Osteoporosis is a well-known, serious complication of long-term high-dose corticosteroid therapy. This study was performed to determine the effects of commonly used doses of oral and inhaled steroids on biochemical indices of bone formation. Initially we examined the long-term effects of oral steroids. Thirty-four outpatients with symptomatic asthma or chronic obstructive airways disease (COAD) receiving long-term oral prednisolone (mean 10.1 mg daily) were compared with 34 control subjects with asthma or COAD matched individually for age, sex, and menopausal status who were not taking oral steroids. Plasma osteocalcin concentrations were significantly lower (patients 6.3 +/- 0.1 ng/ml; control subjects 8.6 +/- 0.5 ng/ml, mean +/- SEM; p < 0.01) in patients on steroids with no difference in alkaline phosphatase. To examine the short-term effects of oral and inhaled corticosteroids, healthy male volunteers were given a 7-d course of either 15 mg oral prednisolone daily (n = 10) or 500 micrograms inhaled beclomethasone twice daily (n = 20). After 1 wk of oral prednisolone, mean plasma osteocalcin decreased from 11.8 +/- 1.1 ng/ml to 6.9 +/- 0.8 ng/ml (p < 0.001). With inhaled beclomethasone mean plasma osteocalcin decreased from 11.6 +/- 0.6 ng/ml to 9.6 +/- 0.6 ng/ml (p < 0.001) with no change in alkaline phosphatase. In doses routinely prescribed for the prophylaxis and treatment of asthma, oral and inhaled steroids suppress osteocalcin levels and may therefore inhibit bone formation. This effect is seen with short courses of steroids and also with chronic administration.(ABSTRACT TRUNCATED AT 250 WORDS)