Clinical Rheumatology

, Volume 26, Issue 2, pp 144–153 | Cite as

Prevention and treatment strategies for glucocorticoid-induced osteoporotic fractures

  • Margaret Gourlay
  • Nora Franceschini
  • Yevgeniy Sheyn
Review

Abstract

Glucocorticoids are the most common cause of drug-related osteoporosis. We reviewed current evidence on risk factors for glucocorticoid-induced osteoporosis (GIOP) and prevention and treatment of GIOP-related fractures. Guidelines for GIOP management published since 2000 were also reviewed. Significant bone loss and increased fracture risk is seen with daily prednisone doses as low as 5 mg. Alternate-day glucocorticoid therapy can lead to similar bone loss. No conclusive evidence exists for a safe minimum dose or duration of glucocorticoid exposure. Physicians should consider risk factors for involutional osteoporosis such as older age, postmenopausal status, and baseline bone density measurements as they assess patients for prevention or treatment of GIOP. Bisphosphonates were reported to reduce GIOP-related vertebral fractures, but inconclusive data exist for hip fractures associated with glucocorticoid use. Hormone replacement therapy and parathyroid hormone analogs are effective in preserving bone density in GIOP. The risk of osteoporosis and fractures should be routinely assessed in patients receiving glucocorticoid therapy. Effective prevention and treatment options are available and can result in meaningful reduction of GIOP-related morbidity and mortality. Current guidelines for GIOP management recommend bisphosphonates, especially alendronate and risedronate, as first-line agents for GIOP, and these guidelines propose the preventive use of bisphosphonates early in the course of glucocorticoid therapy in high-risk patient subgroups.

Keywords

Fracture Glucocorticoid Osteoporosis Prevention Treatment 

Notes

Acknowledgements

Dr. Gourlay is supported by the University of North Carolina Program in Translational Science. Dr Franceschini is supported by the Center for Excellence in Pharmacoepidemiology in the UNC School of Public Health. Dr. Sheyn is supported by an NIH T32 Training grant.

