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Sample records for regulating bone mass

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

    International Nuclear Information System (INIS)

    Recker, Robert R. M.D.

    2002-01-01

    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. Bone mass regulation of leptin and postmenopausal osteoporosis with obesity.

    Science.gov (United States)

    Legiran, Siswo; Brandi, Maria Luisa

    2012-09-01

    Leptin has been known to play a role in weight regulation through food intake and energy expenditure. Leptin also has an important role in bone metabolism. The role of leptin is determined by leptin receptors, either central or peripheral to the bones. We discuss the role of leptin on bone and molecular genetics of osteoporosis in postmenopausal obese women. The role of leptin in bone preserves bone mineral density (BMD) through increased OPG levels leading to bind RANKL, resulting in reducing osteoclast activity. The estrogen role on bone is also mediated by RANKL and OPG. In postmenopausal women who have estrogen deficiency, it increases the rate of RANKL, which increases osteoclastogenesis. Obese individuals who have a high level of leptin will be effected by bone protection. There are similarities in the mechanism between estrogen and leptin in influencing the process of bone remodeling. It may be considered that the role of estrogen can be replaced by leptin. Molecular genetic aspects that play a role in bone remodeling, such as leptin, leptin receptors, cytokines (e.g. RANK, RANKL, and OPG), require further study to be useful, especially regarding osteoporosis therapy based on genetic analysis.

  3. Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway.

    Science.gov (United States)

    Sharan, Kunal; Lewis, Kirsty; Furukawa, Takahisa; Yadav, Vijay K

    2017-09-01

    Tryptophan, an essential amino acid through a series of enzymatic reactions gives rise to various metabolites, viz. serotonin and melatonin, that regulate distinct biological functions. We show here that tryptophan metabolism in the pineal gland favors bone mass accrual through production of melatonin, a pineal-derived neurohormone. Pineal gland-specific deletion of Tph1, the enzyme that catalyzes the first step in the melatonin biosynthesis lead to a decrease in melatonin levels and a low bone mass due to an isolated decrease in bone formation while bone resorption parameters remained unaffected. Skeletal analysis of the mice deficient in MT1 or MT2 melatonin receptors showed a low bone mass in MT2-/- mice while MT1-/- mice had a normal bone mass compared to the WT mice. This low bone mass in the MT2-/- mice was due to an isolated decrease in osteoblast numbers and bone formation. In vitro assays of the osteoblast cultures derived from the MT1-/- and MT2-/- mice showed a cell intrinsic defect in the proliferation, differentiation and mineralization abilities of MT2-/- osteoblasts compared to WT counterparts, and the mutant cells did not respond to melatonin addition. Finally, we demonstrate that daily oral administration of melatonin can increase bone accrual during growth and can cure ovariectomy-induced structural and functional degeneration of bone by specifically increasing bone formation. By identifying pineal-derived melatonin as a regulator of bone mass through MT2 receptors, this study expands the role played by tryptophan derivatives in the regulation of bone mass and underscores its therapeutic relevance in postmenopausal osteoporosis. © 2017 The Authors. Journal of Pineal Research Published by John Wiley & Sons Ltd.

  4. 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

    . In a number of in vitro culture systems, Dlk1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of proinflammatory bone-resorbing cytokines (eg, Il7, Tnfa, and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of Dlk1...... in 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....

  5. 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.

  6. 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.

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

    Science.gov (United States)

    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; Yadav, Vijay K.

    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 physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

  8. SHP1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Menghui Jiang

    2016-07-01

    Full Text Available Osteoblasts and adipocytes are derived from a common precursor, mesenchymal stem cells (MSCs. Alterations in the normal fate of differentiating MSCs are involved in the development of obesity and osteoporosis. Here, we report that viable motheaten (mev mice, which are deficient in the SH2-domain-containing phosphatase-1 (SHP1, develop osteoporosis spontaneously. Consistently, MSCs from mev/mev mice exhibit significantly reduced osteogenic potential and greatly increased adipogenic potential. When MSCs were transplanted into nude mice, SHP1-deficient MSCs resulted in diminished bone formation compared with wild-type MSCs. SHP1 was found to bind to GSK3β and suppress its kinase activity by dephosphorylating pY216, thus resulting in β-catenin stabilization. Mice, in which SHP1 was deleted in MSCs using SHP1fl/flDermo1-cre, displayed significantly decreased bone mass and increased adipose tissue. Taken together, these results suggest a possible role for SHP1 in controlling tissue homeostasis through modulation of MSC differentiation via Wnt signaling regulation.

  9. Establishment of peak bone mass.

    Science.gov (United States)

    Mora, Stefano; Gilsanz, Vicente

    2003-03-01

    Among the main areas of progress in osteoporosis research during the last decade or so are the general recognition that this condition, which is the cause of so much pain in the elderly population, has its antecedents in childhood and the identification of the structural basis accounting for much of the differences in bone strength among humans. Nevertheless, current understanding of the bone mineral accrual process is far from complete. The search for genes that regulate bone mass acquisition is ongoing, and current results are not sufficient to identify subjects at risk. However, there is solid evidence that BMD measurements can be helpful for the selection of subjects that presumably would benefit from preventive interventions. The questions regarding the type of preventive interventions, their magnitude, and duration remain unanswered. Carefully designed controlled trials are needed. Nevertheless, previous experience indicates that weight-bearing activity and possibly calcium supplements are beneficial if they are begun during childhood and preferably before the onset of puberty. Modification of unhealthy lifestyles and increments in exercise or calcium assumption are logical interventions that should be implemented to improve bone mass gains in all children and adolescents who are at risk of failing to achieve an optimal peak bone mass.

  10. 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...

  11. 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...... 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. Because FA1 is colocalized with GH in the pituitary gland, we explored the possible modulation of serum FA1...

  12. Prader-Willi Critical Region, a Non-Translated, Imprinted Central Regulator of Bone Mass: Possible Role in Skeletal Abnormalities in Prader-Willi Syndrome.

    Directory of Open Access Journals (Sweden)

    Ee-Cheng Khor

    Full Text Available Prader-Willi Syndrome (PWS, a maternally imprinted disorder and leading cause of obesity, is characterised by insatiable appetite, poor muscle development, cognitive impairment, endocrine disturbance, short stature and osteoporosis. A number of causative loci have been located within the imprinted Prader-Willi Critical Region (PWCR, including a set of small non-translated nucleolar RNA's (snoRNA. Recently, micro-deletions in humans identified the snoRNA Snord116 as a critical contributor to the development of PWS exhibiting many of the classical symptoms of PWS. Here we show that loss of the PWCR which includes Snord116 in mice leads to a reduced bone mass phenotype, similar to that observed in humans. Consistent with reduced stature in PWS, PWCR KO mice showed delayed skeletal development, with shorter femurs and vertebrae, reduced bone size and mass in both sexes. The reduction in bone mass in PWCR KO mice was associated with deficiencies in cortical bone volume and cortical mineral apposition rate, with no change in cancellous bone. Importantly, while the length difference was corrected in aged mice, consistent with continued growth in rodents, reduced cortical bone formation was still evident, indicating continued osteoblastic suppression by loss of PWCR expression in skeletally mature mice. Interestingly, deletion of this region included deletion of the exclusively brain expressed Snord116 cluster and resulted in an upregulation in expression of both NPY and POMC mRNA in the arcuate nucleus. Importantly, the selective deletion of the PWCR only in NPY expressing neurons replicated the bone phenotype of PWCR KO mice. Taken together, PWCR deletion in mice, and specifically in NPY neurons, recapitulates the short stature and low BMD and aspects of the hormonal imbalance of PWS individuals. Moreover, it demonstrates for the first time, that a region encoding non-translated RNAs, expressed solely within the brain, can regulate bone mass in health

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

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    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.

  14. Phenotypic Dissection of Bone Mineral Density Reveals Skeletal Site Specificity and Facilitates the Identification of Novel Loci in the Genetic Regulation of Bone Mass Attainment

    NARCIS (Netherlands)

    J.P. Kemp (John); M.C. Medina-Gomez (Carolina); K. Estrada Gil (Karol); B. St Pourcain (Beate); D.H.M. Heppe (Denise); N.M. Warrington (Nicole); L. Oei (Ling); S.M. Ring (Susan); C.J. Kruithof (Claudia); N.J. Timpson (Nicholas); L.E. Wolber (Lisa); S. Reppe (Sjur); K.M. Gautvik (Kaare); E. Grundberg (Elin); B. Ge (Bing); B.C.J. van der Eerden (Bram); J. van de Peppel (Jeroen); M.A. Hibbs (Matthew); C.L. Ackert-Bicknell (Cheryl); K. Choi (Kunho); D.L. Koller (Daniel); M.J. Econs (Michael); F.M. Williams (Frances); T. Foroud (Tatiana); M.C. Zillikens (Carola); C. Ohlsson (Claes); A. Hofman (Albert); A.G. Uitterlinden (André); G. Davey-Smith (George); V.W.V. Jaddoe (Vincent); J.H. Tobias (Jon); F. Rivadeneira Ramirez (Fernando); D.M. Evans (David)

    2014-01-01

    textabstractHeritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we

  15. 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 lum.......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....

  16. 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.

  17. Osteoporosis: Peak Bone Mass in Women

    Science.gov (United States)

    ... bone density are seen even during childhood and adolescence. Hormonal factors. The hormone estrogen has an effect on peak bone mass. For example, women who had their first menstrual cycle at an early age and those who use oral contraceptives, which contain estrogen, often have high bone mineral ...

  18. Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation.

    Science.gov (United States)

    McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

    2015-07-01

    Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. © 2015. Published by The Company of Biologists Ltd.

  19. Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.

    Directory of Open Access Journals (Sweden)

    John P Kemp

    2014-06-01

    Full Text Available Heritability of bone mineral density (BMD varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg and residual (re correlations between BMD measured at the upper limbs (UL-BMD, lower limbs (LL-BMD and skull (SK-BMD, using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC. Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78 between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43. Likewise, the residual correlation between BMD at appendicular sites (r(e = 0.55 was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e = 0.20-0.24. To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395, combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites. In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37, whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14. In addition, we report a novel association between RIN3 (previously associated with Paget's disease and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10. Our results suggest that BMD at different skeletal sites is under a mixture of shared and

  20. Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.

    Science.gov (United States)

    Kemp, John P; Medina-Gomez, Carolina; Estrada, Karol; St Pourcain, Beate; Heppe, Denise H M; Warrington, Nicole M; Oei, Ling; Ring, Susan M; Kruithof, Claudia J; Timpson, Nicholas J; Wolber, Lisa E; Reppe, Sjur; Gautvik, Kaare; Grundberg, Elin; Ge, Bing; van der Eerden, Bram; van de Peppel, Jeroen; Hibbs, Matthew A; Ackert-Bicknell, Cheryl L; Choi, Kwangbom; Koller, Daniel L; Econs, Michael J; Williams, Frances M K; Foroud, Tatiana; Zillikens, M Carola; Ohlsson, Claes; Hofman, Albert; Uitterlinden, André G; Davey Smith, George; Jaddoe, Vincent W V; Tobias, Jonathan H; Rivadeneira, Fernando; Evans, David M

    2014-06-01

    Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and

  1. 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....

  2. Regulation of bone remodeling by vitamin K2.

    Science.gov (United States)

    Myneni, V D; Mezey, E

    2017-11-01

    All living tissues require essential nutrients such as amino acids, fatty acids, carbohydrates, minerals, vitamins, and water. The skeleton requires nutrients for development, maintaining bone mass and density. If the skeletal nutritional requirements are not met, the consequences can be quite severe. In recent years, there has been growing interest in promotion of bone health and inhibition of vascular calcification by vitamin K2. This vitamin regulates bone remodeling, an important process necessary to maintain adult bone. Bone remodeling involves removal of old or damaged bone by osteoclasts and its replacement by new bone formed by osteoblasts. The remodeling process is tightly regulated, when the balance between bone resorption and bone formation shifts to a net bone loss results in the development of osteoporosis in both men and women. In this review, we focus on our current understanding of the effects of vitamin K2 on bone cells and its role in prevention and treatment of osteoporosis. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  3. Exercise and bone mass in adults.

    Science.gov (United States)

    Guadalupe-Grau, Amelia; Fuentes, Teresa; Guerra, Borja; Calbet, Jose A L

    2009-01-01

    There is a substantial body of evidence indicating that exercise prior to the pubertal growth spurt stimulates bone growth and skeletal muscle hypertrophy to a greater degree than observed during growth in non-physically active children. Bone mass can be increased by some exercise programmes in adults and the elderly, and attenuate the losses in bone mass associated with aging. This review provides an overview of cross-sectional and longitudinal studies performed to date involving training and bone measurements. Cross-sectional studies show in general that exercise modalities requiring high forces and/or generating high impacts have the greatest osteogenic potential. Several training methods have been used to improve bone mineral density (BMD) and content in prospective studies. Not all exercise modalities have shown positive effects on bone mass. For example, unloaded exercise such as swimming has no impact on bone mass, while walking or running has limited positive effects. It is not clear which training method is superior for bone stimulation in adults, although scientific evidence points to a combination of high-impact (i.e. jumping) and weight-lifting exercises. Exercise involving high impacts, even a relatively small amount, appears to be the most efficient for enhancing bone mass, except in postmenopausal women. Several types of resistance exercise have been tested also with positive results, especially when the intensity of the exercise is high and the speed of movement elevated. A handful of other studies have reported little or no effect on bone density. However, these results may be partially attributable to the study design, intensity and duration of the exercise protocol, and the bone density measurement techniques used. Studies performed in older adults show only mild increases, maintenance or just attenuation of BMD losses in postmenopausal women, but net changes in BMD relative to control subjects who are losing bone mass are beneficial in

  4. Do vegetarians have a normal bone mass?

    Science.gov (United States)

    New, Susan A

    2004-09-01

    Public health strategies targeting the prevention of poor bone health on a population-wide basis are urgently required, with particular emphasis being placed on modifiable factors such as nutrition. The aim of this review was to assess the impact of a vegetarian diet on indices of skeletal integrity to address specifically whether vegetarians have a normal bone mass. Analysis of existing literature, through a combination of observational, clinical and intervention studies were assessed in relation to bone health for the following: lacto-ovo-vegetarian and vegan diets versus omnivorous, predominantly meat diets, consumption of animal versus vegetable protein, and fruit and vegetable consumption. Mechanisms of action for a dietary "component" effect were examined and other potential dietary differences between vegetarians and non-vegetarians were also explored. Key findings included: (i) no differences in bone health indices between lacto-ovo-vegetarians and omnivores; (ii) conflicting data for protein effects on bone with high protein consumption (particularly without supporting calcium/alkali intakes) and low protein intake (particularly with respect to vegan diets) being detrimental to the skeleton; (iii) growing support for a beneficial effect of fruit and vegetable intake on bone, with mechanisms of action currently remaining unclarified. The impact of a "vegetarian" diet on bone health is a hugely complex area since: 1) components of the diet (such as calcium, protein, alkali, vitamin K, phytoestrogens) may be varied; 2) key lifestyle factors which are important to bone (such as physical activity) may be different; 3) the tools available for assessing consumption of food are relatively weak. However, from data available and given the limitations stipulated above, "vegetarians" do certainly appear to have "normal" bone mass. What remains our challenge is to determine what components of a vegetarian diet are of particular benefit to bone, at what levels and under

  5. Gravity and body mass regulation

    Science.gov (United States)

    Warren, L. E.; Horwitz, B. A.; Fuller, C. A.

    1997-01-01

    The effects of altered gravity on body mass, food intake, energy expenditure, and body composition are examined. Metabolic adjustments are reviewed in maintenance of energy balance, neural regulation, and humoral regulation are discussed. Experiments with rats indicate that genetically obese rats respond differently to hypergravity than lean rats.

  6. Corticosteroid therapy and bone mass - comparisOfl of rheumatoid ...

    African Journals Online (AJOL)

    osis Int sis and et of ine in l energy. Tissue. Invasive. -72. cl Med f the ed. The ce ... needs to be re-evaluated, favouring earlier use of such ... There are also very few reports of bone ... compare bone mass at various sites in young, ambulant .... Bone mass ill patients with RA and SLE in relation to ..... on bone in young adults.

  7. Wise regulates bone deposition through genetic interactions with Lrp5.

    Science.gov (United States)

    Ellies, Debra L; Economou, Androulla; Viviano, Beth; Rey, Jean-Philippe; Paine-Saunders, Stephenie; Krumlauf, Robb; Saunders, Scott

    2014-01-01

    In this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise-/- mutant mice we find an increase in the rate of osteoblast proliferation and a transient increase in bone mineral density. This change in proliferation is dependent upon Lrp5, as Wise;Lrp5 double mutants have normal bone mass. This suggests that Wise serves as a negative modulator of Wnt signaling in active osteoblasts. Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent with the temporal onset of their respective increased bone density phenotypes. These data suggest that Wise and Sost may have common roles in regulating bone development through their ability to control the balance of Wnt signaling. We find that Wise is also required to potentiate proliferation in chondrocytes, serving as a potential positive modulator of Wnt activity. Our analyses demonstrate that Wise plays a key role in processes that control the number of osteoblasts and chondrocytes during bone homeostasis and provide important insight into mechanisms regulating the Wnt pathway during skeletal development.

  8. Determinants of bone mass and bone geometry in adolescent and young adult women

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Hoorneman, G.; Väänänen, K.; Charles, P.; Ando, S.; Maggiolini, M.; Charzewska, J.; Rotily, M.; Deloraine, A.; Heikkinen, J.; Juvin, R.; Schaafsma, G.

    2000-01-01

    Bone mass and bone geometry are considered to have independent effects on bone strength. The purpose of this study was to obtain data on bone mass and geometry in young female populations and how they are influenced by body size and lifestyle factors. In a cross-sectional, observational study in six

  9. Peak bone mineral density, lean body mass and fractures

    NARCIS (Netherlands)

    Boot, Annemieke M.; de Ridder, Maria A. J.; van der Sluis, Inge M.; van Slobbe, Ingrid; Krenning, Eric P.; Keizer-Schrama, Sabine M. P. F. de Muinck

    Background: During childhood and adolescence, bone mass and lean body mass (LBM) increase till a plateau is reached. In this longitudinal and cross-sectional study, the age of reaching the plateau was evaluated for lumbar spine and total body bone mass measurements and lean body mass. The

  10. Cell fusion in osteoclasts plays a critical role in controlling bone mass and osteoblastic activity

    International Nuclear Information System (INIS)

    Iwasaki, Ryotaro; Ninomiya, Ken; Miyamoto, Kana; Suzuki, Toru; Sato, Yuiko

    2008-01-01

    The balance between osteoclast and osteoblast activity is central for maintaining the integrity of bone homeostasis. Here we show that mice lacking dendritic cell specific transmembrane protein (DC-STAMP), an essential molecule for osteoclast cell-cell fusion, exhibited impaired bone resorption and upregulation of bone formation by osteoblasts, which do not express DC-STAMP, which led to increased bone mass. On the contrary, DC-STAMP over-expressing transgenic (DC-STAMP-Tg) mice under the control of an actin promoter showed significantly accelerated cell-cell fusion of osteoclasts and bone resorption, with decreased osteoblastic activity and bone mass. Bone resorption and formation are known to be regulated in a coupled manner, whereas DC-STAMP regulates bone homeostasis in an un-coupled manner. Thus our results indicate that inhibition of a single molecule provides both decreased osteoclast activity and increased bone formation by osteoblasts, thereby increasing bone mass in an un-coupled and a tissue specific manner.

  11. Anorexia nervosa: slow regain of bone mass.

    Science.gov (United States)

    Valla, A; Groenning, I L; Syversen, U; Hoeiseth, A

    2000-01-01

    In a retrospective study of women aged 18-30 years, aimed at assessing factors associated with peak bone mass (PBM), 13 of 239 study cases reported having had anorexia nervosa. The mean total femoral and lumbar bone mineral density (BMD) values were not significantly lower in women who had had anorexia than in the pooled group (mean Z-scores of -0.60 and -0.48). Cases with less than 6 years since the anorexia had on average a present weight 5.7 kg less than their premorbid weights, while cases with more than 6 years since the eating disorder had an average weight 22.5 kg above their pre-morbid weights. The cases who had not regained their weight had BMD values significantly lower than the pooled material (mean Z-scores -1.15 and -0.9 in the lumbar spine and total femur respectively). Those who had regained their weight had BMD values as predicted from their present anthropometric data, while those who had not regained their weight had BMD values that were substantially below that predicted from their present weight. Anorexia nervosa seems to be associated with a low BMD which is even lower than that which can be predicted from the weight loss alone. This suggests that weight loss and other factors, such as menstrual dysfunction and estrogen deficiency, are independent and thus additive causes of bone loss in anorexia nervosa. Recovery of BMD seems slow, but the BMD may become as predicted from the anthropometric data after restoration of body weight and menses. The potential for recovery of BMD seems intact for several years after menarche.

  12. Lumbar bone mass predicts low back pain in males

    NARCIS (Netherlands)

    Hoozemans, M.J.M.; Koppes, L.L.J.; Twisk, J.W.R.; Dieën, J.H. van

    2012-01-01

    STUDY DESIGN.: Longitudinal study of lumbar bone mass as predictor of low back pain (LBP). OBJECTIVE.: To investigate whether low bone mineral content (BMC) and bone mineral density (BMD) values at the age of 36 years are associated with the prevalence of LBP at the age of 42 years among the study

  13. Chronic Alcohol Abuse Leads to Low Bone Mass with No General Loss of Bone Structure or Bone Mechanical Strength

    DEFF Research Database (Denmark)

    Ulhøi, Maiken Parm; Meldgaard, Karoline; Steiniche, Torben

    2017-01-01

    Chronic alcohol abuse (CAA) has deleterious effects on skeletal health. This study examined the impact of CAA on bone with regard to bone density, structure, and strength. Bone specimens from 42 individuals with CAA and 42 individuals without alcohol abuse were obtained at autopsy. Dual-energy X......-ray absorptiometry (DEXA), compression testing, ashing, and bone histomorphometry were performed. Individuals with CAA had significantly lower bone mineral density (BMD) in the femoral neck and significantly lower bone volume demonstrated by thinner trabeculae, decreased extent of osteoid surfaces, and lower mean...... wall thickness of trabecular osteons compared to individuals without alcohol abuse. No significant difference was found for bone strength and structure. Conclusion: CAA leads to low bone mass due to a decrease in bone formation but with no destruction of bone architecture nor a decrease in bone...

  14. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    Science.gov (United States)

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  15. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Abbas Jafari

    2017-02-01

    Full Text Available Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

  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. Osteocyte regulation of bone and blood.

    Science.gov (United States)

    Divieti Pajevic, Paola; Krause, Daniela S

    2018-02-16

    This past decade has witnessed a renewed interest in the function and biology of matrix-embedded osteocytes and these cells have emerged as master regulators of bone homeostasis. They secrete two very powerful proteins, sclerostin, a Wnt-inhibitor, that suppresses bone formation, and receptor-activator of NF-kB ligand (RANKL), a cytokine required for osteoclastogenesis. Neutralizing antibodies against these proteins are currently used for the treatment of osteoporosis. Recent studies however, ascribed yet another function to osteocytes: the control of hematopoiesis and the HSPC niche, directly and through secreted factors. In the absence of osteocytes there is an increase in HSC mobilization and abnormal lymphopoiesis whereas in the absence of G s α signaling in these cells there is an increase of myeloid cells. How exactly osteocytes control hematopoiesis or the HSPC niche is still not completely understood. In this review we summarize the actions of osteocytes in bone and then analyze the effects of these cells on hematopoiesis. Future directions and gaps in current knowledge are further discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Regulation of bone blood flow in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Boushel, Robert; Hellsten, Ylva

    2018-01-01

    of cyclooxygenase (COX) enzyme, thus prostaglandin (PG) synthesis on femoral bone marrow blood flow by positron emission tomography in healthy young men at rest and during one leg dynamic exercise. In an additional group of healthy men, the role of adenosine (ADO) in the regulation of BBF during exercise......The mechanisms that regulate bone blood flow (BBF) in humans are largely unknown. Animal studies suggest that nitric oxide (NO) could be involved and in the present study we investigated the effects of inhibition of nitric oxide synthase (NOS) alone and in combination with inhibition.......036), but did not affect BBF significantly during exercise (5.5±1.4 ml/100g/min, p=0.25). On the other hand, while combined NOS and COX inhibition did not cause any further reduction of blood flow at rest (0.6±0.2 ml/100g/min), the combined blockade reduced BBF during exercise by ~21%, to 5.0±1.8 ml/100g/min (p...

  19. 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.

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

    International Nuclear Information System (INIS)

    Fränzle, Andrea; Giske, Kristina; Bretschi, Maren; Bäuerle, Tobias; Hillengass, Jens; Bendl, Rolf

    2013-01-01

    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

  1. DXA measurements in Rett syndrome reveal small bones with low bone mass.

    Science.gov (United States)

    Roende, Gitte; Ravn, Kirstine; Fuglsang, Kathrine; Andersen, Henrik; Nielsen, Jytte Bieber; Brøndum-Nielsen, Karen; Jensen, Jens-Erik Beck

    2011-09-01

    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 with RTT do have low BMD when correcting for smaller bones by examination with dual-energy X-ray absorptiometry (DXA). We compared areal BMD (aBMD(spine) and aBMD(total hip) ) and volumetric bone mineral apparent density (vBMAD(spine) and vBMAD(neck) ) in 61 patients and 122 matched healthy controls. Further, spine and hip aBMD and vBMAD of patients were associated with clinical risk factors of low BMD, low-energy fractures, MECP2 mutation groups, and X chromosome inactivation (XCI). Patients with RTT had reduced bone size on the order of 10% and showed lower values of spine and hip aBMD and vBMAD (p bone mass and small bones are evident in RTT, indicating an apparent low-bone-formation phenotype. Copyright © 2011 American Society for Bone and Mineral Research.

  2. Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner.

    Directory of Open Access Journals (Sweden)

    Tommy Noh

    Full Text Available We investigated the role of Lef1, one of the four transcription factors that transmit Wnt signaling to the genome, in the regulation of bone mass. Microcomputed tomographic analysis of 13- and 17-week-old mice revealed significantly reduced trabecular bone mass in Lef1(+/- females compared to littermate wild-type females. This was attributable to decreased osteoblast activity and bone formation as indicated by histomorphometric analysis of bone remodeling. In contrast to females, bone mass was unaffected by Lef1 haploinsufficiency in males. Similarly, females were substantially more responsive than males to haploinsufficiency in Gsk3beta, a negative regulator of the Wnt pathway, displaying in this case a high bone mass phenotype. Lef1 haploinsufficiency also led to low bone mass in males lacking functional androgen receptor (AR (tfm mutants. The protective skeletal effect of AR against Wnt-related low bone mass is not necessarily a result of direct interaction between the AR and Wnt signaling pathways, because Lef1(+/- female mice had normal bone mass at the age of 34 weeks. Thus, our results indicate an age- and gender-dependent role for Lef1 in regulating bone formation and bone mass in vivo. The resistance to Lef1 haploinsufficiency in males with active AR and in old females could be due to the reduced bone turnover in these mice.

  3. Influence of Body Weight on Bone Mass, Architecture, and Turnover

    Science.gov (United States)

    Iwaniec, Urszula T.; Turner, Russell T.

    2016-01-01

    Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. While the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size. PMID:27352896

  4. 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

  5. An Unusual Neck Mass: Ingested Chicken Bone

    OpenAIRE

    Demirhan, Erhan; İber, Metin; Yağız, Özlem; Kandoğan, Tolga; Çukurova, İbrahim

    2016-01-01

    Background: Foreign bodies in the upper aerodigestive tract are frequently seen in otolaryngological practice, but migration of an ingested foreign body to the neck is a very rare condition. Case Report: We present a 66-year-old woman admitted to our outpatient department with a painful neck mass. She had a history of emergency department admission 4 months prior with odynophagia after eating chicken meal. A physical examination revealed a painful and hyperemic mass on the left neck. Ant...

  6. Tracking of bone mass from childhood to puberty

    DEFF Research Database (Denmark)

    Rønne, M. S.; Heidemann, M.; Schou, A.

    2018-01-01

    health. Introduction: Bone mass development in childhood varies by sex and age, but also by pubertal stage. The objectives of this study were to (1) describe bone mass development in childhood as it relates to pubertal onset and to (2) determine the degree of tracking from childhood to adolescence....... Methods: A longitudinal study with 7 years of follow-up was initiated in 2008 to include 831 children (407 boys) aged 8 to 17 years. Participants underwent whole body dual-energy X-ray absorptiometry (DXA) scanning, blood collection to quantify luteinizing hormone levels, and Tanner stage self...

  7. 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.

  8. Histone deacetylase 3 is required for maintenance of bone mass during aging

    Science.gov (United States)

    McGee-Lawrence, Meghan E.; Bradley, Elizabeth W.; Dudakovic, Amel; Carlson, Samuel W.; Ryan, Zachary C.; Kumar, Rajiv; Dadsetan, Mahrokh; Yaszemski, Michael J.; Chen, Qingshan; An, Kai-Nan; Westendorf, Jennifer J.

    2012-01-01

    Histone deacetylase 3 (Hdac3) is a nuclear enzyme that removes acetyl groups from lysine residues in histones and other proteins to epigenetically regulate gene expression. Hdac3 interacts with bone-related transcription factors and co-factors such as Runx2 and Zfp521, and thus is poised to play a key role in the skeletal system. To understand the role of Hdac3 in osteoblasts and osteocytes, Hdac3 conditional knockout (CKO) mice were created with the Osteocalcin (OCN) promoter driving Cre expression. Hdac3 CKOOCN mice were of normal size and weight, but progressively lost trabecular and cortical bone mass with age. The Hdac3 CKOOCN mice exhibited reduced cortical bone mineralization and material properties and suffered frequent fractures. Bone resorption was lower, not higher, in the Hdac3 CKOOCN mice, suggesting that primary defects in osteoblasts caused the reduced bone mass. Indeed, reductions in bone formation were observed. Osteoblasts and osteocytes from Hdac3 CKOOCN mice showed increased DNA damage and reduced functional activity in vivo and in vitro. Thus, Hdac3 expression in osteoblasts and osteocytes is essential for bone maintenance during aging. PMID:23085085

  9. Relationship of bony trabecular characteristics and age to bone mass

    International Nuclear Information System (INIS)

    Choi, Dong Hoon; Song, Young Han; Yoon, Young Nam; Lee, Wan; Lee, Byung Do

    2006-01-01

    Bony strength is dependent on bone mass and bony structure. So this study was designed to investigate the relationship between the bone mass and bony mass and bony trabecular characteristics. Study subjects were 51 females (average age 68.6 years) and 20 males (average age 66.4 years). Bony mineral density (BMD, grams/cm 2 ) of proximal femur was measured by a dual energy X-ray absorptiometry (DEXA). Regions of interest (ROIs) were selected from the digitized radiographs of proximal femur. A customized computer program processed morphologic operations (MO) of ROIs. 44 skeletal variables of MO were calculated from ROIs on the Ward's triangle and greater trochanter of femur. WHO BMD classes were predicted by MO variables of the same ROI. Classification and Regression Tree analysis was used for calculating weighted kappa values, sensitivity and specificity of MO. The discriminating factors of morphologic operation were branch point, branch point [per cm sq]. Age also played important role in distinguishing osteoporotic classes. The sensitivity of MO at Ward's triangle and Greater Trochanter was 91.8%, 65.6%, respectively. The specificity of MO was 100% at Ward's triangle and Greater Trochanter. Bony trabecular characteristics obtained using radiological bone morphometric analysis seem to be related to bone mass

  10. Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.

    Directory of Open Access Journals (Sweden)

    Sara H Windahl

    Full Text Available Androgens are important regulators of bone mass but the relative importance of testosterone (T versus dihydrotestosterone (DHT for the activation of the androgen receptor (AR in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2, encoded by separate genes (Srd5a1 and Srd5a2. 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05 and cortical bone mineral content (-15%, p<0.05 but unchanged serum androgen levels compared with wild type (WT mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05 in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05. Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.

  11. Peak bone mass density among residents of Metro Manila

    International Nuclear Information System (INIS)

    Lim-Abrahan, M.A.B.; Guanzon, M.L.V.V.; Balderas, J.A.J.; Villaruel, C.M.; Santos, F.

    1996-01-01

    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/cm 2 and 0,91±0.11 g/cm 2 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

  12. Rad GTPase is essential for the regulation of bone density and bone marrow adipose tissue in mice.

    Science.gov (United States)

    Withers, Catherine N; Brown, Drew M; Byiringiro, Innocent; Allen, Matthew R; Condon, Keith W; Satin, Jonathan; Andres, Douglas A

    2017-10-01

    The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates cardiac voltage-gated Ca 2+ channel function. However, its cellular and physiological functions outside of the heart remain to be elucidated. Here we report that Rad GTPase function is required for normal bone homeostasis in mice, as Rad deletion results in significantly lower bone mass and higher bone marrow adipose tissue (BMAT) levels. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed, while in vitro osteoclast differentiation is increased, in the absence of Rad. Microarray analysis revealed that canonical osteogenic gene expression (Runx2, osterix, etc.) is not altered in Rad -/- calvarial osteoblasts; instead robust up-regulation of matrix Gla protein (MGP, +11-fold), an inhibitor of extracellular matrix mineralization and a protein secreted during adipocyte differentiation, was observed. Strikingly, Rad deficiency also resulted in significantly higher marrow adipose tissue levels in vivo and promoted spontaneous in vitro adipogenesis of primary calvarial osteoblasts. Adipogenic differentiation of wildtype calvarial osteoblasts resulted in the loss of endogenous Rad protein, further supporting a role for Rad in the control of BMAT levels. These findings reveal a novel in vivo function for Rad and establish a role for Rad signaling in the complex physiological control of skeletal homeostasis and bone marrow adiposity. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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

    1996-01-01

    of CrossLaps and OCN-Mid corrected for height and weight, had 6%-11% lower bone mass in all regions (p r = -0.13 to r = -0.28, p ....05. In postmenopausal women, the difference in bone mass between the highest and lowest quartiles was 8%-14% (p r = -0.14 to r = -0.32, p r = -0.06 to r = -0.......20 for premenopausal women, NS to p r = -0.01 to r = -0.23, NS to p

  14. [Hormones and osteoporosis update. Regulation of bone remodeling by neuropeptides and neurotransmitters].

    Science.gov (United States)

    Takeda, Shu

    2009-07-01

    From the discovery of the regulation of bone remodelling by leptin, much attention has been focused on neurogenic control of bone remodelling. Various hypothalamic neuropeptides, which are involved in appetite regulation, are now revealed to be important regulators of bone remodelling. More recently, neurotransmitters, such as serotonin or catecholamines, are proven to be bone remodelling regulators.

  15. Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass.

    Science.gov (United States)

    Hirozane, Toru; Tohmonda, Takahide; Yoda, Masaki; Shimoda, Masayuki; Kanai, Yae; Matsumoto, Morio; Morioka, Hideo; Nakamura, Masaya; Horiuchi, Keisuke

    2016-09-28

    Ataxia-telangiectasia mutated (ATM) kinase is a central component involved in the signal transduction of the DNA damage response (DDR) and thus plays a critical role in the maintenance of genomic integrity. Although the primary functions of ATM are associated with the DDR, emerging data suggest that ATM has many additional roles that are not directly related to the DDR, including the regulation of oxidative stress signaling, insulin sensitivity, mitochondrial homeostasis, and lymphocyte development. Patients and mice lacking ATM exhibit growth retardation and lower bone mass; however, the mechanisms underlying the skeletal defects are not fully understood. In the present study, we generated mutant mice in which ATM is specifically inactivated in osteoclasts. The mutant mice did not exhibit apparent developmental defects but showed reduced bone mass due to increased osteoclastic bone resorption. Osteoclasts lacking ATM were more resistant to apoptosis and showed a prolonged lifespan compared to the controls. Notably, the inactivation of ATM in osteoclasts resulted in enhanced NF-κB signaling and an increase in the expression of NF-κB-targeted genes. The present study reveals a novel function for ATM in regulating bone metabolism by suppressing the lifespan of osteoclasts and osteoclast-mediated bone resorption.

  16. Preservation of bone mass and structure in hibernating black bears (Ursus americanus) through elevated expression of anabolic genes.

    Science.gov (United States)

    Fedorov, Vadim B; Goropashnaya, Anna V; Tøien, Øivind; Stewart, Nathan C; Chang, Celia; Wang, Haifang; Yan, Jun; Showe, Louise C; Showe, Michael K; Donahue, Seth W; Barnes, Brian M

    2012-06-01

    Physical inactivity reduces mechanical load on the skeleton, which leads to losses of bone mass and strength in non-hibernating mammalian species. Although bears are largely inactive during hibernation, they show no loss in bone mass and strength. To obtain insight into molecular mechanisms preventing disuse bone loss, we conducted a large-scale screen of transcriptional changes in trabecular bone comparing winter hibernating and summer non-hibernating black bears using a custom 12,800 probe cDNA microarray. A total of 241 genes were differentially expressed (P 1.4) in the ilium bone of bears between winter and summer. The Gene Ontology and Gene Set Enrichment Analysis showed an elevated proportion in hibernating bears of overexpressed genes in six functional sets of genes involved in anabolic processes of tissue morphogenesis and development including skeletal development, cartilage development, and bone biosynthesis. Apoptosis genes demonstrated a tendency for downregulation during hibernation. No coordinated directional changes were detected for genes involved in bone resorption, although some genes responsible for osteoclast formation and differentiation (Ostf1, Rab9a, and c-Fos) were significantly underexpressed in bone of hibernating bears. Elevated expression of multiple anabolic genes without induction of bone resorption genes, and the down regulation of apoptosis-related genes, likely contribute to the adaptive mechanism that preserves bone mass and structure through prolonged periods of immobility during hibernation.

  17. Building strong bones: molecular regulation of the osteoblast lineage.

    Science.gov (United States)

    Long, Fanxin

    2011-12-22

    The past 15 years have witnessed tremendous progress in the molecular understanding of osteoblasts, the main bone-forming cells in the vertebrate skeleton. In particular, all of the major developmental signals (including WNT and Notch signalling), along with an increasing number of transcription factors (such as RUNX2 and osterix), have been shown to regulate the differentiation and/or function of osteoblasts. As evidence indicates that osteoblasts may also regulate the behaviour of other cell types, a clear understanding of the molecular identity and regulation of osteoblasts is important beyond the field of bone biology.

  18. Lack of seasonal variation in bone mass and biochemical estimates of bone turnover

    International Nuclear Information System (INIS)

    Overgaard, K.; Nilas, L.; Johansen, J.S.; Christiansen, C.

    1988-01-01

    Three previous studies have indicated a seasonal variation in bone mineral content, with values during the summer being 1.7% to 7.5% higher than during the winter. We have examined the seasonal influence on both bone mass, biochemical estimates of bone turnover and vitamin D metabolites in 86 healthy women, aged 29-53 years. All participants were followed up for 2 years with examinations every 6 weeks or 3 months. Bone mineral content in the proximal and distal part of the forearm (single photon absorptiometry) did not reveal any significant seasonal variation, whereas bone mineral density of the lumbar spine (dual photon absorptiometry) indicated that the highest values occurred in winter. None of the biochemical parameters showed any statistically significant cyclical changes. Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D3 showed a highly significant seasonal variation, whereas the serum 1,25-dihydroxyvitamin D concentration was virtually unchanged. We conclude that seasonal variation in bone mineral content and bone turnover should not be taken into account when interpreting data from longitudinal studies of healthy pre- and postmenopausal women on a sufficient vitamin D nutriture

  19. Distinct bone marrow blood vessels differentially regulate haematopoiesis.

    Science.gov (United States)

    Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

    2016-04-21

    Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

  20. Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis.

    Science.gov (United States)

    Yao, Song; Zhang, Yali; Tang, Li; Roh, Janise M; Laurent, Cecile A; Hong, Chi-Chen; Hahn, Theresa; Lo, Joan C; Ambrosone, Christine B; Kushi, Lawrence H; Kwan, Marilyn L

    2017-02-01

    The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

  1. BIOCHEMICAL MARKERS OF BONE RESORPTION AND HORMONAL REGULATION OF BONE METABOLISM FOLLOWING LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    V. P. Buzulina

    2013-01-01

    Full Text Available Aim. Comparative evaluation of two biochemical markers of bone resorption and hormonal regulation of bone metabolism in liver recipients. Methods and results. Bоne densitometry of L2–L4 and neck of femur, serum level of some hormones (PTH, vitamin D3, estradiol, testosterone regulating osteoclastogenesis as well as com- parative analyses of two bone resorption markers β-crosslaps and tartrate-resistant acid phosphatase type 5b (TRAP-5b were fulfilled in patients after orthotopic liver transplantation (OLT. In 1 month after OLT bone density reduction of L2–L4 and neck of femur; decrease of vitamin D3, estradiol in women, testosterone in men and increase levels of bone resorption markers were observed. In 1 and 2 years after OLT the rise of bone density, increased levels of PTH, estradiol, testosterone and decreased β-crosslaps levels were revealed, while vitamin D3 and TRAP-5b levels remained stable. Conclusion. TRAP-5b was found to be a more speciffic marker of bone resorption, independent from collagen metabolism in liver. Osteoporosis defined in long-term period after OLT was associated with higher TRAP-5b and revialed in women with low estradiol level. 

  2. 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. Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  3. Regulation of glycogenesis in bone marrow of irradiated body

    Energy Technology Data Exchange (ETDEWEB)

    Barkalaya, A I

    1976-02-01

    In connection with a stimulating effect of insulin on postradiation restoration of medullary hemopoiesis the authors studied the influence of insulin on glycogenesis of bone marrow in comparison with glycogenesis of the liver under the conditions of irradiation. As a result the experiment made on white mice the authors established that the level of glycogen in both tissues on the first two days after irradiation (750 R) increased. Later, the decrease of glycogen concentration was observed and its exhaustion was more marked. Insulin protected bone marrow and the liver from exhaustion of glycogen reserves and ensured a higher level of glycogen in the liver. It is supposed that the regulation mechanisms by means of insulin of glycogenesis in the bone marrow and the liver are mainly of the same type. The influence of insulin on carbohydrate metabolism in the bone marrow is likely to be of significance for postradiation hemopoiesis.

  4. Peak bone mass density among residents of Metro Manila

    International Nuclear Information System (INIS)

    Lim-Abrahan, Mary Anne V.; Gacutan-Liwag, Aretha Ann C.; Balderas, Jubilia Araceli J.; Guanzon, Ma. Vicenta Luz; Guzman, Angel de

    2002-01-01

    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/cm 2 and 1.12±0.21 gm/cm 2 for the males. The highest BMD was 1.23±0.20 gm/cm 2 in the 35-39 year old age group for the females and 1.26±0.31 gm/cm 2 in the 30-34 age group for the males. The mean femoral neck BMD was 0.91±0.12 gm/cm 2 for the females and 1.00±0.13 gm/cm 2 for the males. The highest femoral neck BMD was 0.931±0.12 gm/cm 2 in the 20-24 females and 1.03±0.18 gm/cm 2 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

  5. Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow cells

    International Nuclear Information System (INIS)

    Mogi, Makio; Kondo, Ayami

    2009-01-01

    Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor regulates bone mass by inhibiting osteoclastic bone resorption. mTOR, which is the mammalian target of rapamycin, is a kinase and central regulator of cell growth, proliferation, and survival. By using Rapamycin, we studied whether mTOR pathway is associated with OPG protein production in the mouse bone marrow-derived stromal cell line ST2. Rapamycin markedly increased the level of soluble OPG in ST2 cells. This antibiotic treatment resulted in the suppression of phosphorylation of mTOR. Rapamycin had no effects on the proliferation, differentiation, or apoptosis of the cells. Treatment with bone morphogenetic protein-4, which can induce OPG protein in ST2 cells, also resulted in a decrease in the density of the phospho-mTOR-band, suggesting that the suppression of the phospho-mTOR pathway is necessary for OPG production in ST2 cells. Thus, suitable suppression of mTOR phosphorylation is a necessary requirement for OPG production in bone marrow stromal cells.

  6. [Frontier in bone biology].

    Science.gov (United States)

    Takeda, Shu

    2015-10-01

    Bone is an active organ in which bone mass is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption, i.e., coupling of bone formation and bone resorption. Recent advances in molecular bone biology uncovered the molecular mechanism of the coupling. A fundamental role of osteocyte in the maintenance of bone mass and whole body metabolism has also been revealed recently. Moreover, neurons and neuropeptides have been shown to be intimately involved in bone homeostasis though inter-organ network, in addition to "traditional" regulators of bone metabolism such as soluble factors and cytokines

  7. The role of leptin and other hormones related to bone metabolism and appetite-regulation as determinants of gain in body fat and fat-free mass in 8-11 year old children

    DEFF Research Database (Denmark)

    Dalskov, Stine-Mathilde; Ritz, Christian; Larnkjær, Anni

    2015-01-01

    Background: Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent. Objectives: We examined if baseline fasting levels of ghrelin, adiponectin, leptin, insulin, insulin......-like growth factor I (IGF-1), osteocalcin and intact parathyroid hormone (iPTH) were associated with body composition cross-sectionally and longitudinally in 633 8-11-year-olds. Design: Data on hormones and body composition by Dual-energy X-ray absorptiometry from OPUS School Meal Study were used. We looked...... at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (three and six months) in FMI or FFMI using models with hormones individually or combined. Results: Cross-sectionally, baseline leptin was positively associated with FMI in girls (0...

  8. 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

  9. 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.

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

    Science.gov (United States)

    Nallamshetty, Shriram; Wang, Hong; Rhee, Eun-Jung; Kiefer, Florian W; Brown, Jonathan D; Lotinun, Sutada; Le, Phuong; Baron, Roland; Rosen, Clifford J; Plutzky, Jorge

    2013-01-01

    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.

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

    International Nuclear Information System (INIS)

    Olariu, Agata; Skog, Goeran; Emilian Alexandrescu; Hellborg, Ragnar; Stenstroem, Krstina; Faarinen, Mikko; Persson, Per

    2002-01-01

    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)

  12. Regulation of placental calcium transport and offspring bone health

    Directory of Open Access Journals (Sweden)

    Laura eGoodfellow

    2011-02-01

    Full Text Available Osteoporosis causes considerable morbidity and mortality in later life, and the risk of the disease is strongly determined by peak bone mass, which is achieved in early adulthood. Poor intrauterine and early childhood growth are associated with reduced peak bone mass, and increased risk of osteoporotic fracture in older age. In this review we describe the regulatory aspects of intrauterine bone development, and then summarise the evidence relating early growth to later fracture risk. Physiological systems include vitamin D, PTH; leptin; GH/ IGF-1; finally the potential role of epigenetic processes in the underlying mechanisms will be explored. Thus factors such as maternal lifestyle, diet, body build, physical activity and vitamin D status in pregnancy all appear to influence offspring bone mineral accrual. These data demonstrate a likely interaction between environmental factors and gene expression, a phenomenon ubiquitous in the natural world (developmental plasticity, as the potential key process. Intervention studies are now required to test the hypotheses generated by these epidemiological and physiological findings, to inform potential novel public health interventions aimed at improving childhood bone health and reducing the burden of osteoporotic fracture in future generations.

  13. Poor bone health in underprivileged Indian girls: an effect of low bone mass accrual during puberty.

    Science.gov (United States)

    Khadilkar, Anuradha V; Sanwalka, Neha J; Kadam, Nidhi S; Chiplonkar, Shashi A; Khadilkar, Vaman V; Mughal, M Zulf

    2012-05-01

    A socio-economic gradient exists for most reasons of morbidity and mortality including delayed puberty in lower (LSES) as compared to higher (HSES) socio-economic stratum and puberty is an important factor affecting bone status in children and adolescents. Thus, a cross-sectional study was conducted on 195 age-matched pairs of girls (8-17years) from LSES and HSES in Pune City, India to assess the hypothesis that socio-economic factors working through late puberty would have a negative association with bone status of adolescents. Height, weight and Tanner stage were assessed. Total body bone mineral content (TBBMC), total body bone area (TBBA), total body bone mineral density (TBBMD), lean body mass (LBM) and total body fat mass (TBFM) were measured using GE Lunar DPX Pro Pencil Beam DXA (Wisconsin, USA) scanner. Mean TBBMC (1172±434g), TBBA (1351±356cm(2)), TBBMD (0.846±0.104g/cm(2)), LBM (21,622±5306g) and TBFM (7746±5194g) in LSES girls were significantly lower than that of HSES girls [TBBMC (1483±525g), TBBA (1533±380cm(2)), TBBMD (0.942±0.119g/cm(2)), LBM (24,308±5829g) and TBFM (12,196±7404g)] (pbone parameters. The differences in TBBMC, TBBA, LBM and TBFM between the 2 socio-economic strata at Tanner stage I were not significant (p>0.1) whereas there were significant differences in these parameters from Tanner stages II to V (pbone health in adolescent girls from the lower socio-economic stratum. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Erk1 positively regulates osteoclast differentiation and bone resorptive activity.

    Directory of Open Access Journals (Sweden)

    Yongzheng He

    Full Text Available The extracellular signal-regulated kinases (ERK1 and 2 are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1(-/- bone marrow mononuclear cells (BMMNCs demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2(-/- BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

  15. Legal regulations for handling mass proceedings

    International Nuclear Information System (INIS)

    Kopp, F.

    1980-01-01

    The author explains legal regulations to be found in administrative law and in the drafted version of rules of administrative procedures on the calling-in of third parties, on common attorneys, on the publication of service etc. and on other simplifications of proceedings with the aim to make mass proceedings administerable. As a result, the author considers these special regulations to be largely dispensable and risky with regard to constitutional law. An extension of constitutional guarantees pertaining to administrative procedures is necessary in order not to overburden Courts by tasks which may be fulfilled in a better way by federal agencies. The solution is to be found in substantive law: if necessary by admitting the so-called participation of associations or, even better, by introducing an agent safeguarding public interests in administrative procedures. (HSCH) [de

  16. Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model.

    Science.gov (United States)

    Ardawi, Mohammed-Salleh M; Badawoud, Mohammed H; Hassan, Sherif M; Rouzi, Abdulrahim A; Ardawi, Jumanah M S; AlNosani, Nouf M; Qari, Mohammed H; Mousa, Shaker A

    2016-02-01

    Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2μg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture. Copyright © 2015. Published by Elsevier Inc.

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

    International Nuclear Information System (INIS)

    Hagino, Hiroshi

    1989-01-01

    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)

  18. Analysis of bone mass density of lumbar spine zone of athletes

    African Journals Online (AJOL)

    hope&shola

    2010-10-25

    Oct 25, 2010 ... Strengthening exercises, together with walking and aerobic exercises ... effects of exercises on bone mass, the exercises putting load on the ...... activity, body weight and composition, and muscular strength on bone density in ...

  19. BONE METABOLISM AND ITS REGULATION IN PATIENTS WITH ANKYLOSING SPONDYLITIS

    Directory of Open Access Journals (Sweden)

    O. V. Bugrova

    2016-01-01

    Full Text Available Osteoporosis in ankylosing spondylitis (AS may exacerbate pain and functional disorders and increases the risk of fractures. The mechanisms  of its development in AS have not been adequately studied.Objective: to study bone mineral density (BMD  and its regulation in patients with AS.Subjects and methods. 70 patients (mean age, 43.2±9.2 years with a documented diagnosis of AS (mean disease duration, 17.1±7.8 years and a control group of 30 healthy individuals were examined. All the patients underwent estimation of BMD and the serum concentrations of osteocalcin,  CrossLaps, and key regulators of osteoclastogenesis, such as osteoprotegerin (OPG  and a receptor activator of nuclear factor kappa-B ligand (RANKL by an enzyme immunoassay. Results and discussion. In patients with AS, bone metabolism was characterized  by a decrease in bone formation and by some increase in bone tissue degradation especially in high AS activity. These patients showed the elevated levels of the major blocker of osteoclastogenesis OPG and the OPG/RANKL ratio, which can cause the process of ossification characteristic  of AS.

