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Glucocorticoids, Inflammation, and Bone

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Bone-Metabolic Functions and Modulators

Part of the book series: Topics in Bone Biology ((TBB,volume 7))

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Abstract

Glucocorticoids were first used by Philip Hench in collaboration with Edward Kendall to treat inflammation in the late 1940s. For their successful use of cortisone to treat RA, they were awarded a Nobel Prize in 1950.

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References

  1. Abreu MT, Geller JL, Vasiliauskas EA, Kam LY, Vora P, Martyak LA, Yang H, Hu B, Lin YC, Keenan G, Price J, Landers CJ, Adams JS, Targan SR. Treatment with infliximab is associated with increased markers of bone formation in patients with Crohn’s disease. J Clin Gastroenterol. 2006;40(1):55–63.

    Article  PubMed  CAS  Google Scholar 

  2. Abu-Amer Y, Ross FP, Edwards J, Teitelbaum SL. Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor. J Clin Invest. 1997;100(6):1557–65.

    Article  PubMed  CAS  Google Scholar 

  3. Abu-Amer Y, Erdmann J, Alexopoulou L, Kollias G, Ross FP, Teitelbaum SL. Tumor necrosis factor receptors types 1 and 2 differentially regulate osteoclastogenesis. J Biol Chem. 2000;275(35):27307–10.

    PubMed  CAS  Google Scholar 

  4. Adachi JD, Saag KG, Delmas PD, Liberman UA, Emkey RD, Seeman E, Lane NE, Kaufman JM, Poubelle PE, Hawkins F, Correa-Rotter R, Menkes CJ, Rodriguez-Portales JA, Schnitzer TJ, Block JA, Wing J, McIlwain HH, Westhovens R, Brown J, Melo-Gomes JA, Gruber BL, Yanover MJ, Leite MO, Siminoski KG, Nevitt MC, Sharp JT, Malice MP, Dumortier T, Czachur M, Carofano W, Daifotis A. Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheum. 2001;44(1):202–11.

    Article  PubMed  CAS  Google Scholar 

  5. Adamopoulos IE, Bowman EP. Immune regulation of bone loss by Th17 cells. Arthritis Res Ther. 2008;10(5):225.

    Article  PubMed  CAS  Google Scholar 

  6. Almawi WY, Beyhum HN, Rahme AA, Rieder MJ. Regulation of cytokine and cytokine receptor expression by glucocorticoids. J Leukoc Biol. 1996;60(5):563–72.

    PubMed  CAS  Google Scholar 

  7. Almawi WY, Irani-Hakime N. The antiproliferative effect of glucocorticoids: is it related to induction of TGF-beta? Nephrol Dial Transplant. 1998;13(10):2450–2.

    Article  PubMed  CAS  Google Scholar 

  8. Arron JR, Choi Y. Bone versus immune system. Nature. 2000;408(6812):535–6.

    Article  PubMed  CAS  Google Scholar 

  9. Asadullah K, Schacke H, Cato AC. Dichotomy of glucocorticoid action in the immune system. Trends Immunol. 2002;23(3):120–2.

    Article  PubMed  CAS  Google Scholar 

  10. Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science. 1995;270(5234):286–90.

    Article  PubMed  CAS  Google Scholar 

  11. Aupperle K, Bennett B, Han Z, Boyle D, Manning A, Firestein G. NF-kappa B regulation by I kappa B kinase-2 in rheumatoid arthritis synoviocytes. J Immunol. 2001;166(4):2705–11.

    PubMed  CAS  Google Scholar 

  12. Bansback NJ, Regier DA, Ara R, Brennan A, Shojania K, Esdaile JM, Anis AH, Marra CA. An overview of economic evaluations for drugs used in rheumatoid arthritis: focus on tumour necrosis factor-alpha antagonists. Drugs. 2005;65(4):473–96.

    Article  PubMed  Google Scholar 

  13. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond). 1998;94(6):557–72.

    CAS  Google Scholar 

  14. Baylink DJ, Wergedal JE. Bone formation by osteocytes. Am J Physiol. 1971;221(3):669–78.

    PubMed  CAS  Google Scholar 

  15. Beavan S, Horner A, Bord S, Ireland D, Compston J. Colocalization of glucocorticoid and mineralocorticoid receptors in human bone. J Bone Miner Res. 2001;16(8):1496–504.

    Article  PubMed  CAS  Google Scholar 

  16. Berrebi D, Bruscoli S, Cohen N, Foussat A, Migliorati G, Bouchet-Delbos L, Maillot MC, Portier A, Couderc J, Galanaud P, Peuchmaur M, Riccardi C, Emilie D. Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10. Blood. 2003;101(2):729–38.

    Article  PubMed  CAS  Google Scholar 

  17. Bertini R, Bianchi M, Ghezzi P. Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor. J Exp Med. 1988;167(5):1708–12.

    Article  PubMed  CAS  Google Scholar 

  18. Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med. 1993;119(12):1198–208.

    PubMed  CAS  Google Scholar 

  19. Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol. 2004;6(2):97–105.

    Article  PubMed  CAS  Google Scholar 

  20. Brandstrom H, Bjorkman T, Ljunggren O. Regulation of osteoprotegerin secretion from primary cultures of human bone marrow stromal cells. Biochem Biophys Res Commun. 2001;280(3):831–5.

    Article  PubMed  CAS  Google Scholar 

  21. Buttgereit F, da Silva JA, Boers M, Burmester GR, Cutolo M, Jacobs J, Kirwan J, Kohler L, Van Riel P, Vischer T, Bijlsma JW. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis. 2002;61(8):718–22.

    Article  PubMed  CAS  Google Scholar 

  22. Buxton EC, Yao W, Lane NE. Changes in serum receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1–34). J Clin Endocrinol Metab. 2004;89(7):3332–6.

    Article  PubMed  CAS  Google Scholar 

  23. Caetano-Lopes J, Canhao H, Fonseca JE. Osteoimmunology – the hidden immune regulation of bone. Autoimmun Rev. 2009;8(3):250–5.

