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Sample records for affects bone metabolism

  1. Affective Disorders, Bone Metabolism, and Osteoporosis

    PubMed Central

    2013-01-01

    The nature of the relationship between affective disorders, bone mineral density (BMD), and bone metabolism is unresolved, although there is growing evidence that many medications used to treat affective disorders are associated with low BMD or alterations in neuroendocrine systems that influence bone turnover. The objective of this review is to describe the current evidence regarding the association of unipolar and bipolar depression with BMD and indicators of bone metabolism, and to explore potential mediating and confounding influences of those relationships. The majority of studies of unipolar depression and BMD indicate that depressive symptoms are associated with low BMD. In contrast, evidence regarding the relationship between bipolar depression and BMD is inconsistent. There is limited but suggestive evidence to support an association between affective disorders and some markers of bone turnover. Many medications used to treat affective disorders have effects on physiologic systems that influence bone metabolism, and these conditions are also associated with a range of health behaviors that can influence osteoporosis risk. Future research should focus on disentangling the pathways linking psychotropic medications and their clinical indications with BMD and fracture risk. PMID:23874147

  2. Pinto Bean Hull Extract Supplementation Favorably Affects Markers of Bone Metabolism and Bone Structure in Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bean hulls are rich in phenolic compounds known to possess antioxidant activity that may have beneficial effect on bone health. The aim of this study was to examine the effects of bean hull extract (BHE) from pinto beans on bone structure and serum markers in twelve-month-old male C57BL/6 mice fed e...

  3. High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

    PubMed Central

    Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

    2013-01-01

    Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

  4. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy

    PubMed Central

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-01-01

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or “diabetic osteopathy”. These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint. PMID:27022443

  5. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy.

    PubMed

    McCarthy, Antonio Desmond; Cortizo, Ana María; Sedlinsky, Claudia

    2016-03-25

    Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or "diabetic osteopathy". These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism. Adenosine monophosphate-activated protein kinase (AMPK) modulates multiple metabolic pathways and acts as a sensor of the cellular energy status; recent evidence suggests a critical role for AMPK in bone homeostasis. In addition, AMPK activation is believed to mediate most clinical effects of the insulin-sensitizer metformin. Over the past decade, several research groups have investigated the effects of metformin on bone, providing a considerable body of pre-clinical (in vitro, ex vivo and in vivo) as well as clinical evidence for an anabolic action of metformin on bone. However, two caveats should be kept in mind when considering metformin treatment for a patient with type 2 DM at risk for diabetic osteopathy. In the first place, metformin should probably not be considered an anti-osteoporotic drug; it is an insulin sensitizer with proven macrovascular benefits that can secondarily improve bone metabolism in the context of DM. Secondly, we are still awaiting the results of randomized placebo-controlled studies in humans that evaluate the effects of metformin on bone metabolism as a primary endpoint. PMID:27022443

  6. Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

    PubMed Central

    Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

    2015-01-01

    Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

  7. Adenosine and Bone Metabolism

    PubMed Central

    Mediero, Aránzazu; Cronstein, Bruce N.

    2013-01-01

    Bone is a dynamic organ that undergoes continuous remodeling whilst maintaining a balance between bone formation and resorption. Osteoblasts, which synthesize and mineralize new bone, and osteoclasts, the cells that resorb bone, act in concert to maintain bone homeostasis. In recent years, there has been increasing appreciation of purinergic regulation of bone metabolism. Adenosine, released locally, mediates its physiologic and pharmacologic actions via interactions with G-protein coupled receptors and recent work has indicated that these receptors are involved in the regulation of osteoclast differentiation and function, as well as osteoblast differentiation and bone formation. Moreover, adenosine receptors also regulate chondrocyte and cartilage homeostasis. These recent findings underscore the potential therapeutic importance of adenosine receptors in regulating bone physiology and pathology. PMID:23499155

  8. [Metabolic bone disease osteomalacia].

    PubMed

    Reuss-Borst, M A

    2014-05-01

    Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases. PMID:24811356

  9. Altitude, pasture type, and sheep breed affect bone metabolism and serum 25-hydroxyvitamin D in grazing lambs.

    PubMed

    Willems, Helen; Leiber, Florian; Kohler, Martina; Kreuzer, Michael; Liesegang, Annette

    2013-05-15

    This study aimed to investigate the bone development of two mountain sheep breeds during natural summer grazing either in the lowlands or on different characteristic alpine pastures. Pasture types differed in topographic slope, plant species composition, general nutritional feeding value, Ca and P content, and Ca:P ratio of herbage. Twenty-seven Engadine sheep (ES) lambs and 27 Valaisian Black Nose sheep (VS) lambs were divided into four groups of 6 to 7 animals per breed and allocated to three contrasting alpine pasture types and one lowland pasture type. The lambs were slaughtered after 9 wk of experimental grazing. The steep alpine pastures in combination with a high (4.8) to very high (13.6) Ca:P ratio in the forage decreased total bone mineral content as measured in the middle of the left metatarsus of the lambs from both breeds, and cortical bone mineral content and cortical bone mineral density of ES lambs. Breed × pasture type interactions occurred in the development of total and cortical bone mineral content, and in cortical thickness, indicating that bone metabolism of different genotypes obviously profited differently from the varying conditions. An altitude effect occurred for 25-hydroxyvitamin D with notably higher serum concentrations on the three alpine sites, and a breed effect led to higher concentrations for ES than VS. Despite a high variance, there were pasture-type effects on serum markers of bone formation and resorption. PMID:23471950

  10. Metabolic Bone Disease in Primary Biliary Cirrhosis.

    PubMed

    Glass, Lisa M; Su, Grace Li-Chun

    2016-06-01

    Primary biliary cirrhosis (PBC) is a liver-specific autoimmune disease that primarily affects women (female-to-male ratio, 10:1) between 40 and 60 years of age. Metabolic bone disease is a common complication of PBC, affecting 14% to 52% of patients, depending on the duration and severity of liver disease. The osteoporosis seen in PBC seems mainly due to low bone formation, although increased bone resorption may contribute. Treatment of osteoporosis consists primarily of antiresorptive agents. Additional large prospective, long-term studies in patients with PBC are needed to determine efficacy in improving bone density as well as reducing fracture risk. PMID:27261902

  11. Drugs affecting glycosaminoglycan metabolism.

    PubMed

    Ghiselli, Giancarlo; Maccarana, Marco

    2016-07-01

    Glycosaminoglycans (GAGs) are charged polysaccharides ubiquitously present at the cell surface and in the extracellular matrix. GAGs are crucial for cellular homeostasis, and their metabolism is altered during pathological processes. However, little consideration has been given to the regulation of the GAG milieu through pharmacological interventions. In this review, we provide a classification of small molecules affecting GAG metabolism based on their mechanism of action. Furthermore, we present evidence to show that clinically approved drugs affect GAG metabolism and that this could contribute to their therapeutic benefit. PMID:27217160

  12. Diagnosis of metabolic bone disease

    SciTech Connect

    Grech, P.; Martin, T.J.; Barrington, N.A.; Ell, P.J.

    1986-01-01

    This book presents a reference on the radiologic evaluation, features, and differential diagnosis of metabolic diseases involving the whole skeleton, calcium deficiencies resulting from pharmacologic agents, and bone changes related to endocrine disturbances. It also stresses how radiology, nuclear medicine, and biochemistry - either alone or in concert - contribute to clinical diagnosis. It covers renal bone disease, Paget's disease, hyperphosphatasia, extraskeletal mineralization, metabolic bone disorders related to malnutrition, tumors, plus radionuclide studies including materials and methods.

  13. Modulation of Vitamin D Status and Dietary Calcium Affects Bone Mineral Density and Mineral Metabolism in Göttingen Minipigs

    PubMed Central

    Scholz-Ahrens, Katharina E.; Glüer, Claus-Christian; Bronner, Felix; Delling, Günter; Açil, Yahya; Hahne, Hans-Jürgen; Hassenpflug, Joachim; Timm, Wolfram; Schrezenmeir, Jürgen

    2013-01-01

    Calcium and vitamin D deficiency impairs bone health and may cause rickets in children and osteomalacia in adults. Large animal models are useful to study experimental osteopathies and associated metabolic changes. We intended to modulate vitamin D status and induce nutritional osteomalacia in minipigs. The control group (n = 9) was fed a semisynthetic reference diet with 6 g calcium and 6,500 IU vitamin D3/kg and the experimental group (n = 10) the same diet but with only 2 g calcium/kg and without vitamin D. After 15 months, the deficient animals were in negative calcium balance, having lost bone mineral density significantly (means ± SEM) with −51.2 ± 14.7 mg/cm3 in contrast to controls (−2.3 ± 11.8 mg/cm3), whose calcium balance remained positive. Their osteoid surface was significantly higher, typical of osteomalacia. Their plasma 25(OH)D dropped significantly from 60.1 ± 11.4 nmol/L to 15.3 ± 3.4 nmol/L within 10 months, whereas that of the control group on the reference diet rose. Urinary phosphorus excretion and plasma 1,25-dihydroxyvitamin D concentrations were significantly higher and final plasma calcium significantly lower than in controls. We conclude that the minipig is a promising large animal model to induce nutritional osteomalacia and to study the time course of hypovitaminosis D and associated functional effects. PMID:24062955

  14. Bone metabolism in anorexia nervosa.

    PubMed

    Fazeli, Pouneh K; Klibanski, Anne

    2014-03-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed, chronic nutritional deprivation and distorted body image. AN is associated with a number of medical comorbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  15. Bone Metabolism in Anorexia Nervosa

    PubMed Central

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed chronic nutritional deprivation and distorted body image. AN is associated with a number of medical co-morbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population. PMID:24419863

  16. Bone metabolism during pregnancy.

    PubMed

    Salles, Jean Pierre

    2016-06-01

    During pregnancy, mineral concentrations, of calcium and phosphorus in particular, are maintained at a high level in fetal blood so that the developing skeleton may accrete adequate mineral content. The placenta actively transports minerals for this purpose. Maternal intestinal absorption increases in order to meet the fetal demand for calcium, which is only partly dependent on calcitriol. Mineral regulation is essentially dependent on parathyroid hormone (PTH) and PTH-related protein (PTHrP). The calcium-sensing receptor (CaSR) regulates PTH and PTHrP production. If calcium intake is insufficient, the maternal skeleton will undergo resorption due to PTHrP. After birth, a switch from fetal to neonatal homeostasis occurs through increase in PTH and calcitriol, and developmental adaptation of the kidneys and intestines with bone turnover contributing additional mineral to the circulation. Calcium absorption becomes progressively active and dependent on calcitriol. The postnatal skeleton can transiently present with osteoposis but adequate mineral diet usually allows full restoration. Cases of primary osteoporosis must be identified. Loss of trabecular mineral content occurs during lactation in order to provide calcium to the newborn. This programmed bone loss is dependent on a "brain-breast-bone" circuit. The physiological bone resorption during reproduction does not normally cause fractures or persistent osteoporosis. Women who experience fracture are likely to have other causes of bone loss. PMID:27157104

  17. Periodontitis and bone metabolism

    PubMed Central

    Barbato, Luigi; Francioni, Edoardo; Bianchi, Massimiliano; Mascitelli, Eleonora; Marco, Leila Brancato; Tonelli, Duvina Paolo

    2015-01-01

    Summary Periodontitis is a plaque induced disease characterized by tissue destruction. The extent of the alveolar bone loss depends on the host response stimulated by bacterial infection. Recently researchers have focused on the role of the immune system, of RANK/RANKL/OPG pathway and of cytokines network. Another recent field of interest is osteoimmunology that try to explain the relationship between immune and bone cells in activating bone resorption. Advances in the understanding of the pathogenic mechanisms allowed a better understanding of the relationship with other diseases like osteoporosis and also to hypothesize new therapies based on modulation of host response (host modulatory therapy - HMT). The purpose of this mini-review is to briefly discuss these topics. PMID:26604945

  18. Novel Adipokines and Bone Metabolism

    PubMed Central

    Liu, Yuan; Song, Cheng-Yuan; Wu, Shan-Shan; Liang, Qiu-Hua; Yuan, Ling-Qing; Liao, Er-Yuan

    2013-01-01

    Osteoporosis is a serious social issue nowadays. Both the high morbidity and its common complication osteoporotic fracture load a heavy burden on the whole society. The adipose tissue is the biggest endocrinology organ that has a different function on the bone. The adipocytes are differentiated from the same cell lineage with osteoblast, and they can secrete multiple adipokines with various functions on bone remolding. Recently, several novel adipokines have been identified and investigated thoroughly. In this paper, we would like to highlight the complicated relation between the bone metabolism and the novel adipokines, and it may provide us with a new target for prediction and treatment of osteoporosis. PMID:23431296

  19. OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism.

    PubMed

    Ardeshirpour, Laleh; Dumitru, Cristina; Dann, Pamela; Sterpka, John; VanHouten, Joshua; Kim, Wonnam; Kostenuik, Paul; Wysolmerski, John

    2015-08-01

    Lactation is associated with increased bone turnover and rapid bone loss, which liberates skeletal calcium used for milk production. Previous studies suggested that an increase in the skeletal expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL) coupled with a decrease in osteoprotegerin (OPG) levels likely triggered bone loss during lactation. In this study, we treated lactating mice with recombinant OPG to determine whether bone loss during lactation was dependent on RANKL signaling and whether resorption of the maternal skeleton was required to support milk production. OPG treatment lowered bone resorption rates and completely prevented bone loss during lactation but, surprisingly, did not decrease osteoclast numbers. In contrast, OPG was quite effective at lowering osteoblast numbers and inhibiting bone formation in lactating mice. Furthermore, treatment with OPG during lactation prevented the usual anabolic response associated with reversal of lactational bone loss after weaning. Preventing bone loss had no appreciable effect on milk production, milk calcium levels, or maternal calcium homeostasis when mice were on a standard diet. However, when dietary calcium was restricted, treatment with OPG caused maternal hypocalcemia, maternal death, and decreased milk production. These studies demonstrate that RANKL signaling is a requirement for bone loss during lactation, and suggest that osteoclast activity may be required to increase osteoblast numbers during lactation in preparation for the recovery of bone mass after weaning. These data also demonstrate that maternal bone loss is not absolutely required to supply calcium for milk production unless dietary calcium intake is inadequate. PMID:25961842

  20. OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism

    PubMed Central

    Ardeshirpour, Laleh; Dumitru, Cristina; Dann, Pamela; Sterpka, John; VanHouten, Joshua; Kim, Wonnam; Kostenuik, Paul

    2015-01-01

    Lactation is associated with increased bone turnover and rapid bone loss, which liberates skeletal calcium used for milk production. Previous studies suggested that an increase in the skeletal expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL) coupled with a decrease in osteoprotegerin (OPG) levels likely triggered bone loss during lactation. In this study, we treated lactating mice with recombinant OPG to determine whether bone loss during lactation was dependent on RANKL signaling and whether resorption of the maternal skeleton was required to support milk production. OPG treatment lowered bone resorption rates and completely prevented bone loss during lactation but, surprisingly, did not decrease osteoclast numbers. In contrast, OPG was quite effective at lowering osteoblast numbers and inhibiting bone formation in lactating mice. Furthermore, treatment with OPG during lactation prevented the usual anabolic response associated with reversal of lactational bone loss after weaning. Preventing bone loss had no appreciable effect on milk production, milk calcium levels, or maternal calcium homeostasis when mice were on a standard diet. However, when dietary calcium was restricted, treatment with OPG caused maternal hypocalcemia, maternal death, and decreased milk production. These studies demonstrate that RANKL signaling is a requirement for bone loss during lactation, and suggest that osteoclast activity may be required to increase osteoblast numbers during lactation in preparation for the recovery of bone mass after weaning. These data also demonstrate that maternal bone loss is not absolutely required to supply calcium for milk production unless dietary calcium intake is inadequate. PMID:25961842

  1. Dietary protein level and source differentially affect bone metabolism, strength, and intestinal calcium transporter expression during ad libitum and food-restricted conditions in male rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High protein diets may attenuate bone loss during energy restriction (ER). The objective of the current study was to determine whether high protein diets suppress bone turnover and improve bone quality in rats during ER and whether dietary protein source affects this relationship. Eighty 12-week o...

  2. Bone Metabolism after Bariatric Surgery

    PubMed Central

    Yu, Elaine W.

    2014-01-01

    Bariatric surgery is a popular and effective treatment for severe obesity, but may have negative effects on the skeleton. This review summarizes changes in bone density and bone metabolism from animal and clinical studies of bariatric surgery, with specific attention to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and sleeve gastrectomy (SG). Skeletal imaging artifacts from obesity and weight loss are also considered. Despite challenges in bone density imaging, the preponderance of evidence suggests that bariatric surgery procedures have negative skeletal effects that persist beyond the first year of surgery, and that these effects vary by surgical type. The long-term clinical implications and current clinical recommendations are presented. Further study is required to determine mechanisms of bone loss after bariatric surgery. Although early studies focused on calcium/vitamin D metabolism and mechanical unloading of the skeleton, it seems likely that surgically-induced changes in the hormonal and metabolic profile may be responsible for the skeletal phenotypes observed after bariatric surgery. PMID:24677277

  3. Disrupted Bone Metabolism in Long-Term Bedridden Patients

    PubMed Central

    Endo, Naoto; Uchiyama, Seiji; Takahashi, Yoshinori; Kawashima, Hiroyuki; Watanabe, Kei

    2016-01-01

    Background Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. Methods This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged <30 years at baseline. Results The bone mineral density was reduced (0.58±0.19 g/cm3), and the osteocalcin (13.9±12.4 ng/mL) and urine N-terminal telopeptide (NTX) levels (146.9±134.0 mM BCE/mM creatinine) were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. Conclusions Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients. PMID:27275738

  4. Diabetes mellitus related bone metabolism and periodontal disease

    PubMed Central

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts. PMID:25857702

  5. [Abnormality in bone metabolism after burn].

    PubMed

    Gong, X; Xie, W G

    2016-08-20

    Burn causes bone metabolic abnormality in most cases, including the changes in osteoblasts and osteoclasts, bone mass loss, and bone absorption, which results in decreased bone mineral density. These changes are sustainable for many years after burn and even cause growth retardation in burned children. The mechanisms of bone metabolic abnormality after burn include the increasing glucocorticoids due to stress response, a variety of cytokines and inflammatory medium due to inflammatory response, vitamin D deficiency, hypoparathyroidism, and bone loss due to long-term lying in bed. This article reviews the pathogenesis and regularity of bone metabolic abnormality after burn, the relationship between bone metabolic abnormality and burn area/depth, and the treatment of bone metabolic abnormality, etc. and discusses the research directions in the future. PMID:27562160

  6. Obstructive sleep apnea and metabolic bone disease: Insights in to the relationship between bone and sleep

    PubMed Central

    Swanson, Christine M.; Shea, Steven A.; Stone, Katie L.; Cauley, Jane A.; Rosen, Clifford J.; Redline, Susan; Karsenty, Gerard; Orwoll, Eric S.

    2015-01-01

    Obstructive sleep apnea (OSA) and low bone mass are two prevalent conditions, particularly among older adults, a section of the U.S. population that is expected to grow dramatically over the coming years. OSA, the most common form of sleep disordered breathing, has been linked to multiple cardiovascular, metabolic, hormonal and inflammatory derangements and may have adverse effects on bone. However, little is known about how OSA (including the associated hypoxia and sleep loss) affects bone metabolism. In order to gain insight into the relationship between sleep and bone, we review the growing information on OSA and metabolic bone disease and discuss the pathophysiological mechanisms by which OSA may affect bone metabolism/architecture. PMID:25639209

  7. [Bone metabolic markers and diagnosis of abnormal bone and calcium metabolism].

    PubMed

    Fukunaga, M; Sone, T

    2001-07-01

    Bone metabolic markers increase in blood or urine, when bone formation or bone resorption accelerates. Reference values of bone metabolic markers are determined in male or female, and in pre- or post-menopause, respectively. Values of bone metabolic markers in most patients with primary osteoporosis were distributed within a reference value, mean+/-1.96 SD. When measured values exceeded a reference values, we should survey a possibility of abnormal calcium or bone metabolism such as primary hyperparathyroidism, renal osteodystrophy, hyperthyroidism and Paget's disease of bone or bone metastasis associated with malignant tumor. PMID:15775589

  8. Celiac disease and metabolic bone disease.

    PubMed

    Xing, Yanming; Morgan, Sarah L

    2013-01-01

    Celiac disease is a common autoimmune gastrointestinal disorder affecting multiple organs, precipitated in genetically vulnerable persons by the ingestion of gluten. Gluten is poorly digested and is presented to the intestinal mucosa as a large polypeptide. Binding to human leukocyte antigen-DQ2 and human leukocyte antigen-DQ8 molecules on antigen-presenting cells stimulates cellular and humeral immune reactions. Although common serological tests are available to diagnose celiac disease, the diagnosis of celiac disease is often delayed or missed because of lack of recognition as the disease presentation in adults is highly variable and may be asymptomatic. Celiac disease is a common secondary cause of metabolic bone disease and delayed treatment with gluten-free diet affects bone mineral density and fracture risk, so it is crucial to diagnose and treat celiac disease promptly. In this article, we will review recent studies of celiac disease in adults and provide practical, easily accessible information for busy clinicians. PMID:24090646

  9. Effects of simulated weightlessness on bone mineral metabolism

    NASA Technical Reports Server (NTRS)

    Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

    1984-01-01

    It is pointed out that prolonged space flight, bedrest, and immobilization are three factors which can produce a negative calcium balance, osteopenia, and an inhibition of bone formation. It is not known whether the effects of gravity on bone mineral metabolism are mediated by systemic endocrine factors which affect all bones simultaneously, or by local factors which affect each bone individually. The present investigation has the objective to test the relative importance of local vs. systemic factors in regulating the bone mineral response to conditions simulating weightlessness. Experiments were conducted with male Sprague-Dawley rats. The test conditions made it possible to compare the data from weighted and unweighted bones in the same animal. The obtained findings indicate that a decrease in bone mass relative to control value occurs rapidly under conditions which simulate certain aspects of weightlessness. However, this decrease reaches a plateau after 10 days.

  10. Is Bone Tissue Really Affected by Swimming? A Systematic Review

    PubMed Central

    Gómez-Bruton, Alejandro; Gónzalez-Agüero, Alejandro; Gómez-Cabello, Alba; Casajús, José A.; Vicente-Rodríguez, Germán

    2013-01-01

    Background Swimming, a sport practiced in hypogravity, has sometimes been associated with decreased bone mass. Aim This systematic review aims to summarize and update present knowledge about the effects of swimming on bone mass, structure and metabolism in order to ascertain the effects of this sport on bone tissue. Methods A literature search was conducted up to April 2013. A total of 64 studies focusing on swimmers bone mass, structure and metabolism met the inclusion criteria and were included in the review. Results It has been generally observed that swimmers present lower bone mineral density than athletes who practise high impact sports and similar values when compared to sedentary controls. However, swimmers have a higher bone turnover than controls resulting in a different structure which in turn results in higher resistance to fracture indexes. Nevertheless, swimming may become highly beneficial regarding bone mass in later stages of life. Conclusion Swimming does not seem to negatively affect bone mass, although it may not be one of the best sports to be practised in order to increase this parameter, due to the hypogravity and lack of impact characteristic of this sport. Most of the studies included in this review showed similar bone mineral density values in swimmers and sedentary controls. However, swimmers present a higher bone turnover than sedentary controls that may result in a stronger structure and consequently in a stronger bone. PMID:23950908

  11. Anorexia nervosa and bone metabolism.

    PubMed

    Fazeli, Pouneh K; Klibanski, Anne

    2014-09-01

    Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation with a lifetime prevalence of 2.2% in women. The most common medical co-morbidity in women with AN is bone loss, with over 85% of women having bone mineral density values more than one standard deviation below an age comparable mean. The low bone mass in AN is due to multiple hormonal adaptations to under nutrition, including hypothalamic amenorrhea and growth hormone resistance. Importantly, this low bone mass is also associated with a seven-fold increased risk of fracture. Therefore, strategies to effectively prevent bone loss and increase bone mass are critical. We will review hormonal adaptations that contribute to bone loss in this population as well as promising new therapies that may increase bone mass and reduce fracture risk in AN. PMID:24882734

  12. Anorexia nervosa and bone metabolism

    PubMed Central

    Fazeli, Pouneh K.; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation with a lifetime prevalence of 2.2% in women. The most common medical co-morbidity in women with AN is bone loss, with over 85% of women having bone mineral density values more than one standard deviation below an age comparable mean. The low bone mass in AN is due to multiple hormonal adaptations to under nutrition, including hypothalamic amenorrhea and growth hormone resistance. Importantly, this low bone mass is also associated with a seven-fold increased risk of fracture. Therefore, strategies to effectively prevent bone loss and increase low bone mass are critical. We will review hormonal adaptations that contribute to bone loss in this population as well as promising new therapies that may increase bone mass and reduce fracture risk in AN. PMID:24882734

  13. Calcium and bone metabolism during space flight.

    PubMed

    Smith, Scott M; Heer, Martina

    2002-10-01

    Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss. PMID:12361777

  14. Calcium and bone metabolism during space flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Heer, Martina

    2002-01-01

    Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.

  15. Bone Metabolism on ISS Missions

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

    2014-01-01

    Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those

  16. Bone Metabolism in Adolescents with Anorexia Nervosa

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2013-01-01

    Adolescents with anorexia nervosa (AN) are at risk for low bone mass at multiple sites, associated with decreased bone turnover. Bone microarchitecture is also affected, with a decrease in bone trabecular volume and trabecular thickness, and an increase in trabecular separation. The adolescent years are typically the time when marked increases occur in bone mass accrual towards the attainment of peak bone mass, an important determinant of bone health and fracture risk in later life. AN often begins in the adolescent years, and decreased rates of bone mass accrual at this critical time are therefore also concerning for deficits in peak bone mass. Factors contributing to low bone density and decreased rates of bone accrual include alterations in body composition such as low BMI and lean body mass, and hormonal alterations such as hypogonadism, a nutritionally acquired resistance to growth hormone and low levels of IGF-1, relative hypercortisolemia, low levels of leptin, and increased adiponectin (for fat mass) and peptide YY. Therapeutic strategies include optimizing weight and menstrual recovery, and adequate calcium and vitamin D replacement. Oral estrogen-progesterone combination pills are not effective in increasing bone density in adolescents with AN. RhIGF-1 increases levels of bone formation markers in the short-term, while long-term effects remain to be determined. Bisphosphonates act by decreasing bone resorption, and are not optimal for use in adolescents with AN, in whom the primary defect is low bone formation. PMID:21301203

  17. Anorexia nervosa, obesity and bone metabolism.

    PubMed

    Misra, Madhusmita; Klibanski, Anne

    2013-09-01

    Anorexia nervosa and obesity are conditions at the extreme ends of the nutritional spectrum, associated with marked reductions versus increases respectively in body fat content. Both conditions are also associated with an increased risk for fractures. In anorexia nervosa, body composition and hormones secreted or regulated by body fat content are important determinants of low bone density, impaired bone structure and reduced bone strength. In addition, anorexia nervosa is characterized by increases in marrow adiposity and decreases in cold activated brown adipose tissue, both of which are related to low bone density. In obese individuals, greater visceral adiposity is associated with greater marrow fat, lower bone density and impaired bone structure. In this review, we discuss bone metabolism in anorexia nervosa and obesity in relation to adipose tissue distribution and hormones secreted or regulated by body fat content. PMID:24079076

  18. Anorexia Nervosa, Obesity and Bone Metabolism

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa and obesity are conditions at the extreme ends of the nutritional spectrum, associated with marked reductions versus increases respectively in body fat content. Both conditions are also associated with an increased risk for fractures. In anorexia nervosa, body composition and hormones secreted or regulated by body fat content are important determinants of low bone density, impaired bone structure and reduced bone strength. In addition, anorexia nervosa is characterized by increases in marrow adiposity and decreases in cold activated brown adipose tissue, both of which are related to low bone density. In obese individuals, greater visceral adiposity is associated with greater marrow fat, lower bone density and impaired bone structure. In this review, we discuss bone metabolism in anorexia nervosa and obesity in relation to adipose tissue distribution and hormones secreted or regulated by body fat content. PMID:24079076

  19. Bone Remodeling and Energy Metabolism: New Perspectives

    PubMed Central

    de Paula, Francisco J. A.; Rosen, Clifford J.

    2013-01-01

    Bone mineral, adipose tissue and energy metabolism are interconnected by a complex and multilevel series of networks. Calcium and phosphorus are utilized for insulin secretion and synthesis of high energy compounds. Adipose tissue store lipids and cholecalciferol, which, in turn, can influence calcium balance and energy expenditure. Hormones long-thought to solely modulate energy and mineral homeostasis may influence adipocytic function. Osteoblasts are a target of insulin action in bone. Moreover, endocrine mediators, such as osteocalcin, are synthesized in the skeleton but regulate carbohydrate disposal and insulin secretion. Finally, osteoblasts and adipocytes originate from the same mesenchymal progenitor. The mutual crosstalk between osteoblasts and adipocytes within the bone marrow microenvironment plays a crucial role in bone remodeling. In the present review we provide an overview of the reciprocal control between bone and energy metabolism and its clinical implications. PMID:26273493

  20. Calcium and Bone Metabolism During Spaceflight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.

    2002-01-01

    The ability to understand and counteract weightlessness-induced bone loss will be critical for crew health and safety during and after space station or exploration missions lasting months or years, respectively. Until its deorbit in 2001 , the Mir Space Station provided a valuable platform for long-duration space missions and life sciences research. Long-duration flights are critical for studying bone loss, as the 2- to 3-week Space Shuttle flights are not long enough to detect changes in bone mass. This review will describe human spaceflight data, focusing on biochemical surrogates of bone and calcium metabolism. This subject has been reviewed previously. 1-

  1. Green Tea and Bone Metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteoporosis is a major health problem in elderly men and women. Epidemiological evidence has shown association between tea consumption and age-related bone loss in elderly men and women. The aim of this review is to provide a systemic review of green tea and bone health to cover the following topi...

  2. Green Tea and Bone metabolism

    PubMed Central

    Shen, Chwan-Li; Yeh, James K.; Cao, Jay; Wang, Jia-Sheng

    2009-01-01

    Osteoporosis is a major health problem in both elderly women and men. Epidemiological evidence has shown an association between tea consumption and the prevention of age-related bone loss in elderly women and men. Ingestion of green tea and green tea bioactive compounds may be beneficial in mitigating bone loss of this population and decreasing their risk of osteoporotic fractures. This review describes the effect of green tea or its bioactive components on bone health, with an emphasis on: (i) the prevalence and etiology of osteoporosis, (ii) the role of oxidative stress and antioxidants in osteoporosis, (iii) green tea composition and bioavailability, (iv) the effects of green tea and its active components on osteogenesis, osteoblastogenesis, and osteoclastogenesis from human epidemiological, animal, as well as cell culture studies, (v) possible mechanisms explaining the osteo-protective effects of green tea bioactive compounds, (vi) other bioactive components in tea that benefit bone health, and (vii) a summary and future direction of green tea and bone health research and the translational aspects. In general, tea and its bioactive components might decrease the risk of fracture by improving bone mineral density (BMD) and supporting osteoblastic activities while suppressing osteoclastic activities. PMID:19700031

  3. Metabolic bone disease in children : etiology and treatment options.

    PubMed

    Skowrońska-Jóźwiak, Elzbieta; Lorenc, Roman S

    2006-01-01

    Metabolic bone disease in children includes many hereditary and acquired conditions of diverse etiology that lead to disturbed metabolism of the bone tissue. Some of these processes primarily affect bone; others are secondary to nutritional deficiencies, a variety of chronic disorders, and/or treatment with some drugs. Some of these disorders are rare, but some present public health concerns (for instance, rickets) that have been well known for many years but still persist. The most important clinical consequences of bone metabolic diseases in the pediatric population include reduced linear growth, bone deformations, and non-traumatic fractures leading to bone pain, deterioration of motor development and disability. In this article, we analyze primary and secondary osteoporosis, rickets, osteomalacia (nutritional and hereditary vitamin D-dependent, hypophosphatemic and that due to renal tubular abnormalities), renal osteodystrophy, sclerosing bony disorders, and some genetic bone diseases (hypophosphatasia, fibrous dysplasia, skeletal dysplasia, juvenile Paget disease, familial expansile osteolysis, and osteoporosis pseudoglioma syndrome). Early identification and treatment of potential risk factors is essential for skeletal health in adulthood. In most conditions it is necessary to ensure an appropriate diet, with calcium and vitamin D, and an adequate amount of physical activity as a means of prevention. In secondary bone diseases, treatment of the primary disorder is crucial. Most genetic disorders await prospective gene therapies, while bone marrow transplantation has been attempted in other disorders. At present, affected patients are treated symptomatically, frequently by interdisciplinary teams. The role of exercise and pharmacologic therapy with calcium, vitamin D, phosphate, bisphosphonates, calcitonin, sex hormones, growth hormone, and thiazides is discussed. The perspectives on future therapy with insulin-like growth factor-1, new analogs of vitamin D

  4. Bone metabolism of male rats chronically exposed to cadmium

    SciTech Connect

    Brzoska, Malgorzata M. . E-mail: mmbr@poczta.onet.pl; Moniuszko-Jakoniuk, Janina

    2005-09-15

    Recently, based on a female rat model of human exposure, we have reported that low-level chronic exposure to cadmium (Cd) has an injurious effect on the skeleton. The purpose of the current study was to investigate whether the exposure may also affect bone metabolism in a male rat model and to estimate the gender-related differences in the bone effect of Cd. Young male Wistar rats received drinking water containing 0, 1, 5, or 50 mg Cd/l for 12 months. The bone effect of Cd was evaluated using bone densitometry and biochemical markers of bone turnover. Renal handling of calcium (Ca) and phosphate, and serum concentrations of vitamin D metabolites, calcitonin, and parathormone were estimated as well. At treatment with 1 mg Cd/l, corresponding to the low environmental exposure in non-Cd-polluted areas, the bone mineral content (BMC) and density (BMD) at the femur and lumbar spine (L1-L5) and the total skeleton BMD did not differ compared to control. However, from the 6th month of the exposure, the Z score BMD indicated osteopenia in some animals and after 12 months the bone resorption very clearly tended to an increase. The rats' exposure corresponding to human moderate (5 mg Cd/l) and especially relatively high (50 mg Cd/l) exposure dose- and duration-dependently disturbed the processes of bone turnover and bone mass accumulation leading to formation of less dense than normal bone tissue. The effects were accompanied by changes in the serum concentration of calciotropic hormones and disorders in Ca and phosphate metabolism. It can be concluded that low environmental exposure to Cd may be only a subtle risk factor for skeletal demineralization in men. The results together with our previous findings based on an analogous model using female rats give clear evidence that males are less vulnerable to the bone effects of Cd compared to females.

  5. Bone and Calcium Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.

    2004-01-01

    Understanding bone loss during space flight is one of the most critical challenges for maintaining astronaut health on space exploration missions. Flight and ground-based studies have been conducted to better understand the nature and mechanisms of weightlessness-induced bone loss, and to identify a means to counteract the loss. Maintenance of bone health requires a balance between bone formation and bone resorption. Early space research identified bone loss as a critical health issue, but could not provide a distinction between the bone formation and breakdown processes. The recent identification of collagen crosslinks as markers of bone resorption has made possible a clear understanding that a decrease in bone resorption is an important effect of space flight, with bone formation being unchanged or only slightly decreased. Calcium regulatory factors have also been studied, in an attempt to understand their role in bone loss. The lack of ultraviolet light exposure and insufficient dietary sources of vitamin D often lead to reduced vitamin D stores on long-duration flights. Serum parathyroid hormone (PTH) concentrations are decreased during flight compared to before flight, although small subject numbers often make this hard to document statistically. As expected, reduced PTH concentrations are accompanied by reduced 1,25-dihydroxyvitamin D concentrations. Calcium kinetic studies during space flight confirm and extend the information gained from biochemical markers of bone metabolism. Calcium kinetic studies demonstrate that bone resorption is increased, bone formation is unchanged or decreased, and dietary calcium absorption is reduced during space flight. Evaluations have also been conducted of countermeasures, including dietary, exercise, and pharmacological treatments. In recent studies, many potential countermeasures show promise at mitigating bone loss in ground-based analogs of weightlessness (e.g., bed rest), but require further ground and flight testing to

  6. Metabolic bone disease and parenteral nutrition.

    PubMed

    Hamilton, Cynthia; Seidner, Douglas L

    2004-08-01

    Metabolic bone disease (MBD) is abnormal bone metabolism and includes the common disorders of osteoporosis and osteomalacia, which can develop in patients receiving long-term parenteral nutrition (PN). Patients who require long-term PN have significant gastrointestinal failure and malabsorption, which is generally caused by severe inflammatory bowel disease, intestinal ischemia, or malignancy. The exact cause of MBD in long-term PN patients is unknown, but its origin is thought to be multifactorial, with factors including underlying disease, effect of medications used to treat this disease (eg, corticosteroids), and various components of the PN solution. Caring for patients on long-term PN requires routine assessment and monitoring for MBD. Appropriate adjustments of the PN solution can help reduce the risk for developing PN-associated MBD and in some instances improve bone mineral density. Recent developments in pharmacologic treatment for osteoporosis show promise for patients with MBD receiving PN. PMID:15245704

  7. Post-genomics of bone metabolic dysfunctions and neoplasias.

    PubMed

    Bernardini, Giulia; Braconi, Daniela; Spreafico, Adriano; Santucci, Annalisa

    2012-02-01

    Post-genomic research on osteoblastic and osteoclastic cells, in contrast to that on many other cell types, has only been undertaken recently. Nevertheless, important information has been gained from these investigations on the mechanisms involved in osteoblast differentiation and on markers relevant for tissue regeneration and therapeutic validation of drugs, hormones and growth factors. These protein indicators may also have a diagnostic and prognostic value for bone dysfunctions and tumors. Some reviews have already focused on the application of transcriptomics and/or proteomics for exploring skeletal biology and related disorders. The main goal of the present review is to systematically summarize the most relevant post-genomic studies on various metabolic bone diseases (osteoporosis, Paget's disease and osteonecrosis), neoplasias (osteosarcoma) and metabolic conditions that indirectly affect bone tissue, such as alkaptonuria. PMID:22246652

  8. [Bone and calcium metabolism in life-style related diseases].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2016-03-01

    Accumulating evidence shows that life-style related diseases such as diabetes mellitus, hypertension, dyslipidemia are associated with bone and calcium metabolism. Patients with diabetes mellitus have increased fracture risks, independently of bone mineral density, with abnormality of parathyroid hormone secretion and impaired osteoblastic function. On the other hand, osteocalcin secreted from bone is reported to regulate glucose metabolism. Thus, bone, calcium and glucose metabolism may be deeply associated with each other. In this review, we describe the association between life-style related diseases, especially diabetes mellitus, and metabolism of bone and calcium. PMID:26923977

  9. Bone: from a reservoir of minerals to a regulator of energy metabolism.

    PubMed

    Confavreux, Cyrille B

    2011-04-01

    Besides locomotion, organ protection, and calcium-phosphorus homeostasis, the three classical functions of the skeleton, bone remodeling affects energy metabolism through uncarboxylated osteocalcin, a recently discovered hormone secreted by osteoblasts. This review traces how energy metabolism affects osteoblasts through the central control of bone mass involving leptin, serotoninergic neurons, the hypothalamus, and the sympathetic nervous system. Next, the role of osteocalcin (insulin secretion, insulin sensitivity, and pancreas β-cell proliferation) in the regulation of energy metabolism is described. Then, the connections between insulin signaling on osteoblasts and the release of uncarboxylated osteocalcin during osteoclast bone resorption through osteoprotegerin are reported. Finally, the understanding of this new bone endocrinology will provide some insights into bone, kidney, and energy metabolism in patients with chronic kidney disease. PMID:21346725

  10. Bone: from a reservoir of minerals to a regulator of energy metabolism.

    PubMed

    Confavreux, Cyrille B

    2011-04-01

    Besides locomotion, organ protection, and calcium-phosphorus homeostasis, the three classical functions of the skeleton, bone remodeling affects energy metabolism through uncarboxylated osteocalcin, a recently discovered hormone secreted by osteoblasts. This review traces how energy metabolism affects osteoblasts through the central control of bone mass involving leptin, serotoninergic neurons, the hypothalamus, and the sympathetic nervous system. Next, the role of osteocalcin (insulin secretion, insulin sensitivity, and pancreas β-cell proliferation) in the regulation of energy metabolism is described. Then, the connections between insulin signaling on osteoblasts and the release of uncarboxylated osteocalcin during osteoclast bone resorption through osteoprotegerin are reported. Finally, the understanding of this new bone endocrinology will provide some insights into bone, kidney, and energy metabolism in patients with chronic kidney disease. PMID:26746856

  11. Heritability of markers of bone metabolism

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Zwart, S. R.; Hargens, A. R.

    2005-01-01

    Several classic twin studies show genetic effects on markers of bone health, including bone mineral density and parathyroid hormone (PTH). This study was performed to assess the relative contribution of genetics to biochemical markers of bone metabolism. Fifteen sets of identical twins (8 male, 7 female) were housed in a clinical research center where diet was controlled (15% protein, 55% carbohydrate, 30% fat) for 3 consecutive days. Each day, 24-h urine pools were collected and N-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and serum PTH were measured. The broad-sense heritability factor (H2) is an estimation of the portion of the total variance of a given phenotype that is attributable to genetic variance. H2 was estimated from the correlation coefficient of the phenotype data. H2 for NTX was 94% for males and 80% for females, DPD was 88% for males and 97% for females, urinary calcium excretion was 97% for males and 90% for females, and PTH was 92% for males and 79% for females. Since environmental variability was minimized for the 3 days of data collection, these heritability factors are likely overestimated. Nonetheless, the data support the concept that PTH is a predominantly heritable trait, and suggest that NTX, DPD, and calcium excretion are as well. These biochemical data support the previously documented heritability of bone health.

  12. [Dehydroepiandrosterone(DHEA)and bone metabolism].

    PubMed

    Ohnaka, Keizo

    2016-07-01

    Dehydroepiandrosterone(DHEA), an adrenal androgen, has attracted much attention as an anti-aging hormone as well as a marker for senescence because of its unique change along with aging. DHEA is reported to have beneficial effects such as anti-diabetes, anti-obesity, and anti-atherosclerosis. It is also shown that DHEA has anti-osteoporosis effects to increase bone mineral density in randomized controlled trials(RCTs). As osteoblasts express aromatase which will convert androgen to estrogen, DHEA may act protectively against osteoporosis through its metabolites. Because there is no report on fracture risk by DHEA administration, further studies are required to clarify DHEA effects on human bone metabolism. PMID:27346309

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

    PubMed

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

    2015-09-01

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

  14. Genetic Regulation of Bone Metabolism in the Chicken: Similarities and Differences to Mammalian Systems

    PubMed Central

    Johnsson, Martin; Jonsson, Kenneth B.; Andersson, Leif; Jensen, Per; Wright, Dominic

    2015-01-01

    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. PMID:26023928

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

    PubMed

    Johnsson, Martin; Jonsson, Kenneth B; Andersson, Leif; Jensen, Per; Wright, Dominic

    2015-05-01

    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. PMID:26023928

  16. Metabolic Bone Disease in preterm newborn: an update on nutritional issues

    PubMed Central

    Bozzetti, Valentina; Tagliabue, Paolo

    2009-01-01

    Osteopenia, a condition characterised by a reduction in bone mineral content, is a common disease of preterm babies between the tenth and sixteenth week of life. Prematurely born infants are deprived of the intrauterine supply of minerals affecting bone mineralization. The aetiology is multifactorial: inadequate nutrients intake (calcium, phosphorus and vitamin D), a prolonged period of total parenteral nutrition, immobilisation and the intake of some drugs. The diagnosis of metabolic bone disease is done by biochemical analysis: low serum levels of phosphorus and high levels of alkaline phosphatase are suggestive of metabolic bone disease. The disease can remain clinically silent or presents with symptoms and signs of rachitism depending on the severity of bone demineralisation. An early nutritional intervention can reduce both the prevalence and the severity of osteopenia. This article reviews the pathophysiology of foetal and neonatal bone metabolism, focuses on the nutrient requirements of premature babies and on the ways to early detect and treat osteopenia. PMID:19602277

  17. The role of leptin in regulating bone metabolism

    PubMed Central

    Upadhyay, Jagriti; Farr, Olivia M.; Mantzoros, Christos S.

    2015-01-01

    Leptin was initially best known for its role in energy homeostasis and regulation of energy expenditure. In the past few years we have realized that leptin also plays a major role in neuroendocrine regulation and bone metabolism. Here, we review the literature on indirect and direct pathways through which leptin acts to influence bone metabolism and discuss bone abnormalities related to leptin deficiency in both animal and human studies. The clinical utility of leptin in leptin deficient individuals and its potential to improve metabolic bone disease are also discussed. We are beginning to understand the critical role leptin plays in bone metabolism; future randomized studies are needed to fully assess the potential and risk – benefit of leptin's use in metabolic bone disease particularly in leptin deficient individuals. PMID:25497343

  18. Correlations Between Abnormal Glucose Metabolism and Bone Mineral Density or Bone Metabolism.

    PubMed

    Qu, Yang; Kang, Ming-Yang; Dong, Rong-Peng; Zhao, Jian-Wu

    2016-01-01

    BACKGROUND The aim of this meta-analysis was to explore the correlations of abnormal glucose metabolism (AGM) with bone mineral density (BMD) and bone metabolism. MATERIAL AND METHODS Relevant studies were identified using computerized and manual search strategies. The included studies were in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted with the Comprehensive Meta-analysis 2.0 (Biostat Inc., Englewood, NJ, USA). RESULTS Our present meta-analysis initially searched 844 studies, and 7 studies were eventually incorporated in the present meta-analysis. These 7 cohort studies included 1123 subjects altogether (560 patients with AGM and 563 healthy controls). The results showed that bone mass index (BMI), insulin, and insulin resistance (IR) of patients with AGM were significantly higher than that of the population with normal glucose metabolism (BMI: SMD=1.658, 95% CI=0.663~2.654, P=0.001; insulin: SMD=0.544, 95% CI=0.030~1.058, P=0.038; IR: SMD=8.767, 95% CI=4.178~13.356, P<0.001). However, the results also indicated there was no obvious difference in osteocalcin (OC) and BMD in patients with AGM and the population with normal glucose metabolism (OC: SMD=0.293, 95% CI=-0.023~0.609, P=0.069; BMD: SMD=0.805, 95% CI=-0. 212~1.821, P=0.121). CONCLUSIONS Our meta-analysis results suggest that AGM might lead to increased BMI, insulin, and IR, while it has no significant correlation with BMD or bone metabolism. PMID:26970713

  19. Correlations Between Abnormal Glucose Metabolism and Bone Mineral Density or Bone Metabolism

    PubMed Central

    Qu, Yang; Kang, Ming-Yang; Dong, Rong-Peng; Zhao, Jian-Wu

    2016-01-01

    Background The aim of this meta-analysis was to explore the correlations of abnormal glucose metabolism (AGM) with bone mineral density (BMD) and bone metabolism. Material/Methods Relevant studies were identified using computerized and manual search strategies. The included studies were in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted with the Comprehensive Meta-analysis 2.0 (Biostat Inc., Englewood, NJ, USA). Results Our present meta-analysis initially searched 844 studies, and 7 studies were eventually incorporated in the present meta-analysis. These 7 cohort studies included 1123 subjects altogether (560 patients with AGM and 563 healthy controls). The results showed that bone mass index (BMI), insulin, and insulin resistance (IR) of patients with AGM were significantly higher than that of the population with normal glucose metabolism (BMI: SMD=1.658, 95% CI=0.663~2.654, P=0.001; insulin: SMD=0.544, 95% CI=0.030~1.058, P=0.038; IR: SMD=8.767, 95% CI=4.178~13.356, P<0.001). However, the results also indicated there was no obvious difference in osteocalcin (OC) and BMD in patients with AGM and the population with normal glucose metabolism (OC: SMD=0.293, 95% CI=−0.023~0.609, P=0.069; BMD: SMD=0.805, 95% CI=−0. 212~1.821, P=0.121). Conclusions Our meta-analysis results suggest that AGM might lead to increased BMI, insulin, and IR, while it has no significant correlation with BMD or bone metabolism. PMID:26970713

  20. The Factors Affecting Bone Density in Cirrhosis

    PubMed Central

    Hajiabbasi, Asghar; Shafaghi, Afshin; Fayazi, Haniyeh Sadat; Shenavar Masooleh, Irandokht; Hedayati Emami, Mohammad Hassan; Ghavidel Parsa, Pooneh; Amir Maafi, Alireza

    2015-01-01

    Background: Bone loss is common in cirrhosis. However, the prevalence of osteopenia and osteoporosis has been heterogeneous in different reports. Reduction in bone formation with or without increase in bone resorption appears to be responsible for bone loss in these patients. Objectives: We aimed to investigate bone loss in patients with cirrhosis at different anatomical sites and key factors that might affect it. Patients and Methods: In this cross-sectional study, 97 patients with cirrhosis who were referred to Razi Hospital, Rasht, Iran, from 2008 to 2010, were studied. Cirrhosis was diagnosed using biopsy and/or clinical and paraclinical findings. Bone mineral densitometry was done in L2 through L4 lumbar spine (LS) and femoral neck (FN), using dual-energy X-ray absorptiometry (DEXA) (QDR 1000, Hologic DEXA Inc, Waltham, Massachusetts, the United States). Statistical analysis was performed using SPSS 18. A P value < 0.05 was considered statistically significant. Results: A total of 97 patients with cirrhosis (55.7% male) and the mean age of 51 ± 13 years and median body mass index (BMI) of 22.7 kg/m2 were recruited over a two-year period. Etiologies of cirrhosis were hepatitis C (40.2%), hepatitis B (26.8%), cryptogenic (21.6%), and other causes (11.4%). Child A, B, and C, were seen in 16.5%, 47.4%, and 36.1% of patients, respectively. The DEXA results were abnormal in 78.4% of our participants (osteopenia, 45.4%; osteoporosis, 33%). BMI and calculated glomerular filtration rate (GFRc) had moderate positive and Child score had moderate negative significant correlation with T score in both anatomical sites. There was no significant association between abnormal DEXA and the causes of cirrhosis. The univariate analysis showed that the risk of abnormal results in DEXA was significantly higher in those with low BMI, current smoking, higher Child score, and low GFRc; however, in multivariate analysis, the abnormal results were more frequent in those with lower

  1. Effect of Moderate Aerobic Training on Bone Metabolism Indices among Adult Humans

    PubMed Central

    Alghadir, Ahmad H.; Aly, Farag A.; Gabr, Sami A.

    2014-01-01

    Objective: This study assessed the osteogenic effect (T-Score) and changes in bone markers in healthy subjects by 12-weeks of aerobic training. Methods: Total 65 healthy subjects (36 males, 29 females), their age ranged between 30 and 60 years with normal body mass index, were recruited to participate in this study and they were selected among healthy subjects who do not have any metabolic disorders and were not receiving any medication that could affect the bone turnover. Standardized physical examination and collection of serum samples were performed at base line and after 12 weeks of moderate aerobic training to measure bone formation markers (osteocalcin (OC) and bone specific alkaline Phosphatase (BAP) and bone resorption marker Deoxypyridinoline (DPD), and serum calcium. Each subject participated in exercise training program for 12 weeks, three times per week. Results: The results showed that the 12 weeks of moderate aerobic training produced a significant improvement in all bone metabolism indices including Serum bone-specific alkaline phosphatase, serum osteocalcin, serum free Calcium and bone mineral density among all subjects. Conclusion : Moderate intensity of aerobic training exerts significant positive effects on bone formation marker and bone density associated with a significant decrease in the rate of bone resorption that could assist in preventing or decelerating osteoporosis. PMID:25097528

  2. Effect of odanacatib on root resorption and alveolar bone metabolism during orthodontic tooth movement.

    PubMed

    Wei, X X; Chu, J P; Zou, Y Z; Ru, N; Cui, S X; Bai, Y X

    2015-01-01

    The aim of this study was to investigate the effect of local administration of odanacatib (ODN) on orthodontic root resorption and the status of alveolar bone metabolism in rat molars. All specimens were scanned using microcomputed tomography and then the raw images were reconstructed. The total volume of the root resorption craters of the 60 g-NS (normal saline) group was higher than in the 60 g-ODN group and the control group. In the 60 g-NS group, the bone volume fraction values of alveolar bone were significantly decreased compared with the other 2 groups. There were no significant differences in the bone volume fraction values of the tibiae among the 3 groups. The results of tartrate-resistant acid phosphatase-positive (TRAP+) numbers showed that there was no difference between the 60 g-NS group and the 60 g-ODN group. The expression of cathepsin K was decreased significantly in the 60 g-ODN group. These results indicate that ODN reduces orthodontics-induced external root resorption and increases alveolar bone metabolism. This may be because ODN inhibits the activity of odontoclasts, but maintains the quantity of odontoclasts and enhances bone formation. ODN promotes local alveolar bone metabolism, but does not affect systemic bone metabolism. PMID:26782444

  3. Adynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix.

    PubMed

    Ng, Adeline H; Omelon, Sidney; Variola, Fabio; Allo, Bedilu; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2016-02-01

    Adynamic bone is the most frequent type of bone lesion in patients with chronic kidney disease; long-term use of antiresorptive therapy may also lead to the adynamic bone condition. The hallmark of adynamic bone is a loss of bone turnover, and a major clinical concern of adynamic bone is diminished bone quality and an increase in fracture risk. Our current study aims to investigate how bone quality changes with age in our previously established mouse model of adynamic bone. Young and old mice (4 months old and 16 months old, respectively) were used in this study. Col2.3Δtk (DTK) mice were treated with ganciclovir and pamidronate to create the adynamic bone condition. Bone quality was evaluated using established techniques including bone histomorphometry, microcomputed tomography, quantitative backscattered electron imaging, and biomechanical testing. Changes in mineral and matrix properties were examined by powder X-ray diffraction and Raman spectroscopy. Aging controls had a natural decline in bone formation and resorption with a corresponding deterioration in trabecular bone structure. Bone turnover was severely blunted at all ages in adynamic animals, which preserved trabecular bone loss normally associated with aging. However, the preservation of trabecular bone mass and structure in old adynamic mice did not rescue deterioration of bone mechanical properties. There was also a decrease in cortical bone toughness in old adynamic mice that was accompanied by a more mature collagen matrix and longer bone crystals. Little is known about the effects of metabolic bone disease on bone fracture resistance. We observed an age-related decrease in bone toughness that was worsened by the adynamic condition, and this decrease may be due to material level changes at the tissue level. Our mouse model may be useful in the investigation of the mechanisms involved in fractures occurring in elderly patients on antiresorptive therapy who have very low bone turnover. PMID:26332924

  4. Effects of a prolonged submersion on bone strength and metabolism in young healthy submariners.

    PubMed

    Luria, Tal; Matsliah, Yinnon; Adir, Yochai; Josephy, Noam; Moran, Daniel S; Evans, Rachel K; Abramovich, Amir; Eliakim, Alon; Nemet, Dan

    2010-01-01

    Submariners taking part in prolonged missions are exposed to environmental factors that may adversely affect bone health. Among these, relatively high levels of CO(2), lack of sunlight exposure affecting vitamin D metabolism, limited physical activity, and altered dietary habits. The aims of this study were to examine the effect of a prolonged submersion (30 days) on changes in bone strength using quantitative bone speed of sound and in markers of bone metabolism that include bone turnover (BAP, PINP, TRAP5b, and CTx) and endocrine regulators (serum calcium, PTH, and 25[OH]D) in a group of 32 young healthy male submariners. The prolonged submersion led to increases in body weight and BMI and to a decrease in fitness level. There was a significant decrease in bone strength following the submersion. Speed of sound exhibited continued decline at 4 weeks after return to shore and returned to baseline levels at the 6-month follow-up. There was a significant increase in circulating calcium level. PTH and 25(OH)D levels decreased significantly. Significant decreases were observed in both TRAP5b and CTx levels, markers of bone resorption, as well as in N-terminal propeptide of type I collagen (PINP), a bone formation marker. Prolonged submersion led to a significant decrease in bone strength, accompanied by an overall decrease in bone metabolism. Bone strength was regained only 6 months after return to shore. Prevention and/or rehabilitation programs should be developed following periods of relative disuse even for young submariners. The effects of repeated prolonged submersions on bone health are yet to be determined. PMID:19882096

  5. Generalized metabolic bone disease in Neurofibromatosis type I

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Skeletal abnormalities are a recognized component of Neurofibromatosis type I (NF1), but a generalized metabolic bone defect in NF1 has not been fully characterized thus far. The purpose of this study was to characterize at the densitometric, biochemical, and pathological level the bone involvement ...

  6. Dietary Pseudopurpurin Improves Bone Geometry Architecture and Metabolism in Red-Bone Guishan Goats

    PubMed Central

    Han, TieSuo; Li, Peng; Wang, JianGuo; Liu, GuoWen; Wang, Zhe; Ge, ChangRong; Gao, ShiZheng

    2012-01-01

    Red-colored bones were found initially in some Guishan goats in the 1980s, and they were designated red-boned goats. However, it is not understood what causes the red color in the bone, or whether the red material changes the bone geometry, architecture, and metabolism of red-boned goats. Pseudopurpurin was identified in the red-colored material of the bone in red-boned goats by high-performance liquid chromatography–electrospray ionization–mass spetrometry and nuclear magnetic resonance analysis. Pseudopurpurin is one of the main constituents of Rubia cordifolia L, which is eaten by the goats. The assessment of the mechanical properties and micro-computed tomography showed that the red-boned goats displayed an increase in the trabecular volume fraction, trabecular thickness, and the number of trabeculae in the distal femur. The mean thickness, inner perimeter, outer perimeter, and area of the femoral diaphysis were also increased. In addition, the trabecular separation and structure model index of the distal femur were decreased, but the bone mineral density of the whole femur and the mechanical properties of the femoral diaphysis were enhanced in the red-boned goats. Meanwhile, expression of alkaline phosphatase and osteocalcin mRNA was higher, and the ratio of the receptor activator of the nuclear factor kappa B ligand to osteoprotegerin was markedly lower in the bone marrow of the red-boned goats compared with common goats. To confirm further the effect of pseudopurpurin on bone geometry, architecture, and metabolism, Wistar rats were fed diets to which pseudopurpurin was added for 5 months. Similar changes were observed in the femurs of the treated rats. The above results demonstrate that pseudopurpurin has a close affinity with the mineral salts of bone, and consequently a high level of mineral salts in the bone cause an improvement in bone strength and an enhancement in the structure and metabolic functions of the bone. PMID:22624037

  7. Effects of food enriched with egg yolk hydrolysate (bone peptide) on bone metabolism in orchidectomized dogs

    PubMed Central

    KOBAYASHI, Toyokazu; KOIE, Hiroshi; WATANABE, Arisa; INO, Arisa; WATABE, Kazuya; KIM, Mujo; KANAYAMA, Kiichi; OTSUJI, Kazuya

    2015-01-01

    We examined the effects of chicken egg hydrolysate (also known as “bone peptide” or BP) on bone metabolism in 5- to 8-month-old orchidectomized dogs. The bone formation marker serum bone alkaline phosphatase (BAP) and the bone resorption marker urine deoxypyridinoline (DPD) were used as indicators to measure changes in bone metabolism. The following results were observed that Serum BAP was higher in dogs fed BP-enriched food throughout the clinical investigation. Serum BAP was statistically significantly higher in dogs fed BP-enriched food than in dogs fed non-BP-enriched food at 2 months after orchidectomy. This suggests that BP promoted bone formation immediately after orchidectomy. PMID:25649521

  8. Metabolic bone disease associated with total parenteral nutrition.

    PubMed

    Klein, G L; Coburn, J W

    1984-01-01

    Patients receiving long-term treatment with total parenteral nutrition often develop bony abnormalities characterized by patchy osteomalacia and low bone turnover. The patients present evidence of physiologic hypoparathyroidism, although low levels of iPTH cannot entirely explain the osteomalacia. Abnormally low serum levels of 1,25(OH)2-vitamin D have been demonstrated, but the significance of these reduced levels in the pathogenesis of the bone lesions is not defined. Aluminum has been detected in large quantities in the plasma, urine, and bone of some patients treated with TPN, and there is mounting evidence that aluminum may be associated with skeletal pathology, particularly osteomalacia. There is, however, no clear documentation that aluminum accumulation produces the skeletal lesions observed, although it could be a contributing factor. There has been the unusual empiric observation that the removal of vitamin D2 from the infusate is associated with a decrease in the quantity of unmineralized osteoid in TPN patients. A possible role of vitamin D2 in producing osteomalacia is not easy to understand since normal serum levels of 25(OH)-D2, the circulating form of vitamin D2, have been reported. The long-term consequences of intravenous nutritional support for many aspects of metabolism remain unknown. Administration into the systemic circulation of predetermined quantities of calcium and phosphorus via a route that bypasses their passage across the intestinal mucosa, the portal system and the liver may have adverse consequences. It is possible that bypassing homeostatic mechanisms may affect bone formation and metabolism or lead to alterations in vitamin D sterols. Alternatively, a deficiency of an essential trace metal or the accumulation of a toxic trace substance could be responsible for the bony abnormalities. Much remains to be clarified concerning calcium homeostasis and bone disease during total parenteral nutrition. Among various possible factors, it

  9. Response of Biochemical Markers of Bone Metabolism to Exercise Intensity in Thoroughbred Horses

    PubMed Central

    INOUE, Yoshinobu; MATSUI, Akira; ASAI, Yo; AOKI, Fumiki; YOSHIMOTO, Kenji; MATSUI, Tohru; YANO, Hideo

    2009-01-01

    We studied the response of biochemical markers of bone metabolism to exercise intensity in horses. Four horses were walked on a mechanical walker for one week (pre-exercise). Then they performed low-speed exercise on a high-speed treadmill in the first week and medium-speed exercise in the second week and high-speed exercise in the third week of training. We measured two indices of bone resorption, serum hydroxyproline concentration and the urinary deoxypyridinoline/creatinine ratio, and serum osteocalcin (OC) concentration as an index of bone formation. Both indices of bone resorption gradually decreased during the experiment. Serum OC concentration did not change in the first week but was significantly lower in the second and the third weeks compared to in the pre-exercise period and in the first week. These results suggest that the low-speed exercise decreased bone resorption but did not affect bone formation, which possibly results in increasing bone mineral content and strengthening of bones. The high-speed exercise decreased bone formation and bone resorption, i.e., bone turnover was suppressed. The low-speed exercise may be preferable for increasing bone mineral content. PMID:24833958

  10. [Bone metabolism and fracture risk in anorexia nervosa].

    PubMed

    Fernández Soto, María Luisa; González Jiménez, Amalia; Varsavsky, Mariela

    2010-07-17

    The prevalence of anorexia nervosa has increased in recent years and a large proportion of patients with this disorder have low bone density at diagnosis and, therefore, an increased risk of early and late fractures. The mechanism of bone loss in anorexia nervosa is not well understood, yet it likely includes hypogonadism, alterations of the GH-IGF-1 axis and hypercortisolism. DEXA is the most effective tool for assessing and monitoring bone density in these patients, and it is important to improve or at least stabilize bone metabolism in those with low bone mass. No agent has yet been proven to be effective in improving bone density. However, sustained weight recovery and menses besides an adequate intake of calcium and vitamin D are recommended to optimize the conditions in which bone mass accrual may occur. PMID:19631350

  11. Metabolic bone disease in gut diseases.

    PubMed

    Lipkin, E W

    1998-06-01

    A wide spectrum of gastrointestinal illnesses impairs bone health and can result in bone pain, demineralization, and fracture. This article summarizes current knowledge of the skeletal pathology exhibited in patients with diseases of the liver, biliary tree, pancreas, and bowel. Mechanisms responsible for these syndromes and treatment options are discussed. This article enhances the practicing gastroenterologist's knowledge of the implications of gastrointestinal illness for bone. PMID:9650030

  12. [Biochemical markers of bone metabolism and their importance].

