– Patients could benefit from regular monitoring for BMD, fracture risk

by Salynn Boyles, Contributing Writer
February 07, 2018

Long-term use of inhaled corticosteroids (ICS) at high doses was associated with a modest increase in risk for bone fractures in both men and women with chronic obstructive pulmonary disease (COPD), reported Canadian researchers.

Use of inhaled corticosteroids for 4 years or more at doses of ≥1 mg per day of fluticasone or equivalent was associated with a slightly higher risk of hip and upper extremity fractures, but not non-vertebral fractures, according to Anne Gonzalez, MD, of McGill University Health Centre in Montreal, and colleagues.

The dose-dependent, negative impact of inhaled corticosteroids on bone mineral density (BMD) is well known, but the research is among the first to show an increase in bone fractures in a COPD population, they wrote in Chest.

For this population-based cohort study, the researchers examined 1990-2005 data from two health care databases in Quebec, Canada to identify COPD patients, ages ≥55. The patients were followed until 2007 for hip and upper extremity fractures.

A nested case-control analysis was conducted to match each fracture case with 20 controls for age, sex, and follow-up time. Prescriptions for inhaled corticosteroids during the follow-up period were identified. Conditional logistic regression analysis was used the estimate the adjusted rate ratio of fractures with usage of inhaled corticosteroids.

There were 240,110 patients, ages ≥55, with newly-treated COPD identified between 1990 and 2005. During a mean 5.3 years of follow-up, 19,393 fractures were reported, for a rate of 15.2 cases per 1,000 per year.

The authors reported that any use of inhaled corticosteroids was not associated with an increased rate of fracture (relative risk 1.00, 95% CI 0.97-1.03).

Use of an inhaled corticosteroid for >4 years at daily doses of 1,000 mcg or more in fluticasone-equivalents was associated with a slight increase in risk (RR 1.10, 95% CI 1.02-1.19).

The observed risk increase was similar for men and women.

“Since fractures are more frequent in women than men, our study suggests that the excess number of fractures associated with ICS will be greater in women even though we did not find that the risk increase was particularly higher in women than in men,” said co-author Samy Suissa, PhD, of McGill University’s Lady Davis Institute.

He added that an even larger cohort study would be needed to quantify this excess number.

The researchers concluded that the benefits and risks of prescribing inhaled corticosteroids to patients with COPD need to be carefully considered, and the prescribed dose should be as low as possible in patients who receive the treatment.

In an accompanying editorial two COPD researchers noted that the findings are consistent with that of a trial showing a significant decline in BMD among patients with asthma after 3 years of inhaled corticosteroids treatment, but not 1 year.

“Together, these and other data suggest that long-term ICS therapy in COPD leads to accelerated bone mineralization and increased risk of long-bone and vertebral fractures, particularly among female patients who may have underlying osteopenia or osteoporosis,” wrote Yu Ji Cho, MD, PhD, of the University of British Columbia in Vancouver, and Don D. Sin, MD, of the National University School of Medicine in Jinju, South Korea.

They noted that inhaled corticosteroids are still commonly use in the treatment of COPD, despite calls for large reductions in inhaled corticosteroids use among patients who are not frequent exacerbators.

“For the large majority of COPD patients, ICS is not required; they can be managed with short or long acting bronchodilators,” Cho and Sin wrote, adding that the treatment should be used at the lowest effective dose in patients who require inhaled corticosteroids therapy. Also, patients taking inhaled corticosteroids should undergo regular monitoring for BMD and fracture risk.

“ICS therapy is useful in patients who experience frequent exacerbations. However, they are fraught with significant side effects, which may be dose-dependent,” they wrote. “It is now well established that ICS has deleterious effects on bone that increase the risk of fractures, a side effect that is largely avoidable and can be mitigated by careful monitoring and most importantly by reducing (and in vast majority eliminating) the use of ICS for COPD patients in the community.”

The study had limitations including the fact that data on smoking, BMI, pulmonary function, level of physical activity, and diet were not available in the analyzed databases.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
  

  Primary Source

  CHEST

  Source Reference: Gonzalez A, et al “Long-term use of inhaled corticosteroids in COPD and the risk of fracture” CHEST 2018.

  Secondary Source

  CHEST

  Source Reference: Cho YJ and Sin DD “Inhaled corticosteroids and fractures in COPD: Can we finally put this to bed?” CHEST 2018.