Skip to main content
Top
Published in: Osteoporosis International 10/2007

01-10-2007 | Review

Glucocorticoid-induced osteoporosis: pathophysiology and therapy

Authors: E. Canalis, G. Mazziotti, A. Giustina, J. P. Bilezikian

Published in: Osteoporosis International | Issue 10/2007

Login to get access

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.
Literature
1.
go back to reference Mazziotti G, Angeli A, Bilezikian JP et al (2006) Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 7:144–149 Mazziotti G, Angeli A, Bilezikian JP et al (2006) Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 7:144–149
2.
go back to reference Feldstein AC, Elmer PJ, Nichols GA et al (2005) Practice patterns in patients at risk for glucocorticoid-induced osteoporosis. Osteoporos Int 16:2168–2174PubMed Feldstein AC, Elmer PJ, Nichols GA et al (2005) Practice patterns in patients at risk for glucocorticoid-induced osteoporosis. Osteoporos Int 16:2168–2174PubMed
3.
go back to reference Cruse LM, Valeriano J, Vasey FB et al (2006) Prevalence of evaluation and treatment of glucocorticoid-induced osteoporosis in men. J Clin Rheumatol 12:221–225PubMed Cruse LM, Valeriano J, Vasey FB et al (2006) Prevalence of evaluation and treatment of glucocorticoid-induced osteoporosis in men. J Clin Rheumatol 12:221–225PubMed
4.
go back to reference Saag KG, Gelbach SH, Curtis JR et al (2006) Trends in prevention of glucocorticoid-induced osteoporosis. J Rheumatol 33:1651–1657PubMed Saag KG, Gelbach SH, Curtis JR et al (2006) Trends in prevention of glucocorticoid-induced osteoporosis. J Rheumatol 33:1651–1657PubMed
5.
go back to reference Canalis E (2005) Mechanisms of glucocorticoid action in bone. Curr Osteoporos Rep 3:98–102PubMed Canalis E (2005) Mechanisms of glucocorticoid action in bone. Curr Osteoporos Rep 3:98–102PubMed
6.
go back to reference Canalis E (1984) Effect of cortisol on periosteal and nonperiosteal collagen and DNA synthesis in cultured rat calvariae. Calcif Tissue Int 36:158–166PubMed Canalis E (1984) Effect of cortisol on periosteal and nonperiosteal collagen and DNA synthesis in cultured rat calvariae. Calcif Tissue Int 36:158–166PubMed
7.
go back to reference Canalis E (1983) Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae. Endocrinology 112:931–939PubMedCrossRef Canalis E (1983) Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae. Endocrinology 112:931–939PubMedCrossRef
8.
go back to reference 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 248:87–93PubMed 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 248:87–93PubMed
9.
go back to reference 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 79:118–125PubMed 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 79:118–125PubMed
10.
go back to reference 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 40:84–92PubMed 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 40:84–92PubMed
11.
go back to reference 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 30:685–691PubMed 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 30:685–691PubMed
12.
go back to reference Pereira RC, Delany AM, Canalis E (2004) CCAAT/enhancer binding protein homologous protein (DDIT3) induces osteoblastic cell differentiation. Endocrinology 145:1952–1960PubMed Pereira RC, Delany AM, Canalis E (2004) CCAAT/enhancer binding protein homologous protein (DDIT3) induces osteoblastic cell differentiation. Endocrinology 145:1952–1960PubMed
13.
go back to reference 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 16:4128–4136PubMed 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 16:4128–4136PubMed
14.
go back to reference Wedel A, Ziegler-Heitbrock HW (1995) The C/EBP family of transcription factors. Immunobiology 193:171–185PubMed Wedel A, Ziegler-Heitbrock HW (1995) The C/EBP family of transcription factors. Immunobiology 193:171–185PubMed
15.
go back to reference Schwartz AV, Sellmeyer DE, Vittinghoff E et al (2006) Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 91:3349–3354PubMed Schwartz AV, Sellmeyer DE, Vittinghoff E et al (2006) Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 91:3349–3354PubMed
16.
