Abstract
We conducted a case–control study on fracture risk associated with the use of orally administered prednisolone/prednisone, budesonide, methylprednisolone, and hydrocortisone to assess if the various preparations were associated with different fracture patterns. Cases were all subjects with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. Adjustments were made for concurrent diseases, use of other drugs, and a number of other factors. Oral prednisolone/prednisone was associated with a dose-dependent increase in fracture risk starting from a dose of around 6.7 mg/day. Oral budesonide was not associated with an increase in overall fracture risk, but the doses in general were low (<3 mg/day). Oral hydrocortisone was not associated with overall risk of fractures. Oral methylprednisolone was only used intermittently and was not associated with an increase in overall fracture risk at the low doses used. After termination of oral prednisolone/prednisone, it took more than 1 year for fracture risk to return to the levels of the background population. Oral prednisolone is associated with a dose-dependent increase in overall fracture risk. Budesonide at low doses did not seem to be associated with fracture risk. Hydrocortisone was not associated with an increase in the risk of fractures. It may take a year from last use of prednisolone/prednisone before fracture risk returns to that of the general population.
Similar content being viewed by others
References
van Staa TP, Leufkens HGM, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000
Vestergaard P, Rejnmark L, Mosekilde L (2005) Fracture risk associated with systemic and topical corticosteroids. J Intern Med 257:374–384
Suissa S, Baltzan M, Kremer R, Ernst P (2004) Inhaled and Nasal corticosteroid use and the risk of fracture. Am J Respir Crit Care Med 169:83–88
van Staa TP, Leufkens HGM, Cooper C (2001) Use of inhaled corticosteroids and risk of fractures. J Bone Miner Res 16:581–588
van Staa TP, Bishop N, Leufkens HG, Cooper C (2004) Are inhaled corticosteroids associated with an increased risk of fracture in children? Osteoporos Int 15:785–791
Edsbacker S, Andersson T (2004) Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn’s disease. Clin Pharmacokinet 43:803–821
Lofberg R, Danielsson A, Suhr O, Nilsson A, Schioler R, Nyberg A, Hultcrantz R, Kollberg B, Gillberg R, Willen R, Persson T, Salde L (1996) Oral budesonide versus prednisolone in patients with active extensive and left-sided ulcerative colitis. Gastroenterology 110:1713–1718
Schoon EJ, Bollani S, Mills PR, Israeli E, Felsenberg D, Ljunghall S, Persson T, Hapten-White L, Graffner H, Bianchi PG, Vatn M, Stockbrugger RW (2005) Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn’s disease. Clin Gastroenterol Hepatol 3:113–121
de Vries F, Bracke M, Leufkens HG, Lammers JW, Cooper C, van Staa TP (2007) Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis Rheum 56:208–214
Vestergaard P, Emborg C, Støving RK, Hagen C, Mosekilde L, Brixen K (2002) Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders—a nation-wide register study. Int J Eat Disord 32:301–308
Andersen TF, Madsen M, Jørgensen J, Mellemkjær L, Olsen JH (1999) The Danish National Hospital Register. Dan Med Bull 46:263–268
Mosbech J, Jørgensen J, Madsen M, Rostgaard K, Thornberg K, Poulsen TD (1995) The Danish National Patient Register: evaluation of data quality. Ugeskr Læger 157:3741–3745
Vestergaard P, Rejnmark L, Mosekilde L (2004) Fracture risk associated with use of anti-epileptic drugs. Epilepsia 45:1330–1337
Jones S, Johansen A, Brennan J, Butler J, Lyons RA (2004) The effect of socioeconomic deprivation on fracture incidence in the United Kingdom. Osteoporos Int 15:520–524
Cooper C, Carbone L, Michet CJ, Atkinson EJ, O’Fallon WM, Melton LJ III (1994) Fracture risk in patients with ankylosing spondylitis: a population based study. J Rheumatol 21:1877–1882
Cooper C, Coupland C, Mitchell M (1995) Rheumatoid arthritis, corticosteroid therapy and hip fracture. Ann Rheum Dis 54:49–52
Abildgaard N, Brixen K, Kristensen JE, Vejlgaard T, Charles P, Nielsen JL (1996) Assessment of bone involvement in patients with multiple myeloma using bone densitometry. Eur J Haematol 57:370–376
Vestergaard P, Mosekilde L (2002) Fracture risk in patients with celiac disease, Crohn’s disease, and ulcerative colitis: a nation-wide follow-up study in 16,416 patients in Denmark. Am J Epidemiol 156:1–10
Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis 40:373–383
Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA III, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the litterature and statistical synthesis. J Bone Miner Res 15:721–739
Vestergaard P, Tigaran S, Rejnmark L, Tigaran C, Dam M, Mosekilde L (1999) Fracture risk is increased in epilepsy. Acta Neurol Scand 99:269–275
Jones G, Nguyen T, Sambrook PN, Eisman JA (1995) Thiazide diuretics and fractures: can meta-analysis help? J Bone Miner Res 10:106–111
Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ III (1987) Psychotropic drug use and the risk of hip fracture. N Engl J Med 316:363–369
Ensrud KE, Blackwell T, Mangione CM, Bowman PJ, Bauer DC, Schwartz A, Hanlon JT, Nevitt MC, Whooley MA (2003) Central nervous system active medications and risk for fractures in older women. Arch Intern Med 163:949–957
Vestergaard P, Rejnmark L, Mosekilde L (2006) Socioeconomic aspects of fractures within universal public healthcare: a nationwide case-control study from Denmark. Scand J Public Health 34:371–377
Munk-Jørgensen P, Mortensen PB (1997) The Danish Psychiatric Central Register. Dan Med Bull 44:82–84
Edsbacker S, Andersson T (2004) Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn’s disease. Clin Pharmacokinet 43:803–821
Czock D, Keller F, Rasche FM, Haussler U (2005) Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet 44:61–98
Dilger K, Schwab M, Fromm MF (2004) Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein. Inflamm Bowel Dis 10:578–583
Jonsson G, Astrom A, Andersson P (1995) Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver. Drug Metab Dispos 23:137–142
van Staa TP, Leufkens HGM, Abenhaim L, Zhang B, Cooper C (2000) Fractures and oral corticosteroids: relationship to daily and cumulative dose. Rheumatology 39:1383–1389
Aaron SD, Vandemheen KL, Hebert P, Dales R, Stiell IG, Ahuja J, Dickinson G, Brison R, Rowe BH, Dreyer J, Yetisir E, Cass D, Wells G (2003) Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med 348:2618–2625
Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A (2007) Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 370:657–666
Acknowledgements
The National Bureau of Statistics (Statistics Denmark) is acknowledged for its help, without which this project would not have been possible. Research librarian Ms. Edith Clausen is acknowledged for help with the references. The Danish Medical Research Council provided financial support (grant number 22-04-0495).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vestergaard, P., Rejnmark, L. & Mosekilde, L. Fracture Risk Associated with Different Types of Oral Corticosteroids and Effect of Termination of Corticosteroids on the Risk of Fractures. Calcif Tissue Int 82, 249–257 (2008). https://doi.org/10.1007/s00223-008-9124-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00223-008-9124-7