Skip to main content

Advertisement

Log in

Glucocorticoid Excess Affects Cortical Bone Geometry in Premenopausal, but not Postmenopausal, Women

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Glucocorticoid (GC) excess causes a great increase in fracture risk, but the effects of GC excess on cortical bone geometry are unknown. The present study was performed to examine the effects of GC excess on cortical bone geometry in both premenopausal and postmenopausal women. Ninety-six women receiving oral GC treatments and 10 women with Cushing syndrome (CS) were each compared to age-matched control subjects using peripheral quantitative computed tomography. Total area, periosteal circumference, and polar strength strain index (SSIp) were significantly lower in GC-treated patients compared with control subjects in premenopausal women but not in postmenopausal women. Moreover, cortical area and thickness as well as periosteal circumference and SSIp were significantly lower in patients with CS compared to controls in premenopausal women but not in postmenopausal women. Total area, cortical area, cortical thickness, periosteal circumference, as well as SSIp were significantly lower in GC-treated patients with vertebral fractures compared to those without vertebral fractures in premenopausal women but not in postmenopausal women. In conclusion, endogenous or exogenous GC excess affects bone geometry of forearms of premenopausal, but not postmenopausal, women. These effects of GC excess on bone geometry may provide a strength loss mechanism beneath increased vertebral fracture risk.

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. Sambrook P, Birmingham J, Kempler S, Kelly P, Eberl S, Pecock N, Yeates M, Eisman J (1990) Corticosteroid effects on proximal femur bone loss. J Bone Miner Res 5:1211–1216

    PubMed  CAS  Google Scholar 

  2. 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 48:3224–3229

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. Steinbuch M, Youket TE, Cohen S (2004) Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int 15:323–328

    Article  PubMed  CAS  Google Scholar 

  5. Van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787

    Article  PubMed  Google Scholar 

  6. Kanis JA, Johansson H, Oden AM, Johnell O, de Laet C, Melton LJ III, Tenenhouse A, Reeve J, Silman AJ, Pols HAP, Eisman JA, McCloskey EV, Mellstrom D (2004) A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 19:893–899

    Article  PubMed  Google Scholar 

  7. Manelli F, Giustina A (2000) Glucocorticoid-induced osteoporosis. Trends Endocrinol Metab 11:79–85

    Article  PubMed  CAS  Google Scholar 

  8. Kaltsas G, Manetti L, Grossman AB (2002) Osteoporosis in Cushing’s syndrome. Front Horm Res 30:60–72

    PubMed  CAS  Google Scholar 

  9. Manning PJ, Evans MC, Reid IR (1992) Normal bone mineral density following cure of Cushing’s syndrome. Clin Endocrinol 36:229–234

    Article  CAS  Google Scholar 

  10. Hermus AR, Smals AG, Swinkels LM, Huysmans DA, Pieters GF, Sweep CF, Corstens FH, Kloppenborg PW (1995) Bone mineral density and bone turnover before and after surgical cure of Cushing’s syndrome. J Clin Endocrinol Metab 80:2859–2865

    Article  PubMed  CAS  Google Scholar 

  11. Mancini T, Doga M, Mazziotti G, Giustina A (2004) Cushing’s syndrome and bone. Pituitary 7:243–246

    Article  Google Scholar 

  12. Francucci CM, Pantanetti P, Garrapa GG, Massi F, Arnaldi G, Mantero F (2002) Bone metabolism and mass in women with Cushing’s syndrome and adrenal incidentaloma. Clin Endocrinol 57:587–593

    Article  CAS  Google Scholar 

  13. Vestergaard P, Lindholm J, Jorgensen JOL, Hagen C, Hoeck HC, Laurberg P, Rejnmark L, Brixen K, Kristensen LO, Feldt-Rasmussen U, Mosekilde L (2002) Increased risk of osteoporotic fractures in patients with Cushing’s syndrome. Eur J Endocrinol 146:51–56

    Article  PubMed  CAS  Google Scholar 

  14. Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Suzuki 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. J Bone Miner Metab 23:105–109

    Article  PubMed  Google Scholar 

  15. Kaji H, Yamauchi M, Chihara K, Sugimoto T (2006) The threshold of bone mineral density for vertebral fracture in female patients with glucocorticoid-induced osteoporosis. Endocr J 53:27–34

    Article  PubMed  CAS  Google Scholar 

  16. NIH Consensus Development Panel on Osteoporosis Prevention. Osteoporosis prevention, diagnosis, and the therapy. JAMA 285:785–795

  17. Lehmann R, Wapniarz M, Kvasnicka HM, Baedeker S, Klein K, Allolio B (1992) Reproducibility of bone density measurements of the distal radius using a high resolution special scanner for peripheral quantitative computed tomography (Single Energy PQCT). Radiology 32:177–181