References

  1. 1.
    van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787PubMedCrossRefGoogle Scholar
  2. 2.
    van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford) 39:1383–1389CrossRefGoogle Scholar
  3. 3.
    Gluck OS, Murphy WA, Hahn TJ, Hahn B (1981) Bone loss in adults receiving alternate day glucocorticoid therapy. A comparison with daily therapy. Arthritis Rheum 24:892–898PubMedGoogle Scholar
  4. 4.
    Ruegsegger P, Medici TC, Anliker M (1983) Corticosteroid-induced bone loss. A longitudinal study of alternate day therapy in patients with bronchial asthma using quantitative computed tomography. Eur J Clin Pharmacol 25:615–620PubMedCrossRefGoogle Scholar
  5. 5.
    Hubbard RB, Smith CJ, Smeeth L, Harrison TW, Tattersfield AE (2002) Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med 166:1563–1566PubMedCrossRefGoogle Scholar
  6. 6.
    Israel E, Banerjee T, Fitzmaurice G, Kotlov T, LaHive K, LeBoff M (2001) Effects of inhaled glucocorticoids in premenopausal women. N Engl J Med 345:941–947PubMedCrossRefGoogle Scholar
  7. 7.
    Wong CA, Walsh LJ, Smith CJ, Wisniewski A, Lewis S, Hubbard R, Cawte S, Green D, Pringle M, Tattersfield AE (2000) Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet 355:1399–1403PubMedCrossRefGoogle Scholar
  8. 8.
    Ettinger B, Pressman A, Shah H (2001) Who bears responsibility for glucocorticoid-exposed patients in a large health maintenance organization. J Manag Care Pharm 7(3):228–232Google Scholar
  9. 9.
    Walsh LJ, Wong CA, Pringle M, Tattersfield AE (1996) Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross sectional study. BMJ 313:344–346PubMedGoogle Scholar
  10. 10.
    Gudbjornsson B, Juliusson UI, Gudjonsson FV (2002) Prevalence of long term steroid treatment and the frequency of decision making to prevent steroid induced osteoporosis in daily clinical practice. Ann Rheum Dis 61:32–36PubMedCrossRefGoogle Scholar
  11. 11.
    Kanis JA, Johansson H, Oden A, Johnell O, De Laet C, Melton IL, Tenenhouse A, Reeve J, Silman AJ, Pols HA, Eisman JA, McCloskey EV, Mellstrom D (2004) A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 19:893–899PubMedCrossRefGoogle Scholar
  12. 12.
    Hooyman J, Melton L, Nelson A, O’Fallon W, Riggs B (1984) Fractures after rheumatoid arthritis: a population-based study. Arthritis Rheum 27:1353–1361PubMedGoogle Scholar
  13. 13.
    Dykman TR, Haralson KM, Gluck OS, Murphy WA, Teitelbaum SL, Hahn TJ, Hahn BH (1984) Effect of oral 1,25-dihydroxyvitamin D and calcium on glucocorticoid-induced osteopenia in patients with rheumatic diseases. Arthritis Rheum 27:1336–1343PubMedGoogle Scholar
  14. 14.
    Tobias JH (1999) Management of steroid-induced osteoporosis: what is the current state of play? Rheumatology (Oxford) 38:198–201CrossRefGoogle Scholar
  15. 15.
    van Everdingen A, Jacobs J, Siewertsz Van Reesema D, Bijlsma J (2002) Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 136:1–12PubMedGoogle Scholar
  16. 16.
    Walsh LJ, Lewis SA, Wong CA, Cooper S, Oborne J, Cawte SA, Harrison T, Green DJ, Pringle M, Hubbard R, Tattersfield AE (2002) The impact of oral corticosteroid use on bone mineral density and vertebral fracture. Am J Respir Crit Care Med 166(5):691–695PubMedCrossRefGoogle Scholar
  17. 17.
    Shane E, Rivas M, Silverberg S, Kim T, Taron R, Bilezikian J (1993) Osteoporosis after cardiac transplantation. Am J Med 94:257–264PubMedCrossRefGoogle Scholar
  18. 18.
    Mikuls T, Julian B, Bartolucci A, Saag K (2003) Bone mineral density changes within six months of renal transplantation. Transplantation 75:49–54PubMedCrossRefGoogle Scholar
  19. 19.
    Cortet B, Guyot M-H, Solau E, Pigny P, Dumoulin F, Flipo R-M (2000) Factors influencing bone loss in rheumatoid arthritis: a longitudinal study. Clin Exp Rheumatol 18:683–690PubMedGoogle Scholar
  20. 20.
    Gough A, Lilley J, Eyre S, Holder R, Emery P (1994) Generalised bone loss in patients with early rheumatoid arthritis. Lancet 344:23–27PubMedCrossRefGoogle Scholar