    Article  PubMed  CAS  Google Scholar 

  24. Canalis E, Centrella M, Burch W, McCarthy TL. Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest. 1989;83(1):60–5.

    Article  PubMed  CAS  Google Scholar 

  25. Canalis E, Bilezikian JP, Angeli A, Giustina A. Perspectives on glucocorticoid-induced osteoporosis. Bone. 2004;34(4):593–8.

    Article  PubMed  CAS  Google Scholar 

  26. Canalis E. Mechanisms of glucocorticoid action in bone. Curr Osteoporos Rep. 2005;3(3):98–102.

    Article  PubMed  Google Scholar 

  27. Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007;18(10):1319–28.

    Article  PubMed  CAS  Google Scholar 

  28. Cantley MD, Smith MD, Haynes DR. Pathogenic bone loss in rheumatoid arthritis: mechanisms and therapeutic approaches. Int J Clin Rheumatol. 2009;4(5):561–82.

    Article  Google Scholar 

  29. Chapman KE, Coutinho A, Gray M, Gilmour JS, Savill JS, Seckl JR. Local amplification of ­glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 and its role in the inflammatory response. Ann N Y Acad Sci. 2006;1088:265–73.

    Article  PubMed  CAS  Google Scholar 

  30. Chapman KE, Gilmour JS, Coutinho AE, Savill JS, Seckl JR. 11beta-hydroxysteroid dehydrogenase type 1 – a role in inflammation? Mol Cell Endocrinol. 2006;248(1–2):3–8.

    Article  PubMed  CAS  Google Scholar 

  31. Chapman KE, Coutinho AE, Gray M, Gilmour JS, Savill JS, Seckl JR. The role and regulation of 11beta-hydroxysteroid dehydrogenase type 1 in the inflammatory response. Mol Cell Endocrinol. 2009;301(1–2):123–31.

    Article  PubMed  CAS  Google Scholar 

  32. Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med. 1995;332(20):1351–62.

    Article  PubMed  CAS  Google Scholar 

  33. Cohen A, Shane E. Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int. 2003;14(8):617–30.

    Article  PubMed  Google Scholar 

  34. Cohen S, Levy RM, Keller M, Boling E, Emkey RD, Greenwald M, Zizic TM, Wallach S, Sewell KL, Lukert BP, Axelrod DW, Chines AA. Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 1999;42(11):2309–18.

    Article  PubMed  CAS  Google Scholar 

  35. Cohen S, Hurd E, Cush J, Schiff M, Weinblatt ME, Moreland LW, Kremer J, Bear MB, Rich WJ, McCabe D. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002;46(3):614–24.

    Article  PubMed  CAS  Google Scholar 

  36. Collin-Osdoby P, Rothe L, Anderson F, Nelson M, Maloney W, Osdoby P. Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis. J Biol Chem. 2001;276(23):20659–62.

    Article  PubMed  CAS  Google Scholar 

  37. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D’Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15):1383–95.

    Article  PubMed  CAS  Google Scholar 

  38. Compston J. Management of glucocorticoid-induced osteoporosis. Nat Rev Rheumatol. 2010;6(2):82–8.

    Article  PubMed  CAS  Google Scholar 

  39. Compston JE. Emerging consensus on prevention and treatment of glucocorticoid-induced osteoporosis. Curr Rheumatol Rep. 2007;9(1):78–84.

    Article  PubMed  CAS  Google Scholar 

  40. Conn DL, Lim SS. New role for an old friend: prednisone is a disease-modifying agent in early rheumatoid arthritis. Curr Opin Rheumatol. 2003;15(3):193–6.

    Article  PubMed  CAS  Google Scholar 

  41. Cooper C, Coupland C, Mitchell M. Rheumatoid arthritis, corticosteroid therapy and hip fracture. Ann Rheum Dis. 1995;54(1):49–52.

    Article  PubMed  CAS  Google Scholar 

  42. Cooper MS, Rabbitt EH, Goddard PE, Bartlett WA, Hewison M, Stewart PM. Osteoblastic 11beta-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure. J Bone Miner Res. 2002;17(6):979–86.

    Article  PubMed  CAS  Google Scholar 

  43. Crotti TN, Smith MD, Weedon H, Ahern MJ, Findlay DM, Kraan M, Tak PP, Haynes DR. Receptor activator NF-kappaB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis. Ann Rheum Dis. 2002;61(12):1047–54.

    Article  PubMed  CAS  Google Scholar 

  44. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65.

    Article  PubMed  CAS  Google Scholar 

  45. De Bosscher K, Vanden Berghe W, Haegeman G. The interplay between the glucocorticoid receptor and nuclear factor-kappaB or activator protein-1: molecular mechanisms for gene repression. Endocr Rev. 2003;24(4):488–522.

    Article  PubMed  CAS  Google Scholar 

  46. de Haij S, Adcock IM, Bakker AC, Gobin SJ, Daha MR, van Kooten C. Steroid responsiveness of renal epithelial cells. Dissociation of transrepression and transactivation. J Biol Chem. 2003;278(7):5091–8.

    Article  PubMed  CAS  Google Scholar 

  47. de Nijs RN, Jacobs JW, Lems WF, Laan RF, Algra A, Huisman AM, Buskens E, de Laet CE, Oostveen AC, Geusens PP, Bruyn GA, Dijkmans BA, Bijlsma JW. Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med. 2006;355(7):675–84.

    Article  PubMed  Google Scholar 

  48. Delany AM, Gabbitas BY, Canalis E. Cortisol downregulates osteoblast alpha 1 (I) procollagen mRNA by transcriptional and posttranscriptional mechanisms. J Cell Biochem. 1995;57(3):488–94.

    Article  PubMed  CAS  Google Scholar 

  49. Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C, van der Heide D, Landewe R, Lacey D, Richards WG, Schett G. Dickkopf-1 is a master regulator of joint remodeling. Nat Med. 2007;13(2):156–63.

    Article  PubMed  CAS  Google Scholar 

  50. Doga M, Mazziotti G, Bonadonna S, Patelli I, Bilezikian JP, Canalis E, Giustina A. Prevention and treatment of glucocorticoid-induced osteoporosis. J Endocrinol Invest. 2008;31(7 Suppl):53–8.