    PubMed

    Obermayer-Pietsch, B; Schwetz, V

    2016-06-01

    Laboratory analyses of biochemical markers for bone and mineral metabolism can play a key role in the assessment of patients with osteoporosis. They may help to assess bone turnover in the diagnostic work-up and aid decision-making as well as selection of pharmaceutical therapy options. Recent publications on therapy response have shown that biochemical markers of bone turnover are valuable tools for the evaluation of therapy success in individual osteoporosis patients and the assessment of bone mineral density gain during therapy. PMID:27146404

  13. Effect of Microgravity on Bone Tissue and Calcium Metabolism

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Session TA4 includes short reports concerning: (1) Human Bone Tissue Changes after Long-Term Space Flight: Phenomenology and Possible Mechanics; (2) Prediction of Femoral Neck Bone Mineral Density Change in Space; (3) Dietary Calcium in Space; (4) Calcium Metabolism During Extended-Duration Space Flight; (5) External Impact Loads on the Lower Extremity During Jumping in Simulated Microgravity and the Relationship to Internal Bone Strain; and (6) Bone Loss During Long Term Space Flight is Prevented by the Application of a Short Term Impulsive Mechanical Stimulus.

  14. Relationships among maxillofacial morphologies, bone properties, and bone metabolic markers in patients with jaw deformities.

    PubMed

    Saito, D; Mikami, T; Oda, Y; Hasebe, D; Nishiyama, H; Saito, I; Kobayashi, T

    2016-08-01

    The aim of this study was to determine the relationships among bone properties, bone metabolic markers, and types of jaw deformity. The subjects were 55 female patients with jaw deformities. Skeletal morphology was examined using lateral cephalograms, and the patients were divided into three groups according to the type of anteroposterior skeletal pattern. Serum osteocalcin, bone alkaline phosphatase, and tartrate-resistant acid phosphatase isoform 5b, as well as deoxypyridinoline in urine, were measured as bone metabolic markers. Quantitative ultrasound (QUS) measurements were used to assess bone properties at the calcaneal bone. The bone volume and bone density of the condylar process were measured in 43 patients by computed tomography. There were no significant differences in bone metabolic markers and QUS parameters between the groups, although bone formation and resorption markers tended to be higher in patients with a protrusive mandible. On the other hand, patients with mandibular retrusion had a higher tendency to have small and dense condylar processes. In conclusion, the results suggest that growth depression or a degenerative change in the mandibular condyle is involved in the pathogenesis of mandibular retrusion, although risk factors for progressive condylar resorption were not determined. PMID:26972158

  15. Effects of obesity on bone metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite being a risk factor for many chronic health disorders, obesity is thought to promote bone formation and protect against osteoporosis in humans. Although body mass has a positive effect on bone health, whether mass derived from an obesity condition or excessive fat accumulation is beneficial ...

  16. Osteopenia (metabolic bone disease) of prematurity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteopenia is defined as postnatal bone mineralization that is inadequate to fully mineralize bones. Osteopenia occurs commonly in very low birth weight (VLBW) infants. Prior to the use of high-mineral containing diets for premature infants, which is the current practice, significant radiographic ch...

  17. Melatonin: Bone Metabolism in Oral Cavity

    PubMed Central

    López-Martínez, Fanny; Olivares Ponce, Patricia N.; Guerra Rodríguez, Miriam; Martínez Pedraza, Ricardo

    2012-01-01

    Throughout life, bone tissue undergoes a continuous process of resorption and formation. Melatonin, with its antioxidant properties and its ability to detoxify free radicals, as suggested by Conconi et al. (2000) may interfere in the osteoclast function and thereby inhibit bone resorption, as suggested by Schroeder et al. (1981). Inhibition of bone resorption may be enhanced by a reaction of indoleamine in osteoclastogenesis. That it has been observed melatonin, at pharmacological doses, decrease bone mass resorption by suppressing through down regulation of the RANK-L, as suggested by Penarrocha Diago et al. (2005) and Steflik et al. (1994). These data point an osteogenic effect towards that may be of melatonin of clinical importance, as it could be used as a therapeutic agent in situations in which would be advantageous bone formation, such as in the treatment of fractures or osteoporosis or their use as, a bioactive surface on implant as suggested by Lissoni et al. (1991). PMID:22927853

  18. Endocrine Regulation of Bone and Energy Metabolism in Hibernating Mammals

    PubMed Central

    Doherty, Alison H.; Florant, Gregory L.; Donahue, Seth W.

    2014-01-01

    Precise coordination among organs is required to maintain homeostasis throughout hibernation. This is particularly true in balancing bone remodeling processes (bone formation and resorption) in hibernators experiencing nutritional deprivation and extreme physical inactivity, two factors normally leading to pronounced bone loss in non-hibernating mammals. In recent years, important relationships between bone, fat, reproductive, and brain tissues have come to light. These systems share interconnected regulatory mechanisms of energy metabolism that potentially protect the skeleton during hibernation. This review focuses on the endocrine and neuroendocrine regulation of bone/fat/energy metabolism in hibernators. Hibernators appear to have unique mechanisms that protect musculoskeletal tissues while catabolizing their abundant stores of fat. Furthermore, the bone remodeling processes that normally cause disuse-induced bone loss in non-hibernators are compared to bone remodeling processes in hibernators, and possible adaptations of the bone signaling pathways that protect the skeleton during hibernation are discussed. Understanding the biological mechanisms that allow hibernators to survive the prolonged disuse and fasting associated with extreme environmental challenges will provide critical information regarding the limit of convergence in mammalian systems and of skeletal plasticity, and may contribute valuable insight into the etiology and treatment of human diseases. PMID:24556365

  19. Characterizing the Network of Drugs and Their Affected Metabolic Subpathways

    PubMed Central

    Li, Jing; Han, Junwei; Wang, Shuyuan; Yao, Qianlan; Wang, Yingying; Zhang, Yunpeng; Zhang, Chunlong; Xu, Yanjun; Jiang, Wei; Li, Xia

    2012-01-01

    A fundamental issue in biology and medicine is illustration of the overall drug impact which is always the consequence of changes in local regions of metabolic pathways (subpathways). To gain insights into the global relationship between drugs and their affected metabolic subpathways, we constructed a drug–metabolic subpathway network (DRSN). This network included 3925 significant drug–metabolic subpathway associations representing drug dual effects. Through analyses based on network biology, we found that if drugs were linked to the same subpathways in the DRSN, they tended to share the same indications and side effects. Furthermore, if drugs shared more subpathways, they tended to share more side effects. We then calculated the association score by integrating drug-affected subpathways and disease-related subpathways to quantify the extent of the associations between each drug class and disease class. The results showed some close drug–disease associations such as sex hormone drugs and cancer suggesting drug dual effects. Surprisingly, most drugs displayed close associations with their side effects rather than their indications. To further investigate the mechanism of drug dual effects, we classified all the subpathways in the DRSN into therapeutic and non-therapeutic subpathways representing drug therapeutic effects and side effects. Compared to drug side effects, the therapeutic effects tended to work through tissue-specific genes and these genes tend to be expressed in the adrenal gland, liver and kidney; while drug side effects always occurred in the liver, bone marrow and trachea. Taken together, the DRSN could provide great insights into understanding the global relationship between drugs and metabolic subpathways. PMID:23112813

  20. Bone Health and Associated Metabolic Complications in Neuromuscular Diseases

    PubMed Central

    Joyce, Nanette C.; Hache, Lauren P.; Clemens, Paula R.

    2014-01-01

    Synopsis This article reviews the recent literature regarding bone health as it relates to the patient living with neuromuscular disease (NMD). Poor bone health with related morbidity is a significant problem for patients with NMD. Although the evidence addressing issues of bone health and osteoporosis have increased as a result of the Bone and Joint Decade, studies defining the scope of bone-related disease in NMD are scant. The available evidence is discussed focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy. These problems appear common. Osteomalacia often complicates disease-related baseline osteoporosis and may reduce fracture risk if treated. Future directions are discussed, including the urgent need for studies to both determine the nature and extent of poor bone health, and to evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD. PMID:23137737

  1. Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

    PubMed

    Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

    2016-04-01

    We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. PMID:27001278

  2. Bone metabolism induced by denture insertion in positron emission tomography.

    PubMed

    Suenaga, H; Chen, J; Yamaguchi, K; Sugazaki, M; Li, W; Swain, M; Li, Q; Sasaki, K

    2016-03-01

    18F-fluoride positron emission tomogra-phy (PET) can identify subtle functional variation prior to the major structural change detectable by X-ray. This study aims to investigate the mechanobiological bone reaction around the abutment tooth and in the residual ridge, induced by insertion of removable partial denture (RPD) within two different groups of patients: patients without denture experience (Group 1) and patients with denture experience before (Group 2), using 18F-fluoride PET imaging technique. 18F-fluoride PET/computerised tomography (CT) scan was performed to examine the bone metabolic change in mandible before and after the RPD treatment. Region of interests (ROIs) were placed in alveolar bone around abutment tooth and in residual bone beneath the RPD. Standardised uptake value (SUV), reflecting the accumulation of 18F-fluoride, was measured for each ROI. In all subjects of Group 1, SUVs after insertion were higher than before in both alveolar bone and residual bone, while there was less significant change in SUV in subjects of Group 2. This study demonstrated using longitudinal 18F-fluoride PET scans to effectively examine the bone metabolic change in mandible induced by occlusal loading after RPD insertion. Using this technique, within the six subjects in this study, it was shown that bone metabolism around abutment tooth and residual ridge increased after RPD insertion in case of first-time denture user, while there was no big change in the patient with experience of denture before. This study revealed the effectiveness of applying PET to evaluate bone metabolic activity as mechanobiolo-gical reaction. PMID:26431672

  3. Kinetic aspects of bone mineral metabolism

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1973-01-01

    Two techniques were studied for measuring changes in bone mass in rats. One technique measures the Ar-37 produced from calcium during neutron irradiation and the other measures the changes in the Na-22 content which has been incorporated within the rat bone. Both methods are performed in VIVO and cause no significant physiological damage. The Ar-37 leaves the body of a rat within an hour after being produced, and it can be quantitatively collected and measured with a precision of - or + 2% on the same rat. With appropriate irradiation conditions it appears that the absolute quantity of calcuim in any rat can be determined within - or + 3% regardless of animal size. The Na-22 when uniformly distributed in bone, can be used to monitor bone mineral turnover and this has been demonstrated in conditions of calcium deficiency during growth and also pregnancy coupled with calcium deficiency.

  4. Modifications of histamine receptor signaling affect bone mechanical properties in rats.

    PubMed

    Folwarczna, Joanna; Janas, Aleksandra; Pytlik, Maria; Śliwiński, Leszek; Wiercigroch, Marek; Brzęczek, Anna

    2014-02-01

    Histamine receptors are expressed on bone cells and histamine may be involved in regulation of bone metabolism. The aim of the present study was to investigate the effects of loratadine (an H(1) receptor antagonist), ranitidine (an H(2) receptor antagonist) and betahistine (an H(3) receptor antagonist and H(1) receptor agonist) on bone mechanical properties in rats. Loratadine (5 mg/kg/day, po), ranitidine (50 mg/kg/day, po), or betahistine dihydrochloride (5 mg/kg/day, po), were administered for 4 weeks to non-ovariectomized and bilaterally ovariectomized (estrogen-deficient) 3-month-old rats, and their effects were compared with appropriate controls. Serum levels of bone turnover markers, bone mineralization and mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck were studied. In rats with normal estrogen level, administration of loratadine slightly favorably affected mechanical properties of compact bone, significantly increasing the strength of the femoral neck (p < 0.05), and tending to increase the strength of the femoral diaphysis. Ranitidine did not significantly affect the investigated parameters, and betahistine decreased the strength of the tibial metaphysis (cancellous bone, p < 0.01). There were no significant effects of the drugs on serum bone turnover markers. In estrogen-deficient rats, the drugs did not significantly affect the investigated skeletal parameters. In conclusion, the effects of histamine H(1), H(2) and H(3) receptor antagonists on the skeletal system in rats were differential and dependent on estrogen status. PMID:24905313

  5. Bone metabolism in anorexia nervosa: molecular pathways and current treatment modalities.

    PubMed

    Howgate, D J; Graham, S M; Leonidou, A; Korres, N; Tsiridis, E; Tsapakis, E

    2013-02-01

    Eating disorders are associated with a multitude of metabolic abnormalities which are known to adversely affect bone metabolism and structure. We aimed to comprehensively review the literature on the effects of eating disorders, particularly anorexia nervosa (AN), on bone metabolism, bone mineral density (BMD), and fracture incidence. Furthermore, we aimed to highlight the risk factors and potential management strategies for patients with eating disorders and low BMD. We searched the MEDLINE/OVID (1950-July 2011) and EMBASE (1980-July 2011) databases, focussing on in vitro and in vivo studies of the effects of eating disorders on bone metabolism, bone mineral density, and fracture incidence. Low levels of estrogen, testosterone, dehydroepiandrosterone, insulin-like growth factor-1 (IGF-1), and leptin, and high levels of cortisol, ghrelin, and peptide YY (PYY) are thought to contribute to the 'uncoupling' of bone turnover in patients with active AN, leading to increased bone resorption in comparison to bone formation. Over time, this results in a high prevalence and profound degree of site-specific BMD loss in women with AN, thereby increasing fracture risk. Weight recovery and increasing BMI positively correlate with levels of IGF-1 and leptin, normalisation in the levels of cortisol, as well as markers of bone formation and resorption in both adolescent and adult patients with AN. The only treatments which have shown promise in reversing the BMD loss associated with AN include: physiologic dose transdermal and oral estrogen, recombinant human IGF-1 alone or in combination with the oral contraceptive pill, and bisphosphonate therapy. PMID:22875459

  6. Beyond Glycemic Control in Diabetes Mellitus: Effects of Incretin-Based Therapies on Bone Metabolism

    PubMed Central

    Ceccarelli, Elena; Guarino, Elisa G.; Merlotti, Daniela; Patti, Aurora; Gennari, Luigi; Nuti, Ranuccio; Dotta, Francesco

    2013-01-01

    Diabetes mellitus (DM) and osteoporosis (OP) are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM) and in type 2 (T2DM) diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g., thiazolidinediones, insulin) may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e., GLP-1 receptor agonists and DPP-4 inhibitors) is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells. Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients. PMID:23785355

  7. Gamma images in benign and metabolic bone diseases: volume 1

    SciTech Connect

    Sy, W.M.

    1981-01-01

    Volume 1 of ''Gamma images in benign and metabolic bone diseases'' comprises chapters devoted to: general remarks and considerations, radiopharmaceuticals, Paget disease, osteomyelitis, trauma, benign bone tumors, chronic renal dialysis, acute renal failure, osteomalacia and rickets, and osteoporosis. Although published in 1981, the most recent references in the book were 1978 and most are 1977 or earlier. One of the strongest aspects of the volume are tables which categorize diseases, pathophysiology of disease, and image abnormalities. (JMT)

  8. Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats.

    PubMed

    Gasser, Jürg A; Hulter, Henry N; Imboden, Peter; Krapf, Reto

    2014-03-01

    Chronic metabolic acidosis (CMA) might result in a decrease in vivo in bone mass based on its reported in vitro inhibition of bone mineralization, bone formation, or stimulation of bone resorption, but such data, in the absence of other disorders, have not been reported. CMA also results in negative nitrogen balance, which might decrease skeletal muscle mass. This study analyzed the net in vivo effects of CMA's cellular and physicochemical processes on bone turnover, trabecular and cortical bone density, and bone microarchitecture using both peripheral quantitative computed tomography and μCT. CMA induced by NH4Cl administration (15 mEq/kg body wt/day) in intact and ovariectomized (OVX) rats resulted in stable CMA (mean Δ[HCO3(-)]p = 10 mmol/l). CMA decreased plasma osteocalcin and increased TRAP5b in intact and OVX animals. CMA decreased total volumetric bone mineral density (vBMD) after 6 and 10 wk (week 10: intact normal +2.1 ± 0.9% vs. intact acidosis -3.6 ± 1.2%, P < 0.001), an effect attributable to a decrease in cortical thickness and, thus, cortical bone mass (no significant effect on cancellous vBMD, week 10) attributed to an increase in endosteal bone resorption (nominally increased endosteal circumference). Trabecular bone volume (BV/TV) decreased significantly in both CMA groups at 6 and 10 wk, associated with a decrease in trabecular number. CMA significantly decreased muscle cross-sectional area in the proximal hindlimb at 6 and 10 wk. In conclusion, chronic metabolic acidosis induces a large decrease in cortical bone mass (a prime determinant of bone fragility) in intact and OVX rats and impairs bone microarchitecture characterized by a decrease in trabecular number. PMID:24352505

  9. Human lead metabolism: Chronic exposure, bone lead and physiological models

    NASA Astrophysics Data System (ADS)

    Fleming, David Eric Berkeley

    Exposure to lead is associated with a variety of detrimental health effects. After ingestion or inhalation, lead may be taken up from the bloodstream and retained by bone tissue. X-ray fluorescence was used to make in vivo measurements of bone lead concentration at the tibia and calcaneus for 367 active and 14 retired lead smelter workers. Blood lead levels following a labour disruption were used in conjunction with bone lead readings to examine the endogenous release of lead from bone. Relations between bone lead and a cumulative blood lead index differed depending on time of hiring. This suggests that the transfer of lead from blood to bone has changed over time, possibly as a result of varying exposure conditions. A common polymorphism in the δ-aminolevulinate dehydratase (ALAD) enzyme may influence the distribution of lead in humans. Blood lead levels were higher for smelter workers expressing the more rare ALAD2 allele. Bone lead concentrations, however, were not significantly different. This implies that a smaller proportion of lead in blood is distributed to tissue for individuals expressing the ALAD2 allele. The O'Flaherty physiological model of lead metabolism was modified slightly and tested with input from the personal exposure histories of smelter workers. The model results were consistent with observation in tern of endogenous exposure to lead and accumulation of lead in cortical bone. Modelling the calcaneus as a trabecular bone site did not reproduce observed trends. variations in lead metabolism between different trabecular sites may therefore be significant. The model does not incorporate a genetic component, and its output did not reflect observed differences in this respect. This result provides further support for the influence of the ALAD polymorphism on lead metabolism. Experimental trials with a digital spectrometer revealed superior energy resolution and count throughput relative to the conventional X-ray fluorescence system. The associated

  10. Proteomics approaches for the studies of bone metabolism

    PubMed Central

    Lee, Ji-Hyun; Cho, Je-Yoel

    2014-01-01

    Bone is an active tissue, in which bone formation by osteoblast is followed by bone resorption by osteoclasts, in a repeating cycle. Proteomics approaches may allow the detection of changes in cell signal transduction, and the regulatory mechanism of cell differentiation. LC-MS/MS-based quantitative methods can be used with labeling strategies, such as SILAC, iTRAQ, TMT and enzymatic labeling. When used in combination with specific protein enrichment strategies, quantitative proteomics methods can identify various signaling molecules and modulators, and their interacting proteins in bone metabolism, to elucidate biological functions for the newly identified proteins in the cellular context. In this article, we will briefly review recent major advances in the application of proteomics for bone biology, especially from the aspect of cellular signaling. [BMB Reports 2014; 47(3): 141-148] PMID:24499667

  11. Metabolic Bone Disease in Viral Cirrhosis: A Prospective Study

    PubMed Central

    Goubraim, Rabia; Kabbaj, Nawal; Salihoun, Mouna; Chaoui, Zakia; Nya, M'Hamed; Amrani, Naima

    2013-01-01

    Background/Aim. Metabolic Bone disorders are well-recognized extrahepatic complications of cirrhosis. The aim was to report their prevalence and the associated factors to their development in patients with viral cirrhosis. Patients and Methods. All consecutive patients with viral cirrhosis were prospectively enrolled. Parathyroid hormone, 25-hydroxyvitamin D, liver function, and phosphocalcic tests were measured in all patients. Bone mineral density was measured at the lumbar spine and total hip by dual-energy X-ray absorptiometry. Data were analyzed using SPSS software. Results. Forty-six cirrhotic patients were included with hepatitis C (87%) and hepatitis B (13%). The Child-Pugh score was grade A in 87% of cases and grade B in 13%. Thirty-seven patients had decreased bone mineral density with osteopenia in 24 patients and osteoporosis in 13 patients. Decreased 25-hydroxyvitamin D was found in 95.6% of cases. Bone disorders were significantly more frequent in old patients with low body mass index, long duration of liver disease, and low 25-hydroxyvitamin D level. None of these factors was an independent factor associated with bone disorders. Conclusion. Our study revealed a high prevalence of metabolic bone disorders among viral cirrhotic patients. Consequently, bone mineral density assessment should be performed systematically in all cirrhotic patients.

  12. The effects of acute hyperinsulinemia on bone metabolism

    PubMed Central

    Ivaska, Kaisa K; Heliövaara, Maikki K; Ebeling, Pertti; Bucci, Marco; Huovinen, Ville; Väänänen, H Kalervo; Nuutila, Pirjo; Koistinen, Heikki A

    2015-01-01

    Insulin signaling in bone-forming osteoblasts stimulates bone formation and promotes the release of osteocalcin (OC) in mice. Only a few studies have assessed the direct effect of insulin on bone metabolism in humans. Here, we studied markers of bone metabolism in response to acute hyperinsulinemia in men and women. Thirty-three subjects from three separate cohorts (n=8, n=12 and n=13) participated in a euglycaemic hyperinsulinemic clamp study. Blood samples were collected before and at the end of infusions to determine the markers of bone formation (PINP, total OC, uncarboxylated form of OC (ucOC)) and resorption (CTX, TRAcP5b). During 4 h insulin infusion (40 mU/m2 per min, low insulin), CTX level decreased by 11% (P<0.05). High insulin infusion rate (72 mU/m2 per min) for 4 h resulted in more pronounced decrease (−32%, P<0.01) whereas shorter insulin exposure (40 mU/m2 per min for 2 h) had no effect (P=0.61). Markers of osteoblast activity remained unchanged during 4 h insulin, but the ratio of uncarboxylated-to-total OC decreased in response to insulin (P<0.05 and P<0.01 for low and high insulin for 4 h respectively). During 2 h low insulin infusion, both total OC and ucOC decreased significantly (P<0.01 for both). In conclusion, insulin decreases bone resorption and circulating levels of total OC and ucOC. Insulin has direct effects on bone metabolism in humans and changes in the circulating levels of bone markers can be seen within a few hours after administration of insulin. PMID:26047829

  13. Moderate-intensity rotating magnetic fields do not affect bone quality and bone remodeling in hindlimb suspended rats.

    PubMed

    Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Zhai, Mingming; Tong, Shichao; Xu, Qiaoling; Xie, Kangning; Wu, Xiaoming; Tang, Chi; Xu, Xinmin; Liu, Juan; Guo, Wei; Jiang, Maogang; Luo, Erping

    2014-01-01

    Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF) and static magnetic fields (SMF) on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF), another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU) rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10), HU (n = 10) and HU with RMF exposure (HU+RMF, n = 12) groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T) at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates potentially

  14. Moderate-Intensity Rotating Magnetic Fields Do Not Affect Bone Quality and Bone Remodeling in Hindlimb Suspended Rats

    PubMed Central

    Shen, Guanghao; Zhai, Mingming; Tong, Shichao; Xu, Qiaoling; Xie, Kangning; Wu, Xiaoming; Tang, Chi; Xu, Xinmin; Liu, Juan; Guo, Wei; Jiang, Maogang; Luo, Erping

    2014-01-01

    Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF) and static magnetic fields (SMF) on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF), another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU) rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10), HU (n = 10) and HU with RMF exposure (HU+RMF, n = 12) groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T) at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates potentially

  15. [Clinical evaluation for abnormalities of bone and mineral metabolism in ESKD].

    PubMed

    Yano, Shozo

    2016-09-01

    In patients with end-stage kidney disease(ESKD), bone disorders are characterized by cortical porosity and by abnormal turnover of bone metabolism:adynamic(low turnover)bone disease and high turnover bone due to various degrees of secondary hyperparathyroidism. Abnormalities of bone metabolism are generally assessed by interview, X-ray, bone mineral density(BMD), serum phosphorus, calcium, and parathyroid hormone levels, and bone metabolic markers. Recent clinical studies have demonstrated that high turnover bone representing elevated bone metabolic markers and low BMD are independent risks of bone fractures as well as mortality among this population. Treatment of bone disorders in ESKD patients should be aiming at the normalization of mineral metabolism and the maintenance and/or improvement of BMD. PMID:27561341

  16. Serum markers of bone metabolism show bone loss in hibernating bears

    USGS Publications Warehouse

    Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

    2003-01-01

    Disuse osteopenia was studied in hibernating black bears (Ursus americanus) using serum markers of bone metabolism. Blood samples were collected from male and female, wild black bears during winter denning and active summer periods. Radioimmunoassays were done to determine serum concentrations of cortisol, the carboxy-terminal cross-linked telopeptide, and the carboxy-terminal propeptide of Type I procollagen, which are markers of hone resorption and formation, respectively. The bone resorption marker was significantly higher during winter hibernation than it was in the active summer months, but the bone formation marker was unchanged, suggesting an imbalance in bone remodeling and a net bone loss during disuse. Serum cortisol was significantly correlated with the bone resorption marker, but not with the bone formation marker. The bone formation marker was four- to fivefold higher in an adolescent and a 17-year-old bear early in the remobilization period compared with the later summer months. These findings raise the possibility that hibernating black bears may minimize bone loss during disuse by maintaining osteoblastic function and have a more efficient compensatory mechanism for recovering immobilization-induced bone loss than that of humans or other animals.

  17. Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia

    PubMed Central

    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2016-01-01

    Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients. PMID:27187355

  18. Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia.

    PubMed

    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2016-01-01

    Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients. PMID:27187355

  19. [Morphological analysis of bone dynamics and metabolic bone disease. Histomorphometric concepts of bone remodeling and modeling].

    PubMed

    Takahashi, Hideaki E

    2011-04-01

    In tissue level turnover of bone cells, bone remodeling shows a sequential events of activation, resorption, reversal and formation. This may be observed as secondary osteons in the cortical bone and trabecular packets in the cancellous bone. Microcracks are repaired by targeted remodeling, and calcium is released by non-targeted remodeling. In macromodeling, a macroscopic size of a bone increases with growth, without changing its basic figure. In micromodelimg, a shift of trabecula, a minishift, is biomechnically controlled. New lamellar bone is added parallel to compressive and tensile force, and bone resorption occurs at the opposite surface of formation. In minimodeling new lamellar bone is formed with a sequence of activation, then directly formation, without scalloping at the cement line between newly formed bone and its basic bone. PMID:21447918

  20. Perspective on the impact of weightlessness on calcium and bone metabolism.

    PubMed

    Holick, M F

    1998-05-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health. PMID:9600764

  1. Perspective on the impact of weightlessness on calcium and bone metabolism

    NASA Technical Reports Server (NTRS)

    Holick, M. F.

    1998-01-01

    As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

  2. Influence of indomethacin on experimental bone metabolism in rats

    SciTech Connect

    Toernkvist, H.; Bauer, F.C.; Nilsson, O.S.

    1985-03-01

    The effect of indomethacin on heterotopic and orthotopic bone formation in rats was analyzed with respect to dose and time of initiation of drug administration. Three weeks after implantation of demineralized bone matrix, the ash weight of implants from animals receiving the highest doses of indomethacin was approximately 25% lower than that of controls. The ash weight of implants was only affected in rats receiving indomethacin from the week before implantation or from the time of implantation. In a separate study, no effect on the rate of resorption measured by elimination of /sup 3/H-proline and /sup 45/Ca or on the amount of ash could be detected. Orthotopic bone remained unaffected by indomethacin treatment. The study showed that in order to inhibit experimental new bone formation, indomethacin must be present before or at the time of implantation of demineralized bone matrix.

  3. Alteration of proteoglycan sulfation affects bone growth and remodeling

    PubMed Central

    Gualeni, Benedetta; de Vernejoul, Marie-Christine; Marty-Morieux, Caroline; De Leonardis, Fabio; Franchi, Marco; Monti, Luca; Forlino, Antonella; Houillier, Pascal; Rossi, Antonio; Geoffroy, Valerie

    2013-01-01

    Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model. We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice. Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates. Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice. These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities. Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis. PMID:23369989

  4. TRPV4 deficiency causes sexual dimorphism in bone metabolism and osteoporotic fracture risk.

    PubMed

    van der Eerden, B C J; Oei, L; Roschger, P; Fratzl-Zelman, N; Hoenderop, J G J; van Schoor, N M; Pettersson-Kymmer, U; Schreuders-Koedam, M; Uitterlinden, A G; Hofman, A; Suzuki, M; Klaushofer, K; Ohlsson, C; Lips, P J A; Rivadeneira, F; Bindels, R J M; van Leeuwen, J P T M

    2013-12-01

    We explored the role of transient receptor potential vanilloid 4 (TRPV4) in murine bone metabolism and association of TRPV4 gene variants with fractures in humans. Urinary and histomorphometrical analyses demonstrated reduced osteoclast activity and numbers in male Trpv4(-/-) mice, which was confirmed in bone marrow-derived osteoclast cultures. Osteoblasts and bone formation as shown by serum procollagen type 1 amino-terminal propeptide and histomorphometry, including osteoid surface, osteoblast and osteocyte numbers were not affected in vivo. Nevertheless, osteoblast differentiation was enhanced in Trpv4(-/-) bone marrow cultures. Cortical and trabecular bone mass was 20% increased in male Trpv4(-/-) mice, compared to sex-matched wild type (Trpv4(+/+)) mice. However, at the same time intracortical porosity was increased and bone matrix mineralization was reduced. Together, these lead to a maximum load, stiffness and work to failure of the femoral bone, which were not different compared to Trpv4(+/+) mice, while the bone material was less resistant to stress and less elastic. The differential impacts on these determinants of bone strength were likely responsible for the lack of any changes in whole bone strength in the Trpv4(-/-) mice. None of these skeletal parameters were affected in female Trpv4(-/-) mice. The T-allele of rs1861809 SNP in the TRPV4 locus was associated with a 30% increased risk (95% CI: 1.1-1.6; p=0.013) for non-vertebral fracture risk in men, but not in women, in the Rotterdam Study. Meta-analyses with the population-based LASA study confirmed the association with non-vertebral fractures in men. This was lost when the non-population-based studies Mr. OS and UFO were included. In conclusion, TRPV4 is a male-specific regulator of bone metabolism, a determinant of bone strength, and a potential risk predictor for fractures through regulation of bone matrix mineralization and intra-cortical porosity. This identifies TRPV4 as a unique sexually

  5. Mineral metabolism in isolated mouse long bones: Opposite effects of microgravity on mineralization and resorption

    NASA Technical Reports Server (NTRS)

    Veldhuijzen, Jean Paul; Vanloon, Jack J. W. A.

    1994-01-01

    An experiment using isolated skeletal tissues under microgravity, is reported. Fetal mouse long bones (metatarsals) were cultured for 4 days in the Biorack facility of Spacelab during the IML-1 (International Microgravity Laboratory) mission of the Space Shuttle. Overall growth was not affected, however glucose consumption was significantly reduced under microgravity. Mineralization of the diaphysis was also strongly reduced under microgravity as compared to the on-board 1 g group. In contrast, mineral resorption by osteoclasts was signficantly increased. These results indicate that these fetal mouse long bones are a sensitive and useful model to further study the cellular mechanisms involved in the changed mineral metabolism of skeletal tissues under microgravity.

  6. Leptin: a possible metabolic signal affecting reproduction.

    PubMed

    Spicer, L J

    2001-11-01

    Since its discovery in 1994, leptin, a protein hormone synthesized and secreted by adipose tissue, has been shown to regulate feed intake in several species including sheep and pigs. Although a nimiety of information exists regarding the physiological role of leptin in rodents and humans, the regulation and action of leptin in domestic animals is less certain. Emerging evidence in several species indicates that leptin may also affect the hypothalamo-pituitary-gonadal axis. Leptin receptor mRNA is present in the anterior pituitary and hypothalamus of several species, including sheep. In rats, effects of leptin on GnRH, LH and FSH secretion have been inconsistent, with leptin exhibiting both stimulatory and inhibitory action in vivo and in vitro. Evidence to support direct action of leptin at the level of the gonad indicates that the leptin receptor and its mRNA are present in ovarian tissue of several species, including cattle. These leptin receptors are functional, since leptin inhibits insulin-induced steroidogenesis of both granulosa and thecal cells of cattle in vitro. Leptin receptor mRNA is also found in the testes of rodents. As with the ovary, these receptors are functional, at least in rats, since leptin inhibits hCG-induced testosterone secretion by Leydig cells in vitro. During pregnancy, placental production of leptin may be a major contributor to the increase in maternal leptin in primates but not rodents. However, in both primates and rodents, leptin receptors exist in placental tissues and may regulate metabolism of the fetal-placental unit. As specific leptin immunoassays are developed for domestic animals, in vivo associations may then be made among leptin, body energy stores, dietary energy intake and reproductive function. This may lead to a more definitive role of leptin in domestic animal reproduction. PMID:11872320

  7. [SSRI AND BONE METABOLISM IN HIV + PATIENTS WITH ANTIRETROVIRAL THERAPY].

    PubMed

    Mazzoglio y Nabar, Martín J; Muñiz, Milagros María; Mejías Delamano, Alexis A; Muñoz, Santiago; Magrath Guimet, Nahuel

    2015-01-01

    We report a series of 9 male HIV + patients, average age of 41.2 years, viral load negative (<50 copies RNA/ml), treated with antiretroviral (nucleoside and non-nucleoside inhibitors of reverse transcriptase) without systemic infections, the CNS diseases or marker or corticoidoterapia in progress. Were evaluated and supported by their infectologists interconsultation during the period October 2008-October 2013 by depressive syndrome. Psychotherapeutic and psychiatric treatment was initiated with SSRIs and clonazepam; Neuroimaging control and biochemical laboratory studies at baseline and 2 months of treatment were conducted. In the course of psychopharmacological treatment not suffer fractures due to falls and alterations were detected in bone metabolism markers and images. He studied with endocrinology and interdisciplinary medical clinic, decided to withdraw the SSRIs with normalization of biochemical values and psychotherapeutic treatment was continued. We will raise the associations between the use of SSRIs, disturbances of bone metabolism with clinical correlation and possible drug interactions between antidepressants and antiretroviral. PMID:26650557

  8. Metabolic and clinical consequences of hyperthyroidism on bone density.

    PubMed

    Gorka, Jagoda; Taylor-Gjevre, Regina M; Arnason, Terra

    2013-01-01

    In 1891, Von Recklinghausen first established the association between the development of osteoporosis in the presence of overt hyperthyroidism. Subsequent reports have demonstrated that BMD loss is common in frank hyperthyroidism, and, to a lesser extent, in subclinical presentations. With the introduction of antithyroid medication in the 1940s to control biochemical hyperthyroidism, the accompanying bone disease became less clinically apparent as hyperthyroidism was more successfully treated medically. Consequently, the impact of the above normal thyroid hormones in the pathogenesis of osteoporosis may be presently underrecognized due to the widespread effective treatments. This review aims to present the current knowledge of the consequences of hyperthyroidism on bone metabolism. The vast number of recent papers touching on this topic highlights the recognized impact of this common medical condition on bone health. Our focus in this review was to search for answers to the following questions. What is the mechanisms of action of thyroid hormones on bone metabolism? What are the clinical consequences of hyperthyroidism on BMD and fracture risk? What differences are there between men and women with thyroid disease and how does menopause change the clinical outcomes? Lastly, we report how different treatments for hyperthyroidism benefit thyroid hormone-induced osteoporosis. PMID:23970897

  9. Metabolic bone disease in home total parenteral nutrition.

    PubMed

    McCullough, M L; Hsu, N

    1987-07-01

    Home total parenteral nutrition (HTPN) is in its infancy but has proved to be lifesaving for patients unable to manage on enteral nutrition alone. However, this mode of nutrition therapy is not without problems. Aside from mechanical and other metabolic complications, a peculiar metabolic bone disease has been reported to occur in some HTPN recipients. The disease, characterized by abnormalities in calcium and phosphorus homeostasis, often results in osteomalacia, bone pain, and fractures. Reports of approximately 50 cases of metabolic bone disease have been published by centers in the United States and Canada. Factors that have been implicated as possible causes include infusion of excess vitamin D, aluminum, calcium, protein, or glucose; cyclic vs. continuous TPN administration; and the patient's previous nutritional state. Although removal of vitamin D or aluminum from the TPN solution and discontinuation of TPN altogether have been associated with improvement in symptoms, histology, and laboratory values, no single factor has been identified as the cause of this troubling phenomenon. PMID:3110249

  10. Up-regulation of glycolytic metabolism is required for HIF1α-driven bone formation.

    PubMed

    Regan, Jenna N; Lim, Joohyun; Shi, Yu; Joeng, Kyu Sang; Arbeit, Jeffrey M; Shohet, Ralph V; Long, Fanxin

    2014-06-10

    The bone marrow environment is among the most hypoxic in the body, but how hypoxia affects bone formation is not known. Because low oxygen tension stabilizes hypoxia-inducible factor alpha (HIFα) proteins, we have investigated the effect of expressing a stabilized form of HIF1α in osteoblast precursors. Brief stabilization of HIF1α in SP7-positive cells in postnatal mice dramatically stimulated cancellous bone formation via marked expansion of the osteoblast population. Remarkably, concomitant deletion of vascular endothelial growth factor A (VEGFA) in the mouse did not diminish bone accrual caused by HIF1α stabilization. Thus, HIF1α-driven bone formation is independent of VEGFA up-regulation and increased angiogenesis. On the other hand, HIF1α stabilization stimulated glycolysis in bone through up-regulation of key glycolytic enzymes including pyruvate dehydrogenase kinase 1 (PDK1). Pharmacological inhibition of PDK1 completely reversed HIF1α-driven bone formation in vivo. Thus, HIF1α stimulates osteoblast formation through direct activation of glycolysis, and alterations in cellular metabolism may be a broadly applicable mechanism for regulating cell differentiation. PMID:24912186

  11. The impact of microgravity on bone metabolism in vitro and in vivo.

    PubMed

    Loomer, P M

    2001-01-01

    Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. In-flight measures used to counteract this, including intensive daily exercise regimens, have been only partially successful in reducing the bone loss and in the process have consumed valuable work time. If this bone loss is to be minimized or, preferably, prevented, more effective treatment strategies are required. This, however, requires a greater understanding of the mechanisms through which bone metabolism is affected by microgravity. Various research strategies have been used to examine this problem, including in vitro studies using bone cells and in vivo studies on humans and rats. These have been conducted both in flight and on the ground, by strategies that produce weightlessness to mimic the effects of microgravity. Overall, the majority of the studies have found that marked decreases in gravitation loading result in the loss of bone mass. The processes of bone formation and bone resorption become uncoupled, with an initial transitory increase in resorption accompanied by a prolonged decrease in formation. Loss of bone mass is not uniform throughout the skeleton, but varies at different sites depending on the type of bone and on the mechanical load received. It appears that the skeletal response is a physiologic adaptation to the space environment which, after long space flights or repeated shorter ones, could eventually lead to significant reductions in the ability of the skeletal tissues to withstand the forces of gravity and increased susceptibility to fracture. PMID:11497376

  12. Factors affecting metabolic syndrome by lifestyle

    PubMed Central

    Ki, Nam-Kyun; Lee, Hae-Kag; Cho, Jae-Hwan; Kim, Seon-Chil; Kim, Nak-Sang

    2016-01-01

    [Purpose] The aim of this study was to explore lifestyle factors in relation to metabolic syndrome so as to be able to utilize the results as baseline data for the furtherance of health-care and medical treatment. [Subjects and Methods] This study was conducted with patients who visited a health care center located in Seoul and had abdominal ultrasonography between 2 March 2013 and 28 February, 2014. Heights, weights, and blood pressures were measured by automatic devices. Three radiologists examined the patients using abdominal ultrasonography for gallstone diagnosis. The statuses of patients with regard to smoking, alcohol, coffee, and physical activities were explored for the lifestyle investigation. For investigating baseline demographics, we first used descriptive statistics. We then used the χ2 test to analyze lifestyles and gallstone prevalence with regard to the presence of metabolic syndrome. Lastly, logistic regression analysis was conducted to discover the risk factors of metabolic syndrome. [Results] For men, body mass index, maximum gallstone size, and waist circumference were revealed as risk factors for metabolic syndrome, in descending order of the degree of risk. For females, gallstone presence was the most significant risk factor, followed by waist circumference. [Conclusion] Metabolic disease mainly presents itself along with obesity, and we should become more focused on preventing and treating this disease. A large-scale prospective study is needed in the future, as the cause of nonalcoholic steatohepatitis remained unclear in this study. PMID:26957725

  13. Hormonal regulation of medullary bone metabolism in the laying hen

    SciTech Connect

    Harrison, J.R.

    1987-01-01

    A new organ culture system for the study of bone formation has been developed using medullary bone, a non-structural, metabolically active form of bone which is found in the marrow cavities of egg-laying birds. In the presence of fetal calf serum, bone explants were viable in culture by morphological criteria, and retained large numbers of osteoblasts and osteoclasts. Incorporation of /sup 3/H-proline into collagenase-digestible protein (CDP) and non-collagen protein (NCP) was determined using purified bacterial collagenase. Collagen accounted for over 10% of the total protein labeled. The calcium-regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), caused a dose-dependent inhibition of /sup 3/H-proline incorporation into CDP. The effective dose range of 1,25(OH)2D3 was 0.1 nM to 100 nM, while that of PTH was 1.0 nM to 100 nM. The effect of both hormones was specific for collagen, since /sup 3/H-proline incorporation into NCP was unaffected. Hydroxyproline analysis of bone explants and culture medium revealed that both hormones decreased the total hydroxyroline content of the cultures, suggesting that the inhibition of /sup 3/H-proline incorporation into DCP is due to inhibition of collagen synthesis.

  14. Genetically Low Vitamin D Levels, Bone Mineral Density, and Bone Metabolism Markers: a Mendelian Randomisation Study.

    PubMed

    Li, Shan-Shan; Gao, Li-Hong; Zhang, Xiao-Ya; He, Jin-We; Fu, Wen-Zhen; Liu, Yu-Juan; Hu, Yun-Qiu; Zhang, Zhen-Lin

    2016-01-01

    Low serum 25-hydroxyvitamin D (25OHD) is associated with osteoporosis and osteoporotic fracture, but it remains uncertain whether these associations are causal. We conducted a Mendelian randomization (MR) study of 1,824 postmenopausal Chinese women to examine whether the detected associations between serum 25OHD and bone mineral density (BMD) and bone metabolism markers were causal. In observational analyses, total serum 25OHD was positively associated with BMD at lumbar spine (P = 0.003), femoral neck (P = 0.006) and total hip (P = 0.005), and was inversely associated with intact parathyroid hormone (PTH) (P = 8.18E-09) and procollagen type 1 N-terminal propeptide (P1NP) (P = 0.020). By contract, the associations of bioavailable and free 25OHD with all tested outcomes were negligible (all P > 0.05). The use of four single nucleotide polymorphisms, GC-rs2282679, NADSYN1-rs12785878, CYP2R1-rs10741657 and CYP24A1-rs6013897, as candidate instrumental variables in MR analyses showed that none of the two stage least squares models provided evidence for associations between serum 25OHD and either BMD or bone metabolism markers (all P > 0.05). We suggest that after controlling for unidentified confounding factors in MR analyses, the associations between genetically low serum 25OHD and BMD and bone metabolism markers are unlikely to be causal. PMID:27625044

  15. Amino acid supplementation alters bone metabolism during simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

    2005-01-01

    High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

  16. A longitudinal study of the effect of heparin thromboprophylaxis during pregnancy on maternal bone metabolism

    PubMed Central

    Ogueh, O; Johnson, M R; Benjamin, A

    2009-01-01

    The aim of this study was to determine the effect of heparin thromboprophylaxis during pregnancy on maternal biochemical markers of bone metabolism. This was a prospective longitudinal study of carboxy terminal pro-peptide of type I collagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) levels in 15 women, who had heparin thromboprophylaxis during pregnancy compared with those of 18 normal pregnant controls. During pregnancy, the rate of change of PICP and ICTP in women who had heparin thromboprophylaxis was similar to those of women who did not (P = 0.184 for PICP, and P = 0.129 for ICTP), and PICP and ICTP levels at individual time points were similar in both groups. Therefore, heparin thromboprophylaxis during pregnancy does not affect maternal biochemical markers of bone metabolism.

  17. Celiac disease: A missed cause of metabolic bone disease

    PubMed Central

    Rastogi, Ashu; Bhadada, Sanjay K.; Bhansali, Anil; Kochhar, Rakesh; Santosh, Ramakrishnan

    2012-01-01

    Introduction: Celiac disease (CD) is a highly prevalent autoimmune disease. The symptoms of CD are varied and atypical, with many patients having no gastrointestinal symptoms. Metabolic bone disease (MBD) is a less recognized manifestation of CD associated with spectrum of musculoskeletal signs and symptoms, viz. bone pains, proximal muscle weakness, osteopenia, osteoporosis, and fracture. We here report five patients who presented with severe MBD as the only manifestation of CD. Materials and Methods: Records of 825 patients of CD diagnosed during 2002–2010 were retrospectively analyzed for clinical features, risk factors, signs, biochemical, and radiological parameters. Results: We were able to identify five patients (0.6%) of CD who had monosymptomatic presentation with musculoskeletal symptoms and signs in the form of bone pains, proximal myopathy, and fragility fractures without any gastrointestinal manifestation. All the five patients had severe MBD in the form of osteopenia, osteoporosis, and fragility fractures. Four of the five patients had additional risk factors such as antiepileptic drugs, chronic alcohol consumption, malnutrition, and associated vitamin D deficiency which might have contributed to the severity of MBD. Conclusion: Severe metabolic disease as the only presentation of CD is rare. Patients show significant improvement in clinical, biochemical, and radiological parameters with gluten-free diet, calcium, and vitamin D supplementation. CD should be looked for routinely in patients presenting with unexplained MBD. PMID:23087864

  18. Bone metabolism during antler growth in female reindeer.

    PubMed

    Baksi, S N; Newbrey, J W

    1989-11-01

    Two female reindeer (Rangifer tarandus) were investigated for alterations in skeletal metabolism during the annual antler growth cycle. During July and January, rib samples were obtained by biopsy after double tetracycline labeling for gravimetric, chemical, and histomorphometric analyses. Though antler length increased from 8 to 55 cm between April and September, body weight increased from only 56 to 77 kg. Rib bone density (g/cm3) increased from 1.39 +/- 0.01 (mean +/- SEM) in July to 1.53 +/- 0.01 in January, and Ca content (mg/cm3) increased from 213 +/- 8 to 300 +/- 14, respectively. Histomorphometric data indicated that rib bones were more porous and active in July and had a higher turnover rate than did January samples. Plasma 1,25(OH)2D, parathyroid hormone (PTH), and osteocalcin levels were significantly lower and estradiol levels were significantly higher in the January as opposed to the July samples. The data indicate that during antler growth, female reindeer undergo bone loss that corresponds to the changes in plasma calcemic hormones and estradiol levels. This bone loss is eventually repaired when antler growth stops. PMID:2509019

  19. Bone and energy metabolism parameters in professional cyclists during the Giro d'Italia 3-weeks stage race.

    PubMed

    Lombardi, Giovanni; Lanteri, Patrizia; Graziani, Rosa; Colombini, Alessandra; Banfi, Giuseppe; Corsetti, Roberto

    2012-01-01

    Cycling is a not weight-bearing activity and is known to induce bone resorption. Stage races are really strenuous endurance performances affecting the energy homeostasis. The recently highlighted link, in the co-regulation of bone and energy metabolism, demonstrates a central role for the equilibrium between carboxylated and undercarboxylated forms of osteocalcin. Aim of this study was to understand the acute physiological responses to a cycling stage race in terms of bone turnover and energy metabolism and the possible co-regulative mechanisms underlying their relationship. We studied nine professional cyclists engaged in 2011 Giro d'Italia stage race. Pre-analytical and analytical phases tightly followed academic and anti-doping authority's recommendations. Bone and energy metabolism markers (bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, total and undercarboxylated osteocalcin, leptin and adiponectin) and related hormones (cortisol and testosterone) were measured, by Sandwich Enzyme Immunoassays, at days -1 (pre-race), 12 and 22 during the race. The power output and the energy expenditure (mean and accumulated) were derived and correlated with the biochemical indexes. During the race, bone metabolism showed that an unbalance in behalf of resorption, which is enhanced, occurred along with a relative increase in the concentration of the undercarboxylated form of osteocalcin that was indirectly related to the enhanced energy expenditure, through adipokines modifications, with leptin decrease (high energy consumption) and adiponectin increase (optimization of energy expenditure). The exertion due to heavy effort induced a decrease of cortisol, while testosterone levels resulted unchanged. In conclusion, during a 3-weeks stage race, bone metabolism is pushed towards resorption. A possible relationship between the bone and the energy metabolisms is suggested by the relative correlations among absolute and relative concentrations trends of

  20. Bone and Energy Metabolism Parameters in Professional Cyclists during the Giro d’Italia 3-Weeks Stage Race

    PubMed Central

    Lombardi, Giovanni; Lanteri, Patrizia; Graziani, Rosa; Colombini, Alessandra; Banfi, Giuseppe; Corsetti, Roberto

    2012-01-01

    Cycling is a not weight-bearing activity and is known to induce bone resorption. Stage races are really strenuous endurance performances affecting the energy homeostasis. The recently highlighted link, in the co-regulation of bone and energy metabolism, demonstrates a central role for the equilibrium between carboxylated and undercarboxylated forms of osteocalcin. Aim of this study was to understand the acute physiological responses to a cycling stage race in terms of bone turnover and energy metabolism and the possible co-regulative mechanisms underlying their relationship. We studied nine professional cyclists engaged in 2011 Giro d’Italia stage race. Pre-analytical and analytical phases tightly followed academic and anti-doping authority’s recommendations. Bone and energy metabolism markers (bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, total and undercarboxylated osteocalcin, leptin and adiponectin) and related hormones (cortisol and testosterone) were measured, by Sandwich Enzyme Immunoassays, at days -1 (pre-race), 12 and 22 during the race. The power output and the energy expenditure (mean and accumulated) were derived and correlated with the biochemical indexes. During the race, bone metabolism showed that an unbalance in behalf of resorption, which is enhanced, occurred along with a relative increase in the concentration of the undercarboxylated form of osteocalcin that was indirectly related to the enhanced energy expenditure, through adipokines modifications, with leptin decrease (high energy consumption) and adiponectin increase (optimization of energy expenditure). The exertion due to heavy effort induced a decrease of cortisol, while testosterone levels resulted unchanged. In conclusion, during a 3-weeks stage race, bone metabolism is pushed towards resorption. A possible relationship between the bone and the energy metabolisms is suggested by the relative correlations among absolute and relative concentrations trends of

  1. Early and Sustained Changes in Bone Metabolism After Severe Burn Injury.

    PubMed

    Muschitz, Gabriela Katharina; Schwabegger, Elisabeth; Kocijan, Roland; Baierl, Andreas; Moussalli, Hervé; Fochtmann, Alexandra; Nickl, Stefanie; Tinhofer, Ines; Haschka, Judith; Resch, Heinrich; Rath, Thomas; Pietschmann, Peter; Muschitz, Christian

    2016-04-01

    This study investigated serum burnover marker in male patients after severe burn injury. Ongoing changes suggest alterations in bone metabolism with a likely adverse influence on bone quality and structure. PMID:26789778

  2. The pleiotropic effects of paricalcitol: Beyond bone-mineral metabolism.

    PubMed

    Egido, Jesús; Martínez-Castelao, Alberto; Bover, Jordi; Praga, Manuel; Torregrosa, José Vicente; Fernández-Giráldez, Elvira; Solozábal, Carlos

    2016-01-01

    Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease (CKD) that is characterised by elevated parathyroid hormone (PTH) levels and a series of bone-mineral metabolism anomalies. In patients with SHPT, treatment with paricalcitol, a selective vitamin D receptor activator, has been shown to reduce PTH levels with minimal serum calcium and phosphorus variations. The classic effect of paricalcitol is that of a mediator in mineral and bone homeostasis. However, recent studies have suggested that the benefits of treatment with paricalcitol go beyond PTH reduction and, for instance, it has a positive effect on cardiovascular disease and survival. The objective of this study is to review the most significant studies on the so-called pleiotropic effects of paricalcitol treatment in patients with CKD. PMID:26705959

  3. Human Apolipoprotein E Isoforms differentially affect Bone Mass and Turnover in vivo

    PubMed Central

    Dieckmann, Marco; Beil, F. Timo; Mueller, Brigitte; Bartelt, Alexander; Marshall, Robert P.; Koehne, Till; Amling, Michael; Ruether, Wolfgang; Cooper, Jackie A.; Humphries, Steve E.; Herz, Joachim; Niemeier, Andreas

    2012-01-01

    The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of lipoproteins. However, a new role for apoE as a regulator of bone metabolism in mice has recently been established. In contrast to mice, the human APOE gene is characterized by three common isoforms APOE ε2, ε3 and ε4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans. To clarify this, we investigated bone phenotypes of apoE knock-in mice, which express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of the mouse apoE. Analysis of 12 week-old female knock-in mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k.i. animals as compared to apoE3 k.i. and apoE4 k.i., with a reduced OPG/RANKL ratio in apoE2 k.i., indicating increased turnover with prevailing resorption in apoE2 k.i.. Accordingly, histomorphometric and μCT analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k.i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms. To extend these observations to the human situation, plasma from middle-aged healthy men homozygous for ε2/ε2, ε3/ε3, and ε4/ε4 (n=21, n=80, n=55 respectively) was analyzed with regard to bone turnover markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in the serum of ε2/ε2 carriers as compared to ε3/ε3 and ε4/ε4 individuals (p=0.02 for ε2/ε2 vs ε4/ε4). In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE ε2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans. PMID:22991192

  4. Role of proton receptor OGR1 in bone response to metabolic acidosis?

    PubMed

    Jorgetti, Vanda; Drüeke, Tilman B; Ott, Susan M

    2016-03-01

    Chronic metabolic acidosis stimulates bone resorption, resulting in loss of calcium and bicarbonate from bone. Both osteoblasts and osteoclasts sense extracellular H(+) by the G-protein coupled receptor, OGR1, whose activation leads to increased bone resorption as well as decreased bone formation. Krieger et al. examined the effect of OGR1 knockout in mice. They found an unexpected increase in bone resorption, but nevertheless an increase in bone volume linked to enhanced bone formation. This discovery opens a window of opportunity to explore potential new anabolic treatments for patients with low bone mass. PMID:26880446

  5. Comparison of the effects of whey mineral complexes on bone metabolism in male growing rats.

    PubMed

    Tsuchita, H; Sekiguchi, I; Kuwata, T

    1993-10-01

    The effects of whey mineral complexes (WMC1 and WMC2) on bone metabolism were studied in male growing rats. The contents of Ca, P, and protein in WMC1 were 18.2, 8.4, 2.3%, respectively, whereas those of WMC2 were 26.4, 14.6, and 10.5%, respectively. WMCs were added to diets as a sole source of Ca: the levels of dietary Ca were 0.3 and 0.6%. CaCO3 was used as a reference. There was no difference in body weight gain and quantitative values for Ca balance among the groups at the same level of dietary Ca. Rats fed WMC2 had a higher femoral Ca and bone density of humerus. The bone properties in rats fed WMC1 were not as high as those in rats fed WMC2. The P absorption and absorption rate were affected significantly by the type of dietary Ca source as well as the levels of dietary Ca. The percent of tubular reabsorption of P of rats fed WMC1 or WMC2 had a tendency to be higher than that of rats fed CaCO3 at each dietary Ca level. The results of urinary cAMP excretion showed that the parathyroid hormone function in rats fed WMC2 was relatively lower. The differences in minerals and other constituents between WMC1 and WMC2 are discussed from the viewpoint of bone metabolism. PMID:8120671

  6. Xylitol affects the intestinal microbiota and metabolism of daidzein in adult male mice.

    PubMed

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  7. Xylitol Affects the Intestinal Microbiota and Metabolism of Daidzein in Adult Male Mice

    PubMed Central

    Tamura, Motoi; Hoshi, Chigusa; Hori, Sachiko

    2013-01-01

    This study examined the effects of xylitol on mouse intestinal microbiota and urinary isoflavonoids. Xylitol is classified as a sugar alcohol and used as a food additive. The intestinal microbiota seems to play an important role in isoflavone metabolism. Xylitol feeding appears to affect the gut microbiota. We hypothesized that dietary xylitol changes intestinal microbiota and, therefore, the metabolism of isoflavonoids in mice. Male mice were randomly divided into two groups: those fed a 0.05% daidzein with 5% xylitol diet (XD group) and those fed a 0.05% daidzein-containing control diet (CD group) for 28 days. Plasma total cholesterol concentrations were significantly lower in the XD group than in the CD group (p < 0.05). Urinary amounts of equol were significantly higher in the XD group than in the CD group (p < 0.05). The fecal lipid contents (% dry weight) were significantly greater in the XD group than in the CD group (p < 0.01). The cecal microbiota differed between the two dietary groups. The occupation ratios of Bacteroides were significantly greater in the CD than in the XD group (p < 0.05). This study suggests that xylitol has the potential to affect the metabolism of daidzein by altering the metabolic activity of the intestinal microbiota and/or gut environment. Given that equol affects bone health, dietary xylitol plus isoflavonoids may exert a favorable effect on bone health. PMID:24336061

  8. [Pathogenetic correction of metabolic disturbances in chronic liver affections].

    PubMed

    Romantsov, M G; Petrov, A Iu; Aleksandrova, L N; Sukhanov, D S; Kovalenko, A L

    2012-01-01

    The available drugs for the treatment of chronic liver affections (the adequate model is chronic hepatitis C) include agents of metabolic therapy, whose efficacy is not always enough, that required the search for original mitochondrial substrates on the basis of succinate. Such agents were composed as a pharmaceutical group named "Substrates of Energetic Metabolism" or "Substrate Antihypoxants". The review presents the description of the pharmacological effects of remaxole and cytoflavin, evident from lower levels of active metabolites of oxygen that increases the clinical efficacy of the therapy. Their role in the metabolic reactions in chronic liver affections is exclusive and rather actual. PMID:23700935

  9. Differences in vertebral, tibial, and iliac cancellous bone metabolism in ovariectomized rats.

    PubMed

    Takakura, Aya; Takao-Kawabata, Ryoko; Isogai, Yukihiro; Kajiwara, Makoto; Murayama, Hisashi; Ejiri, Sadakazu; Ishizuya, Toshinori

    2016-05-01

    Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3 days to 26 weeks postoperatively. The trabeculae were thicker in the LV, where bone metabolism was less active than at other sites, and numerous fine trabeculae were observed in the tibia, where bone metabolism was more active. The iliac bone structure and metabolism were intermediate between those of the tibia and LV. Ovariectomy induced lower bone volume and higher bone metabolism in all skeletal sites, but the changes were greatest and occurred earliest in the tibia, followed by the iliac bone and then LV. Ovariectomy caused changes in bone metabolic markers, which occurred earlier than those in bone tissue. Activation frequency (Ac.f) increased after ovariectomy. At week 26 in ovariectomized rats, Ac.f was highest in the tibia (3.13 N/year) but similar between iliac bone (0.87 N/year) and LV (1.39 N/year). Ac.f is reportedly 0.3-0.4 N/year in the iliac bone of postmenopausal women, suggesting that bone turnover in rats is several times higher than in humans. The reference values reported here are useful for translating experimental results from rats to humans. PMID:26082076

  10. Vascular calcification, bone and mineral metabolism after kidney transplantation

    PubMed Central

    D’Marco, Luis; Bellasi, Antonio; Mazzaferro, Sandro; Raggi, Paolo

    2015-01-01

    The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article. PMID:26722649

  11. Gut microbiome phenotypes driven by host genetics affect arsenic metabolism.

    PubMed

    Lu, Kun; Mahbub, Ridwan; Cable, Peter Hans; Ru, Hongyu; Parry, Nicola M A; Bodnar, Wanda M; Wishnok, John S; Styblo, Miroslav; Swenberg, James A; Fox, James G; Tannenbaum, Steven R

    2014-02-17

    Large individual differences in susceptibility to arsenic-induced diseases are well-documented and frequently associated with different patterns of arsenic metabolism. In this context, the role of the gut microbiome in directly metabolizing arsenic and triggering systemic responses in diverse organs raises the possibility that gut microbiome phenotypes affect the spectrum of metabolized arsenic species. However, it remains unclear how host genetics and the gut microbiome interact to affect the biotransformation of arsenic. Using an integrated approach combining 16S rRNA gene sequencing and HPLC-ICP-MS arsenic speciation, we demonstrate that IL-10 gene knockout leads to a significant taxonomic change of the gut microbiome, which in turn substantially affects arsenic metabolism. PMID:24490651

  12. [Cognitive Function and Calcium. The link between dementia and bone and calcium metabolism disorders].

    PubMed

    Yamaguchi, Kiyoshi

    2015-02-01

    Bone and calcium metabolism disorders are closely linked with dementia. Screening for dementia is important since chronic hypercalcemia and hypocalcemia resulting from parathyroid function abnormalities can become a cause of dementia onset. In recent years, it has become clear that vitamin D deficiencies inducing cardiovascular disease and other factors are involved in the pathogenesis of various diseases that in turn become risk factors in dementia, especially Alzheimer's disease. Moreover, osteoporosis and dementia both commonly occur among the elderly. Treating dementia patients for osteoporosis is important since fragility fractures, especially femoral neck fractures, resulting from osteoporosis greatly affect the prognosis of patients with dementia. PMID:25634043

  13. Bone mineral density and disorders of mineral metabolism in chronic liver disease

    PubMed Central

    George, Joe; Ganesh, Hosahithlu K; Acharya, Shrikrishna; Bandgar, Tushar R; Shivane, Vyankatesh; Karvat, Anjana; Bhatia, Shobna J; Shah, Samir; Menon, Padmavathy S; Shah, Nalini

    2009-01-01

    AIM: To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis. METHODS: The study was performed on 72 Indian patients with cirrhosis (63 male, nine female; aged < 50 years). Etiology of cirrhosis was alcoholism (n = 37), hepatitis B (n = 25) and hepatitis C (n = 10). Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density (BMD) was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2. RESULTS: Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium: protein ratio and calcium: phosphorus ratio. Vitamin D deficiency was highly prevalent (92%). There was a high incidence of hypogonadism (41%). Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor (IGF) 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low (68%) and urinary deoxypyridinoline to creatinine ratio was high (79%), which demonstrated low bone formation with high resorption. CONCLUSION: Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level. PMID:19630107

  14. Metabolic analysis of osteoarthritis subchondral bone based on UPLC/Q-TOF-MS.

    PubMed

    Yang, Gang; Zhang, Hua; Chen, Tingmei; Zhu, Weiwen; Ding, Shijia; Xu, Kaiming; Xu, Zhongwei; Guo, Yanlei; Zhang, Jian

    2016-06-01

    Osteoarthritis (OA), one of the most widespread musculoskeletal joint diseases among the aged, is characterized by the progressive loss of articular cartilage and continuous changes in subchondral bone. The exact pathogenesis of osteoarthritis is not completely clear. In this work, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) in combination with multivariate statistical analysis was applied to analyze the metabolic profiling of subchondral bone from 42 primary osteoarthritis patients. This paper described a modified two-step method for extracting the metabolites of subchondral bone from primary osteoarthritis patients. Finally, 68 metabolites were identified to be significantly changed in the sclerotic subchondral bone compared with the non-sclerotic subchondral bone. Taurine and hypotaurine metabolism and beta-alanine metabolism were probably relevant to the sclerosis of subchondral bone. Taurine, L-carnitine, and glycerophospholipids played a vital regulation role in the pathological process of sclerotic subchondral bone. In the sclerotic process, beta-alanine and L-carnitine might be related to the increase of energy consumption. In addition, our findings suggested that the intra-cellular environment of sclerotic subchondral bone might be more acidotic and hypoxic compared with the non-sclerotic subchondral bone. In conclusion, this study provided a new insight into the pathogenesis of subchondral bone sclerosis. Our results indicated that metabolomics could serve as a promising approach for elucidating the pathogenesis of subchondral bone sclerosis in primary osteoarthritis. Graphical Abstract Metabolic analysis of osteoarthritis subchondral bone. PMID:27074781

  15. Dietary phylloquinone depletion and repletion in postmenopausal women: effects on bone and mineral metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin K has been implicated in increased bone fracture risk. Despite a potential role of vitamin K in bone, little is known about the effects of altered dietary vitamin K intake on the underlying components of bone and mineral metabolism. This study was undertaken to assess the effects of vitamin ...

