Osteoporosis International

, Volume 18, Issue 10, pp 1319–1328 | Cite as

Glucocorticoid-induced osteoporosis: pathophysiology and therapy

  • E. Canalis
  • G. Mazziotti
  • A. Giustina
  • J. P. Bilezikian
Review

Abstract

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Fractures, which are often asymptomatic, may occur in as many as 30–50% of patients receiving chronic glucocorticoid therapy. Vertebral fractures occur early after exposure to glucocorticoids, at a time when bone mineral density (BMD) declines rapidly. Fractures tend to occur at higher BMD levels than in women with postmenopausal osteoporosis. In human subjects, the early rapid decline in BMD is followed by a slower progressive decline in BMD. Glucocorticoids have direct and indirect effects on the skeleton. The primary effects are on osteoblasts and osteocytes. Glucocorticoids impair the replication, differentiation and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes. These effects lead to a suppression of bone formation, a central feature in the pathogenesis of GIO. Glucocorticoids also favor osteoclastogenesis and as a consequence increase bone resorption. Bisphosphonates are effective in the prevention and treatment of GIO. Anabolic therapeutic strategies are under investigation.

Keywords

Bone mineral density Fractures Glucocorticoid-induced osteoporosis 

References

  1. 1.
    Mazziotti G, Angeli A, Bilezikian JP et al (2006) Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 7:144–149Google Scholar
  2. 2.
    Feldstein AC, Elmer PJ, Nichols GA et al (2005) Practice patterns in patients at risk for glucocorticoid-induced osteoporosis. Osteoporos Int 16:2168–2174PubMedGoogle Scholar
  3. 3.
    Cruse LM, Valeriano J, Vasey FB et al (2006) Prevalence of evaluation and treatment of glucocorticoid-induced osteoporosis in men. J Clin Rheumatol 12:221–225PubMedGoogle Scholar
  4. 4.
    Saag KG, Gelbach SH, Curtis JR et al (2006) Trends in prevention of glucocorticoid-induced osteoporosis. J Rheumatol 33:1651–1657PubMedGoogle Scholar
  5. 5.
    Canalis E (2005) Mechanisms of glucocorticoid action in bone. Curr Osteoporos Rep 3:98–102PubMedGoogle Scholar
  6. 6.
    Canalis E (1984) Effect of cortisol on periosteal and nonperiosteal collagen and DNA synthesis in cultured rat calvariae. Calcif Tissue Int 36:158–166PubMedGoogle Scholar
  7. 7.
    Canalis E (1983) Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae. Endocrinology 112:931–939PubMedCrossRefGoogle Scholar
  8. 8.
    Eijken M, Koedam M, van Driel M et al (2006) The essential role of glucocorticoids for proper human osteoblast differentiation and matrix mineralization. Mol Cell Endocrinol 248:87–93PubMedGoogle Scholar
  9. 9.
    Sher LB, Harrison JR, Adams DJ et al (2006) Impaired cortical bone acquisition and osteoblast differentiation in mice with osteoblast-targeted disruption of glucocorticoid signaling. Calcif Tissue Int 79:118–125PubMedGoogle Scholar
  10. 10.
    Ito S, Suzuki N, Kato S et al (2007) Glucocorticoids induce the differentiation of a mesenchymal progenitor cell line, ROB-C26 into adipocytes and osteoblasts, but fail to induce terminal osteoblast differentiation. Bone 40:84–92PubMedGoogle Scholar
  11. 11.
    Pereira RC, Delany AM, Canalis E (2002) Effects of cortisol and bone morphogenetic protein-2 on stromal cell differentiation: correlation with CCAAT-enhancer binding protein expression. Bone 30:685–691PubMedGoogle Scholar
  12. 12.
    Pereira RC, Delany AM, Canalis E (2004) CCAAT/enhancer binding protein homologous protein (DDIT3) induces osteoblastic cell differentiation. Endocrinology 145:1952–1960PubMedGoogle Scholar
  13. 13.
