Common Questions
How does corticosteroid dose affect the risk of osteoporosis?
Corticosteroid use has been associated with bone loss and fractures, but studies disagree about whether the cumulative dose is more significant than the daily dose in determining risk (1,2). The most dramatic change in bone mineral density occurs in the first 3-6 months after initiation of corticosteroids (1). Even short duration of corticosteroid use, less than 3 months, and intermittent use, as seen with corticosteroid burst therapy in pulmonary diseases, may cause a significant decrease in BMD and increase in fracture risk (3). Alternate-day dosing regimens do not reduce osteoporosis risk (4).
Studies looking at low dose corticosteroid use, as low as 2.5 mg daily, show an increase in bone loss and fracture risk (2,5). The risk of fracture with corticosteroid use increases with higher doses of steroids. A retrospective cohort study with over 244,000 corticosteroid users compared to non-users showed that the relative risk of vertebral fracture in patients taking daily prednisolone went from 1.55 (1.20-2.01) on less than 2.5 mg, to 2.59 (2.16-3.10) on 2.5-7.5 mg, and to 5.18 (4.25-6.31) on 7.5 mg or higher (5). In another retrospective cohort study, the relative risk for fracture in patients using greater than 10 mg prednisone daily, continuously for over 3 months, was 7.16 at the hip, and 16.94 at the lumbar spine, compared to control patients who had never used oral corticosteroids (3).
The effect of low-dose corticosteroid therapy on BMD and fracture risk has been most closely studied in specific patient populations. Many patients with early diagnosis of rheumatoid arthritis are started on low-dose corticosteroids, less than or equal to 5 mg daily, to prevent the development of rheumatoid arthropathy. Even low-dose corticosteroids in these patients have been shown to decrease BMD and increase fracture risk (6).
Studies evaluating the effect of inhaled steroids on BMD in patients with asthma or chronic obstructive pulmonary disease have shown mixed results. One study showed a dose-related decrease in BMD at the total hip and trochanter in pre-menopausal women on inhaled corticosteroids (7). However, a Cochrane systematic review of inhaled corticosteroid effects on bone metabolism in patients with asthma and mild chronic obstructive pulmonary disease found no evidence of increased risk of bone loss or fractures at conventional doses over a two- three year period (8). A large meta-analysis of case-controlled trials showed a nonsignificant decrease in BMD in patients using moderate to high doses of inhaled corticosteroids as compared to controls (9).
While corticosteroids have been shown to decrease BMD, it is important to remember that corticosteroids have been shown to increase fracture risk without any significant change in BMD. Therefore, all patients on corticosteroids are at higher risk for fractures, even without evidence of decreased BMD on DXA scans (10).
- Tannirandorn P, Epstein S. Drug-Induced Bone Loss. Osteoporosis International 2000; 11: 637-659.
- Van Staa TP, Leufkens HGM, Abenhaim L, Zhang B, Cooper C.. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology 2000; 39: 1383-1389.
- Steinbuch M, Youket TE, Cohen S. Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporosis International 2004; 15: 323-328.
- Gluck OS, Murphy WA, Hahn TJ, Hahn B. Bone loss in adults receiving alternate day glucocorticoid therapy. A comparison with daily therapy. Arthritis Rheum 1981; 24: 892-898.
- Van Staa TP, Leufkens HGM, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures.. Journal of Bone and Mineral Research 2000; 16;6: 993-1000.
- Buckley LM, Leib ES, Cartularo S, Vacek PM, Cooper SM. Calcium and vitamin D supplementation prevents bone loss in the spine secondary to low dose corticosteroids in patients with rheumatoid arthritis: a randomized, double-blind, placebo controlled trial. Annals of Internal Medicine 1996; 125: 961-986.
- Kelly HW. Potential adverse effects of the inhaled corticosteroids. Journal of Allergy and Clinical Immunology 2003; 112;3: 469-478.
- Jones A, Fay JK, Burr M, Stone M, Hood K, Roberts G. Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease. The Cochrane Database of Systematic Reviews 2002; Issue 1.
- Sharma PK, Malhotra S, Pandhi P, Kumar N. Effect of inhaled steroids on bone mineral density: a meta-analysis. Journal of Clinical Pharmacology 2003; 43: 193-197.
- Van Everdingen AA, Siewertsz van Reesema DR, Jacobs JW, Bijlsma JW. Low-dose glucocorticoids in early rheumatoid arthritis: discordant effects on bone mineral density and fractures. Clin Exp Rhematolog 2003; 21;2: 145-147.