Skip to main content
SpringerLink
Log in

Bisphosphonates

Role in Treatment of Corticosteroid-Induced Osteoporosis

  • Review Article
  • Treatment Review
  • Published:
Clinical Immunotherapeutics Aims and scope Submit manuscript

Summary

Bisphosphonates have been shown to be effective in both increasing bone density and reducing vertebral fracture incidence in post-menopausal osteoporosis. Although differences exist between the pathogenesis of corticosteroid-induced osteoporosis and post-menopausal osteoporosis, both exhibit increased bone resorption as one of their major features. This being the case, it might be anticipated that bisphosphonates would be of benefit to patients with corticosteroid-induced osteoporosis.

Evidence to date with cyclical etidronate (etidronic acid) and calcium therapy in patients on long term corticosteroids shows increases in lumbar spine and femoral neck bone mineral densities. In addition, this cyclical etidronate regimen can eliminate the initial phase of fast bone loss associated with corticosteroid therapy. Oral and intravenous pamidronate (pamidronic acid) have also been shown to be associated with spinal bone density gains in patients on long term corticosteroid therapy. At the present time, little data are available on whether these drugs will reduce fracture incidences, although this might be considered likely.

Although further research is required, bisphosphonates should now be considered for the prevention and treatment of 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

Similar content being viewed by others

References

  1. 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 

  2. Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations. Bull Johns Hopkins Hosp 1932; 1: 137–92

    Google Scholar 

  3. Hahn TJ, Boisseau 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 

  4. Schaat O, Bohr H. Bone mineral in lumbar spine, femoral neck and femoral shaft measured by dual-photon absorptiometry with 153-gadolinium in prednisone treatment. Adv Exp Med Biol 1984; 171: 201–8

    Google Scholar 

  5. Maldague B, Malghem J, de Deauxchaisnes CN. Radiologic aspects of glucocorticoid-induced bone disease. Adv Exp Med Biol 1984; 171: 155–90

    PubMed  CAS  Google Scholar 

  6. Deding A, Tougaard L, Jensen MK, et al. Bone changes during prednisone treatment. Acta Med Scand 1977; 202: 253–5

    Article  PubMed  CAS  Google Scholar 

  7. Rickers H, Deding A, Christiansen C, et al. Mineral loss in cortical and trabecular bone during high dose prednisone treatment. Calcif Tissue Int 1984; 36: 269–73

    Article  PubMed  CAS  Google Scholar 

  8. Greenberger PA, Hendix RW, Patterson R, et al. Bone studies in patients on prolonged systemic corticosteroid therapy for asthma. Clin Allergy 1982; 12: 363–8

    Article  PubMed  CAS  Google Scholar 

  9. Sambrook P, Birmingham J, Kempler S, et al. Corticosteroid effects on proximal femur bone loss. J Bone Miner Res 1990; 5: 1211–6

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  11. Nagant de Deuxchaisnes C, Devogelaer JP, Esselinckx W, et al. The effect of low dosage glucocorticoids on bone mass in rheumatoid arthritis: a cross-sectional and a longitudinal study using single photon absorptiometry. Adv Exp Med Biol 1984; 171: 210–39

    Google Scholar 

  12. Ruegsegger P, Medici TC, Anliker M. Corticosteroid-induced bone loss: a longitudinal study of alternate day therapy in patients with bronchial asthma using quantitative computed tomography. Eur J Clin Pharmacol 1983; 25: 615–20

    Article  PubMed  CAS  Google Scholar 

  13. Reid IR. Pathogenesis and treatment of steroid osteoporosis. Clin Endocrinol 1989; 30: 83–103

    Article  CAS  Google Scholar 

  14. Meunier PJ, Dempster DW, Edouard C, et al. Bone histomorphometry in corticosteroid-induced osteoporosis in Cushing’s syndrome. Adv Exp Med Biol 1984; 171: 191–200

    PubMed  CAS  Google Scholar 

  15. Reid DM, Nicoll JJ, Smith MA, et al. Corticosteroids and bone mass in asthma: comparisons with rheumatoid arthritis and polymyalgia rheumatica. BMJ 1986; 293: 1463–6

