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

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.