  16. A study of changes in bone metabolism in cases of gender identity disorder.

    PubMed

    Miyajima, Tsuyoshi; Kim, Yoon Taek; Oda, Hiromi

    2012-07-01

    The aim of this study was to determine the effect of increasing estrogen and decreasing androgen in males and increasing androgen and decreasing estrogen in females on bone metabolism in patients with gender identity disorder (GID). We measured and examined bone mineral density (BMD) and bone metabolism markers retrospectively in GID patients who were treated in our hospital. In addition, we studied the effects of treatment on those who had osteoporosis. Patients who underwent a change from male to female (MtF) showed inhibition of bone resorption and increased L2-4 BMD whereas those who underwent a change from female to male (FtM) had increased bone resorption and decreased L2-4 BMD. Six months after administration of risedronate to FtM patients with osteoporosis, L2-4 BMD increased and bone resorption markers decreased. These results indicate that estrogen is an important element with regard to bone metabolism in males. PMID:22222419

  17. Effect of acceleration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

    NASA Astrophysics Data System (ADS)

    Suzuki, S.; Kitamura, K.; Nemoto, N.; Shimizu, S.; Wada, W.; Kondo, K.; Tabata, T.; Sodeyama, S.; Ijiri, I.; Hattori, H.

    It is well known that hypo-gravity and hyper-gravity influence bone metabolism However basic data concerning the mechanism are a few because no in vitro model system of human bone is available Human bone consists of osteoblasts osteoclasts and the bone matrix No technique for the co-culture of these components has ever been developed Fish scale is a calcified tissue that contains osteoblasts osteoclasts and bone matrix all of which are similar to those found in human bone Recently we developed a new in vitro model system using goldfish scale This system can simultaneously detect the activities of both scale osteoclasts and osteoblasts with tartrate-resistant acid phosphatase and alkaline phosphatase as the respective markers Using this system we analyzed the bone metabolism under acceleration with a custom-made G-load apparatus Osteoclastic activity in the goldfish scales was suppressed under low-acceleration 0 5-G while osteoblastic activity did not change under this acceleration Under high-acceleration 6-G however the osteoblastic activity of the scales increased In addition the osteoclastic activity of the scales decreased These results suggest that both osteoblastic and osteoclastic activities are regulated by the strength of acceleration Therefore we strongly believe that our in vitro system is useful for analysis of bone metabolism under acceleration

  18. Environmental factors affecting pregnancy: endocrine disrupters, nutrients and metabolic pathways.

    PubMed

    Bazer, Fuller W; Wu, Guoyao; Johnson, Gregory A; Wang, Xiaoqiu

    2014-12-01

    Uterine adenogenesis, a unique post-natal event in mammals, is vulnerable to endocrine disruption by estrogens and progestins resulting in infertility or reduced prolificacy. The absence of uterine glands results in insufficient transport of nutrients into the uterine lumen to support conceptus development. Arginine, a component of histotroph, is substrate for production of nitric oxide, polyamines and agmatine and, with secreted phosphoprotein 1, it affects cytoskeletal organization of trophectoderm. Arginine is critical for development of the conceptus, pregnancy recognition signaling, implantation and placentation. Conceptuses of ungulates and cetaceans convert glucose to fructose which is metabolized via multiple pathways to support growth and development. However, high fructose corn syrup in soft drinks and foods may increase risks for metabolic disorders and increase insulin resistance in adults. Understanding endocrine disrupters and dietary substances, and novel pathways for nutrient metabolism during pregnancy can improve survival and growth, and prevent chronic metabolic diseases in offspring. PMID:25224489

  19. The Neuroendocrine Basis of Anorexia Nervosa and Its Impact on Bone Metabolism

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2011-01-01

    Anorexia nervosa (AN) is a condition of profound undernutrition associated with alterations in various neuroendocrine axes, many of which contribute to a marked impairment in bone accrual and low bone mineral density. This review focuses on changes in the hypothalamo-pituitary-gonadal axis, the growth hormone insulin-like growth factor-1 axis, and the hypothalamo-pituitary-adrenal axis in AN, as well as alterations in various appetite-regulating hormones. In addition, the review discusses low bone mineral density and altered bone microarchitecture in AN, the pathophysiology underlying impaired bone metabolism, and possible therapeutic strategies to optimize bone health. PMID:21228564

  20. Gli1 haploinsufficiency leads to decreased bone mass with an uncoupling of bone metabolism in adult mice.

    PubMed

    Kitaura, Yoshiaki; Hojo, Hironori; Komiyama, Yuske; Takato, Tsuyoshi; Chung, Ung-il; Ohba, Shinsuke

    2014-01-01

    Hedgehog (Hh) signaling plays important roles in various development processes. This signaling is necessary for osteoblast formation during endochondral ossification. In contrast to the established roles of Hh signaling in embryonic bone formation, evidence of its roles in adult bone homeostasis is not complete. Here we report the involvement of Gli1, a transcriptional activator induced by Hh signaling activation, in postnatal bone homeostasis under physiological and pathological conditions. Skeletal analyses of Gli1+/- adult mice revealed that Gli1 haploinsufficiency caused decreased bone mass with reduced bone formation and accelerated bone resorption, suggesting an uncoupling of bone metabolism. Hh-mediated osteoblast differentiation was largely impaired in cultures of Gli1+/- precursors, and the impairment was rescued by Gli1 expression via adenoviral transduction. In addition, Gli1+/- precursors showed premature differentiation into osteocytes and increased ability to support osteoclastogenesis. When we compared fracture healing between wild-type and Gli1+/- adult mice, we found that the Gli1+/- mice exhibited impaired fracture healing with insufficient soft callus formation. These data suggest that Gli1, acting downstream of Hh signaling, contributes to adult bone metabolism, in which this molecule not only promotes osteoblast differentiation but also represses osteoblast maturation toward osteocytes to maintain normal bone homeostasis. PMID:25313900

  1. Gli1 Haploinsufficiency Leads to Decreased Bone Mass with an Uncoupling of Bone Metabolism in Adult Mice

    PubMed Central

    Kitaura, Yoshiaki; Hojo, Hironori; Komiyama, Yuske; Takato, Tsuyoshi; Chung, Ung-il; Ohba, Shinsuke

    2014-01-01

    Hedgehog (Hh) signaling plays important roles in various development processes. This signaling is necessary for osteoblast formation during endochondral ossification. In contrast to the established roles of Hh signaling in embryonic bone formation, evidence of its roles in adult bone homeostasis is not complete. Here we report the involvement of Gli1, a transcriptional activator induced by Hh signaling activation, in postnatal bone homeostasis under physiological and pathological conditions. Skeletal analyses of Gli1+/− adult mice revealed that Gli1 haploinsufficiency caused decreased bone mass with reduced bone formation and accelerated bone resorption, suggesting an uncoupling of bone metabolism. Hh-mediated osteoblast differentiation was largely impaired in cultures of Gli1+/− precursors, and the impairment was rescued by Gli1 expression via adenoviral transduction. In addition, Gli1+/− precursors showed premature differentiation into osteocytes and increased ability to support osteoclastogenesis. When we compared fracture healing between wild-type and Gli1+/− adult mice, we found that the Gli1+/− mice exhibited impaired fracture healing with insufficient soft callus formation. These data suggest that Gli1, acting downstream of Hh signaling, contributes to adult bone metabolism, in which this molecule not only promotes osteoblast differentiation but also represses osteoblast maturation toward osteocytes to maintain normal bone homeostasis. PMID:25313900

  2. Stretching Your Energetic Budget: How Tendon Compliance Affects the Metabolic Cost of Running

    PubMed Central

    Uchida, Thomas K.; Hicks, Jennifer L.; Dembia, Christopher L.; Delp, Scott L.

    2016-01-01

    Muscles attach to bones via tendons that stretch and recoil, affecting muscle force generation and metabolic energy consumption. In this study, we investigated the effect of tendon compliance on the metabolic cost of running using a full-body musculoskeletal model with a detailed model of muscle energetics. We performed muscle-driven simulations of running at 2–5 m/s with tendon force–strain curves that produced between 1 and 10% strain when the muscles were developing maximum isometric force. We computed the average metabolic power consumed by each muscle when running at each speed and with each tendon compliance. Average whole-body metabolic power consumption increased as running speed increased, regardless of tendon compliance, and was lowest at each speed when tendon strain reached 2–3% as muscles were developing maximum isometric force. When running at 2 m/s, the soleus muscle consumed less metabolic power at high tendon compliance because the strain of the tendon allowed the muscle fibers to operate nearly isometrically during stance. In contrast, the medial and lateral gastrocnemii consumed less metabolic power at low tendon compliance because less compliant tendons allowed the muscle fibers to operate closer to their optimal lengths during stance. The software and simulations used in this study are freely available at simtk.org and enable examination of muscle energetics with unprecedented detail. PMID:26930416

  3. Dietary Intake Can Predict and Protect Against Changes in Bone Metabolism during Spaceflight and Recovery (Pro K)

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Zwart, S. R.; Shackelford, L.; Heer, M.

    2009-01-01

    Bone loss is not only a well-documented effect of spaceflight on astronauts, but also a condition that affects millions of men and women on Earth each year. Many countermeasures aimed at preventing bone loss during spaceflight have been proposed, and many have been evaluated to some degree. To date, those showing potential have focused on either exercise or pharmacological interventions, but none have targeted dietary intake alone as a factor to predict or minimize bone loss during spaceflight. The "Dietary Intake Can Predict and Protect against Changes in Bone Metabolism during Spaceflight and Recovery" investigation ("Pro K") is one of the first inflight evaluations of a dietary countermeasure to lessen bone loss of astronauts. This protocol will test the hypothesis that the ratio of acid precursors to base precursors (specifically animal protein to potassium) in the diet can predict directional changes in bone mineral during spaceflight and recovery. The ratio of animal protein to potassium in the diet will be controlled for multiple short (4-day) periods before and during flight. Based on multiple sets of bed rest data, we hypothesize that a higher ratio of the intake of animal protein to the intake of potassium will yield higher concentrations of markers of bone resorption and urinary calcium excretion during flight and during recovery from bone mineral loss after long-duration spaceflight.

  4. Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease.

    PubMed

    Lewiecki, E Michael; Baron, Roland; Bilezikian, John P; Gagel, Robert E; Leonard, Mary B; Leslie, William D; McClung, Michael R; Miller, Paul D

    2016-01-01

    The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities. PMID:26750746

  5. The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases.

    PubMed

    Lee, Youngkyun

    2013-10-01

    The balance between osteoblast-dependent bone formation and osteoclast-dependent bone resorption maintains bone homeostasis. In inflammatory conditions, this balance shifts toward bone resorption, causing osteolytic bone lesions observed in rheumatoid arthritis and periodontitis. A recently discovered family of cytokine IL-17 is widely reported to mediate diverse inflammatory processes. During the last decade, novel roles for IL-17 in skeletal homeostasis have been discovered indicating the potential importance of this cytokine in bone metabolism. This review will summarize and discuss the involvement of IL-17 during bone homeostasis in both physiologic and pathologic conditions. A better understanding of the role of IL-17 in skeletal systems warrants an advance in bone biology, as well as development of therapeutic strategies against bone-lytic diseases, such as rheumatoid arthritis and periodontitis. PMID:24148767

  6. Kinetic measurements of bone mineral metabolism: The use of Na-22 as a tracer for long-term bone mineral turnover studies

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1978-01-01

    Sodium-22 was studied as a tracer for bone mineral metabolism in rats and dogs. When incorporated into bone during growth from birth to adulthood, the bone becomes uniformly tagged with (22)Na which is released through the metabolic turnover of the bone. The (22)Na which is not incorporated in the bone matrix is rapidly excreted within a few days when animals are fed high but nontoxic levels of NaCl. The (22)Na tracer can be used to measure bone mineral loss in animals during space flight and in research on bone disease.

  7. Bone development in black ducks as affected by dietary toxaphene

    USGS Publications Warehouse

    Mehrle, P.M.; Finley, M.T.; Ludke, J.L.; Mayer, F.L.; Kaiser, T.E.

    1979-01-01

    Black ducks, Anas rubripes, were exposed to dietary toxaphene concentrations of 0, 10, or 50 μg/g of food for 90 days prior to laying and through the reproductive season. Toxaphene did not affect reproduction or survival, but reduced growth and impaired backbone development in ducklings. Collagen, the organic matrix of bone, was decreased significantly in cervical vertebrae of ducklings fed 50 μg/g, and calcium conentrations increased in vertebrae of ducklings fed 10 or 50 μg/g. The effects of toxaphene were observed only in female ducklings. In contrast to effects on vertebrae, toxaphene exposure did not alter tibia development. Toxaphene residues in carcasses of these ducklings averaged slightly less than the dietary levels.

  8. Prebiotics, probiotics, and synbiotics affect mineral absorption, bone mineral content, and bone structure.

    PubMed

    Scholz-Ahrens, Katharina E; Ade, Peter; Marten, Berit; Weber, Petra; Timm, Wolfram; Açil, Yahya; Glüer, Claus-C; Schrezenmeir, Jürgen

    2007-03-01

    Several studies in animals and humans have shown positive effects of nondigestible oligosaccharides (NDO) on mineral absorption and metabolism and bone composition and architecture. These include inulin, oligofructose, fructooligosaccharides, galactooligosaccharides, soybean oligosaccharide, and also resistant starches, sugar alcohols, and difructose anhydride. A positive outcome of dietary prebiotics is promoted by a high dietary calcium content up to a threshold level and an optimum amount and composition of supplemented prebiotics. There might be an optimum composition of fructooligosaccharides with different chain lengths (synergy products). The efficacy of dietary prebiotics depends on chronological age, physiological age, menopausal status, and calcium absorption capacity. There is evidence for an independent probiotic effect on facilitating mineral absorption. Synbiotics, i.e., a combination of probiotics and prebiotics, can induce additional effects. Whether a low content of habitual NDO would augment the effect of dietary prebiotics or synbiotics remains to be studied. The underlying mechanisms are manifold: increased solubility of minerals because of increased bacterial production of short-chain fatty acids, which is promoted by the greater supply of substrate; an enlargement of the absorption surface by promoting proliferation of enterocytes mediated by bacterial fermentation products, predominantly lactate and butyrate; increased expression of calcium-binding proteins; improvement of gut health; degradation of mineral complexing phytic acid; release of bone-modulating factors such as phytoestrogens from foods; stabilization of the intestinal flora and ecology, also in the presence of antibiotics; stabilization of the intestinal mucus; and impact of modulating growth factors such as polyamines. In conclusion, prebiotics are the most promising but also best investigated substances with respect to a bone-health-promoting potential, compared with probiotics

  9. Factors Affecting Bone Mineral Density in Adults with Cerebral Palsy

    PubMed Central

    Yoon, Young Kwon; Kim, Ae Ryoung; Kim, On Yoo; Lee, Kilchan; Suh, Young Joo

    2012-01-01

    Objective To clarify factors affecting bone mineral density (BMD) in adults with cerebral palsy (CP). Method Thirty-five patients with CP participated in this study. Demographic data including gender, age, body mass index (BMI), subtype according to neuromotor type and topographical distribution, ambulatory function, and functional independence measure (FIM) were investigated. The BMD of the lumbar spine and femur were measured using Dual-energy X-ray absorptiometry, and the factors affecting BMD were analyzed. Results The BMD had no significant association with factors such as gender, age, and subtype in adults with CP. However, BMI was significantly correlated with the BMD of lumbar spine and femur (p<0.05). The FIM score was also positively correlated with the BMD of femur (p<0.05). Moreover, CP patients with higher ambulatory function had significantly higher BMD of femur (p<0.05). Conclusion These findings suggest that BMI and functional levels such as FIM and ambulatory function can affect BMD in adults with CP. The results might be used as basic data, suggesting the importance of treatment including weight bearing exercise and gait training in adults with CP. PMID:23342308

  10. Cellular lead toxicity and metabolism in primary and clonal osteoblastic bone cells

    SciTech Connect

    Long, G.J.; Rosen, J.F.; Pounds, J.G. )

    1990-02-01

    A knowledge of bone lead metabolism is critical for understanding the toxicological importance of bone lead, as a toxicant both to bone cells and to soft tissues of the body, as lead is mobilized from large reservoirs in hard tissues. To further understand the processes that mediate metabolism of lead in bone, it is necessary to determine lead metabolism at the cellular level. Experiments were conducted to determine the intracellular steady-state {sup 210}Pb kinetics in cultures of primary and clonal osteoblastic bone cells. Osteoblastic bone cells obtained by sequential collagenase digestion of mouse calvaria or rat osteosarcoma (ROS 17/2.8) cells were labeled with {sup 210}Pb as 5 microM lead acetate for 20 hr, and kinetic parameters were determined by measuring the efflux of {sup 210}Pb from the cells over a {sup 210}-min period. The intracellular metabolism of {sup 210}Pb was characterized by three kinetic pools of {sup 210}Pb in both cell types. Although the values of these parameters differed between the primary osteoblastic cells and ROS cells, the profile of {sup 210}Pb was remarkably similar in both cell types. Both types exhibited one large, slowly exchanging pool (S3), indicative of mitochondrial lead. These data show that primary osteoblastic bone cells and ROS cells exhibit similar steady-state lead kinetics, and intracellular lead distribution. These data also establish a working model of lead kinetics in osteoblastic bone cells and now permit an integrated view of lead kinetics in bone.

  11. Bone metabolism and renal stone risk during International Space Station missions.

    PubMed

    Smith, Scott M; Heer, Martina; Shackelford, Linda C; Sibonga, Jean D; Spatz, Jordan; Pietrzyk, Robert A; Hudson, Edgar K; Zwart, Sara R

    2015-12-01

    Bone loss and renal stone risk are longstanding concerns for astronauts. Bone resorption brought on by spaceflight elevates urinary calcium and the risk of renal stone formation. Loss of bone calcium leads to concerns about fracture risk and increased long-term risk of osteoporosis. Bone metabolism involves many factors and is interconnected with muscle metabolism and diet. We report here bone biochemistry and renal stone risk data from astronauts on 4- to 6-month International Space Station missions. All had access to a type of resistive exercise countermeasure hardware, either the Advanced Resistance Exercise Device (ARED) or the Interim Resistance Exercise Device (iRED). A subset of the ARED group also tested the bisphosphonate alendronate as a potential anti-resorptive countermeasure (Bis+ARED). While some of the basic bone marker data have been published, we provide here a more comprehensive evaluation of bone biochemistry with a larger group of astronauts. Regardless of exercise, the risk of renal stone formation increased during spaceflight. A key factor in this increase was urine volume, which was lower during flight in all groups at all time points. Thus, the easiest way to mitigate renal stone risk is to increase fluid consumption. ARED use increased bone formation without changing bone resorption, and mitigated a drop in parathyroid hormone in iRED astronauts. Sclerostin, an osteocyte-derived negative regulator of bone formation, increased 10-15% in both groups of astronauts who used the ARED (p<0.06). IGF-1, which regulates bone growth and formation, increased during flight in all 3 groups (p<0.001). Our results are consistent with the growing body of literature showing that the hyper-resorptive state of bone that is brought on by spaceflight can be countered pharmacologically or mitigated through an exercise-induced increase in bone formation, with nutritional support. Key questions remain about the effect of exercise-induced alterations in bone

  12. Imaging Sensitivity of Quiescent Cancer Cells to Metabolic Perturbations in Bone Marrow Spheroids

    PubMed Central

    Cavnar, Stephen P.; Xiao, Annie; Gibbons, Anne E.; Rickelmann, Andrew D.; Neely, Taylor; Luker, Kathryn E.; Takayama, Shuichi; Luker, Gary D.

    2016-01-01

    Malignant cells from breast cancer and other common cancers such as prostate and melanoma may persist in bone marrow as quiescent, non-dividing cells that remain viable for years or even decades before resuming proliferation to cause recurrent disease. This phenomenon, referred to clinically as tumor dormancy, poses tremendous challenges to curing patients with breast cancer. Quiescent tumor cells resist chemotherapy drugs that predominantly target proliferating cells, limiting success of neo-adjuvant and adjuvant therapies. We recently developed a 3D spheroid model of quiescent breast cancer cells in bone marrow for mechanistic and drug testing studies. We combined this model with optical imaging methods for label-free detection of cells preferentially utilizing glycolysis versus oxidative metabolism to investigate the metabolic state of co-culture spheroids with different bone marrow stromal and breast cancer cells. Through imaging and biochemical assays, we identified different metabolic states of bone marrow stromal cells that control metabolic status and flexibilities of co-cultured breast cancer cells. We tested metabolic stresses and targeted inhibition of specific metabolic pathways to identify approaches to preferentially eliminate quiescent breast cancer cells from bone marrow environments. These studies establish an integrated imaging approach to analyze metabolism in complex tissue environments to identify new metabolically-targeted cancer therapies. PMID:27478871

  13. Adiponectin and bone metabolism markers in female rowers: eumenorrheic and oral contraceptive users.

    PubMed

    Jürimäe, J; Vaiksaar, S; Mäestu, J; Purge, P; Jürimäe, T

    2011-12-01

    This study investigated whether adiponectin, bone formation (osteocalcin) and bone resorption [type I carboxyterminal telopeptide (ICTP)] values are influenced by menstrual cycle phase and oral contraceptive use in female rowers. Twenty-four rowers divided into normally cycling athletes (NOC; no.=15) and athletes taking oral contraceptive pills (OC; no.=9) participated in this study. Fasting blood samples, body composition and aerobic capacity measurements were taken during the follicular (FP) and the luteal (LP) phases of the menstrual cycle. Adiponectin, insulin, glucose, insulin resistance, body composition and aerobic capacity did not fluctuate significantly during menstrual cycle in both groups. Osteocalcin and ICTP were lower (p<0.05) in OC compared with NOC, but did not change significantly across menstrual cycle phases in both groups. Estradiol and progesterone were not related to adiponectin, osteocalcin or ICTP (r<0.147; p>0.05). Adiponectin was correlated (p<0.05) with osteocalcin (r=0.452) and fat free mass (r=0.428), and osteocalcin was related (p<0.05) to insulin (r=-0.413), glucose (r=-0.486) and insulin resistance (r=-0.528). In conclusion, adiponectin was not affected by menstrual cycle phase and OC use in female rowers, while bone metabolism markers were lower in OC compared to NOC groups. Adiponectin and osteocalcin were interrelated and may characterise energy homeostasis in female athletes. PMID:21169728

  14. Changes in bone sodium and carbonate in metabolic acidosis and alkalosis in the dog

    PubMed Central

    Burnell, James M.

    1971-01-01

    Metabolic acidosis and alkalosis were produced in adult dogs over 5- to 10-day periods. Midtibial cortical bone was analyzed for calcium, sodium, phosphorus, and carbonate. In acidosis bone CO3/Ca decreased 9.5% and bone Na/Ca decreased 6.3%. In alkalosis bone CO3/Ca increased 3.1% and bone Na/Ca increased 3.0%. Previous attempts to account for changes in net acid balance by summation of extra- and intracellular acid-base changes have uniformly resulted in about 40-60% of acid gained or lost being “unaccounted for.” If it is assumed that changes in tibial cortex reflect changes in the entire skeletal system, changes in bone CO3= are sufficiently large to account for the “unaccounted for” acid change without postulating changes in cellular metabolic acid production. PMID:5540172

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

    PubMed

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

    2016-09-01

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

  16. The effect of LLLT on bone metabolism in children with severe cerebral palsy (a secondary publication)

    PubMed Central

    2014-01-01

    Background and aims: It is said that the average frequency of bone fracture in hospitalized children with severe cerebral palsy (unable to remain seated) is 1% (0.2 to 2.0%). Cerebral palsy patients' bones are known to be vulnerable to fracture, and refractory bone atrophy may be observed. However, the effect of low level laser therapy (LLLT) on bone density or bone metabolism has not been fully investigated. In recent years, tests for bone density or bone metabolism markers have become available. Material and methods: In this study, we evaluated changes in bone density and bone metabolism markers in 4 children with severe cerebral palsy who underwent LLLT for an average of 22 days. Results: B-ALP, a marker of ossification, increased 1 month after the start of irradiation in 3 of the 4 subjects and returned to a level close to the pre-irradiation level 2 months after the start of irradiation. In the remaining subjects in whom B-ALP failed to increase, B-ALP had been low before irradiation. Urinary N-terminal telopeptide (NTx) levels, a marker of bone resorption, decreased in 3 of the 4 subjects after the start of irradiation and remained low even 10 months later. Serum NTx levels tended to decrease in 3 of the 4 subjects. The levels of serum NTx/Crea, Deoxy-Pyridinoline (DPd) and DPd/Crea (DPd/Crea) also decreased in 3 of the 4 subjects. Transient decreases in intact parathyroid hormone (PTH) levels were observed in all 4 cases. Changes were particularly apparent in 2 cases: one with high NTx levels, which showed enhanced bone resorption, and one with high PTH levels, probably due to a vitamin D (VitD) deficiency. Although the metacarpal bone density measured by DIP was found to be lower than in normal children, there were no changes due to LLLT. Conclusion: These results suggest that LLLT has a positive influence on bone metabolism in that it temporarily increases bone formation and suppresses bone resorption while also tending to improve secondary

  17. Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

    PubMed

    Hinton, Pamela S

    2016-08-01

    Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

  18. Evaluation of bone metabolism in newborn twins using quantitative ultrasound and biochemical parameters.

    PubMed

    Kara, Semra; Güzoğlu, Nilüfer; Göçer, Emine; Arıkan, Fatma Inci; Dilmen, Uğur; Dallar Bilge, Yıldız

    2016-03-01

    Metabolic bone disease (MBD) is one of the important complications of prematurity. Early and adequate nutritional interventions may reduce the incidence and potential complications of MBD. The present study aimed to evaluate bone metabolism in twins via biochemical parameters and quantitative ultrasound (QUS) and to compare the results between twin pairs. Moreover, twin infants were evaluated in terms of potential risk factors likely to have impact on MBD. Forty-three pairs of twins were included in the study. Serum calcium, phosphorus, magnesium, and alkaline phosphatase concentrations were assessed and bone mineral density was measured using QUS (speed of sound, SOS) at postnatal 30 d. Co-twin with the higher birth weight was assigned to Group 1 (n = 36) and the other twin was assigned to Group 2 (n = 36). Birth weight and head circumference were significantly higher in the infants of Group 1 compared with Group 2. No significant difference was found among the groups in terms of gender, history of resuscitation, length of stay in intensive care unit (ICU) or in the incubator, duration of total parenteral nutrition (TPN), type of nutrition, vitamin D use, biochemical parameters, and the SOS value. The factors likely to affect SOS, including type of pregnancy, maternal drug use, gender of infant, birth weight, head circumference at birth, gestational week, length of stay at the ICU, duration of TPN, type of nutrition, resuscitation, vitamin D use, and levels of calcium, phosphorus, magnesium, and alkaline phosphatase were entered into the model. The phosphorus level and the maternal drug use were found to be the factors that significantly reduced SOS, whereas pregnancy after assisted reproductive techniques was found to be a significant enhancing factor. PMID:25777793

  19. New insights into tryptophan and its metabolites in the regulation of bone metabolism.

    PubMed

    Michalowska, M; Znorko, B; Kaminski, T; Oksztulska-Kolanek, E; Pawlak, D

    2015-12-01

    Osteoporosis, a debilitating disease caused by an imbalance between the action of osteoblasts and osteoclasts, is becoming an increasing problem in today's aging population. Although many advances in this field have addressed certain aspects of disease progression and pain management, new approaches to treatment are required. This review focuses on the influence of tryptophan, its metabolites and their influence on bone remodeling. Tryptophan is a precursor to serotonin, melatonin, kynurenines and niacin. Changes of tryptophan levels were noticed in bone metabolic diseases. Moreover, some works indicate that tryptophan plays a role in osteoblastic differentiation. Serotonin can exert different effects on bones, which depend on site of serotonin synthesis. Gut-derived serotonin inhibits bone formation, whereas brain-derived serotonin enhances bone formation and decreases bone resorption. Melatonin, increased differentiation of human mesenchymal stem cells into the osteoblastic cell lineage. Results of melatonin action on bone are anabolic and antiresorptive. Activation of the second tryptophan metabolic pathway, the kynurenine pathway, is associated with osteoblastogenesis and can be implicated in the occurrence of bone diseases. Oxidation products like kynurenine stopped proliferation of bone marrow mesenchymal stem cells. This may result in inhibition of osteoblastic proliferation and differentiation. Kynurenic acid acts as an antagonist at glutamate receptors, which are expressed on osteoclasts. Quinolinic acid activates N-methyl-D-aspartate receptors. 3-hydroxyanthranilic acid exhibits pro-oxidant and antioxidant activity. Decreased concentration of 3-hydroxyanthranilic acid can be one of the causes of osteoporosis. 3-hydroxykynurenine reduced the viability of osteoblast-like cells. Picolinic acid exerted osteogenic effect in vitro. Kynurenine derivatives exert various effects on bones. Discovery of the exact mechanism of action of tryptophan metabolites on

  20. Effects of rabeprazole on bone metabolic disorders in a gastrectomized rat model

    PubMed Central

    YAMASAKI, YUKI; FUJIMURA, TAKASHI; OYAMA, KATSUNOBU; HIGASHI, YUKI; HIROSE, ATSUSHI; TSUKADA, TOMOYA; OKAMOTO, KOICHI; KINOSHITA, JUN; NAKAMURA, KEISHI; MIYASHITA, TOMOHARU; TAJIMA, HIDEHIRO; TAKAMURA, HIROYUKI; NINOMIYA, ITASU; FUSHIDA, SACHIO; OHTA, TETSUO

    2016-01-01

    Proton pump inhibitors (PPIs) are frequently prescribed to patients with gastroesophageal reflux disease; however, the number of bone fractures reportedly increased in these patients. Although PPIs have been shown to inhibit the bone resorption by osteoclasts, the effect of PPIs on skeletal metabolism remains controversial. The aim of the present study was to determine the effect of the PPI rabeprazole on skeletal metabolism using gastrectomized rats. Male Wistar rats were divided into four groups: i) Sham-surgery (n=15); ii) total gastrectomy (TG) control (n=20); iii) TG plus rabeprazole (n=20); and iv) TG plus the bisphosphonate minodronic acid (n=20). Twenty-two weeks after TG, the rats were sacrificed, and bone mineral density (BMD), bone strength and markers for bone metabolism were measured. Compared with the control group (50.0±8.1%), the TG-induced decrease in BMD was significantly ameliorated in the rabeprazole group (56.5±7.5%) and the minodronic acid group (59.0±6.0%). However, rabeprazole did not improve bone strength. In conclusion, rabeprazole does not appear to exacerbate bone metabolic disorders in gastrectomized rats, but rather ameliorates the TG-induced BMD decrease. PMID:27330752

  1. Effects of dietary energy and calcium levels on performance, egg shell quality and bone metabolism in hens.

    PubMed

    Jiang, Sha; Cui, Luying; Shi, Cheng; Ke, Xiao; Luo, Jingwen; Hou, Jiafa

    2013-10-01

    This study investigated the effects of dietary energy and calcium levels on laying performance, eggshell quality and bone metabolism of layers. One hundred and sixty-two 19-week-old Hy-Line brown laying hens in 54 battery cages were allocated to one of nine dietary treatments with control, middle and high levels of energy (11.50, 12.68 and 13.37 MJ/kg, respectively) and low, control and high levels of calcium (2.62%, 3.7% and 4.4%, respectively) for 60 days, using a 3 × 3 factorial arrangement. Compared with the control energy diet, high- and middle-energy diets increased fat deposition and egg weight, decreased feed intake and bone quality and had no effects on eggshell quality. The high-energy diet reduced the serum phosphate concentration and elevated osteocalcin mRNA expression in the keel bone without increasing osteocalcin protein. Dietary calcium intake did not affect fat deposition, feed intake or egg weight. Low dietary calcium resulted in weaker eggshells and poorer bone quality than that from hens fed the control diet. High dietary calcium increased serum calcium concentration, osteoprotegerin mRNA and osteocalcin protein and inhibited serum alkaline phosphatase activity and decreased its mRNA compared with low or control dietary calcium. The high-energy and high-calcium diet significantly reduced egg production. Compared with the control energy diet, high- and middle-energy diets increased fat deposition but had negative effects on bone metabolic homeostasis. Dietary calcium did not influence fat deposition but a high-calcium diet benefited bone homeostasis, while a low-calcium diet was associated with poorer eggshell quality and bone homeostasis. PMID:24054908

  2. Effect of carbohydrate feeding on the bone metabolic response to running

    PubMed Central

    Varley, Ian; Jones, Thomas W.; James, Ruth M.; Tang, Jonathan C. Y.; Fraser, William D.; Greeves, Julie P.

    2015-01-01

    Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO·kg body mass−1·h−1) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (V̇o2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P = 0.028; P1NP: P = 0.021; IL-6: P = 0.036), although there was no difference in the short-term response (β-CTX: P = 0.856; P1NP: P = 0.721; IL-6: P = 0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover. PMID:26251510

  3. Effect of carbohydrate feeding on the bone metabolic response to running.

    PubMed

    Sale, Craig; Varley, Ian; Jones, Thomas W; James, Ruth M; Tang, Jonathan C Y; Fraser, William D; Greeves, Julie P

    2015-10-01

    Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO · kg body mass(-1) · h(-1)) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (V̇o2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P = 0.028; P1NP: P = 0.021; IL-6: P = 0.036), although there was no difference in the short-term response (β-CTX: P = 0.856; P1NP: P = 0.721; IL-6: P = 0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover. PMID:26251510

  4. The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club.

    PubMed

    Cavalier, E; Bergmann, P; Bruyère, O; Delanaye, P; Durnez, A; Devogelaer, J-P; Ferrari, S L; Gielen, E; Goemaere, S; Kaufman, J-M; Toukap, A Nzeusseu; Reginster, J-Y; Rousseau, A-F; Rozenberg, S; Scheen, A J; Body, J-J

    2016-07-01

    The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis. PMID:27026330

  5. Fermentation and Hydrogen Metabolism Affect Uranium Reduction by Clostridia

    DOE PAGESBeta

    Gao, Weimin; Francis, Arokiasamy J.

    2013-01-01

    Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction bymore » clostridia demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H 2 ) production.« less

  6. Fermentation and hydrogen metabolism affect uranium reduction by clostridia.

    PubMed

    Gao, Weimin; Francis, Arokiasamy J

    2013-01-01

    Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction by clostridia demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H2) production. PMID:25937978

  7. Fermentation and Hydrogen Metabolism Affect Uranium Reduction by Clostridia

    PubMed Central

    Gao, Weimin; Francis, Arokiasamy J.

    2013-01-01

    Previously, it has been shown that not only is uranium reduction under fermentation condition common among clostridia species, but also the strains differed in the extent of their capability and the pH of the culture significantly affected uranium(VI) reduction. In this study, using HPLC and GC techniques, metabolic properties of those clostridial strains active in uranium reduction under fermentation conditions have been characterized and their effects on capability variance of uranium reduction discussed. Then, the relationship between hydrogen metabolism and uranium reduction has been further explored and the important role played by hydrogenase in uranium(VI) and iron(III) reduction by clostridia demonstrated. When hydrogen was provided as the headspace gas, uranium(VI) reduction occurred in the presence of whole cells of clostridia. This is in contrast to that of nitrogen as the headspace gas. Without clostridia cells, hydrogen alone could not result in uranium(VI) reduction. In alignment with this observation, it was also found that either copper(II) addition or iron depletion in the medium could compromise uranium reduction by clostridia. In the end, a comprehensive model was proposed to explain uranium reduction by clostridia and its relationship to the overall metabolism especially hydrogen (H2) production. PMID:25937978

  8. Effect of low gravity on calcium metabolism and bone formation (L-7)

    NASA Technical Reports Server (NTRS)

    Suda, Tatsuo

    1993-01-01

    Recently, attention has been focused on the disorders of bone and calcium metabolism during space flight. The skeletal system has evolved on the Earth under 1-g. Space flights under low gravity appear to cause substantial changes in bone and calcium homeostasis of the animals adapted to 1-g. A space experiment for the First Materials Processing Test (FMPT) was proposed to examine the effects of low gravity on calcium metabolism and bone formation using chick embryos loaded in a space shuttle. This space experiment was proposed based on the following two experimental findings. First, it has been reported that bone density decreases significantly during prolonged space flight. The data obtained from the US Skylab and the U.S.S.R. Salyut-6 cosmonauts have also documented that the degree of bone loss is related to the duration of space flight. Second, the US-Soviet joints space experiment demonstrated that the decrease in bone density under low gravity appears to be due to the decrease in bone formation rather than the increase in bone resorption. The purpose of our space experiment is, therefore, to investigate further the mechanisms of bone growth under low gravity using fertilized chick embryos.

  9. Bone mineral measurement from Apollo experiment M-078. [derangement of bone mineral metabolism in spacecrews

    NASA Technical Reports Server (NTRS)

    Vogel, J. M.; Rambaut, P. C.; Smith, M. C., Jr.

    1974-01-01

    Loss of mineral from bone during periods of immobilization, recumbency, or weightlessness is examined. This report describes the instrumentation, technique, and bone mineral changes observed preflight and postflight for the Apollo 14, 15, and 16 missions. The bone mineral changes documented during the Apollo Program are reviewed, and their relevance to future missions is discussed.

  10. Pyridoxine deficiency affects biomechanical properties of chick tibial bone

    NASA Technical Reports Server (NTRS)

    Masse, P. G.; Rimnac, C. M.; Yamauchi, M.; Coburn, S. P.; Rucker, R. B.; Howell, D. S.; Boskey, A. L.

    1996-01-01

    The mechanical integrity of bone is dependent on the bone matrix, which is believed to account for the plastic deformation of the tissue, and the mineral, which is believed to account for the elastic deformation. The validity of this model is shown in this study based on analysis of the bones of vitamin B6-deficient and vitamin B6-replete chick bones. In this model, when B6-deficient and control animals are compared, vitamin B6 deficiency has no effect on the mineral content or composition of cortical bone as measured by ash weight (63 +/- 6 vs. 58 +/- 3); mineral to matrix ratio of the FTIR spectra (4.2 +/- 0.6 vs. 4.5 +/- 0.2), line-broadening analyses of the X-ray diffraction 002 peak (beta 002 = 0.50 +/- 0.1 vs. 0.49 +/- 0.01), or other features of the infrared spectra. In contrast, collagen was significantly more extractable from vitamin B6-deficient chick bones (20 +/- 2% of total hydroxyproline extracted vs. 10 +/- 3% p < or = 0.001). The B6-deficient bones also contained an increased amount of the reducible cross-links DHLNL, dehydro-dihydroxylysinonorleucine, (1.03 +/- 0.07 vs. 0.84 +/- 0.13 p < or = 0.001); and a nonsignificant increase in HLNL, dehydro-hydroxylysinonorleucine, (0.51 +/- 0.03 vs. 0.43 +/- 0.03, p < or = 0.10). There were no significant changes in bone length, bone diameter, or area moment of inertia. In four-point bending, no significant changes in elastic modulus, stiffness, offset yield deflection, or fracture deflection were detected. However, fracture load in the B6-deficient animals was decreased from 203 +/- 35 MPa to 151 +/- 23 MPa, p < or = 0.01, and offset yield load was decreased from 165 +/- 9 MPa to 125 +/- 14 MPa, p < or = 0.05. Since earlier histomorphometric studies had demonstrated that the B6-deficient bones were osteopenic, these data suggest that although proper cortical bone mineralization occurred, the alterations of the collagen resulted in changes to bone mechanical performance.

  11. Postnatal Changes in Humerus Cortical Bone Thickness Reflect the Development of Metabolic Bone Disease in Preterm Infants

    PubMed Central

    Tokuriki, Shuko; Igarashi, Aiko; Okuno, Takashi; Ohta, Genrei; Kosaka, Takuya; Ohshima, Yusei

    2016-01-01

    Objective. To use cortical bone thickness (CBT) of the humerus to identify risk factors for the development of metabolic bone disease in preterm infants. Methods. Twenty-seven infants born at <32 weeks of gestational age, with a birth weight of <1,500 g, were enrolled. Humeral CBT was measured from chest radiographs at birth and at 27-28, 31-32, and 36–44 weeks of postmenstrual age (PMA). The risk factors for the development of osteomalacia were statistically analyzed. Results. The humeral CBT at 36–44 weeks of PMA was positively correlated with gestational age and birth weight and negatively correlated with the duration of mechanical ventilation. CBT increased with PMA, except in six very early preterm infants in whom it decreased. Based on logistic regression analysis, gestational age and duration of mechanical ventilation were identified as risk factors for cortical bone thinning. Conclusions. Humeral CBT may serve as a radiologic marker of metabolic bone disease at 36–44 weeks of PMA in preterm infants. Cortical bones of extremely preterm infants are fragile, even when age is corrected for term, and require extreme care to lower the risk of fractures. PMID:27194819

  12. Interactions between dietary boron and thiamine affect lipid metabolism

    SciTech Connect

    Herbel, J.L.; Hunt, C.D. )

    1991-03-15

    An experiment was designed to test the hypothesis that dietary boron impacts upon the function of various coenzymes involved in energy metabolism. In a 2 {times} 7 factorially-arranged experiment, weanling, vitamin D{sub 3}-deprived rats were fed a ground corn-casein-corn oil based diet supplemented with 0 or 2 mg boron/kg and 50% of the requirement for thiamine (TM), riboflavin (RF), pantothenic acid (PA) or pyridoxine (PX); 0% for folic acid (FA) or nicotinic acid (NA). All vitamins were supplemented in adequate amounts in the control diet. At 8 weeks of age, the TM dietary treatment was the one most affected by supplemental dietary boron (SDB). In rats that were fed 50% TM, SDB increased plasma concentrations of triglyceride (TG) and activity of alanine transaminase (ALT), and the liver to body weight (L/B) ratio. However, in the SDB animals, adequate amounts of TM decreased the means of those variables to near that observed in non-SDB rats fed 50% TM. The findings suggest that an interaction between dietary boron and TM affects lipid metabolism.

  13. Cochlear otosclerosis: does bone formation affect cochlear implant surgery?

    PubMed

    Fayad, J; Moloy, P; Linthicum, F H

    1990-05-01

    This study aimed to demonstrate that new bone formation in the scala tympani of patients deaf from otosclerosis does not preclude cochlear implant surgery. In seven temporal bones from patients with otosclerosis, we measured the extent of new bone from the round window to the distal part of the new growth. We compared results to surgical data on the extent of drilling and depth and ease of placement of the electrode in 20 patients deaf from otosclerosis. We also examined clinical performance and voltage requirements for long-term implant use in patients with and patients without ossification of the scala tympani. Findings in our limited sample of patients and bones show that obstruction of the basal turn, which occurs in some otosclerotic patients, does not preclude implant surgery. The dynamic range in the studied sample was relatively stable long-term and clinical performance did not differ between groups with and without an ossified scala tympani. PMID:2188511

  14. The effects of short-term jump training on bone metabolism in females using oral contraceptives.

    PubMed

    Reiger, Jamie; Yingling, Vanessa R

    2016-01-01

    The purpose of this study was to determine the effect of oral contraceptive use on bone serum markers following a 3-week jumping protocol. Twenty-three females (18-25 years) were grouped as oral contraceptive users (OC+) or non-users (OC-). Following a 3-week observation period, participants completed a 3-week (15-day) jump protocol. Jump sessions consisting of ten 42 cm drop jumps with a 30 s rest interval between jumps were completed each day, 5 days per week. Peak vertical ground reaction force and loading rate were measured and the osteogenic index was calculated. Serum markers for bone formation, bone alkaline phosphatase (BAP) and bone resorption, C-terminal telopeptides of type I collagen (CTX) were measured at three time points (pre-, mid-, post-jump). BAP and CTX increased significantly (P = 0.0017, 0.0488) in both groups post-jump; however, bone metabolic markers were not different between the OC+ and OC- groups. Osteogenic index, ground reaction force and vertical jump height were similar between groups. Correlations between markers of bone metabolism and participants' age at menarche, weight, loading rate and years on OC were not significant. A 3-week jumping protocol was found to be effective in stimulating bone metabolism in both OC+ and OC- groups. PMID:26008875

  15. Quantitative PET imaging of bone marrow glucose metabolic response to hematopoietic cytokines

    SciTech Connect

    Yao, W.J.; Hoh, C.K.; Hawkins, R.A.

    1995-05-01

    To evaluate the effects of hematopoietic cytokines on bone marrow glucose metabolism noninvasively, the authors studied serial quantitative FDG-PET images in 18 patients with metastic melanoma and normal bone marrow who were undergoing granulocyte-macrophage colony-stimulating factor (GMCSF) or macrophage colony-stimulating factor (MCSF) administration as an adjunct to chemotherapy. All patients received 14 days of cytokine therapy in three groups; four patients were treated with GMCSF (5 {mu}g/kg/d SQ), eight patients were treated with GMCSF (5 {mu}g/kg/d SQ) and monoclonal antibody (MAbR24) and six patients were treated with MCSF (80 {mu}g/kg/d IVCI) and MAbR24. Dynamic FDG-PET imaging was performed over the lower thoracic or upper lumbar spine at four time points in each patient. Baseline glucose metabolic rates in the bone marrow of these three groups of patients were similar (5.2 {plus_minus} 0.7, 4.4 {plus_minus} 0.8 and 4.8 {plus_minus} 1.2 {mu}g/min/g as mean value and standard deviations, respectively). In both GMCSF and GMCSF + R24 groups, rapid increases in bone marrow glucose metabolic rates were observed during therapy. After GMCSF was stopped, bone marrow glucose metabolic rates rapdily decreased in both groups. The glucose metabolic response in these two groups was not significantly different by pooled t-statistics (p = 0.105). In the MCSF + R24 group, the increase of glucose metabolic rate on Days 3 and 10 was 35% and 31% above baseline on the average, but was not significant. The results support the use of parametric FDG-PET imaging for noninvasive quantitation of bone marrow glucose metabolic changes to hematopoietic cytokines in vivo. 32 refs., 2 figs., 2 tabs.

  16. Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

    NASA Technical Reports Server (NTRS)

    Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

    1996-01-01

    Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non

  17. Analysis of vitamin D metabolism gene expression in human bone: evidence for autocrine control of bone remodelling.

    PubMed

    Ormsby, Renee T; Findlay, David M; Kogawa, Masakazu; Anderson, Paul H; Morris, Howard A; Atkins, Gerald J

    2014-10-01

    The metabolism of 25-hydroxyvitamin D (25D) to active 1α,25-dihydroxyvitamin D (1,25D) by endogenous expression of 25D 1-α hydroxylase (CYP27B1) in bone cells appears to have functional effects in both osteoclasts and osteoblasts. To examine relationships between CYP27B1 expression in bone and its potential function in vivo, we examined the expression of vitamin D metabolism genes (CYP27B1, CYP24A1, VDR) in human trabecular bone samples and compared them by linear regression analysis with the expression of osteoclast (TRAP, CA2, CATK, NFATC1), osteoblast (TNAP, COL1A1, OCN, MEPE, BRIL), osteocyte (DMP1, SOST, PHEX, MEPE, FGF23)-related gene markers, genes associated with osteoblast/osteocyte control of osteoclastogenesis (RANKL, M-CSF, OPG, IL-8, TWEAK) and transcription factors (NFATC1, RUNX2, OSX, MSX2, HIF1A). This revealed multiple significant gene expression relationships between CYP27B1 and the transcription factors RUNX2, NFATC1, consistent with the coordinated expression of this gene by both osteoblast and osteoclast-lineage cells, and with MSX2 and the hypoxia-inducible transcription factor, HIF1A. CYP27B1 expression associated mainly with gene markers of bone resorption. VDR mRNA expression was also associated with resorption-related genes. Against expectations, CYP27B1 expression did not associate with bone expressed genes known to be 1,25D responsive, such as OCN, RANKL and DMP1. The major implication of these relationships in gene expression is that endogenous 1,25D synthesis and the response to 1,25D in human trabecular bone is linked with coordinated functions in both the osteoclastic and osteoblastic compartments towards the control of bone remodelling. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24120913

  18. Bone and mineral metabolism in adult celiac disease

    SciTech Connect

    Caraceni, M.P.; Molteni, N.; Bardella, M.T.; Ortolani, S.; Nogara, A.; Bianchi, P.A.

    1988-03-01

    Bone mineral density (/sup 125/I photon absorptiometry) was lower in 20 untreated adult celiac patients than in sex- and age-matched controls (p less than 0.001), and plasma alkaline phosphatase, parathyroid hormone, urinary hydroxyproline/creatinine levels were higher than normal (p less than 0.05, less than 0.001, less than 0.05, respectively). Gluten-free diet was started, and the patients were divided randomly into two treatment groups, one which received oral 25-hydroxyvitamin D 50 micrograms/day and one which did not. After 12 months' treatment, bone turnover markers showed a decrease, which did not reach statistical significance, and bone mineral density did not show significant modifications compared with base line in either group. It was found that a gluten-free diet followed for 1 yr can prevent further bone loss, but no significant differences were detected between the two groups.

  19. Markers of bone resorption and calcium metabolism are related to dietary intake patterns in male and female bed rest subjects

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Zwart, S. R.; Hargens, A. r.

    2006-01-01

    Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (P<0.05). The ratio of dietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

  20. [Bone metabolism and cardiovascular function update. The estimation of bone material quality in the concept of bone and vascular linkage].

    PubMed

    Saito, Mitsuru; Kida, Yoshikuni; Marumo, Keishi

    2014-07-01

    It has become clear that a reduction in sex hormones from middle age onwards, increasing age, and an increase in oxidative stress related to lifestyle-related diseases can also reduce bone material properties in terms of collagen post-translational modification, crosslink formation. These changes lead to both qualitative and quantitative abnormalities in collagen, which is the major bone matrix protein. The intermolecular cross-link formation of collagen, which regulates bone-material attributes, is a mechanism independent of bone remodeling. In other words, cross-link formation is controlled by the environment surrounding the bone matrix, comprising cellular functions, oxidative stress, and glycation level. Because oxidative stress is also risk factor of arteriosclerosis and cardiovascular event, there is link between low bone quality and arteriosclerosis. High levels of pentosidine in urine or blood, or mild hyperhomocysteinemia which suggest bone collagen abnormalities, might be used as surrogate markers for evaluating bone quality, assessing the risk of bone fracture. Patients with osteoporosis can be divided into 3 types on the basis of bone density and with bone quality. We are entering an age in which the treatment of osteoporosis will be personalized, with drugs administered depending on these types. PMID:24976053

  1. Stem cell origin differently affects bone tissue engineering strategies

    PubMed Central

    Mattioli-Belmonte, Monica; Teti, Gabriella; Salvatore, Viviana; Focaroli, Stefano; Orciani, Monia; Dicarlo, Manuela; Fini, Milena; Orsini, Giovanna; Di Primio, Roberto; Falconi, Mirella

    2015-01-01

    Bone tissue engineering approaches are encouraging for the improvement of conventional bone grafting technique drawbacks. Thanks to their self-renewal and multi-lineage differentiation ability, stem cells are one of the major actors in tissue engineering approaches, and among these adult mesenchymal stem cells (MSCs) hold a great promise for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs) are the first- identified and well-recognized stem cell population used in bone tissue engineering. Nevertheless, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The fruitful selection and combination of tissue engineered scaffold, progenitor cells, and physiologic signaling molecules allowed the surgeon to reconstruct the missing natural tissue. On the basis of these considerations, we analyzed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e., periodontal ligament, maxillary periosteum) as well as adipose-derived stem cells (ASCs), in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, taking into account their specific features, they could be intriguing cell sources in different stem cell-based bone/periodontal tissue regeneration approaches. PMID:26441682

  2. Cyclic cryopreservation affects the nanoscale material properties of trabecular bone.

    PubMed

    Landauer, Alexander K; Mondal, Sumona; Yuya, Philip A; Kuxhaus, Laurel

    2014-11-01

    Tissues such as bone are often stored via freezing, or cryopreservation. During an experimental protocol, bone may be frozen and thawed a number of times. For whole bone, the mechanical properties (strength and modulus) do not significantly change throughout five freeze-thaw cycles. Material properties at the trabecular and lamellar scales are distinct from whole bone properties, thus the impact of freeze-thaw cycling at this scale is unknown. To address this, the effect of repeated freezing on viscoelastic material properties of trabecular bone was quantified via dynamic nanoindentation. Vertebrae from five cervine spines (1.5-year-old, male) were semi-randomly assigned, three-to-a-cycle, to 0-10 freeze-thaw cycles. After freeze-thaw cycling, the vertebrae were dissected, prepared and tested. ANOVA (factors cycle, frequency, and donor) on storage modulus, loss modulus, and loss tangent, were conducted. Results revealed significant changes between cycles for all material properties for most cycles, no significant difference across most of the dynamic range, and significant differences between some donors. Regression analysis showed a moderate positive correlation between cycles and material property for loss modulus and loss tangent, and weak negative correlation for storage modulus, all correlations were significant. These results indicate that not only is elasticity unpredictably altered, but also that damping and viscoelasticity tend to increase with additional freeze-thaw cycling. PMID:25278046

  3. Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

    PubMed

    Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

    2016-05-01

    The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects. PMID:26944960

  4. Clinical potential of RANKL inhibition for the management of postmenopausal osteoporosis and other metabolic bone diseases.

    PubMed

    Delmas, Pierre D

    2008-01-01

    Osteoporosis affects millions of people worldwide, causing decreases in bone strength and a marked increase in fracture risk. Current therapies increase bone mineral density and reduce the risk of fractures, but dosing requirements are often considered inconvenient, and patient compliance with therapy is poor. This review will discuss recent discoveries in bone biology, which have demonstrated that the interaction of osteoprotegerin (OPG), receptor activator of nuclear factor--kappa B (RANK), and RANK ligand (RANKL) is critical for the regulation of bone remodeling. Collectively, these preclinical studies have shown that endogenous RANKL inhibition by OPG underlies the normal mechanism for maintaining the correct balance between bone resorption and bone formation. Multiple clinical trials are in progress to investigate the therapeutic potential of RANKL inhibition by denosumab, a fully human monoclonal anti-RANKL antibody, in the treatment of postmenopausal osteoporosis and other bone loss diseases. The results of these human trials will also be discussed. PMID:18375161

  5. Black leaf streak disease affects starch metabolism in banana fruit.

    PubMed

    Saraiva, Lorenzo de Amorim; Castelan, Florence Polegato; Shitakubo, Renata; Hassimotto, Neuza Mariko Aymoto; Purgatto, Eduardo; Chillet, Marc; Cordenunsi, Beatriz Rosana

    2013-06-12

    Black leaf streak disease (BLSD), also known as black sigatoka, represents the main foliar disease in Brazilian banana plantations. In addition to photosynthetic leaf area losses and yield losses, this disease causes an alteration in the pre- and postharvest behavior of the fruit. The aim of this work was to investigate the starch metabolism of fruits during fruit ripening from plants infected with BLSD by evaluating carbohydrate content (i.e., starch, soluble sugars, oligosaccharides, amylose), phenolic compound content, phytohormones, enzymatic activities (i.e., starch phosphorylases, α- and β-amylase), and starch granules. The results indicated that the starch metabolism in banana fruit ripening is affected by BLSD infection. Fruit from infested plots contained unusual amounts of soluble sugars in the green stage and smaller starch granules and showed a different pattern of superficial degradation. Enzymatic activities linked to starch degradation were also altered by the disease. Moreover, the levels of indole-acetic acid and phenolic compounds indicated an advanced fruit physiological age for fruits from infested plots. PMID:23692371

  6. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

    PubMed Central

    Mitchell, Kathryn A.; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is “a pediatric disease with geriatric consequences.” Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  7. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model.

    PubMed

    Yingling, Vanessa R; Mitchell, Kathryn A; Lunny, Megan

    2016-01-01

    Background. Osteoporosis is "a pediatric disease with geriatric consequences." Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV) at maturity. Methods. Female rats (25 days old) were assigned to a control (C) group (n = 45) that received saline injections (.2 cc) or an experimental group (GnRH-a) (n = 45) that received gonadotropin releasing hormone antagonist injections (.24 mg per dose) for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a). The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R) (n = 15) and (G-R) (n = 15)). The remaining animals had an ovariectomy surgery (OVX) at 185 days of age and were sacrificed 40 days later (C-OVX) (n = 15) and (G-OVX) (n = 15). After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX) and insulin-like growth factor 1 (IGF-1) were measured. Two-way ANOVA (2 groups (GnRH-a and Control) X 3 time points (Injection Protocol, Recovery, post-OVX)) was computed. Results. GnRH-a injections suppressed uterine weights (72%) and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19%) following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  8. Effect of vibration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

    NASA Astrophysics Data System (ADS)

    Suzuki, N.; Kitamura, K.; Nemoto, T.; Shimizu, N.; Wada, S.; Kondo, T.; Tabata, M. J.; Sodeyama, F.; Ijiri, K.; Hattori, A.

    In osteoclastic activity during space flight as well as hind limb unloading by tail suspension, inconsistent results have been reported in an in vivo study. The bone matrix plays an important role in the response to physical stress. However, there is no suitable in vitro co-culture system of osteoblasts and osteoclasts including bone matrix. On the other hand, fish scale is a calcified tissue that contains osteoblasts, osteoclasts, and bone matrix, all of which are similar to those found in human bones. Recently, we developed a new in vitro model system using goldfish scale. This system can detect the activities of osteoclasts and osteoblasts with tartrate-resistant acid phosphatase and alkaline phosphatase as the respective markers and precisely analyze the co-relationship between osteoblasts and osteoclasts. Using this system, we analyzed the bone metabolism under various degrees of acceleration (0.5-, 1-, 2-, 4-, and 6-G) by vibration with a G-load apparatus. After loading for 5 and 10 min, the scales were incubated for 6 and 24 h. The osteoblastic and osteoclastic activities were then measured. The osteoblastic activities gradually increased corresponding to 1-G to 6-G acceleration. In addition, ER mRNA expression was the highest under 6-G acceleration. On the other hand, the osteoclastic activity decreased at 24 h of incubation under low acceleration (0.5- and 1-G). This change coincided with TRAP mRNA expression. Under 2-G acceleration, the strength of suppression in osteoclastic activity was the highest. The strength of the inhibitory action under 4- and 6-G acceleration was lower than that under 2-G acceleration. In our co-culture system, osteoblasts and osteoclasts in the scale sensitively responded to several degrees of acceleration. Therefore, we strongly believe that our in vitro co-culture system is useful for the analysis of bone metabolism under loading or unloading.

  9. Does aspiration of bones and joints affect results of later bone scanning

    SciTech Connect

    Canale, S.T.; Harkness, R.M.; Thomas, P.A.; Massie, J.D.

    1985-01-01

    To determine the effect, if any, of needle aspiration on /sup 99m/Tc bone scanning, three different areas of 15 dogs were first aspirated and then imaged with technetium bone scintigraphy. The hip joint was aspirated, the distal femoral metaphysis was drilled and aspirated, and the tibial periosteum was scraped with an 18- or 20-gauge needle. Varying amounts of trauma were inflicted to simulate varying difficulties at aspiration. /sup 99m/Tc bone scans were obtained from 5 h to 10 days later. There was no evidence of focal technetium uptake after any hip joint aspiration. This was consistent regardless of the amount of trauma inflicted or the time from aspiration to bone scanning. Metaphyseal cortical drilling and tibial periosteal scraping occasionally caused some focal uptake when scanning was delayed greater than 2 days. When osteomyelitis or pyarthrosis is clinically suspected, joint aspiration can be performed without fear of producing a false- positive bone scan.

  10. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

    PubMed Central

    Fan, Hueng-Chuen; Lee, Herng-Shen; Chang, Kai-Ping; Lee, Yi-Yen; Lai, Hsin-Chuan; Hung, Pi-Lien; Lee, Hsiu-Fen; Chi, Ching-Shiang

    2016-01-01

    Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities. PMID:27490534

  11. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.

    PubMed

    Fan, Hueng-Chuen; Lee, Herng-Shen; Chang, Kai-Ping; Lee, Yi-Yen; Lai, Hsin-Chuan; Hung, Pi-Lien; Lee, Hsiu-Fen; Chi, Ching-Shiang

    2016-01-01

    Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities. PMID:27490534

  12. Calcium homeostasis and bone metabolic responses to protein diets and energy restriction: a randomized control trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite some beneficial effects on bone, high protein diets are conventionally considered a primary dietary risk factor for osteoporosis and bone fracture due to the acid load associated with protein catabolism. To test the hypothesis that high dietary protein diets do not negatively affect calcium ...

  13. Bone mineral metabolism in patients with neurofibromatosis type 1 (von Recklingausen disease).

    PubMed

    Petramala, Luigi; Giustini, Sandra; Zinnamosca, Laura; Marinelli, Cristiano; Colangelo, Luciano; Cilenti, Giuseppina; Formicuccia, Maria Chiara; D'Erasmo, Emilio; Calvieri, Stefano; Letizia, Claudio

    2012-05-01

    The neurofibromatosis type 1 (NF1) is characterized by specific cutaneous features (neurofibromas, "café-au-lait" spots of the skin) and alterations of several tissue (nervous, vascular) and bone deformities, such as scoliosis, congenital pseudoarthrosis and bone dysplasia of tibia. Moreover, several studies have shown systemic involvement of bone tissue in NF1 patients, leading to reduced bone mass. The aim of our study was to evaluate some bone mineral metabolism parameters before and after calcium and vitamin D supplementation in NF1 patients. We evaluated in 70 NF1 consecutive patients the mineral metabolism and bone mineral density compared with 40 normal subjects. We showed bone alterations in 35% of patients and the increase of bone formation markers, such as bone isoenzyme of alkaline phosphatase (41.2 ± 15.5 vs. 25.6 ± 8.7 UI; P < 0.05, respectively) and osteocalcin (18.1 ± 5.6 vs. 7.6 ± 1.9 ng/ml; P < 0.05) and reduction of circulating levels of (25OH)-vitamin D (21.8 ± 12.3 ng/ml) with an high percentage of hypovitaminosys D (>60%). Moreover, we revealed a significant reduction of bone mass density at spine (L1-L4) (0.935 ± 0.13 vs. 1.110 ± 0.17 g/cm(2); P < 0.001) and femoral neck side (0.765 ± 0.09 vs. 0.839 ± 0.12 g/cm(2); P < 0.02), with high prevalence of osteopenia (44%) and osteoporosis (18%). After 12 months of calcium (1,200 mg/die) and cholecalciferol (800 UI/die) supplementation, we found a significant increase of (25) OH-vitamin D level (21.8 ± 12.3 vs. 35 ± 13 ng/ml; P < 0.01), without changes in bone mass density. In conclusion, NF1 patients may present a mineral bone involvement, with vitamin D deficiency; calcium and vitamin D supplementation is necessary to restore these bone mineral metabolic alterations. PMID:22120694

  14. [Regulation of bone metabolism in osteoporosis : novel drugs for osteoporosis in development].