    Article  PubMed  CAS  Google Scholar 

  16. Gennari C, Inbimbo B, Montagnani M, et al. Effects of prednisone and deflazacort on mineral metabolism and parathyroid hormone activity in humans. Calcif Tissue Int 1984; 36: 245–52

    Article  PubMed  CAS  Google Scholar 

  17. Kukreja SC, Bowser EN, Hargis GK, et al. Mechanisms of glucocorticoid-induced osteopenia: role of parathyroid glands. Proc Soc Exp Biol Med 1976; 152: 358–61

    PubMed  CAS  Google Scholar 

  18. Feldman D, Dziak R, Koehler R, et al. Cytoplasmic glucocorticoid binding proteins in bone cells. Endocrinology 1975; 96: 29–36

    Article  PubMed  CAS  Google Scholar 

  19. 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: 410–7

    Article  PubMed  CAS  Google Scholar 

  20. Prummel MF, Wiersinga WM, Lips P, et al. The course of biochemical parameters of bone turnover during treatment with corticosteroids. J Clin Endocrinol Metab 1991; 72: 382–6

    Article  PubMed  CAS  Google Scholar 

  21. Sakakura M, Takebe K, Nakagawa S. Inhibition of luteinizing hormone secretion by synthetic LRH by long-term treatment with glucocorticoids in human subjects. J Clin Endocrinol Metab 1975; 40: 774–9

    Article  PubMed  CAS  Google Scholar 

  22. 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 

  23. Klein RG, Arnaud SB, Gallagher JC, et al. Intestinal calcium absorption in exogenous hypercortisolism. Role of 25-hydroxyvitamin D and corticosteroid dose. J Clin Invest 1977; 60: 253–9

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Chesney RW, Mazess RB, Hamstra AJ, et al. Reduction of serum 1,25-dihydroxyvitamin D3 in children receiving glucocorticoids. Lancet 1978; II: 1123–5

    Article  Google Scholar 

  26. Zerwekh JE, Emkey RD, Harris ED. Low dose prednisone therapy in rheumatoid arthritis: effect on vitamin D metabolism. Arthritis Rheum 1984; 27: 1050–2

    Article  PubMed  CAS  Google Scholar 

  27. Hahn TJ, Halstead LR, Baran DT. Effects of short term glucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolite concentrations in man. J Clin Endocrinol Metab 1981; 52: 111–5

    Article  PubMed  CAS  Google Scholar 

  28. Nagant de Deuxchaisnes C, Devogelaer JP, Huaux JP, et al. The effects of small equivalent doses of deflazacort and prednisone on the bone mineral content in male patients with rheumatoid arthritis. J Bone Miner Res 1986; 1Suppl 1: 172S

    Google Scholar 

  29. Preston SJ, Diamond T, Scott A, et al. Methotrexate osteopathy in rheumatic disease. Ann Rheum Dis 1993; 52: 582–5

    Article  PubMed  CAS  Google Scholar 

  30. Movsowitz C, Epstein S, Ismail F, et al. Cyclosporine A in vivo produces severe osteopenia in the rat: effect of dose and duration of administration. Endocrinology 1988; 123: 2571–8

    Article  PubMed  CAS  Google Scholar 

  31. Gluck OS, Murphy WA, Hahn TJ, et al. Bone loss in adults receiving alternate day glucocorticoid therapy: a comparison with daily therapy. Arthritis Rheum 1981; 24: 892–8

    Article  PubMed  CAS  Google Scholar 

  32. 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: 1747–52

    Article  PubMed  CAS  Google Scholar 

  33. Montemurro L, Schiraldi G, Fraioli P, et al. Prevention of corticosteroid-induced osteoporosis with salmon calcitonin in sarcoid patients. Calcif Tissue Int 1991; 49: 71–6