    CAS  Google Scholar 

  18. Martin RB (1991) Determinants of the mechanical properties of bones. J Biomech 24(Suppl 1):79–88

    Article  Google Scholar 

  19. Smith RW Jr, Walker RR (1964) Femoral expansion in aging women: implications for osteoporosis and fractures. Science 145:156–157

    Article  PubMed  Google Scholar 

  20. Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK (2003) Bone loss and bone size after menopause. N Engl J Med 349:327–334

    Article  PubMed  Google Scholar 

  21. Chen Q, Kaji H, Iu MF, Nomura R, Sowa H, Yamauchi M, Tsukamoto T, Sugimoto T, Chihara K (2003) Effects of an excess and a deficiency of endogenous parathyroid hormone on volumetric bone mineral density and bone geometry determined by peripheral quantitative computed tomography in female subjects. J Clin Endocrinol Metab 88:4655–4658

    Article  PubMed  CAS  Google Scholar 

  22. Kaji H, Kosaka R, Yamauchi M, Kuno K, Chihara K, Sugimoto T (2005) Effects of age, grip strength and smoking on forearm volumetric bone mineral density and bone geometry by peripheral quantitative computed tomography: comparisons between female and male. Endocr J 52:659–666

    Article  PubMed  Google Scholar 

  23. Riggs BL, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S (2004) Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites. J Bone Miner Res 19:1945–1954

    Article  PubMed  Google Scholar 

  24. Tsugeno H, Fujita T, Goto B, Sugishita T, Hosaki Y, Ashida K, Mitsunobu F, Tanizaki Y, Shiratori Y (2002) Vertebral fracture and cortical bone changes in corticosteroid-induced osteoporosis. Osteoporos Int 13:650–656

    Article  PubMed  CAS  Google Scholar 

  25. Lian KC, Lang TF, Keyak JH, Modin GW, Rehman Q, Do L, Lane NE (2005) Differences in hip quantitative computed tomography (QCT) measurement on bone mineral density and bone strength between glucocorticoid-treated and glucocortiocid-naïve postmenopausal women. Osteoporos Int 16:642–650

    Article  PubMed  CAS  Google Scholar 

  26. Smith-Bindman R, Cummings SR, Steiger P, Genant HK (1991) A comparison of morphometric definitions of vertebral fractures. J Bone Miner Res 6:25–34

    Article  PubMed  CAS  Google Scholar 

  27. Ruegsegger P, Durand E, Dambacher MA (1991) Localization of regional forearm bone loss from high-resolution computed tomographic images. Osteoporos Int 1:76–80

    Article  PubMed  CAS  Google Scholar 

  28. Schiessl H, Ferretti JL, Tysarczyk-Niemeyer G (1996) Noninvasive bone strength index as analysis by peripheral quantitative computed tomography (pQCT). In: Schonau E (ed) Pediatric osteology. New developments in diagnostics and therapy. Elsevier, Amsterdam, pp 147–160

    Google Scholar 

  29. Ashizawa N, Nonaka K, Michikami S, Mizuki T, Amagai H, Tokuyama K, Suzuki M (1999) Tomographical description of tennis-loaded radius: reciprocal relation between bone size and volumetric BMD. J Appl Phys 86:1347–1351

    CAS  Google Scholar 

  30. Ørtoft G, Oxlund H (1996) Qualitative alterations of cortical bone in female rats after long-term administration of growth hormone and glucocorticoid. Bone 18:581–590

    Article  PubMed  Google Scholar 

  31. Ikeda S, Morishita Y, Tsutsumi H, Ito M, Shiraishi A, Arita S, Asahoshi S, Narusawa K, Nakamura T (2003) Reductions in bone turnover, mineral, and structure associated with mechanical properties of lumbar vertebra and femur in glucocorticoid-treated growing minipigs. Bone 33:779–787

    Article  PubMed  CAS  Google Scholar 

  32. Kaji H, Tobimatsu T, Naito J, Iu MF, Yamauchi M, Sugimoto T, Chihara K (2006) Body composition and vertebral fracture risk in female patients treated with glucocorticoid. Osteoporos Int 17:627–633

    Article  PubMed  CAS  Google Scholar 

  33. Michel BA, Bloch DA, Wolfe F, Fries JF (1993) Fractures in rheumatoid arthritis: an evaluation of associated risk factors. J Rheumatol 20:1666–1669

    PubMed  CAS  Google Scholar 

  34. Ramsey-Goldman R, Dunn JE, Huang CF, Dunlop P, Rairie JE, Fitzgerald S, Manzi S (1999) Frequency for fractures in women with systemic lupus erythematosus: comparison with United States population data. Arthritis Rheum 42:882–890

