Original Article
Potential Effects of Fluticasone Propionate on Bone Mineral Density in Patients With Asthma: A 2-Year Randomized, Double-Blind, Placebo-Controlled Trial

https://doi.org/10.4065/79.4.458Get rights and content

Objective

To evaluate the effects of treatment with fluticasone propionate vs placebo on bone, hypothalamic-pituitary-adrenal (HPA) axis function, and the eyes in patients with asthma.

Patients and Methods

This randomized, double-blind, placebo-controlled study of 160 patients with asthma who had minimal previous exposure to corticosteroids was conducted from July 1994 through June 1997. Patients received fluticasone at 88 µg twice daily, fluticasone at 440 µg twice daily, or placebo twice daily for 2 years. Bone mineral density (BMD) was evaluated every 6 months by lumbar spine, proximal femur, and total body scans. Measurements of HPA axis function and ophthalmic evaluations were conducted at similar intervals.

Results

Among the 3 groups, no significant differences were observed in BMD at week 104 (at any anatomical site). Mean percent change from baseline in the lumbar spine was less than 1% for all 3 groups. At all time points, HPA axis function was similar in the 88-µg fluticasone group compared with the placebo group. For mean change from baseline in corticotropin-stimulated peak cortisol (P=.003 and P=.02 at weeks 24 and 52, respectively) and area under the stimulated plasma cortisol vs time curve (P=.002 and P=.02 at weeks 24 and 52, respectively), statistically significant reductions from baseline were observed in the 440-µg fluticasone group compared with the placebo group. These reductions of 10% to 13% from baseline were not accompanied by other signs of systemic effect and did not persist with continued treatment (at weeks 76 and 104). No important ocular changes were observed.

Conclusion

Long-term treatment with 88 µg of fluticasone twice daily was comparable to placebo in all skeletal, ophthalmic, and HPA axis function assessments. Treatment with fluticasone at 440 µg twice daily resulted in no significant effects on BMD and a statistically significant but not clinically important temporary reduction in cortisol production.

Section snippets

Procedures

This multicenter randomized, double-blind, parallelgroup trial (conducted from July 1994 through June 1997) evaluated the safety of 2 doses (88 µg and 440 µg) of fluticasone administered twice daily with use of a chlorofluorocarbon metered dose inhaler without a spacer device vs placebo for 104 weeks in 160 adult patients with mild asthma (mean forced expiratory volume in 1 second [FEV1] of 82%-85% predicted). Blinded labels (based on a randomization code generated by a statistician at the

Disposition and Demographics

Of the 190 patients screened (ie, entered the 21-day single-blind placebo run-in period), 30 did not meet screening criteria (including 4 with BMD below the limits established for young healthy controls); thus, 160 patients were randomized to treatment (Table 2) in groups balanced across 5 demographic characteristics. More patients in the fluticasone-treated groups compared with the placebo group withdrew from the study. Withdrawals because of adverse events considered at least possibly related

DISCUSSION

The results of this placebo-controlled study in which patients with mild asthma and minimal prior systemic corticosteroid exposure used aerosol fluticasone at 88 µg or 440 µg twice daily (highest recommended dosage for patients not requiring prednisone) for 2 years show that long-term treatment with either dose of fluticasone was comparable to placebo in all assessments of skeletal and ophthalmic function. Treatment with high-dose fluticasone (440 µg twice daily) was associated with a

CONCLUSION

Twice-daily treatment with fluticasone at 88 µg and 440 µg (the highest recommended dose for patients not requiring prednisone) for up to 2 years was well tolerated in adults with mild asthma. Fluticasone at 88 µg had effects comparable to those of placebo on HPA axis function, the skeleton, and the eyes. Fluticasone at 440 µg had minor, transient effects on HPA axis function, consistent with observed effects in studies of shorter duration, but no statistically significant effects on BMD at the

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    This study was funded by GlaxoSmithKline, Research Triangle Park, NC.

    Results of this study were presented at the World Asthma meeting, Chicago, Ill, July 12-15, 2001; the American Thoracic Society meeting, Chicago, Ill, April 25-28, 1998; and the American Society of Bone and Mineral Research meeting, San Francisco, Calif, December 3-6, 1998.

    For editorial comment, see page 453.

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