  20. Rhizoma Dioscoreae extract protects against alveolar bone loss in ovariectomized rats via microRNAs regulation.

    Science.gov (United States)

    Zhang, Zhiguo; Song, Changheng; Zhang, Fangzhen; Xiang, Lihua; Chen, Yanjing; Li, Yan; Pan, Jinghua; Liu, Hong; Xiao, Gary Guishan; Ju, Dahong

    2015-02-16

    The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats underwent either ovariectomy or sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX), estradiol valerate (EV), or RDE. After treatments, the bone mineral density (BMD) and the three-dimensional microarchitecture of the alveolar bone were analyzed to assess bone mass. Microarrays were used to evaluate microRNA expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of microRNAs was validated using real-time quantitative RT-PCR (qRT-PCR), and the target genes of validated microRNAs were predicted and further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using qRT-PCR. Our results show that RDE inhibits alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 8 microRNAs and downregulated expression levels of 8 microRNAs in the alveolar bone in the microarray analysis. qRT-PCR helped validate 13 of 16 differentially expressed microRNAs, and 114 putative target genes of the validated microRNAs were retrieved. The IPA showed that these putative target genes had the potential to code for proteins that were involved in the transforming growth factor (TGF)-β/bone morphogenetic proteins (BMPs)/Smad signaling pathway (Tgfbr2/Bmpr2, Smad3/4/5, and Bcl-2) and interleukin (IL)-6/oncostatin M (OSM)/Jak1/STAT3 signaling pathway (Jak1, STAT3, and Il6r). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may involve the simultaneous inhibition of bone formation and bone resorption, which is associated with modulation of the TGF-β/BMPs/Smad and the IL-6/OSM/Jak1/STAT3 signaling pathways via microRNA regulation.

  1. Development, regulation, metabolism and function of bone marrow adipose tissues.

    Science.gov (United States)

    Li, Ziru; Hardij, Julie; Bagchi, Devika P; Scheller, Erica L; MacDougald, Ormond A

    2018-05-01

    Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Assessment of bone mass by image analysis of metacarpal bone roentgenograms

    International Nuclear Information System (INIS)

    Hayashi, Yasufumi; Yamamoto, Kichizo; Fukunaga, Masao; Ishibashi, Toshinobu; Takahashi, Kichiya; Nishii, Yasuho.

    1990-01-01

    A digital image processing (DIP) method for assessing bone mass was developed on the basis of image analysis of roentgenograms. Linearity between DIP values and the actual calcium carbonate content was scarcely affected even if roentgenograms were made with bone phantoms placed in different depths of water or by altering the voltage of X-ray generation. In clinical studies, coefficients of variation (CV) for various measurements were lower than 2.4%. When the correlation between the DIP values and the bone mineral densities in the distal one-third of the radius, and the 2nd to 4th lumbar vertebrae were investigated in 340 females, there were good positive correlations of r=0.799, and r=0.611, respectively (p<0.001). The DIP value was significantly lower in patients showing a low Singh index and in those with vertebral fractures than in other subjects. These results suggest that the DIP method provides an index with which to assess the efficacy of treatment and which can be used as a criterion in screening for osteoporosis. (author)

  3. Bone mass in schizophrenia and normal populations across different decades of life

    Directory of Open Access Journals (Sweden)

    Chueh Ching-Mo

    2009-01-01

    Full Text Available Abstract Background Chronic schizophrenic patients have been reported as having higher osteoporosis prevalence. Survey the bone mass among schizophrenic patients and compare with that of the local community population and reported data of the same country to figure out the distribution of bone mass among schizophrenic patients. Methods 965 schizophrenic patients aged 20 years and over in Yuli Veterans Hospital and 405 members aged 20 and over of the community living in the same town as the institute received bone mass examination by a heel qualitative ultrasound (QUS device. Bone mass distribution was stratified to analyzed and compared with community population. Results Schizophrenic patients have lower bone mass while they are young. But aging effect on bone mass cannot be seen. Accelerated bone mass loss during menopausal transition was not observed in the female schizophrenic patients as in the subjects of the community female population. Conclusion Schizophrenic patients have lower bone mass than community population since they are young. Further study to investigate the pathophysiological process is necessary to delay or avoid the lower bone mass in schizophrenia patients.

  4. The Relation between Visceral and Subcutaneous Fat to Bone Mass among Egyptian Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Sahar A. El-Masry

    2014-12-01

    CONCLUSIONS: Visceral and subcutaneous fat had significant positive association with bone mass in children; males and females respectively. On the contrary such association disappeared during adolescence.

  5. Evaluating the risk of osteoporosis through bone mass density

    International Nuclear Information System (INIS)

    Sayed, S.A.; Khaliq, A.

    2017-01-01

    Osteoporosis is a bone disorder, characterized by loss of bone mass density. Osteoporosis affects more than 30 percent of post-menopausal women. Osteoporosis is often associated with restricted body movement, pain and joint deformities. Early identification and early intervention can help in reducing these complications. The primary objective of this study was to estimate the burden of Osteoporosis in Urban setting of Sindh among women of different age groups and to access the effect of different protective measures that can reduce the risk of Osteoporosis. Method: In this study, 500 women's of 3 major cities of Sindh were approached by non-probability convenience sampling technique. Women bearing age 20 years or more were included. Women who fall under inclusion criteria were screened for BMD (Bone mineral density) test and were classified as Healthy, Osteopenic and Osteoporotic based on their T-score. The association of different protective measures and risk of osteoporosis was assessed by prevalence relative risk (PRR). Result: The result of this study indicate that the burden of Osteoporosis is very high among the women of Sindh, only 17.4 percent (84) women were found to have normal BMD score. The life style of majority of women was sedentary. The PRR calculated for Exposure to sunlight, regular exercise, and use of nutritional supplement was 12.5, 5.19 and 2.72 folds respectively. Conclusion: The results of study reveal that exposure to sunlight, regular physical exercise and use of nutritional supplements found to be effective in reducing the risk of osteoporosis among women of all age group. Health education and promotion toward osteoporosis prevention can significantly contribute in reducing the morbidity of osteoporosis. (author)

  6. Evaluating The Risk Of Osteoporosis Through Bone Mass Density.

    Science.gov (United States)

    Sayed, Sayeeda Amber; Khaliq, Asif; Mahmood, Ashar

    2016-01-01

    Osteoporosis is a bone disorder, characterized by loss of bone mass density. Osteoporosis affects more than 30% of post-menopausal women. Osteoporosis is often associated with restricted body movement, pain and joint deformities. Early identification and early intervention can help in reducing these complications. The primary objective of this study was to estimate the burden of Osteoporosis in Urban setting of Sindh among women of different age groups and to access the effect of different protective measures that can reduce the risk of Osteoporosis. In this study, 500 women's of 3 major cities of Sindh were approached by non-probability convenience sampling technique. Women bearing age 20 years or more were included. Women who fall under inclusion criteria were screened for BMD (Bone mineral density) test and were classified as Healthy, Osteopenic and Osteoporotic based on their T-score. The association of different protective measures and risk of osteoporosis was assessed by prevalence relative risk (PRR). The result of this study indicate that the burden of Osteoporosis is very high among the women of Sindh, only 17.4% (84) women were found to have normal BMD score. The life style of majority of women was sedentary. The PRR calculated for Exposure to sunlight, regular exercise, and use of nutritional supplement was 12.5, 5.19 and 2.72 folds respectively. The results of study reveal that exposure to sunlight, regular physical exercise and use of nutritional supplements found to be effective in reducing the risk of osteoporosis among women of all age group. Health education and promotion toward osteoporosis prevention can significantly contribute in reducing the morbidity of osteoporosis.

  7. Relationship between body mass, lean mass, fat mass, and limb bone cross-sectional geometry: Implications for estimating body mass and physique from the skeleton.

    Science.gov (United States)

    Pomeroy, Emma; Macintosh, Alison; Wells, Jonathan C K; Cole, Tim J; Stock, Jay T

    2018-05-01

    Estimating body mass from skeletal dimensions is widely practiced, but methods for estimating its components (lean and fat mass) are poorly developed. The ability to estimate these characteristics would offer new insights into the evolution of body composition and its variation relative to past and present health. This study investigates the potential of long bone cross-sectional properties as predictors of body, lean, and fat mass. Humerus, femur and tibia midshaft cross-sectional properties were measured by peripheral quantitative computed tomography in sample of young adult women (n = 105) characterized by a range of activity levels. Body composition was estimated from bioimpedance analysis. Lean mass correlated most strongly with both upper and lower limb bone properties (r values up to 0.74), while fat mass showed weak correlations (r ≤ 0.29). Estimation equations generated from tibial midshaft properties indicated that lean mass could be estimated relatively reliably, with some improvement using logged data and including bone length in the models (minimum standard error of estimate = 8.9%). Body mass prediction was less reliable and fat mass only poorly predicted (standard errors of estimate ≥11.9% and >33%, respectively). Lean mass can be predicted more reliably than body mass from limb bone cross-sectional properties. The results highlight the potential for studying evolutionary trends in lean mass from skeletal remains, and have implications for understanding the relationship between bone morphology and body mass or composition. © 2018 The Authors. American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

  8. Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice.

    Science.gov (United States)

    Fonseca, Tatiana L; Teixeira, Marilia B C G; Miranda-Rodrigues, Manuela; Rodrigues-Miranda, Manuela; Silva, Marcos V; Martins, Gisele M; Costa, Cristiane C; Arita, Danielle Y; Perez, Juliana D; Casarini, Dulce E; Brum, Patricia C; Gouveia, Cecilia H A

    2014-08-15

    To investigate whether thyroid hormone (TH) interacts with the sympathetic nervous system (SNS) to modulate bone mass and structure, we studied the effects of daily T3 treatment in a supraphysiological dose for 12 wk on the bone of young adult mice with chronic sympathetic hyperactivity owing to double-gene disruption of adrenoceptors that negatively regulate norepinephrine release, α(2A)-AR, and α(2C)-AR (α(2A/2C)-AR(-/-) mice). As expected, T3 treatment caused a generalized decrease in the areal bone mineral density (aBMD) of WT mice (determined by DEXA), followed by deleterious effects on the trabecular and cortical bone microstructural parameters (determined by μCT) of the femur and vertebra and on the biomechanical properties (maximum load, ultimate load, and stiffness) of the femur. Surprisingly, α(2A/2C)-AR(-/-) mice were resistant to most of these T3-induced negative effects. Interestingly, the mRNA expression of osteoprotegerin, a protein that limits osteoclast activity, was upregulated and downregulated by T3 in the bone of α(2A/2C)-AR(-/-) and WT mice, respectively. β1-AR mRNA expression and IGF-I serum levels, which exert bone anabolic effects, were increased by T3 treatment only in α(2A/2C)-AR(-/-) mice. As expected, T3 inhibited the cell growth of calvaria-derived osteoblasts isolated from WT mice, but this effect was abolished or reverted in cells isolated from KO mice. Collectively, these findings support the hypothesis of a TH-SNS interaction to control bone mass and structure of young adult mice and suggests that this interaction may involve α2-AR signaling. Finally, the present findings offer new insights into the mechanisms through which TH regulates bone mass, structure, and physiology. Copyright © 2014 the American Physiological Society.

  9. The role of leptin and other hormones related to bone metabolism and appetite regulation as determinants of gain in body fat and fat-free mass in 8-11-year-old children.

    Science.gov (United States)

    Dalskov, Stine-Mathilde; Ritz, Christian; Larnkjær, Anni; Damsgaard, Camilla T; Petersen, Rikke A; Sørensen, Louise B; Ong, Ken K; Astrup, Arne; Mølgaard, Christian; Michaelsen, Kim F

    2015-03-01

    Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent. We examined whether baseline fasting levels of ghrelin, adiponectin, leptin, insulin, IGF-I, osteocalcin, and intact parathyroid hormone (iPTH) were associated with body composition cross sectionally and longitudinally in 633 8-11-year-olds. Data on hormones and body composition by dual-energy x-ray absorptiometry from the OPUS School Meal Study were used. We looked at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (3 and 6 months) in FMI or FFMI using models with hormones individually or combined. Cross-sectionally, baseline leptin was positively associated with FMI in girls (0.211 kg/m(2) pr. μg/mL; 97.5% confidence interval [CI],0.186-0.236; P < .001) and boys (0.231 kg/m(2) pr. μg/mL; 97.5% CI, 0.200-0.261; P < .001). IGF-I in both sexes and iPTH in boys were positively associated with FMI. An inverse association between adiponectin and FFMI in boys and a positive association between IGF-I and FFMI were found in girls. In longitudinal models, baseline leptin was inversely associated with subsequent changes in FMI (-0.018 kg/m(2) pr. μg/mL; 97.5% CI, -0.034 - -0.002; P = .028) and FFMI (-0.014 kg/m(2) pr. μg/mL; 97.5% CI, -0.024 - -0.003; P = .006) in girls. Cross-sectional findings support that leptin is produced in proportion to body fat mass, but the longitudinal observations support that leptin inhibits gains in FMI and FFMI in girls, a finding that may reflect preserved leptin sensitivity in this predominantly normal weight population.

  10. The Proprioceptive System Regulates Morphologic Restoration of Fractured Bones

    Directory of Open Access Journals (Sweden)

    Ronen Blecher

    2017-08-01

    Full Text Available Successful fracture repair requires restoration of bone morphology and mechanical integrity. Recent evidence shows that fractured bones of neonatal mice undergo spontaneous realignment, dubbed “natural reduction.” Here, we show that natural reduction is regulated by the proprioceptive system and improves with age. Comparison among mice of different ages revealed, surprisingly, that 3-month-old mice exhibited more rapid and effective natural reduction than newborns. Fractured bones of null mutants for transcription factor Runx3, lacking functional proprioceptors, failed to realign properly. Blocking Runx3 expression in the peripheral nervous system, but not in limb mesenchyme, recapitulated the null phenotype, as did inactivation of muscles flanking the fracture site. Egr3 knockout mice, which lack muscle spindles but not Golgi tendon organs, displayed a less severe phenotype, suggesting that both receptor types, as well as muscle contraction, are required for this regulatory mechanism. These findings uncover a physiological role for proprioception in non-autonomous regulation of skeletal integrity.

  11. 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

    (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......Peak bone mass is a major determinant of osteoporosis risk in later life. It is under strong genetic control; however, little is known about the identity of the genes involved. In the present study, we investigated the relationship between polymorphisms in the genes encoding the vitamin D receptor...

  12. Energy Balance, Myostatin, and GILZ: Factors Regulating Adipocyte Differentiation in Belly and Bone

    Directory of Open Access Journals (Sweden)

    Xingming Shi

    2007-01-01

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPAR-γ belongs to the nuclear hormone receptor subfamily of transcription factors. PPARs are expressed in key target tissues such as liver, fat, and muscle and thus they play a major role in the regulation of energy balance. Because of PPAR-γ's role in energy balance, signals originating from the gut (e.g., GIP, fat (e.g., leptin, muscle (e.g., myostatin, or bone (e.g., GILZ can in turn modulate PPAR expression and/or function. Of the two PPAR-γ isoforms, PPAR-γ2 is the key regulator of adipogenesis and also plays a role in bone development. Activation of this receptor favors adipocyte differentiation of mesenchymal stem cells, while inhibition of PPAR-γ2 expression shifts the commitment towards the osteoblastogenic pathway. Clinically, activation of this receptor by antidiabetic agents of the thiazolidinedione class results in lower bone mass and increased fracture rates. We propose that inhibition of PPAR-γ2 expression in mesenchymal stem cells by use of some of the hormones/factors mentioned above may be a useful therapeutic strategy to favor bone formation.

  13. Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development.

    Science.gov (United States)

    Migliaccio, Silvia; Greco, Emanuela A; Wannenes, Francesca; Donini, Lorenzo M; Lenzi, Andrea

    2014-01-01

    The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.

  14. 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.

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

    International Nuclear Information System (INIS)

    Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna; Pote, Satish T.; Mittal, Monika; Chattopadhyay, Naibedya; Wani, Mohan R.; Bhat, Manoj Kumar

    2014-01-01

    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

  16. Long term effect of thiazides on bone mass in women with hypercalciuric nephrolithiasis

    OpenAIRE

    Spivacow, Francisco R; Negri, Armando L; del Valle, Elisa E

    2013-01-01

    Background: Decreased bone mineral density and increased prevalence of bone fractures have been found in patients with idiopathic hypercalciuria. It is not yet clear if thiazide treatment prevent these events. Methods: We retrospectively evaluated bone mass and biochemical markers of bone turnover in response to thiazide therapy in 52 consecutive female patients with idiopathic hypercalciuria and nephrolithiasis. Patients were divided in two subgroups according to their menopausal status: 25 ...

  17. Stage 1 Breast Cancer and Bone Mass in Older Women

    National Research Council Canada - National Science Library

    Schneider, Diane

    2002-01-01

    The specific aims of the study are 1) to assess the bone mineral density of women 65 years of age and older with breast cancer in comparison with the bone mineral density of same aged women with normal mammograms; 2...

  18. Oral Contraceptives Use by Young Women Reduces Peak Bone Mass

    National Research Council Canada - National Science Library

    Register, Thomas

    2002-01-01

    ...) OC supplemented with an androgen (methyltestosterone), or 4) an anti-androgen (bicalutamide) to determine the potential role that suppression of androgens plays on bone metabolism, bone architecture, and the attainment of PBM...

  19. Oral Contraceptives Use by Young Women Reduces Peak Bone Mass

    National Research Council Canada - National Science Library

    Register, Thomas

    2001-01-01

    ...) OC supplemented with an androgen (methyltestosterone), or (4) an anti-androgen (bicalutamide) to determine the potential role that suppression of androgens plays on bone metabolism, bone architecture, and the attainment of PBM...

  20. Does fetal smoke exposure affect childhood bone mass? The Generation R Study

    NARCIS (Netherlands)

    D.H.M. Heppe (Denise); M.C. Medina-Gomez (Carolina); A. Hofman (Albert); F. Rivadeneira Ramirez (Fernando); V.W.V. Jaddoe (Vincent)

    2015-01-01

    textabstractSummary: We assessed the intrauterine influence of maternal smoking on childhood bone mass by comparing parental prenatal and postnatal smoking habits. We observed higher bone mass in children exposed to maternal smoking, explained by higher body weight. Maternal smoking or related

  1. Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue.

    Science.gov (United States)

    Shi, Yan-Chuan; Baldock, Paul A

    2012-02-01

    Skeletal research is currently undergoing a period of marked expansion. The boundaries of "bone" research are being re-evaluated and with this, a growing recognition of a more complex and interconnected biology than previously considered. One aspect that has become the focus of particular attention is the relationship between bone and fat homeostasis. Evidence from a number of avenues indicates that bone and adipose regulation are both related and interdependent. This review examines the neuropeptide Y (NPY) system, known to exert powerful control over both bone and fat tissue. The actions of this system are characterized by signaling both within specific nuclei of the hypothalamus and also the target tissues, mediated predominantly through two G-protein coupled receptors (Y1 and Y2). In bone tissue, elevated NPY levels act consistently to repress osteoblast activity. Moreover, both central Y2 receptor and osteoblastic Y1 receptor signaling act similarly to repress bone formation. Conversely, loss of NPY expression or receptor signaling induces increased osteoblast activity and bone mass in both cortical and cancellous envelopes. In fat tissue, NPY action is more complex. Energy homeostasis is powerfully altered by elevations in hypothalamic NPY, resulting in increases in fat accretion and body-wide energy conservation, through the action of locally expressed Y1 receptors, while local Y2 receptors act to inhibit NPY-ergic tone. Loss of central NPY expression has a markedly reduced effect, consistent with a physiological drive to promote fat accretion. In fat tissue, NPY and Y1 receptors act to promote lipogenesis, consistent with their roles in the brain. Y2 receptors expressed in adipocytes also act in this manner, showing an opposing action to their role in the hypothalamus. While direct investigation of these processes has yet to be completed, these responses appear to be interrelated to some degree. The starvation-based signal of elevated central NPY inducing

  2. Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

    Science.gov (United States)

    Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

    2009-01-01

    Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

  3. Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass.

    Science.gov (United States)

    Verroken, Charlotte; Zmierczak, Hans-Georg; Goemaere, Stefan; Kaufman, Jean-Marc; Lapauw, Bruno

    2017-06-01

    In type 2 diabetes mellitus, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry. We aimed to explore this association in a cohort of nondiabetic men at the age of peak bone mass. Nine hundred ninety-six nondiabetic men aged 25 to 45 years were recruited in a cross-sectional, population-based sibling pair study at a university research center. Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR), with insulin and glucose measured from fasting serum samples. Bone geometry was assessed using peripheral quantitative computed tomography at the distal radius and the radial and tibial shafts. In age-, height-, and weight-adjusted analyses, HOMA-IR was inversely associated with trabecular area at the distal radius and with cortical area, periosteal and endosteal circumference, and polar strength strain index at the radial and tibial shafts (β ≤ -0.13, P insulin-like growth factor 1, or sex steroid levels. In this cohort of nondiabetic men at the age of peak bone mass, insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels, suggesting an independent effect of insulin resistance on bone geometry. Copyright © 2017 Endocrine Society

  4. Women Build Long Bones With Less Cortical Mass Relative to Body Size and Bone Size Compared With Men.

    Science.gov (United States)

    Jepsen, Karl J; Bigelow, Erin M R; Schlecht, Stephen H

    2015-08-01

    The twofold greater lifetime risk of fracturing a bone for white women compared with white men and black women has been attributed in part to differences in how the skeletal system accumulates bone mass during growth. On average, women build more slender long bones with less cortical area compared with men. Although slender bones are known to have a naturally lower cortical area compared with wider bones, it remains unclear whether the relatively lower cortical area of women is consistent with their increased slenderness or is reduced beyond that expected for the sex-specific differences in bone size and body size. Whether this sexual dimorphism is consistent with ethnic background and is recapitulated in the widely used mouse model also remains unclear. We asked (1) do black women build bones with reduced cortical area compared with black men; (2) do white women build bones with reduced cortical area compared with white men; and (3) do female mice build bones with reduced cortical area compared with male mice? Bone strength and cross-sectional morphology of adult human and mouse bone were calculated from quantitative CT images of the femoral midshaft. The data were tested for normality and regression analyses were used to test for differences in cortical area between men and women after adjusting for body size and bone size by general linear model (GLM). Linear regression analysis showed that the femurs of black women had 11% lower cortical area compared with those of black men after adjusting for body size and bone size (women: mean=357.7 mm2; 95% confidence interval [CI], 347.9-367.5 mm2; men: mean=400.1 mm2; 95% CI, 391.5-408.7 mm2; effect size=1.2; pbone size (women: mean=350.1 mm2; 95% CI, 340.4-359.8 mm2; men: mean=394.3 mm2; 95% CI, 386.5-402.1 mm2; effect size=1.3; pbone size (female: mean=0.73 mm2; 95% CI, 0.71-0.74 mm2; male: mean=0.70 mm2; 95% CI, 0.68-0.71 mm2; effect size=0.74; p=0.04, GLM). Female femurs are not simply a more slender version of male

  5. Facial nerve paralysis associated with temporal bone masses.

    Science.gov (United States)

    Nishijima, Hironobu; Kondo, Kenji; Kagoya, Ryoji; Iwamura, Hitoshi; Yasuhara, Kazuo; Yamasoba, Tatsuya

    2017-10-01

    To investigate the clinical and electrophysiological features of facial nerve paralysis (FNP) due to benign temporal bone masses (TBMs) and elucidate its differences as compared with Bell's palsy. FNP assessed by the House-Brackmann (HB) grading system and by electroneurography (ENoG) were compared retrospectively. We reviewed 914 patient records and identified 31 patients with FNP due to benign TBMs. Moderate FNP (HB Grades II-IV) was dominant for facial nerve schwannoma (FNS) (n=15), whereas severe FNP (Grades V and VI) was dominant for cholesteatomas (n=8) and hemangiomas (n=3). The average ENoG value was 19.8% for FNS, 15.6% for cholesteatoma, and 0% for hemangioma. Analysis of the correlation between HB grade and ENoG value for FNP due to TBMs and Bell's palsy revealed that given the same ENoG value, the corresponding HB grade was better for FNS, followed by cholesteatoma, and worst in Bell's palsy. Facial nerve damage caused by benign TBMs could depend on the underlying pathology. Facial movement and ENoG values did not correlate when comparing TBMs and Bell's palsy. When the HB grade is found to be unexpectedly better than the ENoG value, TBMs should be included in the differential diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Maternal first-trimester diet and childhood bone mass: the Generation R Study.

    Science.gov (United States)

    Heppe, Denise H M; Medina-Gomez, Carolina; Hofman, Albert; Franco, Oscar H; Rivadeneira, Fernando; Jaddoe, Vincent W V

    2013-07-01

    Maternal diet during pregnancy has been suggested to influence bone health in later life. We assessed the association of maternal first-trimester dietary intake during pregnancy with childhood bone mass. In a prospective cohort study in 2819 mothers and their children, we measured first-trimester daily energy, protein, fat, carbohydrate, calcium, phosphorus, and magnesium intakes by using a food-frequency questionnaire and homocysteine, folate, and vitamin B-12 concentrations in venous blood. We measured childhood total body bone mass by using dual-energy X-ray absorptiometry at the median age of 6.0 y. Higher first-trimester maternal protein, calcium, and phosphorus intakes and vitamin B-12 concentrations were associated with higher childhood bone mass, whereas carbohydrate intake and homocysteine concentrations were associated with lower childhood bone mass (all P-trend childhood bone mass. In the fully adjusted regression model that included all dietary factors significantly associated with childhood bone mass, maternal phosphorus intake and homocysteine concentrations most-strongly predicted childhood bone mineral content (BMC) [β = 2.8 (95% CI: 1.1, 4.5) and β = -1.8 (95% CI: -3.6, 0.1) g per SD increase, respectively], whereas maternal protein intake and vitamin B-12 concentrations most strongly predicted BMC adjusted for bone area [β = 2.1 (95% CI: 0.7, 3.5) and β = 1.8 (95% CI: 0.4, 3.2) g per SD increase, respectively]. Maternal first-trimester dietary factors are associated with childhood bone mass, suggesting that fetal nutritional exposures may permanently influence bone development.

  7. 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

    urinary calcium corrected for creatinine excretion. RESULTS: Women who had undergone premenopausal hysterectomy had similar bone mineral densities compared with women with an intact uterus in all compartments, apart from a 6% to 11% higher bone mineral density (p

  8. 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

  9. 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 ... correlate with increased endometrial thickness and bone mass....

  10. Bone--bone marrow interface (endosteum) potential relationship of microenvironments in the regulation of response to internal emitters

    International Nuclear Information System (INIS)

    Wilson, F.D.; Pool, R.R.; Stitzel, K.; Momeni, M.H.

    1976-01-01

    The interface between bone and bone marrow is examined in relation to radiation effects, with attention to new concepts of hematopoiesis. Such concepts propose a functional role of stroma in regulating the commitment of pluripotent stem cells as well as in the production of colony stimulating activity (CSA) including candidate granulopoietin(s). Morphologic examples are included, underlining the concept that stroma (including bone) and hematopoietic elements respond as a functional unit to injury to marrow elements. The methylcellulose bone marrow culture system is reviewed as it may relate to a method for quantitation of hematopoietic colonies (CFU-C), humoral regulators for granulopoiesis (CSA), and potentially as a method of quantitating mesenchymal progenitor populations (PFU-C). Based on these and other observations cited, a model depicting a tentative positioning of cells at risk relative to bone-seeking radionuclides is presented

  11. Sclerostin Blockade and Zoledronic Acid Improve Bone Mass and Strength in Male Mice With Exogenous Hyperthyroidism.

    Science.gov (United States)

    Tsourdi, Elena; Lademann, Franziska; Ominsky, Michael S; Rijntjes, Eddy; Köhrle, Josef; Misof, Barbara M; Roschger, Paul; Klaushofer, Klaus; Hofbauer, Lorenz C; Rauner, Martina

    2017-11-01

    Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks. Hyperthyroid mice displayed a lower trabecular bone volume at the spine (-42%, P hyperthyroid mice increased trabecular bone volume at the spine by threefold and twofold, respectively. Serum bone formation and resorption markers were increased in hyperthyroid mice and suppressed by treatment with ZOL but not Scl-Ab. Trabecular bone stiffness at the lumbar vertebra was 63% lower in hyperthyroid mice (P hyperthyroidism, was increased by Scl-Ab by 71% and ZOL by 22% (both P hyperthyroid mice was restored by treatment with Scl-Ab and ZOL. Thus, bone-forming and antiresorptive drugs prevent bone loss in hyperthyroid mice via different mechanisms. Copyright © 2017 Endocrine Society.

  12. Artistic versus rhythmic gymnastics: effects on bone and muscle mass in young girls.

    Science.gov (United States)

    Vicente-Rodriguez, G; Dorado, C; Ara, I; Perez-Gomez, J; Olmedillas, H; Delgado-Guerra, S; Calbet, J A L

    2007-05-01

    We compared 35 prepubertal girls, 9 artistic gymnasts and 13 rhythmic gymnasts with 13 nonphysically active controls to study the effect of gymnastics on bone and muscle mass. Lean mass, bone mineral content and areal density were measured by dual energy X-ray absorptiometry, and physical fitness was also assessed. The artistic gymnasts showed a delay in pubertal development compared to the other groups (partistic gymnasts had a 16 and 17 % higher aerobic power and anaerobic capacity, while the rhythmic group had a 14 % higher anaerobic capacity than the controls, respectively (all partistic gymnasts had higher lean mass (partistic and the rhythmic gymnasts (partistic group compared to the other groups. Lean mass strongly correlated with bone mineral content (r=0.84, partistic gymnastic participation is associated with delayed pubertal development, enhanced physical fitness, muscle mass, and bone density in prepubertal girls, eliciting a higher osteogenic stimulus than rhythmic gymnastic.

  13. Regulation of bone morphogenetic proteins in early embryonic development

    Science.gov (United States)

    Yamamoto, Yukiyo; Oelgeschläger, Michael

    2004-11-01

    Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-β family of secreted growth factors, control fundamental events in early embryonic development, organogenesis and adult tissue homeostasis. The plethora of dose-dependent cellular processes regulated by BMP signalling demand a tight regulation of BMP activity. Over the last decade, a number of proteins have been identified that bind BMPs in the extracellular space and regulate the interaction of BMPs with their cognate receptors, including the secreted BMP antagonist Chordin. In the early vertebrate embryo, the localized secretion of BMP antagonists from the dorsal blastopore lip establishes a functional BMP signalling gradient that is required for the determination of the dorsoventral or back to belly body axis. In particular, inhibition of BMP activity is essential for the formation of neural tissue in the development of vertebrate and invertebrate embryos. Here we review recent studies that have provided new insight into the regulation of BMP signalling in the extracellular space. In particular, we discuss the recently identified Twisted gastrulation protein that modulates, in concert with metalloproteinases of the Tolloid family, the interaction of Chordin with BMP and a family of proteins that share structural similarities with Chordin in the respective BMP binding domains. In addition, genetic and functional studies in zebrafish and frog provide compelling evidence that the secreted protein Sizzled functionally interacts with the Chd BMP pathway, despite being expressed ventrally in the early gastrula-stage embryo. These intriguing discoveries may have important implications, not only for our current concept of early embryonic patterning, but also for the regulation of BMP activity at later developmental stages and tissue homeostasis in the adult.

  14. Cytokines and growth factors which regulate bone cell function

    Science.gov (United States)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  15. Clinical study evaluating bone mineral mass in the radius during skeletal growth. Single photon absorptiometry

    Energy Technology Data Exchange (ETDEWEB)

    Hagino, Hiroshi

    1989-01-01

    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.

  16. Improvement of Lumbar Bone Mass after Infliximab Therapy in Crohn’s Disease Patients

    Directory of Open Access Journals (Sweden)

    Marina Mauro

    2007-01-01

    Full Text Available BACKGROUND: Patients with Crohn’s disease (CD have a high risk of developing osteoporosis, but the mechanisms underlying bone mass loss are unclear. Elevated proinflammatory cytokines, such as tumour necrosis factor-alpha (TNFα, have been implicated in the pathogenesis of bone resorption.

  17. A multicenter study of the influence of fat and lean mass on bone mineral content

    DEFF Research Database (Denmark)

    Hla, M M; Davis, J W; Ross, P D

    1996-01-01

    We examined the relative influence of fat and lean mass on bone mineral content (BMC) among 1600 early postmenopausal women aged 45-59 y from four geographical locations (Nottingham, United Kingdom; Portland, OR; Honolulu; and Copenhagen). Bone sites investigated included the major fracture sites...

  18. Maternal first-trimester diet and childhood bone mass: The Generation R Study

    NARCIS (Netherlands)

    D.H.M. Heppe (Denise); M.C. Medina-Gomez (Carolina); A. Hofman (Albert); O.H. Franco (Oscar); F. Rivadeneira Ramirez (Fernando); V.W.V. Jaddoe (Vincent)

    2013-01-01

    textabstractBackground: Maternal diet during pregnancy has been suggested to influence bone health in later life. Objective: We assessed the association of maternal first-trimester dietary intake during pregnancy with childhood bone mass. Design: In a prospective cohort study in 2819 mothers and

  19. Bone Turnover Markers and Lean Mass in Pubescent Boys: Comparison Between Elite Soccer Players and Controls.

    Science.gov (United States)

    Nebigh, Ammar; Abed, Mohamed Elfethi; Borji, Rihab; Sahli, Sonia; Sellami, Slaheddine; Tabka, Zouhair; Rebai, Haithem

    2017-11-01

    The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6-8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.

  20. Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links

    OpenAIRE

    Pardini,Dolores Perovano; Sabino,Anibal Tagliaferri; Meneses,Ana Maria; Kasamatsu,Teresa; Vieira,José Gilberto Henriques

    2000-01-01

    CONTEXT: The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. OBJECTIVE: To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN: Cohort correlational study. SETTING: Academic...

  1. 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,…

  2. [Bone homeostasis and Mechano biology.

    Science.gov (United States)

    Nakashima, Tomoki

    The weight-bearing exercises help to build bones and to maintain them strength. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the regulation of bone remodeling in response to mechanical and endocrine stimuli.

  3. Contributions of Caucasian-associated bone mass loci to the variation in bone mineral density in Vietnamese population.

    Science.gov (United States)

    Ho-Pham, Lan T; Nguyen, Sing C; Tran, Bich; Nguyen, Tuan V

    2015-07-01

    Bone mineral density (BMD) is under strong genetic regulation, but it is not clear which genes are involved in the regulation, particularly in Asian populations. This study sought to determine the association between 29 genes discovered by Caucasian-based genome-wide association studies and BMD in a Vietnamese population. The study involved 564 Vietnamese men and women aged 18 years and over (average age: 47 years) who were randomly sampled from the Ho Chi Minh City. BMD at the femoral neck, lumbar spine, total hip and whole body was measured by DXA (Hologic QDR4500, Bedford, MA, USA). Thirty-two single nucleotide polymorphisms (SNPs) in 29 genes were genotyped using Sequenom MassARRAY technology. The magnitude of association between SNPs and BMD was analyzed by the linear regression model. The Bayesian model average method was used to identify SNPs that are independently associated with BMD. The distribution of genotypes of all, but two, SNPs was consistent with the Hardy-Weinberg equilibrium law. After adjusting for age, gender and weight, 3 SNPs were associated with BMD: rs2016266 (SP7 gene), rs7543680 (ZBTB40 gene), and rs1373004 (MBL2/DKK1 gene). Among the three genetic variants, the SNP rs2016266 had the strongest association, with each minor allele being associated with ~0.02 g/cm(2) increase in BMD at the femoral neck and whole body. Each of these genetic variant explained about 0.2 to 1.1% variance of BMD. All other SNPs were not significantly associated with BMD. These results suggest that genetic variants in the SP7, ZBTB40 and MBL2/DKK1 genes are associated with BMD in the Vietnamese population, and that the effect of these genes on BMD is likely to be modest. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Grubbe, M-C; Thomsen, Jesper Skovhus; 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...... of periosteal BFR/BS (2-fold increase vs. BTX, Pmuscle mass (+29% vs. BTX, Pmuscle CSA (+11%, P=0.064). In conclusion, GH mitigates disuse......BMD, -13%, Pmuscle mass (-69%, Pmuscle cell cross sectional area (CSA) (-73%, P

  5. Regulation of chick bone growth by leptin and catecholamines.

    Science.gov (United States)

    Mauro, L J; Wenzel, S J; Sindberg, G M

    2010-04-01

    Leptin and the sympathetic nervous system have a unique role in linking nutritional status to skeletal metabolism in mammals. Such a regulatory mechanism has not been identified in birds but would be beneficial to signal information about energy reserves to an organ system essential for locomotion, reproduction, and survival. To explore this potential role of leptin and the sympathetic nervous system in birds, an ex vivo chick tibiotarsal model was used to test the effects of leptin and sympathetic activity on longitudinal bone growth and the expression of chondrocyte markers. Reverse transcription-PCR analysis revealed the expression of chicken leptin receptor mRNA as well as both alpha-adrenergic (alpha1A, alpha2A, alpha2B, alpha2C) and beta adrenergic (beta1, beta2) receptor subtype mRNA in the whole bone. Incubation with norepinephrine (NE; 0, 10, or 100 microM for 4 d) caused a significant increase in distal condyle length as compared with vehicle-treated, contralateral tibiotarsi. In contrast, no change in condyle length was detected after leptin treatment (0 or 10 nM or 1 microM for 4 d). Analysis of cell proliferation by bromodeoxyuridine incorporation revealed no increase in bromodeoxyuridine-positive cells in the condyles in response to leptin or NE treatments. Real-time PCR analysis showed that NE enhanced type X collagen mRNA expression, a marker of mature hypertrophic chondrocytes, with no effect on type II collagen mRNA, the matrix protein secreted by proliferating chondrocytes. Leptin treatment had no effect on the expression of either matrix protein. Treatment with agonists specific for alpha- or beta-adrenergic receptors indicates that the activation of alpha-adrenergic receptors is most likely responsible for the sympathetic effect on type X collagen gene expression. These results suggest that NE and other sympathetic agonists have positive effects on bone elongation and the changes in critical genes associated with this process. These

  6. Intercomparison of techniques for the non-invasive measurement of bone mass

    International Nuclear Information System (INIS)

    Cohn, S.H.

    1981-01-01

    A variety of methods are presently available for the non-invasive measurement of bone mass of both normal individuals and patients with metabolic disorders. Chief among these methods are radiographic techniques such as radiogrammetry, photon absorptiometry, computer tomography, Compton scattering and neutron activation analysis. In this review, the salient features of the bone measurement techniques are discussed along with their accuracy and precision. The advantages and disadvantages of the various techniques for measuring bone mass are summarized. Where possible, intercomparisons are made of the various techniques

  7. Bone mass determination from microradiographs by computer-assisted videodensitometry. Pt. 2

    International Nuclear Information System (INIS)

    Kaelebo, P.; Strid, K.G.

    1988-01-01

    Aluminium was evaluated as a reference substance in the assessment of rabbit cortical bone by microradiography followed by videodensitometry. Ten dense, cortical-bone specimens from the same tibia diaphysis were microradiographed using prefiltered 27 kV roentgen radiation together with aluminium step wedges and bone simulating phantoms for calibration. Optimally exposed and processed plates were analysed by previously described computer-assisted videodensitometry. For comparison, the specimens were analysed by physico-chemical methods. A strict proportionality was found between the 'aluminium equivalent mass' and the ash weight of the specimens. The total random error was low with a coefficient of variation within 1.5 per cent. It was concluded that aluminium is an appropriate reference material in the determination of cortical bone, which it resembles in effective atomic number and thus X-ray attenuation characteristics. The 'aluminium equivalent mass' is suitably established as the standard of expressing the results of bone assessment by microradiography. (orig.)

  8. Low bone mass density is associated with hemolysis in brazilian patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Gabriel Baldanzi

    2011-01-01

    Full Text Available OBJECTIVES: To determine whether kidney disease and hemolysis are associated with bone mass density in a population of adult Brazilian patients with sickle cell disease. INTRODUCTION: Bone involvement is a frequent clinical manifestation of sickle cell disease, and it has multiple causes; however, there are few consistent clinical associations between bone involvement and sickle cell disease. METHODS: Patients over 20 years of age with sickle cell disease who were regularly followed at the Hematology and Hemotherapy Center of Campinas, Brazil, were sorted into three groups, including those with normal bone mass density, those with osteopenia, and those with osteoporosis, according to the World Health Organization criteria. The clinical data of the patients were compared using statistical analyses. RESULTS: In total, 65 patients were included in this study: 12 (18.5% with normal bone mass density, 37 (57% with osteopenia and 16 (24.5% with osteoporosis. Overall, 53 patients (81.5% had bone mass densities below normal standards. Osteopenia and osteoporosis patients had increased lactate dehydrogenase levels and reticulocyte counts compared to patients with normal bone mass density (p<0.05. Osteoporosis patients also had decreased hemoglobin levels (p<0.05. Hemolysis was significantly increased in patients with osteoporosis compared with patients with osteopenia, as indicated by increased lactate dehydrogenase levels and reticulocyte counts as well as decreased hemoglobin levels. Osteoporosis patients were older, with lower glomerular filtration rates than patients with osteopenia. There was no significant difference between the groups with regard to gender, body mass index, serum creatinine levels, estimated creatinine clearance, or microalbuminuria. CONCLUSION: A high prevalence of reduced bone mass density that was associated with hemolysis was found in this population, as indicated by the high lactate dehydrogenase levels, increased

  9. Mouse genome-wide association and systems genetics identify Asxl2 as a regulator of bone mineral density and osteoclastogenesis.

    Directory of Open Access Journals (Sweden)

    Charles R Farber

    2011-04-01

    Full Text Available Significant advances have been made in the discovery of genes affecting bone mineral density (BMD; however, our understanding of its genetic basis remains incomplete. In the current study, genome-wide association (GWA and co-expression network analysis were used in the recently described Hybrid Mouse Diversity Panel (HMDP to identify and functionally characterize novel BMD genes. In the HMDP, a GWA of total body, spinal, and femoral BMD revealed four significant associations (-log10P>5.39 affecting at least one BMD trait on chromosomes (Chrs. 7, 11, 12, and 17. The associations implicated a total of 163 genes with each association harboring between 14 and 112 genes. This list was reduced to 26 functional candidates by identifying those genes that were regulated by local eQTL in bone or harbored potentially functional non-synonymous (NS SNPs. This analysis revealed that the most significant BMD SNP on Chr. 12 was a NS SNP in the additional sex combs like-2 (Asxl2 gene that was predicted to be functional. The involvement of Asxl2 in the regulation of bone mass was confirmed by the observation that Asxl2 knockout mice had reduced BMD. To begin to unravel the mechanism through which Asxl2 influenced BMD, a gene co-expression network was created using cortical bone gene expression microarray data from the HMDP strains. Asxl2 was identified as a member of a co-expression module enriched for genes involved in the differentiation of myeloid cells. In bone, osteoclasts are bone-resorbing cells of myeloid origin, suggesting that Asxl2 may play a role in osteoclast differentiation. In agreement, the knockdown of Asxl2 in bone marrow macrophages impaired their ability to form osteoclasts. This study identifies a new regulator of BMD and osteoclastogenesis and highlights the power of GWA and systems genetics in the mouse for dissecting complex genetic traits.

  10. The role of lean body mass and physical activity in bone health in children.

    Science.gov (United States)

    Baptista, Fátima; Barrigas, Carlos; Vieira, Filomena; Santa-Clara, Helena; Homens, Pedro Mil; Fragoso, Isabel; Teixeira, Pedro J; Sardinha, Luís B

    2012-01-01

    In the context of physical education curricula, markers of physical fitness (e.g., aerobic capacity, muscular strength, flexibility, and body mass index or body fat) are usually evaluated in reference to health standards. Despite their possible mediating role in the relationship between weight-bearing or muscle forces and features of bone tissue, these attributes of fitness may not be the most relevant to predict skeletal health. It is therefore important to analyze the relative contribution of these factors to the variability in bone tissue of different parts of the skeleton, and to analyze it by gender, as sensitivity to mechanical loading can diverge for boys and girls. We compared the effects of habitual physical activity (PA) and lean mass, as surrogates of weight-bearing and muscle forces, and of physical fitness (aerobic and muscle capacity of lower and upper limbs) on bone mineral content (BMC) and size of total body, lumbar spine, femoral neck, and 1/3 radius in 53 girls and 64 boys from 7.9 to 9.7 years of age. After controlling for bone age, body mass, body height, and calcium intake, lean mass was the most important predictor of bone size and/or mineral in both genders (p  608 counts/min/day (~105 min/day of moderate and vigorous intensity) showed 13-20% more BMC than those with less physical activity, and girls with a lean mass >19 kg showed 12-19% more BMC than those with less lean mass. These findings suggest that lean mass was the most important predictor of bone size and/or mineralization in both genders, while habitual weight-bearing PA appears to positively impact on bone mineral in prepubertal boys and that both lean mass and PA need to be considered in physical education curricula and other health-enhancing programs.

  11. Low bone mass prevalence and osteoporosis risk factor assessment in African American Wisconsin women.

    Science.gov (United States)

    Kidambi, Srividya; Partington, Susan; Binkley, Neil

    2005-11-01

    Post-menopausal osteoporosis is seen in all racial groups. With the increasing population and longevity of minority groups, osteoporosis is becoming an important health concern. Data regarding risk factors for, and prevalence of, low bone mass and awareness of osteoporosis risk in African American (AA) women are limited. This article evaluates the risk factors for, and prevalence of, low bone mass in a population of urban AA women in Wisconsin and assesses this group's perceived risk for osteoporosis. One hundred fifty consecutive community-dwelling AA women > or = 45 years old from Milwaukee, Wis were asked to complete a questionnaire based on currently accepted osteoporosis risk factors. Additionally, their perception of osteoporosis risk was assessed using a Likert scale. All subjects underwent quantitative calcaneal ultrasound. Subject mean age was 54 +/- 7 years. Mean T- and Z-scores were 0.5 and 0.4, respectively. Applying World Health Organization criteria, osteopenia (bone mineral density T-score 2 children), postmenopausal state, and current smoking were associated with lower calcaneal bone mass. Higher education and presence of diabetes were associated with a higher bone mass. Only 25% of the women surveyed thought they were at moderate to high risk for osteoporosis. Low bone mass was present in 33% of these AA women despite their relative young age. Many AA women do not perceive osteoporosis as a health risk. It is necessary to develop strategies to educate AA women regarding osteoporosis risk.

  12. Sports Practice and Bone Mass in Prepubertal Adolescents and Young Adults: A Cross-sectional Analysis

    Directory of Open Access Journals (Sweden)

    Alessandra Madia Mantovani

    Full Text Available Abstract AIM To compare bone mass and body composition variables between adolescents engaged in high-impact sports and adults who were sedentary during early life. METHOD A cross-sectional study with 155 participants (64 adolescents and 91 adults aged between 11 and 50 years old. Among the adults, history of sports was evaluated during face-to-face interviews, and information regarding the adolescents' training routines was provided by their coaches. Body composition was evaluated using Dual Energy X-Ray Absorptiometry which provided data about bone mineral density (BMD, bone mineral content (BMC, fat mass (FM, and free fat mass (FFM. RESULTS Adults who engaged in sports practice during early life had higher values of BMC (ES-r = 0.063, FFM (ES-r = 0.391, and lower values of FM (ES-r = 0.396 than sedentary adults. Higher values of BMC (ES-r = 0.063 and BMD in lower limbs (ES-r = 0.091 were observed in active adolescents. Adolescents engaged in sports and adults who were sedentary in early life presented similar values in all bone variables, FM, and FFM. CONCLUSIONS Sports involvement in early life is related to higher bone mass in adulthood. Adolescents engaged in sports presented similar bone mass to adults who had been sedentary in early life.

  13. Effect of fat mass and lean mass on bone mineral density in postmenopausal and perimenopausal Thai women

    Directory of Open Access Journals (Sweden)

    Namwongprom S

    2013-02-01

    Full Text Available Sirianong Namwongprom,1 Sattaya Rojanasthien,2 Ampica Mangklabruks,3 Supasil Soontrapa,4 Chanpen Wongboontan,5 Boonsong Ongphiphadhanakul61Clinical Epidemiology Program and Department of Radiology, 2Department of Orthopaedics, 3Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 4Department of Orthopaedics, Faculty of Medicine, Khon Kaen University, Khon Kaen, 5Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 6Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandBackground: The purpose of this study was to investigate the association between fat mass, lean mass, and bone mineral density (BMD in postmenopausal and perimenopausal Thai women.Methods: A cross-sectional study was conducted in 1579 healthy Thai women aged 40–90 years. Total body, lumbar spine, total femur, and femoral neck BMD and body composition were measured by dual x-ray absorptiometry. To evaluate the associations between fat mass and lean mass and various measures of BMD, multivariable linear regression models were used to estimate the regression coefficients for fat mass and lean mass, first in separate equations and then with both fat mass and lean mass in the same equation.Results: Among the study population, 1448 subjects (91.7% were postmenopausal and 131 (8.3% were perimenopausal. In postmenopausal women, after controlling for age, height, and duration of menopause, both fat mass and lean mass were positively correlated with BMD when they were analyzed independently of each other. When included in the same equation, both fat mass and lean mass continued to show a positive effect, but lean mass had a significantly greater impact on BMD than fat mass at all regions except for total body. Lean mass but not fat mass had a positive effect on BMD at all skeletal sites except the lumbar spine, after controlling for age and height in perimenopausal

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

    International Nuclear Information System (INIS)

    Lim-Abrahan, M.A.

    2000-01-01

    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

  15. Expression of microRNA related to bone remodeling regulation in plasma in patients with acromegaly

    Directory of Open Access Journals (Sweden)

    Tatiana A. Grebennikova

    2017-11-01

    Full Text Available Backgraund. MiсroRNA are small regulatory factors that regulate gene expression by post-transcriptional regulation of mRNA, playing an important role in numerous cellular processes including organogenesis, apoptosis, cell proliferation and differentiation. Acromegaly causes bone fragility, but the pathogenetic mechanism is generally unknown. Aim. To evaluate levels of microRNA related to bone remodeling regulation in plasma samples from patients with acromegaly Materials and methods. Fasting plasma samples were taken and stored in aliquot at ≤ -80°C from consecutive subjects with clinically evident and biochemically confirmed active acromegaly and healthy volunteers matched by age, sex and body mass index (BMI. miRNeasy Serum/Plasma Kit, TaqMan Advanced miRNA cDNA Synthesis Kit, TaqMan Advanced miRNA Assays were used to assay plasma miRNA expression. Insulin-like growth factor 1 (IGF1 was measured by immunochemiluminescence assay (Liaison. Results. We enrolled 40 subjects 22 patients suffered from acromegaly and 18 matched healthy controls matched by sex, age and BMI. The median age of patients with acromegaly was 42 years (Q25;Q75 – 37;43 with no difference among the groups, p=0.205; BMI – 28 (24;32 kg/m2, p=0.253. The median IGF1 in subjects with acromegaly – 622 (514;1000 ng/ml was significantly higher as compared to the control group (p<0.001. Patients with acromegaly had significantly higher expression of microRNA-100-5р (p=0.051, microRNA-550а-5р (p=0.048, microRNA-7b-5р (p=0.005 and microRNA-96-5р (p=0.042 among 27 bone-specific microRNA tested in plasma Conclusions. This study reveals that several microRNAs, known to regulate bone remodeling can be detected in plasma samples of patients with acromegaly and may be suggested as biomarkers for skeletal involvement in patients with acromegaly.