go back to reference Ohnaka K, Tanabe M, Kawate H et al (2005) Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. Biochem Biophys Res Commun 329:177–181PubMed Ohnaka K, Tanabe M, Kawate H et al (2005) Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. Biochem Biophys Res Commun 329:177–181PubMed
17.
go back to reference 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 280:2388–2394PubMed 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 280:2388–2394PubMed
18.
go back to reference Westendorf JJ, Kahler RA, Schroeder TM (2004) Wnt signaling in osteoblasts and bone diseases. Gene 341:19–39PubMed Westendorf JJ, Kahler RA, Schroeder TM (2004) Wnt signaling in osteoblasts and bone diseases. Gene 341:19–39PubMed
19.
go back to reference Glass DA, Bialek P, Ahn JD et al (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764PubMed Glass DA, Bialek P, Ahn JD et al (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764PubMed
20.
go back to reference Holmen SL, Zylstra CR, Mukherjee A et al (2005) Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem 280:21162–21168PubMed Holmen SL, Zylstra CR, Mukherjee A et al (2005) Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem 280:21162–21168PubMed
21.
go back to reference Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116:2627–2634PubMed Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116:2627–2634PubMed
22.
go back to reference Delany AM, Gabbitas BY, Canalis E (1995) Cortisol down regulates osteoblast 1(I) procollagen mRNA by transcriptional and post-transcriptional mechanisms. J Cell Biochem 57:488–494PubMed Delany AM, Gabbitas BY, Canalis E (1995) Cortisol down regulates osteoblast 1(I) procollagen mRNA by transcriptional and post-transcriptional mechanisms. J Cell Biochem 57:488–494PubMed
23.
go back to reference 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 19:479–490PubMed 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 19:479–490PubMed
24.
go back to reference 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 145:1835–1841PubMed 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 145:1835–1841PubMed
25.
go back to reference Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316PubMed Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316PubMed
26.
go back to reference Baylink DJ, Wergedal JE (1971) Bone formation by osteocytes. Am J Physiol 221:669–678PubMed Baylink DJ, Wergedal JE (1971) Bone formation by osteocytes. Am J Physiol 221:669–678PubMed
27.
go back to reference 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 21:466–476PubMed 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 21:466–476PubMed
28.
go back to reference Canalis E, Bilezikian JP, Angeli A et al (2004) Perspectives on glucocorticoid-induced osteoporosis. Bone 34:593–598PubMed Canalis E, Bilezikian JP, Angeli A et al (2004) Perspectives on glucocorticoid-induced osteoporosis. Bone 34:593–598PubMed
29.
go back to reference Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289:1504–8.PubMed Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289:1504–8.PubMed
30.
go back to reference 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 140:4382–4389PubMed 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 140:4382–4389PubMed
31.
go back to reference 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 139:1006–1012PubMed 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 139:1006–1012PubMed
32.
go back to reference 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 154:745–751PubMed 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 154:745–751PubMed
33.
go back to reference 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 278:44667–44674PubMed 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 278:44667–44674PubMed
34.
go back to reference 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 147:5592–5599PubMed 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 147:5592–5599PubMed
35.
go back to reference Kim HJ, Zhao H, Kitaura H et al (2006) Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest 116:2152–2160PubMed Kim HJ, Zhao H, Kitaura H et al (2006) Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest 116:2152–2160PubMed
36.
go back to reference Knauper V, Will H, Lopez-Otin C et al (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. J Biol Chem 271:17124–17131PubMed Knauper V, Will H, Lopez-Otin C et al (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. J Biol Chem 271:17124–17131PubMed
37.
go back to reference 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 269:16766–16773PubMed 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 269:16766–16773PubMed
38.
go back to reference Delany AM, Jeffrey JJ, Rydziel S et al (1995) Cortisol increases interstitial collagenase expression in osteoblasts by post-transcriptional mechanisms. J Biol Chem 270:26607–26612PubMed Delany AM, Jeffrey JJ, Rydziel S et al (1995) Cortisol increases interstitial collagenase expression in osteoblasts by post-transcriptional mechanisms. J Biol Chem 270:26607–26612PubMed
39.