    PubMed  CAS  Google Scholar 

  51. Dovio A, Perazzolo L, Saba L, Termine A, Capobianco M, Bertolotto A, Angeli A. High-dose glucocorticoids increase serum levels of soluble IL-6 receptor alpha and its ratio to soluble gp130: an additional mechanism for early increased bone resorption. Eur J Endocrinol. 2006;154(5):745–51.

    Article  PubMed  CAS  Google Scholar 

  52. Ebeling PR. Approach to the patient with transplantation-related bone loss. J Clin Endocrinol Metab. 2009;94(5):1483–90.

    Article  PubMed  CAS  Google Scholar 

  53. Eijken M, Hewison M, Cooper MS, de Jong FH, Chiba H, Stewart PM, Uitterlinden AG, Pols HA, van Leeuwen JP. 11beta-hydroxysteroid dehydrogenase expression and glucocorticoid synthesis are directed by a molecular switch during osteoblast differentiation. Mol Endocrinol. 2005;19(3):621–31.

    Article  PubMed  CAS  Google Scholar 

  54. Elenkov IJ, Chrousos GP. Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Ann N Y Acad Sci. 2002;966:290–303.

    Article  PubMed  CAS  Google Scholar 

  55. Epinat JC, Gilmore TD. Diverse agents act at multiple levels to inhibit the Rel/NF-kappaB signal transduction pathway. Oncogene. 1999;18(49):6896–909.

    Article  PubMed  CAS  Google Scholar 

  56. Farrell RJ, Murphy A, Long A, Donnelly S, Cherikuri A, O’Toole D, Mahmud N, Keeling PW, Weir DG, Kelleher D. High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy. Gastroenterology. 2000;118(2):279–88.

    Article  PubMed  CAS  Google Scholar 

  57. Franzoso G, Carlson L, Xing L, Poljak L, Shores EW, Brown KD, Leonardi A, Tran T, Boyce BF, Siebenlist U. Requirement for NF-kappaB in osteoclast and B-cell development. Genes Dev. 1997;11(24):3482–96.

    Article  PubMed  CAS  Google Scholar 

  58. Freeman L, Hewison M, Hughes SV, Evans KN, Hardie D, Means TK, Chakraverty R. Expression of 11beta-hydroxysteroid dehydrogenase type 1 permits regulation of glucocorticoid bioavailability by human dendritic cells. Blood. 2005;106(6):2042–9.

    Article  PubMed  CAS  Google Scholar 

  59. Gabbitas B, Pash JM, Delany AM, Canalis E. Cortisol inhibits the synthesis of insulin-like growth factor-binding protein-5 in bone cell cultures by transcriptional mechanisms. J Biol Chem. 1996;271(15):9033–8.

    Article  PubMed  CAS  Google Scholar 

  60. Gallo KA, Johnson GL. Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat Rev Mol Cell Biol. 2002;3(9):663–72.

    Article  PubMed  CAS  Google Scholar 

  61. Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002;109(Suppl):S81–96.

    Article  PubMed  CAS  Google Scholar 

  62. Gilbert L, He X, Farmer P, Boden S, Kozlowski M, Rubin J, Nanes MS. Inhibition of osteoblast differentiation by tumor necrosis factor-alpha. Endocrinology. 2000;141(11):3956–64.

    Article  PubMed  CAS  Google Scholar 

  63. Gillespie MT. Impact of cytokines and T lymphocytes upon osteoclast differentiation and function. Arthritis Res Ther. 2007;9(2):103.

    Article  PubMed  CAS  Google Scholar 

  64. Gilmour JS, Coutinho AE, Cailhier JF, Man TY, Clay M, Thomas G, Harris HJ, Mullins JJ, Seckl JR, Savill JS, Chapman KE. Local amplification of glucocorticoids by 11 beta-hydroxysteroid dehydrogenase type 1 promotes macrophage phagocytosis of apoptotic leukocytes. J Immunol. 2006;176(12):7605–11.

    PubMed  CAS  Google Scholar 

  65. Glass 2nd DA, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005;8(5):751–64.

    Article  PubMed  CAS  Google Scholar 

  66. Glass 2nd DA, Karsenty G. Canonical Wnt signaling in osteoblasts is required for osteoclast differentiation. Ann N Y Acad Sci. 2006;1068:117–30.

    Article  PubMed  CAS  Google Scholar 

  67. Goldring SR. Pathogenesis of bone erosions in ­rheumatoid arthritis. Curr Opin Rheumatol. 2002;14(4):406–10.

    Article  PubMed  Google Scholar 

  68. Guler-Yuksel M, Bijsterbosch J, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Hulsmans HM, de Beus WM, Han KH, Breedveld FC, Dijkmans BA, Allaart CF, Lems WF. Changes in bone mineral density in patients with recent onset, active rheumatoid arthritis. Ann Rheum Dis. 2008;67(6):823–8.

    Article  PubMed  CAS  Google Scholar 

  69. Hardy R, Rabbitt EH, Filer A, Emery P, Hewison M, Stewart PM, Gittoes NJ, Buckley CD, Raza K, Cooper MS. Local and systemic glucocorticoid metabolism in inflammatory arthritis. Ann Rheum Dis. 2008;67(9):1204–10.

    Article  PubMed  CAS  Google Scholar 

  70. Haslett C. Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am J Respir Crit Care Med. 1999;160(5 Pt 2):S5–11.

    PubMed  CAS  Google Scholar 

  71. Heasman SJ, Giles KM, Ward C, Rossi AG, Haslett C, Dransfield I. Glucocorticoid-mediated regulation of granulocyte apoptosis and macrophage phagocytosis of apoptotic cells: implications for the resolution of inflammation. J Endocrinol. 2003;178(1):29–36.

    Article  PubMed  CAS  Google Scholar 

  72. Hofbauer LC, Gori F, Riggs BL, Lacey DL, Dunstan CR, Spelsberg TC, Khosla S. Stimulation of ­osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human ­osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology. 1999;140(10):4382–9.

