Osteoporosis

Chapter

Abstract

Osteoporosis in which bone mineral density (BMD) is reduced leads to an increased risk of fracture. In osteoporosis not only the BMD is reduced but even the bone microarchitecture is disrupted, and the amount and variety of proteins in bone is altered. WHO (world health organization) defined osteoporosis in women as a bone mineral density 2.5 standard deviations below peak bone mass (20-year-old healthy female average) as measured by DXA; the term “established osteoporosis” includes the presence of a fragility fracture [1].

Keywords

Nitric Oxide Bone Mineral Density Bone Loss Postmenopausal Bone Loss Isosorbide Mononitrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    WHO (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 843:1–129Google Scholar
  2. 2.
    Feskanich D, Willett WC, Stampfer MJ, Colditz GA (1996) Protein consumption and bone fractures in women. Am J Epidemiol 143:472–479PubMedCrossRefGoogle Scholar
  3. 3.
    Munger RG, Cerhan JR, Chiu BC (1999) Prospective study of dietary protein intake and risk of hip fracture in postmenopausal women. Am J Clin Nutr 69:147–152PubMedGoogle Scholar
  4. 4.
    Rizzoli R, Ammann P, Chevalley T, Bonjour JP (2001) Protein intake and bone disorders in the elderly. Joint Bone Spine 68:383–392PubMedCrossRefGoogle Scholar
  5. 5.
    Schürch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP (1998) Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 128:801–809PubMedGoogle Scholar
  6. 6.
    Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E (2002) Protein consumption and bone mineral density in the elderly: the Rancho Bernardo Study. Am J Epidemiol 155:636–644PubMedCrossRefGoogle Scholar
  7. 7.
    Weikert C, Walter D, Hoffmann K, Kroke A, Bergmann MM, Boeing H (2005) The relation between dietary protein, calcium and bone health in women: results from the EPIC-Potsdam cohort. Ann Nutr Metab 49:312–318PubMedCrossRefGoogle Scholar
  8. 8.
    Sellmeyer DE, Stone KL, Sebastian A, Cummings SR (2001) A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group. Am J Clin Nutr 73:118–122PubMedGoogle Scholar
  9. 9.
    Mardon J, Habauzit V, Trzeciakiewicz A, Davicco MJ, Lebecque P, Mercier S, Tressol JC, Horcajada MN, Demigné C, Coxam V (2008) Influence of high and low protein intakes on age-related bone loss in rats submitted to adequate or restricted energy conditions. Calcif Tissue Int 82:373–382PubMedCrossRefGoogle Scholar
  10. 10.
    Carpenter TO, Mackowiak SJ, Troiano N, Gundberg CM (1992) Osteocalcin and its message: relationship to bone histology in magnesium-deprived rats. Am J Physiol 263(1 Pt 1):E107–E114PubMedGoogle Scholar
  11. 11.
    Seelig MS (1993) Interrelationship of magnesium and estrogen in cardiovascular and bone disorders, eclampsia, migraine and premenstrual syndrome. J Am Coll Nutr 12:442–458PubMedGoogle Scholar
  12. 12.
    Rude RK, Gruber HE, Norton HJ, Wei LY, Frausto A, Kilburn J (2005) Dietary magnesium reduction to 25% of nutrient requirement disrupts bone and mineral metabolism in the rat. Bone 37:211–219PubMedCrossRefGoogle Scholar
  13. 13.
    Rude RK, Gruber HE, Norton HJ, Wei LY, Frausto A, Mills BG (2004) Bone loss induced by dietary magnesium reduction to 10% of the nutrient requirement in rats is associated with increased release of substance P and tumor necrosis factor-alpha. J Nutr 134:79–85PubMedGoogle Scholar
  14. 14.
    Rude RK, Gruber HE, Wei LY, Frausto A (2005) Immunolocalization of RANKL is increased and OPG decreased during dietary magnesium deficiency in the rat. Nutr Metab (Lond) 2:24CrossRefGoogle Scholar
  15. 15.