    Wu Z, Bucher NLR, Farmer SR (1996) Induction of peroxisome proliferator-activated receptor g during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPh, C/EBPy, and glucocorticoids. Mol Cell Biol 16:4128–4136PubMedGoogle Scholar
  14. 14.
    Wedel A, Ziegler-Heitbrock HW (1995) The C/EBP family of transcription factors. Immunobiology 193:171–185PubMedGoogle Scholar
  15. 15.
    Schwartz AV, Sellmeyer DE, Vittinghoff E et al (2006) Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 91:3349–3354PubMedGoogle Scholar
  16. 16.
    Ohnaka K, Tanabe M, Kawate H et al (2005) Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. Biochem Biophys Res Commun 329:177–181PubMedGoogle Scholar
  17. 17.
    Smith E, Frenkel B (2005) Glucocorticoids inhibit the transcriptional activity of LEF/TCF in differentiating osteoblasts in a glycogen synthase kinase-3beta-dependent and -independent manner. J Biol Chem 280:2388–2394PubMedGoogle Scholar
  18. 18.
    Westendorf JJ, Kahler RA, Schroeder TM (2004) Wnt signaling in osteoblasts and bone diseases. Gene 341:19–39PubMedGoogle Scholar
  19. 19.
    Glass DA, Bialek P, Ahn JD et al (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764PubMedGoogle Scholar
  20. 20.
    Holmen SL, Zylstra CR, Mukherjee A et al (2005) Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem 280:21162–21168PubMedGoogle Scholar
  21. 21.
    Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116:2627–2634PubMedGoogle Scholar
  22. 22.
    Delany AM, Gabbitas BY, Canalis E (1995) Cortisol down regulates osteoblast 1(I) procollagen mRNA by transcriptional and post-transcriptional mechanisms. J Cell Biochem 57:488–494PubMedGoogle Scholar
  23. 23.
    Liu Y, Porta A, Peng X et al (2004) Prevention of glucocorticoid-induced apoptosis in osteocytes and osteoblasts by calbindin-D28k. J Bone Miner Res 19:479–490PubMedGoogle Scholar
  24. 24.
    O’Brien CA, Jia D, Plotkin LI et al (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145:1835–1841PubMedGoogle Scholar
  25. 25.
    Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316PubMedGoogle Scholar
  26. 26.
    Baylink DJ, Wergedal JE (1971) Bone formation by osteocytes. Am J Physiol 221:669–678PubMedGoogle Scholar
  27. 27.
    Lane NE, Yao W, Balooch M et al (2006) 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 21:466–476PubMedGoogle Scholar
  28. 28.
    Canalis E, Bilezikian JP, Angeli A et al (2004) Perspectives on glucocorticoid-induced osteoporosis. Bone 34:593–598PubMedGoogle Scholar
  29. 29.
    Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289:1504–8.PubMedGoogle Scholar
  30. 30.
    Hofbauer LC, Gori F, Riggs BL et al (1999) Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 140:4382–4389PubMedGoogle Scholar
  31. 31.
    Rubin J, Biskobing DM, Jadhav L et al (1998) Dexamethasone promotes expression of membrane-bound macrophage colony-stimulating factor in murine osteoblast-like cells. Endocrinology 139:1006–1012PubMedGoogle Scholar
  32. 32.
    Dovio A, Perazzolo L, Saba L et al (2006) 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 154:745–751PubMedGoogle Scholar
  33. 33.
    Takuma A, Kaneda T, Sato T et al (2003) Dexamethasone enhances osteoclast formation synergistically with transforming growth factor-beta by stimulating the priming of osteoclast progenitors for differentiation into osteoclasts. J Biol Chem 278:44667–44674PubMedGoogle Scholar
  34. 34.
    Jia D, O’Brien CA, Stewart SA et al (2006) Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. Endocrinology 147:5592–5599PubMedGoogle Scholar
  35. 35.
    Kim HJ, Zhao H, Kitaura H et al (2006) Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest 116:2152–2160PubMedGoogle Scholar
  36. 36.
    Knauper V, Will H, Lopez-Otin C et al (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. J Biol Chem 271:17124–17131PubMedGoogle Scholar
  37. 37.
