Calcified Tissue International

, Volume 79, Issue 2, pp 69–75 | Cite as

Methotrexate, Azathioprine, Cyclosporine, and Risk of Fracture

  • P. VestergaardEmail author
  • L. Rejnmark
  • L. Mosekilde


We studied the fracture risk associated with use of methotrexate, azathioprine, and cyclosporine. The study was designed as a case-control study. All patients with a fracture (n = 124,655) in the year 2000 in Denmark served as cases. Information on fractures and confounders was retrieved from the National Hospital Discharge Register and a number of other national registers. For each case, three age- and gender-matched controls were randomly drawn from the general population (n = 373,962). Exposure was use of the drugs and a number of covariates including other immunosuppressive drugs, corticosteroids, any cancer, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, psoriasis, liver and kidney disease, prior fracture, and alcoholism. Azathioprine was associated with an increase in overall fracture risk, but besides this, none of the drugs was significantly associated with overall fracture risk or risk of hip, spine, or forearm fracture. Liver [odds ratio (OR) = 1.55, 95% confidence interval (CI) 1.42–1.69] and kidney (OR = 1.26, 95% CI 1.16–1.37) diseases were significantly associated with increased risk of fractures. Azathioprine was associated with an increase in overall fracture risk but not in the risk of spine, hip, or forearm fractures. Methotrexate and cyclosporine were not associated with fracture risk. It thus seems that the underlying disease for which the treatment is administered may be responsible for much of the increase in fracture risk rather than the drugs used to treat the disorder in question.


Methotrexate Azathioprine Cyclosporine Fracture risk 



Danmarks Statistik (Statistics Denmark) is acknowledged for the help without which this project would not have been possible. Research librarian Ms. Edith Clausen is acknowledged for invaluable help with the references. The Danish Medical Research Council granted financial support (grant 22-04-0495).


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of Endocrinology and Metabolism CAarhus Amtssygehus, Aarhus University HospitalAarhus CDenmark

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