    PubMed

    Jakob, F; Genest, F; Baron, G; Stumpf, U; Rudert, M; Seefried, L

    2015-11-01

    Bone is continuously regenerated and remodeled as an adaptation to mechanical load. Bone mass and fracture resistance are maintained by a balanced equilibrium between bone formation and bone resorption. Regeneration and response to mechanical load are, however, impaired in osteoporosis and during aging. Bone resorption is enhanced by chronic inflammation while bone formation is altered by rising levels of inhibitors in the aging organism. Core molecular principles of the regulation of bone metabolism in health and disease have been characterized and developed as therapeutic targets. The receptor activator of nuclear factor kappaB ligand (RANKL) and osteoclast-derived protease cathepsin K are important regulators and effectors of osteoclast differentiation and bone resorption. Bone formation is stimulated by bone morphogenetic proteins (BMP) and via the parathyroid hormone receptor and the Wnt signaling pathway. The principles of osteoclast inhibition using bisphosphonates have now been known for almost three decades. Based on more recent knowledge RANKL and cathepsin K have been developed as new therapeutic targets to inhibit bone resorption. While denosumab, a RANKL antibody, has already been introduced into routine treatment strategies, the cathepsin K antagonist odanacatib is currently in the licensing process. Bone formation can also be stimulated by local administration of BMPs, by systemic treatment with the parathyroid hormone fragment teriparatide and by using antibodies targeting the Wnt inhibitor sclerostin. The latter are presently being tested in phase III clinical studies. In the near future a panel of traditional and novel treatment strategies will be available that will enable us to meet the individual clinical needs during aging and for the treatment of osteoporosis. PMID:26471379

  15. Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse.

    PubMed

    Solomon, Gili; Atkins, Ayelet; Shahar, Ron; Gertler, Arieh; Monsonego-Ornan, Efrat

    2014-01-01

    Leptin's in vivo effect on the rodent skeleton depends on the model used and the mode of administration. Superactive mouse leptin antagonist (SMLA) was produced and then pegylated (PEG) to prolong and enhance its in vivo activity. We blocked leptin signaling by injecting this antagonist peripherally into normal mice at various time points and studied their metabolic and skeletal phenotypes. Subcutaneous PEG-SMLA injections into 4-wk-old female C57BL/6J mice increased weight gain and food consumption significantly after only 1 mo, and the effect lasted for the 3 mo of the experiment, proving its central inhibiting activity. Mice showed a significant increase in serum glucose, cholesterol, triglycerides, insulin, and HOMA-IR throughout the experiment. Quantification of gene expression in "metabolic" tissues also indicated the development of insulin resistance. Bone analyses revealed a significant increase in trabecular and cortical parameters measured in both the lumbar vertebrae and tibiae in PEG-SMLA-treated mice in the 1st and 3rd months as well as a significant increase in tibia biomechanical parameters. Interestingly, 30 days of treatment with the antagonist in older mice (aged 3 and 6 mo) affected body weight and eating behavior, just as they had in the 1-mo-old mice, but had no effect on bone parameters, suggesting that leptin's effect on bones, either directly or through its obesogenic effect, is dependent upon stage of skeletal development. This potent and reversible antagonist enabled us to study leptin's in vivo role in whole body and bone metabolism and holds potential for future therapeutic use in diseases involving leptin signaling. PMID:24169045

  16. Multiple dietary supplements do not affect metabolic and cardiovascular health.

    PubMed

    Soare, Andreea; Weiss, Edward P; Holloszy, John O; Fontana, Luigi

    2013-09-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m2) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24036417

  17. Multiple dietary supplements do not affect metabolic and cardiovascular health

    PubMed Central

    Holloszy, John O.; Fontana, Luigi

    2014-01-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m2) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24659610

  18. Calcium, phosphorus, and bone metabolism in the fetus and newborn.

    PubMed

    Kovacs, Christopher S

    2015-11-01

    The placenta actively transports minerals whereas the intestines and kidneys may be nonessential for fetal mineral homeostasis. Mineral concentrations are higher in fetal blood than in adults in order for the developing skeleton to accrete adequate mineral content. Fetal bone development and serum mineral regulation are dependent upon parathyroid hormone (PTH) and PTH-related protein (PTHrP), but not calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, a switch from fetal to neonatal regulatory mechanisms is triggered by loss of the placental calcium infusion, onset of a breathing, and a postnatal fall in serum calcium and rise in phosphorus. This is followed by an increase in PTH, then a rise in calcitriol, and developmental changes in kidneys and intestines. Serum calcium increases and phosphorus declines over days. The intestines become the main source of mineral, while kidneys reabsorb mineral, and bone turnover contributes additional mineral to the circulation. PMID:26363942

  19. Dietary Sodium Effects on Bone Loss and Calcium Metabolism During Bed Rest

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Arnaud, Sara B.; Abrams, Steven A.; Paloski, W. H. (Technical Monitor)

    2000-01-01

    The acceleration of age-related bone loss is one of the most detrimental effects of space flight. The ability to understand and counteract this loss will be critical for crew health and safety during and after long-duration missions. Studies in healthy ambulatory individuals have linked high salt (sodium) diets, hypercalciuria, and increased renal stone risk. Dietary salt may modulate bone loss through changes in calcium metabolism and the calcium endocrine system. The research proposed here will determine the role of dietary salt in the loss of bone during simulated space flight. Calcium metabolism will be determined through calcium kinetics studies, endocrine and biochemical measurements; and estimates of the mass, distribution and mechanical properties of bone, in subjects fed low (100 mmol sodium/day) or high (250 mmol sodium/day) levels of dietary salt during 28 days of headdown tilt bedrest. This research addresses the role of dietary salt in the loss of bone and calcium in space flight, and integrates the changes in calcium metabolism with those occurring in other physiologic systems. These data will be critical for both countermeasure development, and in determination of nutritional requirements for extended-duration space flight. The potential countermeasures resulting from this research will reduce health risks due to acceleration of age-related osteoporosis and increased risk of renal stone formation..

  20. Diabetes and disordered bone metabolism (diabetic osteodystrophy): time for recognition.

    PubMed

    Epstein, S; Defeudis, G; Manfrini, S; Napoli, N; Pozzilli, P

    2016-06-01

    Diabetes and osteoporosis are rapidly growing diseases. The link between the high fracture incidence in diabetes as compared with the non-diabetic state has recently been recognized. While this review cannot cover every aspect of diabetic osteodystrophy, it attempts to incorporate current information from the First International Symposium on Diabetes and Bone presentations in Rome in 2014. Diabetes and osteoporosis are fast-growing diseases in the western world and are becoming a major problem in the emerging economic nations. Aging of populations worldwide will be responsible for an increased risk in the incidence of osteoporosis and diabetes. Furthermore, the economic burden due to complications of these diseases is enormous and will continue to increase unless public awareness of these diseases, the curbing of obesity, and cost-effective measures are instituted. The link between diabetes and fractures being more common in diabetics than non-diabetics has been widely recognized. At the same time, many questions remain regarding the underlying mechanisms for greater bone fragility in diabetic patients and the best approach to risk assessment and treatment to prevent fractures. Although it cannot cover every aspect of diabetic osteodystrophy, this review will attempt to incorporate current information particularly from the First International Symposium on Diabetes and Bone presentations in Rome in November 2014. PMID:26980458

  1. The Role of Bone Marrow and Visceral Fat on Bone Metabolism

    PubMed Central

    Cauley, Jane A.

    2014-01-01

    The protective effect of total fat mass on bone mineral density (BMD) has been challenged with studies showing no or negative association after adjusting for weight. Subsequently, more studies have evaluated the relationship of regional adiposity with BMD, and findings were inconsistent for central obesity. Advancements in imaging techniques enable us to directly and noninvasively study the role of adiposity on skeletal health. Visceral adiposity measured by computed tomography (CT) has consistently been shown to have negative effects on bone. Availability of magnetic resonance spectroscopy (MRS) also allows us to noninvasively quantify bone marrow fat (BMF), which has been known to be associated with osteoporosis from histomorphometric studies. Using MRS along with dual energy x-ray absorptiometry, studies have reported a detrimental role of BMF on BMD. With the increase in aging and obesity of the population, it is important to continue this effort in identifying the contribution of adipose tissues to bone quality and fracture. PMID:21374105

  2. [Epigenetic Regulation by Androgen Receptor and Possible Function in Bone Metabolism].

    PubMed

    Imai, Yuuki

    2016-07-01

    Epigenetic regulation underlying AR(Androgen receptor)mediated transcription is important component to understand pathophysiology of osteoporosis in men. In this commentary, it is reported recent findings related to epigenetic landscape governed by AR and its cofactors including lysine-specific demethylase 1 (LSD1), and possible implication for bone metabolism. PMID:27346313

  3. Endothelial Barrier and Metabolism: New Kids on the Block Regulating Bone Marrow Vascular Niches.

    PubMed

    Harjes, Ulrike; Verfaillie, Catherine; Carmeliet, Peter

    2016-05-01

    The vasculature of the bone marrow remains poorly characterized, yet crucial to maintain hematopoiesis and retain stem cells in a quiescent state. A recent study by Itkin et al. (2016) in Nature reports how vascular barrier integrity and endothelial cell metabolism regulate hematopoietic stem cell quiescence and leukocyte trafficking. PMID:27165553

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

    PubMed

    Terzi, Rabia; Yılmaz, Zahide

    2016-07-01

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

  5. Effect of simulated weightlessness and chronic 1,25-dihydroxyvitamin D administration on bone metabolism

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Globus, R. K.; Levens, M. J.; Wronski, T. J.; Morey-Holton, E.

    1985-01-01

    Weightlessness, as experienced during space flight, and simulated weightlessness induce osteopenia. Using the suspended rat model to simulate weightlessness, a reduction in total tibia Ca and bone formation rate at the tibiofibular junction as well as an inhibition of Ca-45 and H-3-proline uptake by bone within 5-7 days of skeletal unloading was observed. Between days 7 and 15 of unloading, uptake of Ca-45 and H-3-proline, and bone formation rate return to normal, although total bone Ca remains abnormally low. To examine the relationship between these characteristic changes in bone metabolism induced by skeletal unloading and vitamin D metabolism, the serum concentrations of 25-hydroxyvitamin D (25-OH-D), 24, 25-dihydroxyvitamin D (24,25(OH)2D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) at various times after skeletal unloading were measured. The effect of chronic infusion of 1,25(OH)2D3 on the bone changes associated with unloading was also determined.

  6. A systematic review of psychosocial factors affecting survival after bone marrow transplantation.

    PubMed

    Hoodin, Flora; Weber, Shauncie

    2003-01-01

    An electronic database search identified 15 studies of psychosocial factors affecting survival after bone marrow transplantation. The studies were assessed for methodological quality by two reviewers using the procedures of Bland and colleagues. Although some studies found that psychological variables affect survival after bone marrow transplantation, the reviewers' analysis of the methodologically sound studies suggested that survival after bone marrow transplantation is not substantively affected by depressed mood or other psychopathology in adults or by social support in adults or children. Longer survival may be related to lower "anxious preoccupation," higher "fighting spirit," and better quality of life ratings before and soon after transplant in adults. Overall, however, the literature is insufficiently developed to provide definitive evidence for a relationship between psychological variables and survival after bone marrow transplantation. Future primary studies in this area should be designed to maximize replicability and generalizability. PMID:12724499

  7. Bone Metabolism in a Large Cohort of Patients with Systemic Sclerosis.

    PubMed

    Caimmi, Cristian; Caramaschi, Paola; Barausse, Giovanni; Orsolini, Giovanni; Idolazzi, Luca; Gatti, Davide; Viapiana, Ombretta; Adami, Silvano; Biasi, Domenico; Rossini, Maurizio

    2016-07-01

    The aim of this study was to evaluate in a large size cohort of SSc patients bone mineral density (BMD) and to analyze its possible determinants. 106 consecutive outpatients affected by SSc were enrolled and completely evaluated for bone metabolism and SSc characteristics. For the statistical analysis, we preferred Z score to BMD or T score since the population was composed of patients of different ages and of both sexes. Mean neck Z score was significantly lower than 0. No significant differences were found for other sites. Female patients were shown to have a total femur and neck Z score significantly lower than 0 (p = 0.028 and p < 0.001, respectively). 13 % of patients had at least one morphometric non-clinical vertebral fracture. In univariate analysis, total femur Z score was lower in female (p = 0.050) and positively correlates with BMI (p = 0.001), neck Z score positively correlates with age (p = 0.016), and whole body Z score positively correlates with BMI (p < 0.001). No correlations were found for lumbar Z score. The multivariate analysis confirmed the positive correlation between BMI and total femur and whole body Z score and between age and neck femur Z score (p = 0.005, p < 0.001 and p = 0.040, respectively). Lung involvement was shown to correlate with a lower whole body Z score in multivariate analysis (p = 0.037). We found a modest risk of low BMD in patients with SSc and the important protective role of BMI. Patients with lung involvement showed lower whole body Z score. PMID:26898382

  8. Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model

    NASA Technical Reports Server (NTRS)

    Navidi, Meena; Wolinsky, Ira; Fung, Paul; Arnaud, Sara B.

    1995-01-01

    High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% Ca (LoCa). Final body weights were 9-11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNA diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11-18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absoption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.

  9. Effects of mixed subchronic lead acetate and cadmium chloride on bone metabolism in rats

    PubMed Central

    Yuan, Guiping; Lu, Hongke; Yin, Zhongqiong; Dai, Shujun; Jia, Renyong; Xu, Jiao; Song, Xu; Li, Li

    2014-01-01

    This study aimed to determine the effects of administering a mixture of subchronic lead acetate (Pb (NO3)2) and cadmium chloride (CdCl2·2.5H2O) on the bone metabolism of rats. A control group and three experimental groups consisted of randomly selected rats. Rats in each experimental group were orally administered with a mixture of Pb (NO3)2 and CdCl2·2.5H2O with the following respective doses for 90 consecutive days: 0 mg/kg body weight b.w. (Group I, to serve as a control), 29.96 mg/kg b.w. (Group II, 29.25 + 0.71), 89.88 mg/kg b.w. (Group III, 87.74 + 2.14), and 269.65 mg/kg b.w. (Group IV, 263.23 + 6.42). Serum osteocalcin (OC) and bone-specific alkaline phosphates (BALP) were considered as bone-formation markers, whereas carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in serum acted as bone resorption markers. Calcitonin (CT) and parathormone (PTH) were tested as calciotropic hormones markers. The (Ca) and phosphorus (Pi) concentrations in the serum and urine were determined. These results were indicated by a significant (P < 0.05 - P < 0.01) increase in BALP, CTX, and PTH concentrations and decrease in CT and OC concentrations. Moreover, the concentrations of Ca and Pi in the serum were decreased, whereas those in urine increased. Results indicated that the administration of Pb and Cd induced bone metabolism disorders by decreasing bone formation and increasing bone resorption to destroy the hormonal regulation of mineral metabolism as a result of Ca and Pi imbalance. PMID:24995099

  10. [Inflammatory bowel disease and bone decreased bone mineral density].

    PubMed

    Hisamatsu, Tadakazu; Wada, Yasuyo; Kanai, Takanori

    2015-11-01

    Metabolic bone diseases such as osteopenia and osteoporosis increase the risk of bone fracture that negatively affects quality of life of individuals. Patients with inflammatory bowel disease(IBD), including ulcerative colitis(UC)and Crohn's disease(CD), have been shown to be at increased risk of decreased bone mineral density, however frequency of metabolic bone disease in IBD and identified risk factors are varied among reports. PMID:26503868

  11. Gaucher disease: the role of the specialist on metabolic bone diseases

    PubMed Central

    Masi, Laura; Brandi, Maria Luisa

    2015-01-01

    Summary According to European legislation, a disease can be considered rare or “orphan” when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible. PMID:26604943

  12. The unsolved case of "bone-impairing analgesics": the endocrine effects of opioids on bone metabolism.

    PubMed

    Coluzzi, Flaminia; Pergolizzi, Joseph; Raffa, Robert B; Mattia, Consalvo

    2015-01-01

    The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density. PMID:25848298

  13. Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice.

    PubMed

    Ohshima, T; Schiffmann, R; Murray, G J; Kopp, J; Quirk, J M; Stahl, S; Chan, C C; Zerfas, P; Tao-Cheng, J H; Ward, J M; Brady, R O; Kulkarni, A B

    1999-05-25

    Fabry disease is an X-linked metabolic disorder caused by a deficiency of alpha-galactosidase A (alpha-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with alpha-galactosyl moieties consisting predominantly of globotriaosylceramide (Gb3). In patients with this disorder, glycolipid deposition in endothelial cells leads to renal failure and cardiac and cerebrovascular disease. Recently, we generated alpha-Gal A gene knockout mouse lines and described the phenotype of 10-week-old mice. In the present study, we characterize the progression of the disease with aging and explore the effects of bone marrow transplantation (BMT) on the phenotype. Histopathological analysis of alpha-Gal A -/0 mice revealed subclinical lesions in the Kupffer cells in the liver and macrophages in the skin with no gross lesions in the endothelial cells. Gb3 accumulation and pathological lesions in the affected organs increased with age. Treatment with BMT from the wild-type mice resulted in the clearance of accumulated Gb3 in the liver, spleen, and heart with concomitant elevation of alpha-Gal A activity. These findings suggest that BMT may have a potential role in the management of patients with Fabry disease. PMID:10339603

  14. Biochemical markers for assessment of calcium economy and bone metabolism: application in clinical trials from pharmaceutical agents to nutritional products.

    PubMed

    Bonjour, Jean-Philippe; Kohrt, Wendy; Levasseur, Régis; Warren, Michelle; Whiting, Susan; Kraenzlin, Marius

    2014-12-01

    Nutrition plays an important role in osteoporosis prevention and treatment. Substantial progress in both laboratory analyses and clinical use of biochemical markers has modified the strategy of anti-osteoporotic drug development. The present review examines the use of biochemical markers in clinical research aimed at characterising the influence of foods or nutrients on bone metabolism. The two types of markers are: (i) specific hormonal factors related to bone; and (ii) bone turnover markers (BTM) that reflect bone cell metabolism. Of the former, vitamin D metabolites, parathyroid hormone, and insulin-like growth factor-I indicate responses to variations in the supply of bone-related nutrients, such as vitamin D, Ca, inorganic phosphate and protein. Thus modification in bone remodelling, the key process upon which both pharmaceutical agents and nutrients exert their anti-catabolic or anabolic actions, is revealed. Circulating BTM reflect either osteoclastic resorption or osteoblastic formation. Intervention with pharmacological agents showed that early changes in BTM predicted bone loss and subsequent osteoporotic fracture risk. New trials have documented the influence of nutrition on bone-tropic hormonal factors and BTM in adults, including situations of body-weight change, such as anorexia nervosa, and weight loss by obese subjects. In osteoporosis-prevention studies involving dietary manipulation, randomised cross-over trials are best suited to evaluate influences on bone metabolism, and insight into effects on bone metabolism may be gained within a relatively short time when biochemical markers are monitored. PMID:25394580

  15. Regulation of heme metabolism in normal and sideroblastic bone marrow cells in culture

    SciTech Connect

    Ibraham, N.G.; Lutton, J.D.; Hoffman, R.; Levere, R.D.

    1985-05-01

    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 /sup 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 /sup 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.

  16. [Relationships of hormones of adipose tissue and ghrelin to bone metabolism].

    PubMed

    Zofková, I

    2009-06-01

    Body adipose tissue influences bone metabolism through mechanical load, as well as via hormones released into circulation. Such hormones are adipocytokines--leptin, adiponectin, TNF-alpha, IL-6, resistin and visfatin. Some of them exert an osteoanabolic effect, while the others activate bone resorption. An increasingly discussed adipocytokine is leptin, which fundamental role is regulation of food intake ensuring survival of the organism during starvation. Leptin also stimulates osteoblasts and activates bone formation. The direct osteotropic effect of leptin is modulated by interaction with hypothalamic centers and neurohormones. Apparently, the most important leptin sensitive pathway involved in bone regulation is the beta-adrenergic system. While activation of beta-1-adrenergic receptors by leptin enhances bone formation, activation of beta-2-adrenergic receptors in hypothalamus and in the skeleton increases bone resorption. In humans, an anabolic effect on the skeleton prevails. In pubertal girls, leptin extensively released into circulation at the moment when adipose tissue reaches a critical volume, stimulates synthesis of GnRH and induces puberty, which is followed by striking increases in bone mass. Low leptin levels in anorexia nervosa are associated with amenorrhoea, which slows down increase of bone mass and may induce osteopenia. Important adipocytokine with an unambiguous negative effect on bone is adiponectin. Decreased production of this hormone explains in part the lower prevalence of osteoporosis in obese persons. In this article, the osteotropic importance ofleptin-sensitive neurohormonal mechanisms and other hormones related to adipose tissue are discussed. Clinical importance of the above mentioned hormones to integrity of the skeleton has not yet been verified. PMID:19662887

  17. Metabolic and structural bone disturbances induced by hyperlipidic diet in mice treated with simvastatin.

    PubMed

    Soares, Evelise Aline; Novaes, Rômulo Dias; Nakagaki, Wilson Romero; Fernandes, Geraldo José Medeiros; Garcia, José Antônio Dias; Camilli, José Angelo

    2015-08-01

    Simvastatin can modulate lipid and bone metabolism. However, information related to the interaction between diet and simvastatin on bone structure and biomechanics is scarce. Thus, this study evaluated the effects of simvastatin on femoral biomechanics and cortical/trabecular bone structure in wild-type mice nourished with a hyperlipidic diet. Three-month-old male wild-type mice (C57BL6 strain) were divided into four groups: (1) group W, nourished with a standard diet; (2) group WH, fed a hyperlipidic diet; (3) group WS, nourished with a standard diet plus oral simvastatin (20 mg/kg/day); and (4) group WHS, fed a hyperlipidic diet plus oral simvastatin (20 mg/kg/day). All animals received only their specific diet and water for 60 days. Blood samples were collected for the analysis of calcium, triglycerides, total cholesterol (TC) and fraction serum levels. Diet manipulation was able to induce a dyslipidaemic status in mice, characterized by triglyceride and TC rise in WH animals. Simvastatin prevented hypercholesterolaemia and reduced TC and LDL serum levels, but did not prevent hypertriglyceridaemia and HDL serum levels in the WHS group. In the WH mice the hyperlipidaemia was associated with reduction in trabecular bone thickness, femur structural and material property alterations. Simvastatin prevented these morphological alterations and minimized femur biomechanical changes in WHS mice. Taken together, the results indicated that the hyperlipidic diet intake acts as a risk factor for bone integrity, generating bones with reduced resistance and more susceptible to fractures, an effect attenuated by simvastatin that is potentially related to the modulatory action of this drug on lipid and bone metabolism. PMID:26175225

  18. Assessment of metabolic bone diseases by quantitative computed tomography

    SciTech Connect

    Richardson, M.L.; Genant, H.K.; Cann, C.E.; Ettinger, B.; Gordan, G.S.; Kolb, F.O.; Reiser, U.J.

    1985-05-01

    Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid- induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements.

  19. [Musculoskeletal rehabilitation and bone. Abnormal bone metabolism in female elite athletes].

    PubMed

    Enatsu, Akiko

    2010-04-01

    Recently, female athletes are particularly well, the other hand, many athletes suffer from amenorrhea due to excessive training. Especially, in sports with weight restrictions, they suffer from "Female athlete triad" , eating disorders, amenorrhea and osteoporosis. Amenorrhea is nothing else than a lack of estrogen, action on bone resorption and promote bone formation, by neglect this, it lead to osteoporosis and a stress fracture, and they would often give up their career as elite athletes. So we should consider it as serious sports injury. The problems of amenorrhea is should be recognized as a deficiency of estrogen. A Case of amenorrhea in female athletes, it is necessary to consider the hormone replacement therapy based on the appropriate diagnosis. However, it is important to start the management of body fat and body weight and strength of exercises since adolescent for the prevention the amenorrhea. PMID:20354328

  20. Leptin expression affects metabolic rate in zebrafish embryos (D. rerio)

    PubMed Central

    Dalman, Mark R.; Liu, Qin; King, Mason D.; Bagatto, Brian; Londraville, Richard L.

    2013-01-01

    We used antisense morpholino oligonucleotide technology to knockdown leptin-(A) gene expression in developing zebrafish embryos and measured its effects on metabolic rate and cardiovascular function. Using two indicators of metabolic rate, oxygen consumption was significantly lower in leptin morphants early in development [<48 hours post-fertilization (hpf)], while acid production was significantly lower in morphants later in development (>48 hpf). Oxygen utilization rates in <48 hpf embryos and acid production in 72 hpf embryos could be rescued to that of wildtype embryos by recombinant leptin coinjected with antisense morpholino. Leptin is established to influence metabolic rate in mammals, and these data suggest leptin signaling also influences metabolic rate in fishes. PMID:23847542

  1. Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats

    PubMed Central

    NAGURA, NANA; KOMATSU, JUN; IWASE, HIDEAKI; HOSODA, HIROSHI; OHBAYASHI, OSAMU; NAGAOKA, ISAO; KANEKO, KAZUO

    2015-01-01

    The purpose of the present study was to evaluate the combined effects of vitamin K (VK) and teriparatide (TPTD) on bone mineral density (BMD), mechanical strength and other parameters for bone metabolism using a rat ovariectomized osteoporosis model. Ovariectomized female Sprague-Dawley rats were administered with VK (an oral dose of 30 mg/kg/day), TPTD (a subcutaneous dose of 30 µg/kg, three times a week) or a combination for 8 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA; BMD and mechanical strength were measured by computed tomography and biomechanical testing, respectively at the femoral metaphysis. Additionally, histomorphometry was performed using the toluidine blue-stained coronal sections of distal femur. The combination of VK and TPTD clearly increased the serum levels of Gla-OC (a specific marker for bone formation) and osteoblast surface (the number of osteoblasts attaching with the surface of cancellous bone), compared to VK or TPTD alone. In addition, the combination of the two agents improved the BMD and bone strength of the femur in the ovariectomized rats, compared to VK or TPTD alone. Taken together, these findings suggest that the treatment with VK and TPTD may have a therapeutic advantage over VK or TPTD monotherapy for postmenopausal osteoporosis, possibly by enhancing the bone formation through the actions on OC and osteoblasts. PMID:26137225

  2. Sex‐specific responses of bone metabolism and renal stone risk during bed rest

    PubMed Central

    Morgan, Jennifer L. L.; Heer, Martina; Hargens, Alan R.; Macias, Brandon R.; Hudson, Edgar K.; Shackelford, Linda C.; Zwart, Sara R.; Smith, Scott M.

    2014-01-01

    Abstract The purpose of this study was to directly assess sex differences in bone loss, bone biochemistry, and renal stone risk in bed rest. Bed rest simulates some spaceflight effects on human physiology and can be used to address the potential existence of sex‐specific effects on bone metabolism and renal stone risk in space. We combined data from the control subjects in five head‐down‐tilt bed rest studies (combined n = 50 men, 24 women) of differing durations (14–90 days). All subjects were healthy volunteers. Mean age was 35 ± 9 years for women and 33 ± 8 years for men. The main outcome measures were bone density and biochemistry, and renal stone risk chemistry. Before bed rest began, men had higher bone mineral density and content (P < 0.001), and excreted more biomarkers of bone resorption and calcium per day than did women (P < 0.05). These differences remained during bed rest. A number of urine chemistry analytes increased (e.g., calcium) or decreased (e.g., sodium, citrate, and urine volume) significantly for men and women during bed rest. These changes may predispose men to higher stone risk. Men and women do not have substantially different responses to the skeletal unloading of bed rest. PMID:25107989

  3. Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease

    SciTech Connect

    Garnero, P.; Delmas, P.D.

    1993-10-01

    The authors measured serum bone alkaline phosphatase (B-ALP) with a new immunoradiometric assay (IRMA) in a large sample of healthy controls comprising 173 women and 180 men, 20-88 yr of age, and in patients with metabolic bone disease. Using serum samples from patients with liver disease and patients with Paget's disease with elevated total alkaline phosphatase (T-ALP) as a source of, respectively, liver and bone isoenyzmes, they determined a liver cross-reactivity of the IRMA of 16% that was confirmed by electrophoresis of the circulating alkaline phosphatase isoenzymes. The IRMA was linear for serial sample dilutions, the recovery ranged from 89-110%, and the intra- and interassay variations were below 7% and 9%, respectively. B-ALP increased linearly with age in both sexes, and the mean B-ALP serum levels were not significantly different for women and men (11.3 [+-] 4.8 ng/mL for women; 11.0 [+-] 4.0 ng/mL for men). The increase in B-ALP after the menopause was significantly higher than that in T-ALP (+77% vs. +24%; P<0.001). When the values of postmenopausal women were expressed as the SD from the mean of premenopausal women, the mean Z scores were 2.2[+-] 1.8 for B-ALP and 0.9 [+-] 1.3 for T-ALP (P<0.001 between the two).

  4. How does metabolism affect cell death in cancer?

    PubMed

    Villa, Elodie; Ricci, Jean-Ehrland

    2016-07-01

    In cancer research, identifying a specificity of tumor cells compared with 'normal' proliferating cells for targeted therapy is often considered the Holy Grail for researchers and clinicians. Although diverse in origin, most cancer cells share characteristics including the ability to escape cell death mechanisms and the utilization of different methods of energy production. In the current paradigm, aerobic glycolysis is considered the central metabolic characteristic of cancer cells (Warburg effect). However, recent data indicate that cancer cells also show significant changes in other metabolic pathways. Indeed, it was recently suggested that Kreb's cycle, pentose phosphate pathway intermediates, and essential and nonessential amino acids have key roles. Renewed interest in the fact that cancer cells have to reprogram their metabolism in order to proliferate or resist treatment must take into consideration the ability of tumor cells to adapt their metabolism to the local microenvironment (low oxygen, low nutrients). This variety of metabolic sources might be either a strength, resulting in infinite possibilities for adaptation and increased ability to resist chemotherapy-induced death, or a weakness that could be targeted to kill cancer cells. Here, we discuss recent insights showing how energetic metabolism may regulate cell death and how this might be relevant for cancer treatment. PMID:26498911

  5. Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism.

    PubMed

    Abruzzese, Giselle Adriana; Heber, Maria Florencia; Ferreira, Silvana Rocio; Velez, Leandro Martin; Reynoso, Roxana; Pignataro, Omar Pedro; Motta, Alicia Beatriz

    2016-07-01

    Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. PMID:27179108

  6. Bone mineral density and biochemical markers of bone metabolism in predialysis patients with chronic kidney disease.

    PubMed

    Fidan, Nuri; Inci, Ayca; Coban, Melahat; Ulman, Cevval; Kursat, Seyhun

    2016-04-01

    The aim of the study was to evaluate the usefulness of serum bone turnover markers (BTM) and bone mineral density (BMD) determined by dual-energy X-ray absorptiometry (DEXA) in predialysis patients with chronic kidney disease (CKD). We enrolled 83 patients with CKD, 41 (49.4%) males, 42 (50.6%) females, with mean estimated glomerular filtration rate (eGFR) 23.90±12 (range=6.0-56.0). BMD of the lumbar spine (LS) (anteroposterior, L2 through L4), femoral neck (FN) and femoral trochanter (FT) were measured by DEXA. Biochemical BTM, including calcium (Ca), phosphorus (P), intact parathyroid hormone (PTH), serum specific alkaline phosphatase (serum AP), bone-specific AP (BSAP), plasma bicarbonate and 25-hydroxy-vitamin D (25hD) were used for the prediction of BMD loss. T score results of LS and FN were worse than FT. BMD levels were lower in females than in males (all p<0.05). According to different BMD T score levels, patients with age ≥65 years and patients in menopause were significantly more osteopenic (p=0.026) and there was no relation between different BMD T scores and presence of diabetes (p=0.654). A positive correlation was identified between the BMD of FN T-Z scores (r=0.270, p=0.029, r=0.306, p=0.012), FT T-Z scores (r=0.220, p=0.076, r:0.250, p=0.043) and serum HCO3, while the correlation with serum alkaline phosphatase (AP) and BSAP was considered to be negative. No statistically significant association was found between BMD of all the measured skeletal sites and eGFR. Loss of BMD was identified mostly in females over ≥65 years of age and after menopause. Higher serum levels of BSAP and AP can be determined in the advanced stages of renal failure and they reflect fracture risk of the femur, but not spine. Measurements of BMD by DEXA are useful to demonstrate bone loss, but not technical enough to distinguish the quantity of bone loss between different stages of CKD. PMID:26969749

  7. Assessment of metabolic bone diseases by quantitative computed tomography

    NASA Technical Reports Server (NTRS)

    Richardson, M. L.; Genant, H. K.; Cann, C. E.; Ettinger, B.; Gordan, G. S.; Kolb, F. O.; Reiser, U. J.

    1985-01-01

    Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid-induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements. Knowledge of appendicular cortical mineral status is important in its own right but is not a valid predictor of axial trabecular mineral status, which may be disproportionately decreased in certain diseases. Quantitative CT provides a reliable means of assessing the latter region of the skeleton, correlates well with the spinal fracture index (a semiquantitative measurement of end-organ failure), and offers the clinician a sensitive means of following the effects of therapy.

  8. The bone resorption inhibitors odanacatib and alendronate affect post-osteoclastic events differently in ovariectomized rabbits.

    PubMed

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L; Duong, Le T; Delaissé, Jean-Marie

    2014-02-01

    Odanacatib (ODN) is a bone resorption inhibitor which differs from standard antiresorptives by its ability to reduce bone resorption without decreasing bone formation. What is the reason for this difference? In contrast with other antiresorptives, such as alendronate (ALN), ODN targets only the very last step of the resorption process. We hypothesize that ODN may therefore modify the remodeling events immediately following osteoclastic resorption. These events belong to the reversal phase and include recruitment of osteoblasts, which is critical for connecting bone resorption to formation. We performed a histomorphometric study of trabecular remodeling in vertebrae of estrogen-deficient rabbits treated or not with ODN or ALN, a model where ODN, but not ALN, was previously shown to preserve bone formation. In line with our hypothesis, we found that ODN treatment compared to ALN results in a shorter reversal phase, faster initiation of osteoid deposition on the eroded surfaces, and higher osteoblast recruitment. The latter is reflected by higher densities of mature bone forming osteoblasts and an increased subpopulation of cuboidal osteoblasts. Furthermore, we found an increase in the interface between osteoclasts and surrounding osteoblast-lineage cells. This increase is expected to favor the osteoclast-osteoblast interactions required for bone formation. Regarding bone resorption itself, we show that ODN, but not ALN, treatment results in shallower resorption lacunae, a geometry favoring bone stiffness. We conclude that, compared to standard antiresorptives, ODN shows distinctive effects on resorption geometry and on reversal phase activities which positively affect osteoblast recruitment and may therefore favor bone formation. PMID:24085265

  9. The Association between Metabolic Syndrome, Bone Mineral Density, Hip Bone Geometry and Fracture Risk: The Rotterdam Study

    PubMed Central

    Muka, Taulant; Trajanoska, Katerina; Kiefte-de Jong, Jessica C.; Oei, Ling; Uitterlinden, André G; Hofman, Albert; Dehghan, Abbas; Zillikens, M. Carola; Franco, Oscar H.; Rivadeneira, Fernando

    2015-01-01

    The association between metabolic syndrome (MS) and bone health remains unclear. We aimed to study the association between MS and hip bone geometry (HBG), femoral neck bone mineral density (FN-BMD), and the risk of osteoporosis and incident fractures. Data of 2040 women and 1510 men participants in the third visit (1997–1999) of the Rotterdam Study (RSI-3), a prospective population based cohort, were available (mean follow-up 6.7 years). MS was defined according to the recent harmonized definition. HBG parameters were measured at the third round visit whereas FN-BMD was assessed at the third round and 5 years later. Incident fractures were identified from medical registry data. After correcting for age, body mass index (BMI), lifestyle factors and medication use, individuals with MS had lower bone width (β = -0.054, P = 0.003), lower cortical buckling ratio (β = -0.81, P = 0.003) and lower odds of having osteoporosis (odds ratio =0.56, P = 0.007) in women but not in men. Similarly, MS was associated with higher FN-BMD only in women (β = 0.028, P=0.001). In the analyses of MS components, the glucose component (unrelated to diabetes status) was positively associated with FN-BMD in both genders (β = 0.016, P = 0.01 for women and β = 0.022, P = 0.004 for men). In men, waist circumference was inversely associated with FN-BMD (β = -0.03, P = 0.004). No association was observed with fracture risk in either sex. In conclusion, women with MS had higher FN-BMD independent of BMI. The glucose component of MS was associated with high FN-BMD in both genders, highlighting the need to preserve glycemic control to prevent skeletal complications. PMID:26066649

  10. Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming

    PubMed Central

    Li, Heng-Hong; Wang, Yi-wen; Chen, Renxiang; Zhou, Bin; Ashwell, Jonathan D.; Fornace, Albert J.

    2015-01-01

    Ionizing radiation has a variety of acute and long-lasting adverse effects on the immune system. Whereas measureable effects of radiation on immune cell cytotoxicity and population change have been well studied in human and animal models, little is known about the functional alterations of the surviving immune cells after ionizing radiation. The objective of this study was to delineate the effects of radiation on T cell function by studying the alterations of T cell receptor activation and metabolic changes in activated T cells isolated from previously irradiated animals. Using a global metabolomics profiling approach, for the first time we demonstrate that ionizing radiation impairs metabolic reprogramming of T cell activation, which leads to substantial decreases in the efficiency of key metabolic processes required for activation, such as glucose uptake, glycolysis, and energy metabolism. In-depth understanding of how radiation impacts T cell function highlighting modulation of metabolism during activation is not only a novel approach to investigate the pivotal processes in the shift of T cell homeostasis after radiation, it also may lead to new targets for therapeutic manipulation in the combination of radiotherapy and immune therapy. Given that appreciable effects were observed with as low as 10 cGy, our results also have implications for low dose environmental exposures. PMID:26078715

  11. Biochemical markers of bone metabolism in children with cow's milk allergy

    PubMed Central

    Rowicka, Grażyna; Chelchowska, Magdalena; Gajewska, Joanna; Strucińska, Małgorzata; Laskowska-Klita, Teresa

    2013-01-01

    Introduction Patients with cow's milk allergy (CMA) and following a cow milk protein-free diet for a long time are potentially at risk of developing bone abnormalities. To assess the balance between bone formation and resorption processes, we determined serum concentrations of osteocalcin (OC), bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX), fetuin-A, osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in children with CMA. Material and methods The study included 50 prepubertal children with diagnosed cow's milk allergy, who were under systematic medical and nutritional care at the Institute of Mother and Child and 40 healthy counterparts as a control group. The concentrations of bone metabolism markers were determined by immunoenzymatic assays. Results The diets of all investigated children were correct in terms of phosphorus and magnesium contents but deficient in terms of calcium and vitamin D. Serum OC and CTX as well as fetuin-A concentrations were similar in both studied groups. The BALP activity was significantly (p < 0.05) higher in children with cow's milk allergy than in the controls. Serum OPG concentration was comparable in both groups, but the RANKL level was higher (p < 0.05) in CMA children than in healthy ones. Hence, the ratio of OPG/RANKL was lower in children with CMA. Conclusions Our study demonstrates slight disturbances in the profile of bone metabolism markers in growing children with CMA. The increase in RANKL level and decrease in OPG/RANKL ratio may contribute to intensification of bone resorption in these patients. PMID:25624850

  12. Bone Mass and Mineral Metabolism Alterations in Adult Celiac Disease: Pathophysiology and Clinical Approach

    PubMed Central

    Di Stefano, Michele; Mengoli, Caterina; Bergonzi, Manuela; Corazza, Gino Roberto

    2013-01-01

    Osteoporosis affects many patients with celiac disease (CD), representing the consequence of calcium malabsorption and persistent activation of mucosal inflammation. A slight increase of fracture risk is evident in this condition, particularly in those with overt malabsorption and in postmenopausal state. The adoption of a correct gluten-free diet (GFD) improves bone derangement, but is not able to normalize bone mass in all the patients. Biomarkers effective in the prediction of bone response to gluten-free diet are not yet available and the indications of guidelines are still imperfect and debated. In this review, the pathophysiology of bone loss is correlated to clinical aspects, defining an alternative proposal of management for this condition. PMID:24284619

  13. Bone mass and mineral metabolism alterations in adult celiac disease: pathophysiology and clinical approach.

    PubMed

    Di Stefano, Michele; Mengoli, Caterina; Bergonzi, Manuela; Corazza, Gino Roberto

    2013-11-01

    Osteoporosis affects many patients with celiac disease (CD), representing the consequence of calcium malabsorption and persistent activation of mucosal inflammation. A slight increase of fracture risk is evident in this condition, particularly in those with overt malabsorption and in postmenopausal state. The adoption of a correct gluten-free diet (GFD) improves bone derangement, but is not able to normalize bone mass in all the patients. Biomarkers effective in the prediction of bone response to gluten-free diet are not yet available and the indications of guidelines are still imperfect and debated. In this review, the pathophysiology of bone loss is correlated to clinical aspects, defining an alternative proposal of management for this condition. PMID:24284619

  14. New brittle bone disorder: report of a family with six affected individuals.

    PubMed

    Nishimura, G; Haga, N; Aoki, K; Hamazaki, M; Taniguchi, K; Iwaya, T

    1999-06-01

    We report on a family in which four females and two males in three generations had a previously undescribed brittle bone disorder that was dominantly transmitted through a maternal line. The cardinal manifestations of the disorder comprised dolichocephaly with frontal bossing, hypoplasia of the midface, postpubertal prognathism, micromelic short stature, coarse trabeculae of the entire skeleton, and bone fragility of variable degrees. Mild spondylar modification and iliac hypoplasia were other hallmarks that were recognized in childhood. The proband, a 19-year-old male, was most severely affected with multiple wormian bones in the calvaria, repetitive fractures, intractable bowing of the legs and forearms, and pseudofractures of the long bones with metaphyseal narrowing. His male cousin was next severely affected with angular deformity restricted to the forearm. The four females were much less affected without angular deformity. The mode of inheritance was thus consistent with either an autosomal dominant trait with sex-influence or an X-linked semidominant trait. Histological bone examination in the proband showed atrophy and fibrous degeneration of the lamellar trabeculae and disorganized chondro-osseous junction, which implied that the disorder involved both intramembranous and enchondral ossifications. PMID:10340645

  15. Natural toxins that affect plant amino acid metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A diverse range of natural compounds interfere with the synthesis and other aspects of amino acid metabolism. Some are amino acid analogues, but most are not. This review covers a number of specific natural phytotoxic compounds by molecular target site. Inhibition of glutamine synthetase is of part...

  16. The Role of Nutrition in the Changes in Bone and Calcium Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily R.; Arnaud, Sara B.

    1995-01-01

    On Earth, the primary purpose of the skeleton is provide structural support for the body. In space, the support function of the skeleton is reduced since, without gravity, structures have only mass and no weight. The adaptation to space flight is manifested by shifts in mineral distribution, altered bone turnover, and regional mineral deficits in weight-bearing bones. The shifts in mineral distribution appear to be related to the cephalic fluid shift. The redistribution of mineral from one bone to another or to and from areas in the same bone in response to alterations in gravitational loads is more likely to affect skeletal function than quantitative whole body losses and gains. The changes in bone turnover appear dependent upon changes in body weight with weight loss tending to increase bone resorption as well as decrease bone formation. During bedrest, the bone response to unloading varies depending upon the routine activity level of the subjects with more active subjects showing a greater suppression of bone formation in the iliac crest with inactivity. Changes in body composition during space flight are predicted by bedrest studies on Earth which show loss of lean body mass and increase tn body fat in adult males after one month. In ambulatory studies on Earth, exercising adult males of the same age, height, g weight, body mass index, and shoe size show significantly higher whole body mineral and lean body mass. than non-exercising subjects. Nutritional preference appears to change with activity level. Diet histories in exercisers and nonexercisers who maintain identical body weights show no differences in nutrients except for slightly higher carbohydrate intake in the exercisers. The absence of differences in dietary calcium in men with higher total body calcium is noteworthy. In this situation, the increased bone mineral content was facilitated by the calcium endocrine system. This regulatory system can be by-passed by raising dietary calcium. Increased

  17. Pinto Bean Hull Extract Supplementation Favorably Affects Markers of Bone Metabolism and Bone Structure in Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dry edible beans (Phaseolus vulgaris) have many health benefits attributed to their high content of protein, non-digestible starches, fiber, and other bioactive components. Hulls from dry beans are rich in phenolics known to possess antioxidant activity that is beneficial to human health. The object...

  18. Effect of subchronic exposure to tetradifon on bone remodelling and metabolism in female rat.

    PubMed

    Badraoui, Riadh; Abdelmoula, Nouha Bouayed; Sahnoun, Zouhaier; Fakhfakh, Zouhaier; Rebai, Tarek

    2007-12-01

    This study investigates the effect of subchronic exposure to tetradifon, an organochlorine pesticide with an oestrogen-like structure, in female rat. A single cumulative dose of 2430 mg/kg BW was administrated orally for 12 female rats of 190 g BW. Twelve non-treated additional rats have served as controls. Animals were sacrificed after 6 and 12 weeks of treatment. We studied bone remodelling through histomorphometry and scanning electron microscopy (SEM) analyses. The serum and the right femora were used to determine phosphatase alkaline (AlkP) and/or calcium and phosphorus content. No sign of toxicity was observed until the end of the experiment. The SEM results revealed no structural alteration of the treated animal bone tissue. However, in both treated groups, we have noted an increase in the trabecular distance and a heterogeneous aspect of the endosteum that could be explained by bone-remodelling disturbance, with relative delay of ossification. Following histomorphomotric analysis, these results were coupled with significant increases in Tb.Th and OS/BS. Elsewhere, tetradifon intoxication increased significant serum AlkP level in the group treated for 12 weeks, which could be explained by an osteoblastic hyperactivity. Tetradifon intoxication decreased significantly bone calcium end phosphorus contents. Tetradifon seems not to exert major effects on bone remodelling. However, the osteoblastic hyperactivity could be explained by the oestrogen-like activity of tetradifon and its fatty metabolism. In fact, oestrogen inhibits bone remodelling, and enhances bone formation, which could result in an increase of the osteoid surface and explain the relative delay of ossification. PMID:18068648

  19. Effects of artificial gravity during bed rest on bone metabolism in humans

    PubMed Central

    Smith, S. M.; Zwart, S. R.; Heer, M. A.; Baecker, N.; Evans, H. J.; Feiveson, A. H.; Shackelford, L. C.; LeBlanc, A. D.

    2009-01-01

    We report results from a study designed to explore the utility of artificial gravity (AG) as a countermeasure to bone loss induced by microgravity simulation. After baseline testing, 15 male subjects underwent 21 days of 6° head-down bed rest to simulate the deconditioning associated with spaceflight. Eight of the subjects underwent 1 h of centrifugation (AG; 1 Gz at the heart, 2.5 Gz at the feet) each day for 21 days, whereas seven of the subjects served as untreated controls (Con). Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density (BMD) and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry and peripheral quantitative computerized tomography before and after bed rest. Urinary excretion of bone resorption markers increased during bed rest, but the AG and Con groups did not differ significantly. The same was true for serum C-telopeptide. During bed rest, bone alkaline phosphatase (ALP) and total ALP tended to be lower in the AG group (P = 0.08, P = 0.09). Neither BMC nor BMD changed significantly from the pre-bed rest period in AG or Con groups, and the two groups were not significantly different. However, when AG and Con data were combined, there was a significant (P < 0.05) effect of time for whole body total BMC and total hip and trochanter BMD. These data failed to demonstrate efficacy of this AG prescription to prevent the changes in bone metabolism observed during 3 wk of bed rest. PMID:19074572

  20. Effects of Vibration in Forced Posture on Biochemical Bone Metabolism Indices, and Morphometric and Mechanical Properties of the Lumbar Vertebra

    PubMed Central

    Zhang, Li; Ju, Xiaowei; Zhu, Lvgang; Huang, Changlin; Huang, Tao; Zuo, Xincheng; Gao, Chunfang

    2013-01-01

    Epidemiological studies have shown a relatively strong association between occupational lower back pain (LBP) and long-term exposure to vibration. However, there is limited knowledge of the impact of vibration and sedentariness on bone metabolism of the lumbar vertebra and the mechanism of bone-derived LBP. The aim of this study was to investigate the effects of vibration in forced posture (a seated posture) on biochemical bone metabolism indices, and morphometric and mechanical properties of the lumbar vertebra, and provide a scientific theoretical basis for the mechanism of bone-derived LBP, serum levels of Ca2+, (HPO4)2−, tartrate-resistant acid phosphatase (TRAP), bone-specific alkaline phosphatase (BALP), and bone gla protein (BGP),the pathological changes and biomechanics of lumbar vertebra of New Zealand white rabbits were studied. The results demonstrate that both forced posture and vibration can cause pathological changes to the lumbar vertebra, which can result in bone-derived LBP, and vibration combined with a seated posture could cause further damage to bone metabolism. Serological changes can be used as early markers for clinical diagnosis of bone-derived LBP. PMID:24265702

  1. Cyclophilin D Knock-Out Mice Show Enhanced Resistance to Osteoporosis and to Metabolic Changes Observed in Aging Bone

    PubMed Central

    White, Noelle S; Nadtochiy, Sergiy M.; Bentley, Karen L. de Mesy; Brookes, Paul S; Jonason, Jennifer H.; Eliseev, Roman A.

    2016-01-01

    Pathogenic factors associated with aging, such as oxidative stress and hormone depletion converge on mitochondria and impair their function via opening of the mitochondrial permeability transition pore (MPTP). The MPTP is a large non-selective pore regulated by cyclophilin D (CypD) that disrupts mitochondrial membrane integrity. MPTP involvement has been firmly established in degenerative processes in heart, brain, and muscle. Bone has high energy demands and is therefore expected to be highly sensitive to mitochondrial dysfunction. Despite this, the role of mitochondria and the MPTP in bone maintenance and bone pathology has not been elucidated. Our goal was to determine whether mitochondria are impaired in aging bone and to see if protecting mitochondria from MPTP opening via CypD deletion protects against bone loss. We found that bone mass, strength, and formation progressively decline over the course of 18 months in C57BL/6J mice. Using metabolomics and electron microscopy, we determined that oxidative metabolism is impaired in aging bone leading to a glycolytic shift, imbalance in nucleotides, and decreased NAD+/NADH ratio. Mitochondria in osteocytes appear swollen which is a major marker of MPTP opening. CypD deletion by CypD knockout mouse model (CypD KO) protects against bone loss in 13- and 18-month-old mice and prevents decline in bone formation and mitochondrial changes observed in wild type C57BL/6J mice. Together, these data demonstrate that mitochondria are impaired in aging bone and that CypD deletion protects against this impairment to prevent bone loss. This implicates CypD-regulated MPTP and mitochondrial dysfunction in the impairment of bone cells and in aging-related bone loss. Our findings suggest mitochondrial metabolism as a new target for bone therapeutics and inhibition of CypD as a novel strategy against bone loss. PMID:27183225

  2. Exposure to cadmium and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women

    SciTech Connect

    Rignell-Hydbom, A.; Skerfving, S.; Lundh, T.; Lindh, C.H.; Elmstahl, S.; Bjellerup, P.; Juensson, B.A.G.; Struemberg, U.; Akesson, A.

    2009-11-15

    Environmental contaminants such as cadmium and persistent organochlorine pollutants have been proposed as risk factors of osteoporosis, and women may be at an increased risk. To assess associations between exposure to cadmium and two different POPs (2,2',4,4',5,5'-hexachlorobiphenyl CB-153, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene p,p'-DDE), on one hand, and bone effects, on the other, in a population-based study among postmenopausal (60-70 years) Swedish women with biobanked blood samples. The study included 908 women and was designed to have a large contrast of bone mineral densities, measured with a single photon absorptiometry technique in the non-dominant forearm. Biochemical markers related to bone metabolism were analyzed in serum. Exposure assessment was based on cadmium concentrations in erythrocytes and serum concentrations of CB-153 and p,p'-DDE. Cadmium was negatively associated with bone mineral density and parathyroid hormone, positively with the marker of bone resorption. However, this association disappeared after adjustment for smoking. The major DDT metabolite (p,p'-DDE) was positively associated with bone mineral density, an association which remained after adjustment for confounders, but the effect was weak. There was no evidence that the estrogenic congener (CB-153) was associated with any of the bone markers. In conclusion, no convincing associations were observed between cadmium and POPs, on one hand, and bone metabolism markers and BMD, on the other.

  3. CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation.

    PubMed

    He, Haitao; Chai, Jianshen; Zhang, Shengfu; Ding, Linlin; Yan, Peng; Du, Wenjun; Yang, Zhenzhou

    2016-05-01

    Calcitonin-gene-related peptide (CGRP) is a neuropeptide, which is widely distributed throughout the central and peripheral nervous systems. Numerous mechanisms underlying the action of CGRP in osteoblast-associated cells have been suggested for bone growth and metabolism. The present study was designed to closely investigate the osteoblast‑ and osteoclast-associated mechanisms of the effect of CGRP administration on bone metabolism in primary osteoblasts. Primary osteoblasts were obtained from newborn rabbit calvaria and incubated with different concentrations of human CGRP (hCGRP), hCGRP and hCGRP (8‑37), or without treatment as a control. Intracellular calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) were detected following treatment, as well as the expression levels of osteoblast differentiation markers, including activating transcription factor‑4 (ATF4) and osteocalcin (OC), and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG). The isolated primary osteoblasts were found to stain positively for ALP. hCGRP treatment had no significant effect on transient intracellular Ca2+ in the osteoblasts. Treatment of the osteoblasts with hCGRP led to elevations in the expression levels of cAMP, ATF4 and OPG, and downregulation in the expression of RANKL, in a dose‑dependent manner. These effects were markedly reversed by the addition of hCGRP (8‑37). The results of the present study demonstrated that CGRP administration not only stimulated osteoblast differentiation, as demonstrated by upregulated expression levels of ATF4 and OC in the hCGRP‑treated osteoblasts, but also inhibited OPG/RANKL‑regulated osteoclastogenesis. CGRP may act as a modulator of bone metabolism through osteoblast and osteoclast-associated mechanisms, which result in osteoblast formation with subsequent activation of bone formation. PMID:27035229

  4. Deanol affects choline metabolism in peripheral tissues of mice.

    PubMed

    Haubrich, D R; Gerber, N H; Pflueger, A B

    1981-08-01

    Administration of 2-dimethylaminoethanol (deanol) to mice induced an increase in both the concentration and the rate of turnover of free choline in blood. Treatment with deanol also caused an increase in the concentration of choline in kidneys, and markedly inhibited the rates of oxidation and phosphorylation of intravenously administered [3H-methyl]choline. In the liver, deanol inhibited the rate of phosphorylation of [3H-methyl]choline, but did not inhibit its rate of oxidation or cause an increase in the level of free choline. These findings suggest that deanol increases the choline concentration in blood by inhibition of its metabolism in tissues. Deanol may ultimately produce its central cholinergic effects by inhibition of choline metabolism in peripheral tissues, causing free choline choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors. PMID:7264671

  5. Markers of Bone Metabolism in Patients With Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Pezzilli, Raffaele; Melzi d’Eril, Gian Vico; Barassi, Alessandra

    2015-01-01

    Abstract There are no studies comparing some of the most important markers, such as vitamin D, parathormone, osteocalcin, bone alkaline phosphatase, and calcium, in patients with chronic benign and malignant pancreatic diseases. Our objective was to comparatively evaluate serum markers of bone metabolism in patients with chronic pancreatitis and in those with ductal pancreatic adenocarcinoma. Sixty-three consecutive subjects were studied: 30 patients with a firm diagnosis of chronic pancreatitis and 33 having histologically confirmed pancreatic adenocarcinoma. Serum 25-hydroxyvitamin D, bone alkaline phosphatase, osteocalcin, parathormone, and calcium were determined using commercially available kits. Taking into consideration the clinical variables of all 63 patients studied, 25-hydroxyvitamin D was inversely correlated with only the body mass index (P = 0.007), whereas it was not correlated with age (P = 0.583) or fecal elastase-1 concentrations (P = 0.556). Regarding the other substances studied, parathormone was positively correlated with only the age of the patients (P = 0.015). Of the 5 substances studied, only bone alkaline phosphates were significantly different (P < 0.001) between patients with chronic pancreatitis and those with pancreatic ductal adenocarcinoma. Within the 2 groups of patients, the 23 patients with chronic pancreatitis without diabetes mellitus had serum concentrations of 25-hydroxyvitamin D significantly lower (P = 0.045) than those with chronic pancreatitis having diabetes mellitus, whereas smokers with pancreatic ductal adenocarcinoma had serum concentrations of calcium significantly higher (P < 0.001) as compared to nonsmokers. Altered bone metabolism seems to be associated with chronic diseases of the pancreas; however, the mechanism should be better elucidated. PMID:26496293

  6. Markers of Bone Metabolism in Patients With Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma.

    PubMed

    Pezzilli, Raffaele; Melzi d'Eril, Gian Vico; Barassi, Alessandra

    2015-10-01

    There are no studies comparing some of the most important markers, such as vitamin D, parathormone, osteocalcin, bone alkaline phosphatase, and calcium, in patients with chronic benign and malignant pancreatic diseases. Our objective was to comparatively evaluate serum markers of bone metabolism in patients with chronic pancreatitis and in those with ductal pancreatic adenocarcinoma. Sixty-three consecutive subjects were studied: 30 patients with a firm diagnosis of chronic pancreatitis and 33 having histologically confirmed pancreatic adenocarcinoma. Serum 25-hydroxyvitamin D, bone alkaline phosphatase, osteocalcin, parathormone, and calcium were determined using commercially available kits. Taking into consideration the clinical variables of all 63 patients studied, 25-hydroxyvitamin D was inversely correlated with only the body mass index (P = 0.007), whereas it was not correlated with age (P = 0.583) or fecal elastase-1 concentrations (P = 0.556). Regarding the other substances studied, parathormone was positively correlated with only the age of the patients (P = 0.015). Of the 5 substances studied, only bone alkaline phosphates were significantly different (P < 0.001) between patients with chronic pancreatitis and those with pancreatic ductal adenocarcinoma. Within the 2 groups of patients, the 23 patients with chronic pancreatitis without diabetes mellitus had serum concentrations of 25-hydroxyvitamin D significantly lower (P = 0.045) than those with chronic pancreatitis having diabetes mellitus, whereas smokers with pancreatic ductal adenocarcinoma had serum concentrations of calcium significantly higher (P < 0.001) as compared to nonsmokers. Altered bone metabolism seems to be associated with chronic diseases of the pancreas; however, the mechanism should be better elucidated. PMID:26496293

  7. Early changes in parameters of bone and mineral metabolism during therapy for hyper- and hypothyroidism.

    PubMed

    Sabuncu, T; Aksoy, N; Arikan, E; Ugur, B; Tasan, E; Hatemi, H

    2001-01-01

    The effects of thyroid hormones on various organs and metabolic systems have been the focus of intensive research. In this study we investigated the mechanisms of the changes in some parameters of bone and mineral metabolism before and during treatment of hyper- and hypothyroidism. Our study groups were as follows; 1) Untreated hyperthyroid patients (n= 38), 2) Hyperthyroid patients treated for three months (n=21), 3) Untreated hypothyroid patients (n=27), 4) Hypothyroid patients treated for three months (n= 20), and 5) Euthyroid control subjects (age, weight, sex and menopausal status matched) (n = 47). As expected, the mean serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and urinary Ca/creatinine and deoxypyridinoline (D-Pyr)/creatinine levels were higher in group-1 than in the control group. Serum PTH level was lower in group-1 than in group-5. However, after treatment for three months (group-2) we found that the serum and urinary levels of these parameters (except ALP) were not different than in the control group. Group-3 and group-4 did not show any differences in these parameters compared with group-5. Covariance analysis showed that urinary D-Pyr excretion had a positive, independent relationship to the serum free T3 level and age (P < 0.001 and P = 0.02, respectively). These results suggest that both bone formation and resorption markers increase in hyperthyroid patients, and with the treatment, particularly, in the period of first three months the bone resorption markers decrease rapidly. If the treatment is maintained the decrease slows, becoming more gradual. However, bone formation markers like ALP remain high in hyperthyroid patients during the treatment. In the light of this data, it is possible to conclude that osteoblastic activity lasts longer in hyperthyroidism. On the other hand, we demonstrated that these bone formation and resorption markers do not seem to be different in hypothyroid patients, even during the treatment, compared

  8. Factors associated with bone metabolism in acromegalic patients: hypogonadism and female gender.

    PubMed

    Tütüncü, N B; Erbaş, T

    2004-06-01

    The purpose of the study was to determine the factors associated with bone metabolism in acromegalic patients. Thirty three patients with acromegaly who had been followed on a regular basis in the endocrinology clinic were enrolled for the study. Among the factors acting upon bone metabolism, age, gender, body mass index (BMI), duration and activity of the disease, length of remission, treatment modalities and functional status of the pituitary were evaluated. Their influences on the determinants of bone remodelling and bone mineral density (BMD) were tried to be elucidated. The median age of the 33 acromegalics (19 females, 14 males) was 39.73 +/- 10.1 years. Twenty-three patients (9 males and 14 females) were eugonadal. Ten patients had been diagnosed with history of at least one year of untreated hypogonadism (5 males and 5 females; for 1 - 10 years). The BMD values of the lumbar vertebrae, the femur and the radius were correlated with each other. Patients were grouped according to their T-scores as decreased, normal, and increased BMD. Groups were similar with regard to age, BMI, gender, duration of disease, and remission, GH, IGF-1, IGFBP-3 levels, markers of bone turnover. Presence of hypogonadism and duration of hypogonadism revealed statistically significant difference among the 3 groups (p = 0.005 and p = 0.035, respectively). Hypogonadal acromegalic patients had decreased BMD compared to eugonadal acromegalics and healthy population while the eugonadal female acromegalic patients revealed increased BMD of lumbar vertebrae, femur, and distal radius compared to the sex-matched healthy population. PMID:15216451

  9. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics.

    PubMed

    Zhang, Aihua; Qiu, Shi; Sun, Hui; Zhang, Tianlei; Guan, Yu; Han, Ying; Yan, Guangli; Wang, Xijun

    2016-01-01

    Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of scoparone on lipid metabolism in hepatocytes. The most striking finding was that scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics. PMID:27306123

  10. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics

    PubMed Central

    Zhang, Aihua; Qiu, Shi; Sun, Hui; Zhang, Tianlei; Guan, Yu; Han, Ying; Yan, Guangli; Wang, Xijun

    2016-01-01

    Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of scoparone on lipid metabolism in hepatocytes. The most striking finding was that scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics. PMID:27306123

  11. Environmental factors affecting indole metabolism under anaerobic conditions

    SciTech Connect

    Madsen, E.L.; Francis, A.J.; Bollag, J.M.

    1988-01-01

    The influence of physiological and environmental factors on the accumulation of oxindole during anaerobic indole metabolism was investigated by high-performance liquid chromatography. Under methanogenic conditions, indole was temporarily converted to oxindole in stoichiometric amounts in media inoculated with three freshwater sediments and an organic soil. In media inoculated with methanogenic sewage sludge, the modest amounts of oxindole detected at 35/sup 0/C reached higher concentrations and persisted longer when the incubation temperature was decreased from 35 to 15/sup 0/C. Also, decreasing the concentration of sewage sludge used as an inoculum from 50 to 1% caused an increase in the accumulation of oxindole from 10 to 75% of the indole added. Under denitrifying conditions, regardless of the concentration or source of the inoculum, oxindole appeared in trace amounts but did not accumulate during indole metabolism. In addition, denitrifying consortia which previously metabolized indole degraded oxindole with no lag period. Our data suggest that oxindole accumulation under methanogenic, but not under denitrifying conditions is caused by differences between relative rates of oxindole production and destruction.