    Rude RK, Wei L, Norton HJ, Lu SS, Dempster DW, Gruber HE (2009) TNFalpha receptor knockout in mice reduces adverse effects of magnesium deficiency on bone. Growth Factors 27:370–376PubMedCrossRefGoogle Scholar
  16. 16.
    Ito A, Bebo BF Jr, Matejuk A, Zamora A, Silverman M, Fyfe-Johnson A, Offner H (2001) Estrogen treatment down-regulates TNF-alpha production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice. J Immunol 167:542–552PubMedGoogle Scholar
  17. 17.
    Salem ML (2004) Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production. Curr Drug Targets Inflamm Allergy 3:97–104PubMedCrossRefGoogle Scholar
  18. 18.
    Giraud SN, Caron CM, Pham-Dinh D, Kitabgi P, Nicot AB (2010) Estradiol inhibits ongoing autoimmune neuroinflammation and NFkappaB-dependent CCL2 expression in reactive astrocytes. Proc Natl Acad Sci U S A 107:8416–8421PubMedCrossRefGoogle Scholar
  19. 19.
    Houdeau E, Moriez R, Leveque M, Salvador-Cartier C, Waget A, Leng L, Bueno L, Bucala R, Fioramonti J (2007) Sex steroid regulation of macrophage migration inhibitory factor in normal and inflamed colon in the female rat. Gastroenterology 132:982–993PubMedCrossRefGoogle Scholar
  20. 20.
    Kitzmiller JL, Rocklin RE (1980) Lack of suppression of lymphocyte MIF production by estradiol, progesterone and human chorionic gonadotropin. J Reprod Immunol 1:297–306PubMedCrossRefGoogle Scholar
  21. 21.
    Abrahamsen B, Bonnevie-Nielsen V, Ebbesen EN, Gram J, Beck-Nielsen H (2000) Cytokines and bone loss in a 5-year longitudinal study – hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: the Danish osteoporosis prevention study. J Bone Miner Res 15:1545–1554PubMedCrossRefGoogle Scholar
  22. 22.
    Pfeilschifter J, Köditz R, Pfohl M, Schatz H (2002) Changes in proinflammatory cytokine activity after menopause. Endocr Rev 23:90–119PubMedCrossRefGoogle Scholar
  23. 23.
    Clowes JA, Riggs BL, Khosla S (2005) The role of the immune system in the pathophysiology of osteoporosis. Immunol Rev 208:207–227PubMedCrossRefGoogle Scholar
  24. 24.
    Ginaldi L, Di Benedetto MC, De Martinis M (2005) Osteoporosis, inflammation and ageing. Immun Ageing 2:14PubMedCrossRefGoogle Scholar
  25. 25.
    Ozmen B, Kirmaz C, Aydin K, Kafesciler SO, Guclu F, Hekimsoy Z (2007) Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNF-alpha, TGF-beta1 and bone turnover markers in the treatment of postmenopausal osteoporosis. Eur Cytokine Netw 18:148–153PubMedGoogle Scholar
  26. 26.
    Pino AM, Ríos S, Astudillo P, Fernández M, Figueroa P, Seitz G, Rodríguez JP (2010) Concentration of adipogenic and proinflammatory cytokines in the bone marrow supernatant fluid of osteoporotic women. J Bone Miner Res 25:492–498PubMedCrossRefGoogle Scholar
  27. 27.
    Takeda S, Karsenty G (2001) Central control of bone formation. J Bone Miner Metab 19:195–198PubMedCrossRefGoogle Scholar
  28. 28.
    Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207PubMedCrossRefGoogle Scholar
  29. 29.
    Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317PubMedCrossRefGoogle Scholar
  30. 30.
    Das UN (2001) Is obesity an inflammatory condition? Nutrition 17:953–966PubMedCrossRefGoogle Scholar
  31. 31.