  21. 21.
    Van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C (2003) Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 48:3224–3229PubMedCrossRefGoogle Scholar
  22. 22.
    McKenzie R, Reynolds JC, O’Fallon A, Dale J, Deloria M, Blackwelder W, Straus SE (2000) Decreased bone mineral density during low dose glucocorticoid administration in a randomized, placebo controlled trial. J Rheumatol 27:2222–2226PubMedGoogle Scholar
  23. 23.
    Laan RF, van Riel PL, van de Putte LB, van Erning LJ, van’t Hof MA, Lemmens JA (1993) Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med 119:963–968PubMedGoogle Scholar
  24. 24.
    Maricic M, Gluck O (2004) Densitometry in glucocorticoid-induced osteoporosis. J Clin Densitom 7:359–363PubMedCrossRefGoogle Scholar
  25. 25.
    Ton F, Gunawardene S, Lee H, Neer R (2005) Effects of low-dose prednisone on bone metabolism. J Bone Miner Res 20:464–470PubMedCrossRefGoogle Scholar
  26. 26.
    van Staa TP, Leufkens H, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000PubMedCrossRefGoogle Scholar
  27. 27.
    Saag KG, Koehnke R, Caldwell JR, Brasington R, Burmeister LF, Zimmerman B, Kohler JA, Furst DE (1994) Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 96:115–123PubMedCrossRefGoogle Scholar
  28. 28.
    Naganathan V, Jones G, Nash P, Nicholson G, Eisman J, Sambrook PN (2000) Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use. Arch Intern Med 160:2917–2922PubMedCrossRefGoogle Scholar
  29. 29.
    Orstavik R, Haugeberg G, Mowinckel P, Hoiseth A, Uhlig T, Falch J, Halse J, McCloskey E, Kvien T (2004) Vertebral deformities in rheumatoid arthritis: a comparison with population-based controls. Arch Intern Med 164:420–425PubMedCrossRefGoogle Scholar
  30. 30.
    Baltzan MA, Suissa S, Bauer DC, Cummings SR (1999) Hip fractures attributable to corticosteroid use. Study of Osteoporotic Fractures Group. Lancet 353:1327PubMedCrossRefGoogle Scholar
  31. 31.
    van Staa TP, Abenhaim L, Cooper C, Zhang B, Leufkens HG (2001) Public health impact of adverse bone effects of oral corticosteroids. Br J Clin Pharmacol 51:601–607PubMedGoogle Scholar
  32. 32.
    Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM (1995) Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 332:767–773PubMedCrossRefGoogle Scholar
  33. 33.
    Dargent-Molina P, Douchin MN, Cormier C, Meunier PJ, Breart G (2002) Use of clinical risk factors in elderly women with low bone mineral density to identify women at higher risk of hip fracture: The EPIDOS prospective study. Osteoporos Int 13:593–599PubMedCrossRefGoogle Scholar
  34. 34.
    van Staa T, Geusens P, Pols H, de Laet C, Leufkens H, Cooper C (2005) A simple score for estimating the long-term risk of fracture in patients using oral glucocorticoids. QJM 98(3):191–198PubMedCrossRefGoogle Scholar
  35. 35.
    No authors listed (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 843:1–129Google Scholar
  36. 36.
    Kanis JA, Johnell O, Oden A, De Laet C, Jonsson B, Dawson A (2002) Ten-year risk of osteoporotic fracture and the effect of risk factors on screening strategies. Bone 30:251–258PubMedCrossRefGoogle Scholar
  37. 37.
    Lambrinoudaki I, Chan DT, Lau CS, Wong RW, Yeung SS, Kung AW (2000) Effect of calcitriol on bone mineral density in premenopausal Chinese women taking chronic steroid therapy. A randomized, double blind, placebo controlled study. J Rheumatol 27:1759–1765PubMedGoogle Scholar
  38. 38.
    Adachi JD, Bensen WG, Bianchi F, Cividino A, Pillersdorf S, Sebaldt RJ, Tugwell P, Gordon M, Steele M, Webber C, Goldsmith CH (1996) Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: a 3 year follow-up. J Rheumatol 23:995–1000PubMedGoogle Scholar
  39. 39.
    Homik J, Suarez-Almazor M, Shea B, Cranney A, Wells G, Tugwell P (2000) Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev 2:CD000952PubMedGoogle Scholar
  40. 40.
    Richy F, Ethgen O, Bruyere O, Reginster J-Y (2004) Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate. Osteoporos Int 15:301–310PubMedCrossRefGoogle Scholar