  16. Spontaneous mutation of Dock7 results in lower trabecular bone mass and impaired periosteal expansion in aged female Misty mice.

    Science.gov (United States)

    Le, Phuong T; Bishop, Kathleen A; Maridas, David E; Motyl, Katherine J; Brooks, Daniel J; Nagano, Kenichi; Baron, Roland; Bouxsein, Mary L; Rosen, Clifford J

    2017-12-01

    adipocytes were elevated 3.5 fold over +/+ (p=0.014). Consistent with reduced bone formation, osteoblast gene expression of Alp, Col1a1, Runx-2, Sp7, and Bglap was significantly decreased in m/m whole bone. Furthermore, markers of osteoclasts were either unchanged or suppressed. Bone marrow stromal cell migration and motility were inhibited in culture and changes in senescence markers suggest that osteoblast function may also be inhibited with loss of Dock7 expression in m/m. Finally, increased Oil Red O staining in m/m ear mesenchymal stem cells during adipogenesis highlights a potential shift of cells from the osteogenic to adipogenic lineages. In summary, loss of Dock7 in the aging m/m resulted in an impairment of periosteal and endocortical envelope expansion, but did not alter age-related trabecular bone loss. These studies establish Dock7 as a critical regulator of both cortical and trabecular bone mass, and demonstrate for the first time a novel role of Dock7 in modulating compensatory changes in the periosteum with aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Measurement of spinal or peripheral bone mass to estimate early postmenopausal bone loss

    International Nuclear Information System (INIS)

    Riis, B.J.; Christiansen, C.

    1988-01-01

    This report presents data from 153 healthy, early postmenopausal women who were randomly allocated to two years of treatment with estrogen or placebo. Bone mineral content in the forearms was measured by single-photon absorptiometry, and bone mineral density of the lumbar spine and total-body bone mineral by dual-photon absorptiometry, before and after one and two years of treatment. At the end of the two years, there were highly significant differences of 6 to 7 percent between the estrogen and the placebo groups at all sites measured. The range of the changes of the spine measurement was twice that of the forearm and total-body measurements. It is concluded that measurement of the forearm by single-photon absorptiometry is superior to measurement of the spine by dual-photon absorptiometry both in clinical studies and in the individual patient for detecting estrogen-dependent bone loss and its treatment by estrogen replacement

  18. High bone turnover is associated with low bone mass and spinal fracture in postmenopausal women

    DEFF Research Database (Denmark)

    Ravn, Pernille; Rix, M; Andreassen, H

    1997-01-01

    -eight women had a lumbar spine bone mineral density (BMD) above 0.860 g/cm2, and 278 women had a BMD below 0.860 g/cm2. Spinal fracture was diagnosed from lateral spine X-ray studies and defined as at least 20% height reduction (wedge, compression, or endplate fracture) in at least one vertebra (T4-L4). Bone...

  19. Bone remodelling: its local regulation and the emergence of bone fragility.

    Science.gov (United States)

    Martin, T John; Seeman, Ego

    2008-10-01

    Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.

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

    Science.gov (United States)

    ... Osteoporosis or Low Bone Mass at the Femur Neck or Lumbar Spine in Older Adults: United States, ... on bone mineral density at either the femur neck or lumbar spine? Nine percent of persons aged ...

  1. 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.

  2. Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status, low calcium intake and high bone turnover

    OpenAIRE

    Kruger, Annamarie; Kruger, Marlena C.; Kruger, Iolanthé Marike; Wentzel-Viljoen, Edelweiss

    2011-01-01

    Globally, rural to urban migration is accompanied by changes in dietary patterns and lifestyle that have serious health implications, including development of low bone mass. We hypothesized that serum 25 (OH) vitamin D3 (25[OH]D3) levels will be lower, bone turnover higher, and nutrition inadequate in urban postmenopausal black women, increasing risk for low bone mass. We aimed to assess the prevalence of risk factors for low bone mass in 1261 black women from rural and urban areas in the Nor...

  3. Hypericum perforatum L. treatment restored bone mass changes in swimming stressed rats.

    Science.gov (United States)

    Seferos, Nikos; Petrokokkinos, Loukas; Kotsiou, Antonia; Rallis, George; Tesseromatis, Christine

    2016-01-01

    Stress, via corticosteroids release, influences bone mass density. Hypericum perforatum (Hp) a traditional remedy possess antidepressive activity (serotonin reuptake inhibitor) and wound healing properties. Hp preparation contains mainly hypericin, hyperforin, hyperoside and flavonoids exerting oestrogen-mimetic effect. Cold swimming represents an experimental model of stress associating mental strain and corporal exhaustion. This study investigates the Hp effect on femur and mandible bone mass changes in rats under cold forced swimming procedure. 30 male Wistar rats were randomized into three groups. Group A was treated with Methanolic extract of Hp (Jarsin®) via gastroesophageal catheter, and was submitted to cold swimming stress for 10 min/daily. Group B was submitted to cold stress, since group C served as control. Experiment duration was 10 days. Haematocrite and serum free fatty acids (FFA) were estimated. Furthermore volume and specific weight of each bone as well as bone mass density via dual energy X-Ray absorptiometry (DEXA) were measured. Statistic analysis by t-test. Hp treatment restores the stress injuries. Adrenals and bone mass density regain their normal values. Injuries occurring by forced swimming stress in the rats are significantly improved by Hp treatment. Estrogen-like effects of Hp flavonoids eventually may act favorable in bone remodeling.

  4. Clinical manifestations of low bone mass in amenorrhea patients with elevated follicular stimulating hormone.

    Science.gov (United States)

    Yu, Qi; Lin, Shouqing; He, Fangfang; Li, Baoluo; Lin, Yuan; Zhang, Tao; Zhang, Ying

    2002-09-01

    To study the characteristics of low bone mass in amenorrhea patients with elevated follicular stimulating hormone (FSH). Amenorrhea patients with elevated FSH: Primary amenorrhea 18 cases, secondary amenorrhea 171 cases and age matched controls with normal menstruation, 180 cases. The descriptive parameters were: estrogen, alkaline phosphatase, urinary excretion of calcium to creatine ratio, cortical bone mineral density at the right radius measured by single photon absorptiometry and trabecular bone mineral density at the lumbar vertebra body measured by quantitative computerized tomography. Average E(2) levels in amenorrhea patients is under 150 pmol/L with significantly higher alkaline phosphatase and urine calcium to creatine ratio values than the normal menstruation group. Cortical bone mineral density in the secondary amenorrhea group (655 +/- 69 mg/cm(2)) was significantly lower than that of the normal menstruation group (677 +/- 56 mg/cm(2), P < 0.01). Trabecular bone mineral density in the secondary amenorrhea group (145 +/- 26 mg/cm(3)) was significantly lower than that of the NOR group (192 +/- 28 mg/cm(3), P < 0.001). The disparity with the normal menstruation group is even greater in the primary amenorrhea group. Bone mineral density of the amenorrhea patients was negatively correlated with duration of the menopause. Serum estrodiol levels in amenorrhea patients was so low that bone turnover was accelerated. This led to insufficient bone accumulation and a dramatically drop in trabecular bone mineral density. The extent was closely related to age of onset of amenorrhea and the duration of ovarian failure.

  5. Clinical review: Ethnic differences in bone mass--clinical implications.

    Science.gov (United States)

    Leslie, William D

    2012-12-01

    Differences in bone mineral density (BMD) as assessed with dual-energy x-ray absorptiometry are observed between geographic and ethnic groups, with important implications in clinical practice. PubMed was employed to identify relevant studies. A review of the literature was conducted, and data were summarized and integrated. The available data highlight the complex ethnic variations in BMD, which only partially account for observed variations in fracture rates. Factors contributing to ethnic differences include genetics, skeletal size, body size and composition, lifestyle, and social determinants. Despite BMD differences, the gradient of risk for fracture from BMD and other clinical risk factors appears to be similar across ethnic groups. Furthermore, BMD variation is greater within an ethnic population than between ethnic populations. New imaging technologies have identified ethnic differences in bone geometry, volumetric density, microarchitecture, and estimated bone strength that may contribute to a better understanding of ethnic differences in fracture risk. Factors associated with ethnicity affect BMD and fracture risk through direct and indirect mechanisms.

  6. Quantitative computed tomography in measurement of vertebral trabecular bone mass

    International Nuclear Information System (INIS)

    Nilsson, M.; Johnell, O.; Jonsson, K.; Redlund-Johnell, I.

    1988-01-01

    Measurement of bone mineral concentration (BMC) can be done by several modalities. Quantitative computed tomography (QCT) can be used for measurements at different sites and with different types of bone (trabecular-cortical). This study presents a modified method reducing the influence of fat. Determination of BMC was made from measurements with single-energy computed tomography (CT) of the mean Hounsfield number in the trabecular part of the L1 vertebra. The method takes into account the age-dependent composition of the trabecular part of the vertebra. As the amount of intravertebral fat increases with age, the effective atomic number for these parts decreases. This results in a non-linear calibration curve for single-energy CT. Comparison of BMC values using the non-linear calibration curve or the traditional linear calibration with those obtained with a pixel-by-pixel based electron density calculation method (theoretically better) showed results clearly in favor of the non-linear method. The material consisted of 327 patients aged 6 to 91 years, of whom 197 were considered normal. The normal data show a sharp decrease in trabecular bone after the age of 50 in women. In men a slower decrease was found. The vertebrae were larger in men than in women. (orig.)

  7. A study on assessment of bone mass from aluminum-equivalent image by digital imaging system

    International Nuclear Information System (INIS)

    Kim, Jin Soo; Kim, Jae Duck; Choi, Eui Hwan

    1997-01-01

    The purpose of this study was to evaluated the method for quantitative assessment of bone mass from aluminum-equivalent value of hydroxyapatite by using digital imaging system consisted of Power Macintosh 7200/120, 15-inch color monitor, and GT-9000 scanner with transparency unit. After aluminum-equivalent image made from correlation between aluminum thickness and grey scale, the accuracy of conversion to mass from aluminum-equivalent value was evaluated. Measured bone mass was compared with converted bone mass from aluminum-equivalent value of hydroxyapatite block by correlation formula between aluminum-equivalent value of hydroxy apatite block and hydroxyapatite mass. The results of this study were as follows : 1. Correlation between aluminum thickness and grey level for obtaining aluminum-equivalent image was high positively associated (r2=0.99). Converted masses from aluminum-equivalent value were very similar to measured masses. There was, statistically, no significant difference (P<0.05) between them. 2. Correlation between hydroxyapatite aluminum-equivalent and hydroxyapatite mass was shown to linear relation (r2 =0.95). 3. Converted masses from aluminum-equivalent value of 3 dry mandible segments were similar to measured masses. The difference between the exposure directions was not significantly different (P<0.05).

  8. Genetic regulation of bone metabolism in the chicken: similarities and differences to Mammalian systems.

    Directory of Open Access Journals (Sweden)

    Martin Johnsson

    2015-05-01

    Full Text Available Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL and expression QTL (eQTL mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone.

  9. Effects of Eggshell Calcium Supplementation on Bone Mass in Postmenopausal Vietnamese Women.

    Science.gov (United States)

    Sakai, Seigo; Hien, Vu Thi Thu; Tuyen, Le Danh; Duc, Ha Anh; Masuda, Yasunobu; Yamamoto, Shigeru

    2017-01-01

    Bone mass decreases along with aging, especially for women after menopause because of lower estrogen secretion together with low calcium intake. This study was conducted to study the effect of eggshell calcium supplementation on bone mass in 54 postmenopausal Vietnamese women living in a farming area about 60 km from Hanoi, Vietnam. Sets of 3 subjects matched by age, bone mass, BMI and calcium intake were divided randomly into 3 groups with 18 subjects in each group. The eggshell calcium group was administered 300 mg/d calcium from eggshell, the calcium carbonate group 300 mg/d calcium from calcium carbonate and the placebo group received no calcium supplementation. Bone mass (Speed of Sound (SOS)) was measured at the beginning (the baseline), the middle (6th month) and the end of the study (12th month) by the single blind method. SOS of the eggshell group increased significantly at 12 mo (p0.05). In conclusion, eggshell calcium was more effective in increasing bone mass than calcium carbonate in postmenopausal Vietnamese women.

  10. Insights into relationships between body mass, composition and bone: findings in elite rugby players.

    Science.gov (United States)

    Hind, Karen; Gannon, Lisa; Brightmore, Amy; Beck, Belinda

    2015-01-01

    Recent reports indicate that bone strength is not proportional to body weight in obese populations. Elite rugby players have a similar body mass index (BMI) to obese individuals but differ markedly with low body fat, high lean mass, and frequent skeletal exposure to loading through weight-bearing exercise. The purpose of this study was to determine relationships between body weight, composition, and bone strength in male rugby players characterized by high BMI and high lean mass. Fifty-two elite male rugby players and 32 nonathletic, age-matched controls differing in BMI (30.2 ± 3.2 vs 24.1 ± 2.1 kg/m²; p = 0.02) received 1 total body and one total hip dual-energy X-ray absorptiometry scan. Hip structural analysis of the proximal femur was used to determine bone mineral density (BMD) and cross-sectional bone geometry. Multiple linear regression was computed to identify independent variables associated with total hip and femoral neck BMD and hip structural analysis-derived bone geometry parameters. Analysis of covariance was used to explore differences between groups. Further comparisons between groups were performed after normalizing parameters to body weight and to lean mass. There was a trend for a positive fat-bone relationship in rugby players, and a negative relationship in controls, although neither reached statistical significance. Correlations with lean mass were stronger for bone geometry (r(2): 0.408-0.520) than for BMD (r(2): 0.267-0.293). Relative to body weight, BMD was 6.7% lower in rugby players than controls (p Rugby players were heavier than controls, with greater lean mass and BMD (p rugby players (p rugby players was reduced in proportion to body weight and lean mass. However, their superior bone geometry suggests that overall bone strength may be adequate for loading demands. Fat-bone interactions in athletes engaged in high-impact sports require further exploration. Copyright © 2015. Published by Elsevier Inc.

  11. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

    Directory of Open Access Journals (Sweden)

    Neha S. Dole

    2017-11-01

    Full Text Available Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR. Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRIIocy−/−, we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility.

  12. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling.

    Science.gov (United States)

    Dole, Neha S; Mazur, Courtney M; Acevedo, Claire; Lopez, Justin P; Monteiro, David A; Fowler, Tristan W; Gludovatz, Bernd; Walsh, Flynn; Regan, Jenna N; Messina, Sara; Evans, Daniel S; Lang, Thomas F; Zhang, Bin; Ritchie, Robert O; Mohammad, Khalid S; Alliston, Tamara

    2017-11-28

    Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/- ), we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Published by Elsevier Inc.

  13. Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes.

    Science.gov (United States)

    Alam, Imranul; Reilly, Austin M; Alkhouli, Mohammed; Gerard-O'Riley, Rita L; Kasipathi, Charishma; Oakes, Dana K; Wright, Weston B; Acton, Dena; McQueen, Amie K; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G; Econs, Michael J

    2017-04-01

    Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice overexpressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole-body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions.

  14. Sr/Ca mass ratio determination in bones using fast neutron activation analysis

    International Nuclear Information System (INIS)

    Hult, Mikael; Fessler, Andreas

    1998-01-01

    The Sr/Ca mass ratio in human bones reveals information regarding the diet which is of interest in archaeology. By using fast neutron activation analysis this ratio can be measured in a non-destructive manner, which is important when bones are considered too precious to allow for destructive analysis. Simulations and measurements showed that the nuclear reactions 88 Sr(n, 2n) 87m Sr and 44 Ca(n, p) 44 K are highly useful for the purpose

  15. The peak bone mass of Hawaiian, Filipino, Japanese, and white women living in Hawaii.

    Science.gov (United States)

    Davis, J W; Novotny, R; Ross, P D; Wasnich, R D

    1994-10-01

    Our study compares the bone mass of Hawaiian, Filipino, Japanese, and white women living in Oahu, Hawaii. Eligible women ranged in age from 25 to 34; all had bone mass measurements at the spine, calcaneus, and proximal and distal radius. Their average bone mineral density (BMD) remained stable with age at all four bone sites, indicating that the age range 25-34 may represent the peak bone mass. Bone mass varied, however, between ethnicities; differences in BMD up to 11% were observed. The Hawaiian women had the greatest BMD, and whites had the second greatest BMD at the spine and calcaneus. The Japanese most frequently had the lowest BMD. Differences in body size partly explained the differences; most ethnic differences were reduced or eliminated after adjusting for height and weight. At the spine, the ethnic differences for BMD were also apparent with BMC and with vertebral area. Hawaiian and white women had greater values than Japanese or Filipino women. Differences at the proximal radius resembled the spine, except that whites had the widest proximal widths. The results were more complex for the distal radius. At the distal radius whites had the lowest BMD of the four ethic groups. The difference between whites and Hawaiians derived from the greater bone mineral content (BMC) of the Hawaiian women. By contrast, the difference between whites and the Japanese and Filipinos derived from the wider distal widths of the white women. Compared with the Japanese and Filipino women, the white women appeared to disperse their BMC at the distal radius across a wider bone width.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Estimation of bone Calcium-to-Phosphorous mass ratio using dual-energy nonlinear polynomial functions

    International Nuclear Information System (INIS)

    Sotiropoulou, P; Koukou, V; Martini, N; Nikiforidis, G; Michail, C; Kandarakis, I; Fountos, G; Kounadi, E

    2015-01-01

    In this study an analytical approximation of dual-energy inverse functions is presented for the estimation of the calcium-to-phosphorous (Ca/P) mass ratio, which is a crucial parameter in bone health. Bone quality could be examined by the X-ray dual-energy method (XDEM), in terms of bone tissue material properties. Low- and high-energy, log- intensity measurements were combined by using a nonlinear function, to cancel out the soft tissue structures and generate the dual energy bone Ca/P mass ratio. The dual-energy simulated data were obtained using variable Ca and PO 4 thicknesses on a fixed total tissue thickness. The XDEM simulations were based on a bone phantom. Inverse fitting functions with least-squares estimation were used to obtain the fitting coefficients and to calculate the thickness of each material. The examined inverse mapping functions were linear, quadratic, and cubic. For every thickness, the nonlinear quadratic function provided the optimal fitting accuracy while requiring relative few terms. The dual-energy method, simulated in this work could be used to quantify bone Ca/P mass ratio with photon-counting detectors. (paper)

  17. Association between bone mass as assessed by quantitative ultrasound and physical function in elderly women: The Fujiwara-kyo study

    Directory of Open Access Journals (Sweden)

    Akira Minematsu

    2017-06-01

    Conclusions: Measurements of physical function can effectively identify elderly women with low bone mass at an early stage without the need for bone mass measurements. In particular, one-leg standing time and 10-m gait time were good predictors of low bone mass, and is easy to measure, low-cost, and can be self-measured. These findings will be helpful in the prevention and treatment of osteoporosis.

  18. Assessment of the influence of body composition on bone mass in children and adolescents based on a functional analysis of the muscle-bone relationship.

    Science.gov (United States)

    Golec, Joanna; Chlebna-Sokół, Danuta

    2014-01-01

    The functional model of skeletal development considers the mechanical factor to be the most important skeletal modulant. The aim of the study was a functional analysis of the bone-muscle relationship in children with low and normal bone mass. The study involved 149 children with low and 99 children with normal bone mass (control group). All patients underwent a densitometry examination (DXA). Low bone mass was diagnosed if the Z-score was below values of Z-scores for all parameters in children with low bone mass as compared to the control group. Children with low bone mass had lower content of adipose and muscle tissue and a marked deficit of muscle tissue with regard to height (which according to mechanostat theory leads to lower muscle-generated strain on bones). This group of children had also lower TBBMC/LBM Z-scores, which indicates greater fracture susceptibility. 1. Functional analysis, which showed associations between bone and muscle tissues, can be useful for diagnosing and monitoring skeletal system disorders as well as making therapeutic decisions.2. The study emphasizes the role of proper nutrition and physical activities, which contribute to proper body composition, in the prevention of bone mineralization disorders in childhood and adolescence. 3. The study showed the inadequacy of the classic reference ranges used in interpreting DXA data in children and demonstrated the usefulness of continuous variables for that purpose.

  19. Thin healthy women have a similar low bone mass to women with anorexia nervosa.

    Science.gov (United States)

    Fernández-García, D; Rodríguez, M; García Alemán, J; García-Almeida, J M; Picón, M J; Fernández-Aranda, F; Tinahones, F J

    2009-09-01

    An association between anorexia nerviosa (AN) and low bone mass has been demonstrated. Bone loss associated with AN involves hormonal and nutritional impairments, though their exact contribution is not clearly established. We compared bone mass in AN patients with women of similar weight with no criteria for AN, and a third group of healthy, normal-weight, age-matched women. The study included forty-eight patients with AN, twenty-two healthy eumenorrhoeic women with low weight (LW group; BMI 18.5 kg/m2 (control group), all of similar age. We measured lean body mass, percentage fat mass, total bone mineral content (BMC) and bone mineral density in lumbar spine (BMD LS) and in total (tBMD). We measured anthropometric parameters, leptin and growth hormone. The control group had greater tBMD and BMD LS than the other groups, with no differences between the AN and LW groups. No differences were found in tBMD, BMD LS and total BMC between the restrictive (n 25) and binge-purge type (n 23) in AN patients. In AN, minimum weight (P = 0.002) and percentage fat mass (P = 0.02) explained BMD LS variation (r2 0.48) and minimum weight (r2 0.42; P = 0.002) for tBMD in stepwise regression analyses. In the LW group, BMI explained BMD LS (r2 0.72; P = 0.01) and tBMD (r2 0.57; P = 0.04). We concluded that patients with AN had similar BMD to healthy thin women. Anthropometric parameters could contribute more significantly than oestrogen deficiency in the achievement of peak bone mass in AN patients.

  20. Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls.

    Science.gov (United States)

    Kindler, J M; Pollock, N K; Laing, E M; Jenkins, N T; Oshri, A; Isales, C; Hamrick, M; Lewis, R D

    2016-01-01

    IGF-1 promotes bone growth directly and indirectly through its effects on skeletal muscle. Insulin and IGF-1 share a common cellular signaling process; thus, insulin resistance may influence the IGF-1-muscle-bone relationship. We sought to determine the effect of insulin resistance on the muscle-dependent relationship between IGF-1 and bone mass in premenarcheal girls. This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years. Glucose, insulin, and IGF-1 were measured from fasting blood samples. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Fat-free soft tissue (FFST) mass and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry. Our primary outcome was BMC/height. In our path model, IGF-1 predicted FFST mass (b = 0.018; P = .001), which in turn predicted BMC/height (b = 0.960; P IGF-1 predicted BMC/height (b = 0.001; P = .002), but not after accounting for the mediator of this relationship, FFST mass. The HOMA-IR by IGF-1 interaction negatively predicted FFST mass (b = -0.044; P = .034). HOMA-IR had a significant and negative effect on the muscle-dependent relationship between IGF-1 and BMC/height (b = -0.151; P = .047). Lean body mass is an important intermediary factor in the IGF-1-bone relationship. For this reason, bone development may be compromised indirectly via suboptimal IGF-1-dependent muscle development in insulin-resistant children.

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

    Science.gov (United States)

    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

    2012-02-20

    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. 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. 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. 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.

  2. 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.

  3. High Insulin Levels in KK-Ay Diabetic Mice Cause Increased Cortical Bone Mass and Impaired Trabecular Micro-Structure

    Directory of Open Access Journals (Sweden)

    Cen Fu

    2015-04-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD, micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD, cortical volumetric BMD (vBMD and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV, trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC, bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression.

  4. Relative contributions of lean and fat mass to bone strength in young Hispanic and non-Hispanic girls.

    Science.gov (United States)

    Hetherington-Rauth, Megan; Bea, Jennifer W; Blew, Robert M; Funk, Janet L; Hingle, Melanie D; Lee, Vinson R; Roe, Denise J; Wheeler, Mark D; Lohman, Timothy G; Going, Scott B

    2018-05-22

    With the high prevalence of childhood obesity, especially among Hispanic children, understanding how body weight and its components of lean and fat mass affect bone development is important, given that the amount of bone mineral accrued during childhood can determine osteoporosis risk later in life. The aim of this study was to assess the independent contributions of lean and fat mass on volumetric bone mineral density (vBMD), geometry, and strength in both weight-bearing and non-weight-bearing bones of Hispanic and non-Hispanic girls. Bone vBMD, geometry, and strength were assessed at the 20% distal femur, the 4% and 66% distal tibia, and the 66% distal radius of the non-dominant limb of 326, 9- to 12-year-old girls using peripheral quantitative computed tomography (pQCT). Total body lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). Multiple linear regression was used to assess the independent relationships of fat and lean mass with pQCT bone measures while adjusting for relevant confounders. Potential interactions between ethnicity and both fat and lean mass were also tested. Lean mass was a significant positive contributor to all bone outcomes (p Lean mass is the main determinant of bone strength for appendicular skeletal sites. Fat mass contributes to bone strength in the weight-bearing skeleton but does not add to bone strength in non-weight-bearing locations and may potentially be detrimental. Bone vBMD, geometry, and strength did not differ between Hispanic and non-Hispanic girls; fat mass may be a stronger contributor to bone strength in weight-bearing bones of Hispanic girls compared to non-Hispanic. Copyright © 2018. Published by Elsevier Inc.

  5. 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.

  6. Imaging and mapping of mouse bone using MALDI-imaging mass spectrometry

    Directory of Open Access Journals (Sweden)

    Yoko Fujino

    2016-12-01

    Full Text Available Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS is an advanced method used globally to analyze the distribution of biomolecules on tissue cryosections without any probes. In bones, however, hydroxyapatite crystals make it difficult to determine the distribution of biomolecules using MALDI-IMS. Additionally, there is limited information regarding the use of this method to analyze bone tissues. To determine whether MALDI-IMS analysis of bone tissues can facilitate comprehensive mapping of biomolecules in mouse bone, we first dissected femurs and tibiae from 8-week-old male mice and characterized the quality of multiple fixation and decalcification methods for preparation of the samples. Cryosections were mounted on indium tin oxide-coated glass slides, dried, and then a matrix solution was sprayed on the tissue surface. Images were acquired using an iMScope at a mass-to-charge range of 100–1000. Hematoxylin-eosin, Alcian blue, Azan, and periodic acid-Schiff staining of adjacent sections was used to evaluate histological and histochemical features. Among the various fixation and decalcification conditions, sections from trichloroacetic acid-treated samples were most suitable to examine both histology and comprehensive MS images. However, histotypic MS signals were detected in all sections. In addition to the MS images, phosphocholine was identified as a candidate metabolite. These results indicate successful detection of biomolecules in bone using MALDI-IMS. Although analytical procedures and compositional adjustment regarding the performance of the device still require further development, IMS appears to be a powerful tool to determine the distribution of biomolecules in bone tissues. Keywords: Matrix-assisted laser desorption/ionization-imaging mass spectrometry, Tissue cryosection, Bone, Fixation, Decalcification

  7. Effects of conjugated linoleic acid and exercise on bone mass in young male Balb/C mice

    Directory of Open Access Journals (Sweden)

    O'Shea Marianne

    2006-03-01

    Full Text Available Abstract There is an increase in obesity among the population of industrialized countries, and dietary supplementation with Conjugated Linoleic Acid (CLA has been reported to lower body fat mass. However, weight loss is generally associated with negative effects on bone mass, but CLA is reported to have beneficial effects on bone. Furthermore, another factor that is well established to have a beneficial effect on bone is exercise (EX. However, a combination therapy of CLA and EX on bone health has not been studied. In this paper, we report the beneficial effects of CLA and EX on bone, in four different groups of Balb-C young, male mice. There were 4 groups in our study: 1. Safflower oil (SFO sedentary (SED; 2. SFO EX; 3. CLA SED; 4. CLA EX. Two months old mice, under their respective treatment regimens were followed for 14 weeks. Mice were scanned in vivo using a DEXA scanner before and after treatment. At the end of the treatment period, the animals were sacrificed, the left tibia was removed and scanned using peripheral quantitative computerized tomography (pQCT. The results showed that although CLA decreased gain in body weight by 35%, it however increased bone mass by both reducing bone resorption and increasing bone formation. EX also decreased gain in body weight by 21% and increased bone mass; but a combination of CLA and EX, however, did not show any further increase in bone mass. In conclusion, CLA increases bone mass in both cancellous and cortical bones, and the effects of CLA on bone is not further improved by EX in pure cortical bone of young male mice.

  8. The effect of ethnicity on appendicular bone mass in white, coloured ...

    African Journals Online (AJOL)

    Ethnic differences in the incidence and prevalence of osteoporosis have been shown throughout the world. In South Africa the prevalence of osteoporosis is much higher in whites than in blacks. This is surprising, since factors that might predispose to reduce bone mass are more preponderant in black communities.

  9. Analysis of bone mass density of lumbar spine zone of athletes ...

    African Journals Online (AJOL)

    This study was carried out to evaluate T-Z scores of lumbar spine zone (L1, L2, L3, L4, L1-L4) bone mass density (BMD) of elite active male athletes in different branches and to determine the differences between them. 42 healthy male athletes aged 18 - 25 competing in different branches (Taekwondo 12, wrestling 8, Judo ...

  10. Physical activity and dark skin tone: protective factors against low bone mass in Mexican men.

    Science.gov (United States)

    Vivanco-Muñoz, Nalleli; Jo, Talavera; Gerardo, Huitron-Bravo; Juan, Tamayo; Clark, Patricia

    2012-01-01

    A cross-sectional study was conducted on 268 Mexican men between the ages of 13 and 80 yr to evaluate the association of clinical factors related with bone mass. Men from high schools, universities, and retirement homes were invited to participate. Body mass index (BMI) was measured, and bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry for L1-L4 and total hip. Factors related to bone mass were assessed by questionnaire and analyzed using a logistic regression model. Demographic factors (age, education, and occupation), clinical data (BMI, skin tone, previous fracture, history of osteoporosis [OP], and history of fractures), and lifestyle variables (diet, physical activity, sun exposure, and smoking) were evaluated. Physical activity (≥ 60 min/5 times a week) reduced the risk for low BMD for age, osteopenia, and OP at the spine and total hip (odds ratio [OR]: 0.276; 95% confidence interval [CI]: 0.099-0.769; p=0.014; and OR: 0.184; 95% CI: 0.04-0.849; p=0.03, respectively). Dark skin tone was a protective factor, decreasing the risk by up to 70%. In this population of healthy Mexican men (aged 13-80 yr), dark skin and physical activity were protective factors against low bone mass. Copyright © 2012 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    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

  12. 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.

  13. Bone and fat connection in aging bone.

    Science.gov (United States)

    Duque, Gustavo

    2008-07-01

    The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

  14. Exercise and Regulation of Bone and Collagen Tissue Biology

    DEFF Research Database (Denmark)

    Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja

    2015-01-01

    The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensur...

  15. Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

    Science.gov (United States)

    Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2017-01-01

    Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

  16. TAK1 regulates skeletal muscle mass and mitochondrial function

    Science.gov (United States)

    Hindi, Sajedah M.; Sato, Shuichi; Xiong, Guangyan; Bohnert, Kyle R.; Gibb, Andrew A.; Gallot, Yann S.; McMillan, Joseph D.; Hill, Bradford G.

    2018-01-01

    Skeletal muscle mass is regulated by a complex array of signaling pathways. TGF-β–activated kinase 1 (TAK1) is an important signaling protein, which regulates context-dependent activation of multiple intracellular pathways. However, the role of TAK1 in the regulation of skeletal muscle mass remains unknown. Here, we report that inducible inactivation of TAK1 causes severe muscle wasting, leading to kyphosis, in both young and adult mice.. Inactivation of TAK1 inhibits protein synthesis and induces proteolysis, potentially through upregulating the activity of the ubiquitin-proteasome system and autophagy. Phosphorylation and enzymatic activity of AMPK are increased, whereas levels of phosphorylated mTOR and p38 MAPK are diminished upon inducible inactivation of TAK1 in skeletal muscle. In addition, targeted inactivation of TAK1 leads to the accumulation of dysfunctional mitochondria and oxidative stress in skeletal muscle of adult mice. Inhibition of TAK1 does not attenuate denervation-induced muscle wasting in adult mice. Finally, TAK1 activity is highly upregulated during overload-induced skeletal muscle growth, and inactivation of TAK1 prevents myofiber hypertrophy in response to functional overload. Overall, our study demonstrates that TAK1 is a key regulator of skeletal muscle mass and oxidative metabolism. PMID:29415881

  17. Genetic Regulation of Bone and Cells by Electromagnetic Stimulation Fields and Uses Thereof

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor); Shackelford, Linda C. (Inventor)

    2018-01-01

    The present invention provides methods to modify the genetic regulation of mammalian tissue, bone, cells or any combination thereof by preferential activation, up-regulation and/or down-regulation. The method comprises steps of tuning the predetermined profiles of one or more time-varying stimulation fields by manipulating the B-Field magnitude, rising slew rate, rise time, falling slew rate, fall time, frequency, wavelength, and duty cycle, and exposing mammalian cells or tissues to one or more tuned time-varying stimulation fields with predetermined profiles. Examples of mammalian cells or tissues are chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination. The resulted modification on gene regulation of these cells, tissues or bones may promote the retention, repair of and reduction of compromised mammalian cartilage, bone, and associated tissue.

  18. MR imaging of bone marrow metastasis in patients with neuroblastoma. Comparison between mass-screened cases and clinically detected cases

    International Nuclear Information System (INIS)

    Kanegawa, Kimio; Akasaka, Yoshinori; Kawasaki, Ryuta; Nishiyama, Shoji; Mabuchi, Osamu; Muraji, Toshihiro

    1999-01-01

    Seventy-six patients with neuroblastoma who underwent bone marrow MRI were divided into two groups: the first group consisted of patients detected by mass screening (M group, n=55), and the second group of patients detected clinically (non-M group, n=21). Bone marrow metastasis was morphologically classified into two types, nodular type and diffuse type. We studied the incidence of bone marrow metastasis, relationship between the patterns of bone marrow metastasis and the presence of bone metastasis, and morphological changes of bone marrow metastasis after chemotherapy. In M group, the incidence of bone marrow metastasis was 7.3% (4 patients) and the patterns of bone marrow metastases were all nodular type not accompanied with bone metastasis and disappeared after chemotherapy. In non-M group, the incidence of bone marrow metastasis was 52.4% (11 patients). Bone marrow metastases had both patterns of metastasis. Forty-five per cent of diffuse type of bone marrow metastasis were accompanied with bone metastasis. All bone marrow metastases disappeared after chemotherapy, but in one of 11, there was recurrence of bone marrow metastasis. (author)

  19. Trabecular bone mineral density measured by quantitative CT of the lumbar spine in children and adolescents: reference values and peak bone mass; Trabekulaere Knochendichte der Lendenwirbelsaeule bei Kindern und Jugendlichen in der quantitativen CT: Referenzwerte und Peak Bone Mass

    Energy Technology Data Exchange (ETDEWEB)

    Berthold, L.D.; Alzen, G. [Kinderradiologie, Zentrum fuer Radiologie, Universitaetsklinikum Giessen und Marburg GmbH, Standort Giessen (Germany); Haras, G. [Siemens AG, Medical Solutions, Forchheim (Germany); Mann, M. [AG Medizinische Statistik, Universitaetsklinikum Giessen und Marburg GmbH, Standort Giessen (Germany)

    2006-12-15

    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

  20. Behavioral Intervention in Adolescents Improves Bone Mass, Yet Lactose Maldigestion Is a Barrier

    Directory of Open Access Journals (Sweden)

    Yujin Lee

    2018-03-01

    Full Text Available Calcium intake during adolescence is important for attainment of peak bone mass. Lactose maldigestion is an autosomal recessive trait, leading to lower calcium intake. The Adequate Calcium Today study aimed to determine if a school-based targeted behavioral intervention over one year could improve calcium intake and bone mass in early adolescent girls. The school-randomized intervention was conducted at middle schools in six states over one school year. A total of 473 girls aged 10–13 years were recruited for outcome assessments. Bone mineral content (BMC was determined by dual energy X-ray absorptiometry. Dietary calcium intake was assessed with a semi-quantitative food frequency questionnaire. Baseline calcium intake and BMC were not significantly different between groups. After the intervention period, there were no differences in changes in calcium intake and BMC at any site between groups. An unanticipated outcome was a greater increase in spinal BMC among lactose digesters than lactose maldigesters in the intervention schools only (12 months (6.9 ± 0.3 g vs. 6.0 ± 0.4 g, p = 0.03 and considering the entire study period (18 months (9.9 ± 0.4 vs. 8.7 ± 0.5 g, p < 0.01. Overall, no significant differences between the intervention and control schools were observed. However, lactose digesters who received the intervention program increased bone mass to a greater extent than lactose maldigesters.

  1. Impact of obesity on bone mass throughout adult life: Influence of gender and severity of obesity.

    Science.gov (United States)

    Maïmoun, Laurent; Mura, Thibault; Leprieur, Elodie; Avignon, Antoine; Mariano-Goulart, Denis; Sultan, Ariane

    2016-09-01

    Obesity improves areal bone mineral density (aBMD). However, it is unknown whether gender, ageing or the severity of obesity could modulate this effect and whether different bone sites are similarly affected. The aim of this observational study was to model the aBMD variation in obese patients from peak bone period to old age according to gender, bone localisation and severity of obesity. Five hundred and four obese patients (363 women, 72%) with a mean BMI of 38.5 ± 6.0 kg/m2, aged from 18.1 to 81.9 years (mean age 49.6 ± 14.6 years) were recruited. The whole body (WB), hip, lumbar spine (L1–L4) and one-third radius aBMDs were determined using dual-energy x-ray absorptiometry (DXA). Z-scores were significantly increased, above the age- and gender-related mean, both for women and men at WB (respectively 0.79 SD and 0.32 SD), hip (1.09 SD and 1.06 SD), one-third radius (1.70 SD and 0.45 SD) and L1–L4 levels (0.86 SD for women only). The improvement of Z-scores was significantly more marked in women compared to men at all bone sites, hip excepted. Furthermore, differences compared with normal values were significantly accentuated by ageing, without noticeable gender effect. In women, regardless of BMI and bone site, Z-scores were higher than normal values, this difference being most marked at WB, L1–L4 and hip levels for obese patients with a BMI above 40 kg/m2. Lean mass, but not fat mass, was independently associated with aBMD in men and women. This study demonstrated for the first time that obesity induces an improvement of aBMD, which is modulated by bone site location, severity of obesity, age and gender. The accentuation of peak bone mass combined with a reduction of bone loss rate with ageing may explain why obese patients present a lower prevalence of osteoporosis.

  2. 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.

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

    Science.gov (United States)

    de Paula, Francisco J A; de Araújo, Iana M; Carvalho, Adriana L; Elias, Jorge; Salmon, Carlos E G; Nogueira-Barbosa, Marcello H

    2015-01-01

    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.

  4. 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.

  5. 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

    2016-01-01

    remission (0.0032 vs. 0.0058 g/cm(2)/year; p clinical practice, and only......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). METHODS...

  6. Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Chen, H-L; Tung, Y-T; Chuang, C-H; Tu, M-Y; Tsai, T-C; Chang, S-Y; Chen, C-M

    2015-02-01

    Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased

  7. Fat Mass Is Positively Associated with Estimated Hip Bone Strength among Chinese Men Aged 50 Years and above with Low Levels of Lean Mass.

    Science.gov (United States)

    Han, Guiyuan; Chen, Yu-Ming; Huang, Hua; Chen, Zhanyong; Jing, Lipeng; Xiao, Su-Mei

    2017-04-24

    This study investigated the relationships of fat mass (FM) and lean mass (LM) with estimated hip bone strength in Chinese men aged 50-80 years (median value: 62.0 years). A cross-sectional study including 889 men was conducted in Guangzhou, China. Body composition and hip bone parameters were generated by dual-energy X-ray absorptiometry (DXA). The relationships of the LM index (LMI) and the FM index (FMI) with bone phenotypes were detected by generalised additive models and multiple linear regression. The associations between the FMI and the bone variables in LMI tertiles were further analysed. The FMI possessed a linear relationship with greater estimated hip bone strength after adjustment for the potential confounders ( p maintenance of adequate FM could help to promote bone acquisition in relatively thin men.

  8. A universal scaling relationship between body mass and proximal limb bone dimensions in quadrupedal terrestrial tetrapods.

    Science.gov (United States)

    Campione, Nicolás E; Evans, David C

    2012-07-10

    Body size is intimately related to the physiology and ecology of an organism. Therefore, accurate and consistent body mass estimates are essential for inferring numerous aspects of paleobiology in extinct taxa, and investigating large-scale evolutionary and ecological patterns in the history of life. Scaling relationships between skeletal measurements and body mass in birds and mammals are commonly used to predict body mass in extinct members of these crown clades, but the applicability of these models for predicting mass in more distantly related stem taxa, such as non-avian dinosaurs and non-mammalian synapsids, has been criticized on biomechanical grounds. Here we test the major criticisms of scaling methods for estimating body mass using an extensive dataset of mammalian and non-avian reptilian species derived from individual skeletons with live weights. Significant differences in the limb scaling of mammals and reptiles are noted in comparisons of limb proportions and limb length to body mass. Remarkably, however, the relationship between proximal (stylopodial) limb bone circumference and body mass is highly conserved in extant terrestrial mammals and reptiles, in spite of their disparate limb postures, gaits, and phylogenetic histories. As a result, we are able to conclusively reject the main criticisms of scaling methods that question the applicability of a universal scaling equation for estimating body mass in distantly related taxa. The conserved nature of the relationship between stylopodial circumference and body mass suggests that the minimum diaphyseal circumference of the major weight-bearing bones is only weakly influenced by the varied forces exerted on the limbs (that is, compression or torsion) and most strongly related to the mass of the animal. Our results, therefore, provide a much-needed, robust, phylogenetically corrected framework for accurate and consistent estimation of body mass in extinct terrestrial quadrupeds, which is important for a

  9. A universal scaling relationship between body mass and proximal limb bone dimensions in quadrupedal terrestrial tetrapods

    Directory of Open Access Journals (Sweden)

    Campione Nicolás E

    2012-07-01

    Full Text Available Abstract Background Body size is intimately related to the physiology and ecology of an organism. Therefore, accurate and consistent body mass estimates are essential for inferring numerous aspects of paleobiology in extinct taxa, and investigating large-scale evolutionary and ecological patterns in the history of life. Scaling relationships between skeletal measurements and body mass in birds and mammals are commonly used to predict body mass in extinct members of these crown clades, but the applicability of these models for predicting mass in more distantly related stem taxa, such as non-avian dinosaurs and non-mammalian synapsids, has been criticized on biomechanical grounds. Here we test the major criticisms of scaling methods for estimating body mass using an extensive dataset of mammalian and non-avian reptilian species derived from individual skeletons with live weights. Results Significant differences in the limb scaling of mammals and reptiles are noted in comparisons of limb proportions and limb length to body mass. Remarkably, however, the relationship between proximal (stylopodial limb bone circumference and body mass is highly conserved in extant terrestrial mammals and reptiles, in spite of their disparate limb postures, gaits, and phylogenetic histories. As a result, we are able to conclusively reject the main criticisms of scaling methods that question the applicability of a universal scaling equation for estimating body mass in distantly related taxa. Conclusions The conserved nature of the relationship between stylopodial circumference and body mass suggests that the minimum diaphyseal circumference of the major weight-bearing bones is only weakly influenced by the varied forces exerted on the limbs (that is, compression or torsion and most strongly related to the mass of the animal. Our results, therefore, provide a much-needed, robust, phylogenetically corrected framework for accurate and consistent estimation of body mass in

  10. CUDC-907 Promotes Bone Marrow Adipocytic Differentiation Through Inhibition of Histone Deacetylase and Regulation of Cell Cycle.

    Science.gov (United States)

    Ali, Dalia; Alshammari, Hassan; Vishnubalaji, Radhakrishnan; Chalisserry, Elna Paul; Hamam, Rimi; Alfayez, Musaad; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M

    2017-03-01

    The role of bone marrow adipocytes (BMAs) in overall energy metabolism and their effects on bone mass are currently areas of intensive investigation. BMAs differentiate from bone marrow stromal cells (BMSCs); however, the molecular mechanisms regulating BMA differentiation are not fully understood. In this study, we investigated the effect of CUDC-907, identified by screening an epigenetic small-molecule library, on adipocytic differentiation of human BMSCs (hBMSCs) and determined its molecular mechanism of action. Human bone marrow stromal cells exposed to CUDC-907 (500 nM) exhibited enhanced adipocytic differentiation (∼2.9-fold increase, P < 0.005) compared with that of control cells. Global gene expression and signaling pathway analyses of differentially expressed genes revealed a strong enrichment of genes involved in adipogenesis, cell cycle, and DNA replication. Chromatin immune precipitation combined with quantitative polymerase chain reaction showed significant increase in H3K9ac epigenetic marker in the promoter regions of AdipoQ, FABP4, PPARγ, KLF15, and CEBPA in CUDC-907-treated hBMSCs. Follow-up experiments corroborated that the inhibition of histone deacetylase (HDAC) activity enhanced adipocytic differentiation, while the inhibition of PI3K decreased adipocytic differentiation. In addition, CUDC-907 arrested hBMSCs in the G0-G1 phase of the cell cycle and reduced the number of S-phase cells. Our data reveal that HDAC, PI3K, and cell cycle genes are important regulators of BMA formation and demonstrate that adipocyte differentiation of hBMSCs is associated with complex changes in a number of epigenetic and genetic pathways, which can be targeted to regulate BMA formation.

  11. Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass, Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1.

    Science.gov (United States)

    Tsourdi, Elena; Rijntjes, Eddy; Köhrle, Josef; Hofbauer, Lorenz C; Rauner, Martina

    2015-10-01

    Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has been implicated in thyroid hormone-associated bone loss. Here we tested whether hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed decreased trabecular (-54%, P hyperthyroid mice and low bone turnover in hypothyroid mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (-24%, P hyperthyroid mice (+50%, P hyperthyroid (P hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone-induced changes in bone remodeling are associated with a divergent regulation of DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones may contribute to thyroid hormone-associated bone disease and altered expression of Wnt inhibitors may emerge as potential therapeutic targets.

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

    Science.gov (United States)

    Grubbe, M-C; Thomsen, J S; Nyengaard, J R; Duruox, M; Brüel, A

    2014-12-01

    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 limb. Sixty female Wistar rats, 14 weeks old, were divided into the following groups: baseline, controls, BTX, BTX+GH, and GH. GH was given at a dosage of 5 mg/kg/d for 4 weeks. Compared with controls, BTX resulted in lower periosteal bone formation rate (BFR/BS,-79%, Pbone mineral density (aBMD, -13%, Pbone volume (BV/TV, -26%, Pbone strength (-12%, Pbone 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-induced loss of periosteal BFR/BS at the mid-femur and rectus femoris muscle mass.

  13. Recovery of decreased bone mineral mass after lower-limb fractures in adolescents.

    Science.gov (United States)

    Ceroni, Dimitri; Martin, Xavier E; Delhumeau, Cécile; Farpour-Lambert, Nathalie J; De Coulon, Geraldo; Dubois-Ferrière, Victor; Rizzoli, René

    2013-06-05

    Loss of bone mineral mass, muscle atrophy, and functional limitations are predictable consequences of immobilization and subsequent weight-bearing restriction due to leg or ankle fractures. The aim of this study was to prospectively determine whether decreased bone mineral mass following lower-limb fractures recovers at follow-up durations of six and eighteen months in adolescents. In the present study, we included fifty adolescents who underwent cast immobilization for a leg or ankle fracture. Dual x-ray absorptiometry scans of four different sites (total hip, femoral neck, entire lower limb, and calcaneus) were performed at the time of the fracture, at cast removal, and at follow-ups of six and eighteen months. Patients with fractures were paired with healthy controls according to sex, age, and ethnicity. Dual x-ray absorptiometry values were compared between groups and between injured and non-injured legs in adolescents with fractures. Among those with fractures, lower-limb bone mineral variables were significantly lower at the injured side compared with the non-injured side at cast removal, with differences ranging from 6.2% to 31.7% (p < 0.0001). Similarly, injured adolescents had significantly lower bone mineral values at the level of the injured lower limb compared with healthy controls (p < 0.0001). At the six-month follow-up, there were still significant residual differences between injured and non-injured legs in adolescents with fractures (p < 0.0001). However, a significant residual difference between healthy controls and injured adolescents was present only for femoral neck bone mineral density (p = 0.011). At the eighteen-month follow-up, no significant difference was observed at any lower-limb site. Bone mineral loss following a fracture of the lower limb in adolescents is highly significant and affects the lower limb both proximal to and distal to the fracture site. In contrast to observations in adults, a rapid bone mass reversal occurs with full

  14. A soluble activin type IIA receptor mitigates the loss of femoral neck bone strength and cancellous bone mass in a mouse model of disuse osteopenia.

    Science.gov (United States)

    Lodberg, Andreas; Eijken, Marco; van der Eerden, Bram C J; Okkels, Mette Wendelboe; Thomsen, Jesper Skovhus; Brüel, Annemarie

    2018-05-01

    Disuse causes a rapid and substantial bone loss distinct in its pathophysiology from the bone loss associated with cancers, age, and menopause. While inhibitors of the activin-receptor signaling pathway (IASPs) have been shown to prevent ovariectomy- and cancer-induced bone loss, their application in a model of disuse osteopenia remains to be tested. Here, we show that a soluble activin type IIA receptor (ActRIIA-mFc) increases diaphyseal bone strength and cancellous bone mass, and mitigates the loss of femoral neck bone strength in the Botulinum Toxin A (BTX)-model of disuse osteopenia in female C57BL/6J mice. We show that ActRIIA-mFc treatment preferentially stimulates a dual-effect (anabolic-antiresorptive) on the periosteal envelope of diaphyseal bone, demonstrating in detail the effects of ActRIIA-mFc on cortical bone. These observations constitute a previously undescribed feature of IASPs that mediates at least part of their ability to mitigate detrimental effects of unloading on bone tissue. The study findings support the application of IASPs as a strategy to combat bone loss during disuse. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Effect of Raised Body Fat on Vitamin D, Leptin and Bone Mass

    International Nuclear Information System (INIS)

    Fatima, S. S.; Alam, F.