    Lord GM, Matarese G, Howard JK, Bloom SR, Lechler RI (2002) Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines. J Leukoc Biol 72:330–338PubMedGoogle Scholar
  32. 32.
    Otero M, Lago R, Gómez R, Lago F, Gómez-Reino JJ, Gualillo O (2006) Leptin: a metabolic hormone that functions like a proinflammatory adipokine. Drug News Perspect 19:21–26PubMedCrossRefGoogle Scholar
  33. 33.
    Lappas M, Permezel M, Rice GE (2005) Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factor-kappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase 1/2. Endocrinology 146:3334–3342PubMedCrossRefGoogle Scholar
  34. 34.
    Aleffi S, Petrai I, Bertolani C, Parola M, Colombatto S, Novo E, Vizzutti F, Anania FA, Milani S, Rombouts K, Laffi G, Pinzani M, Marra F (2005) Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology 42:1339–1348PubMedCrossRefGoogle Scholar
  35. 35.
    Flierl MA, Rittirsch D, Huber-Lang M, Sarma JV, Ward PA (2008) Catecholamines – crafty weapons in the inflammatory arsenal of immune/inflammatory cells or opening pandora’s box? Mol Med 14:195–204PubMedGoogle Scholar
  36. 36.
    Flierl MA, Rittirsch D, Nadeau BA, Sarma JV, Day DE, Lentschz AB, Huber-Lang MS, Ward PA (2009) Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response. PLoS One 4:e4414CrossRefGoogle Scholar
  37. 37.
    Flierl MA, Rittirsch D, Nadeau BA, Chen AJ, Sarma JV, Zetoune FS, McGuire SR, List RP, Day DE, Hoesel LM, Gao H, Rooijen NV, Huber-Lang MS, Neubig RR, Ward PA (2007) Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature 449:721–726PubMedCrossRefGoogle Scholar
  38. 38.
    Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ (2003) The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 9:125–134PubMedGoogle Scholar
  39. 39.
    Matthay MA, Ware LB (2004) Can nicotine treat sepsis? Nat Med 10:1161–1162PubMedCrossRefGoogle Scholar
  40. 40.
    Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li HJ, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor a7 subunit is an essential regulator of inflammation. Nature 421:384–388PubMedCrossRefGoogle Scholar
  41. 41.
    Das UN (2004) Anti-inflammatory nature of exercise. Nutrition 20:323–326PubMedCrossRefGoogle Scholar
  42. 42.
    Das UN (2006) Exercise and inflammation. Eur Heart J 27:1385–1386PubMedCrossRefGoogle Scholar
  43. 43.
    Lemos TL, Reis F, Baptista S, Pinto R, Sepodes B, Vala H, Rocha-Pereira P, Correia de Silva G, Teixeira N, Silva SA, Carvalho L, Teixeira F, Das UN (2009) Exercise training decreases proinflammatory profile in Zucker diabetic (type 2) fatty rats. Nutrition 25:330–339CrossRefGoogle Scholar
  44. 44.
    Seals DR, Chase PB (1989) Influence of physical training on heart rate variability and baroreflex circulatory control. J Appl Physiol 66:1886–1895PubMedCrossRefGoogle Scholar
  45. 45.
    O’Leary DS, Seamans DP (1993) Effect of exercise on autonomic mechanisms of baroreflex control of heart rate. J Appl Physiol 75:2251–2257PubMedGoogle Scholar
  46. 46.
    Charlton GA, Crawford MH (1997) Physiologic consequences of training. Cardiol Clin 15:345–354PubMedCrossRefGoogle Scholar
  47. 47.
    Levy WC, Cerqueira MD, Harp GD, Johannessen KA, Abrass IB, Schwartz RS, Stratton JR (1998) Effect of endurance exercise training on heart rate variability at rest in healthy young and older men. Am J Cardiol 82:1236–1241PubMedCrossRefGoogle Scholar
  48. 48.
