Our study provides a deeper insight into the pathophysiology of osteoporosis and identifies IL-6 as a promising target for osteoporosis therapy. PMID:27128729

  14. 色谱纯化和质谱分析法研究牛骨源咸味肽%Separation, Purification and Analysis of Salty Peptides Derived from Bovine Bone by Chromatography and Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    李迎楠; 刘文营; 张顺亮; 成晓瑜

    2016-01-01

    以牛骨为研究对象,通过中空纤维超滤装置、Sephadex G-25凝胶色谱柱对相对分子质量小于5000的酶解产物进行初步分离,选用制备型及分析型高效液相色谱分析仪对咸味肽进行纯化、收集及分析。结果表明:收集得到牛骨源咸味肽为单一组分;用基质辅助激光解析电离-飞行时间质谱仪对咸味肽进行分析,得到其为相对分子质量均小于1000的短肽,其呈现咸味的物质质荷比值可能为679.5109。%The enzymatic hydrolysate of bovine bone with relative molecular weight < 5 000 was separated by hollow fiber ultrafiltration and Sephadex G-25 column chromatography. Two salty peptide fractions from the hydrolysate were purified by preparative high performance liquid chromatography (HPLC) and the pooled samples were analyzed by HPLC. The two fractions were found to consist of a single homogenous component. As analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS), both peptide fractions had a relative molecular weight less than 1000, the salty taste compound of which was m/z 679.510 9.

  15. Pseudomonas Aeruginosa Resistance Phenotypes and Phenotypic Highlighting Methods

    Science.gov (United States)

    BĂLĂŞOIU, MARIA; BĂLĂŞOIU, A.T.; MĂNESCU, RODICA; AVRAMESCU, CARMEN; IONETE, OANA

    2014-01-01

    Pseudomonas aeruginosa genus bacteria are well known for their increased drug resistance (phenotypic ang genotypic resistance). The most important resistance mechanisms are: enzyme production, reduction of pore expression, reduction of the external membrane proteins expression, efflux systems, topoisomerase mutations. These mechanisms often accumulate and lead to multidrug ressitance strains emergence. The most frequent acquired resistance mechanisms are betalactamase-type enzyme production (ESBLs, AmpC, carbapenemases), which determine variable phenotypes of betalactamines resistance, phenotypes which are associated with aminoglycosides and quinolones resistance. The nonenzymatic drug resistance mechanisms are caused by efflux systems, pore reduction and penicillin-binding proteins (PBP) modification, which are often associated to other resistance mechanisms. Phenotypic methods used for testing these mechanisms are based on highlighting these phenotypes using Kirby Bauer antibiogram, clinical breakpoints, and “cut off” values recommended by EUCAST 2013 standard, version 3.1. PMID:25729587

  16. P25 - Growing Strong and Healthy with Mister Bone: An Educational Programme to Ensure Strong Bones Later in Life

    OpenAIRE

    Pampaloni, B.; Bartolini, E.; Fabbri, S.; Tanini, A.; Brandi, M.L.

    2010-01-01

    Bone mass increases steadily until the age of 20–30 years and most bone mass is acquired during the first two decades of life. Nutrition plays a critical role in the achievement of one’s optimal genetically programmed peak bone mass (PBM), reducing the risk of osteoporosis later in life. PBM is the amount of bony tissue present in the skeleton at the end of skeletal maturation. Even though 90% of PBM is acquired by the end of second decade of life, skeletal mass continues to increase for up t...

  17. Age changes in human bone: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, W.D.

    1977-12-03

    The human skeleton steadily changes structure and mass during life because of a variety of internal and external factors. Extracellular substance and bone cells get old, characteristic structural remodeling occurs with age and these age-related changes are important in the discrimination between pathological and physiological changes. Perhaps 20 percent of the bone mass is lost between the fourth and the ninth decades, osteoblasts function less efficiently and gradual loss of bone substance is enhanced by delayed mineralization of an increased surface area of thin and relatively less active osteoid seams. After the fifth decade, osteoclasia and the number of Howship's lacunae increase, and with age, the number of large osteolytic osteocytes increases as the number of small osteocytes declines and empty osteocyte lacunae become more common. The result is greater liability to fracture and diminished healing or replacement of injured bone.

  18. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  19. The Relationship Between Lower Limb Bone and Muscle in Military Recruits, Response to Physical Training, and Influence of Smoking Status

    OpenAIRE

    Puthucheary, Z; Kordi, M.; Rawal, J.; Eleftheriou, K I; Payne, J.; Montgomery, H. E.

    2015-01-01

    The relationship between bone and skeletal muscle mass may be affected by physical training. No studies have prospectively examined the bone and skeletal muscle responses to a short controlled exercise-training programme. We hypothesised that a short exercise-training period would affect muscle and bone mass together. Methods: Femoral bone and Rectus femoris Volumes (RFVOL) were determined by magnetic resonance imaging in 215 healthy army recruits, and bone mineral density (BMD) by Dual X-Ray...

  20. LEPTIN REGULATION OF BONE RESORPTION BY THE SYMPATHETIC NERVOUS SYSTEM AND CART

    Science.gov (United States)

    Bone remodelling, the mechanism by which vertebrates regulate bone mass, comprises two phases, namely resorption by osteoclasts and formation by osteoblasts; osteoblasts are multifunctional cells also controlling osteoclast differentiation. Sympathetic signalling via beta2-adrenergic receptors (Adrb...