Skip to main content
SpringerLink
Log in

Corticosteroid-Induced Osteoporosis

A Guide to Optimum Management

  • Therapy In Practice
  • Published:
Treatments in Endocrinology

Abstract

Corticosteroid-induced osteoporosis is the leading cause of secondary osteoporosis and a significant cause of morbidity in both men and women. Long-term use of even low-dose corticosteroids has been associated with increased risk of bone loss. Recent large randomized controlled trials have generated new knowledge on treatment strategies for patients with corticosteroid-induced osteoporosis. However, the majority of individuals receiving corticosteroids are not receiving prophylaxis for osteoporosis.

Calcium and vitamin D should be recommended to patients initiating therapy with corticosteroids (and should be adequate for those receiving corticosteroids for less than 3 months). For those receiving corticosteroids for greater than 3 months, bisphosphonates are the therapy of choice, with both alendronate (alendronic acid) and risedronate (risedronic acid) approved by the US FDA for use in this indication. Calcitonin can be considered a second-line agent and should be reserved for patients who are intolerant of bisphosphonates or who are experiencing pain from a vertebral fracture. Hormone replacement therapy or testosterone therapy may be offered to those individuals on long-term corticosteroid treatment who are hypogonadal. Teriparatide (recombinant human parathyroid hormone 1-34) shows promise as a future anabolic agent for the prevention and treatment of patients with corticosteroid-induced osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Zelissen PMJ, Croughs RJM, van Rijk PP, et al. Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison disease. Ann Intern Med 1994; 120: 207–10

    PubMed  CAS  Google Scholar 

  2. Ettinger B, Chidambaran P, Pressman A. Prevalence and determinants of osteoporosis drug prescription among patients with high exposure to glucocorticoid drugs. Am J Manag Care 2001; 7(6): 597–605

    PubMed  CAS  Google Scholar 

  3. Walsh LJ, Wong CA, Pringle M, et al. Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross-sectional study. BMJ 1996; 313: 344–6

    Article  PubMed  CAS  Google Scholar 

  4. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 1990; 112(5): 352–64

    PubMed  CAS  Google Scholar 

  5. Saito JK, Davis JW, Wasnich RD, et al. Users of low doses glucocorticoids have increased bone loss rates: a longitudinal study. Calcif Tissue Int 1995; 57: 115–9

    Article  PubMed  CAS  Google Scholar 

  6. Adachi JD, Bensen WG, Bell MJ, et al. Corticosteroid induced osteoporosis: follow-up over 3 years. In: Christiansen C, Overgaard K, editors. Osteoporosis 1990. Copenhagen: Osteopress ApS, 1990: 1745–7

    Google Scholar 

  7. Hahn TJ, Boisveau VC, Avioli LV. Effect of chronic corticosteroid administration on diaphyseal and metaphyseal bone mass. J Clin Endocrinol Metab 1974; 39: 274–82

    Article  PubMed  CAS  Google Scholar 

  8. Sambrook P, Birmingham J, Kelly P, et al. Prevention of corticosteroid osteoporosis: a comparison of calcium, calcitriol, and calcitonin. N Engl J Med 1993; 328(24): 1747–52

    Article  PubMed  CAS  Google Scholar 

  9. Adachi JD, Bensen WG, Brown J, et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med 1997; 337(6): 382–7

    Article  PubMed  CAS  Google Scholar 

  10. Baltzan MA, Suissa S, Bauer DC, et al. Hip fractures attributable to corticosteroid use. Lancet 1999; 353: 1327

    Article  PubMed  CAS  Google Scholar 

  11. van Staa TP, Leufkens HG, Abenhaim L, et al. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxf) 2000; 39(12): 1383–9

    Article  Google Scholar 

  12. Israel E, Banerjee TR, Fitzmaurice GM, et al. Effect of inhaled glucocorticoids on bone density in premenopausal women. N Engl J Med 2001; 345(13): 941–7

    Article  PubMed  CAS  Google Scholar 

  13. Jones A, Fay JK, Stone M, et al. Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 1. Oxford: Update Software, 2001