    Singh P, Hawkley LC, McDade TW, Cacioppo JT, Masi CM (2009) Autonomic tone and C-reactive protein: a prospective population-based study. Clin Auton Res 19:367–374PubMedCrossRefGoogle Scholar
  49. 49.
    Meyer O (2001) Atherosclerosis and connective tissue diseases. Joint Bone Spine 68:564–575PubMedCrossRefGoogle Scholar
  50. 50.
    Bijl M (2003) Endothelial activation, endothelial dysfunction and premature atherosclerosis in systemic autoimmune diseases. Neth J Med 61:273–277PubMedGoogle Scholar
  51. 51.
    Tyrrell PN, Beyene J, Feldman BM, McCrindle BW, Silverman ED, Bradley TJ (2010) Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysis. Arterioscler Thromb Vasc Biol 30:1014–1026PubMedCrossRefGoogle Scholar
  52. 52.
    MacIntyre I, Zaidi M, Alam AS, Datta HK, Moonga BS, Lidbury PS, Hecker M, Vane JR (1991) Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP. Proc Natl Acad Sci U S A 88:2936–2940PubMedCrossRefGoogle Scholar
  53. 53.
    Kasten TP, Collin-Osdoby P, Patel N, Osdoby P, Krukowski M, Misko TP, Settle SL, Currie MG, Nickols GA (1994) Potentiation of osteoclast bone-resorption activity by inhibition of nitric oxide synthase. Proc Natl Acad Sci U S A 91:3569–3573PubMedCrossRefGoogle Scholar
  54. 54.
    Evans DM, Ralston SH (1996) Nitric oxide and bone. J Bone Miner Res 11:300–305PubMedCrossRefGoogle Scholar
  55. 55.
    Kasten TP, Collin-Osdoby P, Patel N, Osdoby P, Krukowski M, Misko TP, Settle SL, Currie MG, Nickols GA (1994) Potentiation of osteoclast bone-resorption activity by inhibition of nitric oxide synthase. Proc Natl Acad Sci U S A 91:3569–3573PubMedCrossRefGoogle Scholar
  56. 56.
    Wimalawansa SJ, De Marco G, Gangula P, Yallampalli C (1996) Nitric oxide donor alleviates ovariectomy-induced bone loss. Bone 18:301–304PubMedCrossRefGoogle Scholar
  57. 57.
    Wimalawansa SJ, Chapa MT, Yallampalli C, Zhang R, Simmons DJ (1997) Prevention of corticosteroid-induced bone loss with nitric oxide donor nitroglycerin in male rats. Bone 21:275–280PubMedCrossRefGoogle Scholar
  58. 58.
    Jamal SA, Browner WS, Bauer DC, Cummings SR (1998) Intermittent use of nitrates increases bone mineral density: the study of osteoporotic fractures. J Bone Miner Res 13:1755–1759PubMedCrossRefGoogle Scholar
  59. 59.
    Pfeilschifter J, Köditz R, Pfohl M, Schatz H (2002) Changes in proinflammatory cytokine activity after menopause. Endocr Rev 23:90–119PubMedCrossRefGoogle Scholar
  60. 60.
    Hao YJ, Tang Y, Chen FB, Pei FX (2005) Different doses of nitric oxide donor prevent osteoporosis in ovariectomized rats. Clin Orthop Relat Res 435:226–231PubMedCrossRefGoogle Scholar
  61. 61.
    Jamal SA, Cummings SR, Hawker GA (2004) Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: a randomized trial. J Bone Miner Res 19:1512–1517PubMedCrossRefGoogle Scholar
  62. 62.
    Rejnmark L, Vestergaard P, Mosekilde L (2006) Decreased fracture risk in users of organic nitrates: a nationwide case-control study. J Bone Miner Res 21:1811–1817PubMedCrossRefGoogle Scholar
  63. 63.