  41. 41.
    Richy F, Schact E, Bruyere O, Ethgen O, Gourlay M, Reginster J-Y (2005) Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis. Calcif Tissue Int 76:176–186PubMedCrossRefGoogle Scholar
  42. 42.
    Hall GM, Daniels M, Doyle DV, Spector TD (1994) Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids. Arthritis Rheum 37(10):1499–1505PubMedGoogle Scholar
  43. 43.
    Kung AW, Chan TM, Lau CS, Wong RW, Yeung SS (1999) Osteopenia in young hypogonadal women with systemic lupus erythematosus receiving chronic steroid therapy: a randomized controlled trial comparing calcitriol and hormonal replacement therapy. Rheumatology (Oxford) 38(12):1239–1244CrossRefGoogle Scholar
  44. 44.
    Luengo M, Pons F, Martinez de Osaba MJ, Picado C (1994) 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 49(11):1099–1102PubMedCrossRefGoogle Scholar
  45. 45.
    Montemurro L, Schiraldi G, Fraioli P, Tosi G, Riboldi A, Rizzato G (1991) Prevention of corticosteroid-induced osteoporosis with salmon calcitonin in sarcoid patients. Calcif Tissue Int 49(2):71–76PubMedGoogle Scholar
  46. 46.
    Adachi JD, Bensen WG, Bell MJ, Bianchi FA, Cividino AA, Craig GL, Sturtridge WC, Sebaldt RJ, Steele M, Gordon M, Themeles E, Tugwell P, Roberts R, Gent M (1997) Salmon calcitonin nasal spray in the prevention of corticosteroid-induced osteoporosis. Br J Rheumatol 36(2):255–259PubMedCrossRefGoogle Scholar
  47. 47.
    Sambrook P, Birmingham J, Kelly P, Kempler S, Nguyen T, Pocock N, Eisman J (1993) Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin. N Engl J Med 328(24):1747–1752PubMedCrossRefGoogle Scholar
  48. 48.
    Kotaniemi A, Piirainen H, Paimela L, Leirisalo-Repo M, Uoti-Reilama K, Lahdentausta P, Ruotsalainen P, Kataja M, Vaisanen E, Kurki P (1996) Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patients with active rheumatoid arthritis receiving low dose glucocorticoid therapy? J Rheumatol 23(11):1875–1879PubMedGoogle Scholar
  49. 49.
    Cranney A, Welch V, Adachi J, Homik J, Shea B, Suarez-Almazor M, Tugwell P, Wells G (2000) Calcitonin for the treatment and prevention of corticosteroid-induced osteoporosis. Cochrane Database Syst Rev 2:CD001983PubMedGoogle Scholar
  50. 50.
    Tascioglu F, Colak O, Armagan O, Alatas O, Oner C (2005) The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin. Rheumatol Int 26:21–29PubMedCrossRefGoogle Scholar
  51. 51.
    Roux C, Oriente P, Laan R, Hughes RA, Ittner J, Goemaere S, Di Munno O, Pouilles JM, Horlait S, Cortet B (1998) Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. Ciblos Study Group. J Clin Endocrinol Metab 83:1128–1133PubMedCrossRefGoogle Scholar
  52. 52.
    Adachi JD, Bensen WG, Brown J, Hanley D, Hodsman A, Josse R, Kendler DL, Lentle B, Olszynski W, Ste-Marie LG, Tenenhouse A, Chines AA (1997) Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med 337:382–387PubMedCrossRefGoogle Scholar
  53. 53.
    Adachi JD, Roux C, Pitt PI, Cooper C, Moniz C, Dequeker J, Ioannidis G, Cawley MI, Jenkins EA, Walker-Bone KE, Pack S, Stephenson GF, Laan RF, Brown J, Geusens P (2000) A pooled data analysis on the use of intermittent cyclical etidronate therapy for the prevention and treatment of corticosteroid induced bone loss. J Rheumatol 27:2424–2431PubMedGoogle Scholar
  54. 54.
    Campbell I, Douglas J, Francis R, Prescott R, Reid D (2004) Five year study of etidronate and/or calcium as prevention and treatment for osteoporosis and fractures in patients with asthma receiving long term oral and/or inhaled glucocorticoids. Thorax 59:761–768PubMedCrossRefGoogle Scholar
  55. 55.
    Adachi JD, Saag KG, Delmas PD, Liberman UA, Emkey RD, Seeman E, Lane NE, Kaufman JM, Poubelle PE, Hawkins F, Correa-Rotter R, Menkes CJ, Rodriguez-Portales JA, Schnitzer TJ, Block JA, Wing J, McIlwain HH, Westhovens R, Brown J, Melo-Gomes JA, Gruber BL, Yanover MJ, Leite MO, Siminoski KG, Nevitt MC, Sharp JT, Malice MP, Dumortier T, Czachur M, Carofano W, Daifotis A (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 44:202–211PubMedCrossRefGoogle Scholar
  56. 56.
    Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, Thamsborg G, Liberman UA, Delmas PD, Malice MP, Czachur M, Daifotis AG (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med 339:292–299PubMedCrossRefGoogle Scholar
  57. 57.
    Gonnelli S, Rottoli P, Cepollaro C, Pondrelli C, Cappiello V, Vagliasindi M, Gennari C (1997) Prevention of corticosteroid-induced osteoporosis with alendronate in sarcoid patients. Calcif Tissue Int 61:382–385PubMedCrossRefGoogle Scholar
  58. 58.
    Yilmaz L, Ozoran K, Gunduz OH, Ucan H, Yucel M (2001) Alendronate in rheumatoid arthritis patients treated with methotrexate and glucocorticoids. Rheumatol Int 20:65–69PubMedCrossRefGoogle Scholar
  59. 59.
    Wallach S, Cohen S, Reid DM, Hughes RA, Hosking DJ, Laan RF, Doherty SM, Maricic M, Rosen C, Brown J, Barton I, Chines AA (2000) Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int 67:277–285PubMedCrossRefGoogle Scholar
  60. 60.
    Reid DM, Hughes RA, Laan RF, Sacco-Gibson NA, Wenderoth DH, Adami S, Eusebio RA, Devogelaer JP (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 15:1006–1013PubMedCrossRefGoogle Scholar
  61. 61.
    Cohen S, Levy RM, Keller M, Boling E, Emkey RD, Greenwald M, Zizic TM, Wallach S, Sewell KL, Lukert BP, Axelrod DW, Chines AA (1999) Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 42:2309–2318PubMedCrossRefGoogle Scholar
  62. 62.
    Ringe J, Dorst A, Faber H, Ibach K, Sorenson F (2003) Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study. Osteoporos Int 14:801–807PubMedCrossRefGoogle Scholar
  63. 63.
    Boutsen Y, Jamart J, Esselinckx W, Devogelaer JP (2001) 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 16:104–112PubMedCrossRefGoogle Scholar
  64. 64.
    Homik J, Cranney A, Shea B, Tugwell P, Wells G, Adachi R, Suarez-Almazor M (2000) Bisphosphonates for steroid-induced osteoporosis. Cochrane Database Syst Rev 2:CD001347PubMedGoogle Scholar
  65. 65.
    Lane NE, Sanchez S, Modin GW, Genant HK, Pierini E, Arnaud CD (2000) 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 15:944–951PubMedCrossRefGoogle Scholar
  66. 66.
    Compston J (2004) US and UK guidelines for glucocorticoid-induced osteoporosis: similarities and differences. Curr Rheumatol Rep 6:66–69PubMedGoogle Scholar
  67. 67.
    American College of Rheumatology (2001) Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 44:1496–1503CrossRefGoogle Scholar
  68. 68.
    Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Zuzuki Y, Tanaka H, Fujiwara S, Miki T, Sagawa A, Nishizawa Y, Seino Y (2005) Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004). J Bone Miner Metab 23:105–109PubMedCrossRefGoogle Scholar
  69. 69.
    Sambrook P, Diamond T, Ferris L, Fiatarone-Singh M, Flicker L, MacLennan A, Nowson C, O’Neill S, Greville H (2001) Corticosteroid induced osteoporosis. Guidelines for treatment. Aust Fam Physician 30:793–796PubMedGoogle Scholar
  70. 70.
    Guidelines working group for the Bone and Tooth Society, National Osteoporosis Society and Royal College of Physicians (2002) Glucocorticoid-induced osteoporosis: guidelines for prevention and treatment. Royal College of Physicians, London, UKGoogle Scholar
  71. 71.
    Geusens PP, de Nijs RN, Lems WF, Laan RF, Struijs A, van Staa TP, Bijlsma JW (2004) Prevention of glucocorticoid osteoporosis: a consensus document of the Dutch Society for Rheumatology. Ann Rheum Dis 63:324–325PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2006

Authors and Affiliations

  • Margaret Gourlay
    • 1
  • Nora Franceschini
    • 2
  • Yevgeniy Sheyn
    • 3
  1. 1.Department of Family MedicineUniversity of North CarolinaChapel HillUSA
  2. 2.Department of Epidemiology, School of Public HealthUniversity of North CarolinaChapel HillUSA
  3. 3.Division of Rheumatology, School of MedicineUniversity of North CarolinaChapel HillUSA

Personalised recommendations