    Google Scholar 

  14. Schwid SR, Goodman AD, Puzas E, et al. Sporadic corticosteroid pulses and osteoporosis in multiple sclerosis. Arch Neurol 1996; 53: 753–7

    Article  PubMed  CAS  Google Scholar 

  15. Buckley LM, Marquez M, Feezor R, et al. Prevention of corticosteroid-induced osteoporosis: results of a patient survey. Arthritis Rheum 1999; 42(8): 1736–9

    Article  PubMed  CAS  Google Scholar 

  16. Hahn TJ, Hahn BH. Osteopenia in patients with rheumatic diseases: principles of diagnosis and therapy. Semin Arthritis Rheum 1976; 6: 165–88

    Article  PubMed  CAS  Google Scholar 

  17. Lukert BP, Adams JS. Calcium and phosphorus homeostasis in man: effect of corticosteroids. Arch Intern Med 1976; 136: 1249–53

    Article  PubMed  CAS  Google Scholar 

  18. Fucik RF, Kukreja SC, Hargis GK, et al. Effect of glucocorticoids on function of the parathyroid glands in man. J Clin Endocrinol Metab 1975; 40: 152–5

    Article  PubMed  CAS  Google Scholar 

  19. Pearce G, Tabensky DA, Delmas PD, et al. Corticosteroid-induced bone loss in men. J Clin Endocrinol Metab 1998; 83: 801–6

    Article  PubMed  CAS  Google Scholar 

  20. Williams GA, Bowser EN, Henderson WJ, et al. Calcium absorption in the rat in relation to excessive vitamin D and cortisone. Proc Soc Exp Biol Med 1960; 5: 354–8

    Google Scholar 

  21. Sjoberg HE. Retention of orally administered 47-calcium in man under normal diseased conditions studies with a whole-body counter technique. Acta Med Scand 1970; (509): 1-28

  22. Favus NJ, Kimberg DV, Miller GN, et al. Effects of cortisone administration on the metabolism and localization of 25-hydroxycholecalciferol in the rat. J Clin Invest 1973; 52: 1328–35

    Article  PubMed  CAS  Google Scholar 

  23. Nielsen HK, Charles P, Moskelide L. The effect of single oral doses of prednisone on the circadian rhythm of serum osteocalcin in normal subjects. J Clin Endocrinol Metab 1988; 67: 1025–30

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Ishida Y, Heersche JNM. Glucocorticoid-induced osteoporosis: both in vivo and in vitro concentrations of glucocorticoids higher than physiological levels attenuate osteoblast differentiation. J Bone Miner Res 1998; 13: 1822–6

    Article  PubMed  CAS  Google Scholar 

  26. Dempster DW, Arlot MA, Meunier PJ. Mean wall thickness and formation periods of trabecular bone packets in corticosteroid-induced osteoporosis. Calcif Tissue Int 1983; 35(4–5): 410–7

    Article  PubMed  CAS  Google Scholar 

  27. Bressot C, Meunier PJ, Chapuy MC, et al. Histomorphometric profile, pathophysiology and reversibility of corticosteroid-induced osteoporosis. Metab Bone Dis Relat Res 1979; 1: 303–11

    Article  Google Scholar 

  28. Chappard D, Legrand E, Basle MF, et al. Altered trabecular architecture induced by corticosteroids: a bone histomorphometric study. J Bone Miner Res 1996; 11(5): 676–85

    Article  PubMed  CAS  Google Scholar 

  29. Hahn TJ, Halstead LR, Teitelbaum SL, et al. Altered mineral metabolism in glucocorticoid induced osteopenia: effect of 25-hydroxyvitamin D administration. J Clin Invest 1979; 64: 655–65

    Article  PubMed  CAS  Google Scholar 

  30. Chesney RW, Mazess RB, Hamstra AJ. Reduction of serum 1,25-dihydroxyvitamin D in children receiving glucocorticoids. Lancet 1978; II: 1123–5