    Ozgocmen S, Kaya H, Fadillioglu E, Aydogan R, Yilmaz Z (2007) Role of antioxidant systems, lipid peroxidation, and nitric oxide in postmenopausal osteoporosis. Mol Cell Biochem 295:45–52PubMedCrossRefGoogle Scholar
  64. 64.
    Taylor BC, Schreiner PJ, Zmuda JM, Li J, Moffett SP, Beck TJ, Cummings SR, Lee JM, Walker K, Ensrud KE; for the SOF Research Group (2006) Association of endothelial nitric oxide synthase genotypes with bone mineral density, bone loss, hip structure, and risk of fracture in older women: the SOF study. Bone 39:174–180PubMedCrossRefGoogle Scholar
  65. 65.
    Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167–1174PubMedGoogle Scholar
  66. 66.
    Hawley SA, Gadalla AE, Olsen GS, Hardie DG (2002) The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 51:2420–2425PubMedCrossRefGoogle Scholar
  67. 67.
    Kanazawa I, Yamaguchi T, Yano S, Yamauchi M, Sugimoto T (2008) Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression. Biochem Biophys Res Commun 375:414–419PubMedCrossRefGoogle Scholar
  68. 68.
    Xue B, Kahn BB (2006) AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J Physiol 574:73–83PubMedCrossRefGoogle Scholar
  69. 69.
    Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, Wang J, Rajala MW, Pocai A, Scherer PE, Steppan CM, Ahima SA, Obici S, Rossetti L, Lazar MA (2004) Regulation of fasted blood glucose by resistin. Science 303:1195–1198PubMedCrossRefGoogle Scholar
  70. 70.
    Yamauchi T, Kamoni J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimurai S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295PubMedCrossRefGoogle Scholar
  71. 71.
    Chen ZP, Stephens TJ, Murthy S, Canny BJ, Hargreaves M, Witters LA, Kemp BE, McConell GK (2003) Effect of exercise intensity on skeletal muscle AMPK signaling in humans. Diabetes 52:2205–2212PubMedCrossRefGoogle Scholar
  72. 72.
    Ho-Jin K, Josef B, Goodyear LJ (2008) LKB1 and AMPK and the regulation of skeletal muscle metabolism. Curr Opin Clin Nutr Metab Care 11:227–232CrossRefGoogle Scholar
  73. 73.
    Shaw RJ, Lamia KA, Vasquez D, Koo S-H, Bardeesy N, DePinho RA, Montminy M, Cantley LC (2005) The Kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310:1642–1646PubMedCrossRefGoogle Scholar
  74. 74.
    Huang X, Wullschleger S, Shpiro N, McGuire VA, Sakamoto K, Woods YL, McBurnie W, Fleming S, Alessi DR (2008) Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J 412:211–221PubMedCrossRefGoogle Scholar
  75. 75.
    Zakikhani M, Dowling RJ, Sonenberg N, Pollak MN (2008) The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase. Cancer Prev Res (Phila Pa) 1:369–375CrossRefGoogle Scholar
  76. 76.
    Kisfalvi K, Eibl G, Sinnett-Smith J, Rozengurt E (2009) Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. Cancer Res 69:6539–6545PubMedCrossRefGoogle Scholar
  77. 77.
    Fujita Y, Hosokawa M, Fujimoto S, Mukai E, Abudukadier A, Obara A, Ogura M, Nakamura Y, Toyoda K, Nagashima K, Seino Y, Inagaki N (2010) Metformin suppresses hepatic gluconeogenesis and lowers fasting blood glucose levels through reactive nitrogen species in mice. Diabetologia 53:1472–1481PubMedCrossRefGoogle Scholar
  78. 78.
