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Bone involvement in exogenous hypercortisolism

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Abstract

Corticosteroids remain a key component in the management of many disorders. Bone loss resulting from long-term administration of these drugs is common and osteoporosis induced by corticosteroids is the most frequent cause of secondary osteoporosis in nearly 50% of individuals on chronic corticosteroid therapy suffering from an osteoporotic fracture at some point. This article reviews the epidemiology and pathogenesis of glucocorticoid-induced osteoporosis.

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References

  1. Walsh LJ, Wong CA, Pringle M, Tattersfield AE. Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross sectional study. BMJ 1996, 313: 344–6.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. van Staa TP, Leufkens HG, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. Q J M 2000, 93: 105–11.

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

    Article  PubMed  Google Scholar 

  5. van Staa TP. The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int 2006, 79: 129–37.

    Article  PubMed  CAS  Google Scholar 

  6. Solomon DH, Katz JN, Jacobs JP, La Tourette AM, Coblyn J. Management of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis: rates and predictors of care in an academic rheumatology practice. Arthritis Rheum 2002, 46: 3136–42.

    Article  PubMed  Google Scholar 

  7. Khosla S, Lufkin EG, Hodgson SF, Fitzpatrick LA, Melton LJ 3rd. Epidemiology and clinical features of osteoporosis in young individuals. Bone 1994, 15: 551–5.

    Article  PubMed  CAS  Google Scholar 

  8. Devogelaer JP. Glucocorticoid-induced osteoporosis: mechanisms and therapeutic approach. Rheum Dis Clin North Am 2006, 32: 733–57.

    Article  PubMed  Google Scholar 

  9. Delany A, Gabbitas B, Canalis E. Cortisol downregulates osteoblast alpha 1 (I) procollagen mRNA by trancriptional and post-transcriptional mechanisms. J Cell Biochem 1995, 57: 488–94.

    Article  PubMed  CAS  Google Scholar 

  10. Delany A, Jeffrey JJ, Rydziel S, Canalis E. Cortisol increases interstitial collagenase expression in osteoblasts by post-transcriptional mechanisms. J Biol Chem 1995, 270: 26607–12.

    Article  PubMed  CAS  Google Scholar 

  11. Canalis E. Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. J Clin Endocrinol Metab 1996, 81: 3441–6.

    PubMed  CAS  Google Scholar 

  12. Pereira RM, Delany AM, Durant D, Canalis E. Cortisol regulates the expression of Notch in osteoblasts. J Cell Biochem 2002, 85: 252–8.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Canalis E, Bilezikian JP, Angeli A, Giustina A. Perspectives on glucocorticoid-induced osteoporosis. Bone 2004, 34: 593–8.

    Article  PubMed  CAS  Google Scholar 

  15. LoCascio V, Bonucci E, Imbimbo B, et al. Bone loss in response to long-term glucocorticoid therapy. Bone Miner 1990, 8: 39–51.

    Article  PubMed  CAS  Google Scholar 

  16. Nielsen HK, Charles P, Mosekilde L. The effect of single oral dose of prednisone on the circadian rithm of serum osteocalcin in normal subjects. J Clin Endocrinol Metab 1988, 67: 1025–30.

    Article  PubMed  CAS  Google Scholar 

  17. 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 glucocrticoid-induced osteoporosis. Endocrinology 1999, 140: 4382–9.

    PubMed  CAS  Google Scholar 

  18. Sivagurunathan S, Muir MM, Brennan TC, Seale JP, Mason RS. Influence of glucocorticoids on human osteoclast generation and activity. J Bone Miner Res 2005, 20: 390–8.

    Article  PubMed  CAS  Google Scholar 

  19. Gennari C, Bernini M, Nardi P, Fusi L, Nami R, Montagnani M. Hormones and the intestinal absorption of calcium and phosphate in man. Horm Res 1984, 20: 13–21.

    Article  PubMed  CAS  Google Scholar 

  20. Bikle DD, Halloran B, Fong L, Steinbach L, Shellito J. Elevated 1,25 dihydroxyvitamin D levels in patients with chronic obstructive pulmonary disease treated with prednisone. J Clin Endocrinol Metab 1993, 76: 456–61.

    PubMed  CAS  Google Scholar 

  21. Cosman F, Nieves J, Herbert J, Shen V, Lindsay R. Highdose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skeleton. J Bone Miner Res 1994, 9: 1097–105.

    Article  PubMed  CAS  Google Scholar 

  22. Seeman E, Kumar R, Hunder GG, Scott M, Heath H 3rd, Riggs BL. Production, degradation and circulating levels of 1,25-dihydroxyvitamin D in health and in chronic glucocorticoid excess. J Clin Invest 1980, 66: 664–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Prummel MF, Wiersinga WM, Lips P, Sanders GT, Sauerwein HP. 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 

  24. Chesney RW, Mazess RB, Hamstra AJ, De Luca HF, O’Reagan S. Reduction of serum-1,25 dihydroxyvitamin D3 in children receiving glucocorticoids. Lancet 1978, ii: 1123–5.

    Article  Google Scholar 

  25. Morris HA, Need AG, O’Loughlin PD, Horowitz M, Bridges A, Nordin BE. Malabsorption of calcium in corticosteroidinduced osteoporosis. Calcif Tissue Int 1990, 46: 305–8.

    Article  PubMed  CAS  Google Scholar 

  26. Akeno N, Matsunuma A, Maeda T, Kawane T, Horiuchi N. Regulation of vitamin D-1 alpha-hydroxylase and 24-hydroxylase expression by dexamethasone in mouse kidney. J endocrinol 2000, 164: 339–48.