    Article  Google Scholar 

  31. Godschalk M, Levy M, Downs RW. Glucocorticoids decrease vitamin D receptor numbers and gene expression in human osteosarcoma cells. J Bone Miner Res 1992; 7: 21–7

    Article  PubMed  CAS  Google Scholar 

  32. Sakakura M. Inhibition of luteinizing hormone secretion induced by synthetic LRH by long-term treatment with glucorticoids in human subjects. J Clin Endocrinol Metab 1975; 40: 774–9

    Article  PubMed  CAS  Google Scholar 

  33. Schaison G, Durand F, Nakagawa S. Effect of glucocorticoids on plasma testerone in men. Acta Endocrinol Metab 1987; 89: 126–31

    Google Scholar 

  34. Eastell R, Reid DM, Compston J, et al. A UK Consensus Group on management of glucocorticoid-induced osteoporosis: an update. J Intern Med 1998; 244(4): 271–92

    Article  PubMed  CAS  Google Scholar 

  35. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: American College of Rheumatology Task Force on Osteoporosis guidelines. Arthritis Rheum 1996; 39: 1791-801

  36. American College of Rheumatology Ad hoc committee on glucocorticoid-induced osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 2001; 44(7): 1496–503

    Article  Google Scholar 

  37. Hart SR, Green B. Osteoporosis prophylaxis during corticosteroid treatment: failure to prescribe. Postgrad Med J 2002; 78: 242–3

    Article  PubMed  CAS  Google Scholar 

  38. Ross PD, Davis JW, Epstein RS, et al. Pre-existing fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med 1991; 114: 919–23

    PubMed  CAS  Google Scholar 

  39. Czerwinski SM, Kurowski TG, O’Neill TM, et al. Initiating regular exercise protects against muscle atrophy from glucocorticoids. J Appl Physiol 1987; 63(4): 1504–10

    PubMed  CAS  Google Scholar 

  40. Hickson RC, Kurowski TT, Andrews GH, et al. Glucocorticoid cytosol binding in exercise induced sparing of muscle atrophy. J Appl Physiol 1986; 60: 1413–9

    PubMed  CAS  Google Scholar 

  41. Nelson ME, Fiatarone MA, Morganti CM, et al. Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures: a randomized controlled trial. JAMA 1994; 272: 1909–14

    Article  PubMed  CAS  Google Scholar 

  42. Adachi JD, Bensen WG, Bianchi F, et al. Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: a 3 year follow-up. J Rheumatol 1996; 23(6): 995–1000

    PubMed  CAS  Google Scholar 

  43. Reginster JY, Kuntz D, Verdickt W, et al. Prophylactic use of alfacalcidol in corticosteroid-induced osteporosis. Osteoporos Int 1999; 9: 75–81

    Article  PubMed  CAS  Google Scholar 

  44. Homik J, Suarez-Almazor ME, Shea B, et al. Calcium and vitamin D for corticosteroid-induced osteoporosis. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2001: CD000952

  45. Amin S, LaValley MP, Simms RW, et al. The role of vitamin D in corticosteroid-induced osteoporosis: a meta-analytic approach. Arthritis Rheum 1999; 42(8): 1740–51

    Article  PubMed  CAS  Google Scholar 

  46. Amin S, Lavalley MP, Simms RW, et al. The comparative efficacy of drug therapies used for the management of corticosteroid-induced osteoporosis: a meta-regression. J Bone Miner Res 2002; 17(8): 1512–26

    Article  PubMed  CAS  Google Scholar 

  47. Dykman TR, Haralson KM, Gluck OS, et al. Effect of oral 1,25 dihydroxyvitamin D and calcium on glucocorticoid-induced osteopenia in patients with rheumatic diseases. Arthritis Rheum 1984; 27: 1336–43

    Article  PubMed  CAS  Google Scholar 

  48. Plotkin LI, Weinstein RS, Parfitt AM, et al. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 1999; 104(10): 1363–74