    Freije JMP, Diez-Itza I, Balbin M et al (1994) Molecular cloning and expression of collagenase 3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem 269:16766–16773PubMedGoogle Scholar
  38. 38.
    Delany AM, Jeffrey JJ, Rydziel S et al (1995) Cortisol increases interstitial collagenase expression in osteoblasts by post-transcriptional mechanisms. J Biol Chem 270:26607–26612PubMedGoogle Scholar
  39. 39.
    Dempster DW, Arlot MA, Meunier PJ (1983) Mean wall thickness and formation periods of trabecular bone packets in corticosteroid-induced osteoporosis. Calcif Tissue Int 35:410–417PubMedGoogle Scholar
  40. 40.
    Stellon AJ, Webb A, Compston JE (1988) Bone histomorphometry and structure in corticosteroid treated chronic active hepatitis. Gut 29:378–384PubMedGoogle Scholar
  41. 41.
    Canalis E, Centrella M, Burch J et al (1989) Insulin-like growth factor I mediates selected anabolic effects of parathyroid hormone in bone cultures. J Clin Invest 83:60–65PubMedGoogle Scholar
  42. 42.
    Rydziel S, Canalis E (1995) Cortisol represses insulin-like growth factor II receptor transcription in skeletal cell cultures. Endocrinology 136:4254–4260PubMedGoogle Scholar
  43. 43.
    Okazaki R, Riggs BL, Conover CA (1994) Glucocorticoid regulation of insulin-like growth factor-binding protein expression in normal human osteoblast-like cells. Endocrinology 134:126–132PubMedGoogle Scholar
  44. 44.
    Gabbitas B, Pash JM, Delany AM et al (1996) Cortisol inhibits the synthesis of insulin-like growth factor binding protein-5 in bone cell cultures by transcriptional mechanisms. J Biol Chem 271:9033–9038PubMedGoogle Scholar
  45. 45.
    Devlin RD, Du Z, Buccilli V et al (2002) Transgenic mice overexpressing insulin-like growth factor binding protein-5 display transiently decreased osteoblastic function and osteopenia. Endocrinology 143:3955–3962PubMedGoogle Scholar
  46. 46.
    Lane NE, Sanchez S, Modin GW et al (1998) Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest 102:1627–1633PubMedGoogle Scholar
  47. 47.
    Huybers S, Naber TH, Bindels RJ et al (2006) Prednisolone-induced Ca2+malabsorption is caused by diminished expression of the epithelial Ca2+channel TRPV6. Am J Physiol Gastrointest Liver Physiol Aug [Epub ahead of print]Google Scholar
  48. 48.
    Rubin MR, Bilezikian JP (2002) The role of parathyroid hormone in the pathogenesis of glucocorticoid-induced osteoporosis: a re-examination of the evidence. J Clin Endocrinol Metab 87:4033–4041PubMedGoogle Scholar
  49. 49.
    Laan RF, Buijs WC, van Erning LJ et al (1993) Differential effects of glucocorticoids on cortical appendicular and cortical vertebral bone mineral content. Calcif Tissue Int 52:5–9PubMedGoogle Scholar
  50. 50.
    Bonadonna S, Burattin A, Nuzzo M et al (2005) Chronic glucocorticoid treatment alters spontaneous pulsatile parathyroid hormone secretory dynamics in human subjects. Eur J Endocrinol 152:199–205PubMedGoogle Scholar
  51. 51.
    Samuels MH, Veldhuis J, Cawley C et al (1993) Pulsatile secretion of parathyroid hormone in normal young subjects: assessment by deconvolution analysis. J Clin Endocrinol Metab 76:399–403Google Scholar
  52. 52.
    Samuels MH, Veldhuis JD, Kramer P et al (1993) Episodic secretion of parathyroid hormone in post-menopausal women: assessment by deconvolution analysis and approximate entropy. J Bone Miner Res 12:616–623Google Scholar
  53. 53.