    Article  PubMed  CAS  Google Scholar 

  73. Hofbauer LC, Rauner M. Minireview: live and let die: molecular effects of glucocorticoids on bone cells. Mol Endocrinol. 2009;23(10):1525–31.

    Article  PubMed  CAS  Google Scholar 

  74. Holmes MC, Kotelevtsev Y, Mullins JJ, Seckl JR. Phenotypic analysis of mice bearing targeted deletions of 11beta-hydroxysteroid dehydrogenases 1 and 2 genes. Mol Cell Endocrinol. 2001;171(1–2):15–20.

    Article  PubMed  CAS  Google Scholar 

  75. Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT. Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun. 1999;265(1):144–50.

    Article  PubMed  CAS  Google Scholar 

  76. Horwood NJ, Elliott J, Martin TJ, Gillespie MT. IL-12 alone and in synergy with IL-18 inhibits osteoclast formation in vitro. J Immunol. 2001;166(8):4915–21.

    PubMed  CAS  Google Scholar 

  77. Hu X, Ho HH, Lou O, Hidaka C, Ivashkiv LB. Homeostatic role of interferons conferred by inhibition of IL-1-mediated inflammation and tissue destruction. J Immunol. 2005;175(1):131–8.

    PubMed  CAS  Google Scholar 

  78. Humphrey EL, Williams JH, Davie MW, Marshall MJ. Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells. Bone. 2006;38(5):652–61.

    Article  PubMed  CAS  Google Scholar 

  79. Iotsova V, Caamano J, Loy J, Yang Y, Lewin A, Bravo R. Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat Med. 1997;3(11):1285–9.

    Article  PubMed  CAS  Google Scholar 

  80. Irikura VM, Hirsch E, Hirsh D. Effects of interleukin-1 receptor antagonist overexpression on infection by Listeria monocytogenes. Infect Immun. 1999;67(4):1901–9.

    PubMed  CAS  Google Scholar 

  81. Jia D, O’Brien CA, Stewart SA, Manolagas SC, Weinstein RS. Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. Endocrinology. 2006;147(12):5592–9.

    Article  PubMed  CAS  Google Scholar 

  82. Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF. Recombinant human parathyroid hormone (1–34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res. 2003;18(11):1932–41.

    Article  PubMed  CAS  Google Scholar 

  83. Jimi E, Aoki K, Saito H, D’Acquisto F, May MJ, Nakamura I, Sudo T, Kojima T, Okamoto F, Fukushima H, Okabe K, Ohya K, Ghosh S. Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. Nat Med. 2004;10(6):617–24.

    Article  PubMed  CAS  Google Scholar 

  84. Karberg K, Zochling J, Sieper J, Felsenberg D, Braun J. Bone loss is detected more frequently in patients with ankylosing spondylitis with syndesmophytes. J Rheumatol. 2005;32(7):1290–8.

    PubMed  Google Scholar 

  85. Katz S. Osteoporosis in patients with inflammatory bowel disease: risk factors, prevention, and treatment. Rev Gastroenterol Disord. 2006;6(2):63–71.

    PubMed  Google Scholar 

  86. Kawakami A, Nakashima T, Sakai H, Hida A, Urayama S, Yamasaki S, Nakamura H, Ida H, Ichinose Y, Aoyagi T, Furuichi I, Nakashima M, Migita K, Kawabe Y, Eguchi K. Regulation of synovial cell apoptosis by proteasome inhibitor. Arthritis Rheum. 1999;42(11):2440–8.

    Article  PubMed  CAS  Google Scholar 

  87. Kim N, Odgren PR, Kim DK, Marks Jr SC, Choi Y. Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene. Proc Natl Acad Sci USA. 2000;97(20):10905–10.

    Article  PubMed  CAS  Google Scholar 

  88. Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Morinaga T, Higashio K, Martin TJ, Suda T. Tumor necrosis ­factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 2000;191(2):275–86.

    Article  PubMed  CAS  Google Scholar 

  89. Kogianni G, Mann V, Ebetino F, Nuttall M, Nijweide P, Simpson H, Noble B. Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis. Life Sci. 2004;75(24):2879–95.

    Article  PubMed  CAS  Google Scholar 

  90. Komuro H, Olee T, Kuhn K, Quach J, Brinson DC, Shikhman A, Valbracht J, Creighton-Achermann L, Lotz M. The osteoprotegerin/receptor activator of nuclear factor kappaB/receptor activator of nuclear factor kappaB ligand system in cartilage. Arthritis Rheum. 2001;44(12):2768–76.

    Article  PubMed  CAS  Google Scholar 

  91. Kondo T, Kitazawa R, Yamaguchi A, Kitazawa S. Dexamethasone promotes osteoclastogenesis by inhibiting osteoprotegerin through multiple levels. J Cell Biochem. 2008;103(1):335–45.

    Article  PubMed  CAS  Google Scholar 

  92. Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, Wong T, Campagnuolo G, Moran E, Bogoch ER, Van G, Nguyen LT, Ohashi PS, Lacey DL, Fish E, Boyle WJ, Penninger JM. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999;402(6759):304–9.

    Article  PubMed  CAS  Google Scholar 

  93. Kurokouchi K, Kambe F, Kikumori T, Sakai T, Sarkar D, Ishiguro N, Iwata H, Seo H. Effects of glucocorticoids on tumor necrosis factor alpha-dependent activation of nuclear factor kappaB and expression of the intercellular adhesion molecule 1 gene in osteoblast-like ROS17/2.8 cells. J Bone Miner Res. 2000;15(9):1707–15.

    Article  PubMed  CAS  Google Scholar 

  94. Laan RF, Buijs WC, Verbeek AL, Draad MP, Corstens FH, van de Putte LB, van Riel PL. Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis. 1993;52(1):21–6.

    Article  PubMed  CAS  Google Scholar 

  95. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165–76.

    Article  PubMed  CAS  Google Scholar 

  96. Lacey DL, Tan HL, Lu J, Kaufman S, Van G, Qiu W, Rattan A, Scully S, Fletcher F, Juan T, Kelley M, Burgess TL, Boyle WJ, Polverino AJ. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol. 2000;157(2):435–48.