    Article  PubMed  CAS  Google Scholar 

  27. Godschalk M, Levy JR, Downs RW Jr. 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 

  28. Gennari C, Imbimbo B, Montagnani M, Bernini M, Nardi P, Avioli LV. Effects of prednisone and deflazacort on mineral metabolism and parathyroid hormone activity in humans. Calcified Tissue Int 1984, 36: 245–52.

    Article  CAS  Google Scholar 

  29. Paz-Pacheco E, Fuleihan GE, Leboff MS. Intact parathyroid hormone levels are not elevated in glucocorticoid treated subjects. J Bone Miner Res 1995, 10: 1713–8.

    Article  PubMed  CAS  Google Scholar 

  30. Rubin MR, Bilezikian JP. The role of parathyroid hormone in the pathogenesis of glucocorticoid-induced osteoporosis: a re-examination of the evidence. J Clin Endocrinol Metab 2002, 87: 4033–41.

    Article  PubMed  CAS  Google Scholar 

  31. Yamamoto I, Potts JT jr, Segre GV. Glucocorticoids increase parathyroid hormone receptors in rat osteoblastic osteosarcoma cells. J Bone Miner Res 1988, 3: 707–12.

    Article  PubMed  CAS  Google Scholar 

  32. Reid IR. Pathogenesis and treatment of steroid osteoporosis. Clin Endocrinol (Oxf) 1989, 30: 83–103.

    Article  CAS  Google Scholar 

  33. Shane E, Rivas M, Staron M, et al. Fracture after cardiac transplantation: a prospective longitudinal study. J Clin Endocrinol Metab 1996, 81: 1740–6.

    PubMed  CAS  Google Scholar 

  34. van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000, 15: 993–1000.

    Article  Google Scholar 

  35. Saito JK, Davis JW, Wasnich D, Ross PD. Users of low-dose glucocorticoids have increased bone loss rates: a longitudinal study. Calcif Tissue Int 1995, 57: 115–9.

    Article  PubMed  CAS  Google Scholar 

  36. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced Osteoporosis: a meta-analysis. Osteoporos Int 2002, 13: 777–87.

    Article  PubMed  Google Scholar 

  37. van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C. Bone density treshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 2003, 48: 3224–9.

    Article  PubMed  CAS  Google Scholar 

  38. Sinigaglia L, Nervetti A, Mela Q, et al. A multicenter cross sectional study on bone mineral density in Rheumatoid Arthritis. Italian Study Group on Bone Mass in Rheumatoid Arthritis. J Rheumatol 2000, 27: 2582–9.

    PubMed  CAS  Google Scholar 

  39. van Staa TP, Leufkens HGM, Cooper C. Use of inhaled corticosteroids and risk of fractures. J Bone Miner Res 2001, 16: 581–8.

    Article  PubMed  Google Scholar 

  40. Michel BA, Bloch DA, Fries JF. Predictors of fractures in early Rheumatoid Arthritis. J Rheumatol 1991, 18: 804–8.

    PubMed  CAS  Google Scholar 

  41. Naganathan V, Jones G, Nash P, Nicholson G, Eisman J, Sambrook P. Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use. Arch Intern Med 2000, 160: 2917–22.

    Article  PubMed  CAS  Google Scholar 

  42. Ho YV, Briganti EM, Duan Y, Buchanan R, Hall S, Seeman E. Polymorphism of the vitamin D receptor gene and corticosteroid-related Osteoporosis. Osteoporos Int 1999, 9: 134–8.

    Article  PubMed  CAS  Google Scholar 

  43. Seckl JR, Walker BR. Minireview: 11 beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocrticoid action. Endocrinology 2001, 142: 1371–6.

    PubMed  CAS  Google Scholar 

  44. Canalis E, Delany AM. 11 beta-hydroxysteroid dehydrogenase, an amplifier of glucocorticoid action in osteoblasts. J Bone Miner Res 2002, 17: 987–90.

    Article  PubMed  Google Scholar 

  45. Cooper MS, Rabbitt EH, Goddard PE, Bartlett WA, Hewison M, Stewart PM. Osteoblastic 11-beta hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure. J Bone Miner Res 2002, 17: 979–86.

    Article  PubMed  CAS  Google Scholar 

  46. Chikanza IC, Kozaci DL. Corticosteroid resistance in rheumatoid arthritis: molecular and cellular perspectives. Rheumatology (Oxford) 2004, 43: 1337–45.

    Article  CAS  Google Scholar 

  47. Pocock NA, Eisman JA, Dunstan CR, Evans R, Thomas DH, Huk NL. Recovery from steroid-induced Osteoporosis. Ann Intern Med 1987, 107: 319–23.

    Article  PubMed  CAS  Google Scholar 

  48. Manning PJ, Evans MC, Reid IR. Normal bone mineral density following cure of Cushing’s syndrome. Clin Endocrinol 1992, 36: 229–34.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Chair and Department of Rheumatology, Gaetano Pini Institute, University of Milan, Milan, Italy

    L. Sinigaglia MD, D. Mazzocchi & M. Varenna

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  1. L. Sinigaglia MD
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  2. D. Mazzocchi
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  3. M. Varenna
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Correspondence to L. Sinigaglia MD.

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Sinigaglia, L., Mazzocchi, D. & Varenna, M. Bone involvement in exogenous hypercortisolism. J Endocrinol Invest 31, 364–370 (2008). https://doi.org/10.1007/BF03346372

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