    Mazziotti G, Cimino V, De Menis E et al (2006) Active acromegaly enhances spontaneous parathyroid hormone pulsatility. Metabolism 55:736–740PubMedGoogle Scholar
  54. 54.
    Urena P, Iida-Klein A, Kong XF et al (1994) Regulation of parathyroid hormone (PTH)/PTHrelated peptide receptor messenger ribonucleic acid by glucocorticoids and PTH in ROS 17/2.8 and OK cells. Endocrinology 134:451–456PubMedGoogle Scholar
  55. 55.
    Giustina A, Veldhuis JD (1998) Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19:717–797PubMedGoogle Scholar
  56. 56.
    Giustina A, Bossoni S, Bodini C et al (1992) Arginine normalizes the growth hormone (GH) response to GH-releasing hormone in adult patients receiving chronic daily immunosuppressive glucocorticoid therapy. J Clin Endocrinol Metab 74:1301–1305PubMedGoogle Scholar
  57. 57.
    Giustina A, Bussi AR, Jacobello C et al (1995) Effects of recombinant human growth hormone (GH) on bone and intermediary metabolism in patients receiving chronic glucocorticoid treatment with suppressed endogenous GH response to GH-releasing hormone. J Clin Endocrinol Metab 80:122–129PubMedGoogle Scholar
  58. 58.
    Manelli F, Carpinteri R, Bossoni S et al (2002) Growth hormone in glucocorticoid-induced osteoporosis. Front Horm Res 30:174–183PubMedGoogle Scholar
  59. 59.
    Malerba M, Bossoni S, Radaeli A et al (2005) Growth hormone response to growth hormone-releasing hormone is reduced in adult asthmatic patients receiving long-term inhaled corticosteroid treatment. Chest 127:515–521PubMedGoogle Scholar
  60. 60.
    van Staa TP (2006) The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int 79:129–137PubMedGoogle Scholar
  61. 61.
    Cohen S, Levy RM, Keller M et al (1999) Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 42:2309–2318PubMedGoogle Scholar
  62. 62.
    Wallach S, Cohen S, Reid DM et al (2000) Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int 67:277–285PubMedGoogle Scholar
  63. 63.
    Angeli A, Guglielmi G, Dovio A et al (2006) High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone 39:253–259PubMedGoogle Scholar
  64. 64.
    Shaker JL, Lukert BP (2005) Osteoporosis associated with excess glucocorticoids. Endocrinol Metab Clin North Am 34:341–356PubMedGoogle Scholar
  65. 65.
    van Staa TP, Leufkens HGM, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a metaanalysis. Osteoporos Int 13:777–787PubMedGoogle Scholar
  66. 66.
    Cohen A, Shane E (2003) Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 14:617–630PubMedGoogle Scholar
  67. 67.
    Steinbuch M, Youket TE, Cohen S (2004) Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int 15:323–328PubMedGoogle Scholar
  68. 68.
    van Rossum EF, Koper JW, van den Beld AW et al (2003) Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol 59:585–592Google Scholar
  69. 69.
    Russcher H, Smit P, van den Akker EL et al (2005) Two polymorphisms in the glucocorticoid receptor gene directly affect glucocorticoid-regulated gene expression. J Clin Endocrinol Metab 90:804–810Google Scholar
  70. 70.
    van Rossum EF, Voorhoeve PG, te Velde SJ et al (2004) The ER22/23EK polymorphism in the glucocorticoid receptor gene is associated with a beneficial body composition and muscle strength in young adults. J Clin Endocrinol Metab 89:4004–4009PubMedGoogle Scholar
  71. 71.
    Kaji H, Tobimatsu T, Naito J et al (2006) Body composition and vertebral fracture risk in female patients treated with glucocorticoid. Osteoporos Int 17:627–633PubMedGoogle Scholar
  72. 72.
    Tomlinson JW, Walker EA, Bujalska IJ et al (2004) 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev 25:31–66Google Scholar
  73. 73.
    Cooper MS, Bujalska I, Rabbitt E et al (2001) Modulation of 11â-hydroxysteroid dehydrogenase isozymes by proinflammatory cytokines in osteoblasts: an autocrine switch from glucocorticoid inactivation to activation. J Bone Miner Res 16:1037–1044PubMedGoogle Scholar
  74. 74.