    Article  PubMed  CAS  Google Scholar 

  97. Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL. TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest. 2000;106(12):1481–8.

    Article  PubMed  CAS  Google Scholar 

  98. Lane NE, Yao W, Balooch M, Nalla RK, Balooch G, Habelitz S, Kinney JH, Bonewald LF. Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. J Bone Miner Res. 2006;21(3):466–76.

    Article  PubMed  CAS  Google Scholar 

  99. Leung DY, de Castro M, Szefler SJ, Chrousos GP. Mechanisms of glucocorticoid-resistant asthma. Ann N Y Acad Sci. 1998;840:735–46.

    Article  PubMed  CAS  Google Scholar 

  100. Lewiecki EM. Denosumab update. Curr Opin Rheumatol. 2009;21(4):369–73.

    Article  PubMed  Google Scholar 

  101. Lianxu C, Hongti J, Changlong Y. NF-kappaBp65-specific siRNA inhibits expression of genes of COX-2, NOS-2 and MMP-9 in rat IL-1beta-induced and TNF-alpha-induced chondrocytes. Osteoarthritis Cartilage. 2006;14(4):367–76.

    Article  PubMed  CAS  Google Scholar 

  102. Liu Y, Cousin JM, Hughes J, Van Damme J, Seckl JR, Haslett C, Dransfield I, Savill J, Rossi AG. Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes. J Immunol. 1999;162(6):3639–46.

    PubMed  CAS  Google Scholar 

  103. Lubberts E, Oppers-Walgreen B, Pettit AR, Van Den Bersselaar L, Joosten LA, Goldring SR, Gravallese EM, Van Den Berg WB. Increase in expression of receptor activator of nuclear factor kappaB at sites of bone erosion correlates with progression of inflammation in evolving collagen-induced arthritis. Arthritis Rheum. 2002;46(11):3055–64.

    Article  PubMed  CAS  Google Scholar 

  104. Lubberts E, Koenders MI, van den Berg WB. The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthritis Res Ther. 2005;7(1):29–37.

    Article  PubMed  CAS  Google Scholar 

  105. Makarov SS. NF-kappaB as a therapeutic target in chronic inflammation: recent advances. Mol Med Today. 2000;6(11):441–8.

    Article  PubMed  CAS  Google Scholar 

  106. Manolagas SC, Weinstein RS. New developments in the pathogenesis and treatment of steroid-induced osteoporosis. J Bone Miner Res. 1999;14(7):1061–6.

    Article  PubMed  CAS  Google Scholar 

  107. Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006;177(10):7303–11.

    PubMed  CAS  Google Scholar 

  108. Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A. Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab. 2006;17(4):144–9.

    Article  PubMed  CAS  Google Scholar 

  109. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429–42.

    Article  PubMed  CAS  Google Scholar 

  110. McIntyre KW, Shuster DJ, Gillooly KM, Dambach DM, Pattoli MA, Lu P, Zhou XD, Qiu Y, Zusi FC, Burke JR. A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis Rheum. 2003;48(9):2652–9.

    Article  PubMed  CAS  Google Scholar 

  111. McManus MT, Sharp PA. Gene silencing in mammals by small interfering RNAs. Nat Rev Genet. 2002;3(10):737–47.

    Article  PubMed  CAS  Google Scholar 

  112. Migliaccio S, Brama M, Malavolta N. Management of glucocorticoids-induced osteoporosis: role of teriparatide. Ther Clin Risk Manag. 2009;5(2):305–10.

    Article  PubMed  CAS  Google Scholar 

  113. Miller PD. Denosumab: anti-RANKL antibody. Curr Osteoporos Rep. 2009;7(1):18–22.

    Article  PubMed  Google Scholar 

  114. Munck A, Naray-Fejes-Toth A. The ups and downs of glucocorticoid physiology. Permissive and suppressive effects revisited. Mol Cell Endocrinol. 1992;90(1):C1–4.

    Article  PubMed  CAS  Google Scholar 

  115. Naganathan V, Jones G, Nash P, Nicholson G, Eisman J, Sambrook PN. Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use. Arch Intern Med. 2000;160(19):2917–22.

    Article  PubMed  CAS  Google Scholar 

  116. Naito A, Azuma S, Tanaka S, Miyazaki T, Takaki S, Takatsu K, Nakao K, Nakamura K, Katsuki M, Yamamoto T, Inoue J. Severe osteopetrosis, defective interleukin-1 signaling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells. 1999;4(6):353–62.

    Article  PubMed  CAS  Google Scholar 

  117. O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS. Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology. 2004;145(4):1835–41.

    Article  PubMed  CAS  Google Scholar 

  118. Ohnaka K, Tanabe M, Kawate H, Nawata H, Takayanagi R. Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. Biochem Biophys Res Commun. 2005;329(1):177–81.

    Article  PubMed  CAS  Google Scholar 

  119. Pacifici R. T cells: critical bone regulators in health and disease. Bone. 2010;47(3):461–71.

    Article  PubMed  CAS  Google Scholar 

  120. Pasco JA, Kotowicz MA, Henry MJ, Nicholson GC, Spilsbury HJ, Box JD, Schneider HG. High-sensitivity C-reactive protein and fracture risk in elderly women. JAMA. 2006;296(11):1353–5.

    Article  PubMed  CAS  Google Scholar 

  121. Peel NF, Barrington NA, Blumsohn A, Colwell A, Hannon R, Eastell R. Bone mineral density and bone turnover in spinal osteoarthrosis. Ann Rheum Dis. 1995;54(11):867–71.

    Article  PubMed  CAS  Google Scholar 

  122. Pettit AR, Ji H, von Stechow D, Muller R, Goldring SR, Choi Y, Benoist C, Gravallese EM. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol. 2001;159(5):1689–99.

    Article  PubMed  CAS  Google Scholar 

  123. Poubelle PE, Chakravarti A, Fernandes MJ, Doiron K, Marceau AA. Differential expression of RANK, RANK-L, and osteoprotegerin by synovial fluid neutrophils from patients with rheumatoid arthritis and by healthy human blood neutrophils. Arthritis Res Ther. 2007;9(2):R25.