    Article  PubMed  CAS  Google Scholar 

  49. Homik JE, Cranney A, Shea B, et al. A metaanalysis on the use of bisphosphonates in corticosteroid induced osteoporosis. J Rheumatol 1999; 26(5): 1148–57

    PubMed  CAS  Google Scholar 

  50. Homik J, Cranney A, Shea B, et al. Bisphosphonates for steroid-induced osteoporosis. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2002: CD001347

    Google Scholar 

  51. 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(5): 292–9

    Article  PubMed  CAS  Google Scholar 

  52. Jenkins EA, Walker-Bone KE, Wood A, et al. The prevention of corticosteroid induced osteoporosis with intermittent cyclical etidronate. Scand J Rheumatol 1999; 28: 152–6

    Article  PubMed  CAS  Google Scholar 

  53. Skingle SJ, Crisp AJ. Increased bone density in patients on steroids with etidronate. Lancet 1994; 344: 543–4

    Article  PubMed  CAS  Google Scholar 

  54. Roux C, Oriente P, Laan R, et al. Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. Ciblos Study Group. J Clin Endocrinol Metab 1998; 83(4): 1128–33

    Article  PubMed  CAS  Google Scholar 

  55. Cohen S, Levy RM, Keller M, et al. Risedronate therapy prevents corticosteroid-induced bone loss. Arthritis Rheum 1999; 42: 2309–18

    Article  PubMed  CAS  Google Scholar 

  56. Boutsen Y, Jamart J, Esselinckx W, et al. Primary prevention of glucocorticoid-induced osteoporosis with intravenous pamidronate and calcium: a prospective controlled 1-year study comparing a single infusion, an infusion given once every 3 months, and calcium alone. J Bone Miner Res 2001; 16(1): 104–12

    Article  PubMed  CAS  Google Scholar 

  57. Gonnelli S, Rottoli P, Cepollaro C, et al. Prevention of corticosteroid-induced osteoporosis with alendronate in sarcoid patients. Calcif Tissue Int 1997; 61(5): 382–5

    Article  PubMed  CAS  Google Scholar 

  58. Mulder H, Struys A. Intermittent cyclical etidronate in the prevention of corticosteroid-induced bone loss. Br J Rheumatol 1994; 33(4): 348–50

    Article  PubMed  CAS  Google Scholar 

  59. Wolfhagen FH, van Buuren HR, Vleggaar FP, et al. Management of osteoporosis in primary biliary cirrhosis. Baillieres Best Pract Res Clin Gastroenterol 2000; 14(4): 629–41

    Article  PubMed  CAS  Google Scholar 

  60. 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(1): 202–11

    Article  PubMed  CAS  Google Scholar 

  61. Pitt P, Li F, Todd P, et al. A double blind placebo controlled study to determine the effects of intermittent cyclical etidronate on bone mineral density in patients on long term oral corticosteroid treatment. Thorax 1998; 53: 351–6

    Article  PubMed  CAS  Google Scholar 

  62. Worth H, Stammen D, Keck E. Therapy of steroid induced bone loss in adult asthmatics with calcium, vitamin D and a diphosphonate. Am J Respir Crit Care Med 1994; 150: 394–7

    PubMed  CAS  Google Scholar 

  63. Reid IR, Heap SW, King AR, et al. Two-year follow-up of biphosphonate (APD) treatment in steroid osteoporosis [letter]. Lancet 1988; II(8620): 1144

    Article  Google Scholar 

  64. Geusens P, Dequeker J, Vanhoof J, et al. Cyclical etidronate increases bone density in the spine and hip of postmenopausal women receiving long term corticosteroid treatment: a double blind randomised placebo controlled study. Ann Rheum Dis 1998; 57(12): 724–7

    Article  PubMed  CAS  Google Scholar 

  65. Reid DM, Hughes RA, Laan RFJM, et al. Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. J Bone Miner Res 2000; 15(6): 1006–13

    Article  PubMed  CAS  Google Scholar 

  66. Reid DM, Adami S, Devogelaer JP, et al. Risedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy. Calcif Tissue Int 2001; 69: 242–7