    2015-01-01

    Objectives: To estimate leptin, vitamin D and bone mineral density levels in individuals with high fat mass, and to assess any correlation. Methods: The cross-sectional study was conducted at the Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, and Aga Khan University, Karachi, from August 2012 to July 2014, and comprised healthy male volunteers between the ages of 18-60 years. Body fat percentage was determined using bioelectrical impedance analysis and the participants were classified as: Group A (15-21.9); Group B (22-27.9); and Group C (>28). Bone mineral density was calculated by ultrasound bone densitometer (T-score between +1 and -1 considered normal). Enzyme-linked immunosorbent assay kits were used to determine the levels of vitamin D and leptin. SPSS 19 was used for statistical analysis. Results: A total of 132 male subjects participated in this study, with each of the 3 groups having 44(33.3 percent). Despite all groups having low Vitamin D, a marked decrease was observed in group C compared to groups A and B (p <0.018). Bone mineral density T-score was <-1; total calcium was within normal range in all three groups. Serum leptin was raised in Group C compared to group A and B (p=0.03). Body fat percentage was negatively associated with vitamin D (p=0.004; r = -0.351), while it was positively correlated with leptin (p =0.038; r = 0.256). Conclusion: Excess of body fat percentage led to decreased vitamin D and raised leptin. However, bone mineral density and calcium levels were within normal range, suggesting that other factors might have played a role in maintaining bone mass in obese individuals, such as leptin. (author)

  16. X-ray dual energy spectral parameter optimization for bone Calcium/Phosphorus mass ratio estimation

    International Nuclear Information System (INIS)

    Sotiropoulou, P I; Martini, N D; Koukou, V N; Nikiforidis, G C; Fountos, G P; Michail, C M; Valais, I G; Kandarakis, I S

    2015-01-01

    Calcium (Ca) and Phosphorus (P) bone mass ratio has been identified as an important, yet underutilized, risk factor in osteoporosis diagnosis. The purpose of this simulation study is to investigate the use of effective or mean mass attenuation coefficient in Ca/P mass ratio estimation with the use of a dual-energy method. The investigation was based on the minimization of the accuracy of Ca/P ratio, with respect to the Coefficient of Variation of the ratio. Different set-ups were examined, based on the K-edge filtering technique and single X-ray exposure. The modified X-ray output was attenuated by various Ca/P mass ratios resulting in nine calibration points, while keeping constant the total bone thickness. The simulated data were obtained considering a photon counting energy discriminating detector. The standard deviation of the residuals was used to compare and evaluate the accuracy between the different dual energy set-ups. The optimum mass attenuation coefficient for the Ca/P mass ratio estimation was the effective coefficient in all the examined set-ups. The variation of the residuals between the different set-ups was not significant. (paper)

  17. 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.

  18. Reduced bone mass in Dutch adolescents fed a macrobiotic diet in early life.

    Science.gov (United States)

    Parsons, T J; van Dusseldorp, M; van der Vliet, M; van de Werken, K; Schaafsma, G; van Staveren, W A

    1997-09-01

    This study investigated the effect of a macrobiotic (vegan-type) diet, low in calcium and vitamin D, consumed in early life, on bone mineral during adolescence. Bone mineral content (BMC) and bone area were measured in 195 adolescents (103 girls, 92 boys) aged 9-15 years, using dual-energy X-ray absorptiometry. Ninety-three adolescents (43 girls, 50 boys) had followed a macrobiotic diet in childhood, and 102 (60 girls, 42 boys) were control subjects. After adjustment for bone area, weight, height, percent body lean, age, and puberty, BMC was significantly lower in macrobiotic subjects, in boys and girls, respectively, at the whole body, -3.4% and -2.5%, spine, -8.5% and -5.0%, femoral neck, -8.0% and -8.2%, midshaft radius, -6.8% and -5.6%, and also in girls, at the trochanter, -5.8% (p < 0.05). No group differences were observed at the wrist. Group differences were not explained by current calcium adjusted bone mass at age 9-15 years, observations which may hold important implications for fracture risk in later life.

  19. Fat Mass Is Positively Associated with Estimated Hip Bone Strength among Chinese Men Aged 50 Years and above with Low Levels of Lean Mass

    Directory of Open Access Journals (Sweden)

    Guiyuan Han

    2017-04-01

    Full Text Available This study investigated the relationships of fat mass (FM and lean mass (LM with estimated hip bone strength in Chinese men aged 50–80 years (median value: 62.0 years. A cross-sectional study including 889 men was conducted in Guangzhou, China. Body composition and hip bone parameters were generated by dual-energy X-ray absorptiometry (DXA. The relationships of the LM index (LMI and the FM index (FMI with bone phenotypes were detected by generalised additive models and multiple linear regression. The associations between the FMI and the bone variables in LMI tertiles were further analysed. The FMI possessed a linear relationship with greater estimated hip bone strength after adjustment for the potential confounders (p < 0.05. Linear relationships were also observed for the LMI with most bone phenotypes, except for the cross-sectional area (p < 0.05. The contribution of the LMI (4.0%–12.8% was greater than that of the FMI (2.0%–5.7%. The associations between the FMI and bone phenotypes became weaker after controlling for LMI. Further analyses showed that estimated bone strength ascended with FMI in the lowest LMI tertile (p < 0.05, but not in the subgroups with a higher LMI. This study suggested that LM played a critical role in bone health in middle-aged and elderly Chinese men, and that the maintenance of adequate FM could help to promote bone acquisition in relatively thin men.

  20. Identification of a dietary pattern prospectively associated with bone mass in Australian young adults.

    Science.gov (United States)

    van den Hooven, Edith H; Ambrosini, Gina L; Huang, Rae-Chi; Mountain, Jenny; Straker, Leon; Walsh, John P; Zhu, Kun; Oddy, Wendy H

    2015-11-01

    Relatively little is known about the relations between dietary patterns and bone health in adolescence, which is a period of substantial bone mass accrual. We derived dietary patterns that were hypothesized to be related to bone health on the basis of their protein, calcium, and potassium contents and investigated their prospective associations with bone mineral density (BMD), bone area, and bone mineral content (BMC) in a cohort of young adults. The study included 1024 young adults born to mothers who were participating in the Western Australian Pregnancy Cohort (Raine) Study. Dietary information was obtained from food-frequency questionnaires at 14 and 17 y of age. Dietary patterns were characterized according to protein, calcium, and potassium intakes with the use of reduced-rank regression. BMD, bone area, and BMC were estimated with the use of a total body dual-energy X-ray absorptiometry scan at 20 y of age. We identified 2 major dietary patterns. The first pattern was positively correlated with intakes of protein, calcium, and potassium and had high factor loadings for low-fat dairy products, whole grains, and vegetables. The second pattern was positively correlated with protein intake but negatively correlated with intakes of calcium and potassium and had high factor loadings for meat, poultry, fish, and eggs. After adjustment for anthropometric, sociodemographic, and lifestyle factors, a higher z score for the first pattern at 14 y of age was positively associated with BMD and BMC at 20 y of age [differences: 8.6 mg/cm(2) (95% CI: 3.0, 14.1 mg/cm(2)) and 21.9 g (95% CI: 6.5, 37.3 g), respectively, per SD increase in z score]. The z score for this same pattern at 17 y of age was not associated with bone outcomes at 20 y of age. The second pattern at 14 or 17 y of age was not associated with BMD, BMC, or bone area. A dietary pattern characterized by high intakes of protein, calcium, and potassium in midadolescence was associated with higher BMD and BMC at 20

  1. Practice and regulations of radiological mass screening in Italy

    International Nuclear Information System (INIS)

    Indovina, P.L.; Romagnoli, S.; Paganini Fioratti, M.

    1987-01-01

    The law setting up the National Health Service in Italy came into force in 1978. This law attributes many public health responsibilities to local government bodies, and these have also power to issue decrees and circulars with regulatory effect. It therefore proved difficult to obtain a complete picture of the regulations in the short time available. However, those laws, decrees and circulars have been traced which impose radiological examinations on individual members of the population as a condition of their carrying out particular activities in work or study. The statistical data on the total number of persons subjected to such examinations each year have been supplied by the Central Institute of Statistics (ISTAT). In some cases it has not been possible to trace any up-to-date statistics. We have understood the term 'mass radiological screening' in a rather wide sense, not as solely mass examination prescribed on the basis of specific regulations. It is for this reason that we have included in the analyses the scoliosis examinations advised by the authorities concerned in only some areas of Italy. For the same reason radiological examination of the dental apparatus has also been taken into consideration, since it is widespread among the population even though there are no regulations on the subject

  2. Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Vickram Tejwani

    2013-05-01

    Full Text Available The elderly chronic kidney disease (CKD population is growing. Both aging and CKD can disrupt calcium (Ca2+ homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD. CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD.

  3. Klotho expression in long bones regulates FGF23 production during renal failure.

    Science.gov (United States)

    Kaludjerovic, Jovana; Komaba, Hirotaka; Sato, Tadatoshi; Erben, Reinhold G; Baron, Roland; Olauson, Hannes; Larsson, Tobias E; Lanske, Beate

    2017-05-01

    Circulating levels of bone-derived fibroblast growth factor 23 (FGF23) increase early during acute and chronic kidney disease and are associated with adverse outcomes. Membrane-bound Klotho acts as a permissive coreceptor for FGF23, and its expression was recently found in osteoblasts/osteocytes. We hypothesized that Klotho in bone cells is part of an autocrine feedback loop that regulates FGF23 expression during renal failure. Thus, we induced renal failure in mice with targeted deletion of Klotho in long bones. Uremic wild-type ( KL fl/fl ) and knockout ( Prx1-Cre;KL fl/fl ) mice both responded with reduced body weight, kidney atrophy, hyperphosphatemia, and increased bone turnover. Importantly, long bones of Prx1-Cre;KL fl/fl mice but not their axial skeleton failed to increase FGF23 expression as observed in uremic KL fl/fl mice. Consequently, Prx1-Cre;KL fl/fl mice had significantly lower serum FGF23 and parathyroid hormone levels, and higher renal 1-α-hydroxylase expression, serum 1,25-dihydroxyvitamin D, and calcium levels than KL fl/fl mice. These results were confirmed in two independent models of renal failure, adenine diet induced and 5/6 nephrectomy. Moreover, FGF23-treated bone cells required Klotho to increase FGF23 mRNA and ERK phosphorylation. In summary, our novel findings show that Klotho in bone is crucial for inducing FGF23 production upon renal failure. We propose the presence of an autocrine feedback loop in which Klotho senses the need for FGF23.-Kaludjerovic, J., Komaba, H., Sato, T., Erben, R. G., Baron, R., Olauson, H., Larsson, T. E., Lanske, B. Klotho expression in long bones regulates FGF23 production during renal failure. © FASEB.

  4. Bioenergetics during calvarial osteoblast differentiation reflect strain differences in bone mass.

    Science.gov (United States)

    Guntur, Anyonya R; Le, Phuong T; Farber, Charles R; Rosen, Clifford J

    2014-05-01

    Osteoblastogenesis is the process by which mesenchymal stem cells differentiate into osteoblasts that synthesize collagen and mineralize matrix. The pace and magnitude of this process are determined by multiple genetic and environmental factors. Two inbred strains of mice, C3H/HeJ and C57BL/6J, exhibit differences in peak bone mass and bone formation. Although all the heritable factors that differ between these strains have not been elucidated, a recent F1 hybrid expression panel (C3H × B6) revealed major genotypic differences in osteoblastic genes related to cellular respiration and oxidative phosphorylation. Thus, we hypothesized that the metabolic rate of energy utilization by osteoblasts differed by strain and would ultimately contribute to differences in bone formation. In order to study the bioenergetic profile of osteoblasts, we measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) first in a preosteoblastic cell line MC3T3-E1C4 and subsequently in primary calvarial osteoblasts from C3H and B6 mice at days 7, 14, and 21 of differentiation. During osteoblast differentiation in media containing ascorbic acid and β-glycerophosphate, all 3 cell types increased their oxygen consumption and extracellular acidification rates compared with the same cells grown in regular media. These increases are sustained throughout differentiation. Importantly, C3H calvarial osteoblasts had greater oxygen consumption rates than B6 consistent with their in vivo phenotype of higher bone formation. Interestingly, osteoblasts utilized both oxidative phosphorylation and glycolysis during the differentiation process although mature osteoblasts were more dependent on glycolysis at the 21-day time point than oxidative phosphorylation. Thus, determinants of oxygen consumption reflect strain differences in bone mass and provide the first evidence that during collagen synthesis osteoblasts use both glycolysis and oxidative phosphorylation to synthesize and

  5. 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 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. Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  6. Handball Practice Enhances Bone Mass in Specific Sites Among Prepubescent Boys.

    Science.gov (United States)

    Missawi, Kawther; Zouch, Mohamed; Chakroun, Yosra; Chaari, Hamada; Tabka, Zouhair; Bouajina, Elyès

    2016-01-01

    This investigation's purpose is to focus on the effects of practicing handball for at least 2 yr on bone acquisition among prepubescent boys. One hundred prepubescent boys aged 10.68 ± 0.85 yr were divided into 2 groups: 50 handball players (HP group) and 50 controls (C group). Bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were evaluated by using dual-photon X-ray absorptiometry on the whole body, lumbar spine (L2-L4), legs, arms, femoral necks, hips and radiuses. Results showed greater values of BMD in both right and left femoral neck and total hip in handball players than in controls. In addition, handball players had higher values of legs and right total hip BMC than controls without any obvious variation of BA measurement in all sites between groups. All results of the paired t-test displayed an obviously marked variation of bone mass parameters between the left and right sides in the trained group without any marked variation among controls. Data showed an increased BMD of the supporting sites between the left and the right leg among handball players. However, "BMC" results exhibited higher values in the right than in the left total hip, and in the right total radius than in the left correspondent site. In addition, differences in the "BA" measurements were observed in the left total hip and in the right arm. Specific bone sites are markedly stimulated by handball training in prepubescent boys. Copyright © 2016 International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  7. An altered hormonal profile and elevated rate of bone loss are associated with low bone mass in professional horse-racing jockeys.

    Science.gov (United States)

    Dolan, Eimear; McGoldrick, Adrian; Davenport, Colin; Kelleher, Grainne; Byrne, Brendan; Tormey, William; Smith, Diarmuid; Warrington, Giles D

    2012-09-01

    Horse-racing jockeys are a group of weight-restricted athletes, who have been suggested as undertaking rapid and extreme weight cycling practices in order to comply with stipulated body-mass standards. The aim of this study was to examine bone mass, turnover and endocrine function in jockeys and to compare this group with age, gender and body mass index matched controls. Twenty male professional jockeys and 20 healthy male controls participated. Dual energy X-ray absorptiometry scans and early morning fasting blood and urine samples were used to measure bone mass, turnover and a hormonal profile. Total body bone mineral density (BMD) was significantly lower in jockeys (1.143 ± 0.05 vs. 1.27 ± 0.06 g cm(-3), p professional jockeys have an elevated rate of bone loss and reduced bone mass that appears to be associated with disrupted hormonal activity. It is likely that this may have occurred in response to the chronic weight cycling habitually experienced by this group.

  8. Bone mass in Indian children--relationships to maternal nutritional status and diet during pregnancy: the Pune Maternal Nutrition Study.

    Science.gov (United States)

    Ganpule, A; Yajnik, C S; Fall, C H D; Rao, S; Fisher, D J; Kanade, A; Cooper, C; Naik, S; Joshi, N; Lubree, H; Deshpande, V; Joglekar, C

    2006-08-01

    Bone mass is influenced by genetic and environmental factors. Recent studies have highlighted associations between maternal nutritional status during pregnancy and bone mass in the offspring. We hypothesized that maternal calcium intakes and circulating micronutrients during pregnancy are related to bone mass in Indian children. DESIGN/SETTING/PARTICIPANTS/MAIN OUTCOME MEASURES: Nutritional status was measured at 18 and 28 wk gestation in 797 pregnant rural Indian women. Measurements included anthropometry, dietary intakes (24-h recall and food frequency questionnaire), physical workload (questionnaire), and circulating micronutrients (red cell folate and plasma ferritin, vitamin B12, and vitamin C). Six years postnatally, total body and total spine bone mineral content and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA) in the children (n = 698 of 762 live births) and both parents. Both parents' DXA measurements were positively correlated with the equivalent measurements in the children (P pregnancy (milk, milk products, pulses, non-vegetarian foods, green leafy vegetables, fruit) had higher total and spine bone mineral content and BMD, and children of mothers with higher folate status at 28 wk gestation had higher total and spine BMD, independent of parental size and DXA measurements. Modifiable maternal nutritional factors may influence bone health in the offspring. Fathers play a role in determining their child's bone mass, possibly through genetic mechanisms or through shared environment.

  9. Exercise and Regulation of Bone and Collagen Tissue Biology.

    Science.gov (United States)

    Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja; Magnusson, S Peter

    2015-01-01

    The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensuring force transmission, storing energy, protecting joint surface and stability, and ensuring the transfer of muscular forces into resulting limb movement. The musculoskeletal connective tissue structure is relatively stable, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the connective tissue, its size, its strength, and its mechanical properties, whereby it can improve its capacity by 5-20% with regular physical activity. For several of the mechanically loaded connective tissues, only limited information regarding molecular and cellular signaling pathways and their adaptation to exercise is available. In contrast to tissue responses with exercise, lack of mechanical tissue loading through inactivity or immobilization of the human body will result in a dramatic loss of connective tissue content, structure, and tolerable load within weeks, to a degree (30-40%) that mimics that of contractile skeletal musculature. This illustrates the importance of regular mechanical load in order to preserve the stabilizing role of the connective tissue for the overall function of the musculoskeletal system in both daily activity and exercise. © 2015 Elsevier Inc. All rights reserved.

  10. '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

  11. Association between circulating levels of adiponectin and indices of bone mass and bone metabolism in middle-aged post-menopausal women.

    Science.gov (United States)

    Tenta, R; Kontogianni, M D; Yiannakouris, N

    2012-03-01

    Adiponectin, a fat derived cytokine, is a potential independent contributor to bone mineral density (BMD); however, its action on bone metabolism in humans is still unclear. The aim of this study was to investigate the relationship of adiponectin with bone mass indices and bone metabolic markers in middle-aged post-menopausal women without diabetes. A random sample consisted of 81 post-menopausal women (age range 45-61 yr, osteopenic/osteoporotic no.=43) was studied. Lumbar-spine BMD (BMD(L2-L4)) and total-body bone mineral content (TBBMC) were measured with dual X-ray absorptiometry. Plasma levels of total and high-molecular weight (HMW) adiponectin, osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and IGF-I were determined. No association was observed between total or HMW adiponectin and BMD(L2-L4) or TBBMC. On the contrary, adiponectin levels were positively associated with OPG levels (partial r=0.276, p=0.015) and negatively with IGF-I (partial r=-0.438, pfailed to show statistically significant association between circulating adiponectin levels and indices of bone mass in women during the postmenopausal period, we showed significant associations with OPG and IGF-I levels, suggesting an anabolic role of adiponectin, which may contribute in the understanding of the interplay between adipose tissue-derived hormones and bone metabolism. © 2012, Editrice Kurtis.

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

    International Nuclear Information System (INIS)

    Lim-Abrahan, M.A.; Guanzon, L.V.; Guzman, A.M. de; Villaruel, C.M.; Santos, F.

    1998-01-01

    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 L 2 L 4 level for females was 1.12±0.11 g/cm 2 and 0.91±0.11 g/cm 2 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

  13. Maternal dietary patterns during pregnancy and childhood bone mass: a longitudinal study.

    Science.gov (United States)

    Cole, Zoe A; Gale, Catharine R; Javaid, M Kassim; Robinson, Sian M; Law, Catherine; Boucher, Barbara J; Crozier, Sarah R; Godfrey, Keith M; Dennison, Elaine M; Cooper, Cyrus

    2009-04-01

    Maternal nutrition is a potentially important determinant of intrauterine skeletal development. Previous studies have examined the effects of individual nutrients, but the pattern of food consumption may be of greater relevance. We therefore examined the relationship between maternal dietary pattern during pregnancy and bone mass of the offspring at 9 yr of age. We studied 198 pregnant women 17-43 yr of age and their offspring at 9 yr of age. Dietary pattern was assessed using principal component analysis from a validated food frequency questionnaire. The offspring underwent measurements of bone mass using DXA at 9 yr of age. A high prudent diet score was characterized by elevated intakes of fruit, vegetables, and wholemeal bread, rice, and pasta and low intakes of processed foods. Higher prudent diet score in late pregnancy was associated with greater (p socioeconomic status, height, arm circumference, maternal smoking, and vitamin D status. Associations with prudent diet score in early pregnancy were weaker and nonsignificant. We conclude that dietary patterns consistent with current advice for healthy eating during pregnancy are associated with greater bone size and BMD in the offspring at 9 yr of age.

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

    International Nuclear Information System (INIS)

    Al-Elq, Abdulmohsen H.; Sultan, Osama A.; Al-Turki, Haifa A.; Sadat-Ali, M.

    2008-01-01

    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)

  15. β3-Adrenergic Regulation of EPC Features Through Manipulation of the Bone Marrow MSC Niche.

    Science.gov (United States)

    Vafaei, Rana; Nassiri, Seyed Mahdi; Siavashi, Vahid

    2017-12-01

    Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow, however, biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3-adrenergic signals will affect EPC features. A selective β3 agonist (BRL37344) or a β3 antagonist (SR59230A) was administered in mice for 2 weeks to determine the potential effects of these regimens on the population of CD133 + stem cells in the bone marrow. Then, bone marrow-derived MSCs and EPCs were harvested and expanded from the mice to examine the effect of changes in the MSC niche on EPC features. Improved MSC colony forming potency with increased bone marrow stromal cell-derived factor 1 (SDF-1) (also known as C-X-C motif chemokine 12 [CXCL12]) expression was shown as a result of intensification of the bone marrow adrenergic signals through BRL37344 injection. On the other hand, the blockage of these signals limited the expression level of SDF-1 and resulted in bone marrow enrichment of CD133 + cells. Manipulation of the MSC niche and decreased SDF-1 expression via SR59230A injection also prompted EPCs to form more colonies with augmented proliferation and differentiation capacity. Overall, our results indicate that the β3-adrenergic signals regulate the MSC niche, thereby resulting in modulation of EPC biological features. J. Cell. Biochem. 118: 4753-4761, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Functions and Epigenetic Regulation of Wwox in Bone Metastasis from Breast Carcinoma: Comparison with Primary Tumors

    Directory of Open Access Journals (Sweden)

    Paola Maroni

    2017-01-01

    Full Text Available Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox. The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1 affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma. In hypoxic-bone metastatic cells, Wwox enhances HIF-1α stabilization, phosphorylation, and nuclear translocation. Consistently, in bone-metastasis specimens Wwox localizes in cytosolic/perinuclear area, while TAZ (transcriptional co-activator with PDZ-binding motif and HIF-1α co-localize in nuclei, playing specific regulatory mechanisms: TAZ is a co-factor of HIF-1, and Wwox regulates HIF-1 activity by controlling HIF-1α. In vitro, DNA methylation affects Wwox-protein synthesis; hypoxia decreases Wwox-protein level; hepatocyte growth factor (HGF phosphorylates Wwox driving its nuclear shuttle, and counteracting a Twist program important for the epithelial phenotype and metastasis colonization. In agreement, in 1833-xenograft mice under DNA-methyltransferase blockade with decitabine, Wwox increases in nuclei/cytosol counteracting bone metastasis with prolongation of the survival. However, Wwox seems relevant for the autophagic process which sustains metastasis, enhancing more Beclin-1 than p62 protein levels, and p62 accumulates under decitabine consistent with adaptability of metastasis to therapy. In conclusion, Wwox methylation as a bone-metastasis therapeutic target would depend on autophagy conditions, and epigenetic mechanisms regulating Wwox may influence the phenotype of bone metastasis.

  17. Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jun-Oh; Lee, Yong Deok; Kim, Haemin; Kim, Min Kyung; Song, Min-Kyoung; Lee, Zang Hee; Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr

    2016-09-02

    Tetraspanin family proteins regulate morphology, motility, fusion, and signaling in various cell types. We investigated the role of the tetraspanin 7 (Tspan7) isoform in the differentiation and function of osteoclasts. Tspan7 was up-regulated during osteoclastogenesis. When Tspan7 expression was reduced in primary precursor cells by siRNA-mediated gene knock-down, the generation of multinuclear osteoclasts was not affected. However, a striking cytoskeletal abnormality was observed: the formation of the podosome belt structure was inhibited and the microtubular network were disrupted by Tspan7 knock-down. Decreases in acetylated microtubules and levels of phosphorylated Src and Pyk2 in Tspan7 knock-down cells supported the involvement of Tspan7 in cytoskeletal rearrangement signaling in osteoclasts. This cytoskeletal defect interfered with sealing zone formation and subsequently the bone-resorbing activity of mature osteoclasts on dentin surfaces. Our results suggest that Tspan7 plays an important role in cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules. - Highlights: • Tspan7 expression is up-regulated during osteoclastogenesis. • Tspan7 regulates podosome belt organization in osteoclasts. • Tspan7 is crucial for sealing zone formation and bone-resorption by osteoclasts. • Src and Pyk2 phosphorylation and microtubule acetylation mediate Tspan7 function.

  18. Epigenetic regulation of fetal bone development and placental transfer of nutrients: progress for osteoporosis.

    Science.gov (United States)

    Bocheva, Georgeta; Boyadjieva, Nadka

    2011-12-01

    Osteoporosis is a common age-related disorder and causes acute and long-term disability and economic cost. Many factors influence the accumulation of bone minerals, including heredity, diet, physical activity, gender, endocrine functions, and risk factors such as alcohol, drug abuse, some pharmacological drugs or cigarette smoking. The pathology of bone development during intrauterine life is a factor for osteoporosis. Moreover, the placental transfer of nutrients plays an important role in the building of bones of fetuses. The importance of maternal calcium intake and vitamin D status are highlighted in this review. Various environmental factors including nutrition state or maternal stress may affect the epigenetic state of a number of genes during fetal development of bones. Histone modifications as histone hypomethylation, histone hypermethylation, hypoacetylation, etc. are involved in chromatin remodeling, known to contribute to the epigenetic landscape of chromosomes, and play roles in both fetal bone development and osteoporosis. This review will give an overview of epigenetic modulation of bone development and placental transfer of nutrients. In addition, the data from animal and human studies support the role of epigenetic modulation of calcium and vitamin D in the pathogenesis of osteoporosis. We review the evidence suggesting that various genes are involved in regulation of osteoclast formation and differentiation by osteoblasts and stem cells. Epigenetic changes in growth factors as well as cytokines play a rol in fetal bone development. On balance, the data suggest that there is a link between epigenetic changes in placental transfer of nutrients, including calcium and vitamin D, abnormal intrauterine bone development and pathogenesis of osteoporosis.

  19. Relationship of total body fat mass to weight-bearing bone volumetric density, geometry, and strength in young girls.

    Science.gov (United States)

    Farr, Joshua N; Chen, Zhao; Lisse, Jeffrey R; Lohman, Timothy G; Going, Scott B

    2010-04-01

    Understanding the influence of total body fat mass (TBFM) on bone during the peri-pubertal years is critical for the development of future interventions aimed at improving bone strength and reducing fracture risk. Thus, we evaluated the relationship of TBFM to volumetric bone mineral density (vBMD), geometry, and strength at metaphyseal and diaphyseal sites of the femur and tibia of young girls. Data from 396 girls aged 8-13 years from the "Jump-In: Building Better Bones" study were analyzed. Bone parameters were assessed using peripheral quantitative computed tomography (pQCT) at the 4% and 20% distal femur and 4% and 66% distal tibia of the non-dominant leg. Bone parameters at the 4% sites included trabecular vBMD, periosteal circumference, and bone strength index (BSI), while at the 20% femur and 66% tibia, parameters included cortical vBMD, periosteal circumference, and strength-strain index (SSI). Multiple linear regression analyses were used to assess associations between bone parameters and TBFM, controlling for muscle cross-sectional area (MCSA). Regression analyses were then repeated with maturity, bone length, physical activity, and ethnicity as additional covariates. Analysis of covariance (ANCOVA) was used to compare bone parameters among tertiles of TBFM. In regression models with TBFM and MCSA, associations between TBFM and bone parameters at all sites were not significant. TBFM explained very little variance in all bone parameters (0.2-2.3%). In contrast, MCSA was strongly related (p<0.001) to all bone parameters, except cortical vBMD. The addition of maturity, bone length, physical activity, and ethnicity did not alter the relationship between TBFM and bone parameters. With bone parameters expressed relative to total body mass, ANCOVA showed that all outcomes were significantly (p<0.001) greater in the lowest compared to the middle and highest tertiles of TBFM. Although TBFM is correlated with femur and tibia vBMD, periosteal circumference, and

  20. High fluoride and low calcium levels in drinking water is associated with low bone mass, reduced bone quality and fragility fractures in sheep.

    Science.gov (United States)

    Simon, M J K; Beil, F T; Rüther, W; Busse, B; Koehne, T; Steiner, M; Pogoda, P; Ignatius, A; Amling, M; Oheim, R

    2014-07-01

    Chronic environmental fluoride exposure under calcium stress causes fragility fractures due to osteoporosis and bone quality deterioration, at least in sheep. Proof of skeletal fluorosis, presenting without increased bone density, calls for a review of fracture incidence in areas with fluoridated groundwater, including an analysis of patients with low bone mass. Understanding the skeletal effects of environmental fluoride exposure especially under calcium stress remains an unmet need of critical importance. Therefore, we studied the skeletal phenotype of sheep chronically exposed to highly fluoridated water in the Kalahari Desert, where livestock is known to present with fragility fractures. Dorper ewes from two flocks in Namibia were studied. Chemical analyses of water, blood and urine were executed for both cohorts. Skeletal phenotyping comprised micro-computer tomography (μCT), histological, histomorphometric, biomechanical, quantitative backscattered electron imaging (qBEI) and energy-dispersive X-ray (EDX) analysis. Analysis was performed in direct comparison with undecalcified human iliac crest bone biopsies of patients with fluoride-induced osteopathy. The fluoride content of water, blood and urine was significantly elevated in the Kalahari group compared to the control. Surprisingly, a significant decrease in both cortical and trabecular bones was found in sheep chronically exposed to fluoride. Furthermore, osteoid parameters and the degree and heterogeneity of mineralization were increased. The latter findings are reminiscent of those found in osteoporotic patients with treatment-induced fluorosis. Mechanical testing revealed a significant decrease in the bending strength, concurrent with the clinical observation of fragility fractures in sheep within an area of environmental fluoride exposure. Our data suggest that fluoride exposure with concomitant calcium deficit (i) may aggravate bone loss via reductions in mineralized trabecular and cortical bone

  1. Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links.

    Science.gov (United States)

    Pardini, D P; Sabino, A T; Meneses, A M; Kasamatsu, T; Vieira, J G

    2000-01-06

    The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. Cohort correlational study. Academic referral center. 53 post-menopausal women, aged 48-58 years. Urinary pyr and d-pyr were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion measured before treatment and after 1, 2, 4 and 12 months. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DEXA) before treatment and after 12 months of HRT. The BMD after HRT was about 4.7% (P < 0.0004); 2% (P < 0.002); and 3% (P < 0. 01) higher than the basal values in lumbar spine, neck and trochanter respectively. There were no significant correlations between pyridinium cross-links and age, weight, menopause duration and BMD. The decrease in pyr and d-pyr was progressive after HRT, reaching 28.9% (P < 0.0002), and 42% (P < 0.0002) respectively after 1 year. Urinary pyridinoline and deoxypyridinoline excretion decreases early in hormone replacement therapy, reflecting a decrease in the bone resorption rate, and no correlation was observed with the bone mass evaluated by densitometry.

  2. 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

    , consisting of four weekly 60-90 min sessions with mean heart rate > 80%HRmax [football group (FG)]. A control group (CG) included eight boys of equivalent age from an obesity clinic located in the same area as the school. Both groups participated in two sessions of 45-90 min physical education per week......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...... at school. Bone mass indicators included whole-boy and lumbar spine bone mineral density (BMD) and bone mineral content (BMC). Physical fitness tests included 5- and 30-m sprints, countermovement jump (CMJ), and Yo-Yo intermittent endurance test level 1 (Yo-Yo IE1). Body composition was evaluated using dual...

  3. 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.

  4. Prevalence of Osteoporosis and Low Bone Mass Among Puerto Rican Older Adults

    Science.gov (United States)

    Noel, Sabrina E; Mangano, Kelsey M; Griffith, John L; Wright, Nicole C; Dawson-Hughes, Bess; Tucker, Katherine L

    2018-01-01

    Historically, osteoporosis has not been considered a public health priority for the Hispanic population. However, recent data indicate that Mexican Americans are at increased risk for this chronic condition. Although it is well established that there is heterogeneity in social, lifestyle, and health-related factors among Hispanic subgroups, there are currently few studies on bone health among Hispanic subgroups other than Mexican Americans. The current study aimed to determine the prevalence of osteoporosis and low bone mass (LBM) among 953 Puerto Rican adults, aged 47 to 79 years and living on the US mainland, using data from one of the largest cohorts on bone health in this population: The Boston Puerto Rican Osteoporosis Study (BPROS). Participants completed an interview to assess demographic and lifestyle characteristics and bone mineral density measures. To facilitate comparisons with national data, we calculated age-adjusted estimates for osteoporosis and LBM for Mexican American, non-Hispanic white, and non-Hispanic black adults, aged ≥50 years, from the National Health and Nutrition Examination Survey (NHANES). The overall prevalence of osteoporosis and LBM were 10.5% and 43.3% for participants in the BPROS, respectively. For men, the highest prevalence of osteoporosis was among those aged 50 to 59 years (11%) and lowest for men ≥70 years (3.7%). The age-adjusted prevalence of osteoporosis for Puerto Rican men was 8.6%, compared with 2.3% for non-Hispanic white, and 3.9% for Mexican American men. There were no statistically significant differences between age-adjusted estimates for Puerto Rican women (10.7%), non-Hispanic white women (10.1%), or Mexican American women (16%). There is a need to understand specific factors contributing to osteoporosis in Puerto Rican adults, particularly younger men. This will provide important information to guide the development of culturally and linguistically tailored interventions to improve bone health in this

  5. Muscle strength and regional lean body mass influence on mineral bone health in young male adults.

    Science.gov (United States)

    Guimarães, Bianca Rosa; Pimenta, Luciana Duarte; Massini, Danilo Alexandre; Dos Santos, Daniel; Siqueira, Leandro Oliveira da Cruz; Simionato, Astor Reis; Dos Santos, Luiz Gustavo Almeida; Neiva, Cassiano Merussi; Pessôa Filho, Dalton Muller

    2018-01-01

    The relationship between muscle strength and bone mineral content (BMC) and bone mineral density (BMD) is supposed from the assumption of the mechanical stress influence on bone tissue metabolism. However, the direct relationship is not well established in younger men, since the enhancement of force able to produce effective changes in bone health, still needs to be further studied. This study aimed to analyze the influence of muscle strength on BMC and BMD in undergraduate students. Thirty six men (24.9 ± 8.6 y/o) were evaluated for regional and whole-body composition by dual energy X-ray absorptiometry (DXA). One repetition maximum tests (1RM) were assessed on flat bench-press (BP), lat-pull down (LPD), leg-curl (LC), knee extension (KE), and leg-press 45° (LP45) exercises. Linear regression modelled the relationships of BMD and BMC to the regional body composition and 1RM values. Measurements of dispersion and error (R2adj and standard error of estimate (SEE)) were tested, setting ρ at ≤0.05. The BMD mean value for whole-body was 1.12±0.09 g/cm2 and BMC attained 2477.9 ± 379.2 g. The regional lean mass (LM) in upper-limbs (UL) (= 6.80±1.21 kg) was related to BMC and BMD for UL (R2adj = 0.74, pBMC and BMD for LL (R2adj = 0.68, pBMC (R2adj = 0.47, pBMC (R2adj = 0.36, pBMC and BMD in young men, strengthening the relationship between force and LM, and suggesting both to parametrizes bone mineral health.

  6. Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women

    DEFF Research Database (Denmark)

    Jensen, L B; Vestergaard, P; Hermann, A P

    2003-01-01

    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 strongest predictor...... of bone changes in untreated women, whereas the change in lean body mass was the strongest predictor when HRT was given. Body weight increases after the menopause. The gain in weight is related to a decrease in working capacity. HRT is associated with a smaller increase in fat mass after menopause. Fat...

  7. 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

  8. The Regulation of Muscle Mass by Endogenous Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Daniel L Marks

    2015-02-01

    Full Text Available Glucocorticoids are highly conserved fundamental regulators of energy homeostasis. In response to stress in the form of perceived danger or acute inflammation, glucocorticoids are released from the adrenal gland, rapidly mobilizing energy from carbohydrate, fat and protein stores. In the case of inflammation, mobilized protein is critical for the rapid synthesis of acute phase reactants and an efficient immune response to infection. While adaptive in response to infection, chronic mobilization can lead to a p rofound depletion of energy stores. Skeletal muscle represents the major body store of protein, and can become substantially atrophied under conditions of chronic inflammation. Glucocorticoids elicit the atrophy of muscle by increasing the rate of protein degradation by the ubiquitin-proteasome system and autophagy lysosome system. Protein synthesis is also suppressed at the level of translational initiation, preventing the production of new myofibrillar protein. Glucocorticoids also antagonize the action of anabolic regulators such as insulin further exacerbating the loss of protein and muscle mass. The loss of muscle mass in the context of chronic disease is a key feature of cachexia and contributes substantially to morbidity and mortality. A growing body of evidence demonstrates that glucocorticoid signaling is a common mediator of wasting, irrespective of the underlying initiator or disease state. This review will highlight fundamental mechanisms of glucocorticoid signaling and detail the mechanisms of glucocorticoid-induced muscle atrophy. Additionally, the evidence for glucocorticoids as a driver of muscle wasting in numerous disease states will be discussed. Given the burden of wasting diseases and the nodal nature of glucocorticoid signaling, effective anti-glucocorticoid therapy would be a valuable clinical tool. Therefore, the progress and potential pitfalls in the development of glucocorticoid antagonists for muscle wasting will

  9. The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults

    Science.gov (United States)

    Kerstetter, Jane E.; Brindisi, Jennifer; Sullivan, Rebecca R.; Mangano, Kelsey M.; Larocque, Sarah; Kotler, Belinda M.; Simpson, Christine A.; Cusano, Anna Maria; Gaffney-Stomberg, Erin; Kleppinger, Alison; Reynolds, Jesse; Dziura, James; Kenny, Anne M.; Insogna, Karl L.

    2015-01-01

    Context: It has been assumed that the increase in urine calcium (Ca) that accompanies an increase in dietary protein was due to increased bone resorption. However, studies using stable Ca isotopes have found that dietary protein increases Ca absorption without increasing bone resorption. Objective: The objective of the study was to investigate the impact of a moderately high protein diet on bone mineral density (BMD). Design: This was a randomized, double-blind, placebo-controlled trial of protein supplementation daily for 18 months. Setting: The study was conducted at two institutional research centers. Participants: Two hundred eight older women and men with a body mass index between 19 and 32 kg/m2 and a self-reported protein intake between 0.6 and 1.0 g/kg participated in the study. Intervention: Subjects were asked to incorporate either a 45-g whey protein or isocaloric maltodextrin supplement into their usual diet for 18 months. Main Outcome Measure: BMD by dual-energy x-ray absorptiometry, body composition, and markers of skeletal and mineral metabolism were measured at baseline and at 9 and 18 months. Results: There were no significant differences between groups for changes in L-spine BMD (primary outcome) or the other skeletal sites of interest. Truncal lean mass was significantly higher in the protein group at 18 months (P = .048). C-terminal telopeptide (P = .0414), IGF-1 (P = .0054), and urinary urea (P < .001) were also higher in the protein group at the end of the study period. There was no difference in estimated glomerular filtration rate at 18 months. Conclusion: Our data suggest that protein supplementation above the recommended dietary allowance (0.8 g/kg) may preserve fat-free mass without adversely affecting skeletal health or renal function in healthy older adults. PMID:25844619

  10. Effects of Denosumab and Calcitriol on Severe Secondary Hyperparathyroidism in Dialysis Patients With Low Bone Mass.

    Science.gov (United States)

    Chen, Chien-Liang; Chen, Nai-Ching; Liang, Huei-Lung; Hsu, Chih-Yang; Chou, Kang-Ju; Fang, Hua-Chang; Lee, Po-Tsang

    2015-07-01

    Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal failure patients with low bone mass. This study aimed to evaluate the short-term effect of coadministration of calcitriol and denosumab on PTH secretion and parathyroid structure and the incidence of adverse effects in patients with SHPT and low bone mass. This was a 24-week, open-label study at Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan. Dialysis patients with SHPT (intact parathyroid hormone [iPTH] > 800 pg/mL) and low bone mass (T score < -2.5) were enrolled. Patients received denosumab (60 mg) and doses of calcitriol adjusted to achieve iPTH < 300 pg/mL. Parathyroid gland volume was assessed upon study initiation and completion. Serum calcium, phosphate, alkaline phosphatase, iPTH, and adverse effects were assessed at each visit (Day 7, 14, and 21, and every month thereafter). iPTH significantly decreased (mean decrease, 58.28 ± 6.12%) with denosumab/calcitriol administration (P < .01) but not in the controls (patients not receiving denosumab). Parathyroid gland volume decreased (mean decrease, 21.98 ± 5.54%) with denosumab/calcitriol administration (P < .01) and progressively increased (20.58 ± 4.48%) in the controls (P < .05). Serum alkaline phosphatase and iPTH levels were significantly correlated to decreased iPTH and regression of parathyroid hyperplasia (P < .05). The most common adverse events were hypocalcemia (33.33%) and respiratory tract infection (4.17%). Hypocalcemia rapidly resolved with calcium and calcitriol supplements. Denosumab allows for supra-physiologic doses of calcitriol resulting in decreased parathyroid secretion and parathyroid hyperplasia. Supervised administration and weekly laboratory and clinical monitoring of serum calcium are recommended during the first month to prevent hypocalcemia.

  11. Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

    Science.gov (United States)

    Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

    2011-12-01

    Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

  12. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R

    2007-01-01

    PAR and produce urokinase (uPA). The purpose of this study was to investigate the role of uPAR in bone remodeling. MATERIALS AND METHODS: In vivo studies were performed in uPAR knockout (KO) and wildtype (WT) mice on a C57Bl6/SV129 (75:25) background. Bone mass was analyzed by pQCT. Excised tibias were subjected......The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts. Their function in bone remodeling is unknown. We report that uPAR-lacking mice display increased BMD, increased osteogenic potential of osteoblasts, decreased osteoclasts formation, and altered cytoskeletal...... of macrophage-colony stimulating factor (M-CSF) and RANKL. Phalloidin staining in osteoclasts served to study actin ring and podosome formation. RESULTS: pQCT revealed increased bone mass in uPAR-null mice. Mechanical tests showed reduced load-sustaining capability in uPAR KO tibias. uPAR KO osteoblasts showed...

  13. A well-balanced diet combined or not with exercise induces fat mass loss without any decrease of bone mass despite bone micro-architecture alterations in obese rat.

    Science.gov (United States)

    Gerbaix, Maude; Metz, Lore; Mac-Way, Fabrice; Lavet, Cédric; Guillet, Christelle; Walrand, Stéphane; Masgrau, Aurélie; Vico, Laurence; Courteix, Daniel

    2013-04-01

    The association of a well-balanced diet with exercise is a key strategy to treat obesity. However, weight loss is linked to an accelerated bone loss. Furthermore, exercise is known to induce beneficial effects on bone. We investigated the impact of a well-balanced isoenergetic reducing diet (WBR) and exercise on bone tissue in obese rats. Sixty male rats had previously been fed with a high fat/high sucrose diet (HF/HS) for 4months to induce obesity. Then, 4 regimens were initiated for 2months: HF/HS diet plus exercise (treadmill: 50min/day, 5days/week), WBR diet plus exercise, HF/HS diet plus inactivity and WBR diet plus inactivity. Body composition and total BMD were assessed using DXA and visceral fat mass was weighed. Tibia densitometry was assessed by Piximus. Bone histomorphometry was performed on the proximal metaphysis of tibia and on L2 vertebrae (L2). Trabecular micro-architectural parameters were measured on tibia and L2 by 3D microtomography. Plasma concentration of osteocalcin and CTX were measured. Both WBR diet and exercise had decreased global weight, global fat and visceral fat mass (pdiet alone failed to alter total and tibia bone mass and BMD. However, Tb.Th, bone volume density and degree of anisotropy of tibia were decreased by the WBR diet (pdiet had involved a significant lower MS/BS and BFR/BS in L2 (pdiet inducing weight and fat mass losses did not affected bone mass and BMD of obese rats despite alterations of their bone micro-architecture. The moderate intensity exercise performed had improved the tibia BMD of obese rats without any trabecular and cortical adaptation. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

    International Nuclear Information System (INIS)

    Brady, Robert T.; O'Brien, Fergal J.; Hoey, David A.

    2015-01-01

    Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

  15. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Brady, Robert T. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); O' Brien, Fergal J. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Hoey, David A., E-mail: david.hoey@ul.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); The Centre for Applied Biomedical Engineering Research, University of Limerick (Ireland); Materials & Surface Science Institute, University of Limerick (Ireland)

    2015-03-27

    Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

  16. Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration.

    Science.gov (United States)

    Aquino-Martínez, Rubén; Angelo, Alcira P; Pujol, Francesc Ventura

    2017-11-16

    Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC) recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca 2+ -containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO 4 ) on MSC migration. In addition, to evaluate the influence of CaSO 4 on MSC differentiation and the potential molecular mechanisms involved. A circular calvarial bone defect (5 mm diameter) was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO 4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO 4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO 4 treatment was also evaluated by qPCR. CaSO 4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO 4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO 4 -containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO 4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO 4 effects on MSC migration. Specific CaSO 4 concentrations induce bone regeneration of calvarial defects in part by acting on the host's undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO 4 regulates BMP-2-induced MSC migration by differentially activating the PI3

  17. Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration

    Directory of Open Access Journals (Sweden)

    Rubén Aquino-Martínez

    2017-11-01

    Full Text Available Abstract Background Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca2+-containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO4 on MSC migration. In addition, to evaluate the influence of CaSO4 on MSC differentiation and the potential molecular mechanisms involved. Methods A circular calvarial bone defect (5 mm diameter was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO4 treatment was also evaluated by qPCR. Results CaSO4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO4-containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO4 effects on MSC migration. Conclusions Specific CaSO4 concentrations induce bone regeneration of calvarial defects in part by acting on the host’s undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO4 regulates BMP-2-induced

  18. E-cadherin and beta-catenin are down-regulated in prostatic bone metastases.

    Science.gov (United States)

    Bryden, A A G; Hoyland, J A; Freemont, A J; Clarke, N W; Schembri Wismayer, D; George, N J R

    2002-03-01

    To determine the E-cadherin and beta-catenin expression phenotype in untreated primary prostate cancer and corresponding bone metastases. Paired bone metastasis and primary prostate specimens were obtained from 14 men with untreated metastatic prostate carcinoma. The tumours were histologically graded by an independent pathologist. Expression of mRNA for E-cadherin and beta-catenin was detected within the tumour cells using in-situ hybridization with a 35S-labelled cDNA probe. The expression of E-cadherin and beta-catenin were graded as uniform, heterogeneous or negative. The mRNA for E-cadherin was expressed in 13 of 14 primary carcinomas and 11 bone metastases; beta-catenin was expressed by 13 and nine, respectively. Of the primary tumours, nine expressed E-cadherin and beta-catenin uniformly; in contrast, all metastases had down-regulated E-cadherin and/or beta-catenin. The down-regulation of E-cadherin and beta-catenin are a feature of the metastatic phenotype, which may be a significant factor in the genesis of bone metastases. However, this does not appear to be reflected in the expression of these molecules in the primary tumours.

  19. Identification of genes differentially regulated in rat alveolar bone wound healing by subtractive hybridization.

    Science.gov (United States)

    Ohira, T; Myokai, F; Shiomi, N; Yamashiro, K; Yamamoto, T; Murayama, Y; Arai, H; Nishimura, F; Takashiba, S

    2004-07-01

    Periodontal healing requires the participation of regulatory molecules, cells, and scaffold or matrix. Here, we hypothesized that a certain set of genes is expressed in alveolar bone wound healing. Reciprocal subtraction gave 400 clones from the injured alveolar bone of Wistar rats. Identification of 34 genes and analysis of their expression in injured tissue revealed several clusters of unique gene regulation patterns, including the up-regulation at 1 wk of cytochrome c oxidase regulating electron transfer and energy metabolism, presumably occurring at the site of inflammation; up-regulation at 2.5 wks of pro-alpha-2 type I collagen involving the formation of a connective tissue structure; and up-regulation at 1 and 2 wks and down-regulation at 2.5 and 4 wks of ubiquitin carboxyl-terminal hydrolase l3 involving cell cycle, DNA repair, and stress response. The differential expression of genes may be associated with the processes of inflammation, wound contraction, and formation of a connective tissue structure.

  20. Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status, low calcium intake, and high bone turnover.

    Science.gov (United States)

    Kruger, Marlena C; Kruger, Iolanthé M; Wentzel-Viljoen, Edelweiss; Kruger, Annamarie

    2011-10-01

    Globally, rural to urban migration is accompanied by changes in dietary patterns and lifestyle that have serious health implications, including development of low bone mass. We hypothesized that serum 25 (OH) vitamin D3 (25[OH]D3) levels will be lower, bone turnover higher, and nutrition inadequate in urban postmenopausal black women, increasing risk for low bone mass. We aimed to assess the prevalence of risk factors for low bone mass in 1261 black women from rural and urban areas in the North West Province of South Africa (Prospective Urban and Rural Epidemiology-South Africa project). Fasting blood samples were taken; and participants were interviewed to complete questionnaires on self-reported diseases, fractures, and dietary intakes. Bone health markers were assessed in a subgroup of 658 women older than 45 years. Specific lifestyle risk factors identified were inactivity, smoking, injectable progestin contraception use, and high alcohol consumption. Dietary risk factors identified were low calcium and high animal protein, phosphorous, and sodium intakes. The 25(OH)D3 and C-terminal telopeptide (CTX) levels were significantly higher in the rural vs the urban women older than 50 years. Parathyroid hormone (PTH) levels increased with age in both groups. The 25(OH)D levels were inversely correlated with CTX and PTH in rural women. In urban women, PTH and CTX were correlated while dietary calcium was inversely correlated with CTX and PTH with 25(OH)D3. The combination of low dietary calcium (<230 mg/d), marginally insufficient 25(OH)D3 status, and raised PTH may result in increased bone resorption. Further research is required to assess bone health and fracture risk in black African women. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Polymorphisms of muscle genes are associated with bone mass and incident osteoporotic fractures in Caucasians

    DEFF Research Database (Denmark)

    Harsløf, Torben; Frost, M; Nielsen, T L

    2013-01-01

    The interaction between muscle and bone is complex. The aim of this study was to investigate if variations in the muscle genes myostatin (MSTN), its receptor (ACVR2B), myogenin (MYOG), and myoD1 (MYOD1) were associated with fracture risk, bone mineral density (BMD), bone mineral content (BMC......), and lean body mass. We analyzed two independent cohorts: the Danish Osteoporosis Prevention Study (DOPS), comprising 2,016 perimenopausal women treated with hormone therapy or not and followed for 10 years, and the Odense Androgen Study (OAS), a cross-sectional, population-based study on 783 men aged 20......-29 years. Nine tag SNPs in the four genes were investigated. In the DOPS, individuals homozygous for the variant allele of the MSTN SNP rs7570532 had an increased risk of any osteoporotic fracture, with an HR of 1.82 (95 % CI 1.15-2.90, p = 0.01), and of nonvertebral osteoporotic fracture, with an HR of 2...

  2. Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

    Science.gov (United States)

    Chung, Hwa-Jin; Kyung Kim, Won; Joo Park, Hyen; Cho, Lan; Kim, Me-Riong; Kim, Min Jeong; Shin, Joon-Shik; Ho Lee, Jin; Ha, In-Hyuk; Kook Lee, Sang

    2016-02-17

    Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. 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

    Science.gov (United States)

    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 minerals that favors initially improving tissue-level properties over structural-level properties. It was therefore hypothesized that adding calcium and phosphorus supplements to the diet may prevent decreases in bone mass and structural strength during a short-term exercise program, while leading to greater bone mass and structural strength than exercise alone after a long-term exercise program. A short-term exercise experiment was done for 3 weeks, and a long-term exercise experiment was done for 8 weeks. For each experiment, male 16-week old C57BL/6 mice were assigned to 4 weight-matched groups–exercise and non-exercise groups fed a control or mineral-supplemented diet. Exercise consisted of treadmill running at 12 m/min, 30 min/day for 7 days/week. After 3 weeks, exercised mice fed the supplemented diet had significantly increased tibial tissue mineral content (TMC) and cross-sectional area over exercised mice fed the control diet. After 8 weeks, tibial TMC, cross-sectional area, yield force, and ultimate force were greater from the combined treatments than from either exercise or supplemented diet alone. Serum markers of bone formation (PINP) and resorption (CTX) were both decreased by exercise on day 2. In exercised mice, day 2 PINP was significantly positively correlated with day 2 serum Ca, a correlation that was weaker and negative in non-exercised mice. Increasing dietary mineral consumption during an exercise program increases bone mass after 3 weeks and

  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.