  12. Suture materials affect peri-implant bone healing and implant osseointegration.

    PubMed

    Villa, Oscar; Lyngstadaas, Staale P; Monjo, Marta; Satué, Maria; Rønold, Hans J; Petzold, Christiane; Wohlfahrt, Johan C

    2015-09-01

    The aim of this study was to evaluate the effects of the remnants of two suture materials on osseointegration of titanium implants in a rabbit tibial model. Calibrated defects were prepared in the tibia of five Chinchilla rabbits. Filaments of nonresorbable (NR) nylon or resorbable (R) chitosan were placed at the bone to implant interface, whereas control sites had no suture material. After a healing period of 4 weeks, a pull-out test procedure was performed followed by enzymatic analyses of the wound fluid and relative quantification of mRNA levels for bone-related and cytokine markers from the peri-implant bone. A trend toward a reduced pull-out force was observed in the NR group (NR: 23.0 ± 12.8 N; R: 33.9 ± 11.3 N; control: 33.6 ± 24.0 N). Similarly, the bone resorption marker vacuolar type H+-ATPase was increased in the NR group compared with that in the control group (P = 0.041). The R group showed trends for lower alkaline phosphatase activity and osteocalcin expression and higher total protein content and RNA compared with the control group. In this submerged healing model, peri-implant bone healing was marginally affected by the two suture materials tested. However, there was a tendency toward better osseointegration and lower expression of bone resorption markers in the R group compared with the control group. PMID:26369486

  13. Effect of cyclosporin A on bone mineral metabolism in experimental diabetes mellitus in the rat.

    PubMed

    Epstein, S; Takizawa, M; Stein, B; Katz, I A; Joffe, I I; Romero, D F; Liang, X G; Li, M; Ke, H Z; Jee, W S

    1994-04-01

    Cyclosporin A (CsA) is widely used in diabetic transplant patients and early type I diabetes mellitus. Diabetes produces a low-turnover osteopenia, and CsA conversely induces high-turnover osteopenia in rats. We investigated whether CsA would exacerbate diabetic osteopenia. Four groups of 10-week-old male Sprague-Dawley rats (n = 11/group) were studied: On day -6, groups A and C received saline and groups B and D received intravenous streptozotocin (55 mg/kg) to induce diabetes. From day 0, groups A and B received CsA vehicle and C and D received CsA (15 mg/kg) by daily gavage. Rats were bled on days -6, 0, 11, and 22 for serum bone gla protein (BGP), 1,25-(OH)2D, PTH, blood ionized Ca, and blood glucose determinations. Double tetracycline labeling was performed on days 9 and 20 for bone histomorphometry. After sacrifice on day 22, histomorphometric analysis was performed. Serum BGP, 1,25-(OH)2D, and PTH levels were significantly decreased in the diabetic alone (B) and diabetic plus CsA (D) groups and significantly increased in the CsA alone (group C). CsA alone (group C) induced cancellous bone loss by stimulated bone resorption. Cancellous bone loss in the diabetic alone rats (group B) was caused primarily by inhibited bone formation. No differences were found in cancellous bone mass, formation, or resorption parameters between diabetic alone (group B) and CsA-treated diabetic rats (group D). Neither CsA alone (group C) nor diabetic alone (group B) nor their combination affected cortical bone mass. CsA alone (group C) stimulated periosteal bone formation and endocortical bone resorption and inhibited endocortical formation, and diabetic alone (group B) inhibited both periosteal and endocortical bone formation. No parameters of tibial diaphyses in CsA-treated diabetic rats (group D) were different from diabetic alone. Thus the addition of CSA to the diabetic treated rats (group D) could not stimulate remodeling and appeared not to worsen significantly some of the

  14. One carbon metabolism and bone homeostasis and remodeling: A review of experimental research and population studies.

    PubMed

    Feigerlova, Eva; Demarquet, Lea; Guéant, Jean-Louis

    2016-07-01

    Homocysteine (HCY) is a degradation product of the methionine pathway. The B vitamins, in particular vitamin B12 and folate, are the primary nutritional determinant of HCY levels and therefore their deficiencies result in hyperhomocysteinaemia (HHCY). Prevalence of hyperhomocysteinemia (HHCY) and related dietary deficiencies in B vitamins and folate increase with age and have been related to osteoporosis and abnormal development of epiphyseal cartilage and bone in rodents. Here we provide a review of experimental and population studies. The negative effects of HHCY and/or B vitamins and folate deficiencies on bone formation and remodeling are documented by cell models, including primary osteoblasts, osteoclast and bone progenitor cells as well as by animal and human studies. However, underlying pathophysiological mechanisms are complex and remain poorly understood. Whether these associations are the direct consequences of impaired one carbon metabolism is not clarified and more studies are still needed to translate these findings to human population. To date, the evidence is limited and somewhat conflicting, however further trials in groups most vulnerable to impaired one carbon metabolism are required. PMID:27086080

  15. Bone metabolism in very preterm infants receiving total parenteral nutrition: do intravenous fat emulsions have an impact?

    PubMed

    Bridges, Kayla M; Pereira-da-Silva, Luis; Tou, Janet C; Ziegler, Jane; Brunetti, Luigi

    2015-12-01

    Very preterm infants (<32 weeks' gestation) are at high risk for impaired skeletal development because of factors that limit the provision of extrauterine nutrients. Cumulative net deficiencies of calcium, phosphorus, docosahexaenoic acid (DHA), and arachidonic acid (ARA) are evident in these infants after prolonged administration of total parenteral nutrition (TPN). This is significant because minerals as well as metabolites of DHA and ARA are important modulators of bone cell differentiation, lengthening of bone, and bone matrix deposition. Furthermore, diets containing only precursors of DHA and ARA result in suboptimal skeletal growth. With the emergence of new intravenous lipid emulsions, it is important to understand the impact of fatty acids on bone metabolism in the third trimester in order to optimize the provision of TPN in very preterm infants. The purpose of this review is to evaluate current evidence regarding intravenous lipid emulsions and bone metabolism in very preterm infants receiving prolonged TPN and to identify areas of research needed. PMID:26518033

  16. Evidence for Chronic Kidney Disease-Mineral and Bone Disorder Associated With Metabolic Pathway Changes

    PubMed Central

    Wu, Qiong; Lai, Xueli; Zhu, Zhenyu; Hong, Zhanying; Dong, Xin; Wang, Tieyun; Wang, Haiyan; Lou, Ziyang; Lin, Qishan; Guo, Zhiyong; Chai, Yifeng

    2015-01-01

    Abstract Abnormalities in the levels of calcium, phosphorus, and parathyroid hormone (PTH) in serum are typical for patients with chronic kidney disease (CKD). They are used routinely to predict the onset of CKD-mineral and bone disorder (MBD). However, CKD-MBD associated with metabolic pathway imbalance is not well understood. The objective of the study was to identify endogenous metabolic signatures in patients with intact PTH using mass spectrometry-based metabolomics. This study was a cross-sectional study. Ultra performance liquid chromatography-Quadrupole Time-of-Flight/mass spectrometry-based metabolic profiling was employed to analyze serum samples from 19 disease controls (DCs) (intact parathyroid hormone [iPTH] 150–300 pg/mL) and 19 secondary hyperparathyroidism (SHPT) patients (iPTH >300 pg/mL) (the training data set) to identify metabolic biomarkers for CKD-MBD. Then, another set of samples including 19 DCs (iPTH 150–300 pg/mL) and 19 SHPT patients (iPTH >300 pg/mL) (the test data set) were used to validate the potential biomarkers identified. Metabolic profiling analyses revealed different patterns of endogenous metabolites between the SHPT and the DC groups. A total of 32 unique metabolites were identified and 30 metabolites were elevated in the iPTH compared with control serum pools. Cytidine and l-phenylalanine were downregulated in the SHPT patients. The metabolic signatures identified were assessed respectively by an internal 10-fold cross validation with an accuracy of 91.4% and an external validation with an accuracy of 71.1%, a sensitivity of 73.7%, and a specificity of 68.4%. Mass spectrometry-based metabolomic analyses for SHPT patients promises immense potential for early diagnosis and therapy monitoring. Our results indicated that the onset of CKD-MBD is associated with pathway changes of protein synthesis and metabolism, amino acid metabolism, energy metabolism, and steroid hormone metabolism, with obvious promise for better

  17. Gravity, calcium, and bone - Update, 1989

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Morey-Holton, Emily

    1990-01-01

    Recent results obtained on skeletal adaptation, calcium metabolism, and bone browth during short-term flights and ground simulated-microgravity experiments are presented. Results demonstrate that two principal components of calcium metabolism respond within days to changes in body position and to weightlessness: the calcium endocrine system and bone characteristics. Furthermore, results of recent studies imply that bone biomechanics are more severely affected by spaceflight exposures than is the bone mass.

  18. The Influence of the Type of Continuous Exercise Stress Applied during Growth Periods on Bone Metabolism and Osteogenesis

    PubMed Central

    Suzuki, Takao; Izawa, Hiromi; Satoh, Atsuko

    2016-01-01

    Background In this study, we examined the influence of exercise loading characteristics on bone metabolic responses and bone morphology in the growth phase and adulthood. Methods Running exercise (RUN) and jumping exercise (JUM) were used for the exercise loading in 28-day-old male Wistar rats. Bone metabolism was measured by blood osteocalcin (OC) and tartrate-resistant acid phosphatase (TRACP) levels. For bone morphology, the maximum bone length, bone weight, and bone strength of the femur and tibia were measured. Results A pre- and post-exercise loading comparison in the growth phase showed significantly increased OC levels in the RUN and JUM groups and significantly decreased TRACP levels in the JUM group. On the other hand, a pre- and post-exercise loading comparison in adulthood showed significantly decreased TRACP levels in the RUN and JUM groups. Femur lengths were significantly shorter in the RUN and JUM groups than in the control (CON) group, while bone weight was significantly greater in the JUM group than in the CON group. Conclusions Exercise loading activates OC levels in the growth phase and suppresses TRACP levels in adulthood. On the other hand, these results suggest that excessive exercise loading may suppress bone length. PMID:27622180

  19. Clinical factors affecting pathological fracture and healing of unicameral bone cysts

    PubMed Central

    2014-01-01

    Background Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. Methods We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. Results The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. Conclusion The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery. PMID:24884661

  20. Bone metabolism status and associated risk factors in elderly patients with chronic obstructive pulmonary disease (COPD).

    PubMed

    Xiaomei, Wang; Hang, Xiao; Lingling, Liu; Xuejun, Li

    2014-09-01

    The prevalence of osteoporosis in older patients with chronic obstructive pulmonary disease (COPD) is higher than in the age-matched elderly patients, but the exact cause in relation to COPD is not clear. We hypothesized that the underlying causes for this difference are related to bone metabolism with the possible risk factors that include the duration of COPD, GOLD grade, cor pulmonale, the frequencies of acute exacerbations within the past year, smoking and inhaled corticosteroid therapy. We conducted a matched-pair study of 100 patients aged older than 65 years at the Southwest Hospital from May to November 2012. The enrolled patients with COPD were matched to controls for age and gender. Clinical characteristics of cohorts were recorded. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and osteoporosis was diagnosed according to the definition of WHO. All cohorts accepted bone metabolism marker measurement, including Procollagen type 1 aminoterminal propeptide (P1NP), β-C-telopeptides of type I collagen (βCTX), and N-terminal midmolecule fragment osteocalcin (N-MID OC). Statistical analysis was calculated using the student's t test, ANOVA and multiple regression analysis at a significance level set at a p < 0.05. Circulating biochemical markers of bone formation (P1NP), resorption (βCTX) and turnover (N-MID OC) were significantly lower in the COPD group than control group, while mean 25-OH Vitamin D was similar in two groups. The P1NP, βCTX, and N-MID OC were still lower in men with COPD, but only P1NP was lower in women with COPD compared to that of controls. Multiple regression analysis in COPD group suggests that age, the frequency of acute exacerbation, and BMD are independent risk factors for P1NP. The frequency of acute exacerbation within the past one year and 25-OH D level are independent risk factors for βCTX; the frequency of acute exacerbation is the only independent risk factor for N-MID OC. These were significant

  1. Albumin Supplement Affects the Metabolism and Metabolism-Related Drug-Drug Interaction of Fenoprofen Enantiomers.

    PubMed

    Wang, Nan; Wang, Feng; Meng, Yu; Yang, Guo-Hui; Chen, Ju-Wu; Wang, Jia-Xiang

    2015-07-01

    The influence of albumin towards the metabolism behavior of fenoprofen enantiomers and relevant drug-drug interaction was investigated in the present study. The metabolic behavior of fenoprofen enantiomers was compared in a phase II metabolic incubation system with and without bovine serum albumin (BSA). BSA supplement increased the binding affinity parameter (Km) of (R)-fenoprofen towards human liver microsomes (HLMs) from 148.3 to 214.4 μM. In contrast, BSA supplement decreased the Km of (S)-fenoprofen towards HLMs from 218.2 to 123.5 μM. For maximum reaction velocity (Vmax), the addition of BSA increased the Vmax of (R)-fenoprofen from 1.3 to 1.6 nmol/min/mg protein. In the contrast, BSA supplement decreased the Vmax value from 3.3 to 1.5 nmol/min/mg protein. Andrographolide-fenoprofen interaction was used as an example to investigate the influence of BSA supplement towards fenoprofen-relevant drug-drug interaction. The addition of 0.2% BSA in the incubation system significantly decreased the inhibition potential of andrographolide towards (R)-fenoprofen metabolism (P < 0.001). Different from (R)-fenoprofen, the addition of BSA significantly increased the inhibition potential of andrographolide towards the metabolism of (S)-fenoprofen. BSA supplement also changed the inhibition kinetic type and parameter of andrographolide towards the metabolism of (S)-fenoprofen. In conclusion, albumin supplement changes the metabolic behavior of fenoprofen enantiomers and the fenoprofen-andrographolide interaction. PMID:26037509

  2. Metabolic differences in temperamental Brahman cattle can affect productivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many factors may adversely affect the growth and productivity of livestock. These include stressors associated with management practices, such as weaning, handling relative to transportation, and vaccination, that can modulate growth through the production of stress-related hormones (i.e., cortisol,...

  3. Bone marrow glucose metabolic response to GMCSF by quantitative FDG PET imaging

    SciTech Connect

    Yao, W.J.; Hoh, C.K.; Hawkins, R.A.

    1994-05-01

    To evaluate noninvasively the recombinant granulocyte-macrophage colony-stimulating factor (GMCSF) effects on bone marrow glucose metabolism, we studied 18 patients with metastatic melanoma with quantitative FDG PET imaging. All patients received 14 days of therapy in 3 groups; group 1: 4 patients treated with GMCSF (5 ug/kg/d SQ), group 2: 8 patients treated with GMCSF (5 ug/kg/d SQ) and monoclonal antibody MAbR24, and group 3: 6 patients treated with MCSF (80 ug/kg/d IVCI) and MAbR24.

  4. Studies of Intercellular Communication and Intracellular Metabolic Responses by Bone Cells to Simulated Weightlessness

    NASA Technical Reports Server (NTRS)

    Doty, Stephen B.

    1997-01-01

    Spaceflight affects the weight bearing skeletal tissues by reducing the rate of new bone formation. This effect on the long bones of flown rats has been quantitated but the effect at the cellular level and the mechanism(s) involved are not understood. We are applying electron microscopy, coupled with histochemistry and immunocytochemistry to determine the cellular functions most affected by spaceflight. The emphasis for study of these samples from SLS-1, a 9-day mission, is on the histochemical and structural changes of the endosteal and perivascular osteoblasts found in diaphyseal bone of femur and tibia. Work is still in progress but some findings are described: (1) An expected decrease in alkaline phosphatase activity in osteoblasts from flight animals, but an increase in enzyme activity in the stromal stem cells adjacent to the osteoblast. (2) An increase in osteoclastic TRAP activity in the trabecular bone region in response to spaceflight. (3) A large increase in procollagen containing secretory granules in osteoblasts in the recovery group, and a significant decrease in granule numbers in the flight group.

  5. Regional differences in oxidative metabolism and mitochondrial activity among cortical bone osteocytes.

    PubMed

    Frikha-Benayed, Dorra; Basta-Pljakic, Jelena; Majeska, Robert J; Schaffler, Mitchell B

    2016-09-01

    Metabolic oxidative stress has been implicated as a cause of osteocyte apoptosis, an essential step in triggering bone remodeling. However, little is known about the oxidative behavior of osteocytes in vivo. We assessed the redox status and distribution of total and active mitochondria in osteocytes of mouse metatarsal cortical bone in situ. Multiphoton microscopy (MPM) was used to measure fluorescence of reduced pyridine nucleotides (NADH) under normoxic conditions and acutely following extreme (postmortem) hypoxic stress. Under non-hypoxic conditions, osteocytes exhibited no detectable fluorescence, indicating rapid NADH re-oxidation. With hypoxia, NADH levels peaked and returned to near baseline levels over 3h. Cells near the periosteal surface reached maximum NADH levels twice as rapidly as osteocytes near the mid-cortex, due to the time required to initiate NADH accumulation; once started, NADH accumulation followed a similar exponential relationship at all sites. Osteocytes near periosteal and endosteal bone surfaces also had higher mitochondrial content than those in mid-cortex based on immunohistochemical staining for mitochondrial ATPase-5A (Complex V ATPase). The content of active mitochondria, assessed in situ using the potentiometric dye TMRM, was also high in osteocytes near periosteum, but low in osteocytes near endocortical surfaces, similar to levels in mid-cortex. These results demonstrate that cortical osteocytes maintain normal oxidative status utilizing mainly aerobic (mitochondrial) pathways but respond to hypoxic stress differently depending on their location in the cortex, a difference linked to mitochondrial content. An apparently high proportion of poorly functional mitochondria in osteocytes near endocortical surfaces, where increased apoptosis mainly occurs in response to bone remodeling stimuli, further suggest that regional differences in oxidative function may in part determine osteocyte susceptibility to undergo apoptosis in response

  6. Suture locking of isolated internal locking knotless suture anchors is not affected by bone quality

    PubMed Central

    Woodmass, Jarret M; Matthewson, Graeme; Ono, Yohei; Bois, Aaron J; Boorman, Richard S; Lo, Ian KY; Thornton, Gail M

    2015-01-01

    Purpose The purpose of this study was to evaluate the mechanical performance of different suture locking mechanisms including: i) interference fit between the anchor and the bone (eg, 4.5 mm PushLock, 5.5 mm SwiveLock), ii) internal locking mechanism within the anchor itself (eg, 5.5 mm SpeedScrew), or iii) a combination of interference fit and internal locking (eg, 4.5 mm MultiFIX P, 5.5 mm MultiFIX S). Methods Anchors were tested in foam blocks representing normal (20/8 foam) or osteopenic (8/8 foam) bone, using standard suture loops pulled in-line with the anchor to isolate suture locking. Mechanical testing included cyclic testing for 500 cycles from 10 N to 60 N at 60 mm/min, followed by failure testing at 60 mm/min. Displacement after 500 cycles at 60 N, number of cycles at 3 mm displacement, load at 3 mm displacement, and maximum load were evaluated. Results Comparing 8/8 foam to 20/8 foam, load at 3 mm displacement and maximum load were significantly decreased (P<0.05) with decreased bone quality for anchors that, even in part, relied on an interference fit suture locking mechanism (ie, 4.5 mm PushLock, 5.5 mm SwiveLock, 4.5 mm MultiFIX P, 5.5 mm MultiFIX S). Bone quality did not affect the mechanical performance of 5.5 mm SpeedScrew anchors which have an isolated internal locking mechanism. Conclusion The mechanical performance of anchors that relied, even in part, on interference fit were affected by bone quality. Isolated internal locking knotless suture anchors functioned independently of bone quality. Anchors with a combined type (interference fit and internal locking) suture locking mechanism demonstrated similar mechanical performance to isolated internal locking anchors in osteopenic foam comparing similar sized anchors. Clinical relevance In osteopenic bone, knotless suture anchors that have an internal locking mechanism (isolated or combined type) may be advantageous for secure tendon fixation to bone. PMID:26124683

  7. Age-associated metabolic dysregulation in bone marrow-derived macrophages stimulated with lipopolysaccharide.

    PubMed

    Fei, Fan; Lee, Keith M; McCarry, Brian E; Bowdish, Dawn M E

    2016-01-01

    Macrophages are major contributors to age-associated inflammation. Metabolic processes such as oxidative phosphorylation, glycolysis and the urea cycle regulate inflammatory responses by macrophages. Metabolic profiles changes with age; therefore, we hypothesized that dysregulation of metabolic processes could contribute to macrophage hyporesponsiveness to LPS. We examined the intracellular metabolome of bone marrow-derived macrophages from young (6-8 wk) and old (18-22 mo) mice following lipopolysaccharide (LPS) stimulation and tolerance. We discovered known and novel metabolites that were associated with the LPS response of macrophages from young mice, which were not inducible in macrophages from old mice. Macrophages from old mice were largely non-responsive towards LPS stimulation, and we did not observe a shift from oxidative phosphorylation to glycolysis. The critical regulatory metabolites succinate, γ-aminobutyric acid, arginine, ornithine and adenosine were increased in LPS-stimulated macrophages from young mice, but not macrophages from old mice. A shift between glycolysis and oxidative phosphorylation was not observed during LPS tolerance in macrophages from either young or old mice. Metabolic bottlenecks may be one of the mechanisms that contribute to the dysregulation of LPS responses with age. PMID:26940652

  8. Age-associated metabolic dysregulation in bone marrow-derived macrophages stimulated with lipopolysaccharide

    NASA Astrophysics Data System (ADS)

    Fei, Fan; Lee, Keith M.; McCarry, Brian E.; Bowdish, Dawn M. E.

    2016-03-01

    Macrophages are major contributors to age-associated inflammation. Metabolic processes such as oxidative phosphorylation, glycolysis and the urea cycle regulate inflammatory responses by macrophages. Metabolic profiles changes with age; therefore, we hypothesized that dysregulation of metabolic processes could contribute to macrophage hyporesponsiveness to LPS. We examined the intracellular metabolome of bone marrow-derived macrophages from young (6–8 wk) and old (18–22 mo) mice following lipopolysaccharide (LPS) stimulation and tolerance. We discovered known and novel metabolites that were associated with the LPS response of macrophages from young mice, which were not inducible in macrophages from old mice. Macrophages from old mice were largely non-responsive towards LPS stimulation, and we did not observe a shift from oxidative phosphorylation to glycolysis. The critical regulatory metabolites succinate, γ-aminobutyric acid, arginine, ornithine and adenosine were increased in LPS-stimulated macrophages from young mice, but not macrophages from old mice. A shift between glycolysis and oxidative phosphorylation was not observed during LPS tolerance in macrophages from either young or old mice. Metabolic bottlenecks may be one of the mechanisms that contribute to the dysregulation of LPS responses with age.

  9. Age-associated metabolic dysregulation in bone marrow-derived macrophages stimulated with lipopolysaccharide

    PubMed Central

    Fei, Fan; Lee, Keith M.; McCarry, Brian E.; Bowdish, Dawn M. E.

    2016-01-01

    Macrophages are major contributors to age-associated inflammation. Metabolic processes such as oxidative phosphorylation, glycolysis and the urea cycle regulate inflammatory responses by macrophages. Metabolic profiles changes with age; therefore, we hypothesized that dysregulation of metabolic processes could contribute to macrophage hyporesponsiveness to LPS. We examined the intracellular metabolome of bone marrow-derived macrophages from young (6–8 wk) and old (18–22 mo) mice following lipopolysaccharide (LPS) stimulation and tolerance. We discovered known and novel metabolites that were associated with the LPS response of macrophages from young mice, which were not inducible in macrophages from old mice. Macrophages from old mice were largely non-responsive towards LPS stimulation, and we did not observe a shift from oxidative phosphorylation to glycolysis. The critical regulatory metabolites succinate, γ-aminobutyric acid, arginine, ornithine and adenosine were increased in LPS-stimulated macrophages from young mice, but not macrophages from old mice. A shift between glycolysis and oxidative phosphorylation was not observed during LPS tolerance in macrophages from either young or old mice. Metabolic bottlenecks may be one of the mechanisms that contribute to the dysregulation of LPS responses with age. PMID:26940652

  10. Spastin Binds to Lipid Droplets and Affects Lipid Metabolism

    PubMed Central

    Papadopoulos, Chrisovalantis; Orso, Genny; Mancuso, Giuseppe; Herholz, Marija; Gumeni, Sentiljana; Tadepalle, Nimesha; Jüngst, Christian; Tzschichholz, Anne; Schauss, Astrid; Höning, Stefan; Trifunovic, Aleksandra; Daga, Andrea; Rugarli, Elena I.

    2015-01-01

    Mutations in SPAST, encoding spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP). HSP is characterized by weakness and spasticity of the lower limbs, owing to progressive retrograde degeneration of the long corticospinal axons. Spastin is a conserved microtubule (MT)-severing protein, involved in processes requiring rearrangement of the cytoskeleton in concert to membrane remodeling, such as neurite branching, axonal growth, midbody abscission, and endosome tubulation. Two isoforms of spastin are synthesized from alternative initiation codons (M1 and M87). We now show that spastin-M1 can sort from the endoplasmic reticulum (ER) to pre- and mature lipid droplets (LDs). A hydrophobic motif comprised of amino acids 57 through 86 of spastin was sufficient to direct a reporter protein to LDs, while mutation of arginine 65 to glycine abolished LD targeting. Increased levels of spastin-M1 expression reduced the number but increased the size of LDs. Expression of a mutant unable to bind and sever MTs caused clustering of LDs. Consistent with these findings, ubiquitous overexpression of Dspastin in Drosophila led to bigger and less numerous LDs in the fat bodies and increased triacylglycerol levels. In contrast, Dspastin overexpression increased LD number when expressed specifically in skeletal muscles or nerves. Downregulation of Dspastin and expression of a dominant-negative variant decreased LD number in Drosophila nerves, skeletal muscle and fat bodies, and reduced triacylglycerol levels in the larvae. Moreover, we found reduced amount of fat stores in intestinal cells of worms in which the spas-1 homologue was either depleted by RNA interference or deleted. Taken together, our data uncovers an evolutionarily conserved role of spastin as a positive regulator of LD metabolism and open up the possibility that dysfunction of LDs in axons may contribute to the pathogenesis of HSP. PMID:25875445

  11. Electromagnetic fields do not affect bone micro-architecture in osteoporotic rats

    PubMed Central

    van der Jagt, O. P.; van der Linden, J. C.; Waarsing, J. H.; Verhaar, J. A. N.; Weinans, H.

    2014-01-01

    Objectives Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing. Methods EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8). As a putative positive control, all rats received bilateral fibular osteotomies to examine the effects on fracture healing. Treatment was applied to one proximal lower leg (three hours a day, five days a week); the lower leg was not treated and served as a control. Bone architectural changes of the proximal tibia and bone formation around the osteotomy were evaluated using in vivo microCT scans at start of treatment and after three and six weeks. Results In both OVX and sham-OVX groups, EMF did not result in cancellous or cortical bone changes during follow-up. Moreover, EMF did not affect the amount of mineralised callus volume around the fibular osteotomy. Conclusions In this study we were unable to reproduce the strong beneficial findings reported by others. This might indicate that EMF treatment is very sensitive to the specific set-up, which would be a serious hindrance for clinical use. No evidence was found that EMF treatment can influence bone mass for the benefit of osteoporotic patients. Cite this article: Bone Joint Res 2014;3:230–5. PMID:25015993

  12. [A study on observation of bone metabolism in middle-aged and senile female Graves' disease].

    PubMed

    Zhu, L Q; Liu, Y H; Zhou, Y B

    1996-08-01

    Sixty-nine cases of middle aged and senile female Graves' desease (GD) patients suffered from abnormal bone metabolism have been studied. They were divided randomly into group A and B, treated separately with antithyroid drugs (Tapazol and inderal, etc.) in group A, and added with Chinese herbal medicine for tonifying Kidney and promoting blood circulation in group B. Before treatment, patients of both groups showed obvious higher blood calcium (Ca) 24-hour urinary Ca, phosphorus (P) and serum clcitonin (CT) levels than that in normal subjects. These patients' serum Ca, moreover, had a parallel relationship with serum T3 levels (r = 0.6142, P < 0.01) and the serum Ca also a paralleled with serum CT levels (r = 0.5714, P < 0.05). After six months of treatment, the serum Ca, 24-hour urinary Ca, P and blood CT values were all reduced in various degree. The decrease of these bone metabolic parameters were more significant in group B than that in group A. PMID:9387746

  13. Lactobacillus acidophilus NCFM affects vitamin E acetate metabolism and intestinal bile acid signature in monocolonized mice

    PubMed Central

    Roager, Henrik M; Sulek, Karolina; Skov, Kasper; Frandsen, Henrik L; Smedsgaard, Jørn; Wilcks, Andrea; Skov, Thomas H; Villas-Boas, Silas G; Licht, Tine R

    2014-01-01

    Monocolonization of germ-free (GF) mice enables the study of specific bacterial species in vivo. Lactobacillus acidophilus NCFMTM (NCFM) is a probiotic strain; however, many of the mechanisms behind its health-promoting effect remain unknown. Here, we studied the effects of NCFM on the metabolome of jejunum, cecum, and colon of NCFM monocolonized (MC) and GF mice using liquid chromatography coupled to mass-spectrometry (LC-MS). The study adds to existing evidence that NCFM in vivo affects the bile acid signature of mice, in particular by deconjugation. Furthermore, we confirmed that carbohydrate metabolism is affected by NCFM in the mouse intestine as especially the digestion of oligosaccharides (penta- and tetrasaccharides) was increased in MC mice. Additionally, levels of α-tocopherol acetate (vitamin E acetate) were higher in the intestine of GF mice than in MC mice, suggesting that NCFM affects the vitamin E acetate metabolism. NCFM did not digest vitamin E acetate in vitro, suggesting that direct bacterial metabolism was not the cause of the altered metabolome in vivo. Taken together, our results suggest that NCFM affects intestinal carbohydrate metabolism, bile acid metabolism and vitamin E metabolism, although it remains to be investigated whether this effect is unique to NCFM. PMID:24717228

  14. Lactobacillus acidophilus NCFM affects vitamin E acetate metabolism and intestinal bile acid signature in monocolonized mice.

    PubMed

    Roager, Henrik M; Sulek, Karolina; Skov, Kasper; Frandsen, Henrik L; Smedsgaard, Jørn; Wilcks, Andrea; Skov, Thomas H; Villas-Boas, Silas G; Licht, Tine R

    2014-01-01

    Monocolonization of germ-free (GF) mice enables the study of specific bacterial species in vivo. Lactobacillus acidophilus NCFM(TM) (NCFM) is a probiotic strain; however, many of the mechanisms behind its health-promoting effect remain unknown. Here, we studied the effects of NCFM on the metabolome of jejunum, cecum, and colon of NCFM monocolonized (MC) and GF mice using liquid chromatography coupled to mass-spectrometry (LC-MS). The study adds to existing evidence that NCFM in vivo affects the bile acid signature of mice, in particular by deconjugation. Furthermore, we confirmed that carbohydrate metabolism is affected by NCFM in the mouse intestine as especially the digestion of oligosaccharides (penta- and tetrasaccharides) was increased in MC mice. Additionally, levels of α-tocopherol acetate (vitamin E acetate) were higher in the intestine of GF mice than in MC mice, suggesting that NCFM affects the vitamin E acetate metabolism. NCFM did not digest vitamin E acetate in vitro, suggesting that direct bacterial metabolism was not the cause of the altered metabolome in vivo. Taken together, our results suggest that NCFM affects intestinal carbohydrate metabolism, bile acid metabolism and vitamin E metabolism, although it remains to be investigated whether this effect is unique to NCFM. PMID:24717228

  15. Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization.

    PubMed

    Lu, Xuanyu; Fukumoto, Satoshi; Yamada, Yoshihiko; Evans, Carla A; Diekwisch, Thomas Gh; Luan, Xianghong

    2016-06-01

    Matrix molecules such as the enamel-related calcium-binding phosphoprotein ameloblastin (AMBN) are expressed in multiple tissues, including teeth, bones, and cartilage. Here we have asked whether AMBN is of functional importance for timely long bone development and, if so, how it exerts its function related to osteogenesis. Adolescent AMBN-deficient mice (AMBN(Δ5-6) ) suffered from a 33% to 38% reduction in femur length and an 8.4% shorter trunk spinal column when compared with WT controls, whereas there was no difference between adult animals. On a cellular level, AMBN truncation resulted in a shortened growth plate and a 41% to 49% reduction in the number of proliferating tibia chondrocytes and osteoblasts. Bone marrow stromal cells (BMSCs) isolated from AMBN mutant mice displayed defects in proliferation and differentiation potential as well as cytoskeleton organization. Osteogenesis-related growth factors, such as insulin-like growth factor 1 (IGF1) and BMP7, were also significantly (46% to 73%) reduced in AMBN-deficient BMSCs. Addition of exogenous AMBN restored cytoskeleton structures in AMBN mutant BMSCs and resulted in a dramatic 400% to 600% increase in BMP2, BMP7, and Col1A expression. Block of RhoA diminished the effect of AMBN on osteogenic growth factor and matrix protein gene expression. Addition of exogenous BMP7 and IGF1 rescued the proliferation and differentiation potential of AMBN-deficient BMSCs. Confirming the effects of AMBN on long bone growth, back-crossing of mutant mice with full-length AMBN overexpressors resulted in a complete rescue of AMBN(Δ5-6) bone defects. Together, these data indicate that AMBN affects extracellular matrix production and cell adhesion properties in the long bone growth plate, resulting in altered cytoskeletal dynamics, increased osteogenesis-related gene expression, as well as osteoblast and chondrocyte proliferation. We propose that AMBN facilitates rapid long bone growth and an important growth spurt during the

  16. Negative Effects of Total Gastrectomy on Bone Tissue Metabolism and Volumetric Bone Mineral Density (vBMD) of Lumbar Spine in 1-Year Study in Men

    PubMed Central

    Krupski, Witold; Tatara, Marcin R.; Bury, Pawel; Szabelska, Anna; Charuta, Anna; Maciejewski, Ryszard; Wallner, Grzegorz; Dabrowski, Andrzej

    2016-01-01

    Abstract Gastrectomy induces severe osteoporosis in humans but its quantitative scale within trabecular and cortical compartments was not estimated. The aim of the study was to determine changes of volumetric bone mineral density (vBMD) in lumbar vertebrae (L1–L4) and biochemical bone metabolism markers in serum of patients 1 year after total gastrectomy. The control group consisted of patients (N = 8) subjected to abdominal surgery due to cardiospasmus. Total gastrectomy was performed in the experimental group (N = 6). Volumetric bone mineral density of trabecular and cortical bone of lumbar spine was measured before (baseline) and 1 year after the gastric surgery using the quantitative computed tomography method. Serum concentrations of insulin, insulin-like growth factor-1, tyroxine, interleukin-6, C-terminal telopeptides of type II collagen and bone formation, and resorption markers were determined at baseline and 1 year later, using ELISA, EIA, and IEMA methods. Total gastrectomy induced significant decrease of vBMD values, up to 16.8% and 10.0%, within the trabecular and cortical bone compartments of lumbar spine (P < 0.05). These negative changes of vBMD were associated with significantly increased serum concentration of bone resorption markers such as deoxypyridinoline, pyridinoline, and C-terminal telopeptides of type I collagen, by 13.5%, 32.2%, and 121.5%, respectively (P < 0.05). Neither vBMD nor biochemical bone turnover markers and hormone concentrations were influenced in the control patients. Dramatic bone loss during the first year in gastrectomized patients has proven dynamic osteoporosis progress indicating an importance of treatment interventions in these patients with emphasis on inhibition of intensive bone resorption processes. PMID:26886633

  17. Controlled trial of the effects of milk basic protein (MBP) supplementation on bone metabolism in healthy adult women.

    PubMed

    Aoe, S; Toba, Y; Yamamura, J; Kawakami, H; Yahiro, M; Kumegawa, M; Itabashi, A; Takada, Y

    2001-04-01

    Milk has more beneficial effects on bone health compared to other food sources. Recent in vitro and in vivo studies showed that milk whey protein, especially its basic protein fraction, contains several components capable of both promoting bone formation and inhibiting bone resorption. However, the effects of milk basic protein (MBP) on bone metabolism of humans are not known. The object of this study was to examine the effects of MBP on bone metabolism of healthy adult women. Thirty-three normal healthy women were randomly assigned to treatment with either placebo or MBP (40 mg per day) for six months. The bone mineral density (BMD) of the left calcaneus of each subject was measured at the beginning of the study and after six months of treatment, by dual-energy x-ray absorptiometry. Serum and urine indices of bone metabolism were measured at the base line, three-month intervals, and the end of the study. Daily intake of nutrients was monitored by a three-day food record made at three and six months. The mean (+/- SD) rate of left calcaneus BMD gain of women in the MBP group (3.42 +/- 2.05%) was significantly higher than that of women in the placebo group (2.01 +/- 1.75%, P = 0.042). As compared with the placebo group, urinary cross-linked N-teleopeptides of type-I collagen/creatinine and deoxypyridinoline/creatinine were significantly decreased in the MBP group (p < 0.05), while no significant differences between the two groups were observed in serum osteocalcin and bone-specific alkaline phosphatase concentrations. A daily MBP supplementation of 40 mg in healthy adult women can significantly increase their BMD independent of dietary intake of minerals and vitamins. This increase in BMD might be primarily mediated through inhibition of osteoclast-mediated bone resorption by the MBP supplementation. PMID:11388472

  18. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    SciTech Connect

    Chen, Y.-J.; Liao, H.-F.; Tsai, T.-H.; Wang, S.-Y.; Shiao, M.-S. . E-mail: msshiao@vghtpe.gov.tw

    2005-11-15

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-{kappa}B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or {gamma}-glutamyl transpeptidase activity. Radiation activated NF-{kappa}B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-{kappa}B activity, without toxicity to bone marrow, liver, and kidney.

  19. Hydroxyapatite crystallinity does not affect the repair of critical size bone defects

    PubMed Central

    CONZ, Marcio Baltazar; GRANJEIRO, José Mauro; SOARES, Gloria de Almeida

    2011-01-01

    Objective The physicochemical properties of hydroxyapatite (HA) granules were observed to affect the biological behavior of graft materials. The aim of this work was to analyze the tissue response of two HA granules with different crystallinity and Ca/P ratio in vivo. Material and Methods The HA granules were produced in the Biomaterials Laboratory (COPPE/UFRJ). The testing materials were HA granules presenting a Ca/P molar ratio of 1.60 and 28% crystallinity (HA-1), and a Ca/P molar ratio of 1.67 and 70% crystallinity (HA-2). Both HAs were implanted into a critical-size calvaria rat defects. Results To note, in the control group, the bone defects were filled with blood clot only. Descriptive and histomorphometric analyses after 1, 3, and 6 months postoperatively showed mild inflammatory infiltrate, mainly comprising macrophage-like and multinucleated giant cells, and an increase in the volume density of the fibrous tissues (p<0.05), which was in contrast to the similar volume density of the newly formed bone and biomaterials in relation to the control group. Conclusion Thus, we concluded that HA-1 and HA-2 are biocompatible and non-degradable, and that crystallinity does not affect bone repair of critical size defects. PMID:21655775

  20. Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity

    PubMed Central

    Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter

    2015-01-01

    Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity. PMID:26061167

  1. Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

    PubMed

    Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter; van Loon, Jack J W A; Muller, Marc

    2015-01-01

    Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity. PMID:26061167

  2. Bone density and anisotropy affect periprosthetic cement and bone stresses after anatomical glenoid replacement: A micro finite element analysis.

    PubMed

    Chevalier, Yan; Santos, Inês; Müller, Peter E; Pietschmann, Matthias F

    2016-06-14

    Glenoid loosening is still a main complication for shoulder arthroplasty. We hypothesize that cement and bone stresses potentially leading to fixation failure are related not only to glenohumeral conformity, fixation design or eccentric loading, but also to bone volume fraction, cortical thickness and degree of anisotropy in the glenoid. In this study, periprosthetic bone and cement stresses were computed with micro finite element models of the replaced glenoid depicting realistic bone microstructure. These models were used to quantify potential effects of bone microstructural parameters under loading conditions simulating different levels of glenohumeral conformity and eccentric loading simulating glenohumeral instability. Results show that peak cement stresses were achieved near the cement-bone interface in all loading schemes. Higher stresses within trabecular bone tissue and cement mantle were obtained within specimens of lower bone volume fraction and in regions of low anisotropy, increasing with decreasing glenohumeral conformity and reaching their maxima below the keeled design when the load is shifted superiorly. Our analyses confirm the combined influences of eccentric load shifts with reduced bone volume fraction and anisotropy on increasing periprosthetic stresses. They finally suggest that improving fixation of glenoid replacements must reduce internal cement and bone tissue stresses, in particular in glenoids of low bone density and heterogeneity. PMID:27087675

  3. A controlled trial of the effect of milk basic protein (MBP) supplementation on bone metabolism in healthy menopausal women.

    PubMed

    Aoe, Seiichiro; Koyama, Takao; Toba, Yasuhiro; Itabashi, Akira; Takada, Yukihiro

    2005-12-01

    Milk has more beneficial effects on bone health than other food sources. Recent in vitro and in vivo studies have shown that milk whey protein, especially its basic protein fraction (milk basic protein, MBP), contains several components capable of promoting bone formation and inhibiting bone resorption. The object of this study was to examine the effect of MBP on the bone metabolism of healthy menopausal women. Thirty-two healthy menopausal women were randomly assigned to treatment with either placebo or MBP (40 mg per day) for 6 months. The bone mineral density (BMD) of the lumbar vertebrae L2-L4 of each subject was measured by dual-energy X-ray absorptiometry (DXA) at 0 and 6 months of treatment. Serum and urine indices of bone metabolism were measured at 0, 3 and 6 months. Twenty-seven subjects who completed the study in accordance with the protocol were included in the analysis. The mean rate of gain of lumbar BMD in the MBP group (1.21%) was significantly higher than in the placebo group (-0.66%, P=0.046). When compared with the placebo group, urinary cross-linked N-telopeptides of type-I collagen (NTx) were significantly decreased in the MBP group at 6 months, but no significant difference in serum osteocalcin was observed between the two groups. The urinary NTx excretion was found to be related to serum osteocalcin in the MBP group at 3 and 6 months, indicating that MBP maintained the balance of bone remodeling. These results suggested that MBP supplementation was effective in preventing bone loss in menopausal women and that this improvement in BMD may be primarily mediated through the inhibition of bone resorption while maintaining the balance of bone remodeling by MBP supplementation. PMID:16133638

  4. Osteoblast-specific expression of Fra-2/AP-1 controls adiponectin and osteocalcin expression and affects metabolism.

    PubMed

    Bozec, Aline; Bakiri, Latifa; Jimenez, Maria; Rosen, Evan D; Catalá-Lehnen, Philip; Schinke, Thorsten; Schett, Georg; Amling, Michael; Wagner, Erwin F

    2013-12-01

    Recent studies have established that the skeleton functions as an endocrine organ affecting metabolism through the osteoblast-derived hormone osteocalcin (Ocn). However, it is not fully understood how many transcription factors expressed in osteoblasts regulate the endocrine function. Here, we show that mice with osteoblast-specific deletion of Fra-2 (Fosl2) have low bone mass but increased body weight. In contrast, transgenic expression of Fra-2 in osteoblasts leads to increased bone mass and decreased body weight accompanied by reduced serum glucose and insulin levels, improved glucose tolerance and insulin sensitivity. In addition, mice lacking Fra-2 have reduced levels of circulating Ocn, but high adiponectin (Adipoq), whereas Fra-2 transgenic mice exhibit high Ocn and low Adipoq levels. Moreover, we found that Adipoq was expressed in osteoblasts and that this expression was transcriptionally repressed by Fra-2. These results demonstrate that Fra-2 expression in osteoblasts represents a novel paradigm for a transcription factor controlling the endocrine function of the skeleton. PMID:24046454

  5. The importance of vitamin D in the pathology of bone metabolism in inflammatory bowel diseases

    PubMed Central

    Krela-Kaźmierczak, Iwona; Szymczak, Aleksandra; Łykowska-Szuber, Liliana; Stawczyk-Eder, Kamila; Klimczak, Katarzyna; Linke, Krzysztof; Horst-Sikorska, Wanda

    2015-01-01

    Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D. PMID:26528347

  6. Polyphosphate: A Morphogenetically Active Implant Material Serving as Metabolic Fuel for Bone Regeneration.

    PubMed

    Müller, Werner E G; Tolba, Emad; Schröder, Heinz C; Wang, Xiaohong

    2015-09-01

    The initial mineralization centers during human bone formation onto osteoblasts are composed of CaCO3 . Those bioseeds are enzymatically formed via carbonic anhydrase(s) in close association with the cell surface of the osteoblasts. Subsequently, the bicarbonate/carbonate anions are exchanged non-enzymatically by inorganic phosphate [Pi ]. One source for the supply of Pi is polyphosphate [polyP] which is a physiological polymer, formed in the osteoblasts as well as in the platelets. The energy-rich acid anhydride bonds within the polyP chain are cleaved by phosphatase(s); during this reaction free-energy might be released that could be re-used, as metabolic fuel, for the maintenance of the steady-state concentrations of the substrates/products during mineralization. Finally it is outlined that polyP, as a morphogenetically active scaffold, is even suitable for 3D cell printing. PMID:25982003

  7. Bone marrow transplantation in the prevention of intellectual disability due to inherited metabolic disease: ethical issues.

    PubMed

    Louhiala, P

    2009-07-01

    Many inherited metabolic diseases may lead to varying degrees of brain damage and thus also to intellectual disability. Bone marrow transplantation (BMT) has been used for over two decades as a form of secondary prevention to stop or reverse the progress of the disease process in some of these conditions. At the population level the impact of BMT on the prevalence of intellectual disability is minute, but at the individual level its impact on the prognosis of the disease and the well-being of the patient can be substantial. The dark side of BMT use is the burden of side effects, complications and transplantation-related mortality in less successful cases. The ethical issues involved in this therapy are discussed in this review. PMID:19567689

  8. The importance of vitamin D in the pathology of bone metabolism in inflammatory bowel diseases.

    PubMed

    Krela-Kaźmierczak, Iwona; Szymczak, Aleksandra; Łykowska-Szuber, Liliana; Eder, Piotr; Stawczyk-Eder, Kamila; Klimczak, Katarzyna; Linke, Krzysztof; Horst-Sikorska, Wanda

    2015-10-12

    Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D. PMID:26528347

  9. A comparative study of the bone metabolic response to dried plum supplementation and PTH treatment in adult, osteopenic ovariectomized rat.

    PubMed

    Smith, Brenda J; Bu, So Young; Wang, Yan; Rendina, Elizabeth; Lim, Yin F; Marlow, Denver; Clarke, Stephen L; Cullen, Diane M; Lucas, Edralin A

    2014-01-01

    Dried plum has been reported to have potent effects on bone in osteopenic animal models, but the mechanisms through which bone metabolism is altered in vivo remain unclear. To address this issue, a study comparing the metabolic response of dried plum to the anabolic agent, parathyroid hormone (PTH), was undertaken. Six month-old female Sprague Dawley rats (n=84) were sham-operated (SHAM) or ovariectomized (OVX) and maintained on a control diet for 6wks until osteopenia was confirmed. Treatments were initiated consisting of a control diet (AIN-93M) supplemented with dried plum (0, 5, 15 or 25%; w/w) or a positive control group receiving PTH. At the end of 6wks of treatment, whole body and femoral bone mineral density (BMD) were restored by the two higher doses of dried plum to the level of the SHAM group. Trabecular bone volume and cortical thickness were also improved with these two doses of dried plum. Dried plum suppressed the OVX-induced increase in bone turnover as indicated by systemic biomarkers of bone metabolism, N-terminal procollagen type 1 (P1NP) and deoxypyridinoline (DPD). Dynamic bone histomorphometric analysis of the tibial metaphysis revealed that dried plum restored the OVX-induced increase in cancellous bone formation rate (BFR) and mineralizing surface (MS/BS) to the SHAM group, but some doses of dried plum increased endocortical mineral apposition rate (MAR). As expected, PTH significantly increased endocortical MAR and BFR, periosteal BFR, and trabecular MAR and BFR beyond that of the OVX and maintained the accelerated rate of bone resorption associated with OVX. Dried plum up-regulated bone morphogenetic protein 4 (Bmp4) and insulin-like growth factor 1 (Igf1) while down-regulating nuclear factor T cell activator 1 (Nfatc1). These findings demonstrate that in the adult osteopenic OVX animal, the effects of dried plum differ from that of PTH in that dried plum primarily suppressed bone turnover with the exception of the indices of bone

  10. Treatment of subclinical hypothyroidism does not affect bone mass as determined by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography and quantitative bone ultrasound in Spanish women

    PubMed Central

    Roncero-Martin, Raul; Calderon-Garcia, Julian F.; Santos-Vivas, Mercedes; Vera, Vicente; Martínez-Alvárez, Mariana; Rey-Sanchez, Purificación

    2015-01-01

    Introduction The results of studies examining the influence of subclinical hypothyroidism (SCH) and levothyroxine (L-T4) replacement therapy on bone have generated considerable interest but also controversy. The present research aims to evaluate the effects of L-T4 treatment on different skeletal sites in women. Material and methods A group of 45 premenopausal (mean age: 43.62 ±6.65 years) and 180 postmenopausal (mean age: 59.51 ±7.90 years) women with SCH who were undergoing L-T4 replacement therapy for at least 6 months were compared to 58 pre- and 180 postmenopausal women with SCH (untreated) matched for age. The mean doses of L-T4 were 90.88 ±42.59 µg/day in the premenopausal women and 86.35 ±34.11 µg/day in the postmenopausal women. Bone measurements were obtained using quantitative bone ultrasound (QUS) for the phalanx, dual-energy X-ray absorptiometry (DXA) for the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT) for the non-dominant distal forearm. Results No differences were observed between patients and untreated controls in these bone measurements except in the bone mineral density (BMD) of the spine (p = 0.0214) in postmenopausal women, which was greater in treated women than in untreated controls. Conclusions Our results indicate that adequate metabolic control through replacement treatment with L-T4 in pre- and postmenopausal women does not affect bone mass. PMID:26528344

  11. Integrating Epigenomic Elements and GWASs Identifies BDNF Gene Affecting Bone Mineral Density and Osteoporotic Fracture Risk

    PubMed Central

    Guo, Yan; Dong, Shan-Shan; Chen, Xiao-Feng; Jing, Ying-Aisha; Yang, Man; Yan, Han; Shen, Hui; Chen, Xiang-Ding; Tan, Li-Jun; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2016-01-01

    To identify susceptibility genes for osteoporosis, we conducted an integrative analysis that combined epigenomic elements and previous genome-wide association studies (GWASs) data, followed by validation at population and functional levels, which could identify common regulatory elements and predict new susceptibility genes that are biologically meaningful to osteoporosis. By this approach, we found a set of distinct epigenomic elements significantly enriched or depleted in the promoters of osteoporosis-associated genes, including 4 transcription factor binding sites, 27 histone marks, and 21 chromatin states segmentation types. Using these epigenomic marks, we performed reverse prediction analysis to prioritize the discovery of new candidate genes. Functional enrichment analysis of all the prioritized genes revealed several key osteoporosis related pathways, including Wnt signaling. Genes with high priority were further subjected to validation using available GWASs datasets. Three genes were significantly associated with spine bone mineral density, including BDNF, PDE4D, and SATB2, which all closely related to bone metabolism. The most significant gene BDNF was also associated with osteoporotic fractures. RNA interference revealed that BDNF knockdown can suppress osteoblast differentiation. Our results demonstrated that epigenomic data could be used to indicate common epigenomic marks to discover additional loci with biological functions for osteoporosis. PMID:27465306

  12. Integrating Epigenomic Elements and GWASs Identifies BDNF Gene Affecting Bone Mineral Density and Osteoporotic Fracture Risk.

    PubMed

    Guo, Yan; Dong, Shan-Shan; Chen, Xiao-Feng; Jing, Ying-Aisha; Yang, Man; Yan, Han; Shen, Hui; Chen, Xiang-Ding; Tan, Li-Jun; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2016-01-01

    To identify susceptibility genes for osteoporosis, we conducted an integrative analysis that combined epigenomic elements and previous genome-wide association studies (GWASs) data, followed by validation at population and functional levels, which could identify common regulatory elements and predict new susceptibility genes that are biologically meaningful to osteoporosis. By this approach, we found a set of distinct epigenomic elements significantly enriched or depleted in the promoters of osteoporosis-associated genes, including 4 transcription factor binding sites, 27 histone marks, and 21 chromatin states segmentation types. Using these epigenomic marks, we performed reverse prediction analysis to prioritize the discovery of new candidate genes. Functional enrichment analysis of all the prioritized genes revealed several key osteoporosis related pathways, including Wnt signaling. Genes with high priority were further subjected to validation using available GWASs datasets. Three genes were significantly associated with spine bone mineral density, including BDNF, PDE4D, and SATB2, which all closely related to bone metabolism. The most significant gene BDNF was also associated with osteoporotic fractures. RNA interference revealed that BDNF knockdown can suppress osteoblast differentiation. Our results demonstrated that epigenomic data could be used to indicate common epigenomic marks to discover additional loci with biological functions for osteoporosis. PMID:27465306

  13. Metabolic syndrome - the consequence of lifelong treatment of bipolar affective disorder.

    PubMed

    Dadić-Hero, Elizabeta; Ruzić, Klementina; Grahovac, Tanja; Petranović, Duska; Graovac, Mirjana; Palijan, Tija Zarković

    2010-06-01

    Mood disturbances are characteristic and dominant feature of Mood disorders. Bipolar Affective Disorder (BAD) is a mood disorder which occurs equally in both sexes. BAD may occur in co morbidity with other mental diseases and disorders such as: Anorexia Nervosa, Bulimia Nervosa, Attention Deficit, Panic Disorder and Social Phobia. However, medical disorders (one or more) can also coexist with BAD. Metabolic syndrome is a combination of metabolic disorders that increase the risk of developing cardiovascular disease. A 61-year old female patient has been receiving continuous and systematic psychiatric treatment for Bipolar Affective Disorder for the last 39 years. The first episode was a depressive one and it occurred after a child delivery. Seventeen years ago the patient developed diabetes (diabetes type II), and twelve years ago arterial hypertension was diagnosed. High cholesterol and triglyceride levels as well as weight gain were objective findings. During the last nine years she has been treated for lower leg ulcer. Since metabolic syndrome includes abdominal obesity, hypertension, diabetes mellitus, increased cholesterol and serum triglyceride levels, the aforesaid patient can be diagnosed with Metabolic Syndrome. When treating Bipolar Affective Disorder, the antipsychotic drug choice should be careful and aware of its side-effects in order to avoid the development or aggravation of metabolic syndrome. PMID:20562789

  14. Metabolic issues in patients affected by schizophrenia: clinical characteristics and medical management

    PubMed Central

    Ventriglio, Antonio; Gentile, Alessandro; Stella, Eleonora; Bellomo, Antonello

    2015-01-01

    Patients affected by psychotic disorders are more likely to develop high rates of co-morbidities, such as obesity, type 2 diabetes, dyslipidemias, hypertension, metabolic syndrome, myocardial infarction, stroke etc., in the long-term. These morbidities have a significant impact on the life-expectancy of these patients. Patients with chronic psychoses show a 2–3-fold increased risk of death mostly from cardiovascular and metabolic diseases. Although there may be an independent link, between schizophrenia and metabolic conditions the cardio-metabolic risk is mostly related to an unhealthy lifestyle and the usage of antipsychotic agents (especially Second Generation Antipsychotics or atypical) even when these remain effective treatments in the management of major psychoses. Recently, many international organizations have developed screening and monitoring guidelines for the control of modifiable risk factors in order to reduce the rate of co-morbidity and mortality among patients affected by schizophrenia. This paper is a review of current knowledge about the metabolic issues of patients affected by schizophrenia and describes clinical characteristics and medical management strategies for such conditions. PMID:26388714

  15. Metabolic changes after MRgFUS treatment of a bone metastasis using PET/CT: A case report

    NASA Astrophysics Data System (ADS)

    Candiano, Giuliana; Russo, Giorgio; Stefano, Alessandro; Marino, Lorenza; Ganguzza, Francesca; Vaccari, Arturo; Tripoli, Vincenzo; Galluzzo, Anna; Pulizzi, Sabina; Messana, Domenico; Borasi, Giovanni; Messa, Cristina; Gilardi, Maria Carla

    2012-11-01

    Aim of the present study is to evaluate the efficacy of the Magnetic Resonance guided Focused Ultrasound (Insightec ExAblate 2000 system) in a clinical case of a pelvic bone metastasis, accessible to the ultrasonic beam. Multiple 18F-FDG PET/CT examinations allowed to follow the metabolic and morphological modification of the cancerous lesion.

  16. Oral contraceptive use by teenage women does not affect peak bone mass: a longitudinal study.

    PubMed

    Lloyd, T; Taylor, D S; Lin, H M; Matthews, A E; Eggli, D F; Legro, R S

    2000-10-01

    This longitudinal observational study determined the effect of oral contraceptive (OC) use during adolescence on peak bone mass (PBM). The sample comprised 62 non-Hispanic, White females in The Penn State Young Women's Health Study, who were studied for 8 years between the ages of 12 and 20. There were 28 OC users who used OCs for a minimum of 6 months and were still using them at age 20, and 34 nonusers who had never used the regimen. Total body bone, dedicated hipbone, and body composition measurements were made by dual-energy roentgenogram absorptiometry. There was no difference between OC users and nonusers in the anthropometric, body composition, or total body bone measurements. By age 20, the average duration of OC use by the user group was 22 months. At this age, the groups remained indistinguishable in anthropometric, body composition, total body, and hipbone measurements, and in age of menarche and sports exercise scores. These findings suggest that OC use by healthy, White, teenage females does not affect acquisition of PBM. PMID:11020515

  17. Total hip replacement in osteoarthritis: the role of bone metabolism and its complications

    PubMed Central

    Bottai, Vanna; Dell'Osso, Giacomo; Celli, Fabio; Bugelli, Giulia; Cazzella, Niki; Cei, Elena; Guido, Giulio; Giannotti, Stefano

    2015-01-01

    Summary Osteoarthritis is one of the most common joint disorder. For treatment of hip symptomatic osteoarthritis, when conservative medical therapy has failed, total hip arthroplasty (THA) is a successful orthopaedic procedures that reduces pain and improves function and quality of life. Incidence of osteoarthritis is constantly increasing with raising life expectancy. This aging process also has led to an increasing number of patients with osteoporosis who need hip replacement for osteoarthritis. Osteoporosis have 3 major potential complications in total hip arthroplasty: perioperative fracture, an increased risk of periprosthetic fracture, and late aseptic loosening. The purpose of the present study was to examine the effects of osteoporosis on total hip replacement procedure outcome and highlight the importance of adequate study of calcium-phosphorus metabolism in patient candidate for hip surgery, and the need to start a suitable therapy to recover the bone mass before surgery. Bone quality of the hip joint has become an important risk factor limiting the durability of THA. PMID:26811704

  18. Bone metabolism and nutritional status during 30-day head-down-tilt bed rest

    PubMed Central

    Morgan, Jennifer L. L.; Zwart, Sara R.; Heer, Martina; Ploutz-Snyder, Robert; Ericson, Karen

    2012-01-01

    Bed rest studies provide an important tool for modeling physiological changes that occur during spaceflight. Markers of bone metabolism and nutritional status were evaluated in 12 subjects (8 men, 4 women; ages 25–49 yr) who participated in a 30-day −6° head-down-tilt diet-controlled bed rest study. Blood and urine samples were collected twice before, once a week during, and twice after bed rest. Data were analyzed using a mixed-effects linear regression with a priori contrasts comparing all days to the second week of the pre-bed rest acclimation period. During bed rest, all urinary markers of bone resorption increased ∼20% (P < 0.001), and serum parathyroid hormone decreased ∼25% (P < 0.001). Unlike longer (>60 days) bed rest studies, neither markers of oxidative damage nor iron status indexes changed over the 30 days of bed rest. Urinary oxalate excretion decreased ∼20% during bed rest (P < 0.001) and correlated inversely with urinary calcium (R = −0.18, P < 0.02). These data provide a broad overview of the biochemistry associated with short-duration bed rest studies and provide an impetus for using shorter studies to save time and costs wherever possible. For some effects related to bone biochemistry, short-duration bed rest will fulfill the scientific requirements to simulate spaceflight, but other effects (antioxidants/oxidative damage, iron status) do not manifest until subjects are in bed longer, in which case longer studies or other analogs may be needed. Regardless, maximizing research funding and opportunities will be critical to enable the next steps in space exploration. PMID:22995395

  19. Bone metabolism and nutritional status during 30-day head-down-tilt bed rest.

    PubMed

    Morgan, Jennifer L L; Zwart, Sara R; Heer, Martina; Ploutz-Snyder, Robert; Ericson, Karen; Smith, Scott M

    2012-11-01

    Bed rest studies provide an important tool for modeling physiological changes that occur during spaceflight. Markers of bone metabolism and nutritional status were evaluated in 12 subjects (8 men, 4 women; ages 25-49 yr) who participated in a 30-day -6° head-down-tilt diet-controlled bed rest study. Blood and urine samples were collected twice before, once a week during, and twice after bed rest. Data were analyzed using a mixed-effects linear regression with a priori contrasts comparing all days to the second week of the pre-bed rest acclimation period. During bed rest, all urinary markers of bone resorption increased ~20% (P < 0.001), and serum parathyroid hormone decreased ~25% (P < 0.001). Unlike longer (>60 days) bed rest studies, neither markers of oxidative damage nor iron status indexes changed over the 30 days of bed rest. Urinary oxalate excretion decreased ~20% during bed rest (P < 0.001) and correlated inversely with urinary calcium (R = -0.18, P < 0.02). These data provide a broad overview of the biochemistry associated with short-duration bed rest studies and provide an impetus for using shorter studies to save time and costs wherever possible. For some effects related to bone biochemistry, short-duration bed rest will fulfill the scientific requirements to simulate spaceflight, but other effects (antioxidants/oxidative damage, iron status) do not manifest until subjects are in bed longer, in which case longer studies or other analogs may be needed. Regardless, maximizing research funding and opportunities will be critical to enable the next steps in space exploration. PMID:22995395

  20. Evaluation of bone metabolism in children with acute lymphoblastic leukemia after induction chemotherapy treatment.

    PubMed

    Athanassiadou, Fani; Tragiannidis, Athanassios; Rousso, Israel; Katsos, Georgios; Sidi, Vassiliki; Koliouskas, Dimitrios; Papastergiou, Cristos; Tsituridis, Ioannis

    2005-06-01

    Osteopenia and osteoporosis are currently receiving particular attention as late effects of therapy in survivors of childhood acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate abnormalities in bone mass and mineral homeostasis in children with ALL after induction therapy (during consolidation treatment). Lumbar spine (L2-L4) bone mineral density (BMD, g/cm(2)) was measured by dual energy X-ray absorptiometry in 20 children with ALL, a median of 25.9 months postdiagnosis and results were expressed as z-scores relative to healthy Caucasian children (controls). Serum levels of intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, phosphate, and magnesium were also analyzed. In addition, the body mass indexes (kg/cm(2)) of patients and controls were calculated. Results were compared with those of 40 healthy controls. Among the 20 children with ALL (12 boys and 8 girls), 12 presented z-scores < 1 SD (normal) and 8 were osteopenic (z-score between 1 and 2.5 SD). In addition, children with ALL had reduced lumbar BMDs (z-score -0.817) in comparison to healthy controls (z-score -0.353) (p = .04). Moreover, alkaline phosphatase and intact parathyroid hormone values were significantly increased compared to controls values. The data demonstrate that bone metabolism in children with ALL during consolidation therapy is disturbed, resulting in a reduced BMD and z-score with respect to healthy controls. Since a reduced BMD predisposes to osteopenia and osteoporosis, specific attention and therapeutic interventions should be considered. PMID:16020115

  1. Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended-Duration Space Flight on the Mir Space Station

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Wastney, Meryl E.; O'Brien, Kimberly O.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Davis-Street, Janis E.; Oganov, Victor; Shackelford, Linda C.

    2005-01-01

    Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that

  2. Calcium metabolism in bone and teeth of rats during exposure to restriction of motor activity and to swimming exercise.