    Article  PubMed  CAS  Google Scholar 

  67. Cranney A, Welch V, Adachi JD, et al. Calcitonin for the treatment and prevention of corticosteroid-induced osteoporosis. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2000: CD001983

    Google Scholar 

  68. Luengo M, Pons F, Martinez de Osaba MJ, et al. Prevention of further bone mass loss by nasal calcitonin in patients on long term glucocorticoid therapy for asthma: a two year follow up study. Thorax 1994; 49(11): 1099–102

    Article  PubMed  CAS  Google Scholar 

  69. Ringe JD, Welzel D. Salmon calcitonin in the therapy of corticosteroid-induced osteoporosis. Eur J Clin Pharmacol 1987; 33: 35–9

    Article  PubMed  CAS  Google Scholar 

  70. Kotaniemi A, Piirainen H, Paimela L, et al. Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patients with active rheumatoid arthritis receiving low dose glucocorticoied therapy? J Rheumatol 1996; 23: 1875–9

    PubMed  CAS  Google Scholar 

  71. Healey JH, Paget SA, Williams-Russo P, et al. A randomized controlled trial of salmon calcitonin to prevent bone loss in corticosteroid-treated temporal arteritis and polymyalgia rheumatica. Calcif Tissue Int 1996; 58(2): 73–80

    Article  PubMed  CAS  Google Scholar 

  72. Hall GM, Daniels M, Doyle D, et al. Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids. Arthritis Rheum 1994; 37: 1499–505

    Article  PubMed  CAS  Google Scholar 

  73. Reid IR, Wattie DJ, Evans MC, et al. Testosterone therapy in glucocorticoid-treated men. Arch Intern Med 1996; 156: 1173–7

    Article  PubMed  CAS  Google Scholar 

  74. Adams JS, Wahl TO, Lukert BP. Effects of hydrochlorothiazide and dietary sodium restriction on calcium metabolism in corticosteroid treated patients. Metabolism 1981; 30: 217–21

    Article  PubMed  CAS  Google Scholar 

  75. Lems WF, Jacobs WG, Bijlsma JW, et al. Effect of sodium fluoride on the prevention of corticosteroid-induced osteoporosis. Osteoporos Int 1997; 7(6): 575–82

    Article  PubMed  CAS  Google Scholar 

  76. Lems WF, Jacobs JW, Bijlsma JW, et al. Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid induced osteoporosis? Ann Rheum Dis 1997; 56(6): 357–63

    Article  PubMed  CAS  Google Scholar 

  77. Meys E, Terreaux-Duvert F, Beaume-Six T, et al. Bone loss after cardiac transplantation: effects of calcium, calcidiol and monofluorophosphate. Osteoporos Int 1993; 3(6): 322–9

    Article  PubMed  CAS  Google Scholar 

  78. Lane NE, Sanchez S, Modin GW, et al. Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis: results of a randomized controlled clinical trial. J Clin Invest 1998; 102(8): 1627–33

    Article  PubMed  CAS  Google Scholar 

  79. Lane NE, Sanchez S, Modin G, et al. Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial. J Bone Miner Res 2000; (14): 944-51

  80. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001; 344(19): 1434–41

    Article  PubMed  CAS  Google Scholar 

  81. Adami S, Fossaluzza V, Rossini M, et al. The prevention of corticosteroid-induced osteoporosis with nandrolone decanoate. Bone Miner 1991; 15(1): 73–81

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review/study.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Queen’s University, Etherington Hall, 94 Stuart Street, Kingston, Ontario, K7L 3N6, Canada

    Ann Cranney

  2. Department of Medicine, McMaster University, Hamilton, Ontario, Canada

    Jonathan D. Adachi

Authors
  1. Ann Cranney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan D. Adachi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cranney, A., Adachi, J.D. Corticosteroid-Induced Osteoporosis. Mol Diag Ther 1, 271–279 (2002). https://doi.org/10.2165/00024677-200201050-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00024677-200201050-00001

Keywords

Search

Navigation