    Science.gov (United States)

    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 minerals that favors initially improving tissue-level properties over structural-level properties. It was therefore hypothesized that adding calcium and phosphorus supplements to the diet may prevent decreases in bone mass and structural strength during a short-term exercise program, while leading to greater bone mass and structural strength than exercise alone after a long-term exercise program. A short-term exercise experiment was done for 3 weeks, and a long-term exercise experiment was done for 8 weeks. For each experiment, male 16-week old C57BL/6 mice were assigned to 4 weight-matched groups-exercise and non-exercise groups fed a control or mineral-supplemented diet. Exercise consisted of treadmill running at 12 m/min, 30 min/day for 7 days/week. After 3 weeks, exercised mice fed the supplemented diet had significantly increased tibial tissue mineral content (TMC) and cross-sectional area over exercised mice fed the control diet. After 8 weeks, tibial TMC, cross-sectional area, yield force, and ultimate force were greater from the combined treatments than from either exercise or supplemented diet alone. Serum markers of bone formation (PINP) and resorption (CTX) were both decreased by exercise on day 2. In exercised mice, day 2 PINP was significantly positively correlated with day 2 serum Ca, a correlation that was weaker and negative in non-exercised mice. Increasing dietary mineral consumption during an exercise program increases bone mass after 3 weeks and increases

  5. Influence of lean and fat mass on bone mineral density (BMD) in postmenopausal women with osteoporosis.

    Science.gov (United States)

    Dytfeld, Joanna; Ignaszak-Szczepaniak, Magdalena; Gowin, Ewelina; Michalak, Michał; Horst-Sikorska, Wanda

    2011-01-01

    Despite known positive association between body mass and bone mineral density (BMD), relative contribution of fat and lean tissue to BMD remains under debate. We aimed at investigating the effect of selected anthropometric parameters, including fat content and lean body mass (LBM) on BMD in postmenopausal, osteoporotic women with body mass index (BMI) > 20 kg/m(2). The study involved 92 never-treated women (mean age 69.5 ± 7.3). L1-L4 and femoral neck (FN) BMD were measured by dual energy X-ray absorptiometry (DEXA). Absolute (kg) and relative (%) fat and LBM were assessed by means of electric bioimpedance method. We showed both FN and L1-L4 BMD were positively correlated with body mass, waist circumference (WC), hip circumference (HC) and LBM (kg). Fat content correlated with FN BMD (r = 0.36, p obese. Obese women displayed the highest BMD. Both L1-L4 and FN BMD were higher in women with WC > 80 cm. In postmenopausal osteoporotic women with BMI > 20 kg/m(2) both fat and lean tissue might contribute to BMD. Positive association between body mass and BMD does not make obesity and osteoporosis mutually exclusive. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress

    OpenAIRE

    Gao, Jing; Feng, Zhihui; Wang, Xueqiang; Zeng, Mengqi; Liu, Jing; Han, Shujun; Xu, Jie; Chen, Lei; Cao, Ke; Long, Jiangang; Li, Zongfang; Shen, Weili; Liu, Jiankang

    2017-01-01

    Recent studies have revealed robust metabolic changes during cell differentiation. Mitochondria, the organelles where many vital metabolic reactions occur, may play an important role. Here, we report the involvement of SIRT3-regulated mitochondrial stress in osteoblast differentiation and bone formation. In both the osteoblast cell line MC3T3-E1 and primary calvarial osteoblasts, robust mitochondrial biogenesis and supercomplex formation were observed during differentiation, accompanied by in...

  7. 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

  8. 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

  9. 201Tl scintigraphic evaluation of tumor mass and viability of bone and soft-tissue tumors

    International Nuclear Information System (INIS)

    Tsuda, Takatoshi; Kubota, Masahiro; Yoshida, Satoru; Shibata, Masahito; Wakabayashi, Jun-ichi; Obata, Hiroyuki; Matsuyama, Toshikatsu; Usui, Masamichi; Ishii, Sei-ichi.

    1994-01-01

    To characterize 201 Tl uptake in patients with bone and soft-tissue tumor, we studied 49 patients with surgically proven tumors and one patient with a tumor diagnosed arteriographically. In 37 of our 50 patients, the tumor was evaluated with 201 Tl and arteriography. Moreover, in 14 of patients with pre-operative chemotherapy, pathologic changes were graded on the basis of percent tumor necrosis as defined histologically. The percent tumor necrosis histologically was compared with changes in the scintigraphic and conventional angiographic studies. Radiologic comparisons demonstrated a high degree of correlation with images of 201 Tl and both arterial and blood pool phase of 99m Tc-HMDP. Ninety-six percent of 28 malignant tumors had positive 201 Tl uptake. None of the patients showed any thallium accumulation in the soft tissues or skeleton adjacent to the lesion. Activity of 201 Tl was mainly dependent upon a tumor blood flow and a vascular density. In of 14 cases with the preoperative chemotherapeutic treatment, 201 Tl scintigraphic changes showed concordance with % tumor necrosis. Thallium-201 was superior to 99m Tc-HMDP in predicting tumor response to chemotherapy. Interestingly, delayed images of 99m Tc-HMDP of 5 responders with >90% tumor necrosis showed decreased uptake in the adjacent bone to the tumor mass lesions. It seems to be quite all right to consider that a major determinant of 201 Tl uptake is intratumoral angiogenecity, which is closely connected with tumor viability. Therefore, 201 Tl is a sensitive radiopharmaceutical for detection of vascular rich bone and soft-tissue tumors, and appears to be a simple and an accurate test for evaluating the response to specific therapeutic regimens of malignant bone and soft-tissue tumors. (author)

  10. Validation of a physical activity questionnaire to measure the effect of mechanical strain on bone mass.

    Science.gov (United States)

    Kemper, Han C G; Bakker, I; Twisk, J W R; van Mechelen, W

    2002-05-01

    Most of the questionnaires available to estimate the daily physical activity levels of humans are based on measuring the intensity of these activities as multiples of resting metabolic rate (METs). Metabolic intensity of physical activities is the most important component for evaluating effects on cardiopulmonary fitness. However, animal studies have indicated that for effects on bone mass the intensity in terms of energy expenditure (metabolic component) of physical activities is less important than the intensity of mechanical strain in terms of the forces by the skeletal muscles and/or the ground reaction forces. The physical activity questionnaire (PAQ) used in the Amsterdam Growth and Health Longitudinal Study (AGAHLS) was applied to investigate the long-term effects of habitual physical activity patterns during youth on health and fitness in later adulthood. The PAQ estimates both the metabolic components of physical activities (METPA) and the mechanical components of physical activities (MECHPA). Longitudinal measurements of METPA and MECHPA were made in a young population of males and females ranging in age from 13 to 32 years. This enabled evaluation of the differential effects of physical activities during adolescence (13-16 years), young adulthood (21-28 years), and the total period of 15 years (age 13-28 years) on bone mineral density (BMD) of the lumbar spine, as measured by dual-energy X-ray absorptiometry (DXA) in males (n = 139) and females (n = 163) at a mean age of 32 years. The PAQ used in the AGAHLS during adolescence (13-16 years) and young adulthood (21-28 years) has the ability to measure the physical activity patterns of both genders, which are important for the development of bone mass at the adult age. MECHPA is more important than METPA. The highest coefficient of 0.33 (p PAQ was established by comparing PAQ scores during four annual measurements in 200 boys and girls with two other objective measures of physical activity: movement

  11. 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.

  12. The relationship between low bone mass and metabolic syndrome in Korean women.

    Science.gov (United States)

    Hwang, D-K; Choi, H-J

    2010-03-01

    We examined the relationship between low bond mass and metabolic syndrome in 2,475 Korean women. After adjustment for all covariates, mean vertebral BMD was significantly lower in women with metabolic syndrome. Moreover, age and weight adjusted vertebral BMD was significantly decreased with additional components of the metabolic syndrome. Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and metabolic syndrome. It has been suggested that proinflammatory cytokines and low-grade systemic inflammation activate bone resorption and may lead to reduced bone mineral density (BMD). The objective of this study was to determine the relationship between low bone mass and metabolic syndrome in Korean women. This is a cross-sectional study of 2,548 women aged 18 years and over who had visited the Health Promotion Center. Physical examination and laboratory tests were performed. Vertebral BMD was measured using dual-energy X-ray absorptiometry. Metabolic syndrome was defined by National Cholesterol Education Program-Adult Treatment Panel III criteria. Among 2,475 women, 511 (21.0%) women had metabolic syndrome. Women with abdominal obesity or hypertriglyceridemia had significantly lower vertebral BMD than women without respective components after adjustment for age, weight, and height. After adjustment for all covariates, mean vertebral BMD was significantly lower in women with metabolic syndrome (p = 0.031). Moreover, age- and weight-adjusted vertebral BMD were significantly decreased with additional components of the metabolic syndrome (p = 0.004). These findings suggest that metabolic syndrome might be another risk factor for osteoporosis and related fractures.

  13. 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.

  14. 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)

    Berthold, L.D.; Alzen, G.; Haras, G.; Mann, M.

    2006-01-01

    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

  15. Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow.

    Science.gov (United States)

    Jung, Younghun; Decker, Ann M; Wang, Jingcheng; Lee, Eunsohl; Kana, Lulia A; Yumoto, Kenji; Cackowski, Frank C; Rhee, James; Carmeliet, Peter; Buttitta, Laura; Morgan, Todd M; Taichman, Russell S

    2016-05-03

    GAS6 and its receptors (Tryo 3, Axl, Mer or "TAM") are known to play a role in regulating tumor progression in a number of settings. Previously we have demonstrated that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells. We have also demonstrated that GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy. Here we investigated the role that endogenous GAS6 and Mer receptor signaling plays in establishing prostate cancer stem cells in the bone marrow microenvironment.We first observed that high levels of endogenous GAS6 are expressed by disseminated tumor cells (DTCs) in the bone marrow, whereas relatively low levels of endogenous GAS6 are expressed in PCa tumors grown in a s.c. Interestingly, elevated levels of endogenous GAS6 were identified in putative cancer stem cells (CSCs, CD133+/CD44+) compared to non-CSCs (CD133-/CD44-) isolated from PCa/osteoblast cocultures in vitro and in DTCs isolated from the bone marrow 24 hours after intracardiac injection. Moreover, we found that endogenous GAS6 expression is associated with Mer receptor expression in growth arrested (G1) PCa cells, which correlates with the increase of the CSC populations. Importantly, we found that overexpression of GAS6 activates phosphorylation of Mer receptor signaling and subsequent induction of the CSC phenotype in vitro and in vivo.Together these data suggest that endogenous GAS6 and Mer receptor signaling contribute to the establishment of PCa CSCs in the bone marrow microenvironment, which may have important implications for targeting metastatic disease.

  16. 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

  17. A path model of sarcopenia on bone mass loss in elderly subjects.

    Science.gov (United States)

    Rondanelli, M; Guido, D; Opizzi, A; Faliva, M A; Perna, S; Grassi, M

    2014-01-01

    Aging is associated with decreases in muscle mass, strength, power (sarcopenia) and bone mineral density (BMD). The aims of this study were to investigate in elderly the role of sarcopenia on BMD loss by a path model, including adiposity, inflammation, and malnutrition associations. Body composition and BMD were measured by dual X-ray absorptiometry in 159 elderly subjects (52 male/107 female; mean age 80.3 yrs). Muscle strength was determined with dynamometer. Serum albumin and PCR were also assessed. Structural equations examined the effect of sarcopenia (measured by Relative Skeletal Muscle Mass, Total Muscle Mass, Handgrip, Muscle Quality Score) on osteoporosis (measured by Vertebral and Femoral T-scores) in a latent variable model including adiposity (measured by Total Fat Mass, BMI, Ginoid/Android Fat), inflammation (PCR), and malnutrition (serum albumin). The sarcopenia assumed a role of moderator in the adiposity-osteoporosis relationship. Specifically, increasing the sarcopenia, the relationship adiposity-osteoporosis (β: -0.58) decrease in intensity. Adiposity also influences sarcopenia (β: -0.18). Malnutrition affects the inflammatory and the adiposity states (β: +0.61, and β: -0.30, respectively), while not influencing the sarcopenia. Thus, adiposity has a role as a mediator of the effect of malnutrition on both sarcopenia and osteoporosis. Malnutrition decreases adiposity; decreasing adiposity, in turn, increase the sarcopenia and osteoporosis. This study suggests such as in a group of elderly sarcopenia affects the link between adiposity and BMD, but not have a pure independent effect on osteoporosis.

  18. Improved workability of injectable calcium sulfate bone cement by regulation of self-setting properties

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zonggang, E-mail: chenzg@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Liu, Huanye [Department of Orthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China); Liu, Xi [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Lian, Xiaojie [College of Mechanics, Taiyuan University of Technology, Taiyuan 030024 (China); Guo, Zhongwu [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Jiang, Hong-Jiang [Wendeng Hospital of Traditional Chinese Orthopedics and Traumatology, Shandong 264400 (China); Cui, Fu-Zhai, E-mail: cuifz@mail.tsinghua.edu.cn [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2013-04-01

    Calcium sulfate hemihydrate (CSH) powder as an injectable bone cement was prepared by hydrothermal synthesis of calcium sulfate dihydrate (CSD). The prepared materials showed X-ray diffraction peaks corresponding to the CSH structure without any secondary phases, implying complete conversion from CSD phase to CSH phase. Thermogravimetric (TG) analyses showed the crystal water content of CSH was about 6.0% (wt.), which is near to the theoretic crystal water value of CSH. From scanning electron microscopy (SEM) micrographs, sheet crystal structure of CSD was observed to transform into rod-like crystal structure of CSH. Most interesting and important of all, CSD as setting accelerator was also introduced into CSH powder to regulate self-setting properties of injectable CSH paste, and thus the self-setting time of CSH paste can be regulated from near 30 min to less than 5 min by adding various amounts of setting accelerator. Because CSD is not only the reactant of preparing CSH but also the final solidified product of CSH, the setting accelerator has no significant effect on the other properties of materials, such as mechanical properties. In vitro biocompatibility and in vivo histology studies have demonstrated that the materials have good biocompatibility and good efficacy in bone regeneration. All these will further improve the workability of CSH in clinic applications. Highlights: ► Calcium sulfate hemihydrate (CSH) can be an injectable bone cement. ► CSH was produced by hydrothermal synthesis of calcium sulfate dihydrate (CSD). ► CSD was introduced into CSH powder to regulate self-setting properties of CSH. ► Setting accelerator has no significant effect on the other properties of materials. ► Injectable CSH has good biocompatibility and good efficacy in bone regeneration.

  19. Regulation of Long Bone Growth in Vertebrates; It Is Time to Catch Up.

    Science.gov (United States)

    Roselló-Díez, Alberto; Joyner, Alexandra L

    2015-12-01

    The regulation of organ size is essential to human health and has fascinated biologists for centuries. Key to the growth process is the ability of most organs to integrate organ-extrinsic cues (eg, nutritional status, inflammatory processes) with organ-intrinsic information (eg, genetic programs, local signals) into a growth response that adapts to changing environmental conditions and ensures that the size of an organ is coordinated with the rest of the body. Paired organs such as the vertebrate limbs and the long bones within them are excellent models for studying this type of regulation because it is possible to manipulate one member of the pair and leave the other as an internal control. During development, growth plates at the end of each long bone produce a transient cartilage model that is progressively replaced by bone. Here, we review how proliferation and differentiation of cells within each growth plate are tightly controlled mainly by growth plate-intrinsic mechanisms that are additionally modulated by extrinsic signals. We also discuss the involvement of several signaling hubs in the integration and modulation of growth-related signals and how they could confer remarkable plasticity to the growth plate. Indeed, long bones have a significant ability for "catch-up growth" to attain normal size after a transient growth delay. We propose that the characterization of catch-up growth, in light of recent advances in physiology and cell biology, will provide long sought clues into the molecular mechanisms that underlie organ growth regulation. Importantly, catch-up growth early in life is commonly associated with metabolic disorders in adulthood, and this association is not completely understood. Further elucidation of the molecules and cellular interactions that influence organ size coordination should allow development of novel therapies for human growth disorders that are noninvasive and have minimal side effects.

  20. Improved workability of injectable calcium sulfate bone cement by regulation of self-setting properties

    International Nuclear Information System (INIS)

    Chen, Zonggang; Liu, Huanye; Liu, Xi; Lian, Xiaojie; Guo, Zhongwu; Jiang, Hong-Jiang; Cui, Fu-Zhai

    2013-01-01

    Calcium sulfate hemihydrate (CSH) powder as an injectable bone cement was prepared by hydrothermal synthesis of calcium sulfate dihydrate (CSD). The prepared materials showed X-ray diffraction peaks corresponding to the CSH structure without any secondary phases, implying complete conversion from CSD phase to CSH phase. Thermogravimetric (TG) analyses showed the crystal water content of CSH was about 6.0% (wt.), which is near to the theoretic crystal water value of CSH. From scanning electron microscopy (SEM) micrographs, sheet crystal structure of CSD was observed to transform into rod-like crystal structure of CSH. Most interesting and important of all, CSD as setting accelerator was also introduced into CSH powder to regulate self-setting properties of injectable CSH paste, and thus the self-setting time of CSH paste can be regulated from near 30 min to less than 5 min by adding various amounts of setting accelerator. Because CSD is not only the reactant of preparing CSH but also the final solidified product of CSH, the setting accelerator has no significant effect on the other properties of materials, such as mechanical properties. In vitro biocompatibility and in vivo histology studies have demonstrated that the materials have good biocompatibility and good efficacy in bone regeneration. All these will further improve the workability of CSH in clinic applications. Highlights: ► Calcium sulfate hemihydrate (CSH) can be an injectable bone cement. ► CSH was produced by hydrothermal synthesis of calcium sulfate dihydrate (CSD). ► CSD was introduced into CSH powder to regulate self-setting properties of CSH. ► Setting accelerator has no significant effect on the other properties of materials. ► Injectable CSH has good biocompatibility and good efficacy in bone regeneration

  1. [Influence of preoperative bone mass density in periprosthetic bone remodeling after implantation of ABG-II prosthesis: A 10-year follow-up].

    Science.gov (United States)

    Aguilar Ezquerra, A; Panisello Sebastiá, J J; Mateo Agudo, J

    2016-01-01

    Preoperative bone mass index has shown to be an important factor in peri-prosthetic bone remodelling in short follow-up studies. Bone density scans (DXA) were used to perform a 10-year follow-up study of 39 patients with a unilateral, uncemented hip replacement. Bone mass index measurements were made at 6 months, one year, 3 years, 5 years, and 10 years after surgery. Pearson coefficient was used to quantify correlations between preoperative bone mass density (BMD) and peri-prosthetic BMD in the 7 Gruen zones at 6 months, one year, 3 years, 5 years, and 10 years. Pre-operative BMD was a good predictor of peri-prosthetic BMD one year after surgery in zones 1, 2, 4, 5 and 6 (Pearson index from 0.61 to 0.75). Three years after surgery it has good predictive power in zones 1, 4 and 5 (0.71-0.61), although in zones 3 and 7 low correlation was observed one year after surgery (0.51 and 0.57, respectively). At the end of the follow-up low correlation was observed in the 7 Gruen zones. Sex and BMI were found to not have a statistically significant influence on peri-prosthetic bone remodelling. Although preoperative BMD seems to be an important factor in peri-prosthetic remodelling one year after hip replacement, it loses its predictive power progressively, until not being a major factor in peri-prosthetic remodelling ten years after surgery. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

  2. Stimulation of liver IGF-1 expression promotes peak bone mass achievement in growing rats: a study with pomegranate seed oil.

    Science.gov (United States)

    Bachagol, Deepa; Joseph, Gilbert Stanley; Ellur, Govindraj; Patel, Kalpana; Aruna, Pamisetty; Mittal, Monika; China, Shyamsundar Pal; Singh, Ravendra Pratap; Sharan, Kunal

    2018-02-01

    Peak bone mass (PBM) achieved at adulthood is a strong determinant of future onset of osteoporosis, and maximizing it is one of the strategies to combat the disease. Recently, pomegranate seed oil (PSO) has been shown to have bone-sparing effect in ovariectomized mice. However, its effect on growing skeleton and its molecular mechanism remain unclear. In the present study, we evaluated the effect of PSO on PBM in growing rats and associated mechanism of action. PSO was given at various doses to 21-day-old growing rats for 90 days by oral gavage. The changes in bone parameters were assessed by micro-computed tomography and histology. Enzyme-linked immunosorbent assay was performed to analyze the levels of serum insulin-like growth factor type 1 (IGF-1). Western blotting from bone and liver tissues was done. Chromatin immunoprecipitation assay was performed to study the histone acetylation levels at IGF-1 gene. The results of the study show that PSO treatment significantly increases bone length, bone formation rate, biomechanical parameters, bone mineral density and bone microarchitecture along with enhancing muscle and brown fat mass. This effect was due to the increased serum levels of IGF-1 and stimulation of its signaling in the bones. Studies focusing on acetylation of histones in the liver, the major site of IGF-1 synthesis, showed enrichment of acetylated H3K9 and H3K14 at IGF-1 gene promoter and body. Further, the increased acetylation at H3K9 and H3K14 was associated with a reduced HDAC1 protein level. Together, our data suggest that PSO promotes the PBM achievement via increased IGF-1 expression in liver and IGF-1 signaling in bone. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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 girls, but active-fit girls had 6.1 % (P girls, which was likely due to their 6.7 % (P active-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.

  4. Peak bone mass from longitudinal data: implications for the prevalence, pathophysiology, and diagnosis of osteoporosis.

    Science.gov (United States)

    Berger, Claudie; Goltzman, David; Langsetmo, Lisa; Joseph, Lawrence; Jackson, Stuart; Kreiger, Nancy; Tenenhouse, Alan; Davison, K Shawn; Josse, Robert G; Prior, Jerilynn C; Hanley, David A

    2010-09-01

    We estimated peak bone mass (PBM) in 615 women and 527 men aged 16 to 40 years using longitudinal data from the Canadian Multicentre Osteoporosis Study (CaMos). Individual rates of change were averaged to find the mean rate of change for each baseline age. The age range for PBM was defined as the period during which bone mineral density (BMD) was stable. PBM was estimated via hierarchical models, weighted according to 2006 Canadian Census data. Lumbar spine PBM (1.046 ± 0.123 g/cm(2)) occurred at ages 33 to 40 years in women and at 19 to 33 years in men (1.066 ± 0.129 g/cm(2)). Total hip PBM (0.981 ± 0.122 g/cm(2)) occurred at ages 16 to 19 years in women and 19 to 21 years in men (1.093 ± 0.169 g/cm(2)). Analysis of Canadian geographic variation revealed that the levels of PBM and of mean BMD in those over age 65 sometimes were discordant, suggesting that PBM and subsequent rates of bone loss may be subject to different genetic and/or environmental influences. Based on our longitudinally estimated PBM values, the estimated Canadian prevalences of osteoporosis (T-score < -2.5) were 12.0% (L(1)-L(4)) and 9.1% (total hip) in women aged 50 years and older and 2.9% (L(1)-L(4)) and 0.9% (total hip) in men aged 50 years and older. These were higher than prevalences using cross-sectional PBM data. In summary, we found that the age at which PBM is achieved varies by sex and skeletal site, and different reference values for PBM lead to different estimates of the prevalence of osteoporosis. Furthermore, lack of concordance of PBM and BMD over age 65 suggests different determinants of PBM and subsequent bone loss. © 2010 American Society for Bone and Mineral Research.

  5. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil, E-mail: hyunil74@hotmail.com; Lee, Zang Hee, E-mail: zang1959@snu.ac.kr

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  6. Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats

    Science.gov (United States)

    Srinivasan, Kritika; Naula, Diana P.; Mijares, Dindo Q.; Janal, Malvin N.; LeGeros, Raquel Z.; Zhang, Yu

    2016-01-01

    Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague-Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-Computed Tomography (μCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. PMID:26914814

  7. 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.

  8. Analysis of a Fossil Bone from Malu Rosu - Giurgiu by Accelerator Mass Spectroscopy

    International Nuclear Information System (INIS)

    Olariu, Agata; Popescu, I.V.; Hellborg, Ragnar; Stenstroem, Kristina; Skog, Goeran; Alexandrescu, E.

    2000-01-01

    In the present work we studied a fossil bone found in the archaeological site at Malu Rosu, near Giurgiu. Other specimens of fossil bones from Malu Rosu had been earlier dated by a chemical method, considering the content of the fluorine by neutron activation analysis. In this paper we have determined the age of a bone from Malu Rosu by the method of radiocarbon using the AMS (accelerator mass spectroscopy) technique. The measurement has been performed at 3 MeV Pelletron accelerator of the Lund University. The preparation of the bone sample was done in 2 steps: extraction of collagen from the structure of the bone by a chemical pretreatment, and then the transformation of collagen to pure carbon. The conversion to the elemental carbon is done also in two steps: formation of CO 2 by collagen combustion, and then the reduction of CO 2 to pure carbon. The sample of bone, as pure carbon is put in a copper holder and is arranged in a wheel in the following sequence: 5 carbon samples and 3 standards (1 standard of anthracite and 2 standards of oxalic acid). The anthracite being a very old coal is considered to have no 14 C traces and by its measurement one gets the background for 14 C both of the accelerator and of preparation installation of samples. Oxalic acid is a standard SRM prepared by USA National Bureau of Standards, with a well known activity of 14 C, measured in the Radiocarbon Dating Laboratory, Lund University, used to normalize the value of the 14 C counting rate, for the sample measured in the same conditions of beam current and time as the standard. The wheel with samples and standards are put in the ion source of the accelerator. The central part of the Lund AMS system is a Pelletron tandem accelerator (model 3UDH, produced by NEC, Wisconsin USA). The accelerator is run at 2.4 MV during AMS experiments, which is optimal for the C 3+ charge state. On the experimental beam line a magnetic quadrupole triplet, a velocity selector and a second analyzing

  9. Reduced bone mass and preserved marrow adipose tissue in patients with inflammatory bowel diseases in long-term remission.

    Science.gov (United States)

    Bastos, C M; Araújo, I M; Nogueira-Barbosa, M H; Salmon, C E G; de Paula, F J A; Troncon, L E A

    2017-07-01

    Bone marrow adipose tissue has not been studied in patients with inactive inflammatory bowel disease. We found that these patients have preserved marrow adiposity even with low bone mass. Factors involved in bone loss in active disease may have long-lasting effects but do not seem to affect bone marrow adiposity. Reduced bone mass is known to occur at varying prevalence in patients with inflammatory bowel diseases (IBD) because of inflammation, malnutrition, and steroid therapy. Osteoporosis may develop in these patients as the result of an imbalanced relationship between osteoblasts and adipocytes in bone marrow. This study aimed to evaluate for the first time bone mass and bone marrow adipose tissue (BMAT) in a particular subgroup of IBD patients characterized by long-term, steroid-free remission. Patients with Crohn's disease (CD; N = 21) and ulcerative colitis (UC; N = 15) and controls (C; N = 65) underwent dual X-ray energy absorptiometry and nuclear magnetic resonance spectroscopy of the L3 lumbar vertebra for BMAT assessment. Both the CD and UC subgroups showed significantly higher proportions of patients than controls with Z-score ≤-2.0 at L1-L4 (C 1.54%; CD 19.05%; UC 20%; p = 0.02), but not at other sites. The proportions of CD patients with a T-score ˂-1.0 at the femoral neck (C 18.46%; CD 47.62%; p = 0.02) and total hip (C 16.92%; CD 42.86%; p = 0.03) were significantly higher than among controls. There were no statistically significant differences between IBD patients and controls regarding BMAT at L3 (C 28.62 ± 8.15%; CD 29.81 ± 6.90%; UC 27.35 ± 9.80%; p = 0.67). IBD patients in long-term, steroid-free remission may have a low bone mass in spite of preserved BMAT. These findings confirm the heterogeneity of bone disorders in IBD and may indicate that factors involved in bone loss in active disease may have long-lasting effects on these patients.

  10. Importance of participation rate in sampling of data in population based studies, with special reference to bone mass in Sweden.

    OpenAIRE

    Düppe, H; Gärdsell, P; Hanson, B S; Johnell, O; Nilsson, B E

    1996-01-01

    OBJECTIVE: To study the effects of participation rate in sampling on "normative" bone mass data. DESIGN: This was a comparison between two randomly selected samples from the same population. The participation rates in the two samples were 61.9% and 83.6%. Measurements were made of bone mass at different skeletal sites and of muscle strength, as well as an assessment of physical activity. SETTING: Malmö, Sweden. SUBJECTS: There were 230 subjects (117 men, 113 women), aged 21 to 42 years. RESUL...

  11. Age-related changes in cortical bone mass: data from a German female cohort

    International Nuclear Information System (INIS)

    Toledo, V.A. Molina; Jergas, M.

    2006-01-01

    To describe data from digital radiogrammetry (DXR) in an unselected German female cohort over a wide age range. Using a retrospective study design we analyzed radiographs of the hand from 540 German women (aged 5-96 years) using an automated assessment of cortical thickness, metacarpal index (MCI), and estimated cortical bone mineral density (DXR-BMD) on digitized radiographs. Both hands were radiographed in 97 women. In this group DXR-BMD and cortical thickness were significantly higher in the right metacarpals while there was no significant difference in MCI. To study the association with age we differentiated young ( 45 years). In young women all parameters increased significantly with age in a linear fashion (r=0.8 for DXR-BMD, r=0.7 for MCI). In those aged 25-45 years DXR-BMD and MCI were highest (peak bone mass). In women aged 45 or older all parameters decreased with age in an almost linear fashion with an annual change ranging from 0.7% to 0.9%. Our results for an unselected German female cohort indicate that DXR is a reliable, widely available osteodensitometric technique based on the refinement of conventional radiogrammetry. These findings are comparable to those from other studies and represent a valid resource for clinical application and for comparisons with other ethnic groups. (orig.)

  12. Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment.

    Science.gov (United States)

    Sromicki, Jerzy Jan; Hess, Bernhard

    2017-06-01

    Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was ≥5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH 4 Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6-8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non-adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH 4 Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid-buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing

  13. Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links

    Directory of Open Access Journals (Sweden)

    Dolores Perovano Pardini

    2000-01-01

    Full Text Available CONTEXT: The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. OBJECTIVE: To study the effect of hormone replacement therapy (HRT on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN: Cohort correlational study. SETTING: Academic referral center. SAMPLE: 53 post-menopausal women, aged 48-58 years. MAIN MEASUREMENTS: Urinary pyr and d-pyr were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion measured before treatment and after 1, 2, 4 and 12 months. Bone mineral density (BMD was measured by dual energy X-ray absorptiometry (DEXA before treatment and after 12 months of HRT. RESULTS: The BMD after HRT was about 4.7% (P < 0.0004; 2% (P < 0.002; and 3% (P < 0.01 higher than the basal values in lumbar spine, neck and trochanter respectively. There were no significant correlations between pyridinium cross-links and age, weight, menopause duration and BMD. The decrease in pyr and d-pyr was progressive after HRT, reaching 28.9% (P < 0.0002, and 42% (P < 0.0002 respectively after 1 year. CONCLUSIONS: Urinary pyridinoline and deoxypyridinoline excretion decreases early in hormone replacement therapy, reflecting a decrease in the bone resorption rate, and no correlation was observed with the bone mass evaluated by densitometry.

  14. Scalp Block for Awake Craniotomy in a Patient With a Frontal Bone Mass: A Case Report

    Science.gov (United States)

    Amiri, Hamid Reza; Kouhnavard, Marjan; Safari, Saeid

    2012-01-01

    “Anesthesia” for awake craniotomy is a unique clinical condition that requires the anesthesiologist to provide changing states of sedation and analgesia, to ensure optimal patient comfort without interfering with electrophysiologic monitoring and patient cooperation, and also to manipulate cerebral and systemic hemodynamics while guaranteeing adequate ventilation and patency of airways. Awake craniotomy is not as popular in developing countries as in European countries. This might be due to the lack of information regarding awake craniotomy and its benefits among the neurosurgeons and anesthetists in developing countries. From the economic perspective, this procedure may decrease resource utilization by reducing the use of invasive monitoring, the duration of the operation, and the length of postoperative hospital stay. All these reasons also favor its use in the developing world, where the availability of resources still remains a challenge. In this case report we presented a successful awake craniotomy in patient with a frontal bone mass. PMID:24904791

  15. Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis

    International Nuclear Information System (INIS)

    Cai, Dongqing; Cao, Jie; Li, Zhen; Zheng, Xin; Yao, Yao; Li, Wanglin; Yuan, Ziqiang

    2009-01-01

    Bone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic breast cancer. cDNA microarray analysis was used to compare the BST2 gene expression between a metastatic to bone human breast cancer cell line (MDA-231BO) and a primary human breast cancer cell line (MDA-231). The BST2 expression in one bone metastatic breast cancer and seven non-bone metastatic breast cancer cell lines were also determined using real-time RT-PCR and Western blot assays. We then employed tissue array to further study the BST2 expression in human breast cancer using array slides containing 20 independent breast cancer tumors that formed metastatic bone lesions, 30 non-metastasis-forming breast cancer tumors, and 8 normal breast tissues. In order to test the feasibility of utilizing BST2 as a serum marker for the presence of bone metastasis in breast cancer, we had measured the BST2 expression levels in human serums by using ELISA on 43 breast cancer patients with bone metastasis, 43 breast cancer patients without bone metastasis, and 14 normal healthy controls. The relationship between cell migration and proliferation and BST2 expression was also studied in a human breast recombinant model system using migration and FACS analysis. The microarray demonstrated over expression of the BST2 gene in the bone metastatic breast cancer cell line (MDA-231BO) compared to the primary human breast cancer cell line (MDA-231). The expression of the BST2 gene was significantly increased in the bone metastatic breast cancer cell lines and tumor tissues compared to non-bone metastatic breast cancer

  16. Prevalence of radiographic hip osteoarthritis is increased in high bone mass.

    Science.gov (United States)

    Hardcastle, S A; Dieppe, P; Gregson, C L; Hunter, D; Thomas, G E R; Arden, N K; Spector, T D; Hart, D J; Laugharne, M J; Clague, G A; Edwards, M H; Dennison, E M; Cooper, C; Williams, M; Davey Smith, G; Tobias, J H

    2014-08-01

    Epidemiological studies have shown an association between increased bone mineral density (BMD) and osteoarthritis (OA), but whether this represents cause or effect remains unclear. In this study, we used a novel approach to investigate this question, determining whether individuals with High Bone Mass (HBM) have a higher prevalence of radiographic hip OA compared with controls. HBM cases came from the UK-based HBM study: HBM was defined by BMD Z-score. Unaffected relatives of index cases were recruited as family controls. Age-stratified random sampling was used to select further population controls from the Chingford and Hertfordshire cohort studies. Pelvic radiographs were pooled and assessed by a single observer blinded to case-control status. Analyses used logistic regression, adjusted for age, gender and body mass index (BMI). 530 HBM hips in 272 cases (mean age 62.9 years, 74% female) and 1702 control hips in 863 controls (mean age 64.8 years, 84% female) were analysed. The prevalence of radiographic OA, defined as Croft score ≥3, was higher in cases compared with controls (20.0% vs 13.6%), with adjusted odds ratio (OR) [95% CI] 1.52 [1.09, 2.11], P = 0.013. Osteophytes (OR 2.12 [1.61, 2.79], P subchondral sclerosis (OR 2.78 [1.49, 5.18], P = 0.001) were more prevalent in cases. However, no difference in the prevalence of joint space narrowing (JSN) was seen (OR 0.97 [0.72, 1.33], P = 0.869). An increased prevalence of radiographic hip OA and osteophytosis was observed in HBM cases compared with controls, in keeping with a positive association between HBM and OA and suggesting that OA in HBM has a hypertrophic phenotype. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. 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. © 2016 John Wiley & Sons Australia, Ltd.

  18. 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.

  19. Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for Cartilage and Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Sajjad Ashraf

    2017-04-01

    Full Text Available Advances in mesenchymal stem cells (MSCs and cell replacement therapies are promising approaches to treat cartilage and bone defects since substantial differentiation capacities of MSCs match the demands of tissue regeneration. Our understanding of the dynamic process requiring indispensable differentiation of MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched in brain regulating gene signature for differentiation of human adipose derived mesenchymal stem cells (ASCs into chondrogenic, osteogenic, and adipogenic lineages. RHEB-overexpression increases the proliferation of the ASCs. RHEB enhances the chondrogenic differentiation of ASCs in 3D culture via upregulation of SOX9 with concomitant increase in glycosaminoglycans (GAGs, and type II collagen (COL2. RHEB increases the osteogenesis via upregulation of runt related transcription factor 2 (RUNX2 with an increase in the calcium and phosphate contents. RHEB also increases the expression of osteogenic markers, osteonectin and osteopontin. RHEB knockdown ASCs were incapable of expressing sufficient SRY (Sex determining region Y-box 9 (SOX9 and RUNX2, and therefore had decreased chondrogenic and osteogenic differentiation. RHEB-overexpression impaired ASCs differentiation into adipogenic lineage, through downregulation of CCAAT/enhancer binding protein beta (C/EBPβ. Conversely, RHEB knockdown abolished the negative regulation of adipogenesis. We demonstrate that RHEB is a novel regulator, with a critical role in ASCs lineage determination, and RHEB-modulated ASCs may be useful as a cell therapy for cartilage and bone defect treatments.

  20. 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)

    Jung, Cheol Kyu; Park, Dong Woo; Seong, Jin Yong; Lee, Kak Soo; Park Choong Ki; Lee, Seung Ro; Hahm, Chang Kok

    2000-01-01

    %, 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Cheol Kyu; Park, Dong Woo; Seong, Jin Yong; Lee, Kak Soo; Park Choong Ki; Lee, Seung Ro; Hahm, Chang Kok [College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    2000-01-01

    flaccida (35%, 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)

  2. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R

    2007-01-01

    of macrophage-colony stimulating factor (M-CSF) and RANKL. Phalloidin staining in osteoclasts served to study actin ring and podosome formation. RESULTS: pQCT revealed increased bone mass in uPAR-null mice. Mechanical tests showed reduced load-sustaining capability in uPAR KO tibias. uPAR KO osteoblasts showed...... a proliferative advantage with no difference in apoptosis, higher matrix mineralization, and earlier appearance of alkaline phosphatase (ALP). Surface RANKL expression at different stages of differentiation was not altered. AP-1 components, such as JunB and Fra-1, were upregulated in uPAR KO osteoblasts, along...

  3. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    International Nuclear Information System (INIS)

    Minegishi, Yoshiki; Sakai, Yasuo; Yahara, Yasuhito; Akiyama, Haruhiko; Yoshikawa, Hideki; Hosokawa, Ko; Tsumaki, Noriyuki

    2014-01-01

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1 Δchon cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone

  4. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    Energy Technology Data Exchange (ETDEWEB)

    Minegishi, Yoshiki [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Department of Plastic and Reconstructive Surgery, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakai, Yasuo [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Plastic Surgery, Bellland General Hospital, 500-3 Higashiyama Naka-ku, Sakai, Osaka 599-8247 (Japan); Yahara, Yasuhito [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Akiyama, Haruhiko [Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagito, Gifu 501-1194 (Japan); Yoshikawa, Hideki [Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Hosokawa, Ko [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsumaki, Noriyuki, E-mail: ntsumaki@cira.kyoto-u.ac.jp [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Japan Science and Technology Agency, CREST, Tokyo 102-0075 (Japan)

    2014-11-07

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.

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

    International Nuclear Information System (INIS)

    Lim-Abrahan, M.A.V.; Guanzon, L.V.V.; De Guzman, A.M.; Villaruel, C.M.; Santos, F.

    1996-01-01

    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)

  6. Amino acid δ13C analysis of hair proteins and bone collagen using liquid chromatography/isotope ratio mass spectrometry

    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 the delta(13)C analysis of hair proteins and bone collagen recovered from six individuals from Uummannaq in Greenland. The analysis of hair and bone amino acids from the same individual, compared for the first time in this study, is of importance in palaeodietary reconstruction. If hair proteins can be used...

  7. The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development.

    Science.gov (United States)

    Lappe, Joan M; Watson, Patrice; Gilsanz, Vicente; Hangartner, Thomas; Kalkwarf, Heidi J; Oberfield, Sharon; Shepherd, John; Winer, Karen K; Zemel, Babette

    2015-01-01

    Childhood and adolescence are critical periods of bone mineral content (BMC) accrual that may have long-term consequences for osteoporosis in adulthood. Adequate dietary calcium intake and weight-bearing physical activity are important for maximizing BMC accrual. However, the relative effects of physical activity and dietary calcium on BMC accrual throughout the continuum of pubertal development in childhood remains unclear. The purpose of this study was to determine the effects of self-reported dietary calcium intake and weight-bearing physical activity on bone mass accrual across the five stages of pubertal development in a large, diverse cohort of US children and adolescents. The Bone Mineral Density in Childhood study was a mixed longitudinal study with 7393 observations on 1743 subjects. Annually, we measured BMC by dual-energy X-ray absorptiometry (DXA), physical activity and calcium intake by questionnaire, and pubertal development (Tanner stage) by examination for up to 7 years. Mixed-effects regression models were used to assess physical activity and calcium intake effects on BMC accrual at each Tanner stage. We found that self-reported weight-bearing physical activity contributed to significantly greater BMC accrual in both sexes and racial subgroups (black and nonblack). In nonblack males, the magnitude of the activity effect on total body BMC accrual varied among Tanner stages after adjustment for calcium intake; the greatest difference between high- and low-activity boys was in Tanner stage 3. Calcium intake had a significant effect on bone accrual only in nonblack girls. This effect was not significantly different among Tanner stages. Our findings do not support differential effects of physical activity or calcium intake on bone mass accrual according to maturational stage. The study demonstrated significant longitudinal effects of weight-bearing physical activity on bone mass accrual through all stages of pubertal development. © 2014 American

  8. A nonlinear model for myogenic regulation of blood flow to bone: equilibrium states and stability characteristics.

    Science.gov (United States)

    Harrigan, T P

    1996-01-01

    A simple compartmental model for myogenic regulation of interstitial pressure in bone is developed, and the interaction between changes in interstitial pressure and changes in arterial and venous resistance is studied. The arterial resistance is modeled by a myogenic model that depends on transmural pressure, and the venous resistance is modeled by using a vascular waterfall. Two series capacitances model blood storage in the vascular system and interstitial fluid storage in the extravascular space. The static results mimic the observed effect that vasodilators work less well in bone than do vasoconstrictors. The static results also show that the model gives constant flow rates over a limited range of arterial pressure. The dynamic model shows unstable behavior at small values of bony capacitance and at high enough myogenic gain. At low myogenic gain, only a single equilibrium state is present, but a high enough myogenic gain, two new equilibrium states appear. At additional increases in gain, one of the two new states merges with and then separates from the original state, and the original state becomes a saddle point. The appearance of the new states and the transition of the original state to a saddle point do not depend on the bony capacitance, and these results are relevant to general fluid compartments. Numerical integration of the rate equations confirms the stability calculations and shows limit cycling behavior in several situations. The relevance of this model to circulation in bone and to other compartments is discussed.

  9. Reference Centile Curves for Body Fat Percentage, Fat-free Mass, Muscle Mass and Bone Mass Measured by Bioelectrical Impedance in Asian Indian Children and Adolescents.

    Science.gov (United States)

    Chiplonkar, Shashi; Kajale, Neha; Ekbote, Veena; Mandlik, Rubina; Parthasarathy, Lavanya; Borade, Ashwin; Patel, Pinal; Patel, Prerna; Khadilkar, Vaman; Khadilkar, Anuradha

    2017-12-15

    To create gender-specific percentile curves for percent body fat (%BF) by Bio electrical Impedance Analysis (BIA) for screening adiposity and risk of hypertension in Indian children and generate reference curves for percent fat-free mass (%FFM), muscle mass (%LM) and bone mineral content (BMC) by using bioelectrical impedance. Secondary analysis of data from previous multicenter cross-sectional studies. Private schools from five regions of India. A random sample of 3850 healthy school children (2067 boys) (5-17 yr) from private schools in five major Indian cities. Anthropometry, blood pressure (BP) and body composition were measured by bioelectrical impedance. Reference curves were generated by the LMS method. %BF, %FFM, %LM, BMC and BP. Median %BF increased by 6% from 5 to 13 years of age and declined (around 2%) up to 17 years in boys. In girls, %BF increased by 8% from 5 to 14 years and thereafter declined by 3%. Based upon the risk of hypertension, the new cut-offs of 75th and 85th percentile of %BF were proposed for detecting over fatness and excess fatness in children. Median %FFM was 90% at 5 yrs and decreased till 12 years, and then showed a slight increase to 84% at 17 yrs in boys. In girls, it was 86% at 5 yrs and decreased till 15 yrs, and plateaued at 71.8% at 17 yrs. Reference curves for percent body fat for Indian children would be useful to screen children for health risk in clinical set up.

  10. The circulating concentration and ratio of total and high molecular weight adiponectin in post-menopausal women with and without osteoporosis and its association with body mass index and biochemical markers of bone metabolism.

    Science.gov (United States)

    Sodi, R; Hazell, M J; Durham, B H; Rees, C; Ranganath, L R; Fraser, W D

    2009-09-01

    There is increasing evidence suggesting that adiponectin plays a role in the regulation of bone metabolism. This was a cross-sectional study of 34 post-menopausal women with and 37 without osteoporosis. All subjects had body mass index (BMI), bone mineral density (BMD), total-, high molecular weight (HMW)-adiponectin and their ratio, osteoprotegerin (OPG), a marker of bone resorption (betaCTX) and formation (P1NP) measured. We observed a positive correlation between BMI and BMD (r=0.44, plean subjects but there was no difference between those with or without osteoporosis. There were significant negative correlations between HMW/total-adiponectin ratio and BMI (r=-0.27, p=0.030) and with OPG (r=-0.44, pproduction of OPG thereby affecting osteoclasts mediated bone resorption.

  11. Loss of lean body mass affects low bone mineral density in patients with rheumatoid arthritis - results from the TOMORROW study.

    Science.gov (United States)

    Okano, Tadashi; Inui, Kentaro; Tada, Masahiro; Sugioka, Yuko; Mamoto, Kenji; Wakitani, Shigeyuki; Koike, Tatsuya; Nakamura, Hiroaki

    2017-11-01

    Osteoporosis is one of the complications for patients with rheumatoid arthritis (RA). Rheumatoid cachexia, the loss of lean body mass, is another. However, the relationship between decreased lean body mass and reduced bone mineral density (BMD) in patients with RA has not been well studied. This study included 413 participants, comprising 208 patients with RA and 205 age- and sex-matched healthy volunteers. Clinical data, BMD, bone metabolic markers (BMM) and body composition, such as lean body mass and percent fat, were collected. Risk factors for osteoporosis in patients with RA including the relationship BMD and body composition were analyzed. Patients with RA showed low BMD and high BMM compared with controls. Moreover, lean body mass was lower and percent fat was higher in patients with RA. Lean body mass correlated positively and percent fat negatively with BMD. Lean body mass was a positive and disease duration was a negative independent factor for BMD in multivariate statistical analysis. BMD and lean body mass were significantly lower in patients with RA compared to healthy controls. Lean body mass correlated positively with BMD and decreased lean body mass and disease duration affected low BMD in patients with RA. [UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/ , UMIN000003876].

  12. Rapid restoration of bone mass after surgical management of hyperthyroidism: A prospective case control study in Southern India.

    Science.gov (United States)

    Karunakaran, Poongkodi; Maharajan, Chandrasekaran; Mohamed, Kamaludeen N; Rachamadugu, Suresh V

    2016-03-01

    The rate and the extent of bone remineralization at cancellous versus cortical sites after treatment of hyperthyroidism is unclear. Few studies have examined the effect of operative management of hyperthyroidism on recovery of bone mass. To evaluate prospectively the bone mineral density (BMD), bone mineral content (BMC), and bone areal size at the spine, hip, and forearm before and after total thyroidectomy. A prospective case control observational study from August 2011 to July 2014 in a single center. This study evaluated 40 overt hyperthyroid patients and 31 age-matched euthyroid controls who were operative candidates. Bone indices were measured at baseline and 6-month postoperatively using dual energy x-ray absorptiometry. Serum levels of alkaline phosphatase and 25-hydroxy vitamin D3 (25OHD) were assessed. Baseline BMD of hyperthyroid subjects at the spine, hip, and forearm were less than euthyroid controls (P = .001) with concomitant increases in serum alkaline phosphatase (mean ± SD, 143 ± 72 vs 72 ± 23 IU/L control; P hyperthyroid patients, posttreatment BMD expressed as g/cm(2) were 0.97 ± 0.12 (vs pretreatment 0.91 ± 0.14; P = .001) at the spine, 0.87 ± 0.12 (vs pretreatment 0.80 ± 0.13; P = .001) at the hip, and 0.67 ± 0.09 (vs pretreatment 0.64 ± 0.11; P = .191) at the forearm. The percent change in BMD was greatest at spine (8.3%) followed by the hip (7.6%) and forearm (3.0%). Operative management with total thyroidectomy improved the bone loss associated with hyperthyroidism as early as 6 months postoperatively at the hip and spine despite concomitant vitamin D deficiency. Delayed recovery of bone indices at the forearm, a cortical bone, requires further long-term evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. 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.

  14. β-cryptoxanthin regulates bone resorption related-cytokine production in human periodontal ligament cells.

    Science.gov (United States)

    Nishigaki, Masaru; Yamamoto, Toshiro; Ichioka, Hiroaki; Honjo, Ken-Ichi; Yamamoto, Kenta; Oseko, Fumishige; Kita, Masakazu; Mazda, Osam; Kanamura, Narisato

    2013-07-01

    β-cryptoxanthin (β-cry) is a type of carotenoid found in certain fruits and vegetables. Although it has been shown that β-cry inhibits alveolar bone resorption, the molecular mechanisms for this have not yet been clarified. In the present study, we investigated the effects of β-cry on bone resorption related-cytokine production in human periodontal ligament (hPDL) cells. hPDL cells were stimulated with β-cry (1×10(-7)mol/l), mechanical stress (1 or 6MPa), and P. gingivalis. The production of interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were analyzed by RT-PCR and ELISA. The production of IL-1β, IL-6, IL-8, and TNF-α was not induced in hPDL cells after stimulation with β-cry, although these cytokines were produced after stimulation with P. gingivalis. On the other hand, IL-6 and IL-8 were produced after exposure to 6MPa of mechanical stress. The production of IL-6 and IL-8 was significantly decreased by the addition of β-cry. Furthermore, β-cry up-regulated the production of OPG, but not RANKL. β-cry inhibited the production of IL-6 and IL-8 induced by mechanical stress and periodontopathogenic bacteria in hPDL cells. Moreover, β-cry up-regulated OPG production. These results suggest that β-cry may prevent bone resorption in periodontitis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Effects of cast-mediated immobilization on bone mineral mass at various sites in adolescents with lower-extremity fracture.