    PubMed

    Zorbas, Y G; Charapakhin, K P; Kuznetsov, N A; Kakurin, V J

    1999-06-01

    The effects of motor activity restriction for 90 days (hypokinesia, HK) and swimming training (T) on calcium metabolism in rat bones and teeth were evaluated. Male Wistar rats were distributed in four groups: untrained vivarium control rats (UVCR), untrained hypokinetic rats (UHKR), trained hypokinetic rats (THKR) and trained vivarium control rats (TVCR). Hypokinesia was obtained keeping the animals for 90 days in small individual cages which restricted their movements in all directions without hindering food and water intakes. Rats of THKR and TVCR were forced to swim for 15 to 90 minutes everyday. On the 1st, 7th, 15th day of a prehypokinetic period and on the 5th, 10th, 20th, 40th, 60th and 90th day of the hypokinetic period, six rats of each group were decapitated. Radioactive calcium was injected to the animals 70 days before autopsy. Calcium and phosphorus in serum, bones (molars, incisors, upper and lower jaws, parietal, scapular, clavicle, pelvic and tibial bones) and in the respective ash residues were measured. Body and bone weights, and radioactive calcium were also determined. Under prolonged exposure to HK (THKR and UHKR groups), bone weights and bone and ash Ca and P concentrations decreased, whereas serum Ca and P and 45Ca resorption increased, in comparison to the respective values in the UVCR and TVCR groups. Swimming exercise apparently did not modify calcium metabolism in the hypokinetic or control rats. PMID:10517263

  3. Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients

    PubMed Central

    Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

    2015-01-01

    Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. Trial Registration: ClinicalTrials.gov NCT02361372 PMID:26655888

  4. Kinin B1 Receptor Deletion Affects Bone Healing in Type 1 Diabetic Mice.

    PubMed

    Cignachi, Natália P; Pesquero, João B; Oliveira, Rogério B; Etges, Adriana; Campos, Maria M

    2015-12-01

    The effects of kinin B1 receptor (B1 R) deletion were examined on femur bone regeneration in streptozotocin (STZ)-type 1 diabetes. Diabetes induction in wild-type C57/BL6 (WTC57BL6) mice led to decrease in body weight and hyperglycemia, compared to the non-diabetic group of the same strain. The lack of B1 R did not affect STZ-elicited body weight loss, but partially prevented hyperglycemia. Diabetic mice had a clear delay in bone regeneration, and displayed large areas of loose connective tissue within the defects, with a reduced expression of the mineralization-related protein osteonectin, when compared to the non-diabetic WTC57/BL6. The non-diabetic and diabetic B1 R knockout (B1 RKO) mice had bone regeneration levels and osteonectin expression comparable to that seen in control WTC57/BL6 mice. WTC57/BL6 STZ-diabetic mice also showed a marked reduction of collagen contents, with increased immunolabeling for the apoptosis marker caspase-3, whereas diabetic B1 RKO had collagen levels and caspase-3 activity comparable to those observed in non-diabetic WTC57/BL6 or B1 RKO mice. No significant difference was detected in the number of tartrate-resistant acid phosphatase (TRAP)-stained cells, or in RANK/RANKL/OPG system immunolabeling throughout the experimental groups. Data bring novel evidence on the relevance of kinin B1 R under type 1 diabetes with regards to its role in bone regeneration. PMID:25969420

  5. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently.

    PubMed

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L; Duong, Le T; Engelholm, Lars H; Delaissé, Jean-Marie

    2014-01-10

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors of the osteoclasts. Here we provide evidence supporting this hypothesis, by comparing the osteoclast-canopy interface in response to two types of bone resorption inhibitors in rabbit lumbar vertebrae. The bisphosphonate alendronate, an inhibitor leading to low bone formation levels, reduces the extent of canopy coverage above osteoclasts. This effect is in accordance with its toxic action on periosteoclastic cells. In contrast, odanacatib, an inhibitor preserving bone formation, increases the extent of the osteoclast-canopy interface. Interestingly, these distinct effects correlate with how fast bone formation follows resorption during these respective treatments. Furthermore, canopy cells exhibit uPARAP/Endo180, a receptor able to bind the collagen made available by osteoclasts, and reported to mediate osteoblast recruitment. Overall these observations support a mechanism where the recruitment of bone forming osteoblasts from the canopy is induced by osteoclastic factors, thereby favoring initiation of bone formation. They lead to a model where the osteoclast-canopy interface is

  6. Bone Tumor

    MedlinePlus

    ... most common types of primary bone cancer are: • Multiple myeloma. Multiple myeloma is the most common primary bone cancer. It ... Any bone can be affected by this cancer. Multiple myeloma affects approximately six people per 100,000 each ...

  7. Use of diphosphonates to correct disorders in calcium metabolism and mineral composition of bone tissue with 60-day hypokinesia in rats

    NASA Technical Reports Server (NTRS)

    Morukov, B. V.; Zaychik, V. YE.; Ivanov, V. M.; Orlov, O. I.

    1988-01-01

    Compounds of the diphosphonate group suppress bone resorption and bone tissue metabolism, from which it was assumed that they can be used for the prevention of osteoporosis and disorders of calcium homeostasis in humans during space flight. Two compounds of this group were used for preventive purposes in 60 day hypokinesia in rats. The results showed that diphosphonates have a marked effect on calcium metabolism and the condition of the bone tissues under conditions of long term hypokinesia: they reduce the content of ionized calcium in blood, delay the loss of calcium and phosphorus by the bone tissue, and to a considerable degree prevent reduction of bone density. This confirms the possibility of using compounds of this group for correcting and preventing changes of bone tissue and mineral metabolism during long term hypokinesia.

  8. Bone mass and markers of bone and calcium metabolism in postmenopausal women treated with 1,25-dihydroxyvitamin D (Calcitriol) for four years.

    PubMed

    Sairanen, S; Kärkkäinen, M; Tähtelä, R; Laitinen, K; Mäkelä, P; Lamberg-Allardt, C; Välimäki, M J

    2000-08-01

    To evaluate the long-term effect of calcitriol treatment on bone mineral density (BMD) of the femoral neck and lumbar spine and the parameters of calcium and bone metabolism in elderly women, 55 healthy, postmenopausal women, all aged 66 years, were enrolled in the study. Eighteen started a 4-year supplementation with 0.5 microg of calcitriol daily and 37 served as controls. Calcium intake of all the subjects was adjusted to 800 mg daily. In 4 years femoral neck BMD increased by 3.0% in the calcitriol group, but decreased by 1.6% in the control group (P = 0.009). The respective changes in lumbar spine BMD were +2.3% and +0.9% (P = 0.067). Two years' treatment with calcitriol increased the intestinal absorption of strontium by 57% (P < 0.001), doubled the urinary excretion of calcium (P < 0. 001), and decreased the mean parathyroid hormone (PTH) level by 32% (P < 0.01). In the calcitriol group the marker of bone formation, serum osteocalcin, decreased by 27% (P < 0.01), and the marker of bone resorption, serum C-telopeptide of type I collagen (CTx), by 33% (P = 0.05) after 2 years. In two subjects the calcitriol dose had to be reduced because of hypercalciuria. We conclude that calcitriol treatment increases bone mass at the femoral neck and lumbar spine, the increases being maintained for up to 4 years. The gain in bone mass results from reduced bone turnover which is partly a consequence of the enhanced intestinal absorption of calcium and suppressed serum PTH levels. PMID:10920216

  9. Alterations of bone mineral metabolism of children with different cell lineage types of acute lymphoblastic leukaemia under chemotherapy

    PubMed Central

    Tragiannidis, A; Dokos, Ch; Sidi, V; Papageorgiou, Th; Koliouskas, D; Karamouzis, M; Papastergiou, Ch; Tsitouridis, I; Katzos, G; Rousso, I; Athanassiadou-Piperopoulou, F

    2011-01-01

    Background: Children with haematological malignancies such as acute lymphoblastic leukaemia (ALL) may have alteration of bone mineral metabolism therefore increased risk for osteopenia and osteoporosis. Patients and Methods: The purpose of this study was to examine the alterations of bone mineral metabolism in two groups of children (n=42) according to immunophenotyping (B-cell type, T-cell type) both quantitative (bone mineral density z-scores) and qualitative (serum osteocalcin - OC and carboxyl-terminal telopeptide of human type I collagen - ICTP) during diagnosis (T=0), after the intensified chemotherapy period (T=0.5) and the consolidation period (T=1). Results: According to our results 15 patients had osteopenia and 1 child developed osteoporosis at T=0.5 and 13 patients had osteopenia at T=1. Mean BMD z-score was significantly decreased in both groups during chemotherapy and especially statistically significant decline of T-cell type ALL group compared with B-cell type ALL patients. OC mean level remains in low levels for both groups reaching in plateau during chemotherapy and ICTP level was increased in T-cell type ALL group of patients compared with B-cell type in both periods of chemotherapy. Conclusions: It seems that not only the combination of chemotherapeutic agents but also the cell lineage of ALL are important parameters of altering bone mineral metabolism. PMID:21607035

  10. The ZOTECT study: Effect of zoledronic acid on bone metabolism in patients with bone metastases from prostate or breast cancer

    PubMed Central

    Hadji, Peyman; Ziller, May; Maurer, Tobias; Autenrieth, Michael; Muth, Mathias; Ruebel, Amelie; May, Christoph; Birkholz, Katrin; Diebel, Erhardt; Gleissner, Jochen; Rothe, Peter; Gschwend, Juergen E.

    2012-01-01

    Purpose The ZOTECT study assesses the effect of zoledronic acid (ZOL) on bone-marker levels and potential correlations with disease outcomes in bisphosphonate-naive patients. Methods This prospective, single-arm, open-label study in bisphosphonate-naive (≥6 months) patients with bone metastases from prostate cancer (PC; n=301) or breast cancer (BC; n=99) enrolled at 98 German sites (May 2006 to July 2008) investigated the effect of ZOL (4 mg intravenously every 4 weeks×4 months, with a final follow-up at 12 months) on bone-marker levels. Secondary assessments: skeletal-related event (SRE) rate, pain, quality of life (QoL), and prostate-specific antigen levels. Endpoints were assessed using summary statistics by visit/tumor type and Kaplan–Meier analyses. Results ZOL treatment significantly decreased bone-marker levels (amino-terminal propeptide of type I collagen [P1NP], C-terminal cross-linking telopeptide of type I collagen [CTX]; P<0.0001), and this decrease was maintained through the final 1-year follow-up visit. Baseline P1NP and CTX levels correlated with extent of bone disease (P<0.0001, each) and on-treatment decreases in marker levels. Skeletal disease burden and bone-marker levels were similar between PC and BC patients, and ZOL did not significantly influence osteoprotegerin/receptor activator of nuclear factor-κB ligand levels. Only 13 SREs occurred in 11 patients, supporting the known ZOL-mediated reduction in SREs. On-treatment bone-marker level changes did not correlate with SRE rate, pain scores, or QoL. Generally, ZOL was well tolerated and adverse events were consistent with its known safety profile. Conclusions This study confirms that ZOL therapy significantly reduces bone turnover (measured as P1NP and CTX levels) in patients with bone metastases from PC or BC. PMID:26909262

  11. Bone cells, sclerostin, and FGF23: what's bred in the bone will come out in the flesh.

    PubMed

    Ott, Susan M

    2015-03-01

    Bone metabolism is linked to systemic diseases, and new research shows that the bone cells have endocrine functions that affect multiple organs. They secrete sclerostin, FGF23, prostaglandins, and osteocalcin. Pereira et al. examined gene expression of cells grown from bone biopsies of adolescents with renal osteodystrophy, as a first step to understanding how the bone-cell abnormalities contribute to cardiovascular and metabolic problems in these patients. PMID:25723633

  12. Effects of boric acid supplementation on bone histomorphometry, metabolism, and biomechanical properties in aged female F-344 rats.

    PubMed

    Gallardo-Williams, Maria T; Maronpot, Robert R; Turner, Charles H; Johnson, Christopher S; Harris, Martha W; Jayo, Manuel J; Chapin, Robert E

    2003-01-01

    Postmenopausal women may benefit from dietary interventions in order to increase bone strength and prevent fractures. Dietary boron (B) may be beneficial for optimal calcium metabolism and, as a consequence, optimal bone metabolism. The present study evaluated the effects of boron, in the form of boric acid, with or without 17beta-estradiol (E2) supplementation (via subcutaneous implant), in ovariectomized (OVX) aged 13- mo-old F-344 rats. Boric acid was administered by gavage at a subtoxic dose (8.7 mg B/kg/d) for 40 d. Results indicate that serum level of minerals as well as osteocalcin (a marker of bone resorption) are dependent to a greater extent on the hormonal status of the animals than on boron supplementation. Boron treatment increased the E2-induced elevation of urinary calcium and magnesium. Bone mineral density (BMD) of the L5 vertebra and proximal femur was highest in the E2-treated groups; no increase in BMD was conferred by boron treatment. By histomorphometry of the proximal tibial metaphysis, osteoblastic, osteoid, and eroded surfaces were significantly suppressed by E2 treatment, but not by boron treatment. In biomechanical testing of femur and vertebra, neither E2 nor boron treatment significantly increased bone strength. At the levels given, boron alone provided no protection against OVX-induced osteopenia. In addition, combination therapy (B + E2) provided no additional benefits over those of 17beta-estradiol treatment alone in this aged rat model. PMID:12835499

  13. AGE-RELATED FACTORS AFFECTING THE POST-YIELD ENERGY DISSIPATION OF HUMAN CORTICAL BONE

    PubMed Central

    Nyman, Jeffry S.; Roy, Anuradha; Tyler, Jerrod H.; Acuna, Rae L.; Gayle, Heather J.; Wang, Xiaodu

    2007-01-01

    The risk of bone fracture depends in part on the quality of the tissue, not just the size and mass. This study assessed the post-yield energy dissipation of cortical bone in tension as a function of age and composition. Tensile specimens were prepared from tibiae of human cadavers in which male and female donors were divided into two age groups: middle aged (51 to 56 years old, n = 9) and elderly (72 to 90 years old, n = 8). By loading, unloading, and reloading a specimen with rest period inserted in between, tensile properties at incremental strain levels were assessed. In addition, the post-yield toughness was estimated and partitioned as follows: plastic strain energy related to permanent deformation, released elastic strain energy related to stiffness loss, and hysteresis energy related to viscous behavior. Porosity, mineral and collagen content, and collagen crosslinks of each specimen were also measured to determine the micro and ultrastructural properties of the tissue. It was found that age affected all the energy terms plus strength but not elastic stiffness. The post-yield energy terms were correlated with porosity, pentosidine (a marker of non-enzymatic crosslinks), and collagen content, all of which significantly varied with age. General linear models with the highest possible R2 value suggested that the pentosidine concentration and collagen content provided the best explanation of the age-related decrease in the post-yield energy dissipation of bone. Among them, pentosidine concentration had the greatest contribution to plastic strain energy and was the best explanatory variable of damage accumulation. PMID:17266142

  14. Transcription Interference and ORF Nature Strongly Affect Promoter Strength in a Reconstituted Metabolic Pathway

    PubMed Central

    Carquet, Marie; Pompon, Denis; Truan, Gilles

    2015-01-01

    Fine tuning of individual enzyme expression level is necessary to alleviate metabolic imbalances in synthetic heterologous pathways. A known approach consists of choosing a suitable combination of promoters, based on their characterized strengths in model conditions. We questioned whether each step of a multiple-gene synthetic pathway could be independently tunable at the transcription level. Three open reading frames, coding for enzymes involved in a synthetic pathway, were combinatorially associated to different promoters on an episomal plasmid in Saccharomyces cerevisiae. We quantified the mRNA levels of the three genes in each strain of our generated combinatorial metabolic library. Our results evidenced that the ORF nature, position, and orientation induce strong discrepancies between the previously reported promoters’ strengths and the observed ones. We conclude that, in the context of metabolic reconstruction, the strength of usual promoters can be dramatically affected by many factors. Among them, transcriptional interference and ORF nature seem to be predominant. PMID:25767795

  15. Negative association between metabolic syndrome and bone mineral density in Koreans, especially in men.

    PubMed

    Kim, Ha Young; Choe, Jae Won; Kim, Hong Kyu; Bae, Sung Jin; Kim, Beom Jun; Lee, Seung Hun; Koh, Jung-Min; Han, Ki Ok; Park, Hyoung Moo; Kim, Ghi Su

    2010-05-01

    Cardiovascular disease and osteoporosis are thought to share common risk factors, and metabolic syndrome (MS) is composed of major risk factors for cardiovascular disease. This study was performed to investigate the relationships between specific MS components and bone mineral density (BMD). BMD was measured at the femoral neck of Korean men aged 40 years or more (n = 1,780) and postmenopausal women (n = 1,108) using dual-energy X-ray absorptiometry. We identified subjects with MS as defined by two criteria, International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI). Body fat and lean mass were measured via bioimpedance analysis. The prevalence of MS was 19.8% and 7.7% in men and 20.8% and 11.6% in postmenopausal women according to the AHA/NHLBI definition and the IDF definition, respectively. After multivariate adjustment, femoral neck BMD was significantly lower in subjects with MS regardless of diagnostic criteria. BMD decreased as the number of MS components increased (P < 0.001 for trends in both sexes). Among MS components, waist circumference was the most important factor in this negative association. When multiple linear regression models were applied to each 5-kg weight stratum to test for a linear trend, waist circumference and fat mass were negatively associated with BMD and lean mass was positively associated with BMD in men but not in women. MS was associated with a lower BMD in Korean men and postmenopausal women, suggesting that visceral fat may lead to bone loss, especially in men. PMID:20354685

  16. Cardiac Metabolic Pathways Affected in the Mouse Model of Barth Syndrome

    PubMed Central

    Huang, Yan; Powers, Corey; Madala, Satish K.; Greis, Kenneth D.; Haffey, Wendy D.; Towbin, Jeffrey A.; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W.; Khuchua, Zaza

    2015-01-01

    Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS. PMID:26030409

  17. Cardiac metabolic pathways affected in the mouse model of barth syndrome.

    PubMed

    Huang, Yan; Powers, Corey; Madala, Satish K; Greis, Kenneth D; Haffey, Wendy D; Towbin, Jeffrey A; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W; Khuchua, Zaza

    2015-01-01

    Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS. PMID:26030409

  18. Leucine metabolism regulates TRI6 expression and affects deoxynivalenol production and virulence in Fusarium graminearum.

    PubMed

    Subramaniam, Rajagopal; Narayanan, Swara; Walkowiak, Sean; Wang, Li; Joshi, Manisha; Rocheleau, Hélène; Ouellet, Thérèse; Harris, Linda J

    2015-11-01

    TRI6 is a positive regulator of the trichothecene gene cluster and the production of trichothecene mycotoxins [deoxynivalenol (DON)] and acetylated forms such as 15-Acetyl-DON) in the cereal pathogen Fusarium graminearum. As a global transcriptional regulator, TRI6 expression is modulated by nitrogen-limiting conditions, sources of nitrogen and carbon, pH and light. However, the mechanism by which these diverse environmental factors affect TRI6 expression remains underexplored. In our effort to understand how nutrients affect TRI6 regulation, comparative digital expression profiling was performed with a wild-type F. graminearum and a Δtri6 mutant strain, grown in nutrient-rich conditions. Analysis showed that TRI6 negatively regulates genes of the branched-chain amino acid (BCAA) metabolic pathway. Feeding studies with deletion mutants of MCC, encoding methylcrotonyl-CoA-carboxylase, one of the key enzymes of leucine metabolism, showed that addition of leucine specifically down-regulated TRI6 expression and reduced 15-ADON accumulation. Constitutive expression of TRI6 in the Δmcc mutant strain restored 15-ADON production. A combination of cellophane breach assays and pathogenicity experiments on wheat demonstrated that disrupting the leucine metabolic pathway significantly reduced disease. These findings suggest a complex interaction between one of the primary metabolic pathways with a global regulator of mycotoxin biosynthesis and virulence in F. graminearum. PMID:26248604

  19. Bromochloromethane, a Methane Analogue, Affects the Microbiota and Metabolic Profiles of the Rat Gastrointestinal Tract

    PubMed Central

    Yang, Yu-Xiang; Mu, Chun-Long; Luo, Zhen

    2015-01-01

    Bromochloromethane (BCM), an inhibitor of methanogenesis, has been used in animal production. However, little is known about its impact on the intestinal microbiota and metabolic patterns. The present study aimed to investigate the effect of BCM on the colonic bacterial community and metabolism by establishing a Wistar rat model. Twenty male Wistar rats were randomly divided into two groups (control and treated with BCM) and raised for 6 weeks. Bacterial fermentation products in the cecum were determined, and colonic methanogens and sulfate-reducing bacteria (SRB) were quantified. The colonic microbiota was analyzed by pyrosequencing of the 16S rRNA genes, and metabolites were profiled by gas chromatography and mass spectrometry. The results showed that BCM did not affect body weight and feed intake, but it did significantly change the intestinal metabolic profiles. Cecal protein fermentation was enhanced by BCM, as methylamine, putrescine, phenylethylamine, tyramine, and skatole were significantly increased. Colonic fatty acid and carbohydrate concentrations were significantly decreased, indicating the perturbation of lipid and carbohydrate metabolism by BCM. BCM treatment decreased the abundance of methanogen populations, while SRB were increased in the colon. BCM did not affect the total colonic bacterial counts but significantly altered the bacterial community composition by decreasing the abundance of actinobacteria, acidobacteria, and proteobacteria. The results demonstrated that BCM treatment significantly altered the microbiotic and metabolite profiles in the intestines, which may provide further information on the use of BCM in animal production. PMID:26567308

  20. Changes in bone structure and metabolism during simulated weightlessness: Endocrine and dietary factors

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Wronski, T. J.

    1985-01-01

    The role of vitamin D, PTH and corticosterone in the skeletal alterations induced by simulated weightlessness was examined. The first objective was to determine if changes in the serum concentrations of Ca, P sub i, osteocalcin, 25-OH-D, 24,25(OH)2D or 1,25(OH)2D also occur following acute skeletal unloading. Animals were either suspended or pair fed for 2, 5, 7, 10, 12 and 15 days and the serum concentrations of Ca, P sub i, osteocalcin and the vitamin D metabolites measured. Bone histology was examined at day 5 after suspension. Acute skeletal unloading produced a transient hypercalcemia, a significant fall in serum osteocalcin and serum 1,25(OH)2D, a slight rise in serum 24,25(OH)2D, but did not affect the serum concentrations of P sub i or 25-OH-D. At the nadir in serum 1,25(OH)2D serum osteocalcin was reduced by 22%, osteoblast surface by 32% and longitudinal bone growth by 21%.

  1. Mode of heparin attachment to nanocrystalline hydroxyapatite affects its interaction with bone morphogenetic protein-2.

    PubMed

    Goonasekera, Chandhi S; Jack, Kevin S; Bhakta, Gajadhar; Rai, Bina; Luong-Van, Emma; Nurcombe, Victor; Cool, Simon M; Cooper-White, Justin J; Grøndahl, Lisbeth

    2015-01-01

    Heparin has a high affinity for bone morphogenetic protein-2 (BMP-2), which is a key growth factor in bone regeneration. The aim of this study was to investigate how the rate of release of BMP-2 was affected when adsorbed to nanosized hydroxyapatite (HAP) particles functionalized with heparin by different methods. Heparin was attached to the surface of HAP, either via adsorption or covalent coupling, via a 3-aminopropyltriethoxysilane (APTES) layer. The chemical composition of the particles was evaluated using X-ray photoelectron spectroscopy and elemental microanalysis, revealing that the heparin grafting densities achieved were dependent on the curing temperature used in the fabrication of APTES-modified HAP. Comparable amounts of heparin were attached via both covalent coupling and adsorption to the APTES-modified particles, but characterization of the particle surfaces by zeta potential and Brunauer-Emmett-Teller measurements indicated that the conformation of the heparin on the surface was dependent on the method of attachment, which in turn affected the stability of heparin on the surface. The release of BMP-2 from the particles after 7 days in phosphate-buffered saline found that 31% of the loaded BMP-2 was released from the APTES-modified particles with heparin covalently attached, compared to 16% from the APTES-modified particles with the heparin adsorbed. Moreover, when heparin was adsorbed onto pure HAP, it was found that the BMP-2 released after 7 days was 5% (similar to that from unmodified HAP). This illustrates that by altering the mode of attachment of heparin to HAP the release profile and total release of BMP-2 can be manipulated. Importantly, the BMP-2 released from all the heparin particle types was found by the SMAD 1/5/8 phosphorylation assay to be biologically active. PMID:26474791

  2. [THE ANALYSIS OF INDICATORS OF MINERAL METABOLISM IN PATIENTS WITH DEGENERATIVE DYSTROPHIC AFFECTIONS OF JOINTS].

    PubMed

    Gasanova, A G; Matveeva, E L; Spirkina, E S

    2015-12-01

    The analysis of indicators of mineral metabolism in patients with degenerative dystrophic affections of joints demonstrated that under development of osteoarthrosis process the alteration of indicators of concentration of electrolytes in blood serum, urine and synovial fluid occurs. The stage II of process is characterized by maximal alterations of indicators. The indicator of relationship between concentration of phosphate-ion and index of phosphatases of blood serum turned out the significant coefficient of correlation. PMID:27032248

  3. Oleanolic acid and ursolic acid affect peptidoglycan metabolism in Listeria monocytogenes.

    PubMed

    Kurek, Anna; Grudniak, Anna M; Szwed, Magdalena; Klicka, Anna; Samluk, Lukasz; Wolska, Krystyna I; Janiszowska, Wirginia; Popowska, Magdalena

    2010-01-01

    The plant pentacyclic triterpenoids, oleanolic and ursolic acids, inhibit the growth and survival of many bacteria, particularly Gram-positive species, including pathogenic ones. The effect of these compounds on the facultative human pathogen Listeria monocytogenes was examined. Both acids affected cell morphology and enhanced autolysis of the bacterial cells. Autolysis of isolated cell walls was inhibited by oleanolic acid, but the inhibitory activity of ursolic acid was less pronounced. Both compounds inhibited peptidoglycan turnover and quantitatively affected the profile of muropeptides obtained after digestion of peptidoglycan with mutanolysin. These results suggest that peptidoglycan metabolism is a cellular target of oleanolic and ursolic acids. PMID:19894138

  4. Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity?

    PubMed

    Chesney, Russell W; Hedberg, Gail E; Rogers, Quinton R; Dierenfeld, Ellen S; Hollis, Bruce E; Derocher, Andrew; Andersen, Magnus

    2009-01-01

    Rickets and fractures have been reported in captive polar bears. Taurine (TAU) is key for the conjugation of ursodeoxycholic acid (UDCA), a bile acid unique to bears. Since TAU-conjugated UDCA optimizes fat and fat-soluble vitamin absorption, we asked if TAU deficiency could cause vitamin D malabsorption and lead to metabolic bone disease in captive polar bears. We measured TAU levels in plasma (P) and whole blood (WB) from captive and free-ranging cubs and adults, and vitamin D3 and TAU concentrations in milk samples from lactating sows. Plasma and WB TAU levels were significantly higher in cubs vs captive and free-ranging adult bears. Vitamin D in polar bear milk was 649.2 +/- 569.2 IU/L, similar to that found in formula. The amount of TAU in polar bear milk is 3166.4 +/- 771 nmol/ml, 26-fold higher than in formula. Levels of vitamin D in bear milk and formula as well as in plasma do not indicate classical nutritional vitamin D deficiency. Higher dietary intake of TAU by free-ranging cubs may influence bile acid conjugation and improve vitamin D absorption. PMID:19239163

  5. Intermittent parathyroid hormone (PTH) treatment and age-dependent effects on rat cancellous bone and mineral metabolism.

    PubMed

    Friedl, Gerald; Turner, Russell T; Evans, Glenda L; Dobnig, Harald

    2007-11-01

    In recent years, intermittent PTH treatment has been investigated extensively for its efficacy in preventing osteoporotic fractures and to improve fracture healing and implant fixation. Although these tasks concern patients of all ages, very little is known about whether aging impacts the bone anabolic response to PTH. Female Sprague-Dawley rats of 1, 3, and 13 months of age were either treated by hPTH-(1-34) or by vehicle solution (CTR) for 1 week. As main outcome measures, we determined the effects on static and dynamic histomorphometry of cancellous bone. In addition, we measured gene expression in femur and serum parameters reflecting bone turnover and mineral metabolism. There was a profound decrease in bone formation rate (BFR) with aging in CTR rats, whereas PTH treatment resulted in a significant relative 1.5-, 3-, and 4.7-fold increase in BFR, without altering indices of bone resorption. Aging decreased and PTH increased mRNA levels for bone matrix proteins and growth factors in a gene-specific manner. In younger animals, PTH-induced a marked stimulation in the mineral apposition rate with no effect on osteoblast number, whereas the latter was increased in older animals (1.0-, 1.7-, and 3.1-fold). Treatment with PTH in young rats led to a significant increase in trabecular number (1.6-2.6/mm, p < 0.05), whereas older rats demonstrated increases in trabecular thickness only (52.8-77.8 microm, p < 0.001). Although PTH increased bone formation at all ages, we found significant age-related differences in the cellular and molecular mechanisms involved in the bone anabolic response to the hormone. PMID:17557320

  6. Osseointegration of dental implants in 3D-printed synthetic onlay grafts customized according to bone metabolic activity in recipient site.

    PubMed

    Tamimi, Faleh; Torres, Jesus; Al-Abedalla, Khadijeh; Lopez-Cabarcos, Enrique; Alkhraisat, Mohammad H; Bassett, David C; Gbureck, Uwe; Barralet, Jake E

    2014-07-01

    Onlay grafts made of monolithic microporous monetite bioresorbable bioceramics have the capacity to conduct bone augmentation. However, there is heterogeneity in the graft behaviour in vivo that seems to correlate with the host anatomy. In this study, we sought to investigate the metabolic activity of the regenerated bone in monolithic monetite onlays by using positron emission tomography-computed tomography (PET-CT) in rats. This information was used to optimize the design of monetite onlays with different macroporous architecture that were then fabricated using a 3D-printing technique. In vivo, bone augmentation was attempted with these customized onlays in rabbits. PET-CT findings demonstrated that bone metabolism in the calvarial bone showed higher activity in the inferior and lateral areas of the onlays. Histological observations revealed higher bone volume (up to 47%), less heterogeneity and more implant osseointegration (up to 38%) in the augmented bone with the customized monetite onlays. Our results demonstrated for the first time that it is possible to achieve osseointegration of dental implants in bone augmented with 3D-printed synthetic onlays. It was also observed that designing the macropore geometry according to the bone metabolic activity was a key parameter in increasing the volume of bone augmented within monetite onlays. PMID:24726538

  7. The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism

    PubMed Central

    Coluzzi, Flaminia; Pergolizzi, Joseph; Raffa, Robert B; Mattia, Consalvo

    2015-01-01

    The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density. PMID:25848298

  8. Absence of cumulus cells during in vitro maturation affects lipid metabolism in bovine oocytes.

    PubMed

    Auclair, Sylvain; Uzbekov, Rustem; Elis, Sébastien; Sanchez, Laura; Kireev, Igor; Lardic, Lionel; Dalbies-Tran, Rozenn; Uzbekova, Svetlana

    2013-03-15

    Cumulus cells (CC) surround the oocyte and are coupled metabolically through regulation of nutrient intake. CC removal before in vitro maturation (IVM) decreases bovine oocyte developmental competence without affecting nuclear meiotic maturation. The objective was to investigate the influence of CC on oocyte cytoplasmic maturation in relation to energy metabolism. IVM with either cumulus-enclosed (CEO) or -denuded (DO) oocytes was performed in serum-free metabolically optimized medium. Transmission electron microscopy revealed different distribution of membrane-bound vesicles and lipid droplets between metaphase II DO and CEO. By Nile Red staining, a significant reduction in total lipid level was evidenced in DO. Global transcriptomic analysis revealed differential expression of genes regulating energy metabolism, transcription, and translation between CEO and DO. By Western blot, fatty acid synthase (FAS) and hormone-sensitive phospholipase (HSL) proteins were detected in oocytes and in CC, indicating a local lipogenesis and lypolysis. FAS protein was significantly less abundant in DO that in CEO and more highly expressed in CC than in the oocytes. On the contrary, HSL protein was more abundant in oocytes than in CC. In addition, active Ser⁵⁶³-phosphorylated HSL was detected in the oocytes only after IVM, and its level was similar in CEO and DO. In conclusion, absence of CC during IVM affected lipid metabolism in the oocyte and led to suboptimal cytoplasmic maturation. Thus, CC may influence the oocyte by orienting the consumption of nutritive storage via regulation of local fatty acid synthesis and lipolysis to provide energy for maturation. PMID:23321473

  9. Alendronate and Resistive Exercise Countermeasures Against Bed Rest-Induced Bone Loss: Biochemical Markers of Bone and Calcium Metabolism

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Nillen, Jeannie L.; Davis-Street, Janis E.; DeKerlegand, Diane E.; LeBlanc, Adrian; Shackelford, Linda C.

    2001-01-01

    Weightlessness-induced bone loss must be counteracted to ensure crew health during extendedduration space missions. Studies were conducted to assess two bone loss countermeasures in a ground-based model: horizontal bed rest. Following a 3-wk ambulatory adaptation period, male and female subjects (aged 21-56 y) completed a 17-wk bed rest protocol. Subjects were assigned to one of three treatments: alendronate (ALEN; 10 mg/d, n=6), resistive exercise (RE; 1.5 h/d, 6 d/wk, n=8), or control (CN; no countermeasure, n=8). Dietary intake was adjusted to maintain body weight. Endocrine and biochemical indices were measured in blood and urine using standard laboratory methods. All data reported are expressed as percent change from individual pre-bedrest data. Serum calcium changed little during bed rest, and tended to decrease (4-8%) in ALEN subjects. In RE subjects, bone alkaline phosphatase and osteocalcin were increased >65 and >30%, respectively, during bed rest, while these were unchanged or decreased in ALEN and CN subjects. Urinary calcium was increased 50% in CN subjects, but was unchanged or decreased in both ALEN and RE groups. Urinary n-telopeptide excretion was increased 40-50% in CN and RE subjects, but decreased 20% in ALEN subjects. Pyridinium crosslink and deoxypyridinoline excretion were increased 20-50% during bed rest. These data suggest that RE countermeasures are effective at increasing markers of bone formation in an analog of weightlessness, while ALEN reduces markers of bone resorption. Counteracting the bone loss of space flight may require both pharmacologic and exercise countermeasures.

  10. Perinatal Exposure to Perfluorooctane Sulfonate Affects Glucose Metabolism in Adult Offspring

    PubMed Central

    Wan, Hin T.; Zhao, Yin G.; Leung, Pik Y.; Wong, Chris K. C.

    2014-01-01

    Perfluoroalkyl acids (PFAAs) are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0) were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21). To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders. PMID:24498028

  11. Which metabolic imaging, besides bone scan with 99mTc-phosphonates, for detecting and evaluating bone metastases in prostatic cancer patients? An open discussion.

    PubMed

    Bombardieri, E; Setti, L; Kirienko, M; Antunovic, L; Guglielmo, P; Ciocia, G

    2015-12-01

    Prostate cancer bone metastases occur frequently in advanced cancer and this is matter of particular attention, due to the great impact on patient's management and considering that a lot of new emerging therapeutic options have been recently introduced. Imaging bone metastases is essential to localize lesions, to establish their size and number, to study characteristics and changes during therapy. Besides radiological imaging, nuclear medicine modalities can image their features and offer additional information about their metabolic behaviour. They can be classified according to physical characteristics, type of detection, mechanism of uptake, availability for daily use. The physiopathology of metastases formation and the mechanisms of tracer uptake are essential to understand the interpretation of nuclear medicine images. Therefore, radiopharmaceuticals for bone metastases can be classified in agents targeting bone (99mTc-phosphonates, 18F-fluoride) and those targeting prostatic cancer cells (18F-fluoromethylcholine, 11C-choline, 18F-fluorodeoxyglucose). The modalities using the first group of tracers are planar bone scan, SPECT or SPECT/CT with 99mTc-diphosphonates, and 18F-fluoride PET/CT, while the modalities using the second group include 18F/11C-choline derivatives PET/CT, 18F-FDG PET/CT and PET/CT scans with several other radiopharmaceuticals described in the literature, such as 18F/11C-acetate derivatives, 18F-fluoro-5α-dihydrotestosterone (FDHT), 18F-anti-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), 18F-2'-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU) and 68Ga-labeled-prostate specific membrane antigen (PMSA) PET/TC. However, since data on clinical validation for these last novel modalities are not conclusive and/or are not still sufficient in number, at present they can be still considered as promising tools under evaluation. The present paper considers the nuclear modalities today available for the clinical routine. This overview wants

  12. Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

    PubMed Central

    Lee, Mi Jin; Lee, Seung Jun; Yun, Su Jin; Jang, Ji-Young; Kang, Hangoo; Kim, Kyongmin; Choi, In-Hong; Park, Sun

    2016-01-01

    The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs’ treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs’ treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS. PMID:26730190

  13. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster

    PubMed Central

    Wagner, Anika E.; Piegholdt, Stefanie; Rabe, Doerte; Baenas, Nieves; Schloesser, Anke; Eggersdorfer, Manfred; Stocker, Achim; Rimbach, Gerald

    2015-01-01

    In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies. PMID:26375250

  14. Evidence that high pCO2 affects protein metabolism in tropical reef corals.

    PubMed

    Edmunds, Peter J; Wall, Christopher B

    2014-08-01

    Early life stages of the coral Seriatopora caliendrum were used to test the hypothesis that the depression of dark respiration in coral recruits by high pCO2 is caused by perturbed protein metabolism. First, the contribution of protein anabolism to respiratory costs under high pCO2 was evaluated by measuring the aerobic respiration of S. caliendrum recruits with and without the protein synthesis inhibitor emetine following 1 to 4 days at 45 Pa versus 77 Pa pCO2. Second, protein catabolism under high pCO2 was evaluated by measuring the flux of ammonium (NH4 (+)) from juvenile colonies of S. caliendrum incubated in darkness at 47 Pa and 90 Pa pCO2. Two days after settlement, respiration of recruits was affected by an interaction between emetine and pCO2, with emetine reducing respiration 63% at 45 Pa pCO2 and 27% at 77 Pa pCO2. The interaction disappeared 5 days after settlement, when respiration was reduced 27% by emetine under both pCO2 conditions. These findings suggest that protein anabolism accounted for a large proportion of metabolic costs in coral recruits and was affected by high pCO2, with consequences detected in aerobic respiration. Juvenile S. caliendrum showed net uptake of NH4 (+) at 45 Pa pCO2 but net release of NH4 (+) at 90 Pa pCO2, indicating that protein catabolism, NH4 (+) recycling, or both were affected by high pCO2. Together, these results are consistent with the hypothesis that high pCO2 affects protein metabolism in corals. PMID:25216504

  15. [Effects of weightlessness on phosphorus and calcium metabolism and bone remodeling].

    PubMed

    Alexandre, C; Chappard, D; Vico, L; Minaire, P; Riffat, G

    1986-05-17

    Weightlessness results in negative calcium balance which can only reflect a redistribution of calcium in the body: the loss of calcium in the faeces and/or urine is constant, but an increase in urinary hydroxyproline indicating bone collagen destruction is not always detectable; moreover, a slowing down of collagen maturation may be suspected. Bone analysis by histomorphometry in animals and by indirect, non-invasive methods in man shows a decrease in bone mass. However, this bone tissue atrophy might only reflect excessive ageing of the bone during weightlessness, as suggested by slow bone formation and lack of variation in bone resorption. Since the experimental results obtained in men and animals during simulated weightlessness on earth are not strictly identical with those observed in space- flights, their validity may be questioned. Additional studies (notably histomorphometric studies) are therefore required for a better knowledge, as well as prevention, of the problems raised by human life in space. PMID:2940573

  16. Effects on bone metabolism of new therapeutic strategies with standard chemotherapy and biologic drugs

    PubMed Central

    Ciolli, Stefania

    2013-01-01

    Summary Recent biological advances have provided the framework for novel therapeutic strategies in oncology. Many new treatments are now based on standard cytotoxic drugs plus biologic agents. In Multiple Myeloma, a plasma cell neoplasm characterized by a severe bone disease, biologic drugs such as proteasome inhibitors and immunomodulatory agents, above their antineoplastic efficacy have a beneficial effects on bone disease. Bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of mesenchymal stem/progenitor cells into osteoblasts, resulting in new bone formation. Immunomodulatory drugs (e.g., thalidomide and lenalidomide), which are active against myeloma, also block the activity of bone-resorbing osteoclasts. These data reflect the utility of targeting endogenous mesenchymal stem/progenitor cells for the purpose of tissue repair and suggest that combining different classes of agents that are antineoplastic and also inhibit bone destruction and increase bone formation should be very beneficial for myeloma patients suffering from severe bone disease. PMID:24554928

  17. Food chain transport of nanoparticles affects behaviour and fat metabolism in fish.

    PubMed

    Cedervall, Tommy; Hansson, Lars-Anders; Lard, Mercy; Frohm, Birgitta; Linse, Sara

    2012-01-01

    Nano-sized (10(-9)-10(-7) m) particles offer many technical and biomedical advances over the bulk material. The use of nanoparticles in cosmetics, detergents, food and other commercial products is rapidly increasing despite little knowledge of their effect on organism metabolism. We show here that commercially manufactured polystyrene nanoparticles, transported through an aquatic food chain from algae, through zooplankton to fish, affect lipid metabolism and behaviour of the top consumer. At least three independent metabolic parameters differed between control and test fish: the weight loss, the triglycerides∶cholesterol ratio in blood serum, and the distribution of cholesterol between muscle and liver. Moreover, we demonstrate that nanoparticles bind to apolipoprotein A-I in fish serum in-vitro, thereby restraining them from properly utilising their fat reserves if absorbed through ingestion. In addition to the metabolic effects, we show that consumption of nanoparticle-containing zooplankton affects the feeding behaviour of the fish. The time it took the fish to consume 95% of the food presented to them was more than doubled for nanoparticle-exposed compared to control fish. Since many nano-sized products will, through the sewage system, end up in freshwater and marine habitats, our study provides a potential bioassay for testing new nano-sized material before manufacturing. In conclusion, our study shows that from knowledge of the molecular composition of the protein corona around nanoparticles it is possible to make a testable molecular hypothesis and bioassay of the potential biological risks of a defined nanoparticle at the organism and ecosystem level. PMID:22384193

  18. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases.

    PubMed

    Ruchat, Stephanie-May; Houde, Andrée-Anne; Voisin, Grégory; St-Pierre, Julie; Perron, Patrice; Baillargeon, Jean-Patrice; Gaudet, Daniel; Hivert, Marie-France; Brisson, Diane; Bouchard, Luigi

    2013-09-01

    Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk for chronic diseases, and one promising mechanism for fetal metabolic programming is epigenetics. Therefore, we postulated that GDM exposure impacts the offspring's methylome and used an epigenomic approach to explore this hypothesis. Placenta and cord blood samples were obtained from 44 newborns, including 30 exposed to GDM. Women were recruited at first trimester of pregnancy and followed until delivery. GDM was assessed after a 75-g oral glucose tolerance test at 24-28 weeks of pregnancy. DNA methylation was measured at>485,000 CpG sites (Infinium HumanMethylation450 BeadChips). Ingenuity Pathway Analysis was conducted to identify metabolic pathways epigenetically affected by GDM. Our results showed that 3,271 and 3,758 genes in placenta and cord blood, respectively, were potentially differentially methylated between samples exposed or not to GDM (p-values down to 1 × 10(-06); none reached the genome-wide significance levels), with more than 25% (n = 1,029) being common to both tissues. Mean DNA methylation differences between groups were 5.7 ± 3.2% and 3.4 ± 1.9% for placenta and cord blood, respectively. These genes were likely involved in the metabolic diseases pathway (up to 115 genes (11%), p-values for pathways = 1.9 × 10(-13)metabolic diseases pathway, with consequences on fetal growth and development, and provide supportive evidence that DNA methylation is involved in fetal metabolic programming. PMID:23975224

  19. Effect of Two-Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non-Obese Younger Adults: A Randomized Clinical Trial.

    PubMed

    Villareal, Dennis T; Fontana, Luigi; Das, Sai Krupa; Redman, Leanne; Smith, Steven R; Saltzman, Edward; Bales, Connie; Rochon, James; Pieper, Carl; Huang, Megan; Lewis, Michael; Schwartz, Ann V

    2016-01-01

    Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1 ± 1.7 kg/m(2) ), younger (age 37.9 ± 7.2 years) adults were randomly assigned to 25% CR (CR group, n = 143) or ad libitum (AL group, n = 75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5 ± 0.4 versus 0.1 ± 0.5 kg), fat mass (-5.3 ± 0.3 versus 0.4 ± 0.4 kg), and fat-free mass (-2.2 ± 0.2 versus -0.2 ± 0.2 kg) decreased in the CR group compared with AL (all between group p < 0.001). Compared with AL, the CR group had greater changes in BMD at 24 months: lumbar spine (-0.013 ± 0.003 versus 0.007 ± 0.004 g/cm(2) ; p < 0.001), total hip (-0.017 ± 0.002 versus 0.001 ± 0.003 g/cm(2) ; p < 0.001), and femoral neck (-0.015 ± 0.003 versus -0.005 ± 0.004 g/cm(2) ; p = 0.03). Changes in bone markers were greater at 12 months for C-telopeptide (0.098 ± 0.012 versus 0.025 ± 0.015 μg/L; p < 0.001), tartrate-resistant acid phosphatase (0.4 ± 0.1 versus 0.2 ± 0.1 U/L; p = 0.004), and bone-specific alkaline phosphatase (BSAP) (-1.4 ± 0.4 versus -0.3 ± 0.5 U/L; p = 0.047) but not procollagen type 1 N-propeptide; at 24 months, only BSAP differed between groups (-1.5 ± 0.4 versus 0.9 ± 0.6 U/L; p = 0.001). The CR group had larger increases in 25-hydroxyvitamin D, cortisol, and adiponectin and decreases in leptin and insulin compared with AL. However, parathyroid hormone and IGF-1 levels did not differ between groups. The CR group also had lower levels of physical activity

  20. Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery.

    PubMed

    Kovacs, Christopher S

    2016-04-01

    During pregnancy and lactation, female physiology adapts to meet the added nutritional demands of fetuses and neonates. An average full-term fetus contains ∼30 g calcium, 20 g phosphorus, and 0.8 g magnesium. About 80% of mineral is accreted during the third trimester; calcium transfers at 300-350 mg/day during the final 6 wk. The neonate requires 200 mg calcium daily from milk during the first 6 mo, and 120 mg calcium from milk during the second 6 mo (additional calcium comes from solid foods). Calcium transfers can be more than double and triple these values, respectively, in women who nurse twins and triplets. About 25% of dietary calcium is normally absorbed in healthy adults. Average maternal calcium intakes in American and Canadian women are insufficient to meet the fetal and neonatal calcium requirements if normal efficiency of intestinal calcium absorption is relied upon. However, several adaptations are invoked to meet the fetal and neonatal demands for mineral without requiring increased intakes by the mother. During pregnancy the efficiency of intestinal calcium absorption doubles, whereas during lactation the maternal skeleton is resorbed to provide calcium for milk. This review addresses our current knowledge regarding maternal adaptations in mineral and skeletal homeostasis that occur during pregnancy, lactation, and post-weaning recovery. Also considered are the impacts that these adaptations have on biochemical and hormonal parameters of mineral homeostasis, the consequences for long-term skeletal health, and the presentation and management of disorders of mineral and bone metabolism. PMID:26887676

  1. Gender- and dose-related effects of cyclosporin A on hepatic and bone metabolism.

    PubMed

    Jäger, Walter; Xu, Huiqing; Wlcek, Katrin; Schüler, Christiane; Rubel, Franz; Erben, Reinhold G

    2012-01-01

    Previous data have shown gender-related differences in the skeletal effects of the immunosuppressive drug cyclosporin A (CsA) in rats. To test the hypothesis that the gender-related skeletal effects of CsA are caused by gender-specific metabolism of this drug, we treated aged male and female sham-operated, gonadectomized (GX) as well as sex hormone-supplemented GX rats with 5 mg/kg CsA three times per week for 2 months, and analyzed the bone phenotype as well as the concentrations of CsA and its major metabolites AM1, AM1c, AM9, and AM4N in blood, urine, and liver tissue. CsA treatment induced high turnover osteopenia in males, but not females. Male rats showed several-fold higher CsA and CsA metabolite blood levels compared with females. Renal clearance data revealed that CsA undergoes selective tubular reabsorption in male, but not female rats. However, a mathematical modeling approach demonstrated that the higher CsA blood levels in males were almost exclusively caused by a 6-fold lower hepatic clearance rate compared with females. In addition, we subcutaneously treated female rats with up to 6-fold higher doses of CsA. Similar to males, high dose CsA induced high turnover osteopenia in female rats. Our data show that the gender-related differences in the skeletal effects of CsA are caused by a higher hepatic clearance rate for CsA in female compared to male rats, and not by a differential skeletal response to CsA. Moreover, our study indicates that CsA blood levels of ≤200 ng/ml measured by HPLC do not induce high turnover osteopenia in aged rats. PMID:22019458

  2. Effects of linseed oil and palm oil on growth performance, tibia fatty acid and biomarkers of bone metabolism in broilers.

    PubMed

    Zhong, X; Gao, S; Wang, J J; Dong, L; Huang, J; Zhang, L L; Wang, T

    2014-01-01

    1. This study was conducted to determine the effects of different dietary fat sources on growth performance, tibia fatty acids and biomarkers of bone metabolism in broilers. 2. One-d-old commercial Arbor Acres broilers were fed with a maize-soya bean basal diet for 42 d, supplemented with oils according to the following 5 treatments: lard (lard group); linseed oil (linseed oil group); palm oil (palm oil group); linseed oil + palm oil (60:40 or 40:60 w/w, LP-1 group and LP-2 group, respectively). 3. No significant differences in weight gain, feed intake and gain/feed ratio were observed between the lard and linseed oil groups. Birds fed on palm oil had significantly greater weight gain and feed intake than those fed on lard or linseed oil. Growth performance in LP-1 and LP-2 was significantly greater than that of single-oil groups. 4. Tibia growth and bone characteristics were not influenced by supplementation with lard, linseed oil, or palm oil alone, but broilers fed on a mixture of fats had significantly greater tibia weight and length compared to broilers fed on linseed oil. Bone mineral density in tibia was significantly increased in LP-1 and LP-2 groups. 5. Supplementation of linseed oil alone or in combination with palm oil enhanced apparent digestibility of calcium, reduced serum calcium and increased tibia calcium concentrations. Moreover, supplementation with linseed oil alone or in combination with palm oil had a positive effect on biomarkers of bone growth. 6. The combination of linseed and palm oils was beneficial for growth performance, tibia growth and biomarkers of bone metabolism. PMID:24641587

  3. Targeting bone metabolism in patients with advanced prostate cancer: current options and controversies.

    PubMed

    Todenhöfer, Tilman; Stenzl, Arnulf; Hofbauer, Lorenz C; Rachner, Tilman D

    2015-01-01

    Maintaining bone health remains a clinical challenge in patients with prostate cancer (PC) who are at risk of developing metastatic bone disease and increased bone loss due to hormone ablation therapy. In patients with cancer-treatment induced bone loss (CTIBL), antiresorptive agents have been shown to improve bone mineral density (BMD) and to reduce the risk of fractures. For patients with bone metastases, both zoledronic acid and denosumab delay skeletal related events (SREs) in the castration resistant stage of disease. Novel agents targeting the Wnt inhibitors dickkopf-1 and sclerostin are currently under investigation for the treatment of osteoporosis and malignant bone disease. New antineoplastic drugs such as abiraterone, enzalutamide, and Radium-223 are capable of further delaying SREs in patients with advanced PC. The benefit of antiresorptive treatment for patients with castration sensitive PC appears to be limited. Recent trials on the use of zoledronic acid for the prevention of bone metastases failed to be successful, whereas denosumab delayed the occurrence of bone metastases by a median of 4.1 months. Currently, the use of antiresorptive drugs to prevent bone metastases still remains a field of controversies and further trials are needed to identify patient subgroups that may profit from early therapy. PMID:25802521

  4. Osteoporosis and bone metabolic parameters in dependence upon calcium intake through milk and milk products.

    PubMed

    Stracke, H; Renner, E; Knie, G; Leidig, G; Minne, H; Federlin, K

    1993-09-01

    The bone mineral content of young adults as well as of osteoporotic patients and age-matched controls without bone disease was measured by single-photon absorptiometry. A retrospective nutrition survey was additionally made to study the relationship between bone mineral content and calcium intake in different periods of life. The bone mineral content and bone mineral density of young adults is directly related to the calcium intake through milk and dairy products. The osteoporotics had a significantly lower bone mineral content than the controls. Calcium intake through milk and milk products in childhood and adolescence had been significantly lower in the patients than in the controls, whereas in the later periods of life (20-30 years prior to the study and at the time of the study) there were no significant differences between the calcium intakes of the two groups. It was also found that an adequate intake of calcium protected against increased bone resorption, as evidenced in particular by the reduced levels of serum osteocalcin, a parameter of bone turnover. In conclusion it can be stated that the data support the hypothesis that adequate calcium intake through milk and milk products in childhood and adolescence is a decisive marker for obtaining a maximum bone mass (peak adult bone mass) and for the prevention of osteoporosis. Furthermore, it can be stated that increased calcium intake in the later years may not reduce the accelerated risk of osteoporosis resulting from inadequate calcium intake during childhood and adolescence. PMID:8243426

  5. [IMPACT OF RADIAL SHOCK-WAVE THERAPY OF A LOW FREQUENCY ON METABOLIC PROCESSES IN THE BONE TISSUE IN TRAUMATIC TIBIAL DEFECTS IN EXPERIMENT].

    PubMed

    Magomedov, A M; Gertsen, G I; Fey, Se; Kuzub, T A; Krinitskaya, O F

    2016-04-01

    Results of investigations on impact of radial shock-wave therapy of low frequency on metabolism of the main protein of the bone tissue (collagen) as well as on the enzymes activity, taking part in a catabolic phase of the protein metabolism, were studied. Changes in content of glycosaminoglycans under impact of the therapy in experimental animals were studied. PMID:27434960

  6. Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives

    PubMed Central

    Mawet, Marie; Maillard, Catherine; Klipping, Christine; Zimmerman, Yvette; Foidart, Jean-Michel; Coelingh Bennink, Herjan J.T.

    2015-01-01

    Abstract Objectives Estetrol (E4) is a natural estrogen produced by the human fetal liver. In combination with drospirenone (DRSP) or levonorgestrel (LNG), E4 blocks ovulation and has less effect on haemostatic biomarkers in comparison with ethinylestradiol (EE) combined with DRSP. This study evaluates the impact of several doses of E4/DRSP and E4/LNG on safety parameters such as liver function, lipid metabolism, bone markers and growth endocrine parameters. Methods This was a dose-finding, single-centre, controlled study performed in healthy women aged 18 to 35 years with a documented pretreatment ovulatory cycle. Participants received 5 mg or 10 mg E4/3 mg DRSP; 5 mg, 10 mg or 20 mg E4/150 μg LNG; or 20 μg EE/3 mg DRSP as a comparator for three consecutive cycles in a 24/4-day regimen. Changes from baseline to end of treatment in liver parameters, lipid metabolism, bone markers and growth endocrinology were evaluated. Results A total of 109 women were included in the study. Carrier proteins were minimally affected in the E4/DRSP and E4/LNG groups, in comparison with the EE/DRSP group, where a significant increase in sex hormone-binding globulin was observed. Similarly, minor effects on lipoproteins were observed in the E4 groups, and the effects on triglycerides elicited by the E4 groups were significantly lower than those in the EE/DRSP group. No imbalances in bone markers were observed in any groups. No alterations in insulin-like growth factor were observed in the E4 groups. Conclusions E4-containing combinations have a limited effect on liver function, lipid metabolism, and bone and growth endocrine parameters. Chinese Abstract 摘要 目的 雌四醇(E4)是来源于人胎儿肝脏的天然雌激素。雌四醇与屈螺酮(DRSP)或左炔诺孕酮(LNG)配伍的复方口服避孕药制剂,能够抑制排卵,同时相较于炔雌醇(EE)与屈螺酮配伍制剂,它对凝血功能的各项指标影响较小。本研究的目的是为了评估不同

  7. Dietary restriction does not adversely affect bone geometry and mechanics in rapidly growing male wistar rats.

    PubMed

    Lambert, Jennifer; Lamothe, Jeremy M; Zernicke, Ronald F; Auer, Roland N; Reimer, Raylene A

    2005-02-01

    The present study assessed the effects of dietary restriction on tibial and vertebral mechanical and geometrical properties in 2-mo-old male Wistar rats. Two-month-old male Wistar rats were randomized to the ad libitum (n=8) or the 35% diet-restricted (DR) feeding group (n=9) for 5 mo. Tibiae and L6 vertebrae were dissected out for microcomputed tomography (microCT) scanning and subsequently fractured in biomechanical testing to determine geometrical and mechanical properties. The DR group had significantly lower mean tibial length, mass, area, and cross-sectional moment of inertia, as well as vertebral energy to maximal load. After adjustment for body mass, however, DR tibial mean maximal load and stiffness, and DR vertebral area, height, volume, and maximal load were significantly greater, relative to ad libitum means. No significant differences were found between the DR and ad libitum mineral ash fractions. Because the material properties of the tibiae between the two groups were not significantly different, presumably the material integrity of the bones was not adversely affected as a consequence of DR. The similar material characteristics were consistent with mineral ash fractions that were not different between the two groups. Vertebral maximal load and stiffness were not significant between the DR and ad libitum animals. Importantly, we show that a level of dietary restriction (35%) that is less severe than many studies (40%), and without micronutrient compensation does not adversely affect tibial and vertebral mechanical properties in young growing male rats when normalized for body mass. PMID:15585686

  8. DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance

    PubMed Central

    Caron, Alexandre; Labbé, Sébastien M.; Mouchiroud, Mathilde; Huard, Renaud; Richard, Denis

    2016-01-01

    We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. PMID:27097662

  9. Nectar resource limitation affects butterfly flight performance and metabolism differently in intensive and extensive agricultural landscapes.

    PubMed

    Lebeau, Julie; Wesselingh, Renate A; Van Dyck, Hans

    2016-05-11

    Flight is an essential biological ability of many insects, but is energetically costly. Environments under rapid human-induced change are characterized by habitat fragmentation and may impose constraints on the energy income budget of organisms. This may, in turn, affect locomotor performance and willingness to fly. We tested flight performance and metabolic rates in meadow brown butterflies (Maniola jurtina) of two contrasted agricultural landscapes: intensively managed, nectar-poor (IL) versus extensively managed, nectar-rich landscapes (EL). Young female adults were submitted to four nectar treatments (i.e. nectar quality and quantity) in outdoor flight cages. IL individuals had better flight capacities in a flight mill and had lower resting metabolic rates (RMR) than EL individuals, except under the severest treatment. Under this treatment, RMR increased in IL individuals, but decreased in EL individuals; flight performance was maintained by IL individuals, but dropped by a factor 2.5 in EL individuals. IL individuals had more canalized (i.e. less plastic) responses relative to the nectar treatments than EL individuals. Our results show significant intraspecific variation in the locomotor and metabolic response of a butterfly to different energy income regimes relative to the landscape of origin. Ecophysiological studies help to improve our mechanistic understanding of the eco-evolutionary impact of anthropogenic environments on rare and widespread species. PMID:27147100

  10. Cannibalism Affects Core Metabolic Processes in Helicoverpa armigera Larvae-A 2D NMR Metabolomics Study.

    PubMed

    Vergara, Fredd; Shino, Amiu; Kikuchi, Jun

    2016-01-01

    Cannibalism is known in many insect species, yet its impact on insect metabolism has not been investigated in detail. This study assessed the effects of cannibalism on the metabolism of fourth-instar larvae of the non-predatory insect Helicoverpa armigera (Lepidotera: Noctuidea). Two groups of larvae were analyzed: one group fed with fourth-instar larvae of H. armigera (cannibal), the other group fed with an artificial plant diet. Water-soluble small organic compounds present in the larvae were analyzed using two-dimensional nuclear magnetic resonance (NMR) and principal component analysis (PCA). Cannibalism negatively affected larval growth. PCA of NMR spectra showed that the metabolic profiles of cannibal and herbivore larvae were statistically different with monomeric sugars, fatty acid- and amino acid-related metabolites as the most variable compounds. Quantitation of ¹H-(13)C HSQC (Heteronuclear Single Quantum Coherence) signals revealed that the concentrations of glucose, glucono-1,5-lactone, glycerol phosphate, glutamine, glycine, leucine, isoleucine, lysine, ornithine, proline, threonine and valine were higher in the herbivore larvae. PMID:27598144

  11. DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance.

    PubMed

    Caron, Alexandre; Labbé, Sébastien M; Mouchiroud, Mathilde; Huard, Renaud; Richard, Denis; Laplante, Mathieu

    2016-06-01

    We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection. PMID:27097662

  12. Factors that affect bone mineral accrual in the adolescent growth spurt.

    PubMed

    Whiting, Susan J; Vatanparast, Hassanali; Baxter-Jones, Adam; Faulkner, Robert A; Mirwald, Robert; Bailey, Donald A

    2004-03-01

    The development of bone mass during the growing years is an important determinant for risk of osteoporosis in later life. Adequate dietary intake during the growth period may be critical in reaching bone growth potential. The Saskatchewan Bone Mineral Accrual Study (BMAS) is a longitudinal study of bone growth in Caucasian children. We have calculated the times of maximal peak bone mineral content (BMC) velocity to be 14.0 +/- 1.0 y in boys and 12.5 +/- 0.9 y in girls; bone growth is maximal approximately 6 mo after peak height velocity. In the 2 y of peak skeletal growth, adolescents accumulate over 25% of adult bone. BMAS data may provide biological data on calcium requirements through application of calcium accrual values to factorial calculations of requirement. As well, our data are beginning to reveal how dietary patterns may influence attainment of bone mass during the adolescent growth spurt. Replacing milk intake by soft drinks appears to be detrimental to bone gain by girls, but not boys. Fruit and vegetable intake, providing alkalinity to bones and/or acting as a marker of a healthy diet, appears to influence BMC in adolescent girls, but not boys. The reason why these dietary factors appear to be more influential in girls than in boys may be that BMAS girls are consuming less than their requirement for calcium, while boys are above their threshold. Specific dietary and nutrient recommendations for adolescents are needed in order to ensure optimal bone growth and consolidation during this important life stage. PMID:14988470

  13. Factors affecting human heterocyclic amine intake and the metabolism of PhIP.

    PubMed

    Knize, Mark G; Kulp, Kristen S; Salmon, Cynthia P; Keating, Garrett A; Felton, James S

    2002-09-30

    We are working to understand possible human health effects from exposure to heterocyclic amines that are formed in meat during cooking. Laboratory-cooked beef, pork, and chicken are capable of producing tens of nanograms of MeIQx, IFP, and PhIP per gram of meat and smaller amounts of other heteroyclic amines. Well-done restaurant-cooked beef, pork, and chicken may contain PhIP and IFP at concentrations as high as tens of nanograms per gram and MeIQx at levels up to 3 ng/g. Although well-done chicken breast prepared in the laboratory may contain large amounts of PhIP, a survey of flame-grilled meat samples cooked in private homes showed PhIP levels in beef steak and chicken breast are not significantly different (P=0.36). The extremely high PhIP levels reported in some studies of grilled chicken are not seen in home-cooked samples.Many studies suggest individuals may have varying susceptibility to carcinogens and that diet may influence metabolism, thus affecting cancer susceptibility. To understand the human metabolism of PhIP, we examined urinary metabolites of PhIP in volunteers following a single well-done meat exposure. Using solid-phase extraction and LC/MS/MS, we quantified four major PhIP metabolites in human urine. In addition to investigating individual variation, we examined the interaction of PhIP with a potentially chemopreventive food. In a preliminary study of the effect of broccoli on PhIP metabolism, we fed chicken to six volunteers before and after eating steamed broccoli daily for 3 days. Preliminary results suggest that broccoli, which contains isothiocyanates shown to induce Phases I and II metabolism in vitro, may affect both the rate of metabolite excretion and the metabolic products of a dietary carcinogen. This newly developed methodology will allow us to assess prevention strategies that reduce the possible risks associated with PhIP exposure. PMID:12351155

  14. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis

    PubMed Central

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  15. Sequences of Regressions Distinguish Nonmechanical from Mechanical Associations between Metabolic Factors, Body Composition, and Bone in Healthy Postmenopausal Women123

    PubMed Central

    Goldberg, Gail R; Prentice, Ann

    2016-01-01

    Background: There is increasing recognition of complex interrelations between the endocrine functions of bone and fat tissues or organs. Objective: The objective was to describe nonmechanical and mechanical links between metabolic factors, body composition, and bone with the use of graphical Markov models. Methods: Seventy postmenopausal women with a mean ± SD age of 62.3 ± 3.7 y and body mass index (in kg/m2) of 24.9 ± 3.8 were recruited. Bone outcomes were peripheral quantitative computed tomography measures of the distal and diaphyseal tibia, cross-sectional area (CSA), volumetric bone mineral density (vBMD), and cortical CSA. Biomarkers of osteoblast and adipocyte function were plasma concentrations of leptin, adiponectin, osteocalcin, undercarboxylated osteocalcin (UCOC), and phylloquinone. Body composition measurements were lean and percent fat mass, which were derived with the use of a 4-compartment model. Sequences of Regressions, a subclass of graphical Markov models, were used to describe the direct (nonmechanical) and indirect (mechanical) interrelations between metabolic factors and bone by simultaneously modeling multiple bone outcomes and their relation with biomarker outcomes with lean mass, percent fat mass, and height as intermediate explanatory variables. Results: The graphical Markov models showed both direct and indirect associations linking plasma leptin and adiponectin concentrations with CSA and vBMD. At the distal tibia, lean mass, height, and adiponectin-UCOC interaction were directly explanatory of CSA (R2 = 0.45); at the diaphysis, lean mass, percent fat mass, leptin, osteocalcin, and age-adiponectin interaction were directly explanatory of CSA (R2 = 0.49). The regression models exploring direct associations for vBMD were much weaker, with R2 = 0.15 and 0.18 at the distal and diaphyseal sites, respectively. Lean mass and UCOC were associated, and the global Markov property of the graph indicated that this association was explained by

  16. Paget's Disease of Bone

    MedlinePlus

    ... page please turn Javascript on. Paget's Disease of Bone What is Paget's Disease of Bone? Click for more information Enlarged and Misshapen Bones Paget's disease of bone causes affected bones to ...