    Article  PubMed  CAS  Google Scholar 

  34. Adami S, Fossaluzza V, Rossini M, et al. The prevention of corticosteroid-induced osteoporosis with nandrolone decanoate. Bone Miner 1991; 15: 72–81

    Article  Google Scholar 

  35. Storm T, Thamsborg G, Steiniche T, et al. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990; 322: 1265–71

    Article  PubMed  CAS  Google Scholar 

  36. Watts NB, Harris ST, Genant HK, et al. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 1990; 323: 73–9

    Article  PubMed  CAS  Google Scholar 

  37. Fleisch H. Chemistry and mechanism of action of diphosphonates. In: Garattini S, editor. Bone resorption, metastasis and diphosphonates. New York: Raven Press, 1985

    Google Scholar 

  38. Francis MD, Russell RGG, Fleisch H. Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathologic calcification in vivo. Science 1969; 165: 1264–6

    Article  PubMed  CAS  Google Scholar 

  39. Fleisch H, Russell RGG, Francis MD. Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture in vivo. Science 1969; 165: 1262–4

    Article  PubMed  CAS  Google Scholar 

  40. Ralston SH, Gardner MD, Dryburgh FJ, et al. Comparison of aminohydroxypropylidene diphosphonate, mithramycin and corticosteroids/calcitonin in treatment of cancer-associated hypercalcaemia. Lancet 1985; II: 907–10

    Article  Google Scholar 

  41. Smith R, Russell RGG, Bishop M. Diphosphonates and Paget’s disease of bone. Lancet 1971; I: 945–7

    Article  Google Scholar 

  42. Heaney RP, Savilie PD. Etidronate disodium in postmenopausal osteoporosis. Clin Pharmacol Ther 1976; 20: 593–604

    PubMed  CAS  Google Scholar 

  43. Anderson C, Cape RD, Crilly RG, et al. Preliminary observations of a form of coherence therapy for osteoporosis. Calcif Tissue Int 1984; 36: 341–3

    Article  PubMed  CAS  Google Scholar 

  44. Nagant de Deuxchaisnes C, Rombouts-Lindemans C, Huaux JP, et al. Diphosphonates and inhibition of bone mineralisation. Lancet 1982; II: 607–8

    Article  Google Scholar 

  45. Boyce BF, Smith L, Fogelman I, et al. Focal osteomalacia, due to low dose bisphosphonate therapy in Paget’s disease. Lancet 1984; I: 821–4

    Article  Google Scholar 

  46. Storm T, Steiniche T, Thamsborg G, et al. Changes in bone histomorphometry after long-term treatment with intermittent cyclic etidronate for postmenopausal osteoporosis. J Bone Miner Res 1993; 8: 199–208

    Article  PubMed  CAS  Google Scholar 

  47. Wimalawansa SJ. Combined therapy with estrogen and etidronate has an additive effect on bone mineral density in the hip and vertebrae: four year randomized study. Am J Med 1995; 99: 36–42

    Article  PubMed  CAS  Google Scholar 

  48. Adamson BB, Gallacher SJ, Byars J, et al. Mineralisation defects with pamidronate therapy for Paget’s disease. Lancet 1993; 342: 1459–60

    Article  PubMed  CAS  Google Scholar 

  49. Adachi JD, Cranney A, Goldsmith CH, et al. Intermittent cyclic therapy with etidronate in the prevention of corticosteroid-induced bone loss. J Rheumatol 1994; 21: 1922–6

    PubMed  CAS  Google Scholar 

  50. Struys A, Snelder AA, Mulder H. Cyclical etidronate reverses bone loss of the spine and proximal femur in patients with established corticosteroid-induced osteoporosis. Am J Med 1995; 99: 235–42

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  52. 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 

  53. 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 

  54. Lowik CWGM, van der Pluijm G, van der Wee-Pals LJA, et al. Migration and phenotypic transformation of osteoblast precursors into mature osteoclasts: the effect of a bisphosphonate. J Bone Miner Res 1988; 3: 185–92

