Dose-related decrease in bone density among asthmatic patients treated with inhaled corticosteroids.
BACKGROUND
Inhaled corticosteroids are being prescribed more commonly and in higher doses than previously in the management of asthma. Although these topically active compounds have less potential for systemic impact than oral steroids, biochemical markers suggest that they are not devoid of systemic side effects. We conducted this study to investigate the effect of commonly prescribed doses of inhaled steroids on bone density.


METHODS
We studied 36 patients with asthma. Those in group A (n = 18) had been taking inhaled beclomethasone dipropionate or budesonide in a dosage of 800 micrograms or more per day for at least 1 year. Those in group B (n = 18) had used only bronchodilator therapy. Adrenal function was assessed by morning serum cortisol level and by short adrenocorticotropic hormone stimulation test. Bone turnover was assessed by measurement of serum osteocalcin, alkaline phosphatase, and urinary pyridinium cross-links. Bone mineral density was measured by dual-energy x-ray absorptiometry with a Hologic QDR-1000 densitometer (Hologic Inc., Waltham, Mass.).


RESULTS
Group A, mean age (SD) = 36.6 (8.4) years, had used inhaled corticosteroids at a mean dose of 1323 micrograms/day (range, 800 to 2000 micrograms/day) for a median duration of 24 months. Group B, mean age (SD) = 33.4 (8.1) years, had not been taking any form of steroid. Four patients from group A had suppressed morning serum cortisol; three of these had abnormal adrenocorticotropic hormone stimulation test results. All patients in group B had normal baseline adrenal function and an appropriate response to adrenocorticotropic hormone. Mean serum osteocalcin level in group A was significantly lower than that in group B (8.8 vs 14.2 ng/ml, p = 0.0003). Bone density measurements showed parallel changes: in group A the mean Z score (SD) of the femoral neck was -0.78 (1.02), significantly below predicted normal values (p = 0.0025). Mean Z scores of the lumbar spine and of femoral Ward's triangle were not significantly reduced. In group B the mean Z scores of the lumbar spine, femoral neck, and femoral Ward's triangle were all within normal limits. In group A the dose duration of inhaled corticosteroid therapy corrected for body mass index correlated negatively with bone density and adrenal function measurements.


CONCLUSIONS
We conclude that the regular use of conventional doses of inhaled corticosteroids by patients with asthma can suppress adrenal function and decrease bone density in a dose-related fashion.
D000280:Administration, Inhalation; D000293:Adolescent; D000311:Adrenal Glands / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000336:Aerosols; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D019819:Budesonide; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D011282:Pregnenediones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D000336:Aerosols; D000893:Anti-Inflammatory Agents; D011282:Pregnenediones; D015675:Osteocalcin; D019819:Budesonide; D000324:Adrenocorticotropic Hormone; D001507:Beclomethasone; D006854:Hydrocortisone