  17. Do the noncaffeine ingredients of energy drinks affect metabolic responses to heavy exercise?

    PubMed

    Pettitt, Robert W; Niemeyer, JoLynne D; Sexton, Patrick J; Lipetzky, Amanda; Murray, Steven R

    2013-07-01

    Energy drinks (EDs) such as Red Bull (RB) are marketed to enhance metabolism. Secondary ingredients of EDs (e.g., taurine) have been purported to improve time trial performance; however, little research exists on how such secondary ingredients affect aerobic metabolism during heavy exercise. The purpose of this study was to investigate the effect of the secondary ingredients of RB on aerobic metabolism during and subsequent to heavy exercise. In double-blind, counterbalanced, and crossover fashion, 8 recreationally trained individuals completed a graded exercise test to determine the gas exchange threshold (GET). Subjects returned on 2 separate occasions and ingested either a 245 ml serving of RB or a control (CTRL) drink with the equivalent caffeine before engaging in two 10-minute constant-load cycling bouts, at an intensity equivalent to GET, with 3 minutes of rest between bouts. Accumulated liters of O2 (10 minutes) were higher for the first bout (17.1 ± 3.5 L) vs. the second bout (16.7 ± 3.5 L) but did not differ between drinks. Similarly, excess postexercise oxygen consumption was higher after the initial bout (RB mean, 2.6 ± 0.85 L; CTRL mean, 2.9 ± 0.90 L) vs. the second bout (RB mean, 1.5 ± 0.85 L; CTRL mean, 1.9 ± 0.87 L) but did not differ between drinks. No differences occurred between drinks for measures of heart rate or rating of perceived exertion. These results indicate that the secondary ingredients contained in a single serving of RB do not augment aerobic metabolism during or subsequent to heavy exercise. PMID:23037611

  18. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model

    PubMed Central

    Tegtmeier, Dorothee; Thompson, Claire L.; Schauer, Christine

    2015-01-01

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success. PMID:26637604

  19. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model.

    PubMed

    Tegtmeier, Dorothee; Thompson, Claire L; Schauer, Christine; Brune, Andreas

    2016-02-01

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success. PMID:26637604

  20. Nonsense mutations in the human. beta. -globin gene affect mRNA metabolism

    SciTech Connect

    Baserga, S.J.; Benz, E.J. Jr. )

    1988-04-01

    A number of premature translation termination mutations (nonsense mutations) have been described in the human {alpha}- and {beta}-globin genes. Studies on mRNA isolated from patients with {beta}{sup 0}-thalassemia have shown that for both the {beta}-17 and the {beta}-39 mutations less than normal levels of {beta}-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human {beta}-globin mRNA). In vitro studies using the cloned {beta}-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. The authors have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, they have studied the effect of five nonsense mutations and two missense mutations on the expression of human {beta}-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation.

  1. Litter Environment Affects Behavior and Brain Metabolic Activity of Adult Knockout Mice

    PubMed Central

    Crews, David; Rushworth, David; Gonzalez-Lima, Francisco; Ogawa, Sonoko

    2009-01-01

    In mammals, the formative environment for social and anxiety-related behaviors is the family unit; in the case of rodents, this is the litter and the mother-young bond. A deciding factor in this environment is the sex ratio of the litter and, in the case of mice lacking functional copies of gene(s), the ratio of the various genotypes in the litter. Both Sex and Genotype ratios of the litter affect the nature and quality of the individual's behavior later in adulthood, as well as metabolic activity in brain nuclei that underlie these behaviors. Mice were raised in litters reconstituted shortly after to birth to control for sex ratio and genotype ratio (wild type pups versus pups lacking a functional estrogen receptor α). In both males and females, the Sex and Genotype of siblings in the litter affected aggressive behaviors as well as patterns of metabolic activity in limbic nuclei in the social behavior network later in adulthood. Further, this pattern in males varied depending upon the Genotype of their brothers and sisters. Principal Components Analysis revealed two components comprised of several amygdalar and hypothalamic nuclei; the VMH showed strong correlations in both clusters, suggesting its pivotal nature in the organization of two neural networks. PMID:19707539

  2. Serum biomarkers of bone metabolism in castration resistant prostate cancer patients with skeletal metastases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value ...

  3. Subtle changes in bone mineralization density distribution in most severely affected patients with chronic obstructive pulmonary disease.

    PubMed

    Misof, B M; Roschger, P; Jorgetti, V; Klaushofer, K; Borba, V Z C; Boguszewski, C L; Cohen, A; Shane, E; Zhou, H; Dempster, D W; Moreira, C A

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is associated with low aBMD as measured by DXA and altered microstructure as assessed by bone histomorphometry and microcomputed tomography. Knowledge of bone matrix mineralization is lacking in COPD. Using quantitative backscatter electron imaging (qBEI), we assessed cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) in 19 postmenopausal women (62.1 ± 7.3 years of age) with COPD. Eight had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. The BMDD outcomes from the patients were compared with healthy reference data and were correlated with previous clinical and histomorphometric findings. In general, the BMDD outcomes for the patients were not significantly different from the reference data. Neither the subgroups of with or without fragility fractures or of who did or did not receive inhaled glucocorticoid treatment, showed differences in BMDD. However, subgroup comparison according to severity revealed 10% decreased cancellous mineralization heterogeneity (Cn.CaWidth) for the most severely affected compared with less affected patients (p=0.042) and compared with healthy premenopausal controls (p=0.021). BMDD parameters were highly correlated with histomorphometric cancellous bone volume (BV/TV) and formation indices: mean degree of mineralization (Cn.CaMean) versus BV/TV (r=0.58, p=0.009), and Cn.CaMean and Ct.CaMean versus bone formation rate (BFR/BS) (r=-0.71, p<0.001). In particular, those with lower BV/TV (<50th percentile) had significantly lower Cn.CaMean (p=0.037) and higher Cn.CaLow (p=0.020) compared with those with higher (>50th percentile) BV/TV. The normality in most of the BMDD parameters and bone formation rates as well as the significant correlations between them suggests unaffected mineralization processes in COPD. Our findings also indicate no significant negative effect of treatment with inhaled glucocorticoids on the bone

  4. Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome

    PubMed Central

    Ravera, Silvia; Dufour, Carlo; Cesaro, Simone; Bottega, Roberta; Faleschini, Michela; Cuccarolo, Paola; Corsolini, Fabio; Usai, Cesare; Columbaro, Marta; Cipolli, Marco; Savoia, Anna; Degan, Paolo; Cappelli, Enrico

    2016-01-01

    Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca2+]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials. PMID:27146429

  5. Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome.

    PubMed

    Ravera, Silvia; Dufour, Carlo; Cesaro, Simone; Bottega, Roberta; Faleschini, Michela; Cuccarolo, Paola; Corsolini, Fabio; Usai, Cesare; Columbaro, Marta; Cipolli, Marco; Savoia, Anna; Degan, Paolo; Cappelli, Enrico

    2016-01-01

    Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca(2+)]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials. PMID:27146429

  6. Safety and efficacy of polycalcium for improving biomarkers of bone metabolism: a 4-week open-label clinical study.

    PubMed

    Choi, Jae-Suk; Park, Mi-Yeon; Kim, Jong-Dae; Cho, Hyung Rae; Choi, In Soon; Kim, Joo-Wan

    2013-03-01

    Polycalcium is a mixture of Polycan and calcium lactate-gluconate 1:9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies. These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety. In total, 30 healthy women (range 40-60 years) were administered 400 mg of Polycalcium for 4 weeks. The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium. After 4 weeks of Polycalcium administration, 27 subjects completed the test plan. Three subjects withdrew their consent to participate. The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by -28.44%, 14.37%, 6.11%, and 1.42%, respectively. Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by -13.40%, 6.67%, -5.13%, -22.43%, and -3.04%, respectively. Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400  mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe. Polycalcium was apparently safe and efficacious. PMID:23477624

  7. Safety and Efficacy of Polycalcium for Improving Biomarkers of Bone Metabolism: A 4-Week Open-Label Clinical Study

    PubMed Central

    Choi, Jae-Suk; Park, Mi-Yeon; Kim, Jong-Dae; Cho, Hyung Rae

    2013-01-01

    Abstract Polycalcium is a mixture of Polycan and calcium lactate–gluconate 1:9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies. These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety. In total, 30 healthy women (range 40–60 years) were administered 400 mg of Polycalcium for 4 weeks. The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium. After 4 weeks of Polycalcium administration, 27 subjects completed the test plan. Three subjects withdrew their consent to participate. The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by −28.44%, 14.37%, 6.11%, and 1.42%, respectively. Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by −13.40%, 6.67%, −5.13%, −22.43%, and −3.04%, respectively. Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400 mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe. Polycalcium was apparently safe and efficacious. PMID:23477624

  8. Mineral Metabolism and Cortical Volumetric Bone Mineral Density in Childhood Chronic Kidney Disease

    PubMed Central

    Tsampalieros, Anne K.; de Boer, Ian H.; Shults, Justine; Kalkwarf, Heidi J.; Zemel, Babette S.; Foerster, Debbie; Stokes, David; Leonard, Mary B.

    2013-01-01

    Context: The relationships among cortical volumetric bone mineral density (CortBMD) and comprehensive measures of mineral metabolism have not been addressed in chronic kidney disease (CKD). Objective: The aim of the study was to identify the determinants of CortBMD in childhood CKD. A secondary objective was to assess whether CortBMD was associated with subsequent fracture. Design and Participants: This prospective cohort study included 171 children, adolescents, and young adults (aged 5–21 years) with CKD stages 2–5D at enrollment and 89 1 year later. Outcomes: Serum measures included vitamin D [25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D], vitamin D-binding protein, intact PTH, fibroblast growth factor 23, calcium, and phosphorus. Tibia quantitative computed tomography measures of CortBMD were expressed as sex-, race-, and age-specific Z-scores based on 675 controls. Multivariable linear regression identified the independent correlates of CortBMD Z-scores and the change in CortBMD Z-scores. Results: Lower calcium (β = .31/1 mg/dL, P = .01) and 25(OH)D (β = .18/10 ng/mL, P = .04) and higher PTH (β = −.02/10%, P = .002) and 1,25(OH)2D (β = −.07/10%, P < .001) were independently associated with lower CortBMD Z-scores at baseline. The correlations of total, free, and bioavailable 25(OH)D with CortBMD did not differ. Higher baseline 1,25(OH)2D (P < .05) and greater increases in PTH (P < .001) were associated with greater declines in CortBMD Z-scores. Greater increases in calcium concentrations were associated with greater increases in CortBMD Z-scores in growing children (interaction P = .009). The hazard ratio for fracture was 1.75 (95% confidence interval 1.15–2.67; P = .009) per SD lower baseline CortBMD. Conclusions: Greater PTH and 1,25(OH)2D and lower calcium concentrations were independently associated with baseline and progressive cortical deficits in childhood CKD. Lower CortBMD Z-score was

  9. The negative bone effects of the disease and of chronic corticosteroid treatment in premenopausal women affected by rheumatoid arthritis.

    PubMed

    Fassio, A; Idolazzi, L; Jaber, M A; Dartizio, C; Viapiana, O; Rossini, M; Gatti, D

    2016-01-01

    Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis (RA). The chronic corticosteroid treatment, the functional impairment associated with RA and the disease itself appear to be the most relevant determinants. Most of the previous studies involved postmenopausal women, in whom the estrogenic deficiency might amplify the negative effect towards bone of both RA and corticosteroid therapy. We decided to evaluate bone health in a cohort of premenopausal RA patients. The study population includes 47 premenopausal women attending our outpatient clinic for RA and twice as many healthy age-matched control women selected from the hospital personnel. The bone density at the spine and femoral neck were significantly lower in patients with RA as compared with controls. When spine bone mineral density (BMD) values were adjusted for the cumulative glucocorticoid (GC) dose alone and for the cumulative GC dose plus body mass index (BMI) the mean differences between two groups decreased but they remained statistically significant. We found no difference when the spine BMD was adjusted for cumulative GC dose, BMI and health assessment questionnaire. The difference in femoral neck BMD remained statistically significant also after all the same adjustments. In conclusion, our study shows that a BMD deficiency is frequent also in premenopausal women affected by RA, especially at femoral site and that the main determinants of this bone loss are not only the disease-related weight loss, corticosteroid therapy and functional impairment, but also the systemic effects of the disease itself. PMID:27608794

  10. Audiologic Patterns of Otic Capsule Preserving Temporal Bone Fracture: Effects of the Affected Subsites

    PubMed Central

    Kim, So Young; Kim, Yoon Joong; Kim, Young Ho; Park, Min-Hyun

    2016-01-01

    Objectives. This study was aimed to assess the relationship between the type of temporal bone area involved and conductive hearing loss. Methods. We enrolled 97 patients who visited the otolaryngology clinics of Seoul National University Hospital or Boramae Medical Center, Seoul Metropolitan Government-Seoul National University with temporal bone fracture between January 2004 and January 2014. Audiometric parameters, including initial and improved air-bone (AB) conduction gap values, were reviewed in accordance with the temporal bone computed tomography (external auditory canal [EAC], middle ear [ME], mastoid [M], and ossicle [O]). Results. Patients with ossicular chain involvement exhibited a larger AB gap compared to those with no ossicular chain involvement at 250, 1,000, 2,000, and 4,000 Hz. Among the groups without ossicular chain involvement, the initial AB gap was largest in patients with EAC+ME+M involvement, followed by the ME+M and M-only involvement groups. The greatest improvement in the AB gap was observed in the EAC+ME+M group followed by the ME+M and M-only groups, irrespective of ossicular chain involvement. Improvements in AB gap values were smallest at 2,000 Hz. Conclusion. Conductive hearing loss pattern differed according to the temporal bone area involved. Therefore, areas such as the hematoma and hemotympanum, as well as the fracture line of the temporal bone area, must be evaluated to predict audiologic patterns with otic capsule preserving temporal bone fracture. PMID:27337953

  11. An evaluation of the effect of age and the peri-parturient period on bone metabolism in dairy cows as measured by serum bone-specific alkaline phosphatase activity and urinary deoxypyridinoline concentration.

    PubMed

    Sato, Reiichiro; Onda, Ken; Kato, Hajime; Ochiai, Hideharu; Kawai, Kazuhiro; Iriki, Tsunenori; Kaneko, Kazuyuki; Yamazaki, Yukio; Wada, Yasunori

    2013-08-01

    Various biochemical markers help to evaluate the state of bone turnover in humans and could be used during the peri-parturient period in dairy cows when calcium (Ca) metabolism changes dramatically. To investigate this, the peri-partum characteristics of serum bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were investigated. Both serum BAP activity and urinary DPD concentrations were increased and demonstrated wide variability in younger animals, and these findings were consistent with other bone turnover markers. Around the time of parturition, serum Ca concentration and serum BAP activity in multiparous cows were significantly lower than in primiparous cows, but urinary DPD concentration was unchanged. The use of BAP as a bone formation marker appears to be valuable for evaluating bone remodelling status in cows, but the specificity of the test needs to be confirmed. The DPD/BAP ratio around parturition demonstrated a clear difference in bone turnover status between the two parity groups with multiparous cows demonstrating increased signs of bone resorption compared with primiparous cows, corresponding to the Ca requirement for milk production. In future studies, the applicability of the ratio of bone resorption marker to bone formation marker should be evaluated for bone turnover assessment. PMID:23422881

  12. A study of stress-free living bone and its application to space flight

    NASA Technical Reports Server (NTRS)

    Leblanc, A.; Spira, M.

    1983-01-01

    Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.

  13. Increasing Phosphatidylinositol (4,5)-Bisphosphate Biosynthesis Affects Basal Signaling and Chloroplast Metabolism in Arabidopsis thaliana

    PubMed Central

    Im, Yang Ju; Smith, Caroline M.; Phillippy, Brian Q.; Strand, Deserah; Kramer, David M.; Grunden, Amy M.; Boss, Wendy F.

    2014-01-01

    One challenge in studying the second messenger inositol(1,4,5)-trisphosphate (InsP3) is that it is present in very low amounts and increases only transiently in response to stimuli. To identify events downstream of InsP3, we generated transgenic plants constitutively expressing the high specific activity, human phosphatidylinositol 4-phosphate 5-kinase Iα (HsPIPKIα). PIP5K is the enzyme that synthesizes phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2); this reaction is flux limiting in InsP3 biosynthesis in plants. Plasma membranes from transgenic Arabidopsis expressing HsPIPKIα had 2–3 fold higher PIP5K specific activity, and basal InsP3 levels in seedlings and leaves were >2-fold higher than wild type. Although there was no significant difference in photosynthetic electron transport, HsPIPKIα plants had significantly higher starch (2–4 fold) and 20% higher anthocyanin compared to controls. Starch content was higher both during the day and at the end of dark period. In addition, transcripts of genes involved in starch metabolism such as SEX1 (glucan water dikinase) and SEX4 (phosphoglucan phosphatase), DBE (debranching enzyme), MEX1 (maltose transporter), APL3 (ADP-glucose pyrophosphorylase) and glucose-6-phosphate transporter (Glc6PT) were up-regulated in the HsPIPKIα plants. Our results reveal that increasing the phosphoinositide (PI) pathway affects chloroplast carbon metabolism and suggest that InsP3 is one component of an inter-organelle signaling network regulating chloroplast metabolism. PMID:27135490

  14. Potato snakin-1 gene silencing affects cell division, primary metabolism, and cell wall composition.

    PubMed

    Nahirñak, Vanesa; Almasia, Natalia Inés; Fernandez, Paula Virginia; Hopp, Horacio Esteban; Estevez, José Manuel; Carrari, Fernando; Vazquez-Rovere, Cecilia

    2012-01-01

    Snakin-1 (SN1) is an antimicrobial cysteine-rich peptide isolated from potato (Solanum tuberosum) that was classified as a member of the Snakin/Gibberellic Acid Stimulated in Arabidopsis protein family. In this work, a transgenic approach was used to study the role of SN1 in planta. Even when overexpressing SN1, potato lines did not show remarkable morphological differences from the wild type; SN1 silencing resulted in reduced height, which was accompanied by an overall reduction in leaf size and severe alterations of leaf shape. Analysis of the adaxial epidermis of mature leaves revealed that silenced lines had 70% to 90% increases in mean cell size with respect to wild-type leaves. Consequently, the number of epidermal cells was significantly reduced in these lines. Confocal microscopy analysis after agroinfiltration of Nicotiana benthamiana leaves showed that SN1-green fluorescent protein fusion protein was localized in plasma membrane, and bimolecular fluorescence complementation assays revealed that SN1 self-interacted in vivo. We further focused our study on leaf metabolism by applying a combination of gas chromatography coupled to mass spectrometry, Fourier transform infrared spectroscopy, and spectrophotometric techniques. These targeted analyses allowed a detailed examination of the changes occurring in 46 intermediate compounds from primary metabolic pathways and in seven cell wall constituents. We demonstrated that SN1 silencing affects cell division, leaf primary metabolism, and cell wall composition in potato plants, suggesting that SN1 has additional roles in growth and development beyond its previously assigned role in plant defense. PMID:22080603

  15. Metabolic syndrome affects breast cancer risk in postmenopausal women: National Cancer Institute of Naples experience.

    PubMed

    Capasso, Immacolata; Esposito, Emanuela; Pentimalli, Francesca; Crispo, Anna; Montella, Maurizio; Grimaldi, Maria; De Marco, MariaRosaria; Cavalcanti, Ernestina; D'Aiuto, Massimiliano; Fucito, Alfredo; Frasci, Giuseppe; Maurea, Nicola; Esposito, Giuseppe; Pedicini, Tonino; Vecchione, Aldo; D'Aiuto, Giuseppe; Giordano, Antonio

    2010-12-15

    Postmenopausal women show the highest incidence of breast cancer in the female population and are often affected by metabolic syndrome. Metabolic syndrome (MS)--characterized by central adiposity, insulin resistance, low serum high-density lipoprotein cholesterol (HDL-C), high serum triglyceride and high blood pressure--seems to be strictly correlated to breast carcinogenesis. We enrolled 777 healthy women and women with breast cancer in our nested case-control study to evaluate the association between MS and breast cancer, analyzing anthropometric parameters (weight, height, BMI, waist and hip circumference), blood pressure, serum HDL-C, triglyceride, fasting plasma glucose, insulin, testosterone and uric acid levels and administering a questionnaire about physical activity, food intake, tobacco use, alcohol abuse, personal and familial history of disease. We found an higher prevalence of metabolic syndrome (30%) in postmenopausal breast cancer patients compared to healthy women (19%). None of the individual MS features was strong enough to be considered responsible for breast carcinogenesis alone. However, of the 63 postmenopausal breast cancer cases associated to MS, 30% presented three or more MS features, suggesting that the activation of multiple molecular pathways underlying MS might contribute to tumorigenesis. Our data support the hypothesis that MS may be an indicator of breast cancer risk in postmenopausal women. The unsettlement of the hormonal arrangement in postmenopausal, along with an increase in visceral adiposity, probably favour the hormone-dependent cell proliferation, which drives tumorigenesis. Adjustments in lifestyle with physical activity intensification and healthy diet could represent modifiable factors for the primary prevention of sporadic breast cancer. PMID:20935521

  16. Factors affecting carisoprodol metabolism in pain patients using urinary excretion data.

    PubMed

    Tse, Stephanie A; Atayee, Rabia S; Ma, Joseph D; Best, Brookie M

    2014-04-01

    Carisoprodol is a skeletal muscle relaxant prescribed to treat pain. Carisoprodol is metabolized to meprobamate, an active metabolite with anxiolytic effects, by the genetically polymorphic CYP2C19 enzyme. Concomitant use of CYP2C19 substrates or inhibitors may alter carisoprodol metabolism, with therapeutic and/or toxic implications for effectively treating patients with pain. This was a retrospective analysis of urinary excretion data collected from patients with pain from March 2008 to May 2011. Carisoprodol and meprobamate urine concentrations were measured by liquid chromatography-tandem mass spectrometry, and the metabolic ratio (MR) of meprobamate to carisoprodol concentrations was determined in 14,965 subjects. The MR geometric mean and 95% confidence interval (95% CI) of the young group (105, 95% CI = 99.1-113) were ∼47.4% higher than the middle-aged group (71.9, 95% CI = 70-73.8) and nearly two times higher than the elderly group (54.4, 95% CI = 51.3-57.6). Females had a 20.7% higher MR compared with males. No significant change in the MR was observed with overall CYP2C19 inhibitor or substrate use. However, evaluation of individual inhibitors showed co-administration with esomeprazole or fluoxetine was associated with a 31.8 and 24.6% reduction in MR, respectively, compared with controls (P < 0.05). Omeprazole did not significantly affect the MR. Patient-specific factors such as age, sex and co-medications may be important considerations for effective carisoprodol therapy. PMID:24488112

  17. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature

    PubMed Central

    Norambuena, Fernando; Morais, Sofia; Emery, James A.; Turchini, Giovanni M.

    2015-01-01

    Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad–time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

  18. Metabolic Bone Disease in the Post-transplant Population: Preventative and Therapeutic Measures.

    PubMed

    Nel, Johan Daniël; Epstein, Sol

    2016-05-01

    Post-transplant bone disease contributes significantly to patients' morbidity and mortality after transplantation and has an impact on their quality of life. This article discusses the major contributors to mechanisms causing bone loss, highlighting the role of preexisting disease in both kidney and liver failure and contributions from glucocorticoids and calcineurin inhibitors. Suggested monitoring and investigations are reviewed as well as treatment as far as the current literature supports, emphasizing the difference between kidney and liver recipients. PMID:27095646

  19. Heterozygous PTCH1 Mutations Impact the Bone Metabolism in Patients With Nevoid Basal Cell Carcinoma Syndrome Likely by Regulating SPARC Expression.

    PubMed

    Hong, Yingying; Zhang, Jianyun; Zhang, Heyu; Li, Xuefen; Qu, Jiafei; Zhai, Jiemei; Zhang, Lei; Chen, Feng; Li, Tiejun

    2016-07-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by bone and skin abnormalities and a predisposition to various tumors. Keratocystic odontogenic tumors (KCOTs), which are common tumors of the jaw that cause extensive damage to the jawbone, are usually accompanied with NBCCS. Germline PTCH1 mutations in NBCCS tumorigenesis have been frequently studied; however, little is known regarding the pathogenesis of bone abnormalities in this disease. This study sought to investigate the mechanism underlying heterozygous PTCH1 mutation-mediated abnormal bone metabolism in patients with NBCCS. Stromal cells were isolated from the fibrous capsules of patients with NBCCS-associated or non-syndromic keratocystic odontogenic tumors and non-syndromic tumor stromal cells without PTCH1 mutations served as controls. Germline PTCH1 heterozygous mutations were confirmed in all NBCCS samples and differential protein expression was identified using tandem mass tag-labeled proteomics analysis. Our findings revealed that osteonectin/SPARC expression was significantly downregulated in syndromic stromal cells compared with non-syndromic stromal cells. SPARC expression was even lower in stromal cells carrying PTCH1 protein truncation mutations. PTCH1 siRNA transfection demonstrated that SPARC downregulation correlates with decreased PTCH1 expression. Furthermore, exogenous SPARC promoted osteogenic differentiation of syndromic stromal cells with enhanced development of calcium nodules. In addition, bone mineral density tests showed that patients with NBCCS exhibit weak bone mass compared with sex- and age-matched controls. This study indicates that germline PTCH1 heterozygous mutations play a major role in bone metabolism in patients with NBCCS, in particular in those with PTCH1 protein truncation mutations. SPARC may represent an important downstream modulator of PTCH1 mediation of bone metabolism. Thus, bone mineral density monitoring is critical

  20. Effect of subcutaneous leptin replacement therapy on bone metabolism in patients with generalized lipodystrophy.

    PubMed

    Simha, Vinaya; Zerwekh, Joseph E; Sakhaee, Khashayar; Garg, Abhimanyu

    2002-11-01

    The adipocyte-derived hormone leptin, which plays an important role in energy homeostasis, has been suggested to have an influence on bone development and remodeling. However, it is not clear from animal studies whether leptin is a stimulator or an inhibitor of bone growth. Cross-sectional studies in humans suggest that serum leptin levels are positively associated with bone mineral density (BMD), but these observations are not consistent, and whether this relationship is independent of obesity remains unclear. We therefore examined the effect of sc leptin administration on BMD and markers of bone turnover in two women, one with congenital generalized lipodystrophy and the other with acquired generalized lipodystrophy. Both patients had regular menstrual cycles. At baseline, the BMD for both patients, measured at the lumbar spine and total hip, was within 1 SD of the peak bone mass. There was no significant change in BMD in both patients after 16-18 months of leptin therapy. Similarly, concentrations of serum osteocalcin and bone-specific alkaline phosphatase or urinary excretion of deoxypyridinoline and N-telopeptides remained unchanged after 6-8 months of leptin therapy, suggesting no effects of leptin on osteoblastic or osteoclastic activity. Our preliminary data suggest that sc leptin replacement in hypoleptinemic patients with generalized lipodystrophy has no effect on the mature adult skeleton. PMID:12414854

  1. Food odors trigger an endocrine response that affects food ingestion and metabolism.

    PubMed

    Lushchak, Oleh V; Carlsson, Mikael A; Nässel, Dick R

    2015-08-01

    Food odors stimulate appetite and innate food-seeking behavior in hungry animals. The smell of food also induces salivation and release of gastric acid and insulin. Conversely, sustained odor exposure may induce satiation. We demonstrate novel effects of food odors on food ingestion, metabolism and endocrine signaling in Drosophila melanogaster. Acute exposure to attractive vinegar odor triggers a rapid and transient increase in circulating glucose, and a rapid upregulation of genes encoding the glucagon-like hormone adipokinetic hormone (AKH), four insulin-like peptides (DILPs) and some target genes in peripheral tissues. Sustained exposure to food odors, however, decreases food intake. Hunger-induced strengthening of synaptic signaling from olfactory sensory neurons (OSNs) to brain neurons increases food-seeking behavior, and conversely fed flies display reduced food odor sensitivity and feeding. We show that increasing the strength of OSN signaling chronically by genetic manipulation of local peptide neuromodulation reduces feeding, elevates carbohydrates and diminishes lipids. Furthermore, constitutively strengthened odor sensitivity altered gene transcripts for AKH, DILPs and some of their targets. Thus, we show that food odor can induce a transient anticipatory endocrine response, and that boosted sensitivity to this odor affects food intake, as well as metabolism and hormonal signaling. PMID:25782410

  2. Plasticity and epistasis strongly affect bacterial fitness after losing multiple metabolic genes.

    PubMed

    D'Souza, Glen; Waschina, Silvio; Kaleta, Christoph; Kost, Christian

    2015-05-01

    Many bacterial lineages lack seemingly essential metabolic genes. Previous work suggested selective benefits could drive the loss of biosynthetic functions from bacterial genomes when the corresponding metabolites are sufficiently available in the environment. However, the factors that govern this "genome streamlining" remain poorly understood. Here we determine the effect of plasticity and epistasis on the fitness of Escherichia coli genotypes from whose genome biosynthetic genes for one, two, or three different amino acids have been deleted. Competitive fitness experiments between auxotrophic mutants and prototrophic wild-type cells in one of two carbon environments revealed that plasticity and epistasis strongly affected the mutants' fitness individually and interactively. Positive and negative epistatic interactions were prevalent, yet on average cancelled each other out. Moreover, epistasis correlated negatively with the expected effects of combined auxotrophy-causing mutations, thus producing a pattern of diminishing returns. Moreover, computationally analyzing 1,432 eubacterial metabolic networks revealed that most pairs of auxotrophies co-occurred significantly more often than expected by chance, suggesting epistatic interactions and/or environmental factors favored these combinations. Our results demonstrate that both the genetic background and environmental conditions determine the adaptive value of a loss-of-biochemical-function mutation and that fitness gains decelerate, as more biochemical functions are lost. PMID:25765095

  3. Rice Debranching Enzyme Isoamylase3 Facilitates Starch Metabolism and Affects Plastid Morphogenesis

    PubMed Central

    Yun, Min-Soo; Umemoto, Takayuki; Kawagoe, Yasushi

    2011-01-01

    Debranching enzymes, which hydrolyze α-1 and 6-glucosidic linkages in α-polyglucans, play a dual role in the synthesis and degradation of starch in plants. A transposon-inserted rice mutant of isoamylase3 (isa3) contained an increased amount of starch in the leaf blade at the end of the night, indicating that ISA3 plays a role in the degradation of transitory starch during the night. An epitope-tagged ISA3 expressed in Escherichia coli exhibited hydrolytic activity on β-limit dextrin and amylopectin. We investigated whether ISA3 plays a role in amyloplast development and starch metabolism in the developing endosperm. ISA3–green fluorescent protein (GFP) fusion protein expressed under the control of the rice ISA3 promoter was targeted to the amyloplast stroma in the endosperm. Overexpression of ISA3 in the sugary1 mutant, which is deficient in ISA1 activity, did not convert water-soluble phytoglycogen to starch granules, indicating that ISA1 and ISA3 are not functionally redundant. Both overexpression and loss of function of ISA3 in the endosperm generated pleomorphic amyloplasts and starch granules. Furthermore, chloroplasts in the leaf blade of isa3 seedlings were large and pleomorphic. These results suggest that ISA3 facilitates starch metabolism and affects morphological characteristics of plastids in rice. PMID:21551159

  4. Campomanesia adamantium extract induces DNA damage, apoptosis, and affects cyclophosphamide metabolism.

    PubMed

    Martello, M D; David, N; Matuo, R; Carvalho, P C; Navarro, S D; Monreal, A C D; Cunha-Laura, A L; Cardoso, C A L; Kassuya, C A L; Oliveira, R J

    2016-01-01

    Campomanesia adamantium (Cambess.) O. Berg. is originally from Brazil. Its leaves and fruits have medicinal properties such as anti-inflammatory, antidiarrheal and antiseptic properties. However, the mutagenic potential of this species has been reported in few studies. This study describes the mutagenic/antimutagenic, splenic phagocytic, and apoptotic activities of C. adamantium hydroethanolic extract with or without cyclophosphamide in Swiss mice. The animals orally received the hydroethanolic extract at doses of 30, 100, or 300 mg/kg with or without 100 mg/kg cyclophosphamide. Mutagenesis was evaluated by performing the micronucleus assay after treatment for 24, 48, and 72 h, while splenic phagocytic and apoptotic effects were investigated after 72 h. Short-term exposure of 30 and 100 mg/kg extract induced mild clastogenic/aneugenic effects and increased splenic phagocytosis and apoptosis in the liver, spleen, and kidneys. When the extract was administered in combination with cyclophosphamide, micronucleus frequency and apoptosis reduced. Extract components might affect cyclophosphamide metabolism, which possibly leads to increased clearance of this chemotherapeutic agent. C. adamantium showed mutagenic activity and it may decrease the effectiveness of drugs with metabolic pathways similar to those associated with cyclophosphamide. Thus, caution should be exercised while consuming these extracts, especially when received in combination with other drugs. PMID:27173259

  5. Inhibition of mitochondrial complex II affects dopamine metabolism and decreases its uptake into striatal synaptosomes.

    PubMed

    Cakała, Magdalena; Drabik, Jacek; Kaźmierczak, Anna; Kopczuk, Dorota; Adamczyk, Agata

    2006-01-01

    The mitochondrial toxin, 3-nitropropionic acid (3-NP), is a specific inhibitor of succinate dehydrogenase, complex II in the mitochondrial respiratory chain. The aim of our study was to determine the relationship between inhibition of mitochondrial complex II and dopamine (DA) metabolism and its transport into rat striatal synaptosomes after exposure to 3-NP. The study was carried out using spectrophotometric, radiochemical and HPLC methods. Our data showed that inhibition of succinate dehydrogenase by intraperitoneal (i.p.) injection of 3-NP (cumulated dose 100 mg/kg in 4 days) significantly affected DA metabolism, leading to the accumulation of its metabolites, 3,4-dihydroxylphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the rat striatum. These experimental conditions had no effect on free radical dependent lipid peroxidation in the brain. In vitro experiments revealed that DA and DOPAC significantly decrease lipid peroxidation in the brain homogenate. Moreover, 3-NP significantly inhibited [3H]DA uptake into striatal synaptosomes by specific dopamine transporter (DAT). The scavengers of superoxide radical (O2-) Tempol and Trolox had no effect on DAT function, but the nitric oxide synthase (NOS) inhibitor N w-nitro-L-arginine (100 microM) prevented 3-NP-evoked DAT down-regulation. In summary, our results indicate that inhibition of mitochondrial complex II by 3-NP enhances DA degradation and decreases its uptake into synaptosomes. It is suggested that NO and energy failure are responsible for alteration of the dopaminergic system in the striatum. PMID:17183449

  6. Failure of caffeine to affect metabolism during 60 min submaximal exercise.

    PubMed

    Titlow, L W; Ishee, J H; Riggs, C E

    1991-01-01

    Caffeine consumption prior to athletic performance has become commonplace. The usual dosage is approximately 200 mg, a level of caffeine ingestion equivalent to two cups of brewed coffee. This study was designed to examine the effects of a common level of caffeine ingestion, specifically 200 mg, on metabolism during submaximal exercise performance in five males. The subjects performed two 60-min monitored treadmill workouts at 60% maximal heart rate during a 2-week period. The subjects were randomly assigned, double-blind to receive a caffeine or placebo capsule 60 min prior to exercise. Testing was performed in the afternoon following a midnight fast. Venous blood was withdrawn pre-exercise, every 15 min during the workout, and 10 min after recovery. Blood was analysed for free fatty acid, triglycerides, glucose, lactic acid, haemoglobin and haematocrit. The respiratory exchange ratio (R), perceived exertion (RPE) and oxygen uptake were measured every 4 min during exercise. An examination of the data with repeated-measures ANOVA revealed no significant differences between the two groups. Within the limitations of the study, it was concluded that 200 mg caffeine failed to affect metabolism during 60 min submaximal exercise. PMID:1856908

  7. Factors Affecting the Absorption, Metabolism, and Excretion of Cocoa Flavanols in Humans.

    PubMed

    Cifuentes-Gomez, Tania; Rodriguez-Mateos, Ana; Gonzalez-Salvador, Isidro; Alañon, María Elena; Spencer, Jeremy P E

    2015-09-01

    Cocoa is rich in a subclass of flavonoids known as flavanols, the cardiovascular health benefits of which have been extensively reported. The appearance of flavanol metabolites in the systemic circulation after flavanol-rich food consumption is likely to mediate the physiological effects on the vascular system, and these levels are influenced by numerous factors, including food matrix, processing, intake, age, gender, or genetic polymorphisms, among others. This review will focus on our current understanding of factors affecting the absorption, metabolism, and excretion of cocoa flavanols in humans. Second, it will identify gaps in these contributing factors that need to be addressed to conclusively translate our collective knowledge into the context of public health, dietary guidelines, and evidence-based dietary recommendations. PMID:25711140

  8. Escherichia coli carbon source metabolism affects longevity of its predator Caenorhabditis elegans.

    PubMed

    Brokate-Llanos, Ana María; Garzón, Andrés; Muñoz, Manuel J

    2014-01-01

    Nutrition is probably the most determinant factor affecting aging. Microorganisms of the intestinal flora lay in the interface between available nutrients and nutrients that are finally absorbed by multicellular organisms. They participate in the processing and transformation of these nutrients in a symbiotic or commensalistic relationship. In addition, they can also be pathogens. Alive Escherichia coli OP50 are usually used to culture the bacteriovorus nematode Caenorhabditis elegans. Here, we report a beneficial effect of low concentration of saccharides on the longevity of C. elegans. This effect is only observed when the bacterium can metabolize the sugar, suggesting that physiological changes in the bacterium feeding on the saccharides are the cause of this beneficial effect. PMID:25263107

  9. Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway.

    PubMed

    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

  10. Histopathologic investigation of the effects of prostaglandin E2 administered by different methods on tooth movement and bone metabolism

    PubMed Central

    Erdem, Abdulvahit

    2012-01-01

    Objective The aim of this study was to investigate and compare the in vivo effects of prostaglandin E2 (PGE2) administered by different methods on orthodontic tooth movement and bone metabolism macroscopically, histopatologically, and biochemically. Methods Forty-five young adult New Zealand rabbits were randomly divided into 3 experimental groups (n = 10/group), 1 positive control group (n = 10), and 1 negative control group (n = 5). The experimental rabbits were fitted with springs exerting 20-g reciprocal force on the maxillary incisors and PGE2 (10 µg/mL) was administered by the intravenous, submucosal, or intraligamentous route after appliance insertion and on days 1, 3, 7, and 14 thereafter. All rabbits were sacrificed on day 21 and their premaxillae were resected for histologic evaluation. Results Tooth movement was observed in the experimental and positive control groups, but the intraligamentous PGE2 group had the highest values of all analyzed parameters, including serum calcium and phosphorus levels and osteoclastic and osteoblastic populations (p < 0.001). Conclusions Submucosal and intraligamentous PGE2 administration significantly increases orthodontic tooth movement and bone metabolism, but the intraligamentous route seems to be more effective. PMID:23112942

  11. Bone quality is affected by food restriction and by nutrition-induced catch-up growth.

    PubMed

    Pando, Rakefet; Masarwi, Majdi; Shtaif, Biana; Idelevich, Anna; Monsonego-Ornan, Efrat; Shahar, Ron; Phillip, Moshe; Gat-Yablonski, Galia

    2014-12-01

    Growth stunting constitutes the most common effect of malnutrition. When the primary cause of malnutrition is resolved, catch-up (CU) growth usually occurs. In this study, we have explored the effect of food restriction (RES) and refeeding on bone structure and mechanical properties. Sprague-Dawley male rats aged 24 days were subjected to 10 days of 40% RES, followed by refeeding for 1 (CU) or 26 days long-term CU (LTCU). The rats fed ad libitum served as controls. The growth plates were measured, osteoclasts were identified using tartrate-resistant acid phosphatase staining, and micro-computed tomography (CT) scanning and mechanical testing were used to study structure and mechanical properties. Micro-CT analysis showed that RES led to a significant reduction in trabecular BV/TV and trabecular number (Tb.N), concomitant with an increase in trabecular separation (Tb.Sp). Trabecular BV/TV and Tb.N were significantly greater in the CU group than in the RES in both short- and long-term experiments. Mechanical testing showed that RES led to weaker and less compliant bones; interestingly, bones of the CU group were also more fragile after 1 day of CU. Longer term of refeeding enabled correction of the bone parameters; however, LTCU did not achieve full recovery. These results suggest that RES in young rats attenuated growth and reduced trabecular bone parameters. While nutrition-induced CU growth led to an immediate increase in epiphyseal growth plate height and active bone modeling, it was also associated with a transient reduction in bone quality. This should be taken into consideration when treating children undergoing CU growth. PMID:25248555

  12. Hyperketonemia during lipopolysaccharide-induced mastitis affects systemic and local intramammary metabolism in dairy cows.

    PubMed

    Zarrin, M; Wellnitz, O; van Dorland, H A; Gross, J J; Bruckmaier, R M

    2014-01-01

    Hyperketonemia interferes with the metabolic regulation in dairy cows. It is assumed that metabolic and endocrine changes during hyperketonemia also affect metabolic adaptations during inflammatory processes. We therefore studied systemic and local intramammary effects of elevated plasma β-hydroxybutyrate (BHBA) before and during the response to an intramammary lipopolysaccharide (LPS) challenge. Thirteen dairy cows received intravenously either a Na-DL-β-OH-butyrate infusion (n = 5) to achieve a constant plasma BHBA concentration (1.7 ± 0.1 mmol/L), with adjustments of the infusion rates made based on immediate measurements of plasma BHBA every 15 min, or an infusion with a 0.9% NaCl solution (control; n = 8) for 56 h. Infusions started at 0900 h on d 1 and continued until 1700 h 2 d later. Two udder quarters were challenged with 200 μg of Escherichia coli LPS and 2 udder quarters were treated with 0.9% saline solution as control quarters at 48 h after the start of infusion. Blood samples were taken at 1 wk and 2h before the start of infusions as reference samples and hourly during the infusion. Mammary gland biopsies were taken 1 wk before, and 48 and 56 h (8h after LPS challenge) after the start of infusions. The mRNA abundance of key factors related to BHBA and fatty acid metabolism, and glucose transporters was determined in mammary tissue biopsies. Blood samples were analyzed for plasma glucose, BHBA, nonesterified fatty acid, urea, insulin, glucagon, and cortisol concentrations. Differences were not different for effects of BHBA infusion on the mRNA abundance of any of the measured target genes in the mammary gland before LPS challenge. Intramammary LPS challenge increased plasma glucose, cortisol, glucagon, and insulin concentrations in both groups but increases in plasma glucose and glucagon concentration were less pronounced in the Na-DL-β-OH-butyrate infusion group than in controls. In response to LPS challenge, plasma BHBA concentration decreased

  13. Somatostatin Analogue Treatment of a TSH-Secreting Adenoma Presenting With Accelerated Bone Metabolism and a Pericardial Effusion

    PubMed Central

    Mousiolis, Athanasios C.; Rapti, Eleni; Grammatiki, Maria; Yavropoulou, Maria; Efstathiou, Maria; Foroglou, Nikolaos; Daniilidis, Michalis; Kotsa, Kalliopi

    2016-01-01

    Abstract Increased bone turnover and other less frequent comorbidities of hyperthyroidism, such as heart failure, have only rarely been reported in association with central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma (TSHoma). Treatment is highly empirical and relies on eliminating the tumor and the hyperthyroid state. We report here an unusual case of a 39-year-old man who was initially admitted for management of pleuritic chest pain and fever of unknown origin. Diagnostic work up confirmed pericarditis and pleural effusion both refractory to treatment. The patient had a previous history of persistently elevated levels of alkaline phosphatase (ALP), indicative of increased bone turnover. He had also initially been treated with thyroxine supplementation due to elevated TSH levels. During the diagnostic process a TSHoma was revealed. Thyroxine was discontinued, and resection of the pituitary tumor followed by treatment with a somatostatin analog led to complete recession of the effusions, normalization of ALP, and shrinkage of pituitary tumor. Accelerated bone metabolism and pericardial and pleural effusions attributed to a TSHoma may resolve after successful treatment of the tumor. The unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with these rare pituitary adenomas. PMID:26765410

  14. Calcium metabolism and oxidative stress in bone fractures: role of antioxidants.

    PubMed

    Sheweita, S A; Khoshhal, K I

    2007-06-01

    Calcium ion is an essential structural component of the skeleton. There is growing evidence for the importance of nutrition in the maintenance of bones and joints health. Nutritional imbalance combined with endocrine abnormalities may be involved in osteoporosis. For example, essential fatty acids and their metabolites were reported to have beneficial action in osteoporosis. The mechanism by which fatty acids prevent osteoporosis may involve inhibition of pro-inflammatory cytokines, which are known to have a major role in osteoporosis through induction of oxidative stress which had adverse effects on the skeleton. Other risk factors for osteoporosis, such as smoking, hypertension and diabetes mellitus are also associated with increased oxidative stress and free radicals levels. When bone fracture occurs, a remarkable yield of free radicals is generated by the damaged tissues. However, controlled production of free radicals by normally functioning osteoclasts could accelerate destruction of calcified tissues and assist bone remodeling. Enhanced osteoclastic activity observed in bone disorders may have been responsible for increased production of reactive oxygen species [ROS] in the form of superoxide, which is evident by increased levels of serum malondialdehyde [MDA] levels. One of the most damaging effects of ROS is lipid peroxidation, the end product of which is MDA which also served as a measure of osteoclastic activity. Inhibition of the antioxidant enzymes activities, such as superoxide dismutase and glutathione peroxidase, was found to increase superoxide production by the osteoclasts which represented by increased levels of MDA. Therefore, oxidative stress is an important mediator of bone loss since deficiency of antioxidant vitamins has been found to be more common in the elderly osteoporotic patients. It is concluded from this review that increased free radical production overwhelms the natural antioxidants defense mechanisms, subjecting individuals to

  15. Frequency of Teriparatide Administration Affects the Histological Pattern of Bone Formation in Young Adult Male Mice.

    PubMed

    Yamamoto, Tomomaya; Hasegawa, Tomoka; Sasaki, Muneteru; Hongo, Hiromi; Tsuboi, Kanako; Shimizu, Tomohiro; Ota, Masahiro; Haraguchi, Mai; Takahata, Masahiko; Oda, Kimimitsu; Luiz de Freitas, Paulo Henrique; Takakura, Aya; Takao-Kawabata, Ryoko; Isogai, Yukihiro; Amizuka, Norio

    2016-07-01

    Evidence supports that daily and once-weekly administration of teriparatide, human (h)PTH(1-34), enhance bone mass in osteoporotic patients. However, it is uncertain whether different frequencies of hPTH(1-34) administration would induce bone formation similarly in terms of quantity and quality. To investigate that issue, mice were subjected to different frequencies of PTH administration, and their bones were histologically examined. Frequencies of administration were 1 time/2 days, 1 time a day, and 2 and 4 times a day. Mice were allocated to either to control or to 3 different dosing regimens: 80 μg/kg of hPTH(1-34) per injection (80 μg/kg per dose), 80 μg/kg of hPTH(1-34) per day (80 μg/kg · d), or 20 μg/kg of hPTH(1-34) per day (20 μg/kg · d). With the regimens of 80 μg/kg per dose and 80 μg/kg · d, high-frequency hPTH(1-34) administration increased metaphyseal trabecular number. However, 4 doses per day induced the formation of thin trabeculae, whereas the daily PTH regimen resulted in thicker trabeculae. A similar pattern was observed with the lower daily hPTH(1-34) dose (20 μg/kg · d): more frequent PTH administration led to the formation of thin trabeculae, showing a thick preosteoblastic cell layer, several osteoclasts, and scalloped cement lines that indicated accelerated bone remodeling. On the other hand, low-frequency PTH administration induced new bone with mature osteoblasts lying on mildly convex surfaces representative of arrest lines, which suggests minimodeling-based bone formation. Thus, high-frequency PTH administration seems to increase bone mass rapidly by forming thin trabeculae through accelerated bone remodeling. Alternatively, low-frequency PTH administration leads to the formation of thicker trabeculae through bone remodeling and minimodeling. PMID:27227535

  16. Effects of myokines on bone.

    PubMed

    Kaji, Hiroshi

    2016-01-01

    The links between muscle and bone have been recently examined because of the increasing number of patients with osteoporosis and sarcopenia. Myokines are skeletal muscle-derived humoral cytokines and growth factors, which exert physiological and pathological functions in various distant organs, including the regulation of glucose, energy and bone metabolism. Myostatin is a crucial myokine, the expression of which is mainly limited to muscle tissues. The inhibition of myostatin signaling increases bone remodeling, bone mass and muscle mass, and it may provide a target for the treatment of both sarcopenia and osteoporosis. As myostatin is involved in osteoclast formation and bone destruction in rheumatoid arthritis, myostatin may be a target myokine for the treatment of accelerated bone resorption and joint destruction in rheumatoid arthritis. Numerous other myokines, including transforming growth factor-β, follistatin, insulin-like growth factor-I, fibroblast growth factor-2, osteoglycin, FAM5C, irisin, interleukin (IL)-6, leukemia inhibitory factor, IL-7, IL-15, monocyte chemoattractant protein-1, ciliary neurotrophic factor, osteonectin and matrix metalloproteinase 2, also affect bone cells in various manners. However, the effects of myokines on bone metabolism are largely unknown. Further research is expected to clarify the interaction between muscle and bone, which may lead to greater diagnosis and the development of the treatment for muscle and bone disorders, such as osteoporosis and sarcopenia. PMID:27579164

  17. Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism

    PubMed Central

    Moller, S; Hansen, M; Hillingso, J; Jensen, J; Henriksen, J

    1999-01-01

    BACKGROUND—The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy. 
AIMS—To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis. 
METHODS—In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured. 
RESULTS—Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism. 
CONCLUSIONS—ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis. 

 Keywords: bone mineral density; carboxy terminal cross linked telopeptide of type I collagen; chronic liver disease; fibrosis; hepatic osteodystrophy; portal hypertension PMID:10026331

  18. Influence of ferutinin on bone metabolism in ovariectomized rats. II: Role in recovering osteoporosis

    PubMed Central

    Ferretti, Marzia; Bertoni, Laura; Cavani, Francesco; Zavatti, Manuela; Resca, Elisa; Carnevale, Gianluca; Benelli, Augusta; Zanoli, Paola; Palumbo, Carla

    2010-01-01

    The aim of the present investigation, which represents an extension of a previous study, was to investigate the effect of ferutinin in recovering severe osteoporosis due to estrogen deficiency after rat ovariectomy and to compare phytoestrogen effects with those of estrogens commonly used in hormone replacement therapy (HRT) by women with postmenopausal osteoporosis. The animal model used was the Sprague–Dawley ovariectomized rat. Ferutinin was orally administered (2 mg kg−1 per day) for 30 or 60 days starting from 2 months after ovariectomy (i.e. when osteoporosis was clearly evident) and its effects were compared with those of estradiol benzoate (1.5 μg per rat twice a week, subcutaneously injected) vs. vehicle-treated ovariectomized (OVX) and sham-operated (SHAM) rats. Histomorphometric analyses were performed on trabecular bone of lumbar vertebrae (4th and 5th) and distal femoral epiphysis, as well as on cortical bone of femoral diaphysis. Bone histomorphometric analyses showed that ferutinin seems to display the same effects on bone mass recorded with estradiol benzoate, thus suggesting that it could enhance the recovery of bone loss due to severe estrogen deficiency in OVX rats. On this basis, the authors propose listing ferutinin among the substances representing a potential alternative for the treatment of postmenopausal osteoporosis, which occurs as a result of estrogen deficiency. PMID:20492429

  19. Hoof position during limb loading affects dorsoproximal bone strains on the equine proximal phalanx.

    PubMed

    Singer, Ellen; Garcia, Tanya; Stover, Susan

    2015-07-16

    Sagittal fractures of the proximal phalanx (P1) in the racehorse appear to be associated with turf racing surfaces, which are known to restrict forward slide of the foot at impact. We hypothesized that restriction of forward foot slip would result in higher P1 bone strains during metacarpophalangeal joint (MCPJ) hyperextension. Unilateral limbs from six equine cadavers were instrumented with strain gauges and bone reference markers to measure dorsoproximal P1 bone strains and MCPJ extension, collateromotion and axial rotation during in vitro limb loading to 10,500 N. By limiting movement of the distal actuator platform, three different foot conditions (forward, free, and restricted) were applied in a randomised block design. Bone reference markers, recorded by video, were analyzed to determine motion of P1 relative to MC3. Rosette strain data were reduced to principal and shear magnitudes and directions. A mixed model ANOVA determined the effect of foot position on P1 bone strains and MCPJ angles. At 10,000 N load, the restricted condition resulted in higher P1 axial compressive (p=0.015), maximum shear (p=0.043) and engineering shear (p=0.046) strains compared to the forward condition. The restricted condition had higher compressive (p=0.025) and lower tensile (p=0.043) principal strains compared to the free condition. For the same magnitude of principal or shear strains, axial rotation and collateromotion angles were greatest for the restricted condition. Therefore, the increase in P1 principal compressive and shear bone strains associated with restricted foot slip indicate that alterations in foot:ground interaction may play a role in fracture occurrence in horses. PMID:26003484

  20. SILICON AND BONE HEALTH

    PubMed Central

    JUGDAOHSINGH, R.

    2009-01-01

    Low bone mass (osteoporosis) is a silent epidemic of the 21st century, which presently in the UK results in over 200,000 fractures annually at a cost of over one billion pounds. Figures are set to increase worldwide. Understanding the factors which affect bone metabolism is thus of primary importance in order to establish preventative measures or treatments for this condition. Nutrition is an important determinant of bone health, but the effects of the individual nutrients and minerals, other than calcium, is little understood. Accumulating evidence over the last 30 years strongly suggest that dietary silicon is beneficial to bone and connective tissue health and we recently reported strong positive associations between dietary Si intake and bone mineral density in US and UK cohorts. The exact biological role(s) of silicon in bone health is still not clear, although a number of possible mechanisms have been suggested, including the synthesis of collagen and/or its stabilization, and matrix mineralization. This review gives an overview of this naturally occurring dietary element, its metabolism and the evidence of its potential role in bone health. PMID:17435952

  1. Drought stress affects chloroplast lipid metabolism in rape (Brassica napus) leaves.

    PubMed

    Benhassaine-Kesri, Ghouziel; Aid, Fatiha; Demandre, Chantal; Kader, Jean-Claude; Mazliak, Paul

    2002-06-01

    Rape (Brassica napus L. var. Bienvenue) is a 16:3 plant which contains predominantly prokaryotic species of monogalactosyldiacylglycerol i.e. sn-1 C18, sn-2 C16 (C18/C16 MGDG). Rape plants were exposed to a restricted water supply for 12 days. Under drought conditions, considerable changes in lipid metabolism were observed. Drought stress provoked a decline in leaf polar lipids, which is mainly due to a decrease in MGDG content. Determination of molecular species in phosphatidylcholine (PC) and MGDG indicated that the prokaryotic molecular species of MGDG (C18/C16) decreased after drought stress while the eukaryotic molecular species (C18/C18) remained stable. Drought stress had different effects on two key enzymes of PC and MGDG synthesis. The in vitro activity of MGDG synthase (EC. 2.4.1.46) was reduced in drought stressed plants whereas cholinephosphotransferase (EC. 2.7.8.2) activity was not affected. Altogether these results suggest that the prokaryotic pathway leading to MGDG synthesis was strongly affected by drought stress while the eukaryotic pathway was not. It was also observed that the molecular species of leaf PC became more saturated in drought stressed plants. This could be due to a specific decrease in oleate desaturase activity. PMID:12060239

  2. Sydnone SYD-1 affects the metabolic functions of isolated rat hepatocytes.

    PubMed

    Brandt, Anna Paula; Pires, Amanda do Rocio Andrade; Rocha, Maria Eliane Merlin; Noleto, Guilhermina Rodrigues; Acco, Alexandra; de Souza, Carlos Eduardo Alves; Echevarria, Aurea; Canuto, André Vinícius dos Santos; Cadena, Sílvia Maria Suter Correia

    2014-07-25

    Previously, we demonstrated that sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) impairs the mitochondrial functions linked to energy provision and suggested that this effect could be associated with its antitumor activity. Herein, we evaluated the effects of SYD-1 (25 and 50 μM) on rat hepatocytes to determine its cytotoxicity on non-tumor cells. SYD-1 (25 and 50 μM) did not affect the viability of hepatocytes in suspension after 1-40 min of incubation. However, the viability of the cultured hepatocytes was decreased by ∼66% as a consequence of treatment with SYD-1 (50 μM) for 18 h. Under the same conditions, SYD-1 promoted an increase in the release of LDH by ∼19%. The morphological changes in the cultured cells treated with SYD-1 (50 μM) were suggestive of cell distress, which was demonstrated by the presence of rounded hepatocytes, cell fragments and monolayer impairment. Furthermore, fluorescence microscopy showed an increase in the annexin label after treatment with SYD-1 (50 μM), suggesting that apoptosis had been induced in these cells. SYD-1 did not affect the states of respiration in the suspended hepatocytes, but the pyruvate levels were decreased by ∼36%, whereas the lactate levels were increased by ∼22% (for the 50 μM treatment). The basal and uncoupled states of respiration of the cultured hepatocytes were inhibited by ∼79% and ∼51%, respectively, by SYD-1 (50 μM). In these cells, SYD-1 (50 μM) increased the pyruvate and lactate levels by ∼84% and ∼16%, respectively. These results show that SYD-1 affects important metabolic functions related to energy provision in hepatocytes and that this effect was more pronounced on cells in culture than those in suspension. PMID:24836382

  3. Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain

    PubMed Central

    Omata, Yo; Salvador, Gabriela A.; Oteiza, Patricia I.

    2013-01-01

    A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells. This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA). GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells. γ-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD). The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls. The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD. Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells. Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration. Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low. In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels. This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors. PMID:23377617

  4. Environmentally Relevant Dose of Bisphenol A Does Not Affect Lipid Metabolism and Has No Synergetic or Antagonistic Effects on Genistein’s Beneficial Roles on Lipid Metabolism

    PubMed Central

    Fan, Ying; Li, Hongyu; Zhao, Nana; Yang, Huiqin; Ye, Xiaolei; He, Dongliang; Yang, Hui; Jin, Xin; Tian, Chong; Ying, Chenjiang

    2016-01-01

    Both bisphenol A (BPA, an endocrine disrupting chemicals) and genistein (a phytoestrogen mainly derived from leguminosae) are able to bind to estrogen receptors, but they are considered to have different effects on metabolic syndrome, surprisingly. We here investigate the effects of an environmentally relevant dose of BPA alone and the combined effects with genistein on lipid metabolism in rats. Eight groups of adult male Wistar rats, fed with either standard chow diet or high-fat diet, were treated with BPA (50μg/kg/day), genistein (10mg/kg/day), and BPA plus genistein for 35 weeks, respectively. Metabolic parameters in serum and liver were determined; the hematoxylin/eosin and oil Red O staining were used to observe liver histologically; gene expressions related to hepatic lipid metabolism were analyzed by Real-time PCR; protein expressions of PPARγ, PPARα and LC3 in liver were analyzed by western blotting. No difference of body weight gain, total energy intake, liver weight/body weight or body fat percentage in both STD- and HFD-fed sub-groups was observed after treatment with BPA, genistein, or BPA plus genistein (P>0.05). Genistein alleviated lipid metabolism disorder and decreased the mRNA and protein expression of PPARγ (P<0.05), and increased the protein expression of LC3II (P<0.05) in liver of HFD-fed rats. However, BPA treatment had no effect on lipid metabolism in rats alone (P>0.05) or combined with genistein. Our findings suggest that long-term environmentally relevant dose of BPA did not affect lipid metabolism, and had no synergetic or antagonistic roles on genistein’s beneficial function on hepatic lipid metabolism. PMID:27171397

  5. Multiple dietary supplements do not affect metabolic and cardio-vascular health.

    PubMed

    Soare, Andreea; Weiss, Edward P; Holloszy, John O; Fontana, Luigi

    2014-02-01

    Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m(2)) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals. PMID:24659610

  6. Metabolic rate, latitude and thermal stability of roosts, but not phylogeny, affect rewarming rates of bats.

    PubMed

    Menzies, Allyson K; Webber, Quinn M R; Baloun, Dylan E; McGuire, Liam P; Muise, Kristina A; Coté, Damien; Tinkler, Samantha; Willis, Craig K R

    2016-10-01

    Torpor is an adaptation that allows many endotherms to save energy by abandoning the energetic cost of maintaining elevated body temperatures. Although torpor reduces energy consumption, the metabolic heat production required to arouse from torpor is energetically expensive and can impact the overall cost of torpor. The rate at which rewarming occurs can impact the cost of arousal, therefore, factors influencing rewarming rates of heterothermic endotherms could have influenced the evolution of rewarming rates and overall energetic costs of arousal from torpor. Bats are a useful taxon for studies of ecological and behavioral correlates of rewarming rate because of the widespread expression of heterothermy and ecological diversity across the >1200 known species. We used a comparative analysis of 45 bat species to test the hypothesis that ecological, behavioral, and physiological factors affect rewarming rates. We used basal metabolic rate (BMR) as an index of thermogenic capacity, and local climate (i.e., latitude of geographic range), roost stability and maximum colony size as ecological and behavioral predictors of rewarming rate. After controlling for phylogeny, high BMR was associated with rapid rewarming while species that live at higher absolute latitudes and in less thermally stable roosts also rewarmed most rapidly. These patterns suggests that some bat species rely on passive rewarming and social thermoregulation to reduce costs of rewarming, while others might rely on thermogenic capacity to maintain rapid rewarming rates in order to reduce energetic costs of arousal. Our results highlight species-specific traits associated with maintaining positive energy balance in a wide range of climates, while also providing insight into possible mechanisms underlying the evolution of heterothermy in endotherms. PMID:27317837

  7. Benzothiadiazole (BTH) activates sterol pathway and affects vitamin D3 metabolism in Solanum malacoxylon cell cultures.

