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Current Rheumatology Reports
Published in: Current Rheumatology Reports 3/2011

Open Access 01-06-2011

Advances in Glucocorticoid-Induced Osteoporosis

Authors: Debby den Uyl, Irene E. M. Bultink, Willem F. Lems

Published in: Current Rheumatology Reports | Issue 3/2011

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Abstract

Glucocorticoid-induced osteoporosis (GIOP) is one of the most important side effects of glucocorticoid use, as it leads to an increased risk of fractures. Recently, many published studies have focused on the cellular and molecular mechanisms of bone metabolism, the pathophysiology of GIOP, and the intervention options to prevent GIOP. In this review, recent advances in GIOP are summarized, particularly recent progress in our understanding of the mechanisms of GIOP resulting in improved insight that might result in the development of new treatment options in the near future.
Literature
1.
Kanis JA, Johansson H, Oden A, et al. A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res. 2004;19:893–9.PubMedCrossRef
2.
van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13:777–87.PubMedCrossRef
3.
Gudbjornsson B, Juliusson UI, Gudjonsson FV. Prevalence of long term steroid treatment and the frequency of decision making to prevent steroid induced osteoporosis in daily clinical practice. Ann Rheum Dis. 2002;61:32–6.PubMedCrossRef
4.
Natsui K, Tanaka K, Suda M, et al. High-dose glucocorticoid treatment induces rapid loss of trabecular bone mineral density and lean body mass. Osteoporos Int. 2006;17:105–8.PubMedCrossRef
5.
Adachi JD, Saag KG, Delmas PD, et al. 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;44:202–11.PubMedCrossRef
6.
Cohen S, Levy RM, Keller M, et al. Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 1999;42:2309–18.PubMedCrossRef
7.
•• Reid DM, Devogelaer JP, Saag K, et al.: 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, 373:1253-63. In this double-blind study, zoledronic acid was compared with risedronate in the prevention of GIOP in men and women receiving treatment with prednisolone. Zoledronic acid increased BMD of the spine more than risedronate and showed a faster inhibitory effect on bone markers. Therefore, this study showed that zoledronic acid is an important additional treatment option for GIOP.
8.
Cooper C, Coupland C, Mitchell M. Rheumatoid arthritis, corticosteroid therapy and hip fracture. Ann Rheum Dis. 1995;54:49–52.PubMedCrossRef
9.
van Staa TP, Geusens P, Pols HA, de Laet C, Leufkens HG, Cooper C. A simple score for estimating the long-term risk of fracture in patients using oral glucocorticoids. QJM. 2005;98:191–8.PubMedCrossRef
10.
van Staa TP. The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int. 2006;79:129–37.PubMedCrossRef
11.
De Vries F, Bracke M, Leufkens HG, et al. Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis Rheum. 2007;56:208–14.PubMedCrossRef
12.
Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int. 2005;16:581–9.PubMedCrossRef
13.
Lems WF. Bisphosphonates and glucocorticoids: effects on bone quality. Arthritis Rheum. 2007;56:3518–22.PubMedCrossRef
14.
van Staa TP, Leufkens HG, Abenhaim L, et al. Use of oral corticosteroids in the United Kingdom. QJM. 2000;93:105–11.PubMedCrossRef
15.
van Staa TP, Laan RF, Barton IP, et al. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum. 2003;48:3224–9.PubMedCrossRef
16.
McKay LI, Cidlowski JA. Cross-talk between nuclear factor-kappa B and the steroid hormone receptors: mechanisms of mutual antagonism. Mol Endocrinol. 1998;12:45–56.PubMedCrossRef
17.
Vayssiere BM, Dupont S, Choquart A, et al. Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol. 1997;11:1245–55.PubMedCrossRef
18.
Buttgereit F, Straub RH, Wehling M, Burmester GR. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum. 2004;50:3408–17.PubMedCrossRef
19.
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;102:274–82.PubMedCrossRef
20.
O’Brien CA, Jia D, Plotkin LI, et al. Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology. 2004;145:1835–41.PubMedCrossRef
21.
Liu Y, Porta A, Peng X, et al. Prevention of glucocorticoid-induced apoptosis in osteocytes and osteoblasts by calbindin-D28k. J Bone Miner Res. 2004;19:479–90.PubMedCrossRef
22.
Yun SI, Yoon HY, Jeong SY, Chung YS. Glucocorticoid induces apoptosis of osteoblast cells through the activation of glycogen synthase kinase 3beta. J Bone Miner Metab. 2009;27:140–8.PubMedCrossRef
23.
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;329:177–81.PubMedCrossRef
24.
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;149:1793–801.PubMedCrossRef
25.
Pereira RC, Delany AM, Canalis E. Effects of cortisol and bone morphogenetic protein-2 on stromal cell differentiation: correlation with CCAAT-enhancer binding protein expression. Bone. 2002;30:685–91.PubMedCrossRef
26.