    Science.gov (United States)

    Ceroni, Dimitri; Martin, Xavier; Delhumeau, Cécile; Rizzoli, René; Kaelin, André; Farpour-Lambert, Nathalie

    2012-02-01

    Leg or ankle fractures occur commonly in the pediatric population and are primarily treated with closed reduction and cast immobilization. The most predictable consequences of immobilization and subsequent weight-bearing restriction are loss of bone mineral mass, substantial muscle atrophy, and functional limitations. The purposes of this study were to determine if lower-limb fractures in adolescents are associated with abnormal bone mineral density or content at the time of fracture, and to quantify bone mineral loss at various sites due to cast-mediated immobilization and limited weight-bearing. We recruited fifty adolescents aged ten to sixteen years who had undergone cast immobilization for a leg or ankle fracture. Dual x-ray absorptiometry scans of the total body, lumbar spine, hip, leg, and calcaneus were performed at the time of fracture and at cast removal. Patients with a fracture were paired with healthy controls according to sex and age. Values at baseline and at cast removal, or at equivalent time intervals in the control group, were compared between groups and between the injured and uninjured legs of the adolescents with the fracture. At the time of fracture, there were no observed differences in the bone mineral density or bone mineral content Z-scores of the total body or the lumbar spine, or in the bone mineral density Z-scores of the calcaneus, between the injured and healthy subjects. At cast removal, bone mineral parameters on the injured side were significantly lower than those on the uninjured side in the injured group. Differences ranged from -5.8% to -31.7% for bone mineral density and from -5.2% to -19.4% for bone mineral content. During the cast period, the injured adolescents had a significant decrease of bone mineral density at the hip, greater trochanter, calcaneus, and total lower limb as compared with the healthy controls. Lower-limb fractures are not related to osteopenia in adolescents at the time of fracture. However, osteopenia

  16. Bim: guardian of tissue homeostasis and critical regulator of the immune system, tumorigenesis and bone biology.

    Science.gov (United States)

    Akiyama, Toru; Tanaka, Sakae

    2011-08-01

    One of the most important roles of apoptosis is the maintenance of tissue homeostasis. Impairment of apoptosis leads to a number of pathological conditions. In response to apoptotic signals, various proteins are activated in a pathway and signal-specific manner. Recently, the pro-apoptotic molecule Bim has attracted increasing attention as a pivotal regulator of tissue homeostasis. The Bim expression level is strictly controlled in both transcriptional and post-transcriptional levels. This control is dependent on cell, tissue and apoptotic stimuli. The phenotype of Bim-deficient mice is a systemic lupus erythematosus-like autoimmune disease with an abnormal accumulation of hematopoietic cells. Bim is thus a critical regulator of hematopoietic cells and immune system. Further studies have revealed the critical roles of Bim in various normal and pathological conditions, including bone homeostasis and tumorigenesis. The current understanding of Bim signaling and roles in the maintenance of tissue homeostasis is reviewed in this paper, focusing on the immune system, bone biology and tumorigenesis to illustrate the diversified role of Bim.

  17. Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Patricia Sarrión

    Full Text Available 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.

  18. Relations of diet and physical activity to bone mass and height in black and white adolescents

    Directory of Open Access Journals (Sweden)

    Yanbin Dong

    2011-06-01

    Full Text Available Because the development of healthy bodies during the years of growth has life-long health consequences, it is important to understand the early influences of diet and physical activity (PA. One way to generate hypotheses concerning such influences is to conduct cross-sectional studies of how diet and PA are related to different components of body composition. The subjects were 660 black and white adolescents. Total body bone mineral content (BMC was measured with dual-energy X-ray absorptiometry; free-living diet and PA were assessed with 4-7 separate 24-h recalls. The main dietary variables investigated were: total energy intake, macronutrient distribution (%, dairy servings, vitamin D, and calcium. The main PA variables were hours of moderate PA (3-6 METs and vigorous PA (>6 METs. BMC was higher in blacks than in whites (P<0.01 and it increased more in boys than in girls (age by sex interaction as age increased (P<0.01. After adjustment for age, race and sex, higher levels of BMC were associated with higher levels of energy intake, dairy servings, calcium, vitamin D, and vigorous PA (all P 's<0.05. In the multivariable model, significant and independent proportions of the variance in BMC were explained by race, the age by sex interaction, calcium, and vigorous PA (all P 's<0.01. When height was used as the outcome variable, similar diet results were obtained; however, there was a sex by vigorous PA interaction, such that vigorous PA was associated with height only in the girls. These data are consistent with the hypothesis that the bone mass and height of growing youths are positively influenced by higher dietary intake of energy and dairy foods, along with sufficient amounts of vigorous PA. This hypothesis needs to be tested in randomized controlled trials.

  19. Trends in osteoporosis and low bone mass in older US adults, 2005-2006 through 2013-2014.

    Science.gov (United States)

    Looker, A C; Sarafrazi Isfahani, N; Fan, B; Shepherd, J A

    2017-06-01

    This study examined trends in osteoporosis and low bone mass in older US adults between 2005 and 2014 using bone mineral density (BMD) data from the National Health and Nutrition Examination Survey (NHANES). Osteoporosis and low bone mass appear to have increased at the femur neck but not at the lumbar spine during this period. Recent preliminary data from Medicare suggest that the decline in hip fracture incidence among older US adults may have plateaued in 2013-2014, but comparable data on BMD trends for this time period are currently lacking. This study examined trends in the prevalence of osteoporosis and low bone mass since 2005 using BMD data from NHANES. The present study also updated prevalence estimates to 2013-2014 and included estimates for non-Hispanic Asians. Femur neck and lumbar spine BMD by DXA were available for 7954 adults aged 50 years and older from four NHANES survey cycles between 2005-2006 and 2013-2014. Significant trends (quadratic or linear) were observed for the femur neck (mean T-score and osteoporosis in both sexes; low bone mass in women) but not for the lumbar spine. The trend in femur neck status was somewhat U-shaped, with prevalences being most consistently significantly higher (by 1.1-6.6 percentage points) in 2013-2014 than 2007-2008. Adjusting for changes in body mass index, smoking, milk intake, and physician's diagnosis of osteoporosis between surveys did not change femur neck trends. In 2013-2014, the percent of older adults with osteoporosis was 6% at the femur neck, 8% at the lumbar spine, and 11% at either site. There was some evidence of a decline in femur neck BMD between 2005-2006 and 2013-2014, but not in lumbar spine BMD. Changes in the risk factors that could be examined did not explain the femur neck BMD trends.

  20. Role of clinical indications of bone mass measurement with bi-photonic X-ray absorptiometry. Interet et indications cliniques des mesures de masse osseuse par absorptiometrie biphotonique a rayons X

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    Bone densitometry by precise, reliable and non-traumatic methods such as X-ray bi-phonon absorptiometry, is the only way to predict osteoporosis fractures risks. The whole epidemiological studies establish that bone mass loss and osteoporosis risk are directly linked. The measurement of the bone mass is the basis of osteoporosis prevention for elderly women, and of other clinical situations. This paper gives, by a critical analysis of available data, advantages and limits of bone mass measurements by X-ray bi-phonon absorptiometry, and essential clinical indications. (A.B.). 181 refs.

  1. Smoking is associated with impaired bone mass development in young adult men: a 5-year longitudinal study.

    Science.gov (United States)

    Rudäng, Robert; Darelid, Anna; Nilsson, Martin; Nilsson, Staffan; Mellström, Dan; Ohlsson, Claes; Lorentzon, Mattias

    2012-10-01

    It has previously been shown that smoking is associated with reduced bone mass and increased fracture risk, but no longitudinal studies have been published investigating altered smoking behavior at the time of bone mass acquisition. The aim of this study was to investigate the development of bone density and geometry according to alterations in smoking behavior in a 5-year, longitudinal, population-based study of 833 young men, age 18 to 20 years (baseline). Furthermore, we aimed to examine the cross-sectional, associations between current smoking and parameters of trabecular microarchitecture of the radius and tibia, using high-resolution peripheral quantitative computed tomography (HR-pQCT), in young men aged 23 to 25 years (5-year follow-up). Men who had started to smoke since baseline had considerably smaller increases in areal bone mineral density (aBMD) at the total body (mean ± SD, 0.020 ± 0.047 mg/cm(2) versus 0.043 ± 0.040 mg/cm(2) , p young adulthood have poorer development of their aBMD at clinically important sites such as the spine and hip than nonsmokers, possibly due to augmented loss of trabecular density and impaired growth of cortical cross-sectional area. Copyright © 2012 American Society for Bone and Mineral Research.

  2. Effect of Teriparatide, Vibration and the Combination on Bone Mass and Bone Architecture in Chronic Spinal Cord Injury

    Science.gov (United States)

    2015-12-01

    osteoporosis. J Bone Miner Res, 2003. 18(3): p. 539-43. 10. Ma, Y., et al., Parathyroid hormone and mechanical usage have a synergistic effect in rat tibial...directions, respectively. Material nonlinearity was modeled as bilinear elastic– plastic with a postyield modulus that was 5% of the pre-yield modulus(31...Injury Poster Sessions, Presentation Number: SA0435 Session: Poster Session I & Poster Tours Saturday, October 5, 2013 12:00 PM - 2:00 PM, Baltimore

  3. Periosteal PTHrP regulates cortical bone modeling during linear growth in mice.

    Science.gov (United States)

    Wang, Meina; VanHouten, Joshua N; Nasiri, Ali R; Tommasini, Steven M; Broadus, Arthur E

    2014-07-01

    The modeling of long bone surfaces during linear growth is a key developmental process, but its regulation is poorly understood. We report here that parathyroid hormone-related peptide (PTHrP) expressed in the fibrous layer of the periosteum (PO) drives the osteoclastic (OC) resorption that models the metaphyseal-diaphyseal junction (MDJ) in the proximal tibia and fibula during linear growth. PTHrP was conditionally deleted (cKO) in the PO via Scleraxis gene targeting (Scx-Cre). In the lateral tibia, cKO of PTHrP led to a failure of modeling, such that the normal concave MDJ was replaced by a mound-like deformity. This was accompanied by a failure to induce receptor activator of NF-kB ligand (RANKL) and a 75% reduction in OC number (P ≤ 0.001) on the cortical surface. The MDJ also displayed a curious threefold increase in endocortical osteoblast mineral apposition rate (P ≤ 0.001) and a thickened cortex, suggesting some form of coupling of endocortical bone formation to events on the PO surface. Because it fuses distally, the fibula is modeled only proximally and does so at an extraordinary rate, with an anteromedial cortex in CD-1 mice that was so moth-eaten that a clear PO surface could not be identified. The cKO fibula displayed a remarkable phenotype, with a misshapen club-like metaphysis and an enlargement in the 3D size of the entire bone, manifest as a 40-45% increase in the PO circumference at the MDJ (P ≤ 0.001) as well as the mid-diaphysis (P ≤ 0.001). These tibial and fibular phenotypes were reproduced in a Scx-Cre-driven RANKL cKO mouse. We conclude that PTHrP in the fibrous PO mediates the modeling of the MDJ of long bones during linear growth, and that in a highly susceptible system such as the fibula this surface modeling defines the size and shape of the entire bone. © 2014 Anatomical Society.

  4. 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.

  5. Risk of Fracture in Women with Sarcopenia, Low Bone Mass, or Both.

    Science.gov (United States)

    Harris, Rebekah; Chang, Yuefang; Beavers, Kristen; Laddu-Patel, Deepika; Bea, Jennifer; Johnson, Karen; LeBoff, Meryl; Womack, Catherine; Wallace, Robert; Li, Wenjun; Crandall, Carolyn; Cauley, Jane

    2017-12-01

    To determine whether women with sarcopenia and low bone mineral density (BMD) are at greater risk of clinical fractures than those with sarcopenia or low BMD alone. Women's Health Initiative (WHI) Observational and Clinical trials. Three U.S. clinical centers (Pittsburgh, PA; Birmingham, AL; Phoenix/Tucson, AZ). Women (mean age 63.3 ± 0.07) with BMD measurements (N = 10,937). Sarcopenia was defined as appendicular lean mass values corrected for height and fat mass. Low BMD was defined as a femoral neck T-score less than -1.0 based on the Third National Health and Nutrition Examination Survey reference database for white women. Cox proportional hazards analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). We followed women for incident fractures over a median of 15.9 years. Participants were classified into mutually exclusive groups based on BMD and sarcopenia status: normal BMD and no sarcopenia (n = 3,857, 35%), sarcopenia alone (n = 774, 7%), low BMD alone (n = 4,907, 45%), and low BMD and sarcopenia (n = 1,399, 13%). Women with low BMD, with (HR = 1.72, 95% CI = 1.44-2.06) or without sarcopenia (HR = 1.58, 95% CI = 1.37-1.83), had greater risk of fracture than women with normal BMD; the difference remained statistically significant after adjustment for important covariates. Women with low BMD, with (HR = 2.78, 95% CI = 1.78-4.30 and without (HR = 2.42, 95% CI = 1.63-3.59) sarcopenia had higher risk of hip fractures. Women with sarcopenia alone had similar HRs to women with normal BMD. Compared to women with normal BMD. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  6. Association of nonalcoholic fatty liver disease with low bone mass in postmenopausal women.

    Science.gov (United States)

    Moon, Seong-Su; Lee, Young-Sil; Kim, Sung Woo

    2012-10-01

    Osteoporosis is a disease associated with insulin resistant states such as central obesity, diabetes, and metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is also increased in such conditions. However, little is known about whether osteoporosis and nonalcoholic fatty liver disease are etiologically related to each other or not. We examined whether bone mineral density (BMD) is associated with NAFLD in pre- and postmenopausal women. Four hundred eighty-one female subjects (216 premenopausal and 265 postmenopausal) were enrolled. Lumbar BMD was measured using dual-energy X-ray absorptiometry. Liver ultrasonography was done to check the severity of fatty liver. We excluded subjects with a secondary cause of liver disease. Blood pressure, lipid profile, fasting plasma glucose, alanine aminotransferase (ALT), aspartate aminotransferase, and body mass index were measured in every subject. Mean lumbar BMD was lower in subjects with NAFLD than those without NAFLD in postmenopausal women (0.98 ± 0.01 vs. 1.01 ± 0.02 g/cm², P = 0.046). Multiple correlation analysis revealed a significant association between mean lumbar BMD and NAFLD in postmenopausal subjects after adjusting for age, body mass index, ALT, smoking status, and alcohol consumption (β coefficient -0.066, 95% CI -0.105 to -0.027, P = 0.001). Even after adjusting the presence of metabolic syndrome, the significance was maintained (β coefficient -0.043, 95% CI -0.082 to -0.004, P = 0.031). Lumbar BMD is related with NAFLD in postmenopausal females. We suggest that postmenopausal women with NAFLD may have a higher risk of osteoporosis than those without.

  7. Effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats.

    Science.gov (United States)

    Iwamoto, Jun; Matsumoto, Hideo; Takeda, Tsuyoshi; Sato, Yoshihiro; Yeh, James K

    2010-09-01

    The purpose of the present study was to examine the effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats. Thirty-four female Sprague-Dawley retired breeder rats were randomized into three groups: age-matched control, sciatic neurectomy (NX), and NX + vitamin K2 administration (menatetrenone, 30 mg/kg/day p.o., three times a week). At the end of the 8-week experiment, bone histomorphometric analysis was performed on cortical and cancellous bone of the tibial diaphysis and proximal metaphysis, respectively, and osteocyte lacunar system and porosity were evaluated on cortical bone of the tibial diaphysis. NX decreased cortical and cancellous bone mass compared with age-matched controls as a result of increased endocortical and trabecular bone erosion and decreased trabecular mineral apposition rate (MAR). Vitamin K2 ameliorated the NX-induced increase in bone erosion, prevented the NX-induced decrease in MAR, and increased bone formation rate (BFR/bone surface) in cancellous bone, resulting in an attenuation of NX-induced cancellous bone loss. However, vitamin K2 did not significantly influence cortical bone mass. NX also decreased osteocyte density and lacunar occupancy and increased porosity in cortical bone compared with age-matched controls. Vitamin K2 ameliorated the NX-induced decrease in lacunar occupancy by viable osteocytes and the NX-induced increase in porosity. The present study showed the efficacy of vitamin K2 for cancellous bone mass and cortical lacunar occupancy by viable osteocytes and porosity in sciatic NX rats.

  8. 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)

    Vladimir Zaichick; German Davydov; Tatyana Epatova; Sofia Zaichick

    2015-01-01

    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)

  9. Injectable calcium sulfate/mineralized collagen-based bone repair materials with regulable self-setting properties.

    Science.gov (United States)

    Chen, Zonggang; Liu, Huanye; Liu, Xi; Cui, Fu-Zhai

    2011-12-15

    An injectable and self-setting bone repair materials (nano-hydroxyapatite/collagen/calcium sulfate hemihydrate, nHAC/CSH) was developed in this study. The nano-hydroxyapatite/collagen (nHAC) composite, which is the mineralized fibril by self-assembly of nano-hydrocyapatite and collagen, has the same features as natural bone in both main hierarchical microstructure and composition. It is a bioactive osteoconductor due to its high level of biocompatibility and appropriate degradation rate. However, this material lacks handling characteristics because of its particle or solid-preformed block shape. Herein, calcium sulfate hemihydrate (CSH) was introduced into nHAC to prepare an injectable and self-setting in situ bone repair materials. The morphology of materials was observed using SEM. Most important and interesting of all, calcium sulfate dihydrate (CSD), which is not only the reactant of preparing CSH but also the final solidified product of CSH, was introduced into nHAC as setting accelerator to regulate self-setting properties of injectable nHAC/CSH composite, and thus the self-setting time of nHAC/CSH composite can be regulated from more than 100 min to about 30 min and even less than 20 min by adding various amount of setting accelerator. The compressive properties of bone graft substitute after final setting are similar to those of cancellous bone. CSD as an excellent setting accelerator has no significant effect on the mechanical property and degradability of bone repair materials. In vitro biocompatibility and in vivo histology studies demonstrated that the nHAC/CSH composite could provide more adequate stimulus for cell adhesion and proliferation, embodying favorable cell biocompatibility and a strong ability to accelerate bone formation. It can offer a satisfactory biological environment for growing new bone in the implants and for stimulating bone formation. Copyright © 2011 Wiley Periodicals, Inc.

  10. Regulation of body fat mass by the gut microbiota

    DEFF Research Database (Denmark)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik

    2016-01-01

    New insight suggests gut microbiota as a component in energy balance. However, the underlying mechanisms by which gut microbiota can impact metabolic regulation is unclear. A recent study from our lab shows, for the first time, a link between gut microbiota and energy balance circuitries...

  11. Low bone mass and changes in the osteocyte network in mice lacking autophagy in the osteoblast lineage.

    Science.gov (United States)

    Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Han, Li; Thostenson, Jeff D; Almeida, Maria; O'Brien, Charles A

    2016-04-11

    Autophagy maintains cell function and homeostasis by recycling intracellular components. This process is also required for morphological changes associated with maturation of some cell types. Osteoblasts are bone forming cells some of which become embedded in bone and differentiate into osteocytes. This transformation includes development of long cellular projections and a reduction in endoplasmic reticulum and mitochondria. We examined the role of autophagy in osteoblasts by deleting Atg7 using an Osterix1-Cre transgene, which causes recombination in osteoblast progenitors and their descendants. Mice lacking Atg7 in the entire osteoblast lineage had low bone mass and fractures associated with reduced numbers of osteoclasts and osteoblasts. Suppression of autophagy also reduced the amount of osteocyte cellular projections and led to retention of endoplasmic reticulum and mitochondria in osteocytes. These results demonstrate that autophagy in osteoblasts contributes to skeletal homeostasis and to the morphological changes associated with osteocyte formation.

  12. Collaborative Research and Support of Fitzsimmons Army Medical Center DWH Research Program Projects. The Effects of Region-Specific Resistance Exercises on Bone Mass in Premenopausal Military Women, Protocol 8

    National Research Council Canada - National Science Library

    Hayes, Robert

    1995-01-01

    .... The purpose of this study is to determine if peak bone mass can be improved after age 20, the age at which peak bone mass is usually reached, and to compare the effects of region-specific resistance...

  13. LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women.

    Science.gov (United States)

    Giroux, Sylvie; Elfassihi, Latifa; Cardinal, Guy; Laflamme, Nathalie; Rousseau, François

    2007-05-01

    Bone mineral density has a strong genetic component but it is also influenced by environmental factors making it a complex trait to study. LRP5 gene was previously shown to be involved in rare diseases affecting bone mass. Mutations associated with gain-of-function were described as well as loss-of-function mutations. Following this discovery, many frequent LRP5 polymorphisms were tested against the variation of BMD in the normal population. Heel bone parameters (SOS, BUA) were measured by right calcaneal QUS in 5021 healthy French-Canadian women and for 2104 women, BMD evaluated by DXA at two sites was available (femoral neck (FN) and lumbar spine (LS)). Among women with QUS measures and those with DXA measures, 26.5% and 32.8% respectively were premenopausal, 9.2% and 10.7% were perimenopausal and 64.2% and 56.5% were postmenopausal. About a third of the peri- and postmenopausal women never received hormone therapy. Two single nucleotide coding polymorphisms (Val667Met and Ala1330Val) in LRP5 gene were genotyped by allele-specific PCR. All bone measures were tested individually for associations with each polymorphism by analysis of covariance with adjustment for non genetic risk factors. Furthermore, haplotype analysis was performed to take into account the strong linkage disequilibrium between the two polymorphisms. The two LRP5 polymorphisms were found to be associated with all five bone measures (L2L4 and femoral neck DXA as well as heel SOS, BUA and stiffness index) in the whole sample. Premenopausal women drove the association as expected from the proposed role of LRP5 in peak bone mass. Our results suggest that the Val667Met polymorphism is the causative variant but this remains to be functionally proven.

  14. Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

    Science.gov (United States)

    Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

    2014-08-01

    Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

  15. Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.

    Science.gov (United States)

    Perosky, Joseph E; Khoury, Basma M; Jenks, Terese N; Ward, Ferrous S; Cortright, Kai; Meyer, Bethany; Barton, David K; Sinder, Benjamin P; Marini, Joan C; Caird, Michelle S; Kozloff, Kenneth M

    2016-12-01

    Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Massardo, T.; Gonzalez, P.; Coll, C.; Rodriguez, J.L.; Solis, I.; Oviedo, S.

    2002-01-01

    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/cm 2 ) 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/m 2 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

  17. 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

  18. 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

    in iliac crest bone biopsies from patients with the HBM phenotype and controls. We also used retrovirus-mediated gene transduction to establish three different human mesenchymal stem cell (hMSC) strains stably expressing wildtype LRP5 (hMSC-LRP5WT), LRP5T244 (hMSC-LRP5T244, inactivation mutation leading...... to osteoporosis), or LRP5T253 (hMSC-LRP5T253, activation mutation leading to high bone mass). We characterized Wnt signaling activation using a dual luciferase assay, cell proliferation, lineage biomarkers using real-time PCR, and in vivo bone formation. Results: In bone biopsies, we found increased trabecular...... 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 to increase...

  19. Regulation of bone morphogenetic protein signalling and cranial osteogenesis by Gpc1 and Gpc3.

    Science.gov (United States)

    Dwivedi, Prem P; Grose, Randall H; Filmus, Jorge; Hii, Charles S T; Xian, Cory J; Anderson, Peter J; Powell, Barry C

    2013-08-01

    From birth, the vault of the skull grows at a prodigious rate, driven by the activity of osteoblastic cells at the fibrous joints (sutures) that separate the bony calvarial plates. One in 2500 children is born with a medical condition known as craniosynostosis because of premature bony fusion of the calvarial plates and a cessation of bone growth at the sutures. Bone morphogenetic proteins (BMPs) are potent growth factors that promote bone formation. Previously, we found that Glypican-1 (GPC1) and Glypican-3 (GPC3) are expressed in cranial sutures and are decreased during premature suture fusion in children. Although glypicans are known to regulate BMP signalling, a mechanistic link between GPC1, GPC3 and BMPs and osteogenesis has not yet been investigated. We now report that human primary suture mesenchymal cells coexpress GPC1 and GPC3 on the cell surface and release them into the media. We show that they inhibit BMP2, BMP4 and BMP7 activities, which both physically interact with BMP2 and that immunoblockade of endogenous GPC1 and GPC3 potentiates BMP2 activity. In contrast, increased levels of GPC1 and GPC3 as a result of overexpression or the addition of recombinant protein, inhibit BMP2 signalling and BMP2-mediated osteogenesis. We demonstrate that BMP signalling in suture mesenchymal cells is mediated by both SMAD-dependent and SMAD-independent pathways and that GPC1 and GPC3 inhibit both pathways. GPC3 inhibition of BMP2 activity is independent of attachment of the glypican on the cell surface and post-translational glycanation, and thus appears to be mediated by the core glypican protein. The discovery that GPC1 and GPC3 regulate BMP2-mediated osteogenesis, and that inhibition of endogenous GPC1 and GPC3 potentiates BMP2 responsiveness of human suture mesenchymal cells, indicates how downregulation of glypican expression could lead to the bony suture fusion that characterizes craniosynostosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. 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

    or deflazacort. Bone mineral content (BMC) was measured in the lumbar spine and in the distal forearm before treatment and three, six, and 12 months after treatment. RESULTS: At three months the decrease in lumbar BMC and bone mineral density (BMD) was significantly greater in the deflazacort group than...

  1. 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

  2. Relationships between bone mass and dietary/lifestyle habits in Japanese women at 3-4 months postpartum.

    Science.gov (United States)

    Hoshino, A; Yamada, A; Tanabe, R; Noda, S; Nakaoka, K; Oku, Y; Katayama, C; Haraikawa, M; Nakano, H; Harada, M; Uenishi, K; Goseki-Sone, M

    2017-11-01

    The relationships between calcaneal bone mass and dietary/lifestyle habits in women at 3-4 months postpartum were examined in the context of osteoporosis prevention. Cross-sectional survey. We measured bone mass using calcaneal ultrasound in mothers who brought their 3- to 4-month-old babies to healthcare centers in Japan for health examination and administered a self-report questionnaire on physical characteristics and dietary/lifestyle habits to those who agreed to participate in the survey. Valid data were available for 1220 women (valid response rate, 97.5%). Based on their stiffness score, a measure of bone mass, 70.9% (n = 865) of the participants were classified as 'no apparent abnormality (stiffness score ≥78.8)' (low-risk group), 18.2% (n = 222) as 'guidance required (≥70.1-healthy eating habits, such as increased consumption of calcium-rich foods, and prevent osteoporosis. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Park, Soung Ock; Lee, In Ja; Shin, Gwi Soon

    2008-01-01

    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/m 2 . 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.

  4. Alfacalcidol improves muscle power, muscle function and balance in elderly patients with reduced bone mass.

    Science.gov (United States)

    Schacht, E; Ringe, Johann D

    2012-01-01

    We investigated the effect of daily therapy with 1 mcg alfacalcidol (Doss(®)-TEVA/AWD-pharma) on muscle power, muscle function, balance performance and fear of falls in an open, multi-centered, uncontrolled, prospective study on a cohort of patients with reduced bone mass. Among the 2,097 participants, 87.1% were post-menopausal women and 12.9% were men. Mean age was 74.8 years and mean body mass index (BMI) 26.3 kg/m². A total of 75.3% of the study population had osteoporosis, 81% a diagnosis of "increased risk of falls" and 70.1% had a creatinine clearance (CrCl) of power tests at onset and after 3 and 6 months: the timed up and go test (TUG) and the chair rising test (CRT). At baseline and after 6 months, participants performed the tandem gait test (TGT) and filled out a questionnaire evaluating fear of falling. Successful performance in the muscle tests is associated with a significantly lower risk of falls and non-vertebral fractures in elderly patients (successful test performance: TUG ≤ 10 s (sec), CRT ≤ 10 s, TGT ≥ 8 steps). A significant improvement in the performance of the two muscle tests was proved already after 3 months of treatment with alfacalcidol and further increased by the end of the therapeutic intervention. There were significant increases in the number of participants able to successfully perform the tests: 24.6% at baseline and 46.3% at the end of trial for the TUG (P balance test (TGT) increased from 36.0% at onset to 58.6% at the end of the trial (P power, muscle function and balance and reduces fear of falls. The significant improvement in the three muscle and balance tests and fear of falls may have a preventative effect on falls and fractures. We suggest that the quantitative risk tests used in this study could be reliable surrogate parameters for the risk of falls and fractures in elderly patients.

  5. Neonatal High Bone Mass With First Mutation of the NF-κB Complex: Heterozygous De Novo Missense (p.Asp512Ser) RELA (Rela/p65).

    Science.gov (United States)

    Frederiksen, Anja L; Larsen, Martin J; Brusgaard, Klaus; Novack, Deborah V; Knudsen, Peter Juel Thiis; Schrøder, Henrik Daa; Qiu, Weimin; Eckhardt, Christina; McAlister, William H; Kassem, Moustapha; Mumm, Steven; Frost, Morten; Whyte, Michael P

    2016-01-01

    Heritable disorders that feature high bone mass (HBM) are rare. The etiology is typically a mutation(s) within a gene that regulates the differentiation and function of osteoblasts (OBs) or osteoclasts (OCs). Nevertheless, the molecular basis is unknown for approximately one-fifth of such entities. NF-κB signaling is a key regulator of bone remodeling and acts by enhancing OC survival while impairing OB maturation and function. The NF-κB transcription complex comprises five subunits. In mice, deletion of the p50 and p52 subunits together causes osteopetrosis (OPT). In humans, however, mutations within the genes that encode the NF-κB complex, including the Rela/p65 subunit, have not been reported. We describe a neonate who died suddenly and unexpectedly and was found at postmortem to have HBM documented radiographically and by skeletal histopathology. Serum was not available for study. Radiographic changes resembled malignant OPT, but histopathological investigation showed morphologically normal OCs and evidence of intact bone resorption excluding OPT. Furthermore, mutation analysis was negative for eight genes associated with OPT or HBM. Instead, accelerated bone formation appeared to account for the HBM. Subsequently, trio-based whole exome sequencing revealed a heterozygous de novo missense mutation (c.1534_1535delinsAG, p.Asp512Ser) in exon 11 of RELA encoding Rela/p65. The mutation was then verified using bidirectional Sanger sequencing. Lipopolysaccharide stimulation of patient fibroblasts elicited impaired NF-κB responses compared with healthy control fibroblasts. Five unrelated patients with unexplained HBM did not show a RELA defect. Ours is apparently the first report of a mutation within the NF-κB complex in humans. The missense change is associated with neonatal osteosclerosis from in utero increased OB function rather than failed OC action. These findings demonstrate the importance of the Rela/p65 subunit within the NF-κB pathway for human

  6. RKIP Suppresses Breast Cancer Metastasis to the Bone by Regulating Stroma-Associated Genes

    International Nuclear Information System (INIS)

    Bevilacqua, E.; Frankenberger, C.A.; Rosner, M.R.

    2012-01-01

    In the past decade cancer research has recognized the importance of tumor stroma interactions for the progression of primary tumors to an aggressive and invasive phenotype and for colonization of new organs in the context of metastasis. The dialogue between tumor cells and the surrounding stroma is a complex and dynamic phenomenon, as many cell types and soluble factors are involved. While the function of many of the players involved in this cross talk have been studied, the regulatory mechanisms and signaling pathways that control their expression have not been investigated in depth. By using a novel, interdisciplinary approach applied to the mechanism of action of the metastasis suppressor, Raf kinase inhibitory protein (RKIP), we identified a signaling pathway that suppresses invasion and metastasis through regulation of stroma-associated genes. Conceptually, the approach we developed uses a master regulator and expression arrays from breast cancer patients to formulate hypotheses based on clinical data. Experimental validation is followed by further bioinformatics analysis to establish the clinical significance of discoveries. Using RKIP as an example we show here that this multi-step approach can be used to identify gene regulatory mechanisms that affect tumor-stroma interactions that in turn influence metastasis to the bone or other organs

  7. The Preventive Effect of Calcium Supplementation on Weak Bones Caused by the Interaction of Exercise and Food Restriction in Young Female Rats During the Period from Acquiring Bone Mass to Maintaining Bone Mass.

    Science.gov (United States)

    Aikawa, Yuki; Agata, Umon; Kakutani, Yuya; Kato, Shoyo; Noma, Yuichi; Hattori, Satoshi; Ogata, Hitomi; Ezawa, Ikuko; Omi, Naomi

    2016-01-01

    Increasing calcium (Ca) intake is important for female athletes with a risk of weak bone caused by inadequate food intake. The aim of the present study was to examine the preventive effect of Ca supplementation on low bone strength in young female athletes with inadequate food intake, using the rats as an experimental model. Seven-week-old female Sprague-Dawley rats were divided into four groups: the sedentary and ad libitum feeding group (SED), voluntary running exercise and ad libitum feeding group (EX), voluntary running exercise and 30% food restriction group (EX-FR), and a voluntary running exercise, 30% food-restricted and high-Ca diet group (EX-FR+Ca). To Ca supplementation, we used 1.2% Ca diet as "high-Ca diet" that contains two-fold Ca of normal Ca diet. The experiment lasted for 12 weeks. As a result, the energy availability, internal organ weight, bone strength, bone mineral density, and Ca absorption in the EX-FR group were significantly lower than those in the EX group. The bone strength and Ca absorption in the EX-FR+Ca group were significantly higher than those in the EX-FR group. However, the bone strength in the EX-FR+Ca group did not reach that in the EX group. These results suggested that Ca supplementation had a positive effect on bone strength, but the effect was not sufficient to prevent lower bone strength caused by food restriction in young female athletes.

  8. Lean mass and fat mass predict bone mineral density in middle-aged individuals with noninsulin-requiring type 2 diabetes mellitus.

    Science.gov (United States)

    Moseley, Kendall F; Dobrosielski, Devon A; Stewart, Kerry J; De Beur, Suzanne M Jan; Sellmeyer, Deborah E

    2011-05-01

    Despite high bone mineral density (BMD), persons with type 2 diabetes are at greater risk of fracture. The relationship between body composition and BMD in noninsulin-requiring diabetes is unclear. The aim was to examine how fat and lean mass independently affect the skeleton in this population. Subjects for this cross-sectional analysis were men (n = 78) and women (n = 56) aged 40-65 years (56 ± 6 years) with uncomplicated, noninsulin-requiring type 2 diabetes. Total body fat and lean mass, total body, hip and lumbar spine BMD were measured with dual energy X-ray absorptiometry. Magnetic resonance imaging measured total abdominal, visceral and subcutaneous (SQ) fat. Subjects had normal all-site BMD and were obese to overweight (body mass index 29-41 kg/m(2)) with controlled diabetes (HbA1c women 6·6 ± 1·2%, men 6·7 ± 1·6%). Lean mass was positively associated with total body, hip, femoral neck and hip BMD in both sexes. Fat mass, abdominal total and SQ fat were associated with total body and hip BMD in women. In multivariate analyses adjusted for sex, lean mass significantly predicted total, hip and femoral neck BMD in men and women. In unadjusted models, lean mass continued to predict BMD at these sites in men; fat mass also predicted total body, femoral and hip BMD in women. In men and women with uncomplicated, noninsulin-requiring diabetes, lean mass significantly predicted BMD at the total body, hip and femoral neck. Further research is needed to determine whether acquisition or maintenance of lean mass in T2DM can prevent hip fracture in this at-risk population. © 2011 Blackwell Publishing Ltd.

  9. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Nitrogen regulation of transpiration controls mass-flow acquisition of nutrients.

    Science.gov (United States)

    Matimati, Ignatious; Verboom, G Anthony; Cramer, Michael D

    2014-01-01

    Transpiration may enhance mass-flow of nutrients to roots, especially in low-nutrient soils or where the root system is not extensively developed. Previous work suggested that nitrogen (N) may regulate mass-flow of nutrients. Experiments were conducted to determine whether N regulates water fluxes, and whether this regulation has a functional role in controlling the mass-flow of nutrients to roots. Phaseolus vulgaris were grown in troughs designed to create an N availability gradient by restricting roots from intercepting a slow-release N source, which was placed at one of six distances behind a 25 μm mesh from which nutrients could move by diffusion or mass-flow (termed 'mass-flow' treatment). Control plants had the N source supplied directly to their root zone so that N was available through interception, mass-flow, and diffusion (termed 'interception' treatment). 'Mass-flow' plants closest to the N source exhibited 2.9-fold higher transpiration (E), 2.6-fold higher stomatal conductance (gs), 1.2-fold higher intercellular [CO2] (Ci), and 3.4-fold lower water use efficiency than 'interception' plants, despite comparable values of photosynthetic rate (A). E, gs, and Ci first increased and then decreased with increasing distance from the N source to values even lower than those of 'interception' plants. 'Mass-flow' plants accumulated phosphorus and potassium, and had maximum concentrations at 10mm from the N source. Overall, N availability regulated transpiration-driven mass-flow of nutrients from substrate zones that were inaccessible to roots. Thus when water is available, mass-flow may partially substitute for root density in providing access to nutrients without incurring the costs of root extension, although the efficacy of mass-flow also depends on soil nutrient retention and hydraulic properties.

  11. Bone Mass in Young Adulthood Following Gonadotropin-Releasing Hormone Analog Treatment and Cross-Sex Hormone Treatment in Adolescents With Gender Dysphoria

    NARCIS (Netherlands)

    Klink, D.T.; Caris, M.G.; Heijboer, A.C.; van Trotsenburg, M.; Rotteveel, J.

    2015-01-01

    Context: Sex steroids are important for bone mass accrual. Adolescents with gender dysphoria (GD) treated with gonadotropin-releasing hormone analog (GnRHa) therapy are temporarily sex-steroid deprived until the addition of cross-sex hormones (CSH). The effect of this treatment on bone mineral

  12. Effects of probiotics, prebiotics, and synbiotics on mineral metabolism in ovariectomized rats — impact of bacterial mass, intestinal absorptive area and reduction of bone turn-over

    Directory of Open Access Journals (Sweden)

    Katharina E. Scholz-Ahrens

    2016-08-01

    Conclusion: SYN exerted a synergistic effect on bone mineralization, presumably due to changes in gut microbiota and ecology associated with large bowel digesta weight (most likely reflecting microbial mass and with large bowel weight (reflecting absorptive area, while bone turnover tended to be reduced as indicated by BAP.

  13. The effect ofethnicity on appendicular bone m.ass in white, coloured ...

    African Journals Online (AJOL)

    impression of a lower incidence of osteoporosis in coloured WOInen than ..... greater physical activity in black and coloured females throughout ... porosis: incidence of hip fractures in mental instirutions. J Bone ... Underweight: a nutritional risk.

  14. Identification of microRNAs regulating the developmental pathways of bone marrow derived mast cells.

    Directory of Open Access Journals (Sweden)

    Yang Xiang

    Full Text Available MicroRNAs (miRNAs play important roles in leukocyte differentiation, although those utilised for specific programs and key functions remain incompletely characterised. As a global approach to gain insights into the potential regulatory role of miRNA in mast cell differentiation we characterised expression in BM cultures from the initiation of differentiation. In cultures enriched in differentiating mast cells we characterised miRNA expression and identified miRNA targeting the mRNA of putative factors involved in differentiation pathways and cellular identity. Detailed pathway analysis identified a unique miRNA network that is intimately linked to the mast cell differentiation program.We identified 86 unique miRNAs with expression patterns that were up- or down- regulated at 5-fold or more during bone marrow derived mast cells (BMMC development. By employing TargetScan and MeSH databases, we identified 524 transcripts involved in 30 canonical pathways as potentially regulated by these specific 86 miRNAs. Furthermore, by applying miRanda and IPA analyses, we predict that 7 specific miRNAs of this group are directly associated with the expression of c-Kit and FcεRIα and likewise, that 18 miRNAs promote expression of Mitf, GATA1 and c/EBPα three core transcription factors that direct mast cell differentiation. Furthermore, we have identified 11 miRNAs that may regulate the expression of STATs-3, -5a/b, GATA2 and GATA3 during differentiation, along with 13 miRNAs that target transcripts encoding Ndst2, mMCP4 and mMCP6 and thus may regulate biosynthesis of mast cell secretory mediators.This investigation characterises changes in miRNA expression in whole BM cultures during the differentiation of mast cells and predicts functional links between miRNAs and their target mRNAs for the regulation of development. This information provides an important resource for further investigations of the contributions of miRNAs to mast cell differentiation and

  15. 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.

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

    Science.gov (United States)

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

    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. PMID:26161291

  17. Association between low lean mass and low bone mineral density in 653 women with hip fracture: does the definition of low lean mass matter?

    Science.gov (United States)

    Di Monaco, Marco; Castiglioni, Carlotta; Di Monaco, Roberto; Tappero, Rosa

    2017-12-01

    Loss of both muscle and bone mass results in fragility fractures with increased risk of disability, poor quality of life, and death. Our aim was to assess the association between low appendicular lean mass (aLM) defined according to different criteria and low bone mineral density (BMD) in hip-fracture women. Six hundred fifty-three women admitted to our rehabilitation hospital underwent dual energy X-ray absorptiometry 19.1 ± 4.1 (mean ± SD) days after hip-fracture occurrence. Low aLM was identified according to either Baumgartner's definition (aLM/height 2 less than two standard deviations below the mean of the young reference group) or FNIH criteria: aLM definition, the association between low aLM/height 2 and low BMD was significant: χ 2 (1, n = 653) = 8.52 (p = 0.004), but it was erased by adjustments for age and fat mass. Using the FNIH definition the association between low aLM and low BMD was significant: χ 2 (1, n = 653) = 42.5 (p definition based on aLM/BMI ratio the association between low aLM/BMI ratio and low BMD was nonsignificant: χ 2 (1, n = 653) = 0.003 (p = 0.957). The association between low aLM and low BMD in women with hip fracture dramatically depends on the adopted definition of low aLM. FNIH threshold for aLM (<15.02 kg) emerges as a useful tool to capture women with damage of the muscle-bone unit.

  18. Omics analysis of human bone to identify genes and molecular networks regulating skeletal remodeling in health and disease.

    Science.gov (United States)

    Reppe, Sjur; Datta, Harish K; Gautvik, Kaare M

    2017-08-01

    The skeleton is a metabolically active organ throughout life where specific bone cell activity and paracrine/endocrine factors regulate its morphogenesis and remodeling. In recent years, an increasing number of reports have used multi-omics technologies to characterize subsets of bone biological molecular networks. The skeleton is affected by primary and secondary disease, lifestyle and many drugs. Therefore, to obtain relevant and reliable data from well characterized patient and control cohorts are vital. Here we provide a brief overview of omics studies performed on human bone, of which our own studies performed on trans-iliacal bone biopsies from postmenopausal women with osteoporosis (OP) and healthy controls are among the first and largest. Most other studies have been performed on smaller groups of patients, undergoing hip replacement for osteoarthritis (OA) or fracture, and without healthy controls. The major findings emerging from the combined studies are: 1. Unstressed and stressed bone show profoundly different gene expression reflecting differences in bone turnover and remodeling and 2. Omics analyses comparing healthy/OP and control/OA cohorts reveal characteristic changes in transcriptomics, epigenomics (DNA methylation), proteomics and metabolomics. These studies, together with genome-wide association studies, in vitro observations and transgenic animal models have identified a number of genes and gene products that act via Wnt and other signaling systems and are highly associated to bone density and fracture. Future challenge is to understand the functional interactions between bone-related molecular networks and their significance in OP and OA pathogenesis, and also how the genomic architecture is affected in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Park, Soung Ock; Lee, In Ja; Shin, Gwi Soon [Dept. of Radiologic Techology, Dongnam Health College, Suwon (Korea, Republic of)

    2008-12-15

    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/m{sup 2}. 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.

  20. Adsorption of zinc ions on bone char using helical coil-packed bed columns and its mass transfer modeling

    DEFF Research Database (Denmark)

    Moreno-Pérez, J.; Bonilla-Petriciolet, A.; Rojas-Mayorga, C. K.

    2016-01-01

    This study reports the assessment of helical coil-packed bed columns for Zn2+ adsorption on bone char. Zn2+ adsorption breakthrough curves have been obtained using helical coil columns with different characteristics and a comparison has been conducted with respect to the results of straight fixed-bed...... columns. Results showed that the helical coil adsorption columns may offer an equivalent removal performance than that obtained for the traditional packed bed columns but using a compact structure. However, the coil diameter, number of turns, and feed flow appear to be crucial parameters for obtaining...... the best performance in this packed-bed geometry. A mass transfer model for a mobile fluid flowing through a porous media was used for fitting and predicting the Zn2+ breakthrough curves in helical coil bed columns. Results of adsorbent physicochemical characterization showed that Zn2+ adsorption on bone...

  1. Influence of muscle strength, physical activity and weight on bone mass in a population-based sample of 1004 elderly women.

    Science.gov (United States)

    Gerdhem, P; Ringsberg, K A M; Akesson, K; Obrant, K J

    2003-09-01

    High physical activity level has been associated with high bone mass and low fracture risk and is therefore recommended to reduce fractures in old age. The aim of this study was to estimate the effect of potentially modifiable variables, such as physical activity, muscle strength, muscle mass and weight, on bone mass in elderly women. The influence of isometric thigh muscle strength, self-estimated activity level, body composition and weight on bone mineral density (dual energy X-ray absorptiometry; DXA) in total body, hip and spine was investigated. Subjects were 1004 women, all 75 years old, taking part in the Malmö Osteoporosis Prospective Risk Assessment (OPRA) study. Physical activity and muscle strength accounted for 1-6% of the variability in bone mass, whereas weight, and its closely associated variables lean mass and fat mass, to a much greater extent explained the bone mass variability. We found current body weight to be the variable with the most substantial influence on the total variability in bone mass (15-32% depending on skeletal site) in a forward stepwise regression model. Our findings suggest that in elderly women, the major fracture-preventive effect of physical activity is unlikely to be mediated through increased bone mass. Retaining or even increasing body weight is likely to be beneficial to the skeleton, but an excess body weight increase may have negative effects on health. Nevertheless, training in elderly women may have advantages by improving balance, co-ordination and mobility and therefore decreasing the risk of fractures.

  2. Factors affecting bone mineral mass loss after lower-limb fractures in a pediatric population.

    Science.gov (United States)

    Ceroni, Dimitri; Martin, Xavier; Kherad, Omar; Salvo, Davide; Dubois-Ferrière, Victor

    2015-06-01

    The purpose of this study was to assess the effects of the durations of cast immobilization and non-weight-bearing periods, and decreases in vigorous physical activity (VPA) on bone mineral parameters in a pediatric population treated for a lower-limb fracture. Fifty children and teenagers who had undergone a cast-mediated immobilization for a leg or ankle fracture were prospectively recruited. The durations of cast immobilization and non-weight-bearing periods were recorded for each participant. Dual-energy x-ray absorptiometry scans were performed at the time of fracture treatment (baseline) and at cast removal. Physical activity during cast immobilization was assessed using accelerometers. A strong negative correlation was found between the total duration of cast immobilization and decreases in both calcaneal bone mineral density (BMD) (r=-0.497) and total lower-limb bone mineral content (BMC) (r=-0.405). A strong negative correlation was also noted between the durations of the non-weight-bearing periods and alterations in calcaneal BMD (r=-0.420). No apparent correlations were found between lower BMD and BMC and decreased VPA. Bone mineral loss was correlated to the total duration of cast immobilization for all measurement sites on the affected leg, whereas it was only correlated to the durations of non-weight-bearing periods for calcaneal BMD and total lower-limb BMC. However, no correlations were noted between bone mineral loss and decreased VPA.

  3. Intracellular glutathione status regulates mouse bone marrow monocyte-derived macrophage differentiation and phagocytic activity

    International Nuclear Information System (INIS)

    Kim, Jin-Man; Kim, Hyunsoo; Kwon, Soon Bok; Lee, Soo Young; Chung, Sung-Chang; Jeong, Dae-Won; Min, Byung-Moo

    2004-01-01

    Although a redox shift can regulate the development of cells, including proliferation, differentiation, and survival, the role of the glutathione (GSH) redox status in macrophage differentiation remains unclear. In order to elucidate the role of a redox shift, macrophage-like cells were differentiated from the bone marrow-derived monocytes that were treated with a macrophage colony stimulating factor (M-CSF or CSF-1) for 3 days. The macrophagic cells were characterized by a time-dependent increase in three major symptoms: the number of phagocytic cells, the number of adherent cells, and the mRNA expression of c-fms, a M-CSF receptor that is one of the macrophage-specific markers and mediates development signals. Upon M-CSF-driven macrophage differentiation, the GSH/GSSG ratio was significantly lower on day 1 than that observed on day 0 but was constant on days 1-3. To assess the effect of the GSH-depleted and -repleted status on the differentiation and phagocytosis of the macrophages, GSH depletion by BSO, a specific inhibitor of the de novo GSH synthesis, inhibited the formation of the adherent macrophagic cells by the down-regulation of c-fms, but did not affect the phagocytic activity of the macrophages. To the contrary, GSH repletion by the addition of NAC, which is a GSH precursor, or reduced GSH in media had no effect on macrophage differentiation, and led to a decrease in the phagocytic activity. Furthermore, we observed that there is checkpoint that is capable of releasing from the inhibition of the formation of the adherent macrophagic cells according to GSH depletion by BSO. Summarizing, these results indicate that the intracellular GSH status plays an important role in the differentiation and phagocytosis of macrophages

  4. Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation.

    Science.gov (United States)

    Asmussen, Niels; Lin, Zhao; McClure, Michael J; Schwartz, Zvi; Boyan, Barbara D

    2017-12-09

    Endochondral bone formation is a precise and highly ordered process whose exact regulatory framework is still being elucidated. Multiple regulatory pathways are known to be involved. In some cases, regulation impacts gene expression, resulting in changes in chondrocyte phenotypic expression and extracellular matrix synthesis. Rapid regulatory mechanisms are also involved, resulting in release of enzymes, factors and micro RNAs stored in extracellular matrisomes called matrix vesicles. Vitamin D metabolites modulate endochondral development via both genomic and rapid membrane-associated signaling pathways. 1α,25-dihydroxyvitamin D3 [1α,25(OH) 2 D 3 ] acts through the vitamin D receptor (VDR) and a membrane associated receptor, protein disulfide isomerase A3 (PDIA3). 24R,25-dihydroxyvitamin D3 [24R,25(OH) 2 D 3 ] affects primarily chondrocytes in the resting zone (RC) of the growth plate, whereas 1α,25(OH) 2 D 3 affects cells in the prehypertrophic and upper hypertrophic cell zones (GC). This includes genomically directing the cells to produce matrix vesicles with zone specific characteristics. In addition, vitamin D metabolites produced by the cells interact directly with the matrix vesicle membrane via rapid signal transduction pathways, modulating their activity in the matrix. The matrix vesicle payload is able to rapidly impact the extracellular matrix via matrix processing enzymes as well as providing a feedback mechanism to the cells themselves via the contained micro RNAs. Copyright © 2017. Published by Elsevier Inc.

  5. Regulation of Oligodendrocyte Progenitor Cell Maturation by PPARδ: Effects on Bone Morphogenetic Proteins

    Directory of Open Access Journals (Sweden)

    Maria Vittoria Simonini

    2009-12-01

    Full Text Available In EAE (experimental autoimmune encephalomyelitis, agonists of PPARs (peroxisome proliferator-activated receptors provide clinical benefit and reduce damage. In contrast with PPARγ, agonists of PPARδ are more effective when given at later stages of EAE and increase myelin gene expression, suggesting effects on OL (oligodendrocyte maturation. In the present study we examined effects of the PPARδ agonist GW0742 on OPCs (OL progenitor cells, and tested whether the effects involve modulation of BMPs (bone morphogenetic proteins. We show that effects of GW0742 are mediated through PPARδ since no amelioration of EAE clinical scores was observed in PPARδ-null mice. In OPCs derived from E13 mice (where E is embryonic day, GW0742, but not the PPARγ agonist pioglitazone, increased the number of myelin-producing OLs. This was due to activation of PPARδ since process formation was reduced in PPARδ-null compared with wild-type OPCs. In both OPCs and enriched astrocyte cultures, GW0742 increased noggin protein expression; however, noggin mRNA was only increased in astrocytes. In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes. These findings demonstrate that PPARδ plays a role in OPC maturation, mediated, in part, by regulation of BMP and BMP antagonists.

