Bone turnover markers, BMD and TBS after short-term, high-dose glucocorticoid therapy in patients with Graves’ orbitopathy: a small prospective pilot study

  • S. Censi
  • J. Manso
  • G. Pandolfo
  • G. Franceschet
  • E. Cavedon
  • Y. H. Zhu
  • S. Carducci
  • W. Gomiero
  • M. Plebani
  • M. Zaninotto
  • S. Watutantrige-Fernando
  • C. Mian
  • V. CamozziEmail author
Original Article



Chronic GC administration has numerous side effects, but little is known about the side effects of their short-term use (< 3 months)—particularly, when high doses are involved, as in the treatment of Graves’ orbitopathy (GO). We investigated the effects of short-term, high-dose GC on bone turnover markers, bone mineral density (BMD), and trabecular bone scores (TBS).


Eleven patients (10 females and 1 male; median age 56 years) with active GO who were candidates for treatment with intravenous (iv) methylprednisone were consecutively enrolled. All patients were pretreated with a loading dose of 300,000 units of cholecalciferol, then given a median cumulative dose of 4.5 g (range 1.5–5.25 g) iv methylprednisone. Biochemical parameters of bone metabolism (25OHD3, PTH, P1NP, CTX and bALP) were measured at the baseline, and then 1 week and 1, 3, 6 and 12 months. BMD and TBS were obtained by X-ray absorptiometry (DXA) at the baseline and at 6 and 12 months. On DXA image, morphometric vertebral fracture assessment (VFA) was done.


There were no significant changes in PTH, bALP or P1NP. A significant drop in CTX was seen at 1 month (down Δ49.31% from the baseline, p = 0.02), with a return to the baseline at the 3-month measurement. There was a moderate (not significant), but persistent reduction in P1NP. No changes in BMD or TBS came to light. No vertebral fractures were documented.


Short-term, high-dose GC treatment caused a rapid, transient suppression of bone resorption, with no effects on BMD or bone micro-architecture (TBS).


Glucocorticoid Bone turnover markers Bone mineral density 




Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethical approval

This study was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments.

Informed consent

Written informed consent was obtained from all patients included in this study.