    Article  PubMed  CAS  Google Scholar 

  55. Lufkin EG, Argueta R, Whitaker MD, et al. Pamidronate: an unrecognized problem in gastrointestinal tolerability. Osteoporosis Int 1994; 4: 320–2

    Article  CAS  Google Scholar 

  56. Gallacher SJ, Ralston SH, Patel U, et al. Side effects of pamidronate. Lancet 1989; II: 42–3

    Article  Google Scholar 

  57. Gallacher SJ, Fraser WD, Cruickshank AM, et al. The response of plasma interleukin-6 (IL-6) to pamidronate. Bone 1990; 11: 384 (P25)

    Article  Google Scholar 

  58. Schweitzer DH, Oostendorp-Van de Ruit M, van der Pluijm G, et al. Interleukin-6 and the acute phase response during treatment of patients with Paget’s disease with the nitrogen containing bisphosphonate dimethylaminopropylidene bisphosphonate. J Bone Miner Res 1995; 10: 956–62

    Article  PubMed  CAS  Google Scholar 

  59. Reid IR, King AR, Alexander CJ, et al. Prevention of steroid-induced osteoporosis with (3-amino-l-hydroxypropylidene)-1,1-bisphosphonate. Lancet 1988; I: 143–6

    Article  Google Scholar 

  60. Reid IR, Heap SW, King AR, et al. Two year follow-up of bisphosphonate (APD) treatment in steroid osteoporosis. Lancet 1988; II: 1144

    Article  Google Scholar 

  61. 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 

  62. Schenk R, Eggli P, Felix H, et al. Quantitative morphometric evaluation of the inhibitory activity of new aminobis-phosphonates on bone resorption in the rat. Calcif Tissue Int 1986; 38: 342–9

    Article  PubMed  CAS  Google Scholar 

  63. O’Doherty DP, Bickerstaff DR, McCloskey EV, et al. Treatment of Paget’s disease of bone with aminohydroxybutylidene bisphosphonate. J Bone Miner Res 1990; 5: 483–91

    Article  PubMed  Google Scholar 

  64. Chestnut C, McClung MR, Ensmiel KE, et al. Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodelling. Am J Med 1995; 99: 144–52

    Article  Google Scholar 

  65. Liberman UA, Weiss SR, Broil J, et al. Effect of oral alendronate on bone mineral density and the incidence of fracture in postmenopausal women. N Engl J Med 1995; 333: 1437–43

    Article  PubMed  CAS  Google Scholar 

  66. Shapiro D, Thomson DE, Karpf DB, et al. Non-vertebral fracture incidence in patients treated with alendronate. J Bone Miner Res 1995; 10Suppl. 1: S176 (150)

    Google Scholar 

  67. Giannini S, DiAngelo A, Malvasi L, et al. Effect of one year cyclical treatment with clodronate on postmenopausal bone loss. Bone 1993; 14: 137–41

    Article  PubMed  CAS  Google Scholar 

  68. Gallacher SJ, Anderson K, Speekenbrink T, et al. A comparison of the effects of etidronate, pamidronate, clodronate and calcium in patients with corticosteroid-dependent lung disease [abstract]. Calcif Tissue Int 1995; 56: 447

    Google Scholar 

  69. Spector TD, Sambrook PN. Steroid osteoporosis. BMJ 1993; 307: 519–20

    Article  PubMed  CAS  Google Scholar 

  70. Eastell R. Management of corticosteroid-induced osteoporosis. J Intern Med 1995; 237: 439–47

    Article  PubMed  CAS  Google Scholar 

  71. Peat DI, Healy S, Reid DM, et al. Steroid-induced osteoporosis: an opportunity for prevention? Ann Rheum Dis 1995; 54: 66–8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Unit B, Southern General Hospital NHS Trust, 1345 Govan Road, Glasgow, G51 4TF, Scotland

    Stephen J. Gallacher

Authors
  1. Stephen J. Gallacher
    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

Gallacher, S.J. Bisphosphonates. Clin. Immunother. 6, 154–162 (1996). https://doi.org/10.1007/BF03259512

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03259512

Keywords

Search

Navigation