One year prospective open study of the eVect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density

Background—Inhaled corticosteroids are recognised as the most eVective agents in the treatment of asthma. However, concerns have been expressed about the eVects of high doses of inhaled corticosteroids on safety in relation to bone resorption and formation. This study measures the eVects of two inhaled corticosteroids on bone markers and bone mineral density (BMD) over one year. Methods—A one year randomised, prospective, open parallel study comparing inhaled fluticasone propionate (FP), 500 μg twice daily in 30 patients, and budesonide (BUD), 800 μg twice daily in 29 patients, delivered by metered dose inhaler and large volume spacers was performed in adults with moderate to severe asthma. Biochemical markers of bone turnover (osteocalcin, procollagen type 1 C-terminal propeptide (PICP), immunoreactive free deoxypyridinoline (iFDpd), N-terminal crosslinked telopeptides of type I collagen (NTx)), BMD at the spine and femoral neck, and serum cortisol concentrations were measured at baseline and 12 months later. Results—There were no significant diVerences between the inhaled steroids on bone markers of bone resorption and formation or bone mineral density. Bone mineral density of the spine increased slightly in both groups over the 12 month period. Serum osteocalcin levels increased from baseline in both treatment groups (FP 16.9%, p = 0.02; BUD 14.3%, p = 0.04). PICP did not diVer significantly from baseline. Both markers of bone resorption (iFDpd, NTx) varied considerably with no significant changes after one year. There was a significant correlation in percentage change from baseline between BMD of the spine and osteocalcin at 12 months (r = 0.4, p = 0.017). Mean serum cortisol levels remained within the normal range in both groups following treatment. Conclusion—There was no evidence of a decrease in BMD during 12 months of treatment with high doses of either FP or BUD. The change in spine BMD correlated with the increase in osteocalcin. Studies extending over several years are needed to establish whether these findings persist. (Thorax 1999;54:223–229)