  6. Selective effect of hydroxyapatite nanoparticles on osteoporotic and healthy bone formation correlates with intracellular calcium homeostasis regulation.

    Science.gov (United States)

    Zhao, Rui; Xie, Pengfei; Zhang, Kun; Tang, Zhurong; Chen, Xuening; Zhu, Xiangdong; Fan, Yujiang; Yang, Xiao; Zhang, Xingdong

    2017-09-01

    Adequate bone substitutes osseointegration has been difficult to achieve in osteoporosis. Hydroxyapatite of the osteoporotic bone, secreted by pathologic osteoblasts, had a smaller crystal size and lower crystallinity than that of the normal. To date, little is known regarding the interaction of synthetic hydroxyapatite nanoparticles (HANPs) with osteoblasts born in bone rarefaction. The present study investigated the biological effects of HANPs on osteoblastic cells derived from osteoporotic rat bone (OVX-OB), in comparison with the healthy ones (SHM-OB). A selective effect of different concentrations of HANPs on the two cell lines was observed that the osteoporotic osteoblasts had a higher tolerance. Reductions in cell proliferation, ALP activity, collagen secretion and osteoblastic gene expressions were found in the SHM-OB when administered with HANPs concentration higher than 25µg/ml. In contrast, those of the OVX-OB suffered no depression but benefited from 25 to 250µg/ml HANPs in a dose-dependent manner. We demonstrated that the different effects of HANPs on osteoblasts were associated with the intracellular calcium influx into the endoplasmic reticulum. The in vivo bone defect model further confirmed that, with a critical HANPs concentration administration, the osteoporotic rats had more and mechanically matured new bone formation than the non-treated ones, whilst the sham rats healed no better than the natural healing control. Collectively, the observed epigenetic regulation of osteoblastic cell function by HANPs has significant implication on defining design parameters for a potential therapeutic use of nanomaterials. In this study, we investigated the biological effects of hydroxyapatite nanoparticles (HANPs) on osteoporotic rat bone and the derived osteoblast. Our findings revealed a previously unrecognized phenomenon that the osteoporotic individuals could benefit from higher concentrations of HANPs, as compared with the healthy individuals. The in

  7. The p27 Pathway Modulates the Regulation of Skeletal Growth and Osteoblastic Bone Formation by Parathyroid Hormone-Related Peptide.

    Science.gov (United States)

    Zhu, Min; Zhang, Jing; Dong, Zhan; Zhang, Ying; Wang, Rong; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2015-11-01

    Parathyroid hormone-related peptide (PTHrP) 1-84 knock-in mice (Pthrp KI) develop skeletal growth retardation and defective osteoblastic bone formation. To further examine the mechanisms underlying this phenotype, microarray analyses of differential gene expression profiles were performed in long bone extracts from Pthrp KI mice and their wild-type (WT) littermates. We found that the expression levels of p27, p16, and p53 were significantly upregulated in Pthrp KI mice relative to WT littermates. To determine whether p27 was involved in the regulation by PTHrP of skeletal growth and development in vivo, we generated compound mutant mice, which were homozygous for both p27 deletion and the Pthrp KI mutation (p27(-/-) Pthrp KI). We then compared p27(-/-) Pthrp KI mice with p27(-/-), Pthrp KI, and WT littermates. Deletion of p27 in Pthrp KI mice resulted in a longer lifespan, increased body weight, and improvement in skeletal growth. At 2 weeks of age, skeletal parameters, including length of long bones, size of epiphyses, numbers of proliferating cell nuclear antigen (PCNA)-positive chondrocytes, bone mineral density, trabecular bone volume, osteoblast numbers, and alkaline phosphatase (ALP)-, type I collagen-, and osteocalcin-positive bone areas were increased in p27(-/-) mice and reduced in both Pthrp KI and p27(-/-) Pthrp KI mice compared with WT mice; however, these parameters were increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. As well, protein expression levels of PTHR, IGF-1, and Bmi-1, and the numbers of total colony-forming unit fibroblastic (CFU-f) and ALP-positive CFU-f were similarly increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. Our results demonstrate that deletion of p27 in Pthrp KI mice can partially rescue defects in skeletal growth and osteoblastic bone formation by enhancing endochondral bone formation and osteogenesis. These studies, therefore, indicate that the p27 pathway may function downstream in the action

  8. Gut microbiome and bone.

    Science.gov (United States)

    Ibáñez, Lidia; Rouleau, Matthieu; Wakkach, Abdelilah; Blin-Wakkach, Claudine

    2018-04-11

    The gut microbiome is now viewed as a tissue that interacts bidirectionally with the gastrointestinal, immune, endocrine and nervous systems, affecting the cellular responses in numerous organs. Evidence is accumulating of gut microbiome involvement in a growing number of pathophysiological processes, many of which are linked to inflammatory responses. More specifically, data acquired over the last decade point to effects of the gut microbiome on bone mass regulation and on the development of bone diseases (such as osteoporosis) and of inflammatory joint diseases characterized by bone loss. Mice lacking a gut microbiome have bone mass alteration that can be reversed by gut recolonization. Changes in the gut microbiome composition have been reported in mice with estrogen-deficiency osteoporosis and have also been found in a few studies in humans. Probiotic therapy decreases bone loss in estrogen-deficient animals. The effect of the gut microbiome on bone tissue involves complex mechanisms including modulation of CD4 + T cell activation, control of osteoclastogenic cytokine production and modifications in hormone levels. This complexity may contribute to explain the discrepancies observed betwwen some studies whose results vary depending on the age, gender, genetic background and treatment duration. Further elucidation of the mechanisms involved is needed. However, the available data hold promise that gut microbiome manipulation may prove of interest in the management of bone diseases. Copyright © 2018 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

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

    Science.gov (United States)

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

    2015-08-01

    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). 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) measurements. Total hip BMD levels of obese menopausal and premenopausal women and men were significantly higher compared to overweight or normal weight subjects, while lumbar spine BMD levels of only menopausal women and men were higher among obese subjects. Age-adjusted linear regression analysis showed that BMI is a significant independent associate of lumbar spine and total hip BMD in menopausal women and men. Despite positive association between BMI and lumbar spine and total hip BMD in menopausal women, presence of more obese and osteoporotic subjects among menopausal women represent a population at risk for fractures because of poor balance and frequent falls; therefore, both obesity and osteoporosis prevention efforts should begin early on in life.

  10. Conjugated linoleic acid prevents age-induced bone loss in mice by regulating both osteoblastogenesis and adipogenesis.

    Science.gov (United States)

    Lin, Guanlin; Wang, Huan; Dai, Jun; Li, Xiao; Guan, Ming; Gao, Shutao; Ding, Qing; Wang, Huaixi; Fang, Huang

    2017-08-26

    Osteoporosis (OP) can increase the risk of bone fracture and other complications, which is a major clinical problem. Previous researches have revealed that conjugated linoleic acid (CLA) can promote the bone formation. But the mechanisms are not clear. Thus, we tested the hypothesis that CLA acts on bone formation might be via mTOR Complex1 (mTORC 1) pathway by in vitro and vivo assays. We studied the effect of CLA mix on MC3T3-E1 pre-osteoblasts differentiation into osteoblasts, and bone formation under osteoporotic conditions. At the same time, 3T3-L1 pre-adipocyte with the same CLA mix concentration gradient for 8 days with adipogenic differentiation medium. We found that Alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) expressions of pre-osteoblasts were up-regulated. Moreover in presence of CLA, peroxisome proliferators-activated receptor γ(PPARγ) and CCAAT/enhancer-binding protein (C/EBPα) were down-regulated. Osteoporosis mice bone parameters in the distal femoral meraphysis were significantly increased compared with placebo mice. Furthermore, the phosphor-S6 (P-S6) was suppressed and phosphor-AKT (P-AKT) was up-regulated. Consistently, CLA can stimulate differentiation of osteoblasts and inhibited pre-adipocytes differentiated into adipocytes via AKT/mTORC1 signal pathway. Overall CLA thus be a suitable candidate for the treatment of patients with postmenopausal osteoporosis and obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Peak lean tissue mass accrual precedes changes in bone strength indices at the proximal femur during the pubertal growth spurt.

    Science.gov (United States)

    Jackowski, Stefan A; Faulkner, Robert A; Farthing, Jonathan P; Kontulainen, Saija A; Beck, Thomas J; Baxter-Jones, Adam D G

    2009-06-01

    We examined the timing of the age and the magnitude of peak lean tissue mass accrual (PLTV) relative to the age and magnitude of two variables of bone strength [peak cross sectional area velocity (PCSAV), and peak section modulus velocity, (PZV)] at the proximal femur in males and females during the adolescent growth spurt. We hypothesized that the age of PLTV would precede the ages of PCSAV and PZV and that there is a positive relationship between the magnitude of PLTV and both PCSAV and PZV in both genders. 41 males and 42 females aged 8-18 years were selected from the Saskatchewan Pediatric Bone Mineral Accrual Study (1991-2005). Participants' total body lean tissue mass was assessed annually for 6 consecutive years using DXA. Narrow neck and femoral shaft cross sectional areas (CSA) and section modulus (Z) were determined using the hip structural analysis (HSA) program. Participants were aligned by maturational age (years from peak height velocity). Lean tissue mass, CSA, and Z were converted into whole year velocities and the maturational age of peak tissue velocities was determined using a cubic spline curve fitting procedure. A 2 x 3 (gender x tissue) factorial MANOVA with repeated measures was used to test for differences between age of PLTV and the ages of PCSAV and PZV between genders. Multiple regression analyses were used to examine the relationship between PLTV and both PCSAV and PZV. There were no sex differences in the ages at which tissue peaks occurred when aligned by maturational age. There were significant differences between the age of PLTV and both PCSAV and PZV at the narrow neck (p=0.001) and femoral shaft (p=0.03), where the age of PLTV preceded both PCSAV and PZV when pooled by gender. PLTV was a significant predictor of the magnitude of both PCSAV and PZV at all sites (ptheory that muscle development is an important factor in affecting bone strength.

  12. Development of the Fetal Bone Marrow Niche and Regulation of HSC Quiescence and Homing Ability by Emerging Osteolineage Cells

    Directory of Open Access Journals (Sweden)

    Süleyman Coşkun

    2014-10-01

    Full Text Available Hematopoietic stem cells (HSCs reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5, coincident with marrow vascularization, and were contained within the c-Kit+Sca-1+Lin− (KSL population. We used Osterix-null (Osx−/− mice that form vascularized marrow but lack osteolineage cells to dissect the role(s of these cellular components in HSC development. Osx−/− fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential.

  13. Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells.

    Science.gov (United States)

    Coşkun, Süleyman; Chao, Hsu; Vasavada, Hema; Heydari, Kartoosh; Gonzales, Naomi; Zhou, Xin; de Crombrugghe, Benoit; Hirschi, Karen K

    2014-10-23

    Hematopoietic stem cells (HSCs) reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5), coincident with marrow vascularization, and were contained within the c-Kit(+)Sca-1(+)Lin(-) (KSL) population. We used Osterix-null (Osx(-/-)) mice that form vascularized marrow but lack osteolineage cells to dissect the role(s) of these cellular components in HSC development. Osx(-/-) fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Inter-species investigation of the mechano-regulation of bone healing: comparison of secondary bone healing in sheep and rat.

    Science.gov (United States)

    Checa, Sara; Prendergast, Patrick J; Duda, Georg N

    2011-04-29

    Inter-species differences in regeneration exist in various levels. One aspect is the dynamics of bone regeneration and healing, e.g. small animals show a faster healing response when compared to large animals. Mechanical as well as biological factors are known to play a key role in the process. However, it remains so far unknown whether different animals follow at all comparable mechano-biological rules during tissue regeneration, and in particular during bone healing. In this study, we investigated whether differences observed in vivo in the dynamics of bone healing between rat and sheep are only due to differences in the animal size or whether these animals have a different mechano-biological response during the healing process. Histological sections from in vivo experiments were compared to in silico predictions of a mechano-biological computer model for the simulation of bone healing. Investigations showed that the healing processes in both animal models occur under significantly different levels of mechanical stimuli within the callus region, which could explain histological observations of early intramembranous ossification at the endosteal side. A species-specific adaptation of a mechano-biological model allowed a qualitative match of model predictions with histological observations. Specifically, when keeping cell activity processes at the same rate, the amount of tissue straining defining favorable mechanical conditions for the formation of bone had to be increased in the large animal model, with respect to the small animal, to achieve a qualitative agreement of model predictions with histological data. These findings illustrate that geometrical (size) differences alone cannot explain the distinctions seen in the histological appearance of secondary bone healing in sheep and rat. It can be stated that significant differences in the mechano-biological regulation of the healing process exist between these species. Future investigations should aim towards

  15. The fat mass and obesity associated gene FTO functions in the brain to regulate postnatal growth in mice.

    Directory of Open Access Journals (Sweden)

    Xue Gao

    2010-11-01

    Full Text Available FTO (fat mass and obesity associated was identified as an obesity-susceptibility gene by several independent large-scale genome association studies. A cluster of SNPs (single nucleotide polymorphism located in the first intron of FTO was found to be significantly associated with obesity-related traits, such as body mass index, hip circumference, and body weight. FTO encodes a protein with a novel C-terminal α-helical domain and an N-terminal double-strand β-helix domain which is conserved in Fe(II and 2-oxoglutarate-dependent oxygenase family. In vitro, FTO protein can demethylate single-stranded DNA or RNA with a preference for 3-methylthymine or 3-methyluracil. Its physiological substrates and function, however, remain to be defined. Here we report the generation and analysis of mice carrying a conditional deletion allele of Fto. Our results demonstrate that Fto plays an essential role in postnatal growth. The mice lacking Fto completely display immediate postnatal growth retardation with shorter body length, lower body weight, and lower bone mineral density than control mice, but their body compositions are relatively normal. Consistent with the growth retardation, the Fto mutant mice have reduced serum levels of IGF-1. Moreover, despite the ubiquitous expression of Fto, its specific deletion in the nervous system results in similar phenotypes as the whole body deletion, indicating that Fto functions in the central nerve system to regulate postnatal growth.

  16. Bone mass and vitamin D levels in Parkinson's disease: is there any difference between genders?

    Science.gov (United States)

    Ozturk, Erhan Arif; Gundogdu, Ibrahim; Tonuk, Burak; Kocer, Bilge Gonenli; Tombak, Yasemin; Comoglu, Selcuk; Cakci, Aytul

    2016-08-01

    [Purpose] The aim of this study was to determine the bone mineral density, vitamin D level, and frequencies of osteopenia and osteoporosis in patients with Parkinson's disease and to compare male and female patients with the controls separately. [Subjects and Methods] One hundred fifteen Parkinson's disease patients (47 males, 68 females; age range: 55-85 years) and 117 age- and gender-matched controls (47 males, 70 females) were enrolled in the study. Bone mineral density measured by dual-energy X-ray absorptiometry and serum D vitamin levels of each participant were recorded. [Results] The mean lumbar spine, femur neck, and total femur bone mineral density levels, T-scores, and vitamin D levels were found to be significantly lower in Parkinson's disease patients in both genders. Furthermore, osteoporosis rates were found be significantly higher only in female Parkinson's disease patients compared with female controls. [Conclusion] Data from the present study revealed that while osteoporosis was significantly higher only in female Parkinson's disease patients, all Parkinson's disease patients had lower bone mineral density scores and vitamin D levels compared with the controls regardless of gender, suggesting that clinicians should pay attention to the osteoporosis risk in Parkinson's disease and that adequate preventive measures should be taken in order to limit the future risk due to osteoporotic fractures.

  17. 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 ...

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

    International Nuclear Information System (INIS)

    Yang Jieping; Murthy, Sreemala; Winata, Therry; Werner, Sean; Abe, Masumi; Prahalad, Agasanur K.; Hock, Janet M.

    2006-01-01

    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

  19. Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha (China); Wu, Chuanlong [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Guangwang [Department of Orthopaedic Surgery, The Central Hospital of Xuzhou, Affiliated Hospital of Medical Collage of Southeast University, Xuzhou (China); Fan, Qiming; Tang, Tingting [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Dai, Kerong, E-mail: krdai@163.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

    2014-01-10

    Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.

  20. Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

    International Nuclear Information System (INIS)

    Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei; Ouyang, Zhengxiao; Wu, Chuanlong; Liu, Guangwang; Fan, Qiming; Tang, Tingting; Qin, An; Dai, Kerong

    2014-01-01

    Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases

  1. Massage therapy during early postnatal life promotes greater lean mass and bone growth, mineralization, and strength in juvenile and young adult rats.

    Science.gov (United States)

    Chen, H; Miller, S; Shaw, J; Moyer-Mileur, L

    2009-01-01

    The objects of this study were to investigate the effects of massage therapy during early life on postnatal growth, body composition, and skeletal development in juvenile and young adult rats. Massage therapy was performed for 10 minutes daily from D6 to D10 of postnatal life in rat pups (MT, n=24). Body composition, bone area, mineral content, and bone mineral density were measured by dual energy X-ray absorptiometry (DXA); bone strength and intrinsic stiffness on femur shaft were tested by three-point bending; cortical and cancellous bone histomorphometric measurements were performed at D21 and D60. Results were compared to age- and gender-matched controls (C, n=24). D21 body weight, body length, lean mass, and bone area were significantly greater in the MT cohort. Greater bone mineral content was found in male MT rats; bone strength and intrinsic stiffness were greater in D60 MT groups. At D60 MT treatment promoted bone mineralization by increasing trabecular mineral apposition rate in male and endosteal mineral surface in females, and also improved micro-architecture by greater trabeculae width in males and decreasing trabecular separation in females. In summary, massage therapy during early life elicited immediate and prolonged anabolic effects on postnatal growth, lean mass and skeletal developmental in a gender-specific manner in juvenile and young adult rats.

  2. Does body mass play a role in the regulation of food intake?

    Science.gov (United States)

    Speakman, John R; Stubbs, R James; Mercer, Julian G

    2002-11-01

    It is widely believed that body fatness (and hence total body mass) is regulated by a lipostatic feedback system. This system is suggested to involve at least one peripheral signalling compound, which signals to the brain the current size of body fat stores. In the brain the level of the signal is compared with a desirable target level, and food intake and energy expenditure are then regulated to effect changes in the size of body fat stores. There is considerable support for this theory at several different levels of investigation. Patterns of body-mass change in subjects forced into energy imbalance seem to demonstrate homeostasis, and long-term changes in body mass are minor compared with the potential changes that might result from energy imbalance. Molecular studies of signalling compounds have suggested a putative lipostatic signal (leptin) and a complex network of downstream processing events in the brain, polymorphisms of which lead to disruption of body-mass regulation. This network of neuropeptides provides a rich seam of potential pharmaceutical targets for the control of obesity. Despite this consistent explanation for the observed phenomena at several different levels of enquiry, there are alternative explanations. In the present paper we explore the possibility that the existence of lipostatic regulation of body fatness is an illusion generated by the links between body mass and energy expenditure and responses to energy imbalance that are independent of body mass. Using computer-based models of temporal patterns in energy balance we show that common patterns of change in body mass following perturbation can be adequately explained by this 'non-lipostatic' model. This model has some important implications for the interpretations that we place on the molecular events in the brain, and ultimately in the search for pharmaceutical agents for alleviation of obesity.

  3. Spatial regulation of bone morphogenetic proteins (BMPs) in postnatal articular and growth plate cartilage

    Science.gov (United States)

    Garrison, Presley; Yue, Shanna; Hanson, Jeffrey; Baron, Jeffrey; Lui, Julian C.

    2017-01-01

    Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers—the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation. To investigate the presence of a similar expression gradient in articular cartilage, we used laser capture microdissection (LCM) to separate murine growth plate and articular cartilage from the proximal tibia into their six constituent zones, and used a solution hybridization assay with color-coded probes (nCounter) to quantify mRNAs for 30 different BMP-related genes in each zone. In situ hybridization and immunohistochemistry were then used to confirm spatial expression patterns. Expression gradients for Bmp2 and 6 were observed across growth plate cartilage with highest expression in hypertrophic zone. However, intracellular BMP signaling, assessed by phospho-Smad1/5/8 immunohistochemical staining, appeared to be higher in the proliferative zone and prehypertrophic area than in hypertrophic zone, possibly due to high expression of Smad7, an inhibitory Smad, in the hypertrophic zone. We also found BMP expression gradients across the articular cartilage with BMP agonists primarily expressed in the superficial zone and BMP functional antagonists primarily expressed in the deep zone. Phospho-Smad1/5/8 immunohistochemical staining showed a similar gradient. In combination with previous evidence that BMPs regulate chondrocyte proliferation and differentiation, the current findings suggest that BMP signaling gradients exist across both growth plate and articular cartilage and that these gradients may

  4. Isotopic analysis of calcium in blood plasma and bone from mouse samples by multiple collector-ICP-mass spectrometry

    International Nuclear Information System (INIS)

    Hirata, Takafumi; Tanoshima, Mina; Suga, Akinobu; Tanaka, Yu-ki; Nagata, Yuichi; Shinohara, Atsuko; Chiba, Momoko

    2008-01-01

    The biological processing of Ca produces significant stable isotope fractionation. The level of isotopic fractionation can provide key information about the variation in dietary consumption or Ca metabolism. To investigate this, we measured the 43 Ca/ 42 Ca and 44 Ca/ 42 Ca ratios for bone and blood plasma samples collected from mice of various ages using multiple collector-ICP-mass spectrometry (MC-ICP-MS). The 44 Ca/ 42 Ca ratio in bones was significantly (0.44 - 0.84 per mille) lower than the corresponding ratios in the diet, suggesting that Ca was isotopically fractionated during Ca metabolism for bone formation. The resulting 44 Ca/ 42 Ca ratios for blood plasma showed almost identical, or slightly higher, values (0.03 - 0.2 per mille) than found in a corresponding diet. This indicates that a significant amount of Ca in the blood plasma was from dietary sources. Unlike that discovered for Fe, there were not significant differences in the measured 44 Ca/ 42 Ca ratios between female and male specimens (for either bone or blood plasma samples). Similarity, the 44 Ca/ 42 Ca ratios suggests that there were no significant differences in Ca dietary consumption or Ca metabolism between female and male specimens. In contrast, the 44 Ca/ 42 Ca ratios of blood plasma from mother mice during the lactation period were significantly higher than those for all other adult specimens. This suggests that Ca supplied to infants through lactation was isotopically lighter, and the preferential supply of isotropically lighter Ca resulted in isotopically heavier Ca in blood plasma of mother mice during the lactation period. The data obtained here clearly demonstrate that the Ca isotopic ratio has a potential to become a new tool for evaluating changes in dietary consumption, or Ca metabolism of animals. (author)

  5. Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass

    NARCIS (Netherlands)

    Petretto, Enrico; Sarwar, Rizwan; Grieve, Ian; Lu, Han; Kumaran, Mande K.; Muckett, Phillip J.; Mangion, Jonathan; Schroen, Blanche; Benson, Matthew; Punjabi, Prakash P.; Prasad, Sanjay K.; Pennell, Dudley J.; Kiesewetter, Chris; Tasheva, Elena S.; Corpuz, Lolita M.; Webb, Megan D.; Conrad, Gary W.; Kurtz, Theodore W.; Kren, Vladimir; Fischer, Judith; Hubner, Norbert; Pinto, Yigal M.; Pravenec, Michal; Aitman, Timothy J.; Cook, Stuart A.

    2008-01-01

    Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac

  6. Association between Interleukin-15 and Obesity: Interleukin-15 as a Potential Regulator of Fat Mass

    DEFF Research Database (Denmark)

    Nielsen, Anders Rinnov; Hojman, Pernille; Erikstrup, Christian

    2008-01-01

    Objective: IL-15 decreases lipid deposition in preadipocytes and decreases the mass of white adipose tissue in rats, indicating that IL-15 may take part in regulating this tissue. IL-15 is expressed in human skeletal muscle and skeletal muscle may be a source of plasma IL-15 and in this way...

  7. 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.

  8. IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

    Science.gov (United States)

    Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

    2016-02-01

    Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data

  9. Oxygen tension regulates the osteogenic, chondrogenic and endochondral phenotype of bone marrow derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Sheehy, Eamon J.; Buckley, Conor T. [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Dublin 2 (Ireland); Kelly, Daniel J., E-mail: kellyd9@tcd.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Dublin 2 (Ireland)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Expansion in low oxygen enhances MSC proliferation and osteogenesis. Black-Right-Pointing-Pointer Differentiation in low oxygen enhances chondrogenesis and suppresses hypertrophy. Black-Right-Pointing-Pointer Oxygen can regulate the MSC phenotype for use in tissue engineering applications. -- Abstract: The local oxygen tension is a key regulator of the fate of mesenchymal stem cells (MSCs). The objective of this study was to investigate the effect of a low oxygen tension during expansion and differentiation on the proliferation kinetics as well as the subsequent osteogenic and chondrogenic potential of MSCs. We first hypothesised that expansion in a low oxygen tension (5% pO{sub 2}) would improve both the subsequent osteogenic and chondrogenic potential of MSCs compared to expansion in a normoxic environment (20% pO{sub 2}). Furthermore, we hypothesised that chondrogenic differentiation in a low oxygen environment would suppress hypertrophy of MSCs cultured in both pellets and hydrogels used in tissue engineering strategies. MSCs expanded at 5% pO{sub 2} proliferated faster forming larger colonies, resulting in higher cell yields. Expansion at 5% pO{sub 2} also enhanced subsequent osteogenesis of MSCs, whereas differentiation at 5% pO{sub 2} was found to be a more potent promoter of chondrogenesis than expansion at 5% pO{sub 2}. Greater collagen accumulation, and more intense staining for collagen types I and X, was observed in pellets maintained at 20% pO{sub 2} compared to 5% pO{sub 2}. Both pellets and hydrogels stained more intensely for type II collagen when undergoing chondrogenesis in a low oxygen environment. Differentiation at 5% pO{sub 2} also appeared to inhibit hypertrophy in both pellets and hydrogels, as demonstrated by reduced collagen type X and Alizarin Red staining and alkaline phosphatase activity. This study demonstrates that the local oxygen environment can be manipulated in vitro to either stabilise a

  10. P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis.

    Science.gov (United States)

    Wang, Ning; Agrawal, Ankita; Jørgensen, Niklas Rye; Gartland, Alison

    2018-02-22

    Post-menopausal osteoporosis is a condition that affects millions worldwide and places a huge socio-economic burden on society. Previous research has shown an association of loss of function SNPs in the gene for the purinergic receptor P2X7R with low bone mineral density, increased rates of bone loss and vertebral fractures in post-menopausal women. In this study we use a mouse model of oestrogen deficiency-induced bone loss and the BALB/cJ P2X7R -/- to show that absence of the P2X7R resulted in increased bone loss. Osteoclast precursors were isolated from both BALB/cJ P2X7R -/- and BALB/cJ P2X7R +/+ mice and then cultured in vitro to form mature resorbing osteoclasts. The BALB/cJ P2X7R -/- derived precursors generated slightly more osteoclasts but with a significant reduction in the amount of resorption per osteoclast. Furthermore, when using modified culture conditions osteoclast activity was additionally increased in the absence of the P2X7R suggest that P2X7R may regulate the lifespan and activity of osteoclasts. Finally using mechanical loading as an anabolic stimulus for bone formation, we demonstrated that the increased oestrogen-deficient bone loss could be rescued, even in the absence of P2X7R. This study paves the way for clinical intervention for women with post-menopausal osteoporosis and P2XR7 loss of function polymorphisms.

  11. Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome.

    Science.gov (United States)

    Nakamura, Tomomi; Tsuburai, Taku; Tokinaga, Aya; Nakajima, Izumi; Kitayama, Reiko; Imai, Yuichi; Nagata, Tomoko; Yoshida, Hiroshi; Hirahara, Fumiki; Sakakibara, Hideya

    2015-01-01

    Estrogen replacement therapy (ERT) is necessary for uterine development and bone mass acquisition in women with Turner syndrome (TS) suffering from ovarian insufficiency. However, adequate ERT regimens have not yet been established. The aim of this study was to evaluate the efficacy of ERT for both uterine development and bone mass acquisition. One hundred TS patients from Yokohama City University Hospital (88 with primary amenorrhea (PA) and 12 patients with spontaneous menstrual cycles (MC)) were enrolled after obtaining consent. Clinical profiles, uterine length (UL) measured by ultrasonic examination, and bone mineral density (BMD) of the lumbar vertebrae (L2-4) assessed by DEXA were evaluated. At the time of the first visit, the ULs of patients in the PA group were significantly shorter than those in the MC group. After receiving ERT, there were no significant differences in UL between patients with PA and MC. Forty-seven patients for whom the ERT initiation age was known were investigated to clarify the influence on BMD. The results showed that the BMD in the late initiation (18 years or older) group at the latest visit (0.770 ± 0.107 g/cm2: n = 16) was significantly lower than that in the early initiation (under 18 years) group (0.858 ± 0.119 g/cm2: n = 21) or the MC group (0.941 ± 0.118 g/cm2: n = 10). No significant differences were seen between the early initiation and MC group. ERT was effective in increasing UL and BMD. However, early initiation of ERT is necessary to increase BMD.

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    ) at the distal forearm at least 1.5 standard deviations below the premenopausal mean peak value. A total of 141 women (78%) completed the first year, and 119 women (66%) the second year of the study. The dose-response data of the first year have been published previously (Ravn et al. Bone 19...... with the highest doses of ibandronate (1.0-5.0 mg) (p

  13. The effect of hemiplegia on bone mass and soft tissue body composition

    International Nuclear Information System (INIS)

    Iversen, E.; Hassager, C.; Christiansen, C.

    1989-01-01

    The content of bone mineral (BMC), lean tissue, and fat tissue were measured by single and dual photon absorptiometry in both the paretic and the nonparetic limbs of 15 patients, hemiplegic due to cerebrovascular accident 23-38 weeks earlier. Compared with the non-paretic arm, the paretic arm had approximately 10% lower (P < 0.01) BMC. This difference was largest at the measuring site with the highest ratio of trabecular to compact bone. The paretic leg had a 4% (P < 0.001) lower BMC than the non-paretic leg. For both the arms and the legs, the lean content was lower (P < 0.05) and the fat content higher (P < 0.01) in the paretic than in the non-paretic. This was relatively more pronounced in the arms than in the legs. We conclude that partial immobilization, owing to parasis after a cerebrovascular accident, results in characteristic changes in the affected limbs, with a marked decrease in the content of bone and lean tissue and a pronounced increase in fatty tissue. (author)

  14. Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

    Science.gov (United States)

    Wang, T. M.; Hsu, J. F.; Jee, W. S.; Matthews, J. L.

    1993-01-01

    The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

  15. Application and Effect of Mobiletype-Bone Health Intervention in Korean Young Adult Women with Low Bone Mass: A Randomized Control Trial

    Directory of Open Access Journals (Sweden)

    Young-Joo Park, PhD, RN

    2017-03-01

    Conclusion: Although both experimental groups exhibited positive outcomes in regards to the promotion of bone health, this study did not show an additional effect of the mobile application on self-management ability for the promotion of bone health. Nonetheless, the SbFb application is very meaningful as it is the first application developed with the aim of improving women's bone health.

  16. Osteocyte regulation of phosphate homeostasis and bone mineralization underlies the pathophysiology of the heritable disorders of rickets and osteomalacia

    Science.gov (United States)

    Feng, Jian Q.; Clinkenbeard, Erica L.; Yuan, Baozhi; White, Kenneth E.; Drezner, Marc K.

    2013-01-01

    Although recent studies have established that osteocytes function as secretory cells that regulate phosphate metabolism, the biomolecular mechanism(s) underlying these effects remain incompletely defined. However, investigations focusing on the pathogenesis of X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), and autosomal recessive hypophosphatemic rickets (ARHR), heritable disorders characterized by abnormal renal phosphate wasting and bone mineralization, have clearly implicated FGF23 as a central factor in osteocytes underlying renal phosphate wasting, documented new molecular pathways regulating FGF23 production, and revealed complementary abnormalities in osteocytes that regulate bone mineralization. The seminal observations leading to these discoveries were the following: 1) mutations in FGF23 cause ADHR by limiting cleavage of the bioactive intact molecule, at a subtilisin-like protein convertase (SPC) site, resulting in increased circulating FGF23 levels and hypophosphatemia; 2) mutations in DMP1 cause ARHR, not only by increasing serum FGF23, albeit by enhanced production and not limited cleavage, but also by limiting production of the active DMP1 component, the C-terminal fragment, resulting in dysregulated production of DKK1 and β-catenin, which contributes to impaired bone mineralization; and 3) mutations in PHEX cause XLH both by altering FGF23 proteolysis and production and causing dysregulated production of DKK1 and β-catenin, similar to abnormalities in ADHR and ARHR, but secondary to different central pathophysiological events. These discoveries indicate that ADHR, XLH, and ARHR represent three related heritable hypophosphatemic diseases that arise from mutations in, or dysregulation of, a single common gene product, FGF23 and, in ARHR and XLH, complimentary DMP1 and PHEX directed events that contribute to abnormal bone mineralization. PMID:23403405

  17. Can the growth factors PTHrP, Ihh and VEGF, together regulate the development of a long bone?

    Science.gov (United States)

    Brouwers, J E M; van Donkelaar, C C; Sengers, B G; Huiskes, R

    2006-01-01

    Endochondral ossification is the process of differentiation of cartilaginous into osseous tissue. Parathyroid hormone related protein (PTHrP), Indian hedgehog (Ihh) and vascular endothelial growth factor (VEGF), which are synthesized in different zones of the growth plate, were found to have crucial roles in regulating endochondral ossification. The aim of this study was to evaluate whether the three growth factors PTHrP, Ihh and VEGF, together, could regulate longitudinal growth in a normal human, fetal femur. For this purpose, a one-dimensional finite element (FE) model, incorporating growth factor signaling, was developed of the human, distal, femoral growth plate. It included growth factor synthesis in the relevant zones, their transport and degradation and their effects. Simulations ran from initial hypertrophy in the center of the bone until secondary ossification starts at approximately 3.5 months postnatal. For clarity, we emphasize that no mechanical stresses were considered. The FE model showed a stable growth plate in which the bone growth rate was constant and the number of cells per zone oscillated around an equilibrium. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates resulted, respectively, in more and less cells per zone and in increased and decreased bone growth rates. The FE model correctly reflected the development of a growth plate and the rate of bone growth in the femur. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates reflected growth plate pathologies and growth plates in PTHrP-/- and Ihh-/- mice. The three growth factors, PTHrP, Ihh and VEGF, could potentially together regulate tissue differentiation.

  18. LIVER AND BONE MARROW STEM/PROGENITOR CELLS AS REGULATORS OF REPARATIVE REGENERATION OF DAMAGED LIVER

    Directory of Open Access Journals (Sweden)

    А. V. Lundup

    2010-01-01

    Full Text Available In this review the modern information about effectiveness of liver insufficiency treatment by stem/ progenitor cells of liver (oval cells and bone marrow (hemopoietic cells and mesenchymal cells was presented. It is shown that medical action of these cells is referred on normalization of liver cell interaction and reorganization of processes of a reparative regeneration in damaged liver. It is believed that application of mesenchymal stromal cells from an autological bone marrow is the most perspective strategy. However, for definitive judgement about regenerative possibilities of the autological bone marrow cells it is necessary to carry out large-scale double blind clinical researches. 

  19. 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)

    Meema, S.; Meema, H.E.

    1982-01-01

    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.)

  20. The effect of feeding different sugar-sweetened beverages to growing female Sprague-Dawley rats on bone mass and strength.

    Science.gov (United States)

    Tsanzi, Embedzayi; Light, Heather R; Tou, Janet C

    2008-05-01

    Consumption of sugar beverages has increased among adolescents. Additionally, the replacement of sucrose with high fructose corn syrup (HFCS) as the predominant sweetener has resulted in higher fructose intake. Few studies have investigated the effect of drinking different sugar-sweetened beverages on bone, despite suggestions that sugar consumption negatively impacts mineral balance. The objective of this study was to determine the effect of drinking different sugar-sweetened beverages on bone mass and strength. Adolescent (age 35d) female Sprague-Dawley rats were randomly assigned (n=8-9/group) to consume deionized distilled water (ddH2O, control) or ddH2O containing 13% w/v glucose, sucrose, fructose or high fructose corn syrup (HFCS-55) for 8weeks. Tibia and femur measurements included bone morphometry, bone turnover markers, determination of bone mineral density (BMD) and bone mineral content (BMC) by dual energy X-ray absorptiometry (DXA) and bone strength by three-point bending test. The effect of sugar-sweetened beverage consumption on mineral balance, urinary and fecal calcium (Ca) and phosphorus (P) was measured by inductively coupled plasma optical emission spectrometry. The results showed no difference in the bone mass or strength of rats drinking the glucose-sweetened beverage despite their having the lowest food intake, but the highest beverage and caloric consumption. Only in comparisons among the rats provided sugar-sweetened beverage were femur and tibia BMD lower in rats drinking the glucose-sweetened beverage. Differences in bone and mineral measurements appeared most pronounced between rats drinking glucose versus fructose-sweetened beverages. Rats provided the glucose-sweetened beverage had reduced femur and tibia total P, reduced P and Ca intake and increased urinary Ca excretion compared to the rats provided the fructose-sweetened beverage. The results suggested that glucose rather than fructose exerted more deleterious effects on mineral

  1. Dopamine D2 Receptor-Mediated Regulation of Pancreatic β Cell Mass

    Directory of Open Access Journals (Sweden)

    Daisuke Sakano

    2016-07-01

    Full Text Available Understanding the molecular mechanisms that regulate β cell mass and proliferation is important for the treatment of diabetes. Here, we identified domperidone (DPD, a dopamine D2 receptor (DRD2 antagonist that enhances β cell mass. Over time, islet β cell loss occurs in dissociation cultures, and this was inhibited by DPD. DPD increased proliferation and decreased apoptosis of β cells through increasing intracellular cAMP. DPD prevented β cell dedifferentiation, which together highly contributed to the increased β cell mass. DRD2 knockdown phenocopied the effects of domperidone and increased the number of β cells. Drd2 overexpression sensitized the dopamine responsiveness of β cells and increased apoptosis. Further analysis revealed that the adenosine agonist 5′-N-ethylcarboxamidoadenosine, a previously identified promoter of β cell proliferation, acted with DPD to increase the number of β cells. In humans, dopamine also modulates β cell mass through DRD2 and exerts an inhibitory effect on adenosine signaling.

  2. MFAP5 promotes tumor progression and bone metastasis by regulating ERK/MMP signaling pathways in breast cancer.

    Science.gov (United States)

    Wu, Zhiqiang; Wang, Ting; Fang, Meng; Huang, Wending; Sun, Zhengwang; Xiao, Jianru; Yan, Wangjun

    2018-04-06

    Breast cancer accounts for about 30% of all cancers in women, while approximately 70% breast cancer patients developed bone metastases throughout the course of their disease, highlighting the importance of exploring new therapeutic targets. Microfibrillar-associated protein 5 (MFAP5) is a component of extracellular elastic microfibril which has been confirmed to function in tissue development and cancer progression. But the role of MFAP5 in breast cancer remains unclear. The present study demonstrated that MFAP5 was up-regulated in breast cancers compared with that in normal breast tissues, and further increased in breast cancer bone metastasis. Functionally, MFAP5 overexpression accelerated breast cancer cell proliferation and migration, while an opposite effect was observed when MFAP5 was knocked down. In addition, up-regulation of MFAP5 increased the expression of MMP2 and MMP9 and activated the ERK signaling pathway. Conversely, inhibition of MFAP5 suppressed the expression of MMP2, MMP9, p-FAK, p-Erk1/2 and p-cJun. These findings may provide a better understanding about the mechanism of breast cancer and suggest that MFAP5 may be a potential prognostic biomarker and therapeutic target for breast cancer, especially for bone metastasis of breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Relationship between parity and bone mass in postmenopausal women according to number of parities and age.

    Science.gov (United States)

    Heidari, Behzad; Heidari, Parnaz; Nourooddini, Haj Ghorban; Hajian-Tilaki, Karim Ollah

    2013-01-01

    To investigate the impact of multiple pregnancies on postmenopausal bone mineral density (BMD). BMD at the femoral neck (FN) and lumbar spine (LS) was measured by dual energy X-ray absorptiometry (DXA) method. Diagnosis of osteoporosis (OP) was confirmed by World Health Organization criteria. Women were stratified according to number of parity as 7 parity groups as well as in age groups of or = 65 years. BMD values and frequency of OP were compared across the groups according to age. Multiple logistic regression analysis with calculation of adjusted odds ratio (OR) was used for association. A total of 264 women with mean age of 63 +/- 8.7 and mean menopausal duration of 15.8 +/- 10.2 years were studied. LS-OP and FN-OP were observed in 28% and 58.3% of women, respectively. There were significant differences in BMD values across different parity groups at both sites of LS and FN (p = 0.011 and p = 0.036, respectively). Parity 4-7 (vs. 7 significantly decreased LS-BMD and FN-BMD as compared with 0-7 parity (p = 0.006 and p = 0.009, respectively). Parity > 7 increased the risk of LS-OP by OR = 1.81 (95% CI 1.03-3.1, p = 0.037) and FN-OP by OR = 1.67 (95% CI 0.97-2.8, p = 0.063). In addition, women with high parity had lower BMD decline at LS and FN by age (> or = 65 vs. 7 is associated with spinal trabecular bone loss in younger postmenopausal women as well as an osteoprotective effect against age-related bone loss, which counteracts the early negative effect. Therefore, parity should not be considered as a risk factor for postmenopausal osteoporosis.

  4. Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

    Science.gov (United States)

    Davey, Jonathan R.; Watt, Kevin I.; Parker, Benjamin L.; Chaudhuri, Rima; Ryall, James G.; Cunningham, Louise; Qian, Hongwei; Sartorelli, Vittorio; Chamberlain, Jeffrey; James, David E.

    2016-01-01

    The transforming growth factor-β (TGF-β) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-β network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-β network–responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles. PMID:27182554

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

    International Nuclear Information System (INIS)

    McCloskey, E.V.; Dey, A.; Bostock, J.; Parr, R.M.; Aras, N.; Balogh, A.; Borelli, A.; Krishnan, S.; Lobo, G.; Qin, L.L.

    2004-01-01

    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)

  6. Adaptive bone formation in acellular vertebrae of sea bass (Dicentrarchus labrax L.)

    NARCIS (Netherlands)

    Kranenbarg, S.; Cleynenbreugel, van T.; Schipper, H.; Leeuwen, van J.L.

    2005-01-01

    Mammalian bone is an active tissue in which osteoblasts and osteoclasts balance bone mass. This process of adaptive modelling and remodelling is probably regulated by strain-sensing osteocytes. Bone of advanced teleosts is acellular yet, despite the lack of osteocytes, it is capable of an adaptive

  7. The protective effect of Rhizoma Dioscoreae extract against alveolar bone loss in ovariectomized rats via regulating Wnt and p38 MAPK signaling.

    Science.gov (United States)

    Zhang, Zhiguo; Xiang, Lihua; Bai, Dong; Wang, Wenlai; Li, Yan; Pan, Jinghua; Liu, Hong; Wang, Shaojun; Xiao, Gary Guishan; Ju, Dahong

    2014-12-12

    The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats were subjected to either ovariectomy or a sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX) or RDE by oral gavage or with 17β-estradiol (E2) subcutaneously. After treatments, the bone mineral density (BMD), the three-dimensional bone architecture of the alveolar bone and the plasma biomarkers of bone turnover were analyzed to assess bone metabolism, and the histomorphometry of the alveolar bone was observed. Microarrays were used to evaluate gene expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of genes was further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using real-time quantitative RT-PCR (qRT-PCR). Our results showed that RDE inhibited alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 207 genes and downregulated expression levels of 176 genes in the alveolar bone. The IPA showed that several genes had the potential to code for proteins that were involved in the Wnt/β-catenin signaling pathway (Wnt7a, Fzd2, Tcf3, Spp1, Frzb, Sfrp2 and Sfrp4) and the p38 MAPK signaling pathway (Il1rn and Mapk14). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may be involved in the reduced abnormal bone remodeling, which is associated with the modulation of the Wnt/β-catenin and the p38 MAPK signaling pathways via gene regulation.

  8. mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass

    Directory of Open Access Journals (Sweden)

    Mee-Sup Yoon

    2017-10-01

    Full Text Available Maintenance of skeletal muscle mass is regulated by the balance between anabolic and catabolic processes. Mammalian target of rapamycin (mTOR is an evolutionarily conserved serine/threonine kinase, and is known to play vital roles in protein synthesis. Recent findings have continued to refine our understanding of the function of mTOR in maintaining skeletal muscle mass. mTOR controls the anabolic and catabolic signaling of skeletal muscle mass, resulting in the modulation of muscle hypertrophy and muscle wastage. This review will highlight the fundamental role of mTOR in skeletal muscle growth by summarizing the phenotype of skeletal-specific mTOR deficiency. In addition, the evidence that mTOR is a dual regulator of anabolism and catabolism in skeletal muscle mass will be discussed. A full understanding of mTOR signaling in the maintenance of skeletal muscle mass could help to develop mTOR-targeted therapeutics to prevent muscle wasting.

  9. Pleiotrophin Regulates the Retention and Self-Renewal of Hematopoietic Stem Cells in the Bone Marrow Vascular Niche

    Directory of Open Access Journals (Sweden)

    Heather A. Himburg

    2012-10-01

    Full Text Available The mechanisms through which the bone marrow (BM microenvironment regulates hematopoietic stem cell (HSC fate remain incompletely understood. We examined the role of the heparin-binding growth factor pleiotrophin (PTN in regulating HSC function in the niche. PTN−/− mice displayed significantly decreased BM HSC content and impaired hematopoietic regeneration following myelosuppression. Conversely, mice lacking protein tyrosine phosphatase receptor zeta, which is inactivated by PTN, displayed significantly increased BM HSC content. Transplant studies revealed that PTN action was not HSC autonomous, but rather was mediated by the BM microenvironment. Interestingly, PTN was differentially expressed and secreted by BM sinusoidal endothelial cells within the vascular niche. Furthermore, systemic administration of anti-PTN antibody in mice substantially impaired both the homing of hematopoietic progenitor cells to the niche and the retention of BM HSCs in the niche. PTN is a secreted component of the BM vascular niche that regulates HSC self-renewal and retention in vivo.

  10. Low calcium-phosphate intakes modulate the low-protein diet-related effect on peak bone mass acquisition: a hormonal and bone strength determinants study in female growing rats.

    Science.gov (United States)

    Fournier, C; Rizzoli, R; Ammann, P

    2014-11-01

    Peak bone mass acquisition is influenced by environmental factors including dietary intake. A low-protein diet delays body and skeletal growth in association with a reduction in serum IGF-1 whereas serum FGF21 is increased by selective amino acid deprivation. Calcium (Ca) and phosphorous (P) are also key nutrients for skeletal health, and inadequate intakes reduce bone mass accrual in association with calciotropic hormone modulation. Besides, the effect of calcium supplementation on bone mass in prepubertal children appears to be influenced by protein intake. To further explore the interaction of dietary protein and Ca-P intake on bone growth, 1-month-old female rats were fed with an isocaloric 10%, 7.5%, or 5% casein diet containing normal or low Ca-P for an 8-week period (6 groups). Changes in tibia geometry, mineral content, microarchitecture, strength, and intrinsic bone quality were analyzed. At the hormonal level, serum IGF-1, fibroblast growth factor 21 (FGF21), PTH, 1,25-dihydroxyvitamin D3 (calcitriol), and FGF23 were investigated as well as the Ghr hepatic gene expression. In normal dietary Ca-P conditions, bone mineral content, trabecular and cortical bone volume, and bone strength were lower in the 5% casein group in association with a decrease in serum IGF-1 and an increase in FGF21 levels. Unexpectedly, the low-Ca-P diet attenuated the 5% casein diet-related reduction of serum IGF-1 and Ghr hepatic gene expression, as well as the low-protein diet-induced decrease in bone mass and strength. However, this was associated with lower cortical bone material level properties. The low-Ca-P diet increased serum calcitriol but decreased FGF23 levels. Calcitriol levels positively correlated with Ghr hepatic mRNA levels. These results suggest that hormonal modulation in response to a low-Ca-P diet may modify the low-protein diet-induced effect on Ghr hepatic mRNA levels and consequently the impact of low protein intakes on IGF-1 circulating levels and skeletal

  11. T3 Regulates a Human Macrophage-Derived TSH-β Splice Variant: Implications for Human Bone Biology.

    Science.gov (United States)

    Baliram, R; Latif, R; Morshed, S A; Zaidi, M; Davies, T F

    2016-09-01

    TSH and thyroid hormones (T3 and T4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-β splice variant (TSH-βv) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblastogenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-β variant in human macrophages. Real-time PCR analyses using human TSH-β-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-βv previously reported. We then examined TSH-βv regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T3 showed a 14-fold induction of human TSH-βv mRNA and variant protein. Furthermore, these human TSH-βv-positive cells, induced by T3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-βv, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors.

  12. Protective effect of Rhizoma Dioscoreae extract against alveolar bone loss in ovariectomized rats via regulation of IL-6/STAT3 signaling.

    Science.gov (United States)

    Zhang, Zhi-Guo; Chen, Yan-Jing; Xiang, Li-Hua; Pan, Jing-Hua; Wang, Zhen; Xiao, Gary Guishan; Ju, Da-Hong

    2017-11-01

    The aim of the present study was to assess the effectiveness of Rhizoma Dioscoreae extract (RDE) on preventing rat alveolar bone loss induced by ovariectomy (OVX), and to determine the role of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in this effect. Female Wistar rats were subjected to OVX or sham surgery. The rats that had undergone OVX were treated with RDE (RDE group), vehicle (OVX group) or 17β-estradiol subcutaneous injection (E2 group). Subsequently, bone metabolic activity was assessed by analyzing 3-D alveolar bone construction, bone mineral density, as well as the plasma biomarkers of bone turnover. The gene expression of alveolar bone in the OVX and RDE groups was evaluated by IL-6/STAT3 signaling pathway polymerase chain reaction (PCR) arrays, and differentially expressed genes were determined through reverse transcription-quantitative PCR. The inhibitory effect of RDE on alveolar bone loss in the OVX group was demonstrated in the study. In comparison with the OVX group, the RDE group exhibited 19 downregulated genes and 1 upregulated gene associated with the IL-6/STAT3 signaling pathway in alveolar bone. Thus, RDE was shown to relieve OVX-induced alveolar bone loss in rats, an effect which was likely associated with decreased abnormal bone remodeling via regulation of the IL-6/STAT3 signaling pathway.

  13. Regulation of heme metabolism in normal and sideroblastic bone marrow cells in culture

    International Nuclear Information System (INIS)

    Ibraham, N.G.; Lutton, J.D.; Hoffman, R.; Levere, R.D.

