EFFECTS OF LONG-TERM USE OF HIGH-DOSE INHALED STEROIDS ON BONE-DENSITY AND CALCIUM-METABOLISM

Background: Inhaled steroids are the mainstay in the antiinflammatory treatment of asthma. In the last few years, these agents have been used in increasing doses. Because high doses of inhaled steroids can reduce serum osteocalcin levels, there are concerns regarding their long-term effects on bone metabolism. Methods: We examined the effects of doses of 800 mu g/day or greater of beclomethasone or budesonide for more than 18 months in 37 asthmatic subjects (group A), matched to a control group of 37 asthmatic subjects using little or no inhaled steroids (< 500 mu g group B). All had a clinical evaluation measurements of expiratory flows, and determination of serum creatinine, calcium phosphate, gamma-glutamyl transpeptidase, alkaline phosphatase, cortisol, and osteocalcin levels. A 2-hour urinary sample was obtained for creatinine, calcium, phosphate, hydroxyproline, and cortisol measurements. Bone density was assessed at the lumbar spine level and at the hip with a Hologic-QDR-2000 osteodensitometer (Hologic, Boston Mass.). Results: The mean (+/-SD) daily dose of inhaled steroids over the last 2 years was 1140 +/- 353 mu g in group A (mean duration of use of >800 mu g/day, 34.2 +/- 13.0 months) and 89 +/- 98 mu g for group B (mean duration of use of <500 mu g/day, 15.7 +/- 18.8 months). The number of oral steroid treatments (<15 days) during the last 2 pears was small in the two groups, 0.92 +/- 1.27 in group A and 0.05 +/- 0.23 in group B (p > 0.05). The only differences between our two groups in terms of serum or urinary parameters were for mean osteocalcin level, which was lower in group A (2.16 +/- 1.09 ng/nl) than in group B (2.70 +/- 0.98 ng/ml) (p = 0.029), and in mean urinary phosphorous level, which was higher in group A (1.44 +/- 0.76 mmol/2 hr) than in group B (1.26 +/- 0.89 mmol/2 hr (p = 0.034). Mean urinary hydroxyproline levels were 15.51 +/- 6.98 mu mol/2 hr in group A and 13.53 +/- 7.13 mu mol/2 hr in group B (p > 0.05). Mean mineral bone densities of the lumbar spine and hip were similar in the two groups with values of 0.923 +/- 0.136 gm/cm(2) and 0.719 +/- 0.147 gm/cm(2) in group A and 0.933 +/- 0.154 gm/cm2 and 0.694 +/- 0.095 gm/cm(2) in group B (p > 0.05). The T and Z scores for lumbar spine were - 1.32 +/- 1.22 and -0.85 +/- 1.02 in group A and -1.19 +/- 1.33 and -0.72 +/- 1.08 in group B (p > 0.05). There was no correlation between the duration or dose of steroid use and bone density or osteocalcin. Although the serum osteocalcin level was lower in tire group of subjects using high-dose inhaled steroids, suggesting an osteoblastic depression, bone density was not significantly different compared with the control group. Conclusions: This study shows that although the serum osteocalcin level was lower and the urinary phosphorus level was higher in subjects using high-dose inhaled steroids for a mean of 34 months, compared with a control group, no significant difference in bone density or other markers of bone metabolism was found between the two groups.