  1. 1.
    van Staa TP, Leufkens HG, Abenhaim L et al (2000) Use of oral corticosteroids in the United Kingdom. QJM 93:105–111CrossRefGoogle Scholar
  2. 2.
    Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 18:1319–1328. CrossRefGoogle Scholar
  3. 3.
    Canalis E, Bilezikian JP, Angeli A, Giustina A (2004) Perspectives on glucocorticoid-induced osteoporosis. Bone 34:593–598. CrossRefGoogle Scholar
  4. 4.
    Rubin J, Biskobing DM, Jadhav L et al (1998) Dexamethasone promotes expression of membrane-bound macrophage colony-stimulating factor in murine osteoblast-like cells. Endocrinology 139:1006–1012. CrossRefGoogle Scholar
  5. 5.
    Angeli A, Guglielmi G, Dovio A et al (2006) High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone 39:253–259. CrossRefGoogle Scholar
  6. 6.
    Buckley L, Guyatt G, Fink HA et al (2017) 2017 American College of Rheumatology Guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 69:1095–1110. CrossRefGoogle Scholar
  7. 7.
    Pothuaud L, Carceller P, Hans D (2008) Correlations between grey-level variations in 2D projection images (TBS) and 3D microarchitecture: applications in the study of human trabecular bone microarchitecture. Bone 42:775–787. CrossRefGoogle Scholar
  8. 8.
    Silva BC, Leslie WD, Resch H et al (2014) Trabecular bone score: a noninvasive analytical method based upon the DXA image. J Bone Miner Res 29:518–530. CrossRefGoogle Scholar
  9. 9.
    Laan RF, van Riel PL, van de Putte LB et al (1993) Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med 119:963–968CrossRefGoogle Scholar
  10. 10.
    Hardy RS, Zhou H, Seibel MJ, Cooper MS (2018) Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy. Endocr Rev 39:519–548. CrossRefGoogle Scholar
  11. 11.
    Mak W, Shao X, Dunstan CR et al (2009) Biphasic glucocorticoid-dependent regulation of Wnt expression and its inhibitors in mature osteoblastic cells. Calcif Tissue Int 85:538–545. CrossRefGoogle Scholar
  12. 12.
    Jia D, O’Brien CA, Stewart SA et al (2006) Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. Endocrinology 147:5592–5599. CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Bartalena L, Baldeschi L, Boboridis K et al (2016) The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy. Eur Thyroid J 5:9–26. CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Bandirali M, Poloni A, Sconfienza LM et al (2015) Short-term precision assessment of trabecular bone score and bone mineral density using dual-energy X-ray absorptiometry with different scan modes: an in vivo study. Eur Radiol 25:2194–2198. CrossRefGoogle Scholar
  15. 15.
    Genant HK, Wu CY, van Kuijk C, Nevitt MC (2009) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148. CrossRefGoogle Scholar
  16. 16.
    Harris EK, Yasaka T (1983) On the calculation of a “reference change” for comparing two consecutive measurements. Clin Chem 29:25–30Google Scholar
  17. 17.
    Fraser CG, Harris EK (1989) Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 27:409–437. CrossRefGoogle Scholar
  18. 18.
    Eastell R, Szulc P (2017) Use of bone turnover markers in postmenopausal osteoporosis. Lancet Diabetes Endocrinol 5:908–923. CrossRefGoogle Scholar
  19. 19.
    Vasikaran S, Cooper C, Eastell R et al (2011) International osteoporosis foundation and international federation of clinical chemistry and laboratory medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med 49:1271–1274. CrossRefGoogle Scholar
  20. 20.
    Ton FN, Gunawardene SC, Lee H, Neer RM (2005) Effects of low-dose prednisone on bone metabolism. J Bone Miner Res 20:464–470. CrossRefGoogle Scholar
  21. 21.
    Bornefalk E, Dahlén I, Michaëlsson K et al (1998) Age-dependent effect of oral glucocorticoids on markers of bone resorption in patients with acute asthma. Calcif Tissue Int 63:9–13CrossRefGoogle Scholar
  22. 22.
    Lems WF, Van Veen GJ, Gerrits MI et al (1998) Effect of low-dose prednisone (with calcium and calcitriol supplementation) on calcium and bone metabolism in healthy volunteers. Br J Rheumatol 37:27–33CrossRefGoogle Scholar
  23. 23.
    Luisetto G, Zangari M, Camozzi V et al (2001) Recovery of bone mineral density after surgical cure, but not by ketoconazole treatment, in Cushing’s syndrome. Osteoporos Int 12:956–960. CrossRefGoogle Scholar
  24. 24.
    Paglia F, Dionisi S, De Geronimo S et al (2001) Biomarkers of bone turnover after a short period of steroid therapy in elderly men. Clin Chem 47:1314–1316Google Scholar
  25. 25.
    Dovio A, Perazzolo L, Osella G et al (2004) Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis. J Clin Endocrinol Metab 89:4923–4928. CrossRefGoogle Scholar
  26. 26.
    Weiss MJ, Ray K, Henthorn PS et al (1988) Structure of the human liver/bone/kidney alkaline phosphatase gene. J Biol Chem 263:12002–12010Google Scholar
  27. 27.
    Schousboe JT, Vokes T, Broy SB et al (2008) Vertebral fracture assessment: the 2007 ISCD official positions. J Clin Densitom 11:92–108. CrossRefGoogle Scholar
  28. 28.
    Rossini M, Adami S, Viapiana O et al (2012) Dose-dependent short-term effects of single high doses of oral vitamin D(3) on bone turnover markers. Calcif Tissue Int 91:365–369. CrossRefGoogle Scholar
  29. 29.
    Rubin MR, Bilezikian JP (2002) Clinical review 151: 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. CrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2018

Authors and Affiliations

  • S. Censi
    • 1
  • J. Manso
    • 1
  • G. Pandolfo
    • 1
  • G. Franceschet
    • 1
  • E. Cavedon
    • 1
  • Y. H. Zhu
    • 1
  • S. Carducci
    • 1
  • W. Gomiero
    • 2
  • M. Plebani
    • 3
  • M. Zaninotto
    • 3
  • S. Watutantrige-Fernando
    • 1
  • C. Mian
    • 1
  • V. Camozzi
    • 1
    Email author
  1. 1.Endocrinology Unit, Department of Medicine (DIMED)Università di PadovaPaduaItaly
  2. 2.Sport and Exercise Medicine Division, Department of Medicine (DIMED)Università di PadovaPaduaItaly
  3. 3.Laboratory Medicine, Department of Medicine (DIMED)Università di PadovaPaduaItaly

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