    Williams LJ, Lyons V, MacLeod I et al (2000) C/EBP regulates hepatic transcription of 11beta-hydroxysteroid dehydrogenase type1. A novel mechanism for cross-talk between the C/EBP and glucocorticoid signaling pathways. J Biol Chem 275:30232–30239PubMedGoogle Scholar
  75. 75.
    Cooper MS, Rabbitt EH, Goddard PE et al (2002) Osteoblastic 11â-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure. J Bone Miner Res 17:979–986PubMedGoogle Scholar
  76. 76.
    van Hogezand RA, Hamdy NA (2006) Skeletal morbidity in inflammatory bowel disease. Scand J Gastroenterol 243:S59–S64Google Scholar
  77. 77.
    Romas E (2005) Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates. Best Pract Res Clin Rheumatol 19:1065–1079PubMedGoogle Scholar
  78. 78.
    Lekamwasam S, Trivedi DP, Khaw KT (2002) An association between respiratory function and bone mineral density in women from the general community: a cross sectional study. Osteoporos Int 13:710–715PubMedGoogle Scholar
  79. 79.
    Sin DD, Man JP, Man SF (2003) The risk of osteoporosis in Caucasian men and women with obstructive airways disease. Am J Med 114:10–14PubMedGoogle Scholar
  80. 80.
    Khan AA, Hanley DA, Bilezikian JP et al (2006) Standards for performing DXA in individuals with secondary causes of osteoporosis. J Clin Densitom 9:47–57PubMedGoogle Scholar
  81. 81.
    Bonadonna S, Mazziotti G, Nuzzo M et al (2005) Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. J Bone Miner Res 20:1837–1844PubMedGoogle Scholar
  82. 82.
    Mazziotti G, Bianchi A, Bonadonna S et al (2006) Increased prevalence of radiological spinal deformities in adult patients with GH deficiency: influence of GH replacement therapy. J Bone Miner Res 21:520–528PubMedGoogle Scholar
  83. 83.
    Van Staa TP, Laan RF, Barton IP et al (2003) Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 48:3224–3229PubMedGoogle Scholar
  84. 84.
    Compston J (2004) US and UK guidelines for glucocorticoid-induced osteoporosis: similarities and differences. Curr Rheumatol Rep 6:66–69PubMedGoogle Scholar
  85. 85.
    Cefalu CA (2004) Is bone mineral density predictive of fracture risk reduction? Curr Med Res Opin 20:341–349PubMedGoogle Scholar
  86. 86.
    Lunt M, Felsenberg D, Reeve J et al (1997) Bone density variation and its effects on risk of vertebral deformity in men and women studied in thirteen European centers: the EVOS Study. J Bone Min Res 12:1883–1894Google Scholar
  87. 87.
    Olesik A, Ott SM, Vedi S et al (2000) Bone structure in patients with low bone mineral density with or without vertebral fractures. J Bone Min Res 15:1368–1375Google Scholar
  88. 88.
    Carballido-Gamio J, Majumdar S (2006) Clinical utility of microarchitecture measurements of trabecular bone. Curr Osteoporos Rep 4:64–70PubMedGoogle Scholar
  89. 89.
    Masaki H, Miki T (2006) The biochemical markers of bone in steroid (glucocorticoid)-induced osteoporosis (GIOP). Clin Calcium 16:51–60Google Scholar
  90. 90.
    Natsui K, Tanaka K, Suda M et al (2006) High-dose glucocorticoid treatment induces rapid loss of trabecular bone mineral density and lean body mass. Osteoporos Int 17:105–108PubMedGoogle Scholar
  91. 91.
    Gilson H, Schakman O, Combaret L et al (2007) Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinology 148:452–460PubMedGoogle Scholar
  92. 92.
    American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis (2001) Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum 44:1496–1503Google Scholar
  93. 93.