    Article  PubMed  CAS  Google Scholar 

  124. Purnell JQ, Brandon DD, Isabelle LM, Loriaux DL, Samuels MH. Association of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-free cortisol levels with body composition, leptin levels, and aging in adult men and women. J Clin Endocrinol Metab. 2004;89(1):281–7.

    Article  PubMed  CAS  Google Scholar 

  125. Quinn JM, Saleh H. Modulation of osteoclast function in bone by the immune system. Mol Cell Endocrinol. 2009;310(1–2):40–51.

    Article  PubMed  CAS  Google Scholar 

  126. Ramirez F, Fowell DJ, Puklavec M, Simmonds S, Mason D. Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro. J Immunol. 1996;156(7):2406–12.

    PubMed  CAS  Google Scholar 

  127. Redlich K, Ziegler S, Kiener HP, Spitzauer S, Stohlawetz P, Bernecker P, Kainberger F, Grampp S, Kudlacek S, Woloszczuk W, Smolen JS, Pietschmann P. Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus. Ann Rheum Dis. 2000;59(4):308–10.

    Article  PubMed  CAS  Google Scholar 

  128. Redlich K, Hayer S, Ricci R, David JP, Tohidast-Akrad M, Kollias G, Steiner G, Smolen JS, Wagner EF, Schett G. Osteoclasts are essential for TNF-alpha-mediated joint destruction. J Clin Invest. 2002;110(10):1419–27.

    PubMed  CAS  Google Scholar 

  129. Rehman Q, Lang TF, Arnaud CD, Modin GW, Lane NE. Daily treatment with parathyroid hormone is associated with an increase in vertebral cross-sectional area in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int. 2003;14(1):77–81.

    Article  PubMed  CAS  Google Scholar 

  130. Reid DM, Adami S, Devogelaer JP, Chines AA. Risedronate increases bone density and reduces ­vertebral fracture risk within one year in men on ­corticosteroid therapy. Calcif Tissue Int. 2001;69(4):242–7.

    Article  PubMed  CAS  Google Scholar 

  131. Reid DM, Devogelaer JP, Saag K, Roux C, Lau CS, Reginster JY, Papanastasiou P, Ferreira A, Hartl F, Fashola T, Mesenbrink P, Sambrook PN. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet. 2009;373(9671):1253–63.

    Article  PubMed  CAS  Google Scholar 

  132. Ren Y, Stuart L, Lindberg FP, Rosenkranz AR, Chen Y, Mayadas TN, Savill J. Nonphlogistic clearance of late apoptotic neutrophils by macrophages: efficient phagocytosis independent of beta 2 integrins. J Immunol. 2001;166(7):4743–50.

    PubMed  CAS  Google Scholar 

  133. Reynolds RM, Dennison EM, Walker BR, Syddall HE, Wood PJ, Andrew R, Phillips DI, Cooper C. Cortisol secretion and rate of bone loss in a population-based cohort of elderly men and women. Calcif Tissue Int. 2005;77(3):134–8.

    Article  PubMed  CAS  Google Scholar 

  134. Rivera J, Colbert RA. Healing the Syk through kinase inhibitors. N Engl J Med. 2010;63(14):1362–4.

    Article  Google Scholar 

  135. Roman-Blas JA, Jimenez SA. NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage. 2006;14(9):839–48.

    Article  PubMed  CAS  Google Scholar 

  136. Romas E, Sims NA, Hards DK, Lindsay M, Quinn JW, Ryan PF, Dunstan CR, Martin TJ, Gillespie MT. Osteoprotegerin reduces osteoclast numbers and prevents bone erosion in collagen-induced arthritis. Am J Pathol. 2002;161(4):1419–27.

    Article  PubMed  CAS  Google Scholar 

  137. Rubin J, Biskobing DM, Jadhav L, Fan D, Nanes MS, Perkins S, Fan X. Dexamethasone promotes expression of membrane-bound macrophage colony-stimulating factor in murine osteoblast-like cells. Endocrinology. 1998;139(3):1006–12.

    Article  PubMed  CAS  Google Scholar 

  138. Ruocco MG, Karin M. IKK{beta} as a target for treatment of inflammation induced bone loss. Ann Rheum Dis. 2005;64 Suppl 4:vi81–5.

    Google Scholar 

  139. Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, Thamsborg G, Liberman UA, Delmas PD, Malice MP, Czachur M, Daifotis AG. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-induced osteoporosis intervention study group. N Engl J Med. 1998;339(5):292–9.

    Article  PubMed  CAS  Google Scholar 

  140. Saag KG, Shane E, Boonen S, Marin F, Donley DW, Taylor KA, Dalsky GP, Marcus R. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357(20):2028–39.

    Article  PubMed  CAS  Google Scholar 

  141. Sandeep TC, Walker BR. Pathophysiology of ­modulation of local glucocorticoid levels by 11beta-hydroxysteroid dehydrogenases. Trends Endocrinol Metab. 2001;12(10):446–53.

    Article  PubMed  CAS  Google Scholar 

  142. Schacke H, Docke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002;96(1):23–43.

    Article  PubMed  CAS  Google Scholar 

  143. Schett G, Kiechl S, Weger S, Pederiva A, Mayr A, Petrangeli M, Oberhollenzer F, Lorenzini R, Redlich K, Axmann R, Zwerina J, Willeit J. High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med. 2006;166(22):2495–501.

    Article  PubMed  CAS  Google Scholar 

  144. Schett G, Teitelbaum SL. Osteoclasts and arthritis. J Bone Miner Res. 2009;24(7):1142–6.

    Article  Google Scholar 

  145. Schreiber W, Pollmacher T, Fassbender K, Gudewill S, Vedder H, Wiedemann K, Galanos C, Holsboer F. Endotoxin- and corticotropin-releasing hormone-induced release of ACTH and cortisol. A comparative study in men. Neuroendocrinology. 1993;58(1):123–8.

    Article  PubMed  CAS  Google Scholar 

  146. Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004;75(2):163–89.

