Potential effects of fluticasone propionate on bone mineral density in patients with asthma: a 2-year randomized, double-blind, placebo-controlled trial

Mayo Clin Proc. 2004 Apr;79(4):458-66. doi: 10.4065/79.4.458.

Abstract

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

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Androstadienes / administration & dosage
  • Androstadienes / adverse effects*
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / adverse effects*
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / adverse effects*
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Bone Density / drug effects*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Monitoring
  • Eye Diseases / chemically induced
  • Female
  • Fluticasone
  • Forced Expiratory Volume
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / drug effects
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / drug effects
  • Time Factors
  • Treatment Outcome

Substances

  • Androstadienes
  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Fluticasone
  • Hydrocortisone