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OBJECTIVE: This study examined the effects of daily and cumulative oral corticosteroid doses on the risk of fractures. METHODS: Information was obtained from the General Practice Research Database, which contains medical records of general practitioners in England and Wales. The study included 244 235 oral corticosteroid users and 244 235 controls. RESULTS: Patients taking higher doses (at least 7. 5 mg daily of prednisolone or equivalent) had significantly increased risks of non-vertebral fracture [relative rate (RR)=1.44, 95% confidence interval (CI) 1.34-1.54], hip fracture (RR=2.21, 95% CI 1.85-2.64) and vertebral fracture (RR=2.83, 95% CI 2.35-2.40) relative to patients using oral corticosteroids at lower doses (less than 2.5 mg per day). Fracture risk was also elevated among people with higher cumulative exposure to oral corticosteroids over the study period, but this effect was almost wholly removed by adjustment for daily dose, age, gender and other confounding variables. CONCLUSIONS: These findings suggest that the adverse skeletal effects of oral corticosteroids manifest rapidly and are related to daily dose. The level of previous exposure to oral corticosteroids was not a strong determinant of the risk of fracture. Preventive measures against corticosteroid-induced osteoporosis should therefore be instituted as soon after the commencement of glucocorticoid therapy as possible.

Original publication




Journal article


Rheumatology (Oxford, England)

Publication Date





1383 - 1389


Department of Pharmacoepidemiology and Pharmacotherapy, University of Utrecht, Sorbonnelaan 16, Utrecht, The Netherlands.


Humans, Osteoporosis, Adrenal Cortex Hormones, Administration, Oral, Registries, Risk Factors, Dose-Response Relationship, Drug, Adult, Aged, Middle Aged, Female, Fractures, Bone