    PubMed

    Burlini, Nedda; Iriti, Marcello; Daghetti, Anna; Faoro, Franco; Ruggiero, Antonietta; Bernasconi, Silvana

    2011-11-01

    Benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH), a particularly efficient inducer of systemic acquired resistance (SAR), was developed as an immunizing agent to sensitize various crop species against pathogen infections. Recent works highlighted its activating effect on different metabolic pathways, concerning both primary and secondary metabolites. In this study, we investigated the effect of BTH treatment on sterol levels and vitamin D(3) metabolism in Solanum malacoxylon cultures. Calli of S. malacoxylon were incubated in Gamborg B5 liquid medium alone or added with 50 μM BTH for different times (one, two or three cycles of light). Histocytochemical investigations performed on our experimental system using 3,3'-diaminobenzidine (DAB) for hydrogen peroxide (H(2)O(2)) detection and phloroglucinol for lignin staining showed that BTH causes H(2)O(2) accumulation and lignin deposition in treated calli. Gas chromatographic analysis of principal cell membrane sterols (β-sitosterol, campesterol, stigmasterol) showed that BTH transiently increases their cellular levels. Callus cultures were found to contain also cholesterol, 7-dehydrocholesterol, the putative precursor of vitamin D(3), and the hydroxylated metabolites 25-hydroxyvitamin D(3) [25(OH)D(3)] and 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)]. BTH treatment enhanced 7-dehydrocholesterol while reduced cholesterol. HPLC analysis of sample extracts showed that BTH does not affect the cell content of vitamin D(3), though results of ELISA tests highlighted that this elicitor moderately enhances the levels of 25(OH)D(3) and 1α,25(OH)(2)D(3) metabolites. In conclusion, BTH treatment not only causes cell wall strengthening, a typical plant defence response, as just described in other experimental models, but in the same time increases the cellular level of the main sterols and 7-dehydrocholesterol. PMID:21779826

  8. Calcium homeostasis and bone metabolic responses to high-protein diets during energy deficit in healthy young adults: a randomized control trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although consuming dietary protein above current recommendations during energy deficit enhances blood lipid profiles and preserves lean body mass, concerns have been raised regarding effects of high-protein diets on bone health. To determine whether calcium homeostasis and bone turnover are affected...

  9. The behavior of the micro-mechanical cement-bone interface affects the cement failure in total hip replacement

    PubMed Central

    Waanders, Daan; Janssen, Dennis; Mann, Kenneth A.; Verdonschot, Nico

    2010-01-01

    In the current study, the effects of different ways to implement the complex micro-mechanical behavior of the cement-bone interface on the fatigue failure of the cement mantle was investigated. In an FEA-model of a cemented hip reconstruction the cement-bone interface was modeled and numerically implemented in four different ways: (I) as infinitely stiff, (II) as infinitely strong with a constant stiffness, (III) a mixed-mode failure response with failure in tension and shear, and (IV) realistic mixed mode behavior obtained from micro FEA-models. Case II, III and IV were analyzed using data from a stiff and a compliant micro-FEA model and their effects on cement failure were analyzed. The data used for Case IV was derived from experimental specimens that were tested previously. Although the total number of cement cracks was low for all cases, the compliant Case II resulted in twice as many cracks as Case I. All cases caused similar stress distributions at the interface. In all cases, the interface did not display interfacial softening; all stayed the elastic zone. Fatigue failure of the cement mantle resulted in a more favorable stress distribution at the cement-bone interface in terms of less tension and lower shear tractions. We conclude that immediate cement-bone interface failure is not likely to occur, but its local compliancy does affect the formation of cement cracks. This means that at a macro-level the cement-bone interface should be modeled as a compliant layer. However, implementation of interfacial post-yield softening does seem to be necessary. PMID:21036358

  10. Rye Affects Bacterial Translocation, Intestinal Viscosity, Microbiota Composition and Bone Mineralization in Turkey Poults

    PubMed Central

    Tellez, Guillermo; Latorre, Juan D.; Kuttappan, Vivek A.; Hargis, Billy M.; Hernandez-Velasco, Xochitl

    2015-01-01

    Previously, we have reported that rye significantly increased both viscosity and Clostridium perfringens proliferation when compared with corn in an in vitro digestive model. Two independent trials were conducted to evaluate the effect of rye as a source of energy on bacterial translocation, intestinal viscosity, gut microbiota composition, and bone mineralization, when compared with corn in turkey poults. In each experiment, day-of-hatch, turkey poults were randomly assigned to either a corn or a rye diet (n = 0 /group). At 10 d of age, in both experiments, 12 birds/group were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood and liver samples were collected to evaluate the passage of FITC-d and bacterial translocation (BT) respectively. Duodenum, ileum and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with a rye diet showed increased (p<0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that turkey poults fed with rye had increased the number of total lactic acid bacteria (LAB) in all three sections of the gastrointestinal tract evaluated when compared to turkey poults fed with corn. Turkey poults fed with rye also had significantly higher coliforms in duodenum and ileum but not in the ceca, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in turkey poults fed with rye when compared with corn fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that increased intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition and bone mineralization. Studies to evaluate dietary inclusion of selected Direct-Fed Microbial (DFM) candidates that produce exogenous enzymes in rye fed turkey poults are

  11. Rye affects bacterial translocation, intestinal viscosity, microbiota composition and bone mineralization in Turkey poults.

    PubMed

    Tellez, Guillermo; Latorre, Juan D; Kuttappan, Vivek A; Hargis, Billy M; Hernandez-Velasco, Xochitl

    2015-01-01

    Previously, we have reported that rye significantly increased both viscosity and Clostridium perfringens proliferation when compared with corn in an in vitro digestive model. Two independent trials were conducted to evaluate the effect of rye as a source of energy on bacterial translocation, intestinal viscosity, gut microbiota composition, and bone mineralization, when compared with corn in turkey poults. In each experiment, day-of-hatch, turkey poults were randomly assigned to either a corn or a rye diet (n = 0 /group). At 10 d of age, in both experiments, 12 birds/group were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d). After 2.5 h of oral gavage, blood and liver samples were collected to evaluate the passage of FITC-d and bacterial translocation (BT) respectively. Duodenum, ileum and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with a rye diet showed increased (p<0.05) intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that turkey poults fed with rye had increased the number of total lactic acid bacteria (LAB) in all three sections of the gastrointestinal tract evaluated when compared to turkey poults fed with corn. Turkey poults fed with rye also had significantly higher coliforms in duodenum and ileum but not in the ceca, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in turkey poults fed with rye when compared with corn fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that increased intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition and bone mineralization. Studies to evaluate dietary inclusion of selected Direct-Fed Microbial (DFM) candidates that produce exogenous enzymes in rye fed turkey poults are

  12. Acid diet (high meat protein) effects on calcium metabolism and bone health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose of review: Update recent advancements regarding the effect of high animal protein on calcium utilization and bone health. Recent findings: Increased potential renal acid load resulting from a high protein (meat) intake has been closely associated with increased urinary calcium excretion. How...

  13. Study of bone mineral metabolism. [during body immobilization, bed rest, and space flight

    NASA Technical Reports Server (NTRS)

    Palmer, H. E.

    1975-01-01

    The use of Sr-85 as an indicator of the skeletal location and relative amount of bone demineralization which occurs during immobilization of the body or body parts, bed-rest or space flight was studied. The bone mineral replacement which occurs after immobilization was measured rather than the bone loss which occurs during immobilization. In a study with two adult beagle dogs, the Sr-85 uptake in a leg which had been immobilized for two months was 400 percent higher than the uptake in the legs in regular use. This increased uptake probably resulted from only a few percent loss in bone mineral and indicates that losses less than one percent can be easily detected and located. The sensitivity, simplicity, and low radiation dose associated with the use of this method indicates that it should receive consideration for use on humans in bed-rest and space flight studies. Methods for measuring changes in total body nitrogen and in assisting the Johnson Space Center in calibrating a whole body counter for total body potassium measurements were also investigated.

  14. The Effects of Tualang Honey on Bone Metabolism of Postmenopausal Women

    PubMed Central

    Mohd Effendy, Nadia; Mohamed, Norazlina; Muhammad, Norliza; Mohamad, Isa Naina; Shuid, Ahmad Nazrun

    2012-01-01

    Osteoporosis which is characterized by low bone mass and microarchitectural deterioration with a consequent increase in bone fragility can be associated with various stimuli such as oxidative stress and inflammation. Postmenopausal women are more prone to osteoporosis due to reduction in estrogen which may further lead to elevation of oxidative stress and lipid accumulation which will promote osteoblasts apoptosis. Proinflammatory cytokines are elevated following estrogen deficiency. These cytokines are important determinants of osteoclasts differentiation and its bone resorption activity. The main treatment for postmenopausal osteoporosis is estrogen replacement therapy (ERT). Despite its effectiveness, ERT, however, can cause many adverse effects. Therefore, alternative treatment that is rich in antioxidant and can exert an anti-inflammatory effect can be given to replace the conventional ERT. Tualang honey is one of the best options available as it contains antioxidant as well as exerting anti-inflammatory effect which can act as a free radical scavenger, reducing the oxidative stress level as well as inhibiting proinflammatory cytokine. This will result in survival of osteoblasts, reduced osteoclastogenic activity, and consequently, reduce bone loss. Hence, Tualang honey can be used as an alternative treatment of postmenopausal osteoporosis with minimal side effects. PMID:22973408

  15. Therapeutic effects of radix dipsaci, pyrola herb, and cynomorium songaricum on bone metabolism of ovariectomized rats

    PubMed Central

    2012-01-01

    Background The objective of this study was to evaluate the effects of herbal medicines, such as Radix Dipsaci (RDD), Pyrola Herb (PHD), and Cynomorium songaricum decoction (CSD), on osteoporotic rats induced by ovariectomy (OVX). Methods OVX or sham operations were performed on 69 virgin Wistar rats that were divided into six groups: sham (sham, n = 12), OVX control group (OVX, n = 12), and OVX rats with treatments (diethylstilbestrol, E2, n = 12; RDD, n = 11, PHD, n = 11, and CSD, n = 11). Non-surgical rats served as normal control (NC, n = 12). The treatments began four weeks after surgery and lasted for 12 weeks. Bone mass and bone turnover were analyzed by histomorphometry. Levels of protein expression and mRNA of OPG and RANKL in osteoblasts (OB) and bone marrow stromal cells (bMSC) were evaluated by immunohistochemistry and in situ hybridization. Results Compared to NC and sham rats, trabecular bone formation was significantly reduced in OVX rats, but restored in E2-treated rats. Treatment with either RDD or PHD enhanced trabecular bone formation remarkably. No significant change of bone formation was observed in CSD-treated rats. OPG expression of protein and mRNA was reduced significantly in OB and bMSC of OVX control rats. RANKL expression of protein and mRNA was increased significantly in OB and bMSC of OVX control rats. These effects were substantially reversed (increased in OPG and decreased in RANKL) by treatment with E2, RDD, or PHD in OB and bMSC of OVX rats. No significant changes in either OPG or RANKL expression were observed in OB and bMSC of OVX rats treated with CSD. Conclusions Our study showed that RDD and PHD increased bone formation by stimulating overexpression of OPG and downregulation of RANKL in OB and bMSC. This suggests that RDD and PHD may be used as alternative therapeutic agents for postmenopausal osteoporosis. PMID:22639966

  16. Influence of Vitamin D and Parathyroid Hormone on Bone and Metabolic Risk in Women with Previous Gestational Diabetes

    PubMed Central

    Serra, Monica C.; Ryan, Alice S.

    2016-01-01

    The purpose of this study was to compare plasma 25-hydroxy vitamin D (25(OH)D) and parathyroid hormone (PTH), VO2max, bone (by DXA), and metabolic outcomes across age and race-matched postmenopausal women (54±1 years; mean±SEM): 1) with previous gestational diabetes (GDM) (32±1 kg/m2; N=17), 2) without previous GDM, but with a similar BMI to GDM (32±1 kg/m2; N=17), and 3) without previous GDM, but with a higher BMI than GDM (36±1 kg/m2; N=17; P<0.01). The prevalence of 25(OH)D insufficiency and deficiency was high (~80%), but not different across groups, while PTH tended to be ~30% lower in women with a history of GDM (P=0.09). Women with a history of GDM had lower HDL cholesterol and higher diastolic blood pressure and fasting and 2-hr glucose levels (by oral glucose tolerance test) (vs. groups 2 and 3; P’s<0.05). Bone mineral density (BMD) tended to be slightly higher in women with prior GDM than the BMI matched women with no prior GDM (P=0.09). Overall, higher PTH was associated with lower femoral neck (r=−0.33) and (r=−0.38) (P’s<0.05), while lower 25(OH)D was associated with lower VO2max (r=0.25, P=0.05) and higher fasting glucose (r=−0.14) and insulin (r=−0.29 (P’s<0.05). We observe that the poor metabolic profiles of postmenopausal women with a history of GDM are independent of 25(OH)D and PTH. However, due to associations between 25(OH)D and PTH with bone and metabolic outcomes, maintaining recommended 25(OH)D and PTH concentrations is important regardless of a previous history of GDM. PMID:26882050

  17. Interindividual anatomical variations affect the plate-to-bone fit during osteosynthesis of distal radius fractures.

    PubMed

    Yoneda, Hidemasa; Iwatsuki, Katsuyuki; Hara, Tatsuya; Kurimoto, Shigeru; Yamamoto, Michiro; Hirata, Hitoshi

    2016-06-01

    We hypothesized that interindividual variations in the teardrop, which represents the volar projection of the lunate facet of the distal radius, cause unsatisfactory fitting of the volar locking plate to the bone. This can cause flexor tendon ruptures. Herein, we conducted a cross-sectional study and measured the ratio of teardrop height and the teardrop inclination angle as parameters of teardrop configuration for 200 standardized lateral radiographs (average age of the patients, 51 years). We also quantified the influence of the teardrop morphology by analyzing the fit of three locking plates to three radii with differing teardrop inclination angles using a three-dimensional computer-aided design system. The average ratios of the teardrop height and teardrop inclination angle were 0.42° (0.30-0.56°) and 28.8° (9.9-44.9°), respectively. The teardrop inclination angle was moderately correlated with age in men but not in women. In the plate-to-bone fit analyses, the fit of all the plates was significantly different between bones, with the configuration of the radius with the lowest teardrop inclination angle being the closest approximation to that of each plate. We demonstrated the interindividual variation in the shape of the teardrop and its influence on the fit of the volar plate, highlighting the importance of careful plate selection for achieving osteosynthesis of bones with a high teardrop inclination angle. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:953-960, 2016. PMID:26648456

  18. Dietary arginine affects energy metabolism through polyamine turnover in juvenile Atlantic salmon (Salmo salar).

    PubMed

    Andersen, Synne M; Holen, Elisabeth; Aksnes, Anders; Rønnestad, Ivar; Zerrahn, Jens-Erik; Espe, Marit

    2013-12-14

    In the present study, quadruplicate groups of juvenile Atlantic salmon (Salmo salar) were fed plant protein-based diets with increasing arginine inclusions (range 28·8-37·4 g/kg DM) to investigate whether arginine supplementation affects growth and lipid accumulation through an elevated polyamine turnover. Dietary lysine was held at a constant concentration, just below the requirement. All other amino acids were balanced and equal in the diets. Arginine supplementation increased protein and fat accretion, without affecting the hepatosomatic or visceralsomatic indices. Dietary arginine correlated with putrescine in the liver (R 0·78, P= 0·01) and with ornithine in the muscle, liver and plasma (P= 0·0002, 0·003 and 0·0002, respectively). The mRNA of ornithine decarboxylase, the enzyme producing putrescine, was up-regulated in the white adipose tissue of fish fed the high-arginine inclusion compared with those fed the low-arginine diet. Concomitantly, spermidine/spermine-(N1)-acetyltransferase, the rate-limiting enzyme for polyamine turnover that consumes acetyl-CoA, showed an increased activity in the liver of fish fed the arginine-supplemented diets. In addition, lower acetyl-CoA concentrations were observed in the liver of fish fed the high-arginine diet, while ATP, which is used in the process of synthesising spermidine and spermine, did not show a similar trend. Gene expression of the rate-limiting enzyme for β-oxidation of long-chain fatty acids, carnitine palmitoyl transferase-1, was up-regulated in the liver of fish fed the high-arginine diet. Taken together, the data support that increased dietary arginine activates polyamine turnover and β-oxidation in the liver of juvenile Atlantic salmon and may act to improve the metabolic status of the fish. PMID:23656796

  19. Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis

    PubMed Central

    Pountos, Ippokratis; Georgouli, Theodora; Calori, Giorgio M.; Giannoudis, Peter V.

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients. PMID:22272177

  20. Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis.

    PubMed

    Pountos, Ippokratis; Georgouli, Theodora; Calori, Giorgio M; Giannoudis, Peter V

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) play an essential part in our approach to control pain in the posttraumatic setting. Over the last decades, several studies suggested that NSAIDs interfere with bone healing while others contradict these findings. Although their analgesic potency is well proven, clinicians remain puzzled over the potential safety issues. We have systematically reviewed the available literature, analyzing and presenting the available in vitro animal and clinical studies on this field. Our comprehensive review reveals the great diversity of the presented data in all groups of studies. Animal and in vitro studies present so conflicting data that even studies with identical parameters have opposing results. Basic science research defining the exact mechanism with which NSAIDs could interfere with bone cells and also the conduction of well-randomized prospective clinical trials are warranted. In the absence of robust clinical or scientific evidence, clinicians should treat NSAIDs as a risk factor for bone healing impairment, and their administration should be avoided in high-risk patients. PMID:22272177

  1. Metabolic and transcriptional response of central metabolism affected by root endophytic fungus Piriformospora indica under salinity in barley.

    PubMed

    Ghaffari, Mohammad Reza; Ghabooli, Mehdi; Khatabi, Behnam; Hajirezaei, Mohammad Reza; Schweizer, Patrick; Salekdeh, Ghasem Hosseini

    2016-04-01

    The root endophytic fungus Piriformospora indica enhances plant adaptation to environmental stress based on general and non-specific plant species mechanisms. In the present study, we integrated the ionomics, metabolomics, and transcriptomics data to identify the genes and metabolic regulatory networks conferring salt tolerance in P. indica-colonized barley plants. To this end, leaf samples were harvested at control (0 mM NaCl) and severe salt stress (300 mM NaCl) in P. indica-colonized and non-inoculated barley plants 4 weeks after fungal inoculation. The metabolome analysis resulted in an identification of a signature containing 14 metabolites and ions conferring tolerance to salt stress. Gene expression analysis has led to the identification of 254 differentially expressed genes at 0 mM NaCl and 391 genes at 300 mM NaCl in P. indica-colonized compared to non-inoculated samples. The integration of metabolome and transcriptome analysis indicated that the major and minor carbohydrate metabolism, nitrogen metabolism, and ethylene biosynthesis pathway might play a role in systemic salt-tolerance in leaf tissue induced by the root-colonized fungus. PMID:26951140

  2. Sitamaquine-resistance in Leishmania donovani affects drug accumulation and lipid metabolism.

    PubMed

    Imbert, L; Cojean, S; Libong, D; Chaminade, P; Loiseau, P M

    2014-09-01

    This study focuses on the mechanism of sitamaquine-resistance in Leishmania donovani. Sitamaquine accumulated 10 and 1.4 fold more in cytosol than in membranes of wild-type (WT) and of sitamaquine-resistant (Sita-R160) L. donovani promastigotes, respectively. The sitamaquine accumulation was a concentration-dependent process in WT whereas a saturation occurred in Sita-R160 suggesting a reduced uptake or an increase of the sitamaquine efflux. Membrane negative phospholipids being the main target for sitamaquine uptake, a lipidomic analysis showed that sitamaquine-resistance did not rely on a decrease of membrane negative phospholipid rate in Sita-R160, discarding the hypothesis of reduced uptake. However, sterol and phospholipid metabolisms were strongly affected in Sita-R160 suggesting that sitamaquine-resistance could be related to an alteration of phosphatidylethanolamine-N-methyl-transferase and choline kinase activities and to a decrease in cholesterol uptake and of ergosterol biosynthesis. Preliminary data of proteomics analysis exhibited different protein profiles between WT and Sita-160R remaining to be characterized. PMID:25201056

  3. Alkyl-methylimidazolium ionic liquids affect the growth and fermentative metabolism of Clostridium sp

    SciTech Connect

    Nancharaiah, Y.V.; Francis, A.

    2011-06-01

    In this study, the effect of ionic liquids, 1-ethyl-3-methylimidazolium acetate [EMIM][Ac], 1-ethyl-3-methylimidazolium diethylphosphate [EMIM][DEP], and 1-methyl-3-methylimidazolium dimethylphosphate [MMIM][DMP] on the growth and glucose fermentation of Clostridium sp. was investigated. Among the three ionic liquids tested, [MMIM][DMP] was found to be least toxic. Growth of Clostridium sp. was not inhibited up to 2.5, 4 and 4 g L{sup -1} of [EMIM][Ac], [EMIM][DEP] and [MMIM][DMP], respectively. [EMIM][Ac] at <2.5 g L{sup -1}, showed hormetic effect and stimulated the growth and fermentation by modulating medium pH. Total organic acid production increased in the presence of 2.5 and 2 g L{sup -1} of [EMIM][Ac] and [MMIM][DMP]. Ionic liquids had no significant influence on alcohol production at <2.5 g L{sup -1}. Total gas production was affected by ILs at {ge}2.5 g L{sup -1} and varied with type of methylimidazolium IL. Overall, the results show that the growth and fermentative metabolism of Clostridium sp. is not impacted by ILs at concentrations below 2.5 g L{sup -1}.

  4. Mono-(2-ethylhexyl) phthalate targets glycogen debranching enzyme and affects glycogen metabolism in rat testis.

    PubMed

    Kuramori, Chikanori; Hase, Yasuyoshi; Hoshikawa, Koichi; Watanabe, Keiko; Nishi, Takeyuki; Hishiki, Takako; Soga, Tomoyoshi; Nashimoto, Akihiro; Kabe, Yasuaki; Yamaguchi, Yuki; Watanabe, Hajime; Kataoka, Kohsuke; Suematsu, Makoto; Handa, Hiroshi

    2009-05-01

    Phthalate esters are commonly used plasticizers; however, some are suspected to cause reproductive toxicity. Administration of high doses of di-(2-ethylhexyl) phthalate (DEHP) induces germ cell death in male rodents. Mono-(2-ethylhexyl) phthalate (MEHP), a hydrolyzed metabolite of DEHP, appears to be responsible for this testicular toxicity; however, the underlying mechanism of this chemical's action remains unknown. Here, using a one-step affinity purification procedure, we identified glycogen debranching enzyme (GDE) as a phthalate-binding protein. GDE has oligo-1,4-1,4-glucanotransferase and amylo-1,6-glucosidase activities, which are responsible for the complete degradation of glycogen to glucose. Our findings demonstrate that MEHP inhibits the activity of oligo-1,4-1,4-glucanotransferase, but not of amylo-1,6-glucosidase. Among various phthalate esters tested, MEHP specifically binds to and inhibits GDE. We also show that DEHP administration affects glycogen metabolism in rat testis. Thus, inhibition of GDE by MEHP may play a role in germ cell apoptosis in the testis. PMID:19240039

  5. Developmental changes in carbon and nitrogen metabolism affect tea quality in different leaf position.

    PubMed

    Li, Zhi-Xin; Yang, Wei-Jun; Ahammed, Golam Jalal; Shen, Chen; Yan, Peng; Li, Xin; Han, Wen-Yan

    2016-09-01

    Leaf position represents a specific developmental stage that influences both photosynthesis and respiration. However, the precise relationships between photosynthesis and respiration in different leaf position that affect tea quality are largely unknown. Here, we show that the effective quantum yield of photosystem II [ΦPSⅡ] as well as total chlorophyll concentration (TChl) of tea leaves increased gradually with leaf maturity. Moreover, respiration rate (RR) together with total nitrogen concentration (TN) decreased persistently, but total carbon remained unchanged during leaf maturation. Analyses of major N-based organic compounds revealed that decrease in TN was attributed to a significant decrease in the concentration of caffeine and amino acids (AA) in mature leaves. Furthermore, soluble sugar (SS) decreased, but starch concentration increased with leaf maturity, indicating that source-sink relationship was altered during tea leaf development. Detailed correlation analysis showed that ΦPSⅡ was negatively correlated with RR, SS, starch, tea polyphenol (TP), total catechins and TN, but positively correlated with TChl; while RR was positively correlated with TN, SS, TP and caffeine, but negatively correlated with TChl and starch concentrations. Our results suggest that biosynthesis of chlorophyll, catechins and polyphenols is closely associated with photosynthesis and respiration in different leaf position that greatly influences the relationship between primary and secondary metabolism in tea plants. PMID:27380366

  6. Dietary and Urinary Sulfur can Predict Changes in Bone Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Zwart, Sara R.; Heer, Martina; Shackelford, Linda; Smith, Scott M.

    2015-01-01

    Mitigating space flight-induced bone loss is critical for space exploration, and diet can play a major role in this effort. Previous ground-based studies provide evidence that dietary composition can influence bone resorption during bed rest. In this study we examined the role of dietary intake patterns as one factor that can influence bone mineral loss in astronauts during space flight. Crew members were asked to consume, for 4 days at a time, prescribed menus with either a low (0.3-0.6 g/mEq) or high (1.0-1.3 g/mEq) ratio of animal protein to potassium (APro:K). Menus were developed for each crewmember, and were designed to meet both crew preferences and study constraints. Intakes of energy, total protein, calcium, and sodium were held relatively constant between the two diets. The order of the menus was randomized, and crews completed each set (low and high) once before and twice during space flight, for a total of 6 controlled diet sessions. One inflight session and three postflight sessions (R+30, R+180, R+365) monitored typical dietary intake. As of this writing, data are available from 14 crew members. The final three subjects' inflight samples are awaiting return from the International Space Station via Space-X. On the last day of each of the 4-d controlled diet sessions, 24-h urine samples were collected, along with a fasting blood sample on the morning of the 5th day. Preliminary analyses show that urinary excretion of sulfate (normalized to lean body mass) is a significant predictor of urinary n-telopeptide (NTX). Dietary sulfate (normalized to lean body mass) is also a significant predictor of urinary NTX. The results from this study, will be important to better understand diet and bone interrelationships during space flight as well as on Earth. This study was funded by the Human Health Countermeasures Element of the NASA Human Research Program.

  7. Metabolic bone disease in the preterm infant: Current state and future directions

    PubMed Central

    Rehman, Moghis Ur; Narchi, Hassib

    2015-01-01

    Neonatal osteopenia is an important area of interest for neonatologists due to continuing increased survival of preterm infants. It can occur in high-risk infants such as preterm infants, infants on long-term diuretics or corticosteroids, and those with neuromuscular disorders. Complications such as rickets, pathological fractures, impaired respiratory function and poor growth in childhood can develop and may be the first clinical evidence of the condition. It is important for neonatologists managing such high-risk patients to regularly monitor biochemical markers for evidence of abnormal bone turnover and inadequate mineral intake in order to detect the early phases of impaired bone mineralization. Dual-energy X-ray absorptiometry has become an increasingly used research tool for assessing bone mineral density in children and neonates, but more studies are still needed before it can be used as a useful clinical tool. Prevention and early detection of osteopenia are key to the successful management of this condition and oral phosphate supplements should be started as soon as is feasible. PMID:26413483

  8. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain.

    PubMed

    Paes, Fabio M; Serafini, Aldo N

    2010-03-01

    Bone pain due to skeletal metastases constitutes the most common type of chronic pain among patients with cancer. It significantly decreases the patient's quality of life and is associated with comorbidities, such as hypercalcemia, pathologic fractures and spinal cord compression. Approximately 65% of patients with prostate or breast cancer and 35% of those with advanced lung, thyroid, and kidney cancers will have symptomatic skeletal metastases. The management of bone pain is extremely difficult and involves a multidisciplinary approach, which usually includes analgesics, hormone therapies, bisphosphonates, external beam radiation, and systemic radiopharmaceuticals. In patients with extensive osseous metastases, systemic radiopharmaceuticals should be the preferred adjunctive therapy for pain palliation. In this article, we review the current approved radiopharmaceutical armamentarium for bone pain palliation, focusing on indications, patient selection, efficacy, and different biochemical characteristics and toxicity of strontium-89 chloride, samarium-153 lexidronam, and rhenium-186 etidronate. A brief discussion on the available data on rhenium-188 is presented focusing on its major advantages and disadvantages. We also perform a concise appraisal of the other available treatment options, including pharmacologic and hormonal treatment modalities, external beam radiation, and bisphosphonates. Finally, the available data on combination therapy of radiopharmaceuticals with bisphosphonates or chemotherapy are discussed. PMID:20113678

  9. Urinary Acid Excretion Can Predict Changes in Bone Metabolism During Space Flight

    NASA Technical Reports Server (NTRS)

    Zwart, Sara R.; Smith, Scott M.

    2011-01-01

    Mitigating space flight-induced bone loss is critical for space exploration, and a dietary countermeasure would be ideal. We present here preliminary data from a study where we examined the role of dietary intake patterns as one factor that can influence bone mineral loss in astronauts during space flight. Crewmembers (n=5) were asked to consume a prescribed diet with either a low (0.3-0.6) or high (1.0-1.3) ratio of animal protein to potassium (APro:K) before and during space flight for 4-d periods. Diets were controlled for energy, total protein, calcium, and sodium. 24-h urine samples were collected on the last day of each of the 4-d controlled diet sessions. 24-h urinary acid excretion, which was predicted by dietary potential renal acid load, was correlated with urinary n-telopeptide (NTX, Pearson R = 0.99 and 0.80 for the high and low APro:K sessions, respectively, p<0.001). The amount of protein when expressed as the percentage of total energy (but not as total grams) was also correlated with urinary NTX (R = 0.66, p<0.01). These results, from healthy individuals in a unique environment, will be important to better understand diet and bone interrelationships during space flight as well as on Earth. The study was funded by the NASA Human Research Program.

  10. Inulin, oligofructose and bone health: experimental approaches and mechanisms.

    PubMed

    Weaver, Connie M

    2005-04-01

    Inulin-type fructans have been proposed to benefit mineral retention, thereby enhancing bone health. Many, but not all, experimental animal studies have shown increased mineral absorption by feeding non-digestible oligosaccharides. Possible reasons for inconsistencies are explored. A few studies have reported an enhanced bone mineral density or content. Bone health can be evaluated in chronic feeding studies with bone densitometry, bone breaking strength, bone mineral concentration and bone structure. Isotopic Ca tracers can be used to determine the point of metabolism affected by feeding a functional food ingredient. These methods and the effects of feeding inulin-type fructose are reviewed. Inulin-type fructans enhance Mg retention. Chicory long-chain inulin and oligofructose enhance femoral Ca content, bone mineral density and Ca retention through enhanced Ca absorption and suppressed bone turnover rates, but it is not bone-promoting under all conditions. PMID:15877902

  11. Bone tumor

    MedlinePlus

    ... physical exam. Tests that may be done include: Alkaline phosphatase blood level Bone biopsy Bone scan Chest x- ... also affect the results of the following tests: Alkaline phosphatase isoenzyme Blood calcium level Parathyroid hormone Blood phosphorus ...

  12. GENOME-WIDE LINKAGE ANALYSIS TO IDENTIFY CHROMOSOMAL REGIONS AFFECTING PHENOTYPIC TRAITS IN THE CHICKEN. IV. METABOLIC TRAITS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study is a comprehensive genome analysis to detect QTL affecting metabolic traits in chickens. Two unique F2 crosses generated from a commercial broiler male line and two genetically distinct lines (Leghorn and Fayoumi) were used in the present study. The plasma glucagons, insulin, lactate, g...

  13. Dietary folate and choline status differentially affect lipid metabolism and behavior-mediated neurotransmitters in young rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The relationship between choline and folate metabolisms is an important issue due to the essential role of these nutrients in brain plasticity and cognitive functions. Present study was designed to investigate whether modification of the dietary folate-choline status in young rats would affect brain...

  14. Metabolomic Profiles Delineate Signature Metabolic Shifts during Estrogen Deficiency-Induced Bone Loss in Rat by GC-TOF/MS

    PubMed Central

    Zhang, Qi; Ying, Hanjie; A, Jiye; Sun, Jianguo; Wu, Di; Wang, Yonglu; Li, Jing; Liu, Yinhui

    2013-01-01

    Postmenopausal osteoporosis is a complicated and multi-factorial disease. To study the metabolic profiles and pathways activated in osteoporosis, Eight rats were oophorectomized (OVX group) to represent postmenopausal osteoporosis and the other eight rats were sham operated (Sham group) to be the control. The biochemical changes were assessed with metabolomics using a gas chromatography/time-of-flight mass spectrometry. Metabolomic profile using serial blood samples obtained prior to and at different time intervals after OVX were analyzed by principal component analysis (PCA) and Partial least squares-discriminant analysis (PLS-DA). The conventional indicators (bone mineral density, serum Bone alkaline phosphatase (B-ALP) and N-telopeptide of type I collagen (NTx) of osteoporosis in rats were also determined simultaneously. In OVX group, the metabolomics method could describe the endogenous changes of the disease more sensitively and systematically than the conventional criteria during the progression of osteoporosis. Significant metabolomic difference was also observed between the OVX and Sham groups. The metabolomic analyses of rat plasma showed that levels of arachidonic acid, octadecadienoic acid, branched-chain amino acids (valine, leucine and isoleucine), homocysteine, hydroxyproline and ketone bodies (3-Hydroxybutyric Acid) significantly elevated, while levels of docosahexaenoic acid, dodecanoic acid and lysine significantly decreased in OVX group compared with those in the homeochronous Sham group. Considering such metabolites are closely related to the pathology of the postmenopausal osteoporosis, the results suggest that potential biomarkers for the early diagnosis or the pathogenesis of osteoporosis might be identified via metabolomic study. PMID:23408954

  15. FGF23-FGF Receptor/Klotho Pathway as a New Drug Target for Disorders of Bone and Mineral Metabolism.

    PubMed

    Fukumoto, Seiji

    2016-04-01

    Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced by bone and works by binding to Klotho-FGF receptor complex. Excessive and deficient actions of FGF23 result in hypophosphatemic and hyperphosphatemic diseases, respectively. Therefore, it is reasonable to think that modulating FGF23 activities may be a novel therapeutic measure for these diseases. Several preclinical reports indicate that the inhibition of FGF23 activities ameliorates hypophosphatemic rickets/osteomalacia caused by excessive actions of FGF23. In addition, phase I-II clinical trials of anti-FGF23 antibody in adult patients with X-linked hypophosphatemia rickets, the most prevalent cause of genetic FGF23-related hypophosphatemic rickets, indicated that the antibody enhances renal tubular phosphate reabsorption and increases serum phosphate. However, it is not known whether the inhibition of FGF23 activities actually brings clinical improvement of rickets and osteomalacia. Available data indicate that FGF23-FGF receptor/Klotho pathway can be a new drug target for disorders of phosphate and bone metabolism. PMID:26126937

  16. [THE MARKERS OF BONE TISSUE METABOLISM. THE REFERENCE VALUES FOR THE KHANTY-MANSI AUTONOMOUS OKRUG-YUGRA].

    PubMed

    Kutchin, R V; Nenenko, N D; Tchernitsina, N V; Maksimova, T A

    2016-03-01

    The article defines reference values of particular markers of metabolism of bone tissue common to residents of the Khanty-Mansi Autonomous Okrug-Yugra. The enzyme-linked immunosorbent assay was applied to analyze blood serum of 86 patients (43 males, 43 females) detecting concentration of C-tailed telopeptide of collagen type I, osteocalcin, calcitonin, parathyroid hormone and 1.25(OH)2 vitamin D. The following reference values were derived. The C-tailed telopeptide (ng/ml): 0.111 (0.071-0.162) for females and 0.146 (0.066-0.255) for males. The osteocalcin (ng/ml): 20.6 (12.9-33.0) for females and 27.6 (12.0-61.9) for males. Calcitonin (pg/ml) - 2.55 (1.90-3.76); parathyroid hormone (pg/ml) - 39 (13-88); 1.25(OH)2 vitamin D (pg/ml) - 10.5 (3.9-46.4). It was also noted that decreasing of average indicators of vitamin D level and increasing of level of parathyroid hormone among residents of the Khanty-Mansi Autonomous Okrug-Yugra can cause increasing of intensity of accumulation of minerals in bone tissue as compared with residents of middle latitudes. PMID:27506104

  17. Influence of racing on the serum concentrations of acute-phase proteins and bone metabolism biomarkers in racing greyhounds.

    PubMed

    Tharwat, M; Al-Sobayil, F; Buczinski, S

    2014-11-01

    This study was designed to evaluate the influence of racing on the serum concentrations of the acute-phase proteins (APPs) C-reactive protein (CRP), haptoglobin (Hp) and serum amyloid A (SAA) in 32 endurance-racing greyhounds. The study also aimed to investigate the effect of a 7 km race on the bone biomarkers osteocalcin (OC), bone-specific alkaline phosphatase (b-ALP) and pyridinoline cross-links (PYD). Total white blood cell (WBC) count, and the serum concentrations of cortisol, tumour necrosis factor-α (TNF-α), vitamin D and testosterone were also determined. Blood samples were collected 24 h prior to (T0) and within 2 h of completion of the race (T1). Compared to baseline values, WBC count did not change significantly (P = 0.2300), serum cortisol, Hp and SAA increased, while TNF-α and CRP decreased (P <0.0001 for each). There were no significant differences between the pre- and post-race serum concentrations of OC and PYD (P = 0.9500 and P = 0.2600, respectively), but serum b-ALP increased significantly (P = 0.0004). Serum concentrations of vitamin D and testosterone increased after racing (P = 0.0100 and P <0.0001, respectively). In this study, a 7 km race stimulated an acute-phase response, demonstrated by significant increases in the serum concentrations Hp and SAA in racing greyhounds. Increased serum b-ALP post-race probably indicates a change in bone metabolism and deserves further study. PMID:25294662

  18. Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

    PubMed Central

    Yuan, Tong-ling; Chen, Jin; Tong, Yan-li; Zhang, Yan; Liu, Yuan-yuan; Wei, James Cheng-Chung; Liu, Yi; Herrmann, Martin

    2016-01-01

    Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p < 0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p < 0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p < 0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p < 0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort. Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis. PMID:27314037

  19. Impact of high fat diets on bone strength and metabolism in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review is on the effect of high fat diets on poultry growth and metabolism. Results from our lab and in the literature show that high fat diets do not cause increase body weights but reduce lean meat percentage. High fat diets containing up to 15% animal fats did not cause femoral head separati...

  20. Culture surfaces coated with various implant materials affect chondrocyte growth and metabolism.

    PubMed

    Hambleton, J; Schwartz, Z; Khare, A; Windeler, S W; Luna, M; Brooks, B P; Dean, D D; Boyan, B D

    1994-07-01

    to culture surface was comparable, differing primarily in magnitude. Cell maturation-dependent effects were evident when enzyme activity in trypsinized and scraped cells was compared. These results indicate that different surface materials affect chondrocyte metabolism and phenotypic expression in vitro and suggest that implant materials may modulate the phenotypic expression of cells in vivo. PMID:7520486

  1. Factors that affect postnatal bone growth retardation in the twitcher murine model of Krabbe disease

    PubMed Central

    Contreras, Miguel Agustin; Ries, William Louis; Shanmugarajan, Srinivasan; Arboleda, Gonzalo; Singh, Inderjit; Singh, Avtar Kaur

    2010-01-01

    Krabbe disease is an inherited lysosomal disorder in which galactosylsphingosine (psychosine) accumulates mainly in the central nervous system. To gain insight into the possible mechanism(s) that may be participating in the inhibition of the postnatal somatic growth described in the animal model of this disease (twitcher mouse, twi), we studied their femora. This study reports that twi femora are smaller than of those of wild type (wt), and present with abnormality of marrow cellularity, bone deposition (osteoblastic function), and osteoclastic activity. Furthermore, lipidomic analysis indicates altered sphingolipid homeostasis, but without significant changes in the levels of sphingolipid-derived intermediates of cell death (ceramide) or the levels of the osteoclast-osteoblast coupling factor (sphingosine-1-phosphate). However, there was significant accumulation of psychosine in the femora of adult twi animals as compared to wt, without induction of tumor necrosis factor-alpha or interleukin-6. Analysis of insulin-like growth factor-1 (IGF-1) plasma levels, a liver secreted hormone known to play a role in bone growth, indicated a drastic reduction in twi animals when compared to wt. To identify the cause of the decrease, we examined the IGF-1 mRNA expression and protein levels in the liver. The results indicated a significant reduction of IGF-1 mRNA as well as protein levels in the liver from twi as compared to wt littermates. Our data suggest that a combination of endogenous (psychosine) and endocrine (IGF-1) factors play a role in the inhibition of postnatal bone growth in twi mice; and further suggest that derangements of liver function may be contributing, at least in part, to this alteration. PMID:20441793

  2. Age and skeletal sites affect BMP-2 responsiveness of human bone marrow stromal cells.

    PubMed

    Osyczka, Anna Maria; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O

    2009-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular, and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be due partly to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible, and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin, and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  3. Age and Skeletal Sites Affect BMP-2 Responsiveness of Human Bone Marrow Stromal Cells

    PubMed Central

    Osyczka, Anna M.; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O.

    2010-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be partly due to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  4. Change of urinary fluoride and bone metabolism indicators in the endemic fluorosis areas of southern china after supplying low fluoride public water

    PubMed Central

    2013-01-01

    Background Few studies have evaluated health impacts, especially biomarker changes, following implementation of a new environmental policy. This study examined changes in water fluoride, urinary fluoride (UF), and bone metabolism indicators in children after supplying low fluoride public water in endemic fluorosis areas of Southern China. We also assessed the relationship between UF and serum osteocalcin (BGP), calcitonin (CT), alkaline phosphatase (ALP), and bone mineral density to identify the most sensitive bone metabolism indicators related to fluoride exposure. Methods Four fluorosis-endemic villages (intervention villages) in Guangdong, China were randomly selected to receive low-fluoride water. One non-endemic fluorosis village with similar socio-economic status, living conditions, and health care access, was selected as the control group. 120 children aged 6-12 years old were randomly chosen from local schools in each village for the study. Water and urinary fluoride content as well as serum BGP, CT, ALP and bone mineral density were measured by the standard methods and compared between the children residing in the intervention villages and the control village. Benchmark dose (BMD) and benchmark dose lower limit (BMDL) were calculated for each bone damage indicator. Results Our study found that after water source change, fluoride concentrations in drinking water in all intervention villages (A-D) were significantly reduced to 0.11 mg/l, similar to that in the control village (E). Except for Village A where water change has only been taken place for 6 years, urinary fluoride concentrations in children of the intervention villages were lower or comparable to those in the control village after 10 years of supplying new public water. The values of almost all bone indicators in children living in Villages B-D and ALP in Village A were either lower or similar to those in the control village after the intervention. CT and BGP are sensitive bone metabolism

  5. Human calcium metabolism including bone resorption measured with {sup 41}Ca tracer

    SciTech Connect

    Freeman, S.P.H.T.; King, J.C.; Vieira, N.E.; Woodhouse, L.R.; Yergey, A.L.

    1996-08-01

    Accelerator mass spectrometry is so sensitive to small quantities of {sup 41}Ca that it might be used as a tracer in the study of human calcium kinetics to generate unique kinds of data. In contrast with the use of other Ca isotopic tracers, {sup 41}Ca tracer can be so administered that the tracer movements between the various body pools achieve a quasi steady state. Resorbing bone may thus be directly measured. We have tested such a protocol against a conventional stable isotope experiment with good agreement.

  6. The Impact of Vitamin D, Calcium, Protein Supplementation, and Physical Exercise on Bone Metabolism After Bariatric Surgery: The BABS Study.

    PubMed

    Muschitz, Christian; Kocijan, Roland; Haschka, Judith; Zendeli, Afrodite; Pirker, Thomas; Geiger, Corinna; Müller, Andrea; Tschinder, Bettina; Kocijan, Annemarie; Marterer, Christina; Nia, Arastoo; Muschitz, Gabriela Katharina; Resch, Heinrich; Pietschmann, Peter

    2016-03-01

    Laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are common and effective methods to treat severe obesity, but these procedures can adversely influence bone metabolism and areal bone mineral density (aBMD). This was a prospective 24-month single-center interventional two-arm study in 220 women and similarly aged men (median age 40.7 years) with a body mass index (BMI) >38 kg/m(2) after RYGB and SG procedures. Patients were randomized into: 1) an intervention group receiving: 28,000 IU cholecalciferol/wk for 8 weeks before bariatric surgery, 16,000 IU/wk and 1000 mg calciummonocitrate/d after surgery, daily BMI-adjusted protein supplementation and physical exercise (Nordic walking, strength perseverance, and equipment training); 2) a non-intervention group: no preoperative loading, nutritional supplementation, or obligatory physical exercise. At study endpoint, when comparing the intervention group to the non-intervention group, the relative percentage changes of serum levels of sclerostin (12.1% versus 63.8%), cross-linked C-telopeptide (CTX, 82.6% versus 158.3%), 25-OH vitamin D (13.4% versus 18.2%), phosphate (23.7% versus 32%, p < 0.001 for all), procollagen type 1 amino-terminal propeptide (P1NP, 12% versus 41.2%), intact parathyroid hormone (iPTH, -17.3% versus -7.6%), and Dickkopf-1 (-3.9% versus -8.9%, p < 0.05 for all) differed. The decline in lumbar spine, total hip and total body aBMD, changes in BMI, lean body mass (LBM), as well as changes in trabecular bone score (TBS) values (p < 0.005 for all) were less, but significantly, pronounced in the intervention group. We conclude that vitamin D loading and ongoing vitamin D, calcium, and BMI-adjusted protein supplementation in combination with physical exercise decelerates the loss of aBMD and LBM after bariatric surgery. Moreover, the well-known increases of bone turnover markers are less pronounced. PMID:26350034

  7. Host-related metabolic cues affect colonization strategies of a root endophyte

    PubMed Central

    Lahrmann, Urs; Ding, Yi; Banhara, Aline; Rath, Magnus; Hajirezaei, Mohammad R.; Döhlemann, Stefanie; von Wirén, Nicolaus; Parniske, Martin; Zuccaro, Alga

    2013-01-01

    The mechanisms underpinning broad compatibility in root symbiosis are largely unexplored. The generalist root endophyte Piriformospora indica establishes long-lasting interactions with morphologically and biochemically different hosts, stimulating their growth, alleviating salt stress, and inducing local and systemic resistance to pathogens. Cytological studies and global investigations of fungal transcriptional responses to colonization of barley and Arabidopsis at different symbiotic stages identified host-dependent colonization strategies and host-specifically induced effector candidates. Here, we show that in Arabidopsis, P. indica establishes and maintains biotrophic nutrition within living epidermal cells, whereas in barley the symbiont undergoes a nutritional switch to saprotrophy that is associated with the production of secondary thinner hyphae in dead cortex cells. Consistent with a diversified trophic behavior and with the occurrence of nitrogen deficiency at the onset of saprotrophy in barley, fungal genes encoding hydrolytic enzymes and nutrient transporters were highly induced in this host but not in Arabidopsis. Silencing of the high-affinity ammonium transporter PiAMT1 gene, whose transcripts are accumulating during nitrogen starvation and in barley, resulted in enhanced colonization of this host, whereas it had no effect on the colonization of Arabidopsis. Increased levels of free amino acids and reduced enzymatic activity for the cell-death marker VPE (vacuolar-processing enzyme) in colonized barley roots coincided with an extended biotrophic lifestyle of P. indica upon silencing of PiAMT1. This suggests that PiAmt1 functions as a nitrogen sensor mediating the signal that triggers the in planta activation of the saprotrophic program. Thus, host-related metabolic cues affect the expression of P. indica’s alternative lifestyles. PMID:23918389

  8. Metabolic stressors and signals differentially affect energy allocation between reproduction and immune function.

    PubMed

    Carlton, Elizabeth D; Cooper, Candace L; Demas, Gregory E

    2014-11-01

    Most free-living animals have finite energy stores that they must allocate to different physiological and behavioral processes. In times of energetic stress, trade-offs in energy allocation among these processes may occur. The manifestation of trade-offs may depend on the source (e.g., glucose, lipids) and severity of energy limitation. In this study, we investigated energetic trade-offs between the reproductive and immune systems by experimentally limiting energy availability to female Siberian hamsters (Phodopus sungorus) with 2-deoxy-d-glucose, a compound that disrupts cellular utilization of glucose. We observed how glucoprivation at two levels of severity affected allocation to reproduction and immunity. Additionally, we treated a subset of these hamsters with leptin, an adipose hormone that provides a direct signal of available fat stores, in order to determine how increasing this signal of fat stores influences glucoprivation-induced trade-offs. We observed trade-offs between the reproductive and immune systems and that these trade-offs depended on the severity of energy limitation and exogenous leptin signaling. The majority of the animals experiencing mild glucoprivation entered anestrus, whereas leptin treatment restored estrous cycling in these animals. Surprisingly, virtually all animals experiencing more severe glucoprivation maintained normal estrous cycling throughout the experiment; however, exogenous leptin resulted in lower antibody production in this group. These data suggest that variation in these trade-offs may be mediated by shifts between glucose and fatty acid utilization. Collectively, the results of the present study highlight the context-dependent nature of these trade-offs, as trade-offs induced by the same metabolic stressor can manifest differently depending on its intensity. PMID:25125082

  9. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson BH. Principles of Anatomy and Physiology . 14th ed. Hoboken, NJ: John H Wiley and Sons; 2013: ...

  10. Water deficit alters differentially metabolic pathways affecting important flavor and quality traits in grape berries of Cabernet Sauvignon and Chardonnay

    PubMed Central

    Deluc, Laurent G; Quilici, David R; Decendit, Alain; Grimplet, Jérôme; Wheatley, Matthew D; Schlauch, Karen A; Mérillon, Jean-Michel; Cushman, John C; Cramer, Grant R

    2009-01-01

    Background Water deficit has significant effects on grape berry composition resulting in improved wine quality by the enhancement of color, flavors, or aromas. While some pathways or enzymes affected by water deficit have been identified, little is known about the global effects of water deficit on grape berry metabolism. Results The effects of long-term, seasonal water deficit on berries of Cabernet Sauvignon, a red-wine grape, and Chardonnay, a white-wine grape were analyzed by integrated transcript and metabolite profiling. Over the course of berry development, the steady-state transcript abundance of approximately 6,000 Unigenes differed significantly between the cultivars and the irrigation treatments. Water deficit most affected the phenylpropanoid, ABA, isoprenoid, carotenoid, amino acid and fatty acid metabolic pathways. Targeted metabolites were profiled to confirm putative changes in specific metabolic pathways. Water deficit activated the expression of numerous transcripts associated with glutamate and proline biosynthesis and some committed steps of the phenylpropanoid pathway that increased anthocyanin concentrations in Cabernet Sauvignon. In Chardonnay, water deficit activated parts of the phenylpropanoid, energy, carotenoid and isoprenoid metabolic pathways that contribute to increased concentrations of antheraxanthin, flavonols and aroma volatiles. Water deficit affected the ABA metabolic pathway in both cultivars. Berry ABA concentrations were highly correlated with 9-cis-epoxycarotenoid dioxygenase (NCED1) transcript abundance, whereas the mRNA expression of other NCED genes and ABA catabolic and glycosylation processes were largely unaffected. Water deficit nearly doubled ABA concentrations within berries of Cabernet Sauvignon, whereas it decreased ABA in Chardonnay at véraison and shortly thereafter. Conclusion The metabolic responses of grapes to water deficit varied with the cultivar and fruit pigmentation. Chardonnay berries, which lack any

  11. Culture perfusion schedules influence the metabolic activity and granulocyte-macrophage colony-stimulating factor production rates of human bone marrow stromal cells.

    PubMed

    Caldwell, J; Palsson, B O; Locey, B; Emerson, S G

    1991-05-01

    The metabolic function and GM-CSF production rates of adherent human bone marrow stromal cells were investigated as functions of medium and serum feeding rates. A range of medium exchange schedules was studied, ranging from a typical Dexter culture protocol of one weekly medium exchange to a full media exchange daily, which more closely approximates what bone marrow cells experience in situ. Glucose consumption was found to be significantly higher at full daily exchange rate than at any other exchange schedule examined. However, the lactate yield on glucose was a constant, at 1.8 mol/mol, under all conditions considered. Differential serum vs. medium exchange experiment showed that both serum supply and medium nutrients were responsible for the altered behavior at high exchange rates. Glutamine consumption was found to be insignificant under all culture conditions examined. A change in exchange schedule from 50% daily medium exchange to full daily medium exchange after 14 days of culture was found to result in a transient production of GM-CSF and a change in metabolic behavior to resemble that of cultures which had full daily exchange from day one. These results suggest that both stromal cell metabolism and GM-CSF production are sensitive to medium exchange schedules. Taken together, the data presented indicate that attempts to model the function of human bone marrow in vitro may be well served by beginning with medium exchange schedules that more closely mimic the in vivo physiologic state of bone marrow. PMID:2040665

  12. Effect of Pulsed Electromagnetic Field on Bone Formation and Lipid Metabolism of Glucocorticoid-Induced Osteoporosis Rats through Canonical Wnt Signaling Pathway.

    PubMed

    Jiang, Yuan; Gou, Hui; Wang, Sanrong; Zhu, Jiang; Tian, Si; Yu, Lehua

    2016-01-01

    Pulsed electromagnetic field (PEMF) has been suggested as a promising method alternative to drug-based therapies for treating osteoporosis (OP), but the role of PEMF in GIOP animal models still remains unknown. This study was performed to investigate the effect of PEMF on bone formation and lipid metabolism and further explored the several important components and targets of canonical Wnt signaling pathway in GIOP rats. After 12 weeks of intervention, bone mineral density (BMD) level of the whole body increased significantly, serum lipid levels decreased significantly, and trabeculae were thicker in GIOP rats of PEMF group. PEMF stimulation upregulated the mRNA and protein expression of Wnt10b, LRP5, β-catenin, OPG, and Runx2 and downregulated Axin2, PPAR-γ, C/EBPα, FABP4, and Dkk-1. The results of this study suggested that PEMF stimulation can prevent bone loss and improve lipid metabolism disorders in GIOP rats. Canonical Wnt signaling pathway plays an important role in bone formation and lipid metabolism during PEMF stimulation. PMID:26941827

  13. Biochemical Assessment of Bone Health in Working Obese Egyptian Females with Metabolic Syndrome; the Effect of Weight Loss by Natural Dietary Therapies

    PubMed Central

    Moaty, Maha I. A.; Fouad, Suzanne; Shebini, Salwa M. El; Kazem, Yusr I.; Tapozada, Salwa T.

    2015-01-01

    AIM: To investigate the relation between bone parameters and the metabolic syndrome criteria, before and after the administration of two different natural dietary supplements in middle aged working obese Egyptian women suffering from metabolic syndrome (MetS). SUBJECTS AND METHODS: Fifty eight middle aged obese female volunteers suffering from metabolic syndrome were divided into two groups. During the first period, group (A) consumed a low caloric diet and nutritional supplement consisting of doum flour biscuits, while group (B) consumed whole meal wheat flour biscuit with the same instructions. During the second period, both supplements were omitted. Assessment of blood pressure, relevant anthropometric parameters, lipid accumulation product, fasting blood glucose, uric acid, 25 hydroxy vitamin D (25 (OH) D), parathyroid hormone (PTH) and bone-specific alkaline phosphatase were performed. RESULTS: Data showed that although both supplements improved the MetS criteria and the bone health parameters, the supplement containing the doum flour proved to be more effective. CONCLUSION: These results confirm the benefit of doum in improving bone health parameter [25 (OH) D/PTH axis] in the MetS patients, beside the MetS criteria. So, we can conclude that natural effective supplements lead towards the optimization of biochemical parameters in favor of a healthy outcome. PMID:27275291

  14. Effect of Pulsed Electromagnetic Field on Bone Formation and Lipid Metabolism of Glucocorticoid-Induced Osteoporosis Rats through Canonical Wnt Signaling Pathway

    PubMed Central

    Jiang, Yuan; Gou, Hui; Wang, Sanrong; Zhu, Jiang; Tian, Si; Yu, Lehua

    2016-01-01

    Pulsed electromagnetic field (PEMF) has been suggested as a promising method alternative to drug-based therapies for treating osteoporosis (OP), but the role of PEMF in GIOP animal models still remains unknown. This study was performed to investigate the effect of PEMF on bone formation and lipid metabolism and further explored the several important components and targets of canonical Wnt signaling pathway in GIOP rats. After 12 weeks of intervention, bone mineral density (BMD) level of the whole body increased significantly, serum lipid levels decreased significantly, and trabeculae were thicker in GIOP rats of PEMF group. PEMF stimulation upregulated the mRNA and protein expression of Wnt10b, LRP5, β-catenin, OPG, and Runx2 and downregulated Axin2, PPAR-γ, C/EBPα, FABP4, and Dkk-1. The results of this study suggested that PEMF stimulation can prevent bone loss and improve lipid metabolism disorders in GIOP rats. Canonical Wnt signaling pathway plays an important role in bone formation and lipid metabolism during PEMF stimulation. PMID:26941827

  15. Effects of cortisol secreted via a 12-h infusion of adrenocorticotropic hormone on mineral homeostasis and bone metabolism in ovariectomized cows.

    PubMed

    Kim, D; Yamagishi, N; Devkota, B; Furuhama, K

    2012-10-01

    To evaluate the effects of endogenously secreted cortisol on mineral homeostasis and bone metabolism in cows, 4 ovariectomized Holstein cows were infused for 12 h with either an adrenocorticotropic hormone (ACTH) solution (0.5 mg/2 L isotonic NaCl solution per cow) or isotonic NaCl solution in a 2×2 crossover design. ACTH infusion stimulated cortisol secretion and increased plasma cortisol concentrations for 18 h (P<0.001), leading to an elevated plasma glucose concentration until 36 h (P<0.001). Plasma calcium and magnesium concentrations in ACTH-infused cows fluctuated within normal ranges, whereas hypophosphatemia was observed unequivocally. The biochemical bone resorption markers tartrate-resistant acid phosphatase 5b and hydroxyproline decreased following ACTH infusion (P<0.001 and P=0.003, respectively). Similarly, the bone formation marker, bone-specific alkaline phosphatase, decreased continuously until 72 h after the ACTH infusion (P<0.001). These results demonstrate that increased secretion of cortisol via a 12-h ACTH infusion disrupted homeostasis of inorganic phosphate and suppressed bone metabolism in ovariectomized cows without involving gonadal steroid hormones. PMID:22591952

  16. Comparison of pro-inflammatory cytokines and bone metabolism mediators around titanium and zirconia dental implant abutments following a minimum of six months of clinical function

    PubMed Central

    Barwacz, Christopher A.; Brogden, Kim A.; Stanford, Clark M.; Dawson, Deborah V.; Recker, Erica N.; Blanchette, Derek

    2014-01-01

    Objectives Dental implant abutments are fundamental prosthetic components within dentistry that require optimal biocompatibility. The primary aim of this cross-sectional study was to preliminarily assess differences in the pro-inflammatory cytokine and bone metabolism mediator protein expression in the peri-implant crevicular fluid adjacent to transmucosal abutments. Material and Methods Abutments were fabricated from either titanium or zirconia in patients previously receiving single-tooth implant therapy. All subjects sampled in this study had an identical implant system and implant-abutment connection. Participants (n=46) had an average time of clinical function for 22 months (6.2–72.8 months, ±SD 17.0 months) and received a clinical and radiographic exam of the implant site at the time of peri-implant crevicular fluid (PICF) sampling using a paper strip-based sampling technique. Cytokine, chemokine, and bone metabolism mediator quantities (picograms/30 s) were determined using a commercial 22-multiplexed fluorescent bead-based immunoassay instrument. A total of 19 pro-inflammatory cytokines and 7 bone metabolism mediators were evaluated. Results Multivariable analyses provided no evidence of a group (titanium or zirconia), gender, or age effect with regard to the expression of pro-inflammatory mediators evaluated. Significant (p=0.022) differences were observed for the bone-mediator leptin, with titanium abutments demonstrating significantly elevated levels in comparison to zirconia. Osteopontin demonstrated a significant (p=0.0044) correlation with age of the subjects. Conclusions No significant differences in pro-inflammatory cytokine or bone metabolism mediator profiles were observed biochemically, with the exception of leptin, for the abutment biomaterials of titanium or zirconia The molecular PICF findings support the observed clinical biocompatibility of both titanium and zirconia abutments. PMID:24417614

  17. Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the Mir Space Station

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. Bo...

  18. Metabolic dynamics analysis by massive data integration: application to tsunami-affected field soils in Japan.

    PubMed

    Ogura, Tatsuki; Date, Yasuhiro; Tsuboi, Yuuri; Kikuchi, Jun

    2015-08-21

    A new metabolic dynamics analysis approach has been developed in which massive data sets from time-series of (1)H and (13)C NMR spectra are integrated in combination with microbial variability to characterize the biomass degradation process using field soil microbial communities. On the basis of correlation analyses that revealed relationships between various metabolites and bacteria, we efficiently monitored the metabolic dynamics of saccharides, amino acids, and organic acids, by assessing time-course changes in the microbial and metabolic profiles during biomass degradation. Specific bacteria were found to support specific steps of metabolic pathways in the degradation process of biomass to short chain fatty acids. We evaluated samples from agricultural and abandoned fields contaminated by the tsunami that followed the Great East earthquake in Japan. Metabolic dynamics and activities in the biomass degradation process differed considerably between soil from agricultural and abandoned fields. In particular, production levels of short chain fatty acids, such as acetate and propionate, which were considered to be produced by soil bacteria such as Sedimentibacter sp. and Coprococcus sp., were higher in the soil from agricultural fields than from abandoned fields. Our approach could characterize soil activity based on the metabolic dynamics of microbial communities in the biomass degradation process and should therefore be useful in future investigations of the environmental effects of natural disasters on soils. PMID:25997449

  19. Effect of Nasal Calcitonin on the Health-Related Quality of Life in Postmenopause Women Affected With Low Bone Density

    PubMed Central

    Shohrati, Majid; Bayat, Noushin; Saburi, Amin; Abbasi, Zahra

    2015-01-01

    Background: Physical activity and mental health could be affected by osteoporosis and various therapeutic options such as calcitonin may influence Quality Of Life (QOL) of these patients with Low Bone Density (LBD). Objectives: This study aimed to evaluate the effect of nasal calcitonin on QOL in post menopause women with LBD. Patients and Methods: This clinical trial study was performed on one hundred and fifteen menopause women with LBD less than 1 SD in Bone Mineral Densitometry (BMD) referred to Baqiyatallah Hospital in Tehran, Iran, during 2009 - 2010. They were assigned to receive 200 IU calcitonin nasal spray along with calcium (1000 mg) and vitamin D (400 IU) for 6 months. Quality of life was assessed by Short-Form 36 (SF-36) questionnaire (Persian-validated version). Results: The mean age (± SD) of the participants was 58.75 ± 8.15 years. Intranasal spray of calcitonin increased QOL scores significantly (88.05 ± 15.63 vs. 92.15 ± 13.22, P value = 0.000). Bone mineral density of spine was increased from 0.834 ± 0.11 to 0.12 ± 0.852 and this difference in BMD of lumbar spine was statistically significant (P value: 0.003) but not significant in femur’s BMD (P value = 0.061). In comparison with BMD indexes, The QOL scores especially Mental Health domain changes had only a significant correlation with the changes of total T score in BMD (P = 0.031, Coef