Effect of once-daily fluticasone furoate/vilanterol versus vilanterol alone on bone mineral density in patients with COPD: a randomized, controlled trial

Abstract

Background: The relationship between inhaled corticosteroids and bone mineral density (BMD) remains uncertain despite extensive research. Methods: This was an international, multicenter, randomized, double-blind, parallel-group, 3-year noninferiority study. Patients with chronic obstructive pulmonary disease (COPD) (⩾40 years of age; smoking history ⩾10 pack years) and at least one native hip evaluable for BMD were enrolled and randomized 1:1, stratified by sex, to treatment with vilanterol (VI) 25 µg or fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg. BMD measurements were taken via dual-energy X-ray absorptiometry every 6 months. The primary endpoint was assessment of the noninferiority of change from baseline in total hip BMD per year at the −1% noninferiority level. Change from baseline in BMD at the lumbar spine and BMD measurements by sex were secondary endpoints. Incidences of COPD exacerbations and bone fractures throughout the study were also recorded. Results: Of 283 randomized patients, 170 (60%) completed the study. Noninferiority was demonstrated for FF/VI versus VI with regards to change from baseline in total hip BMD per year, with changes of −0.27% and 0.18%, respectively, and a treatment difference of −0.46% per year [95% confidence interval (CI) −0.97 to 0.06]. The treatment difference for FF/VI versus VI regarding lumbar spine BMD was −0.51% per year (95% CI −1.11 to 0.10). COPD exacerbations and bone fracture rates were similar between treatment groups. Conclusion: FF/VI showed noninferiority to VI for change from baseline in total hip BMD per year, when assessed at the −1% noninferiority margin in a combined sample of men and women with COPD. The reviews of this paper are available via the supplemental material section.

Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD

“…In one study, BMDs of the lumbar spine ( p=0.007) and the femoral neck ( p<0.001) were significantly lower in the ICS group (triamcinolone) versus placebo after for budesonide 320 μg compared with all other treatments for total lumbar spine BMD ( p⩽0.037) and for budesonide 320 μg versus formoterol for total hip BMD ( p=0.012) [35]. However, the remaining six RCTs did not find such an effect [9,21,28,29,31,32].…”

“…In total, 12 studies reported this outcome (eight RCTs, two cohort studies and one case-control study). The reporting methods for bone mineral density (BMD) data in the RCTs precluded pooling results in a meta-analysis [9,21,28,29,31,32,35,42]. In one study, BMDs of the lumbar spine ( p=0.007) and the femoral neck ( p<0.001) were significantly lower in the ICS group (triamcinolone) versus placebo after for budesonide 320 μg compared with all other treatments for total lumbar spine BMD ( p⩽0.037) and for budesonide 320 μg versus formoterol for total hip BMD ( p=0.012) [35].…”

“…Only one of the three NCC studies found a significant association between ICS use and cataract development [86], but no association with glaucoma was described [85,93,96] (table 2). [18] CALVERLEY [9] DRANSFIELD [25] MALTAIS [31] VESTBO [14] VESTBO […”

“…A dose-dependent increase in risk associated with ICS use was observed.FracturesIn total, 19 studies reported this outcome: nine RCTs, five cohort studies and five NCC studies. The pooled analysis of 10 RCTs with 41 342 participants did not observe a higher risk of fracture with exposure to ICSs (RR 1.10, 95% CI 0.97-1.25; p=0.13; I 2 =0%)[9,14, 16, 18, 24,25,27,31,34,43]…”