    Boonen S, Vanderschueren D, Haentjens P et al (2006) Calcium and vitamin D in the prevention and treatment of osteoporosis - a clinical update. J Intern Med 259:539–552PubMedGoogle Scholar
  94. 94.
    Shiraishi A, Takeda S, Masaki T et al (2000) Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis: distinct actions from estrogen. J Bone Miner Res 15:770–779PubMedGoogle Scholar
  95. 95.
    de Nijs RN, Jacobs JW, Algra A et al (2004) Prevention and treatment of glucocorticoid-induced osteoporosis with active vitamin D(3) analogues: a review with meta-analysis of randomized controlled trials including organ transplantation studies. Osteoporos Int 15:589–602PubMedGoogle Scholar
  96. 96.
    Schacht E (1999) Rationale for treatment of involutional osteoporosis in women and for prevention and treatment of corticosteroid-induced osteoporosis with alfacalcidol. Calcif Tissue Int 65:317–327PubMedGoogle Scholar
  97. 97.
    Buckley LM, Leib ES, Cartularo KS et al (1996) Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 125:961–968PubMedGoogle Scholar
  98. 98.
    Heaney RP (2005) The Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol 97:13–19PubMedGoogle Scholar
  99. 99.
    Amin S, Lavalley MP, Simms RW et al (2002) The comparative efficacy of drug therapies used for the management of corticosteroid-induced osteoporosis: a meta-regression. J Bone Miner Res 17:1512–1526PubMedGoogle Scholar
  100. 100.
    de Nijs RN, Jacobs JW, Lems WF et al (2006) Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med 355:675–684PubMedGoogle Scholar
  101. 101.
    Saag KG, Emkey R, Schnitzer TJ et al (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 339:292–299PubMedGoogle Scholar
  102. 102.
    Reid DM, Hughes RA, Laan RF et al (2000) Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study. J Bone Miner Res 15:1006–1013PubMedGoogle Scholar
  103. 103.
    Adachi JD, Saag KG, Delmas PD et al (2001) 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 44:202–211PubMedGoogle Scholar
  104. 104.
    van Staa TP, Geusens P, Bijlsma JW et al (2006) Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 54:3104–3112PubMedGoogle Scholar
  105. 105.
    Franchimont N, Canalis E (2003) Management of glucocorticoid induced osteoporosis in premenopausal women with autoimmune disease. Autoimmun Rev 4:224–228Google Scholar
  106. 106.
    Jilka RL, Weinstein RS, Bellido T et al (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104:439–446PubMedGoogle Scholar
  107. 107.
    Iu MF, Kaji H, Naito J et al (2005) Low-dose parathyroid hormone and estrogen reverse alkaline phosphatase activity suppressed by dexamethasone in mouse osteoblastic cells. J Bone Miner Metab 23:450–455PubMedGoogle Scholar
  108. 108.
    Calvi LM, Adams GB, Weibrecht KW et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846PubMedGoogle Scholar
  109. 109.
    Lane NE, Sanchez S, Modin GW et al (1998) Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest 102:1627–1633PubMedCrossRefGoogle Scholar
  110. 110.
    Lane NE, Sanchez S, Genant HK et al (2000) Short-term increases in bone turnover markers predict parathyroid hormone-induced spinal bone mineral density gains in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int 11:434–442PubMedGoogle Scholar
  111. 111.
    Rehman Q, Lang TF, Arnaud CD et al (2003) Daily treatment with parathyroid hormone is associated with an increase in vertebral cross-sectional area in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int 14:77–81PubMedGoogle Scholar
  112. 112.
    Buxton EC, Yao W, Lane NE (2004) 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 89:3332–3336PubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • E. Canalis
    • 1
    • 2
  • G. Mazziotti
    • 3
  • A. Giustina
    • 3
  • J. P. Bilezikian
    • 4
  1. 1.Saint Francis Hospital and Medical CenterHartfordUSA
  2. 2.University of Connecticut School of MedicineFarmingtonUSA
  3. 3.Department of Internal MedicineUniversity of BresciaBresciaItaly
  4. 4.Department of Medicine, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

Personalised recommendations