    1985-01-01

    Heme metabolism was examined in developing in vitro erythroid colonies (CFUE) and in bone marrow samples taken directly from four normal donors and four patients with sideroblastic anemia. Maximum activities of delta-aminolevulinic acid synthase (ALAS), ALA dehydratase (ALAD), and 14 C-ALA incorporation into heme were achieved in normal marrow CFUE after 8 days of culture, whereas heme oxygenase progressively decreased to low levels of activity during the same period. Assays on nucleated bone marrow cells taken directly from patients revealed that ALAS activity was considerably reduced in idiopathic sideroblastic anemia (IASA) and X-linked sideroblastic anemia (X-SA) bone marrow specimens, whereas the activity increased more than twofold (normal levels) when cells were assayed from 8-day CFUE. In all cases, ALAD activity appeared to be within normal levels. Measurement of heme synthesis revealed that normal levels of 14 C-ALA incorporation into heme were achieved in IASA cells but were reduced in X-SA cells. In marked contrast to levels in normal cells, heme oxygenase was found to be significantly elevated (two- to fourfold) in bone marrow cells taken directly from patients with IASA and X-SA. Results from this study demonstrate that IASA and X-SA bone marrow cells have disturbances in ALAS and heme metabolism, and that erythropoiesis (CFUE) can be restored to normal levels when cells are cultured in methylcellulose

  14. Mass and elemental concentrations of air bone particles at Kuala Lumpur site in 2000 to 2006

    International Nuclear Information System (INIS)

    Abdul Khalik Wood; Mohd Suhaimi Hamzah; Shamsiah Abdul Rahman

    2008-01-01

    Atmospheric Pollution due to air bone particle is a major concern to many cities in the Southeast Asian region, including Kuala Lumpur. Within the last six years air particulate samples have been collected from a site in Kuala Lumpur and measured for their PM10, PM2.5 and elemental concentrations. The results showed that the daily PM10 (<10μ diameter) concentrations were generally acceptable but the values occasionally very high, especially during the haze episodes. The PM10 annual average values were just below the national set standard and these values were mostly contributed by the fine particles (<2μ diameter) concentration. The annual average for PM2.5 (fine particle) concentrations over the past few years were considerably high where elemental carbon, sulfur and potassium were the main components. (Author)

  15. The Intriguing Regulators of Muscle Mass in Sarcopenia and Muscular Dystrophy

    OpenAIRE

    Sakuma, Kunihiro; Aoi, Wataru; Yamaguchi, Akihiko

    2014-01-01

    Recent advances in our understanding of the biology of muscle have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle mass and increased intramuscular fibrosis occur in both sarcopenia and muscular dystrophy. Several regulators (mammalian target of rapamycin, serum response factor, atrogin-1, myostatin, etc.) seem to modulate protein synthesis and degradation or transcription of muscle-specific genes during both sarcopenia and muscular dystrophy. This revie...

  16. Determinants of Growth, Adiposity and Bone Mass in Early Life : The Generation R Study

    NARCIS (Netherlands)

    D.H.M. Heppe (Denise)

    2016-01-01

    markdownabstractAbstract Environmental influences during fetal life and early infancy have been suggested to influence body composition throughout the life-course. Especially poor fetal nutrition and fetal growth restriction have been designated important risk factors for gaining high fat mass

  17. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    NARCIS (Netherlands)

    Xu, Cui-Ping; Ji, Wen-Min; van den Brink, Gijs R.; Peppelenbosch, Maikel P.

    2006-01-01

    To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. Fifty-four adult male Wistar rats were randomly

  18. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    NARCIS (Netherlands)

    Xu, Cui-Ping; Ji, Wen-Min; van den Brink, Gijs R.; Peppelenbosch, Maikel P.

    2006-01-01

    AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. METHODS: Fifty-four adult male Wistar rats

  19. CDK2 phosphorylation of Smad2 disrupts TGF-beta transcriptional regulation in resistant primary bone marrow myeloma cells.

    Science.gov (United States)

    Baughn, Linda B; Di Liberto, Maurizio; Niesvizky, Ruben; Cho, Hearn J; Jayabalan, David; Lane, Joseph; Liu, Fang; Chen-Kiang, Selina

    2009-02-15

    Resistance to growth suppression by TGF-beta1 is common in cancer; however, mutations in this pathway are rare in hematopoietic malignancies. In multiple myeloma, a fatal cancer of plasma cells, malignant cells accumulate in the TGF-beta-rich bone marrow due to loss of both cell cycle and apoptotic controls. Herein we show that TGF-beta activates Smad2 but fails to induce cell cycle arrest or apoptosis in primary bone marrow myeloma and human myeloma cell lines due to its inability to activate G(1) cyclin-dependent kinase (CDK) inhibitors (p15(INK4b), p21(CIP1/WAF1), p27(KIP1), p57(KIP2)) or to repress c-myc and Bcl-2 transcription. Correlating with aberrant activation of CDKs, CDK-dependent phosphorylation of Smad2 on Thr(8) (pT8), a modification linked to impaired Smad activity, is elevated in primary bone marrow myeloma cells, even in asymptomatic monoclonal gammopathy of undetermined significance. Moreover, CDK2 is the predominant CDK that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2. Our findings provide the first direct evidence that pT8 Smad2 couples dysregulation of CDK2 to TGF-beta resistance in primary cancer cells, and they suggest that disruption of Smad2 function by CDK2 phosphorylation acts as a mechanism for TGF-beta resistance in multiple myeloma.

  20. A Biochemical Approach to Understanding the Fanconi Anemia Pathway-Regulated Nucleases in Genome Maintenance for Preventing Bone Marrow Failure and Cancer

    Science.gov (United States)

    2014-04-01

    the Fanconi Anemia Pathway- Regulated Nucleases in Genome Maintenance for Preventing Bone Marrow Failure and Cancer PRINCIPAL INVESTIGATOR...GRANT NUMBER 4. TITLE AND SUBTITLE A Biochemical Approach to Understanding the Fanconi Anemia Pathway-Regulated Nucleases in Genome Maintenance for...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Fanconi anemia is the most prevalent inherited BMF syndromes, caused by mutations in

  1. Assessment of bone mineral status in children with Marfan syndrome

    Science.gov (United States)

    Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-ßeta, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone minerali...

  2. 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

    .0 +/- 1.4%); nutrient group: 0.953 +/- 0.051 to 0.978 +/- 0.043 g/mm(3) (3.8 +/- 3.4%)] when adjusted for age, body mass index, and BMD at inclusion. Bone formation displayed an interaction (P increased osteocalcin at 24 wk in the nutrient group. In conclusion, we report...... that 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......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...

  3. 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

    .4%); nutrient group: 0.953 ± 0.051 to 0.978 ± 0.043 g/mm3 (3.8 ± 3.4%)] when adjusted for age, body mass index, and BMD at inclusion. Bone formation displayed an interaction (P increased osteocalcin at 24 wk in the nutrient group. In conclusion, we report that 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 maintenance.......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...

  4. Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway.

    Science.gov (United States)

    Rowe, Peter S N

    2012-01-01

    More than 300 million years ago, vertebrates emerged from the vast oceans to conquer gravity and the dry land. With this transition, new adaptations occurred that included ingenious changes in reproduction, waste secretion, and bone physiology. One new innovation, the egg shell, contained an ancestral protein (ovocleidin-116) that likely first appeared with the dinosaurs and was preserved through the theropod lineage in modern birds and reptiles. Ovocleidin-116 is an avian homolog of matrix extracellular phosphoglycoprotein (MEPE) and belongs to a group of proteins called short integrin-binding ligand-interacting glycoproteins (SIBLINGs). These proteins are all localized to a defined region on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of SIBLING proteins is an acidic serine aspartate-rich MEPE-associated motif (ASARM). Recent research has shown that the ASARM motif and the released ASARM peptide have regulatory roles in mineralization (bone and teeth), phosphate regulation, vascularization, soft-tissue calcification, osteoclastogenesis, mechanotransduction, and fat energy metabolism. The MEPE ASARM motif and peptide are physiological substrates for PHEX, a zinc metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets (HYP). There is evidence that PHEX interacts with another ASARM motif containing SIBLING protein, dentin matrix protein-1 (DMP1). DMP1 mutations cause bone and renal defects that are identical with the defects caused by a loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both HYP and ARHR, increased FGF23 expression plays a major role in the disease and in autosomal dominant hypophosphatemic rickets (ADHR), FGF23 half-life is increased by activating mutations. ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. FGF23 is a member of the fibroblast growth factor (FGF) family of cytokines, which surfaced 500

  5. Reduced bone mass in obese young rats through PPAR omega suppression of wnt/beta-catenin signaling and direct action of free fatty acids (NEFA)

    Science.gov (United States)

    The relationship of obesity to skeletal development is unclear. We utilized total enteral nutrition to feed high and low fat diets (HFD and LFD) to rats for 4 wks to produce obesity. Weight gain was matched but fat mass, serum leptin and NEFA were increased by HFD (P < 0.05). HFD lowered total bone ...

  6. 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 study was designed 1) to determine whether treatment with basic fibroblast growth factor (bFGF) and PTH is more efficacious than treatment with PTH alone for increasing bone mass and strength and improving trabecular microarchitecture in osteopenic ovariectomized rats, and 2) to assess whethe...

  7. A Phase 2 Trial on the Effect of Low-Dose Versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1)

    Science.gov (United States)

    2015-10-01

    versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1...regulatory processes have taken more time than anticipated in the Statement of Work. An IND from the FDA to use high-dose vitamin D in the NF1

  8. The transcription factor Jdp2 controls bone homeostasis and antibacterial immunity by regulating osteoclast and neutrophil differentiation.

    Science.gov (United States)

    Maruyama, Kenta; Fukasaka, Masahiro; Vandenbon, Alexis; Saitoh, Tatsuya; Kawasaki, Takumi; Kondo, Takeshi; Yokoyama, Kazunari K; Kidoya, Hiroyasu; Takakura, Nobuyuki; Standley, Daron; Takeuchi, Osamu; Akira, Shizuo

    2012-12-14

    Jdp2 is an AP-1 family transcription factor that regulates the epigenetic status of histones. Previous in vitro studies revealed that Jdp2 is involved in osteoclastogenesis. However, the roles of Jdp2 in vivo and its pleiotropic functions are largely unknown. Here we generated Jdp2(-/-) mice and discovered its crucial roles not only in bone metabolism but also in differentiation of neutrophils. Jdp2(-/-) mice exhibited osteopetrosis resulting from impaired osteoclastogenesis. Jdp2(-/-) neutrophils were morphologically normal but had impaired surface expression of Ly6G, bactericidal function, and apoptosis. We also found that ATF3 was an inhibitor of neutrophil differentiation and that Jdp2 directly suppresses its expression via inhibition of histone acetylation. Strikingly, Jdp2(-/-) mice were highly susceptible to Staphylococcus aureus and Candida albicans infection. Thus, Jdp2 plays pivotal roles in in vivo bone homeostasis and host defense by regulating osteoclast and neutrophil differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Usefulness of circuit training at home for improving bone mass and muscle mass while losing fat mass in undergraduate female students.

    Science.gov (United States)

    Takahata, Yoko

    2018-05-09

    The purpose of this study was to determine whether or not circuit training at home affects the calcaneus quantitative ultrasound status as well as other indices of body composition among undergraduate female students. Forty-one adolescents were recruited (18.5 ± 0.6 years old). The stiffness index of the calcaneus, broadband ultrasound attenuation of the calcaneus, speed of sound of the calcaneus, and body frame index. This was a three-month intervention study, so the measurements were conducted at baseline, 2 months later, and 3 months later while the subjects underwent circuit training at home. The subjects were divided into two groups: namely, the exercising group and non-exercising group. In the exercising group, broadband ultrasound attenuation of the calcaneus was higher 2 months later (p = 0.033) as well as 3 months later (p = 0.036), and the speed of sound of the calcaneus was higher 3 months later (p = 0.018). In addition, the muscle mass was strongly positively correlated with the calcaneus QUS-SOS (p = 0.004), while the body fat percentage was a strongly negatively correlated with the calcaneus QUS-BUA (p = 0.043). In the non-exercising group, the stiffness index of the calcaneus was higher 2 months later (p = 0.002) as well as 3 months later (p = 0.002). Furthermore, the body percentage was strongly positively correlated with the calcaneus QUS-SI (p = 0.009). These findings suggest that the calcaneus quantitative ultrasound status and muscle mass while losing fat mass may be improved by means of a simple exercise regimen within a short period among undergraduate female students.

  10. Bone Mass Density and Risk of Breast Cancer and Survival in Older Women

    International Nuclear Information System (INIS)

    Ganry, O.; Baudoin, C.; Fardellone, P.; Peng, J.; Raverdy, N.

    2004-01-01

    Study objective: Older women with high bone mineral density (BMD) have an increased risk of breast cancer but it is not well known whether this association is associated with the stage of the tumor. The objective of the study is to determine if older women with high BMD are likely to develop a more aggressive form of breast cancer, as defined by mortality. Patients: We prospectively studied 1504 women who were 75 years of age or older at the entry in the study (range, 75-90 years), between 1992 and 1994. BMD was measured by dual-photon X-ray absorptiometry at three skeletal sites (trochanter, Ward's triangle, femoral neck). The women were followed for a mean of 7 years for the occurrence of breast cancer. Cox proportional-hazards models were used to obtain estimates of the relative risk of breast cancer and relative risk of death according to the BMD. Main results: Forty-five incident breast cancer cases were identified. In multivariate analyses of the risk of breast cancer for women in the highest tertile of BMD was greater than for women in the lowest tertile. Indeed, the women with a trochanter BMD in the highest tertile were at 2.3-fold increased risk compared with women in the lowest tertile. The women with highest tertile BMD measured at the Ward's triangle and at the femoral neck were respectively at 2.2-and 3.3-fold increased risk compared with women at the lowest risk. The 7-year survival rates were markedly less favorable for women in the second and third tertile of the three skeletal sites compared with the lowest tertile. The risk of death was greater for women in the highest tertile of BMD than for women in the lowest tertile at every skeletal site. Conclusion: Elderly women with high BMD have an increased risk of breast cancer, especially advanced cancer, compared with women with low BMD

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

    International Nuclear Information System (INIS)

    Olariu, Agata; Skog, Goeran; Hellborg, Ragnar; Stenstroem, Kristina; Faarinen, Mikko; Persson, Per; Alexandrescu, Emilian

    2005-01-01

    In this study we have dated two 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 de Fier, have been dated to the age 30150 ± 800 years BP, and the skull, from the Cioclovina cave has been dated to the age 29000 ± 700 years BP. These are among the most ancient dated human fossil remains from Romania, possibly belonging to the upper Paleolithic, the Aurignacian period. (authors)

  12. Regulation of skeletal muscle oxidative capacity and muscle mass by SIRT3.

    Directory of Open Access Journals (Sweden)

    Ligen Lin

    Full Text Available We have previously reported that the expression of mitochondrial deacetylase SIRT3 is high in the slow oxidative muscle and that the expression of muscle SIRT3 level is increased by dietary restriction or exercise training. To explore the function of SIRT3 in skeletal muscle, we report here the establishment of a transgenic mouse model with muscle-specific expression of the murine SIRT3 short isoform (SIRT3M3. Calorimetry study revealed that the transgenic mice had increased energy expenditure and lower respiratory exchange rate (RER, indicating a shift towards lipid oxidation for fuel usage, compared to control mice. The transgenic mice exhibited better exercise performance on treadmills, running 45% further than control animals. Moreover, the transgenic mice displayed higher proportion of slow oxidative muscle fibers, with increased muscle AMPK activation and PPARδ expression, both of which are known regulators promoting type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3 reduced muscle mass up to 30%, likely through an up-regulation of FOXO1 transcription factor and its downstream atrophy gene MuRF-1. In summary, these results suggest that SIRT3 regulates the formation of oxidative muscle fiber, improves muscle metabolic function, and reduces muscle mass, changes that mimic the effects of caloric restriction.

  13. Disp1 regulates growth of mammalian long bones through the control of Ihh distribution.

    Science.gov (United States)

    Tsiairis, Charisios D; McMahon, Andrew P

    2008-05-15

    Dispatched1 (Disp1) is required for the release of cholesterol modified hedgehog (Hh) proteins from producing cells. We investigated the role of Disp1 in Indian hedgehog (Ihh) signaling in the developing bone bypassing the lethality of the Disp1(C829F) allele at early somite stages through the supply of non-cholesterol modified Sonic hedgehog (N-Shh). The long bones that develop in the absence of wild-type Disp1, while clearly shorter, have a juxtaposition of proliferating and non-proliferating hypertrophic chondrocytes that is markedly more normal in organization than those of ihh null mutants. Direct analysis of Ihh trafficking in the target field demonstrates that Ihh is distributed well beyond Ihh expressing cells though the range of movement and signaling action is more restricted than in wild-type long bones. Consequently, a PTHrP-Ihh feedback loop is established, but over a shorter distance, reflecting the reduced range of Ihh movement. These analyses of the Disp1(C829F) mutation demonstrate that Disp1 is not absolutely required for the paracrine signaling role of Ihh in the skeleton. However, Disp1 is critical for the full extent of signaling within the chondrocyte target field and consequently the establishment of a normal skeletal growth plate.

  14. Bone mineralization is regulated by signaling cross talk between molecular factors of local and systemic origin: the role of fibroblast growth factor 23.

    Science.gov (United States)

    Sapir-Koren, Rony; Livshits, Gregory

    2014-01-01

    Body phosphate homeostasis is regulated by a hormonal counter-balanced intestine-bone-kidney axis. The major systemic hormones involved in this axis are parathyroid hormone (PTH), 1,25-dihydroxyvitamin-D, and fibroblast growth factor-23 (FGF23). FGF23, produced almost exclusively by the osteocytes, is a phosphaturic hormone that plays a major role in regulation of the bone remodeling process. Remodeling composite components, bone mineralization and resorption cycles create a continuous influx-efflux loop of the inorganic phosphate (Pi) through the skeleton. This "bone Pi loop," which is formed, is controlled by local and systemic factors according to phosphate homeostasis demands. Although FGF23 systemic actions in the kidney, and for the production of PTH and 1,25-dihydroxyvitamin-D are well established, its direct involvement in bone metabolism is currently poorly understood. This review presents the latest available evidence suggesting two aspects of FGF23 bone local activity: (a) Regulation of FGF23 production by both local and systemic factors. The suggested local factors include extracellular levels of Pi and pyrophosphate (PPi), (the Pi/PPi ratio), and another osteocyte-derived protein, sclerostin. In addition, 1,25-dihydroxyvitamin-D, synthesized locally by bone cells, may contribute to regulation of FGF23 production. The systemic control is achieved via PTH and 1,25-dihydroxyvitamin-D endocrine functions. (b) FGF23 acts as a local agent, directly affecting bone mineralization. We support the assumption that under balanced physiological conditions, sclerostin, by para- autocrine signaling, upregulates FGF23 production by the osteocyte. FGF23, in turn, acts as a mineralization inhibitor, by stimulating the generation of the major mineralization antagonist-PPi. © 2014 International Union of Biochemistry and Molecular Biology.

  15. Model of the regulation of the rate of multiplication of the stem cells of the bone marrow. [X radiation, gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gruzdev, G P; Monichev, A Ya

    1975-01-01

    A mathematical model of regulation of the rate of multiplication of the stem cells of the bone marrow has been constructed and investigated. Two possible variants of regulation of the proliferative activity of the irradiated stem cells are compared: at the level of tissue and subtissue units. Comparison of the results of modeling with the results of experimental investigations supports the latter mechanism of regulation of the proliferation of the stem cells.

  16. Bone phenotypes of P2 receptor knockout mice

    DEFF Research Database (Denmark)

    Orriss, Isabel; Syberg, Susanne; Wang, Ning

    2011-01-01

    The action of extracellular nucleotides is mediated by ionotropic P2X receptors and G-protein coupled P2Y receptors. The human genome contains 7 P2X and 8 P2Y receptor genes. Knockout mice strains are available for most of them. As their phenotypic analysis is progressing, bone abnormalities have...... been observed in an impressive number of these mice: distinct abnormalities in P2X7-/- mice, depending on the gene targeting construct and the genetic background, decreased bone mass in P2Y1-/- mice, increased bone mass in P2Y2-/- mice, decreased bone resorption in P2Y6-/- mice, decreased bone...... formation and bone resorption in P2Y13-/- mice. These findings demonstrate the unexpected importance of extracellular nucleotide signalling in the regulation of bone metabolism via multiple P2 receptors and distinct mechanisms involving both osteoblasts and osteoclasts....

  17. Evaluation of the peak bone mass by quantitative heel ultrasound in young women of the centre of Italy

    Directory of Open Access Journals (Sweden)

    A. Puxeddu

    2011-09-01

    Full Text Available Objective: To measure the reference young adult mean values in healthy women of the centre of Italy by Quantitative heel UltraSound (QUS. Methods: The study group was composed by 70 caucasian women: mean age was 25.4 years (Standard Deviation 4.7, mean weight was 58 Kg (SD 8.2, mean height was 166 cm (SD 5.8, mean BMI was 20.9 kg/m2 (SD 2.5. Every subject was evaluated firstly with an original questionnaire to discover risk factors (like for example steroids consumption, recent fractures of the lower limb, then was measured by quantitative heel ultrasonometry Hologic Sahara. Results: Mean extimated Bone Mineral Density (BMD 0.588 g/cm2 (SD 0.124 mean Quantitative Ultrasound Index (QUI 105.0 (SD 19.6, mean Speed of Sound (SOS 1564.2 m/s (SD 31.4, mean Broadband Ultrasound Attenuation (BUA 84.8 dB/MHz (SD 17.4. No significant correlation was found between QUS parameters and anthropometric data. A correlation was found between every QUS parameters. No significant differences were found about QUI and extimated BMD, between our results and Hologic normative data for European women. Conclusions: It is very important to develop specific reference values for any measurement device and site of skeleton especially in the age of reaching the peak bone mass because the T score is then measured referring to these data. Usually the normative data are supplied by manufacturer and are based on large multicentric study. In our opinion it could be helpful to verify if these data are compatible with the population examined in every region.

  18. Rapid maxillary anterior teeth retraction en masse by bone compression: a canine model.

    Directory of Open Access Journals (Sweden)

    Chufeng Liu

    Full Text Available The present study sought to establish an animal model to study the feasibility and safety of rapid retraction of maxillary anterior teeth en masse aided by alveolar surgery in order to reduce orthodontic treatment time.Extraction of the maxillary canine and alveolar surgery were performed on twelve adult beagle dogs. After that, the custom-made tooth-borne distraction devices were placed on beagles' teeth. Nine of the dogs were applied compression at 0.5 mm/d for 12 days continuously. The other three received no force as the control group. The animals were killed in 1, 14, and 28 days after the end of the application of compression.The tissue responses were assessed by craniometric measurement as well as histological examination. Gross alterations were evident in the experimental group, characterized by anterior teeth crossbite. The average total movements of incisors within 12 days were 4.63±0.10 mm and the average anchorage losses were 1.25±0.12 mm. Considerable root resorption extending into the dentine could be observed 1 and 14 days after the compression. But after consolidation of 28 days, there were regenerated cementum on the dentine. There was no apparent change in the control group. No obvious tooth loosening, gingival necrosis, pulp degeneration, or other adverse complications appeared in any of the dogs.This is the first experimental study for testing the technique of rapid anterior teeth retraction en masse aided by modified alveolar surgery. Despite a preliminary animal model study, the current findings pave the way for the potential clinical application that can accelerate orthodontic tooth movement without many adverse complications.It may become a novel method to shorten the clinical orthodontic treatment time in the future.

  19. Dating of cremated bones

    OpenAIRE

    Lanting, JN; Aerts-Bijma, AT; van der Plicht, J; Boaretto, E.; Carmi, I.

    2001-01-01

    When dating unburnt bone, bone collagen, the organic fraction of the bone, is used. Collagen does not survive the heat of the cremation pyre, so dating of cremated bone has been considered impossible. Structural carbonate in the mineral fraction of the bone, however, survives the cremation process. We developed a method of dating cremated bone by accelerator mass spectrometry (AMS), using this carbonate fraction. Here we present results for a variety of prehistoric sites and ages, showing a r...

  20. Unicameral bone cyst of a cervical vertebral body and lateral mass with associated pathological fracture in a child. Case report and review of the literature.

    Science.gov (United States)

    Snell, B E; Adesina, A; Wolfla, C E

    2001-10-01

    The authors present the case of a 10-year-old girl with a history of cervical trauma in whom a cystic lesion was found to involve all three columns of C-7 with evidence of pathological fracture. Computerized tomography scanning revealed a lytic lesion with sclerotic margins involving the left vertebral body, pedicle, lateral mass, and lamina of C-7 with an associated pathological compression fracture. Magnetic resonance imaging demonstrated mixed signal on both T1- and T2-weighted sequences, with cystic and enhancing solid portions. Magnetic resonance angiography demonstrated anterior displacement of the left vertebral artery at C-7. The patient underwent C-7 subtotal corpectomy and posterior resection of the tumor mass; anterior and posterior fusion were performed in which instrumentation was placed. Histological examination disclosed cystic areas lined by fibromembranous tissue with calcification and osteoid deposits consistent with unicameral bone cyst. Of the four previously reported cases of unicameral bone cysts in the cervical spine, none involved all three columns simultaneously or was associated with pathological fracture. The most common differential diagnostic considerations for cystic lesions in the spine are aneurysmal bone cyst, osteoblastoma, or giant cell tumor of bone. Unicameral bone cyst, in this location, although rare, must be considered in the differential diagnosis and may require resection and spinal reconstruction.

  1. Radiological mass screening within the Member States of the European Community. Regulations, practices, effectiveness

    Energy Technology Data Exchange (ETDEWEB)

    Lochard, J. (ed.)

    1987-01-01

    Proceedings of the seminar ''Radiological mass screening within the Member States of the European Community'' organized by the Commission of the European Community in collaboration with the Commissariat a l'Energie Atomique and the Centre d'etude sur l'Evaluation de la Protection dans le domaine Nucleaire, France, from 3 to 4 December 1985. Part I presents rapporteurs' papers which summarize the salient points concerning: the status of regulations and practices in the different countries, mass chest screening, mammography screening and infants' hip dysplasia screening. Part II presents all the technical papers contributed by the participants. The overall conclusions of the seminar pointed up the importance of assessing the effectiveness of screening or prevention practices more systematically. Although some aspects of the problems associated with radiological mass screening were only qualitatively addressed, the papers presented did explain why the use of certain medical practices must be justified. It is hoped that these proceedings will be useful to national experts and bodies in the planning of future public health programmes which, in the light of current practices, will have to take account of the medical, economic and social dimension of mass screening.

  2. Resveratrol attenuates bone cancer pain through regulating the expression levels of ASIC3 and activating cell autophagy.

    Science.gov (United States)

    Zhu, Haili; Ding, Jieqiong; Wu, Ji; Liu, Tingting; Liang, Jing; Tang, Qiong; Jiao, Ming

    2017-11-01

    Bone cancer pain (BCP) is one of the most common pains in patients with malignant cancers. The mechanism underlying BCP is largely unknown. Our previous studies and the increasing evidence both have shown that acid-sensing ion channels 3 (ASIC3) is an important protein in the pathological pain state in some pain models. We hypothesized that the expression change of ASIC3 might be one of the factors related to BCP. In this study, we established the BCP model through intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone destruction, increased mechanical pain sensitivities and up-regulated ASIC3 protein expression levels in L4-L6 dorsal root ganglion. Then, resveratrol, which was intraperitoneally injected into the BCP rats on post-operative Day 21, dose-dependently increased the paw withdrawal threshold of BCP rats, reversed the pain behavior, and had an antinociceptive effect on BCP rats. In ASIC3-transfected SH-SY5Y cells, the ASIC3 protein expression levels were regulated by resveratrol in a dose- and time-dependent manner. Meanwhile, resveratrol also had an antinociceptive effect in ASIC3-mediated pain rat model. Furthermore, resveratrol also enhanced the phosphorylation of AMPK, SIRT1, and LC3-II levels in ASIC3-transfected SH-SY5Y cells, indicating that resveratrol could activate the AMPK-SIRT1-autophagy signal pathway in ASIC3-transfected SH-SY5Y cells. In BCP rats, SIRT1 and LC3-II were also down-regulated. These findings provide new evidence for the use of resveratrol as a therapeutic treatment during BCP states. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal

    DEFF Research Database (Denmark)

    Bagger, Yu Z; Tankó, László B; Alexandersen, Peter

    2003-01-01

    for 7, 5, or 3 yr, respectively. Bone mineral density of the lumbar spine, hip, and forearm was measured by dual-energy x-ray absorptiometry. Biochemical markers of bone turnover were induced serum C-terminal telopeptides of type I collagen (CTX) and osteocalcin. Women who received alendronate (2...... was found in women treated with alendronate 20 mg per day for 2 yr (9.7%, P=0.01 vs. placebo). The rate of bone loss after alendronate withdrawal was comparable to the bone loss observed in the placebo group. Bone markers tended to reverse back to normal levels, but were still affected even several years...

  4. Stiffness of a wobbling mass models analysed by a smooth orthogonal decomposition of the skin movement relative to the underlying bone.

    Science.gov (United States)

    Dumas, Raphaël; Jacquelin, Eric

    2017-09-06

    The so-called soft tissue artefacts and wobbling masses have both been widely studied in biomechanics, however most of the time separately, from either a kinematics or a dynamics point of view. As such, the estimation of the stiffness of the springs connecting the wobbling masses to the rigid-body model of the lower limb, based on the in vivo displacements of the skin relative to the underling bone, has not been performed yet. For this estimation, the displacements of the skin markers in the bone-embedded coordinate systems are viewed as a proxy for the wobbling mass movement. The present study applied a structural vibration analysis method called smooth orthogonal decomposition to estimate this stiffness from retrospective simultaneous measurements of skin and intra-cortical pin markers during running, walking, cutting and hopping. For the translations about the three axes of the bone-embedded coordinate systems, the estimated stiffness coefficients (i.e. between 2.3kN/m and 55.5kN/m) as well as the corresponding forces representing the connection between bone and skin (i.e. up to 400N) and corresponding frequencies (i.e. in the band 10-30Hz) were in agreement with the literature. Consistently with the STA descriptions, the estimated stiffness coefficients were found subject- and task-specific. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Influence of Nordic Walking Training on Muscle Strength and the Electromyographic Activity of the Lower Body in Women With Low Bone Mass

    Directory of Open Access Journals (Sweden)

    Ossowski Zbigniew

    2016-06-01

    Full Text Available Introduction. Osteoporosis and osteopenia are related to changes in the quantity and quality of skeletal muscle and contribute to a decreased level of muscle strength. The purpose of this study was to evaluate the impact of Nordic walking training on muscle strength and the electromyographic (EMG activity of the lower body in women with low bone mass. Material and methods. The participants of the study were 27 women with low bone mass. The sample was randomly divided into two groups: a control group and an experimental group. Women from the experimental group participated in 12 weeks of regular Nordic walking training. Functional strength was assessed with a 30-second chair stand test. The EMG activities of the gluteus maximus (GMax, rectus femoris (RF, biceps femoris (BF, soleus (SOL, and lumbar (LB muscles were measured using a surface electromyogram. Results. Nordic walking training induced a significant increase in the functional strength (p = 0.006 of the lower body and activity of GMax (p = 0.013 and a decrease in body mass (p = 0.006 in women with reduced bone mass. There was no statistically significant increase in the EMG activities of the RF, BF, SOL, or LB muscles. The study did not indicate any significant changes in functional muscle strength, the EMG activity of the lower body, or anthropometry in women from the control group. Conclusions. Nordic walking training induces positive changes in lower body strength and the electromyographic activity of the gluteus maximus as well as a decrease in body mass in women with low bone mass.

  6. High-intensity intermittent "5-10-15" running reduces body fat, and increases lean body mass, bone mineral density, and performance in untrained subjects

    DEFF Research Database (Denmark)

    Ravnholt, Tanja Højegaard; Tybirk, Jonas; Jørgensen, Niklas Rye

    2018-01-01

    , and 5 s low-, moderate-, and high-speed running, respectively. Body fat mass was 4.3% lower (P bone mineral density was 1.1 and 0.9% higher (P bone turnover markers osteocalcin......The present study examined the effect of intense intermittent running with 5 s sprints on body composition, fitness level, and performance in untrained subjects aged 36-53 years. For 7 weeks, the subjects carried out 3 days a week 5-10-15 training consisting of 3-9 blocks of 4 repetitions of 15, 10...

  7. Role and mechanism of action of Sclerostin in bone

    Science.gov (United States)

    Delgado-Calle, Jesus; Sato, Amy Y.; Bellido, Teresita

    2016-01-01

    After discovering that lack of Sost/sclerostin expression is the cause of the high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive animal experimentation and clinical studies demonstrated that sclerostin plays a critical role in bone homeostasis and that its deficiency or pharmacological neutralization increases bone formation. Dysregulation of sclerostin expression also underlies the pathophysiology of skeletal disorders characterized by loss of bone mass as well as the damaging effects of some cancers in bone. Thus, sclerostin has quickly become a promising molecular target for the treatment of osteoporosis and other skeletal diseases, and beneficial skeletal outcomes are observed in animal studies and clinical trials using neutralizing antibodies against sclerostin. However, the anabolic effect of blocking sclerostin decreases with time, bone mass accrual is also accompanied by anti-catabolic effects, and there is bone loss over time after therapy discontinuation. Further, the cellular source of sclerostin in the bone/bone marrow microenvironment under physiological and pathological conditions, the pathways that regulate sclerostin expression and the mechanisms by which sclerostin modulates the activity of osteocytes, osteoblasts, and osteoclasts remain unclear. In this review, we highlight the current knowledge on the regulation of Sost/sclerotin expression and its mechanism(s) of action, discuss novel observations regarding its role in signaling pathways activated by hormones and mechanical stimuli in bone, and propose future research needed to understand the full potential of therapeutic interventions that modulate Sost/sclerostin expression. PMID:27742498

  8. Mass

    International Nuclear Information System (INIS)

    Quigg, Chris

    2007-01-01

    In the classical physics we inherited from Isaac Newton, mass does not arise, it simply is. The mass of a classical object is the sum of the masses of its parts. Albert Einstein showed that the mass of a body is a measure of its energy content, inviting us to consider the origins of mass. The protons we accelerate at Fermilab are prime examples of Einsteinian matter: nearly all of their mass arises from stored energy. Missing mass led to the discovery of the noble gases, and a new form of missing mass leads us to the notion of dark matter. Starting with a brief guided tour of the meanings of mass, the colloquium will explore the multiple origins of mass. We will see how far we have come toward understanding mass, and survey the issues that guide our research today.

  9. Lrp4, a novel receptor for Dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turnover in vivo.

    Directory of Open Access Journals (Sweden)

    Hong Y Choi

    2009-11-01

    Full Text Available Lrp4 is a multifunctional member of the low density lipoprotein-receptor gene family and a modulator of extracellular cell signaling pathways in development. For example, Lrp4 binds Wise, a secreted Wnt modulator and BMP antagonist. Lrp4 shares structural elements within the extracellular ligand binding domain with Lrp5 and Lrp6, two established Wnt co-receptors with important roles in osteogenesis. Sclerostin is a potent osteocyte secreted inhibitor of bone formation that directly binds Lrp5 and Lrp6 and modulates both BMP and Wnt signaling. The anti-osteogenic effect of sclerostin is thought to be mediated mainly by inhibition of Wnt signaling through Lrp5/6 within osteoblasts. Dickkopf1 (Dkk1 is another potent soluble Wnt inhibitor that binds to Lrp5 and Lrp6, can displace Lrp5-bound sclerostin and is itself regulated by BMPs. In a recent genome-wide association study of bone mineral density a significant modifier locus was detected near the SOST gene at 17q21, which encodes sclerostin. In addition, nonsynonymous SNPs in the LRP4 gene were suggestively associated with bone mineral density. Here we show that Lrp4 is expressed in bone and cultured osteoblasts and binds Dkk1 and sclerostin in vitro. MicroCT analysis of Lrp4 deficient mutant mice revealed shortened total femur length, reduced cortical femoral perimeter, and reduced total femur bone mineral content (BMC and bone mineral density (BMD. Lumbar spine trabecular bone volume per total volume (BV/TV was significantly reduced in the mutants and the serum and urinary bone turnover markers alkaline phosphatase, osteocalcin and desoxypyridinoline were increased. We conclude that Lrp4 is a novel osteoblast expressed Dkk1 and sclerostin receptor with a physiological role in the regulation of bone growth and turnover, which is likely mediated through its function as an integrator of Wnt and BMP signaling pathways.

  10. 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.

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

    International Nuclear Information System (INIS)

    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 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

  12. Bone morphogenetic proteins regulate osteoprotegerin and its ligands in human vascular smooth muscle cells

    DEFF Research Database (Denmark)

    Knudsen, Kirsten Quyen Nguyen; Olesen, Ping; Ledet, Thomas

    2007-01-01

    The bone-related protein osteoprotegerin (OPG) may be involved in the development of vascular calcifications, especially in diabetes, where it has been found in increased amounts in the arterial wall. Experimental studies suggest that members of the TGF-superfamily are involved in the transformat......The bone-related protein osteoprotegerin (OPG) may be involved in the development of vascular calcifications, especially in diabetes, where it has been found in increased amounts in the arterial wall. Experimental studies suggest that members of the TGF-superfamily are involved...... in the transformation of human vascular smooth muscle cells (HVSMC) to osteoblast-like cells. In this study, we evaluated the effect of BMP-2, BMP-7 and transforming growth factor beta (TGF-beta1) on the secretion and mRNA expression of OPG and its ligands receptor activator of nuclear factor-kappabeta ligand (RANKL......) and TNF-related apoptosis-inducing ligand (TRAIL) in HVSMC. All three growth factors decreased OPG protein production significantly; these results were paralleled by reduced OPG mRNA expression. TRAIL mRNA levels were also decreased. RANKL mRNA expression declined when treated with TGF-beta1 but were...

  13. Circulating levels of IGF-1 directly regulate bone growth and density

    Science.gov (United States)

    Yakar, Shoshana; Rosen, Clifford J.; Beamer, Wesley G.; Ackert-Bicknell, Cheryl L.; Wu, Yiping; Liu, Jun-Li; Ooi, Guck T.; Setser, Jennifer; Frystyk, Jan; Boisclair, Yves R.; LeRoith, Derek

    2002-01-01

    IGF-1 is a growth-promoting polypeptide that is essential for normal growth and development. In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS). This complex prolongs the half-life of serum IGFs and facilitates their endocrine actions. Liver IGF-1–deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively. Double gene disrupted mice were generated by crossing LID+ALSKO mice. These mice exhibited further reductions in serum IGF-1 levels and a significant reduction in linear growth. The proximal growth plates of the tibiae of LID+ALSKO mice were smaller in total height as well as in the height of the proliferative and hypertrophic zones of chondrocytes. There was also a 10% decrease in bone mineral density and a greater than 35% decrease in periosteal circumference and cortical thickness in these mice. IGF-1 treatment for 4 weeks restored the total height of the proximal growth plate of the tibia. Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis. PMID:12235108

  14. Preventing Cartilage Degeneration in Warfighters by Elucidating Novel Mechanisms Regulating Osteocyte-Mediated Perilacunar Bone Remodeling

    Science.gov (United States)

    2016-10-01

    hypothesis using mouse models and human PTOA tissue. We aim to determine: 1) the extent to which mechanical loading regulates PLR in a TGFβ- dependent manner ...the major goals of the project? Major Goals Aim 1: Determine the extent to which mechanical loading regulates PLR in a TGFβ- dependent manner . Aim...dependent manner . Overview: We conducted all of the analyses proposed in Aim 1. As described below, these studies convincingly demonstrate that PLR

  15. Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation.

    Science.gov (United States)

    Taipaleenmäki, Hanna; Bjerre Hokland, Lea; Chen, Li; Kauppinen, Sakari; Kassem, Moustapha

    2012-03-01

    Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases.

  16. Bone mineral density in postmenopausal Mexican-Mestizo women with normal body mass index, overweight, or obesity.

    Science.gov (United States)

    Méndez, Juan Pablo; Rojano-Mejía, David; Pedraza, Javier; Coral-Vázquez, Ramón Mauricio; Soriano, Ruth; García-García, Eduardo; Aguirre-García, María Del Carmen; Coronel, Agustín; Canto, Patricia

    2013-05-01

    Obesity and osteoporosis are two important public health problems that greatly impact mortality and morbidity. Several similarities between these complex diseases have been identified. The aim of this study was to analyze if different body mass indexes (BMIs) are associated with variations in bone mineral density (BMD) among postmenopausal Mexican-Mestizo women with normal weight, overweight, or different degrees of obesity. We studied 813 postmenopausal Mexican-Mestizo women. A structured questionnaire for risk factors was applied. Height and weight were used to calculate BMI, whereas BMD in the lumbar spine (LS) and total hip (TH) was measured by dual-energy x-ray absorptiometry. We used ANCOVA to examine the relationship between BMI and BMDs of the LS, TH, and femoral neck (FN), adjusting for confounding factors. Based on World Health Organization criteria, 15.13% of women had normal BMI, 39.11% were overweight, 25.96% had grade 1 obesity, 11.81% had grade 2 obesity, and 7.99% had grade 3 obesity. The higher the BMI, the higher was the BMD at the LS, TH, and FN. The greatest differences in size variations in BMD at these three sites were observed when comparing women with normal BMI versus women with grade 3 obesity. A higher BMI is associated significantly and positively with a higher BMD at the LS, TH, and FN.

  17. Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice.

    Science.gov (United States)

    Huo, Feifei; Li, Dongbei; Zhao, Bo; Luo, Yadong; Zhao, Bingjie; Zou, Xueyang; Li, Yi; Yang, Wei

    2018-02-01

    As a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that affect the differentiation of T cells toward distinct subpopulations and participate in the immune response and tolerance, thereby playing an important role in maintaining homeostasis. To determine the role of Aire in maintaining immune tolerance by bone marrow-derived dendritic cells (BMDCs), in the present study we utilized Aire-knockout mice to examine the changes of maturation status and TRAs expression on BMDCs, additionally investigate the differentiation of CD4 + T cells. The results showed that expression of costimulatory molecule and major histocompatibility complex class II (MHC-II) molecule was increased and expression of various TRAs was decreased in BMDCs from Aire-knockout mice. Aire deficiency reduced the differentiation of naïve CD4 + T cells into type 2T helper (Th2) cells and regulatory T cells (Tregs) but enhanced the differentiation of naïve CD4 + T cells into Th1 cells, Th17 cells, and follicular helper T (Tfh) cells. The results demonstrate that Aire expressed by BMDCs plays an important role in the maintenance of homeostasis by regulating TRA expression and the differentiation of T cell subsets.

  18. Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice.

    Science.gov (United States)

    Zhang, Y; Wang, L; Song, Y; Zhao, X; Wong, M S; Zhang, W

    2016-03-01

    The skeletal renin-angiotensin system contributes to the development of osteoporosis. The renin inhibitor aliskiren exhibited beneficial effects on trabecular bone of osteoporotic mice, and this action might be mediated through angiotensin and bradykinin receptor pathways. This study implies the potential application of renin inhibitor in the management for postmenopausal osteoporosis. The skeletal renin-angiotensin system plays key role in the pathological process of osteoporosis. The present study is designed to elucidate the effect of renin inhibitor aliskiren on trabecular bone and its potential action mechanism in ovariectomized (OVX) mice. The OVX mice were treated with low dose (5 mg/kg) or high dose (25 mg/kg) of aliskiren or its vehicle for 8 weeks. The bone turnover markers were measured by ELISA. The structural parameters of trabecular bone at lumbar vertebra (LV) and distal femoral metaphysis were measured by micro-CT. The expression of messenger RNA (mRNA) and protein was studied by RT-PCR and immunoblotting, respectively. Aliskiren treatment reduced urinary excretion of calcium and serum level of tartrate-resistant acid phosphatase in OVX mice. The treatment with aliskiren significantly increased bone volume (BV/TV) and connectivity density (Conn.D) of trabecular bone at LV-2 and LV-5 as well as dramatically enhanced BV/TV, Conn.D, bone mineral density (BMD/BV) and decreased bone surface (BS/BV) at the distal femoral end. Aliskiren significantly down-regulated the expression of angiotensinogen, angiotensin II (Ang II), Ang II type 1 receptor, bradykinin receptor (BR)-1, and osteocytic-specific gene sclerostin as well as the osteoclast-specific genes, including carbonic anhydrase II, matrix metalloproteinase-9, and cathepsin K. This study revealed that renin inhibitor aliskiren exhibited the beneficial effects on trabecular bone of ovariectomy-induced osteoporotic mice, and the underlying mechanism for this action might be mediated through Ang II and

  19. Genetic manipulation of the ghrelin signaling system in male mice reveals bone compartment specificity of acylated and unacylated ghrelin in the regulation of bone remodeling

    Science.gov (United States)

    Ghrelin receptor-deficient (Ghsr-/-) mice that lack acylated ghrelin (AG) signaling retain a metabolic response to unacylated ghrelin (UAG). Recently, we showed that Ghsr-deficiency affects bone metabolism. The aim of this study was to further establish the impact of AG and UAG on bone metabolism. W...

  20. Kindergarten Self-Regulation as a Predictor of Body Mass Index and Sports Participation in Fourth Grade Students

    Science.gov (United States)

    Piche, Genevieve; Fitzpatrick, Caroline; Pagani, Linda S.

    2012-01-01

    Identifying early precursors of body mass index (BMI) and sports participation represents an important concern from a public health perspective and can inform the development of preventive interventions. This article examines whether kindergarten child self-regulation, as measured by classroom engagement and behavioral regulation, predicts healthy…

  1. Case Study: The Effect of 32 Weeks of Figure-Contest Preparation on a Self-Proclaimed Drug-Free Female's Lean Body and Bone Mass.

    Science.gov (United States)

    Petrizzo, John; DiMenna, Frederick J; Martins, Kimberly; Wygand, John; Otto, Robert M

    2017-12-01

    To achieve the criterion appearance before competing in a physique competition, athletes undergo preparatory regimens involving high-volume intense resistance and aerobic exercise with hypocaloric energy intake. As the popularity of "drug-free" competition increases, more athletes are facing this challenge without the recuperative advantage provided by performance-enhancing drugs. Consequently, the likelihood of loss of lean body and/or bone mass is increased. The purpose of this investigation was to monitor changes in body composition for a 29-year-old self-proclaimed drug-free female figure competitor during a 32-week preparatory regimen comprising high-volume resistance and aerobic exercise with hypocaloric energy intake. We used dual-energy x-ray absorptiometry (DXA) to evaluate regional fat and bone mineral density. During the initial 22 weeks, the subject reduced energy intake and engaged in resistance (4-5 sessions/week) and aerobic (3 sessions/week) training. During the final 10 weeks, the subject increased exercise frequency to 6 (resistance) and 4 (aerobic) sessions/week while ingesting 1130-1380 kcal/day. During this 10-week period, she consumed a high quantity of protein (~55% of energy intake) and nutritional supplements. During the 32 weeks, body mass and fat mass decreased by 12% and 55%, respectively. Conversely, lean body mass increased by 1.5%, an amount that exceeded the coefficient of variation associated with DXA-derived measurement. Total bone mineral density was unchanged throughout. In summary, in preparation for a figure competition, a self-proclaimed drug-free female achieved the low body-fat percentage required for success in competition without losing lean mass or bone density by following a 32-week preparatory exercise and nutritional regimen.

  2. Adhesive and mechanical regulation of mesenchymal stem cell differentiation in human bone marrow and periosteum-derived progenitor cells

    Directory of Open Access Journals (Sweden)

    Jeroen Eyckmans

    2012-08-01

    It has previously been demonstrated that cell shape can influence commitment of human bone marrow-derived mesenchymal stem cells (hBMCs to adipogenic, osteogenic, chondrogenic, and other lineages. Human periosteum-derived cells (hPDCs exhibit multipotency similar to hBMCs, but hPDCs may offer enhanced potential for osteogenesis and chondrogenesis given their apparent endogenous role in bone and cartilage repair in vivo. Here, we examined whether hPDC differentiation is regulated by adhesive and mechanical cues comparable to that reported for hBMC differentiation. When cultured in the appropriate induction media, hPDCs at high cell seeding density demonstrated enhanced levels of adipogenic or chondrogenic markers as compared with hPDCs at low cell seeding density. Cell seeding density correlated inversely with projected area of cell spreading, and directly limiting cell spreading with micropatterned substrates promoted adipogenesis or chondrogenesis while substrates promoting cell spreading supported osteogenesis. Interestingly, cell seeding density influenced differentiation through both changes in cell shape and non-shape-mediated effects: density-dependent adipogenesis and chondrogenesis were regulated primarily by cell shape whereas non-shape effects strongly influenced osteogenic potential. Inhibition of cytoskeletal contractility by adding the Rho kinase inhibitor Y27632 further enhanced adipogenic differentiation and discouraged osteogenic differentiation of hPDCs. Together, our results suggest that multipotent lineage decisions of hPDCs are impacted by cell adhesive and mechanical cues, though to different extents than hBMCs. Thus, future studies of hPDCs and other primary stem cell populations with clinical potential should consider varying biophysical metrics for more thorough optimization of stem cell differentiation.

  3. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche

    Directory of Open Access Journals (Sweden)

    LM McNamara

    2012-01-01

    Full Text Available Mesenchymal stem cells (MSCs within their native environment of the stem cell niche in bone receive biochemical stimuli from surrounding cells. These stimuli likely influence how MSCs differentiate to become bone precursors. The ability of MSCs to undergo osteogenic differentiation is well established in vitro;however, the role of the natural cues from bone’s regulatory cells, osteocytes and osteoblasts in regulating the osteogenic differentiation of MSCs in vivo are unclear. In this study we delineate the role of biochemical signalling from osteocytes and osteoblasts, using conditioned media and co-culture experiments, to understand how they direct osteogenic differentiation of MSCs. Furthermore, the synergistic relationship between osteocytes and osteoblasts is examined by transwell co-culturing of MSCs with both simultaneously. Osteogenic differentiation of MSCs was quantified by monitoring alkaline phosphatase (ALP activity, calcium deposition and cell number. Intracellular ALP was found to peak earlier and there was greater calcium deposition when MSCs were co-cultured with osteocytes rather than osteoblasts, suggesting that osteocytes are more influential than osteoblasts in stimulating osteogenesis in MSCs. Osteoblasts initially stimulated an increase in the number of MSCs, but ultimately regulated MSC differentiation down the same pathway. Our novel co-culture system confirmed a synergistic relationship between osteocytes and osteoblasts in producing biochemical signals to stimulate the osteogenic differentiation of MSCs. This study provides important insights into the mechanisms at work within the native stem cell niche to stimulate osteogenic differentiation and outlines a possible role for the use of co-culture or conditioned media methodologies for tissue engineering applications.

  4. Selected factors affecting bone mass in students with diagnosed obesity, aged 7–10 years, from Łódź

    Directory of Open Access Journals (Sweden)

    Anna Łupińska

    2017-12-01

    Full Text Available Introduction: Obesity may be a risk factor for mineralisation and bone structure disorders, contrary to a common belief in its protective effects on bone tissue. Aim: The aim of the study was to assess the relationship between selected risk factors and obesity indicators and bone mass in obese children. Material and methods: The study included 80 children aged between 7 and 10 years with excessive body weight (60 obese and 20 overweight; the reference group included 37 children with body weight appropriate for height. All patients underwent physical examination with anthropometric measurements. Parents were asked to complete a questionnaire. The average daily intake of selected nutrients was analysed using Dieta 2 software package. Densitometry (dual-energy X-ray absorptiometry, DXA was performed in all children to evaluate bone mass. Results: Obese and overweight children had statist