    Article  PubMed  CAS  Google Scholar 

  35. Faggiano A, Pivonello R, Filippella M, Di Somma C, Orio F Jr, Lombard G, Colao A (2001) Spine abnormalities and damage in patients cured from Cushing’s disease. Pituitary 4:153–161

    Article  PubMed  CAS  Google Scholar 

  36. Chiodini I, Carnevale V, Torlontano M, Fusilli S, Guglielmi G, Peleri M, Modoni S, Di Giorgio A, Liuzzi A, Minisola S, Cammisa M, Trischotta V, Scillitani A (1998) Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing’s syndrome. J Clin Endocrinol Metab 83:1863–1867

    Article  PubMed  CAS  Google Scholar 

  37. Rubin MR, Bilezikian JP (2002) The role of parathyroid hormone in the pathogenesis of glucocorticoid-induced osteoporosis: a re-examination of the evidence. J Clin Endocrinol Metab 87:4033–4041

    Article  PubMed  CAS  Google Scholar 

  38. Unsi-Rasi K, Semanick IM, Zanchetta JR, Bogado CZ, Eriksen EF, Sato M, Beck IJ (2005) Effects of teriparatide [rhPTH(1–34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women. Bone 36:948–958

    Article  CAS  Google Scholar 

  39. Ferretti JL, Capozza RF, Mondelo N, Zanchetta JR (1993) Interrelationships between densitometric, geometric, and mechanical properties of rat femora: inferences concerning mechanical regulation of bone modeling. J Bone Miner Res 8:1389–1396

    PubMed  CAS  Google Scholar 

  40. Myers ER, Hecker AT, Rooks DS, Hipp JA, Hayes WC (1993) Geometric variables from DXA of the radius predict forearm fracture load in vitro. Calcif Tissue Int 52:199–204

    Article  PubMed  CAS  Google Scholar 

  41. Oleksik A, Ott SM, Vedi S, Bravenboer N, Compston J, Lips P (2000) Bone structure in patients with low bone mineral density with or without vertebral fractures. J Bone Miner Res 15:1368–1375

    Article  PubMed  CAS  Google Scholar 

  42. Yamauchi M, Sugimoto T, Chihara K (2004) Determinants of vertebral fragility: the participation of cortical bone factors. J Bone Miner Metab 22:79–85

    Article  PubMed  Google Scholar 

  43. Karavitaki N, Ioannidis G, Giannakopoulos F, Marvrokefalos P, Thalassinos N (2004) Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing’s syndrome. Clin Endocrinol 60:264–270

    Article  CAS  Google Scholar 

  44. Di Somma C, Pivonello R, Loche S, Faggiano A, Klain M, Salvatore M, Lombardi G, Colao A (2003) Effect of 2 years of cortisol normalization on the impared bone mass and turnover in adolescent and adult patients with Cushing’s disease: a prospective study. Clin Endocrinol 58:302–308

    Article  CAS  Google Scholar 

  45. Di Somma C, Pivonello R, Loche S, Faggiano A, Marzullo P, Di Sarno A, Klain M, Salvatore M, Lombardi G, Colao A (2002) Severe impairment of bone mass and turnover in Cushing’s disease: comparison between childhood-onset and adulthood-onset disease. Clin Endocrinol 56:153–158

    Article  Google Scholar 

  46. Ruegsegger P, Medici T, Anliker M (1983) Corticosteroid-induced bone loss: a longitudinal study of alternate therapy in patients with bronchial asthma using quantitative computed tomography. Eur J Clin Parmacol 25:615–620

    Article  CAS  Google Scholar 

  47. Seeman E (1997) From density to structure: growing up and growing old on the surfaces of bone. J Bone Miner Res 12:509–521

    Article  PubMed  CAS  Google Scholar 

  48. Russo CR, Lauretani F, Bandinelli S, Bartali B, Di Iorio A, Volpato S, Guralnik JM, Harris T, Ferrucci L (2003) Aging bone in men and women: beyond changes in bone mineral density. Osteoporos Int 14:531–538

    Article  PubMed  CAS  Google Scholar 

  49. Vanderschueren D, Venken K, Ophoff J, Bouillon R, Boonen S (2006) Sex steroids and the periosteum—reconsidering the roles of androgens and estrogens in periosteal expansion. J Clin Endcocrinol Metab 91:378–382

    Article  CAS  Google Scholar 

  50. Saxon LK, Turner CH (2006) Low-dose estrogen treatment suppresses periosteal bone formation in response to mechanical loading. Bone 39:1261–1267

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroshi Kaji.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaji, H., Yamauchi, M., Chihara, K. et al. Glucocorticoid Excess Affects Cortical Bone Geometry in Premenopausal, but not Postmenopausal, Women. Calcif Tissue Int 82, 182–190 (2008). https://doi.org/10.1007/s00223-008-9106-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-008-9106-9

Keywords

Navigation