    Sheng JZ, Arshad F, Braun JE, Braun AP (2008) Estrogen and the Ca2+-mobilizing agonist ATP evoke acute NO synthesis via distinct pathways in an individual human vascular endothelium-derived cell. Am J Physiol Cell Physiol 294:C1531–C1541PubMedCrossRefGoogle Scholar
  79. 79.
    Hamilton CA, Groves S, Carswell HV, Brosnan MJ, Graham D, Dominiczak AF (2006) Estrogen treatment enhances nitric oxide bioavailability in normotensive but not hypertensive rats. Am J Hypertens 19:859–866PubMedCrossRefGoogle Scholar
  80. 80.
    Das UN (2002) Nitric oxide as the mediator of the antiosteoporotic actions of estrogen, statins, and essential fatty acids. Exp Biol Med (Maywood) 227:88–93Google Scholar
  81. 81.
    Das UN (2002) Estrogen, statins, and polyunsaturated fatty acids: similarities in their actions and benefits-is there a common link? Nutrition 18:178–188PubMedCrossRefGoogle Scholar
  82. 82.
    Bhattacharya A, Rahman M, Banu J, Lawrence RA, McGuff HS, Garrett IR, Fischbach M, Fernandes G (2005) Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Fas(lpr) mice by N-3 fatty acids. J Am Coll Nutr 24:200–209PubMedGoogle Scholar
  83. 83.
    Högström M, Nordström P, Nordström A (2007) n-3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO2 study. Am J Clin Nutr 85:803–807PubMedGoogle Scholar
  84. 84.
    Serhan CN (2004) Clues for new therapeutics in osteoporosis and periodontal disease: new roles for lipoxygenases? Expert Opin Ther Targets 8:643–652PubMedCrossRefGoogle Scholar
  85. 85.
    Kühn H, O’Donnell VB (2006) Inflammation and immune regulation by 12/15-lipoxygenases. Prog Lipid Res 45:334–356PubMedCrossRefGoogle Scholar
  86. 86.
    Leitzbach D, Weckler N, Madajka M, Malinski T, Wiemer G, Linz W (2005) Restoration of endothelial function via enhanced nitric oxide synthesis after long-term treatment of raloxifene in adult hypertensive rats. Arzneimittelforschung 55:86–92PubMedGoogle Scholar
  87. 87.
    Xavier DO, Amaral LS, Gomes MA, Rocha MA, Campos PR, Cota BD, Tafuri LS, Paiva AM, Silva JH, Andrade SP, Belo AV (2010) Metformin inhibits inflammatory angiogenesis in a murine sponge model. Biomed Pharmacother 64:220–225PubMedCrossRefGoogle Scholar
  88. 88.
    Ersoy C, Kiyici S, Budak F, Oral B, Guclu M, Duran C, Selimoglu H, Erturk E, Tuncel E, Imamoglu S (2008) The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients. Diabetes Res Clin Pract 81:56–60PubMedCrossRefGoogle Scholar
  89. 89.
    Takemura Y, Osuga Y, Yoshino O, Hasegawa A, Hirata T, Hirota Y, Nose E, Morimoto C, Harada M, Koga K, Tajima T, Yano T, Taketani Y (2007) Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. J Clin Endocrinol Metab 92:3213–3218PubMedCrossRefGoogle Scholar
  90. 90.
    Hattori Y, Suzuki K, Hattori S, Kasai K (2006) Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension 47:1183–1188PubMedCrossRefGoogle Scholar
  91. 91.
    Vila-Bedmar R, Lorenzo M, Fernández-Veledo S (2010) Adenosine 5′-monophosphate-activated protein kinase-mammalian target of rapamycin cross talk regulates brown adipocyte differentiation. Endocrinology 151:980–992PubMedCrossRefGoogle Scholar

Copyright information

© Springer Netherlands 2011

Authors and Affiliations

  1. 1.UND Life ScienceShaker HeightsUSA
  2. 2.School of BiotechnologyJawaharlal Nehru Technological UniversityKakinadaIndia

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