Butler JS, Queally JM, Devitt BM, et al. Silencing Dkk1 expression rescues dexamethasone-induced suppression of primary human osteoblast differentiation. BMC Musculoskelet Disord. 2010;11:210.PubMedCrossRef
27.
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;76:518–27.PubMedCrossRef
28.
Carcamo-Orive I, Gaztelumendi A, Delgado J, et al. Regulation of human bone marrow stromal cell proliferation and differentiation capacity by glucocorticoid receptor and AP-1 crosstalk. J Bone Miner Res. 2010;25:2115–25.PubMedCrossRef
29.
Hofbauer LC, Gori F, Riggs BL, et al. 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;140:4382–9.PubMedCrossRef
30.
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.PubMedCrossRef
31.
Kim HJ, Zhao H, Kitaura H, et al. Glucocorticoids suppress bone formation via the osteoclast. J Clin Invest. 2006;116:2152–60.PubMedCrossRef
32.
Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007;18:1319–28.PubMedCrossRef
33.
Gillespie LD, Robertson MC, Gillespie WJ, et al.: Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev 2009, (2):CD007146.
34.
Lips P. Relative value of 25(OH)D and 1, 25(OH)2D measurements. J Bone Miner Res. 2009;22:1668–71.CrossRef
35.
Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370:657–66.PubMedCrossRef
36.
Kanis JA, Burlet N, Cooper C, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2008;19:399–428.PubMedCrossRef
37.
Amin S, Lavalley MP, Simms RW, Felson DT. The comparative efficacy of drug therapies used for the management of corticosteroid-induced osteoporosis: a meta-regression. J Bone Miner Res. 2002;17:1512–26.PubMedCrossRef
38.
Reid DM, Hughes RA, Laan RF, et al. 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. 2000;15:1006–13.PubMedCrossRef
39.
Saag KG, Emkey R, Schnitzer TJ, et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med. 1998;339:292–9.PubMedCrossRef
40.
Stoch SA, Saag KG, Greenwald M, et al. Once-weekly oral alendronate 70 mg in patients with glucocorticoid-induced bone loss: a randomized, placebo-controlled clinical trial. J Rheumatol. 2009;36:1705–14.PubMedCrossRef
41.
Wallach S, Cohen S, Reid DM, et al. Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int. 2000;67:277–85.PubMedCrossRef
42.
Fahrleitner-Pammer A, Piswanger-Soelkner JC, Pieber TR, et al. Ibandronate prevents bone loss and reduces vertebral fracture risk in male cardiac transplant patients: a randomized double-blind, placebo-controlled trial. J Bone Miner Res. 2009;24:1335–44.PubMedCrossRef
43.
Yao W, Cheng Z, Pham A, et al. 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;58:3485–97.PubMedCrossRef
44.
Saag KG, Shane E, Boonen S, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357:2028–39.PubMedCrossRef
45.
•• Saag KG, Zanchetta JR, Devogelaer JP, et al.: Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum 2009, 60:3346-55. This article provides the extended results of the randomized controlled trial comparing the anabolic drug teriparatide with the antiresorptive drug alendronate, including data on fracture risk. After 36 months, teriparatide was superior to alendronate in preventing bone loss and in reducing fracture risk in individuals with GIOP.
46.
Langdahl BL, Rajzbaum G, Jakob F, et al. Reduction in fracture rate and back pain and increased quality of life in postmenopausal women treated with teriparatide: 18-month data from the European Forsteo Observational Study (EFOS). Calcif Tissue Int. 2009;85:484–93.PubMedCrossRef
47.
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;151:2641–9.PubMedCrossRef
48.
•• Grossman JM, Gordon R, Ranganath VK, et al.: American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res 2010,62:1515-26. In this article, the new American College of Rheumatology recommendations are presented, offering an up-to-date guideline for GIOP prevention and treatment.
49.
• Netelenbos JC, Geusens PP, Ypma G, Buijs SJ: Adherence and profile of non-persistence in patients treated for osteoporosis-a large-scale, long-term retrospective study in The Netherlands. Osteoporos Int 2010 Sep 14 (Epub ahead of print). Although more knowledge was gained in treatment options for GIOP, this study showed that persistence to osteoporosis medication still is an important factor in daily practice.
50.
de Bekker-Grob EW, Essink-Bot ML, Meerding WJ, Koes BW, Steyerberg EW. Preferences of GPs and patients for preventive osteoporosis drug treatment: a discrete-choice experiment. Pharmacoeconomics. 2009;27:211–9.PubMedCrossRef
51.
Newman ED, Matzko CK, Olenginski TP, et al. Glucocorticoid-Induced Osteoporosis Program (GIOP): a novel, comprehensive, and highly successful care program with improved outcomes at 1 year. Osteoporos Int. 2006;17:1428–34.PubMedCrossRef
Metadata
Title
Advances in Glucocorticoid-Induced Osteoporosis
Authors
Debby den Uyl
Irene E. M. Bultink
Willem F. Lems
Publication date
01-06-2011
Publisher
Current Science Inc.
Published in
Current Rheumatology Reports / Issue 3/2011
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-011-0173-y

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