Dec. 12, 2002 -- Like their pill-form counterparts, evidence is mounting that inhaled corticosteroids, among the most effective drug treatments for persistent asthma, can raise the risk of bone fractures. And the higher the dose, the greater the risk.
In the latest published report, British researchers found a slight but steady risk of hip fractures among elderly women who took inhaled steroids such as Azmacort and Flovent. Their study examined the use of various types of corticosteroids by more than 16,000 elderly people who had hip fractures compared with 30,000 others without fractures.
"Our data suggests that in older patients, there is a small dose-related association between the recent use of inhaled corticosteroid and the risk of hip fracture," they write in the December 2002 issue of the American Journal of Respiratory and Critical Care Medicine. The researchers found that the risk of hip fracture associated with the use of inhaled corticosteroids was increased by almost 30%.
Since the 1950s, long-term use of oral corticosteroids -- prescribed for asthma, rheumatoid arthritis, bowel disease, and other conditions -- has been linked with a significant increase in the risk of osteoporosis, which can result in hip and other bone fractures. That's because these drugs act like cortisol, a naturally produced hormone that helps regulate blood sugar and metabolism, but also accelerates bone loss by preventing calcium absorption in the gut, and increasing calcium loss through urine. These drugs can also cause damage to the cells that help build bone. Some studies indicate that bone fractures occur in up to half the patients who use oral corticoids for longer than three consecutive months.
But evidence continues to accumulate linking accelerated bone loss resulting from the use of inhaled steroids as well, which decrease inflammation and swelling in the airways and boost the effect of bronchodilator medications. Although prescribed in lower doses than oral steroids, inhalers today deliver more corticosteroids per puff and have higher potency than those previously available.
The British researchers, like previous investigators, found hip fracture risk increased steadily with increasing duration of use. They also found the same relationship of a steady increase in the risk of fracture with increasing dosages.
Stavros C. Manolagas, MD, PhD, director of the Center for Osteoporosis and Metabolic Bone Disease at the University of Arkansas, says he not surprised by the findings. He says oral steroids have higher concentrations of cortisol-acting properties, but inhaled steroids are often used for longer than three months, a period that has been implicated with higher fracture risk.
"If you expect to take inhaled corticosteroids for longer than three months, my advice is that you talk to your doctor about also prescribing a bisphosphonate such as Fosamax, which is used to treat osteoporosis," he tells WebMD.
More advice for asthmatics using these drugs: Speak to your doctor about putting you on the lowest possible dose to treat your condition.
The British researchers only examined elderly female patients, who are prone to hip fracture since osteoporosis risk increases following menopause and estrogen loss -- whether or not corticosteroids are used. However, this age group is also being diagnosed with asthma in record numbers. In both the U.S and the U.K., roughly one in 10 seniors are already known to have asthma or chronic lung disease. The American Lung Association reports some 25 million Americans have been diagnosed with asthma, including more than 2 million who are older than age 65.
But it's not just the elderly who face increased fracture risk from inhaled steroids. A study in the New England Journal of Medicine last year found that women between ages 18 and 45 who used inhaled corticosteroids to treat persistent asthma had accelerated hip bone loss and that these losses increased with the number of puffs per day. In fact, the researchers calculated that a 30-year-old woman taking six puffs of Azmacort twice daily would have the same bone loss at age 50 as a 65-year-old who didn't use inhaled steroids.
SOURCES: American Journal of Respiratory and Critical Care Medicine, December 2002 • New England Journal of Medicine, Sept. 27, 2001 • Journal of Bone and Mineral Research, March 2001 • Journal of Bone and Mineral Research, June 2000 • American Lung Association• Stavros C. Manolagas, MD, PhD, director, Center for Osteoporosis and Metabolic Bone Disease; and director of Endocrinology and Metabolism at the University of Arkansas College of Medicine.