go back to reference Dempster DW, Arlot MA, Meunier PJ (1983) Mean wall thickness and formation periods of trabecular bone packets in corticosteroid-induced osteoporosis. Calcif Tissue Int 35:410–417PubMed Dempster DW, Arlot MA, Meunier PJ (1983) Mean wall thickness and formation periods of trabecular bone packets in corticosteroid-induced osteoporosis. Calcif Tissue Int 35:410–417PubMed
40.
go back to reference Stellon AJ, Webb A, Compston JE (1988) Bone histomorphometry and structure in corticosteroid treated chronic active hepatitis. Gut 29:378–384PubMed Stellon AJ, Webb A, Compston JE (1988) Bone histomorphometry and structure in corticosteroid treated chronic active hepatitis. Gut 29:378–384PubMed
41.
go back to reference 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 83:60–65PubMed 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 83:60–65PubMed
42.
go back to reference Rydziel S, Canalis E (1995) Cortisol represses insulin-like growth factor II receptor transcription in skeletal cell cultures. Endocrinology 136:4254–4260PubMed Rydziel S, Canalis E (1995) Cortisol represses insulin-like growth factor II receptor transcription in skeletal cell cultures. Endocrinology 136:4254–4260PubMed
43.
go back to reference Okazaki R, Riggs BL, Conover CA (1994) Glucocorticoid regulation of insulin-like growth factor-binding protein expression in normal human osteoblast-like cells. Endocrinology 134:126–132PubMed Okazaki R, Riggs BL, Conover CA (1994) Glucocorticoid regulation of insulin-like growth factor-binding protein expression in normal human osteoblast-like cells. Endocrinology 134:126–132PubMed
44.
go back to reference 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 271:9033–9038PubMed 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 271:9033–9038PubMed
45.
go back to reference 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 143:3955–3962PubMed 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 143:3955–3962PubMed
46.
go back to reference 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 102:1627–1633PubMed 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 102:1627–1633PubMed
47.
go back to reference 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] 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]
48.
go back to reference 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 87:4033–4041PubMed 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 87:4033–4041PubMed
49.
go back to reference 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 52:5–9PubMed 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 52:5–9PubMed
50.
go back to reference 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 152:199–205PubMed 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 152:199–205PubMed
51.
go back to reference 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 76:399–403 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 76:399–403
52.
go back to reference 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 12:616–623 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 12:616–623
53.
go back to reference Mazziotti G, Cimino V, De Menis E et al (2006) Active acromegaly enhances spontaneous parathyroid hormone pulsatility. Metabolism 55:736–740PubMed Mazziotti G, Cimino V, De Menis E et al (2006) Active acromegaly enhances spontaneous parathyroid hormone pulsatility. Metabolism 55:736–740PubMed
54.
go back to reference 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 134:451–456PubMed 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 134:451–456PubMed
55.
go back to reference Giustina A, Veldhuis JD (1998) Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19:717–797PubMed Giustina A, Veldhuis JD (1998) Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19:717–797PubMed
56.
go back to reference 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 74:1301–1305PubMed 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 74:1301–1305PubMed
57.
go back to reference 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 80:122–129PubMed 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 80:122–129PubMed
58.
go back to reference Manelli F, Carpinteri R, Bossoni S et al (2002) Growth hormone in glucocorticoid-induced osteoporosis. Front Horm Res 30:174–183PubMed Manelli F, Carpinteri R, Bossoni S et al (2002) Growth hormone in glucocorticoid-induced osteoporosis. Front Horm Res 30:174–183PubMed
59.
go back to reference 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 127:515–521PubMed 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 127:515–521PubMed
60.
go back to reference van Staa TP (2006) The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int 79:129–137PubMed van Staa TP (2006) The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int 79:129–137PubMed
61.
go back to reference 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 42:2309–2318PubMed 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 42:2309–2318PubMed
62.
go back to reference 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 67:277–285PubMed 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 67:277–285PubMed
63.
go back to reference 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 39:253–259PubMed 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 39:253–259PubMed
64.
go back to reference Shaker JL, Lukert BP (2005) Osteoporosis associated with excess glucocorticoids. Endocrinol Metab Clin North Am 34:341–356PubMed Shaker JL, Lukert BP (2005) Osteoporosis associated with excess glucocorticoids. Endocrinol Metab Clin North Am 34:341–356PubMed
65.
go back to reference van Staa TP, Leufkens HGM, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a metaanalysis. Osteoporos Int 13:777–787PubMed van Staa TP, Leufkens HGM, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a metaanalysis. Osteoporos Int 13:777–787PubMed
66.
go back to reference Cohen A, Shane E (2003) Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 14:617–630PubMed Cohen A, Shane E (2003) Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 14:617–630PubMed
67.
go back to reference Steinbuch M, Youket TE, Cohen S (2004) Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int 15:323–328PubMed Steinbuch M, Youket TE, Cohen S (2004) Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int 15:323–328PubMed
68.
go back to reference 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 59:585–592 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 59:585–592
69.
go back to reference 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 90:804–810 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 90:804–810
70.
go back to reference 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 89:4004–4009PubMed 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 89:4004–4009PubMed
71.
go back to reference Kaji H, Tobimatsu T, Naito J et al (2006) Body composition and vertebral fracture risk in female patients treated with glucocorticoid. Osteoporos Int 17:627–633PubMed Kaji H, Tobimatsu T, Naito J et al (2006) Body composition and vertebral fracture risk in female patients treated with glucocorticoid. Osteoporos Int 17:627–633PubMed
72.
go back to reference Tomlinson JW, Walker EA, Bujalska IJ et al (2004) 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev 25:31–66 Tomlinson JW, Walker EA, Bujalska IJ et al (2004) 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev 25:31–66
73.
go back to reference 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 16:1037–1044PubMed 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 16:1037–1044PubMed
74.
go back to reference 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 275:30232–30239PubMed 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 275:30232–30239PubMed
75.
go back to reference 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 17:979–986PubMed 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 17:979–986PubMed
76.
go back to reference van Hogezand RA, Hamdy NA (2006) Skeletal morbidity in inflammatory bowel disease. Scand J Gastroenterol 243:S59–S64 van Hogezand RA, Hamdy NA (2006) Skeletal morbidity in inflammatory bowel disease. Scand J Gastroenterol 243:S59–S64
77.
go back to reference Romas E (2005) Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates. Best Pract Res Clin Rheumatol 19:1065–1079PubMed Romas E (2005) Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates. Best Pract Res Clin Rheumatol 19:1065–1079PubMed
78.
go back to reference 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 13:710–715PubMed 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 13:710–715PubMed
79.
go back to reference Sin DD, Man JP, Man SF (2003) The risk of osteoporosis in Caucasian men and women with obstructive airways disease. Am J Med 114:10–14PubMed Sin DD, Man JP, Man SF (2003) The risk of osteoporosis in Caucasian men and women with obstructive airways disease. Am J Med 114:10–14PubMed
80.
go back to reference Khan AA, Hanley DA, Bilezikian JP et al (2006) Standards for performing DXA in individuals with secondary causes of osteoporosis. J Clin Densitom 9:47–57PubMed Khan AA, Hanley DA, Bilezikian JP et al (2006) Standards for performing DXA in individuals with secondary causes of osteoporosis. J Clin Densitom 9:47–57PubMed
81.
go back to reference 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 20:1837–1844PubMed 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 20:1837–1844PubMed
82.
go back to reference 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 21:520–528PubMed 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 21:520–528PubMed
83.
go back to reference 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 48:3224–3229PubMed 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 48:3224–3229PubMed
84.
go back to reference Compston J (2004) US and UK guidelines for glucocorticoid-induced osteoporosis: similarities and differences. Curr Rheumatol Rep 6:66–69PubMed Compston J (2004) US and UK guidelines for glucocorticoid-induced osteoporosis: similarities and differences. Curr Rheumatol Rep 6:66–69PubMed
85.
go back to reference Cefalu CA (2004) Is bone mineral density predictive of fracture risk reduction? Curr Med Res Opin 20:341–349PubMed Cefalu CA (2004) Is bone mineral density predictive of fracture risk reduction? Curr Med Res Opin 20:341–349PubMed
86.
go back to reference 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 12:1883–1894 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 12:1883–1894
87.
go back to reference 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 15:1368–1375 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 15:1368–1375
88.
go back to reference Carballido-Gamio J, Majumdar S (2006) Clinical utility of microarchitecture measurements of trabecular bone. Curr Osteoporos Rep 4:64–70PubMed Carballido-Gamio J, Majumdar S (2006) Clinical utility of microarchitecture measurements of trabecular bone. Curr Osteoporos Rep 4:64–70PubMed
89.
go back to reference Masaki H, Miki T (2006) The biochemical markers of bone in steroid (glucocorticoid)-induced osteoporosis (GIOP). Clin Calcium 16:51–60 Masaki H, Miki T (2006) The biochemical markers of bone in steroid (glucocorticoid)-induced osteoporosis (GIOP). Clin Calcium 16:51–60
90.
go back to reference 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 17:105–108PubMed 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 17:105–108PubMed
91.
go back to reference Gilson H, Schakman O, Combaret L et al (2007) Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinology 148:452–460PubMed Gilson H, Schakman O, Combaret L et al (2007) Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinology 148:452–460PubMed
92.
go back to reference 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 44:1496–1503 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 44:1496–1503
93.
go back to reference 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 259:539–552PubMed 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 259:539–552PubMed
94.
go back to reference 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 15:770–779PubMed 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 15:770–779PubMed
95.
go back to reference 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 15:589–602PubMed 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 15:589–602PubMed
96.
go back to reference 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 65:317–327PubMed 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 65:317–327PubMed
97.
go back to reference 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 125:961–968PubMed 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 125:961–968PubMed
98.
go back to reference Heaney RP (2005) The Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol 97:13–19PubMed Heaney RP (2005) The Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol 97:13–19PubMed
99.
go back to reference 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 17:1512–1526PubMed 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 17:1512–1526PubMed
100.
go back to reference de Nijs RN, Jacobs JW, Lems WF et al (2006) Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med 355:675–684PubMed de Nijs RN, Jacobs JW, Lems WF et al (2006) Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis. N Engl J Med 355:675–684PubMed
101.
go back to reference 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 339:292–299PubMed 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 339:292–299PubMed
102.
go back to reference 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 15:1006–1013PubMed 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 15:1006–1013PubMed
103.
go back to reference 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 44:202–211PubMed 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 44:202–211PubMed
104.
go back to reference 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 54:3104–3112PubMed 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 54:3104–3112PubMed
105.
go back to reference Franchimont N, Canalis E (2003) Management of glucocorticoid induced osteoporosis in premenopausal women with autoimmune disease. Autoimmun Rev 4:224–228 Franchimont N, Canalis E (2003) Management of glucocorticoid induced osteoporosis in premenopausal women with autoimmune disease. Autoimmun Rev 4:224–228
106.
go back to reference Jilka RL, Weinstein RS, Bellido T et al (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104:439–446PubMed Jilka RL, Weinstein RS, Bellido T et al (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104:439–446PubMed
107.
go back to reference 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 23:450–455PubMed 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 23:450–455PubMed
108.
go back to reference Calvi LM, Adams GB, Weibrecht KW et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846PubMed Calvi LM, Adams GB, Weibrecht KW et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846PubMed
109.
go back to reference 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 102:1627–1633PubMedCrossRef 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 102:1627–1633PubMedCrossRef
110.
go back to reference 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 11:434–442PubMed 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 11:434–442PubMed
111.
go back to reference 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 14:77–81PubMed 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 14:77–81PubMed
112.
go back to reference 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 89:3332–3336PubMed 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 89:3332–3336PubMed
Metadata
Title
Glucocorticoid-induced osteoporosis: pathophysiology and therapy
Authors
E. Canalis
G. Mazziotti
A. Giustina
J. P. Bilezikian
Publication date
01-10-2007
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 10/2007
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-007-0394-0

Other articles of this Issue 10/2007

Osteoporosis International 10/2007 Go to the issue