Prevalence and progression of osteoporosis in patients with COPD: results from the TOwards a Revolution in COPD Health study.
BACKGROUND
Osteoporosis is common in patients with COPD, but its prevalence and progression are not well characterized. Concerns have been raised over the possible deleterious effect of long-term therapy with inhaled corticosteroids (ICSs) on bone density in this population. Here, we investigated the long-term effects of therapy with fluticasone propionate (FP) alone, salmeterol (SAL) alone, and a SAL/FP combination (SFC) on bone mineral density (BMD) and bone fractures in patients with moderate-to-severe COPD in the TOwards a Revolution in COPD Health (TORCH) study.


METHODS
A randomized, double-blind, parallel-group, placebo-controlled study conducted at 88 US centers involving 658 patients (a subset of 6,184 international subjects in TORCH). Therapy with placebo, SAL (50 microg), FP (500 microg), or SFC (SAL 50 microg/FP 500 microg) twice daily was administered for 3 years. Baseline and yearly measurements of BMD at the hip and lumbar spine were performed. The incidence of traumatic and nontraumatic bone fractures was recorded.


RESULTS
At baseline, 18% of men and 30% of women had osteoporosis, and 42% of men and 41% of women had osteopenia based on BMD assessments. Forty-three percent of subjects completed all testing. The changes in BMD at the hip and lumbar spine over 3 years were small. No significant differences were observed between treatment arms (adjusted mean percent change from baseline at hip was -3.1% for placebo, -1.7% for SAL, -2.9% for FP, and -3.2% for SFC therapy, respectively; while, the corresponding changes for the lumbar spine were 0, 1.5%, -0.3%, and -0.3% for placebo, respectively, SAL, FP, and SFC therapy). The incidence of fractures was low and was similar for all treatments (5.1% to 6.3%).


CONCLUSIONS
Osteoporosis is highly prevalent in patients with COPD, irrespective of gender. In the TORCH study, no significant effect on BMD was detected for ICS therapy compared with placebo.


BACKGROUND
ClinicalTrials.gov Identifier: NTC00268216.
Ferguson
Gary T
GT
Pulmonary Research Institute of Southeast Michigan, Livonia, MI. Electronic address: garytferguson@msn.com.
Calverley
Peter M A
PMA
Department of Medicine, University Hospital Aintree, Liverpool, UK.
Anderson
Julie A
JA
Respiratory Medicines Centre, GlaxoSmithKline, Middlesex, UK.
Jenkins
Christine R
CR
Woolcock Institute of Medical Research, Camperdown, NSW, Australia.
Jones
Paul W
PW
Division of Cardiac and Vascular Science, St. George's, University of London, London, UK.
Willits
Lisa R
LR
Respiratory Medicines Centre, GlaxoSmithKline, Middlesex, UK.
Yates
Julie C
JC
Respiratory Medicines Centre, GlaxoSmithKline, Triangle Park, NC.
Vestbo
Jørgen
J
Department of Cardiology and Respiratory Medicine, Hvidovre Hospital, Hvidovre, Denmark; North West Lung Centre, Wythenshawe Hospital, Manchester, UK.
Celli
Bartolome
B
Pulmonary and Critical Care Division, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA.
D000368:Aged; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000730:Androstadienes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D000068298:Fluticasone; D000068297:Fluticasone-Salmeterol Drug Combination; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology*; D015995:Prevalence; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000188:drug therapy*; D012307:Risk Factors; D000068299:Salmeterol Xinafoate; D016896:Treatment Outcome; D014481:United States
D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol