Skip to main content
Log in

Pathogenesis and Treatment of Glucocorticoid-Induced Osteoporosis

  • Review Article
  • Adverse Effects
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Summary

Aging is associated with a marked decline in bone mineral density (BMD), an increased likelihood of falling and a much greater propensity for fracture. Several factors contribute to aging-related bone loss, including reduced bone formation, increased bone resorption, recent bodyweight loss, poor nutritional status and the coexistence of other, often rheumatological, conditions. Any of these factors can lead to an uncoupling of the bone remodelling unit. In addition, the frequent use of glucocorticoids to treat a vast array of conditions has contributed to an ever-expanding group of elderly individuals who are at extremely high risk for spine and hip fractures. Owing to the surprisingly high morbidity and mortality associated with these fractures in the elderly, an understanding of the pathogenesis and epidemiology of glucocorticoid-induced osteoporosis is paramount. The factors that contribute to bone loss in older individuals treated with glucocorticoids include reduced muscle mass, poor nutrition, hypogonadism, vitamin D deficiency and secondary hyperparathyroidism. Recent studies suggest that a prophylactic approach to this problem could have a huge impact on the medical, social and economic costs of osteoporosis.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cushing H. Basophil adenomas of the pituitary body and their clinical manifestations. Bull Johns Hopkins Hosp 1932; 50: 137–95

    Google Scholar 

  2. Adler RA, Rosen CJ. Glucocorticoids and osteoporosis. Endocrinol Metab Clin 1994; 23: 641–54

    CAS  Google Scholar 

  3. Hui SL, Slemenda CW, Johnston CC. Baseline measurement of bone mass predicts fracture in white women. Ann Intern Med 1989; 11: 355–61

    Google Scholar 

  4. Kiel DP. The approach to osteoporosis in the elderly patient. In: Rosen CJ, editor. Osteoporosis: diagnostic and therapeutic principles. Totowa (NJ): Humana Press, 1996: 225–39

    Google Scholar 

  5. Hui SL, Wiske PS, Norton JA. A prospective study of change in bone mass with age in postmenopausal women. J Chronic Dis 1982; 35: 715–25

    Article  PubMed  CAS  Google Scholar 

  6. Cummings SR, Nevitt MC, Browner WS. Risk factors for hip fractures in white women. N Engl J Med 1995; 332: 767–73

    Article  PubMed  CAS  Google Scholar 

  7. Greenspan SL, Maitland LA, Myers ER, et al. Femoral bone loss progress with age: a longitudinal study in women over age 65. J Bone Miner Res 1994; 9: 1959–65

    Article  PubMed  CAS  Google Scholar 

  8. Ravn P, Hetland ML, Overgaard K, et al. Premenopausal and postmenopausal changes in BMD of the proximal femur measured by dual energy X-ray absorptiometry. J Bone Miner Res 1994; 9: 1975–80

    Article  PubMed  CAS  Google Scholar 

  9. Garnero P, Shih WG, Gineyts E, et al. Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate. J Clin Endocrinol Metab 1994; 79: 1693–700

    Article  PubMed  CAS  Google Scholar 

  10. Jones G, Nguyen T, Sambrook P, et al. Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study. BMJ 1994; 309: 691–5

    Article  PubMed  CAS  Google Scholar 

  11. Kessenich CR, Rosen CJ. The pathophysiology of osteoporosis. In: Rosen CJ, editor. Osteoporosis: diagnostic and therapeutic principles. Totowa (NJ): Humana Press, 1996: 47–63

    Google Scholar 

  12. Dawson-Hughes B, Dallai GE, Krall EA, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 1990; 323: 878–83

    Article  PubMed  CAS  Google Scholar 

  13. NIH Consensus Conference: optimal calcium intake. JAMA 1995; 272: 1942–8

    Google Scholar 

  14. Doppelt SH, Neer RM, Daly M, et al. Vitamin D deficiency and osteomalacia in patients with hip fractures. Orthop Trans 1983; 7: 512–3

    Google Scholar 

  15. Sowers MF, Wallace RB, Hollis BW, et al. Parameters related to 25 OHD levels in a population based study of women. Am J Clin Nutr 1986; 43: 621–8

    PubMed  CAS  Google Scholar 

  16. Rosen CJ. The role of insulin-like growth factor in senescence: clues for interventional strategies in the elderly. Endocrinologist 1996; 6: 102–8

    Article  Google Scholar 

  17. Hayden JM, Mohan S, Baylink DJ. The insulin like growth factor system and the coupling of formation to resorption. Bone 1994; 17: 93S–8S

    Article  Google Scholar 

  18. Rosen CJ, Donahue LR, Hunter SJ. IGFs and bone: the osteoporosis connection. Proc Soc Exp Biol Med 1994; 206: 83–103

    Article  PubMed  CAS  Google Scholar 

  19. Rudman D. Growth hormone, body composition and aging. J Am Geriatr Soc 1985; 33: 800–7

    PubMed  CAS  Google Scholar 

  20. Mohan S, Farley J, Baylink DJ. Age-related changes in IGFBP-4 and IGFBP-5 in human serum and bone: implications for the bone loss of aging. Prog Growth Factor Res 1995; 4: 465–73

    Article  Google Scholar 

  21. Rosen CJ, Donahue LR, Hunter SJ, et al. The 24/25 kD IGFBP is increased in elderly women with hip and spine fractures. J Clin Endocrinol Metab 1992; 74: 24–7

    Article  PubMed  CAS  Google Scholar 

  22. Rajaram S, Baylink DJ, Mohan S. IGFBPs in serum and other biological fluids: regulation and function. Endocr Rev 1997; 18: 801–32

    Article  PubMed  CAS  Google Scholar 

  23. Lukert BP, Kream BE. Clinical and basic aspects of glucocorticoid action in bone. In: Bilezikian JP, Raisz LG, Rodan G, editors. Principles of bone biology. San Diego (CA): Academic Press, 1996: 533–48

    Google Scholar 

  24. Canalis E. Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity and DNA content in cultured rat calvariae. Endocrinology 1988; 112: 931–5

    Article  Google Scholar 

  25. Dempster D. Bone histomorphometry in glucocorticoid-induced osteoporosis. J Bone Miner Res 1989; 4: 137–41

    Article  PubMed  CAS  Google Scholar 

  26. Delaney AM, Gabbitas BY, Canalis E. Cortisol down regulates osteoblast alpha I procollagen mRNA by transcriptional and post transcriptional mechanisms. J Cell Biochem 1995; 57: 488–94

    Article  Google Scholar 

  27. McCarthy TL, Centrella M, Canalis E. Cortisol inhibits synthesis of IGF-I in skeletal cells. Endocrinology 1990; 126: 1569–75

    Article  PubMed  CAS  Google Scholar 

  28. Conover CA, Bale LK, Clarkson JT. Regulation of IGFBP-5 messenger RNA expression and protein availability in rat osteoblastic like cells. Endocrinology 1993; 132: 2525–30

    Article  PubMed  CAS  Google Scholar 

  29. Godshalk MF, Downs RW. Effect of short term glucocorticoids on serum osteocalcin in healthy young men. J Bone Miner Res 1988; 3: 113–5

    Article  Google Scholar 

  30. Morris HA, Need AG, O’Loughlin PD, et al. Malabsorption of calcium in corticosteroid induced osteoporosis. Calcif Tissue Int 1990; 46: 305–8

    Article  PubMed  CAS  Google Scholar 

  31. Suzuki Y, Ichikawa Y, Saito E, et al. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients undergoing glucocorticoid therapy. Metabolism 1983; 32: 151–6

    Article  PubMed  CAS  Google Scholar 

  32. Delaney AM, Dong Y, Canalis E. Mechanisms of glucocorticoid action in bone cells. J Cell Biochem 1994; 56: 295–302

    Article  Google Scholar 

  33. Libanti CR, Baylink DJ. Prevention and treatment of glucocorticoid-induced osteoporosis. Chest 1992; 102: 1426–35

    Article  Google Scholar 

  34. MacAdams MR, White RH, Chipps BE. Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med 1986; 104: 648–51

    PubMed  CAS  Google Scholar 

  35. Manolagas SC, Jilka RL. Bone marrow, cytokines and bone remodeling. N Engl J Med 1995; 332: 305–11

    Article  PubMed  CAS  Google Scholar 

  36. Keene G, Parker M, Pryor G. Mortality and morbidity after hip fractures. BMJ 1993; 307: 1248–50

    Article  PubMed  CAS  Google Scholar 

  37. Myers AH, Robinson EG, Van Natta ML, et al. Hip fractures among the elderly: factors associated with in-hospital mortality. Am J Epidemiol 1991; 134: 1128–37

    PubMed  CAS  Google Scholar 

  38. US Congress of Technology Assessment. Hip fracture outcomes in people age 50 and over. Washington, DC: US Government Printing Office, 1994: OTA-BP-H 120

  39. Riggs BL, Wahner HW, Seeman E, et al. Changes in BMD of the proximal femur and spine with aging. J Clin Invest 1982; 70: 716–23

    Article  PubMed  CAS  Google Scholar 

  40. Kanis JA, Delmas P, Burckhardt P, et al. Guidelines for diagnosis and management of osteoporosis. Osteoporos Int 1997; 7: 390–6

    Article  PubMed  CAS  Google Scholar 

  41. Cooper C, Campion G, Melton LJ. Hip fractures in the elderly: a worldwide projection. Osteoporos Int 1992; 2: 285–9

    Article  PubMed  CAS  Google Scholar 

  42. Verstraeten A, Dequeker J. Vertebral and peripheral bone mineral content and fracture evidence in postmenopausal patients with rheumatoid arthritis: effects of low dose steroids. Ann Rheum Dis 1986; 45: 852–7

    Article  PubMed  CAS  Google Scholar 

  43. Michel BA, Block DA, Fries JF. Predictors of fracture in early rheumatoid arthritis. J Rheumatol 1991; 18: 804–8

    PubMed  CAS  Google Scholar 

  44. Cooper C, Coupland C, Mitchell M. Rheumatoid arthritis, corticosteroid therapy, and hip fracture. Ann Rheum Dis 1994; 53: 49–52

    Google Scholar 

  45. Saag KJ, Koehnke R, Caldwell JR, et al. Low dose long term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 1994; 96: 115–23

    Article  PubMed  CAS  Google Scholar 

  46. Hanania NA, Chapman KR, Sturtridge WC, et al. Dose related decrease in bone density among asthmatic patients treated with inhaled corticosteroids. J Allergy Clin Immunol 1995; 96 (5 Pt 1): 571–9

    Article  PubMed  CAS  Google Scholar 

  47. Adinoff AD, Hollister JR. Steroid induced fractures and bone loss in patients with asthma. N Engl J Med 1983; 309: 265–8

    Article  PubMed  CAS  Google Scholar 

  48. Walsh LJ, Wong CA, Pringle M, et al. Use of oral glucocorticoids in the community and the prevention of secondary osteoporosis. BMJ 1996; 313: 344–6

    Article  PubMed  CAS  Google Scholar 

  49. Lems WF, Jahangier ZN, Jacobs JWG, et al. Vertebral fractures with rheumatoid arthritis patients treated with corticosteroids. Clin Exp Rheumatol 1995; 13: 293–7

    PubMed  CAS  Google Scholar 

  50. Wolfe AM. The epidemiology of rheumatoid arthritis: a review. Bull Rheum Dis 1968; 19: 518–28

    PubMed  CAS  Google Scholar 

  51. Chuang TY, Hunder GG, Ilstrup DM, et al. Polymyalgia rheumatica: a 10 yr epidemiologic and clinical study. Ann Intern Med 1982; 97: 672–7

    PubMed  CAS  Google Scholar 

  52. Spector TD, Hall GM, McCloskey EV, et al. Risk of vertebral fracture in women with rheumatoid arthirits. BMJ 1993; 306: 558–68