    Article  PubMed  CAS  Google Scholar 

  147. Sher LB, Woitge HW, Adams DJ, Gronowicz GA, Krozowski Z, Harrison JR, Kream BE. Transgenic expression of 11beta-hydroxysteroid dehydrogenase type 2 in osteoblasts reveals an anabolic role for endogenous glucocorticoids in bone. Endocrinology. 2004;145(2):922–9.

    Article  PubMed  CAS  Google Scholar 

  148. Sher LB, Harrison JR, Adams DJ, Kream BE. Impaired cortical bone acquisition and osteoblast differentiation in mice with osteoblast-targeted disruption of glucocorticoid signaling. Calcif Tissue Int. 2006;79(2):118–25.

    Article  PubMed  CAS  Google Scholar 

  149. Shi XM, Blair HC, Yang X, McDonald JM, Cao X. Tandem repeat of C/EBP binding sites mediates PPARgamma2 gene transcription in glucocorticoid-induced adipocyte differentiation. J Cell Biochem. 2000;76(3):518–27.

    Article  PubMed  CAS  Google Scholar 

  150. Shigeyama Y, Pap T, Kunzler P, Simmen BR, Gay RE, Gay S. Expression of osteoclast differentiation factor in rheumatoid arthritis. Arthritis Rheum. 2000;43(11):2523–30.

    Article  PubMed  CAS  Google Scholar 

  151. Sims NA, Green JR, Glatt M, Schlict S, Martin TJ, Gillespie MT, Romas E. Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen-induced arthritis. Arthritis Rheum. 2004;50(7):2338–46.

    Article  PubMed  CAS  Google Scholar 

  152. Smith E, Frenkel B. Glucocorticoids inhibit the transcriptional activity of LEF/TCF in differentiating osteoblasts in a glycogen synthase kinase-3beta-dependent and -independent manner. J Biol Chem. 2005;280(3):2388–94.

    Article  PubMed  CAS  Google Scholar 

  153. Swanson C, Lorentzon M, Conaway HH, Lerner UH. Glucocorticoid regulation of osteoclast differentiation and expression of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand, osteoprotegerin, and receptor activator of NF-kappaB in mouse calvarial bones. Endocrinology. 2006;147(7):3613–22.

    Article  PubMed  CAS  Google Scholar 

  154. Tabardel Y, Duchateau J, Schmartz D, Marecaux G, Shahla M, Barvais L, Leclerc JL, Vincent JL. Corticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men. Surgery. 1996;119(1):76–80.

    Article  PubMed  CAS  Google Scholar 

  155. Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner EF, Mak TW, Kodama T, Taniguchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002;3(6):889–901.

    Article  PubMed  CAS  Google Scholar 

  156. Takayanagi H. Mechanistic insight into osteoclast differentiation in osteoimmunology. J Mol Med. 2005;83(3):170–9.

    Article  PubMed  CAS  Google Scholar 

  157. Takuma A, Kaneda T, Sato T, Ninomiya S, Kumegawa M, Hakeda Y. Dexamethasone enhances osteoclast formation synergistically with transforming growth factor-beta by stimulating the priming of osteoclast progenitors for differentiation into osteoclasts. J Biol Chem. 2003;278(45):44667–74.

    Article  PubMed  CAS  Google Scholar 

  158. Tauchmanova L, Colao A, Lombardi G, Rotoli B, Selleri C. Bone loss and its management in ­long-term survivors from allogeneic stem cell ­transplantation. J Clin Endocrinol Metab. 2007;92(12):4536–45.

    Article  PubMed  CAS  Google Scholar 

  159. Teitelbaum SL. Bone resorption by osteoclasts. Science. 2000;289(5484):1504–8.

    Article  PubMed  CAS  Google Scholar 

  160. Theoleyre S, Wittrant Y, Tat SK, Fortun Y, Redini F, Heymann D. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev. 2004;15(6):457–75.

    Article  PubMed  CAS  Google Scholar 

  161. Tomita T, Takeuchi E, Tomita N, Morishita R, Kaneko M, Yamamoto K, Nakase T, Seki H, Kato K, Kaneda Y, Ochi T. Suppressed severity of collagen-induced arthritis by in vivo transfection of nuclear factor kappaB decoy oligodeoxynucleotides as a gene therapy. Arthritis Rheum. 1999;42(12):2532–42.

    Article  PubMed  CAS  Google Scholar 

  162. Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM. 11beta-Hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev. 2004;25(5):831–66.

    Article  PubMed  CAS  Google Scholar 

  163. Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J Bone Miner Res. 2000;15(6):993–1000.

    Article  PubMed  Google Scholar 

  164. van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford). 2000;39(12):1383–9.

    Article  Google Scholar 

  165. van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54(10):3104–12.

    Article  PubMed  Google Scholar 

  166. van Staa TP. The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int. 2006;79(3):129–37.

    Article  PubMed  CAS  Google Scholar 

  167. Varga G, Ehrchen J, Tsianakas A, Tenbrock K, Rattenholl A, Seeliger S, Mack M, Roth J, Sunderkoetter C. Glucocorticoids induce an activated, anti-inflammatory monocyte subset in mice that resembles myeloid-derived suppressor cells. J Leukoc Biol. 2008;84(3):644–50.

    Article  PubMed  CAS  Google Scholar 

  168. Vidal NO, Brandstrom H, Jonsson KB, Ohlsson C. Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: downregulation by glucocorticoids. J Endocrinol. 1998;159(1):191–5.

    Article  PubMed  CAS  Google Scholar 

  169. Wang FS, Ko JY, Yeh DW, Ke HC, Wu HL. Modulation of dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss. Endocrinology. 2008;149(4):1793–801.

    Article  PubMed  CAS  Google Scholar 

  170. Webster JI, Carlstedt-Duke J. Involvement of multidrug resistance proteins (MDR) in the modulation of glucocorticoid response. J Steroid Biochem Mol Biol. 2002;82(4–5):277–88.