    Article  PubMed  CAS  Google Scholar 

  53. Cooper CC, Wickham C. Rheumatoid arthritis, corticosteroid therapy and hip fracture. In: Christiansen C, Overgaard K, editors. Osteoporosis. Copenhagen: Osteopress, 1990

    Google Scholar 

  54. Laan RFJM, Bujjs WCAM, Verbeek ALM, et al. Bone mineral density in patients with recent onset of rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis 1993; 52: 21–6

    Article  PubMed  CAS  Google Scholar 

  55. Dykman TR, Gluck OS, Murphy WA, et al. Evaluation of factors associated with glucocorticoid induced osteopenia in patients with rheumatic diseases. Arthritis Rheum 1985; 28: 361–81

    Article  PubMed  CAS  Google Scholar 

  56. Hall GM, Spector TD, Griffin JA, et al. The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women. Arthritis Rheum 1993; 36: 1510–6

    Article  PubMed  CAS  Google Scholar 

  57. Manning PJ, Evans MR, Reid IR. Normal bone density following cure of Cushing’s syndrome. Clin Endocrinol 1992; 36: 229–54

    Article  CAS  Google Scholar 

  58. Laan RF, van Riel PL, va de Putte LB, et al. Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis: a randomized, controlled study. Ann Intern Med 1993 Nov 15; 119(10): 963–8

    PubMed  CAS  Google Scholar 

  59. Adachi JD, Bessen WD, Brown J, et al. Intermittent etidronate to prevent corticosteroid induced osteoporosis. N Engl J Med 1997; 337: 382–7

    Article  PubMed  CAS  Google Scholar 

  60. Schnitzer TJ. Alendronate and glucocorticoid induced osteoporosis [abstract 1174]. Arthritis Rheum 1997; 40 (9 Suppl. 2)

    Google Scholar 

  61. Sambrook P, Birmingham J, Kelly P, et al. Prevention of corticosteroid induced osteoporosis. N Engl J Med 1993; 328: 1747–52

    Article  PubMed  CAS  Google Scholar 

  62. Gallacher SJ, Fenner JAK, Anderson K, et al. Intravenous pamidronate in the treatment of osteoporosis associated with corticosteroid dependent lung disease: an open pilot study. Thorax 1992; 47: 932–6

    Article  PubMed  CAS  Google Scholar 

  63. Mulder H, Struys A. Intermittent cyclical etidronate in the prevention of corticosteroid induced bone loss. Br J Rheum 1994; 33: 348–50

    Article  CAS  Google Scholar 

  64. Diamond T, McGuigan L, Barbagallo S, et al. Cyclical etidronate plus ergocalciferol prevents glucocorticoid induced bone loss in postmenopausal women. Am J Med 1995; 98: 459–63

    Article  PubMed  CAS  Google Scholar 

  65. Grecu EO, Simmons R, Baylink DJ, et al. Effects of medroxyprogesterone on some parameters of calcium metabolism in patients with glucocorticoid induced osteoporosis. Bone Miner 1991; 13: 153–61

    Article  PubMed  CAS  Google Scholar 

  66. Lukert BP, Johnson BE, Robinson RG. Estrogen and progesterone replacement therapy reduces glucocorticoid induced bone loss. J Bone Miner Res 1992; 7: 1063–9

    Article  PubMed  CAS  Google Scholar 

  67. Buckley LM, Leib ES, Cartularo KS, et al. 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 1996 Dec 15; 125: 961–8

    PubMed  CAS  Google Scholar 

  68. Healey JH, Paget SA, Williamsrusso P, et al. A randomized placebo-controlled trial of salmon calcitonin for bone loss in glucocorticoid-treated temporal arteritis and polymyalgia rheumatica. Calcif Tissue Int 1996; 58: 73–80

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Clifford J. Rosen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rackoff, P.J., Rosen, C.J. Pathogenesis and Treatment of Glucocorticoid-Induced Osteoporosis. Drugs & Aging 12, 477–484 (1998). https://doi.org/10.2165/00002512-199812060-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199812060-00005

Keywords

Navigation