    Article  PubMed  CAS  Google Scholar 

  171. Wedel A, Ziegler-Heitbrock HW. The C/EBP family of transcription factors. Immunobiology. 1995;193(2–4):171–85.

    Article  PubMed  CAS  Google Scholar 

  172. Weinblatt ME, Kavanaugh A, Genovese MC, Musser TK, Grossbard EB, Magilavy DB. An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis. N Engl J Med. 2010;363(14):1303–12.

    Article  PubMed  CAS  Google Scholar 

  173. Weinstein RS, Jilka RL, Almeida M, Roberson PK, Manolagas SC. Intermittent parathyroid hormone administration counteracts the adverse effects of glucocorticoids on osteoblast and osteocyte viability, bone formation, and strength in mice. Endocrinology. 2010;151(6):2641–9.

    Article  PubMed  CAS  Google Scholar 

  174. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest. 1998;102(2):274–82.

    Article  PubMed  CAS  Google Scholar 

  175. Weinstein RS. Glucocorticoids, osteocytes, and skeletal fragility: the role of bone vascularity. Bone. 2009;46(3):564–70.

    Article  PubMed  CAS  Google Scholar 

  176. Weinstein RS. Glucocorticoids, osteocytes, and skeletal fragility: the role of bone vascularity. Bone. 2010;46(3):564–70.

    Article  PubMed  CAS  Google Scholar 

  177. Weinstein RS, Wan C, Liu Q, Wang Y, Almeida M, O’Brien CA, Thostenson J, Roberson PK, Boskey AL, Clemens TL, Manolagas SC. Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice. Aging Cell. 2010;9(2):147–61.

    Article  PubMed  CAS  Google Scholar 

  178. Wiegers GJ, Reul JM. Induction of cytokine receptors by glucocorticoids: functional and pathological significance. Trends Pharmacol Sci. 1998;19(8):317–21.

    Article  PubMed  CAS  Google Scholar 

  179. Wilkinson CW, Petrie EC, Murray SR, Colasurdo EA, Raskind MA, Peskind ER. Human glucocorticoid feedback inhibition is reduced in older individuals: evening study. J Clin Endocrinol Metab. 2001;86(2):545–50.

    Article  PubMed  CAS  Google Scholar 

  180. Wu Z, Bucher NL, Farmer SR. Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3 T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Mol Cell Biol. 1996;16(8):4128–36.

    PubMed  CAS  Google Scholar 

  181. Wust S, Van Rossum EF, Federenko IS, Koper JW, Kumsta R, Hellhammer DH. Common polymorphisms in the glucocorticoid receptor gene are associated with adrenocortical responses to psychosocial stress. J Clin Endocrinol Metab. 2004;89(2):565–73.

    Article  PubMed  CAS  Google Scholar 

  182. Yang JP, Merin JP, Nakano T, Kato T, Kitade Y, Okamoto T. Inhibition of the DNA-binding activity of NF-kappa B by gold compounds in vitro. FEBS Lett. 1995;361(1):89–96.

    Article  PubMed  CAS  Google Scholar 

  183. Yao W, Cheng Z, Pham A, Busse C, Zimmermann EA, Ritchie RO, Lane NE. Glucocorticoid-induced bone loss in mice can be reversed by the actions of parathyroid hormone and risedronate on different pathways for bone formation and mineralization. Arthritis Rheum. 2008;58(11):3485–97.

    Article  PubMed  CAS  Google Scholar 

  184. Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology. 1998;139(3):1329–37.

    Article  PubMed  Google Scholar 

  185. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 1998;95(7):3597–602.

    Article  PubMed  CAS  Google Scholar 

  186. Yeager MP, Guyre PM, Munck AU. Glucocorticoid regulation of the inflammatory response to injury. Acta Anaesthesiol Scand. 2004;48(7):799–813.

    Article  PubMed  CAS  Google Scholar 

  187. Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M. The IkappaB kinase complex (IKK) ­contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell. 1997;91(2):243–52.

    Article  PubMed  CAS  Google Scholar 

  188. Zhang TY, Ding X, Daynes RA. The expression of 11 beta-hydroxysteroid dehydrogenase type I by lymphocytes provides a novel means for intracrine regulation of glucocorticoid activities. J Immunol. 2005;174(2):879–89.

    PubMed  CAS  Google Scholar 

  189. Zhang TY, Daynes RA. Macrophages from 11beta-hydroxysteroid dehydrogenase type 1-deficient mice exhibit an increased sensitivity to lipopolysaccharide stimulation due to TGF-beta-mediated up-regulation of SHIP1 expression. J Immunol. 2007;179(9):6325–35.

    PubMed  CAS  Google Scholar 

  190. Zwerina J, Redlich K, Polzer K, Joosten L, Kronke G, Distler J, Hess A, Pundt N, Pap T, Hoffmann O, Gasser J, Scheinecker C, Smolen JS, van den Berg W, Schett G. TNF-induced structural joint damage is mediated by IL-1. Proc Natl Acad Sci USA. 2007;104(28):11742–7.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology and Diabetes, St. Vincent’s Hospital, 41 Victoria Parade, Fitzroy, VIC, 3065, Australia

    Kong Wah Ng M.D.

  2. Bone Cell Biology and Disease, St. Vincent’s Institute of Medical Research, 9 Princes Street, Fitzroy, VIC, 3065, Australia

    T. John Martin M.D., D.Sc.

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  1. Health Center, Dept. Pharmacology, University of Connecticut, Farmington Ave. 263, Farmington, 06030-6125, Connecticut, USA

    Felix Bronner

  2. , Department of Biochemistry and Cell Biol, Rice University, 6100 Main Street, Houston, 77005, Texas, USA

    Mary C. Farach-Carson

  3. , General Hospital, University of Southampton, Southampton, SO16 6YD, United Kingdom

    Helmtrud I. Roach

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Ng, K.W., Martin, T.J. (2012). Glucocorticoids, Inflammation, and Bone. In: Bronner, F., Farach-Carson, M., Roach, H. (eds) Bone-Metabolic Functions and Modulators. Topics in Bone Biology, vol 7. Springer, London. https://doi.org/10.1007/978-1-4471-2745-1_7

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