Study Disputes Association Between Inhaled Steroids and Osteoporosis

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Long-term use of inhaled corticosteroids (ICS) by older women with asthma or COPD does not increase their risk for major osteoporotic fractures, show the results of a Canadian published in Osteoporosis International.

“Previous studies in asthma focused mainly on children and young adults, while studies in COPD predominantly studied older men. Our study evaluates the skeletal impact of long-term inhaled corticosteroid use in older women, an important population since older women are already at higher risk for osteoporosis and major osteoporotic fractures,” explained lead author Bryan Ng, from the Faculty of Pharmaceutical Sciences, at the University of British Columbia in Vancouver.

The effects of inhaled corticosteroids on fracture risk in older women with chronic respiratory diseases are not well established, he added.

To get a better understanding of the impact of inhaled corticosteroids onrisk of osteoporotic fractures in this group, the researchers crossmatched data from the bone mineral density (BMD) registry in the province of Manitoba to data in other health administrative databases to identify women aged ≥ 40 years of age who had a recorded diagnosis of asthma and/or chronic obstructive pulmonary disease (COPD) within the 3 years preceding their baseline BMD. They identified 6880 such women: 38% had asthma and 62% had COPD. All had received their baseline BMD test between 1996 and 2013.

Over a mean follow up period of 7.7 years, 810 (12%) women experienced a major osteoporotic fracture.

One in five women used oral corticosteroids within the first year of their BMD assessment, and 48.1% at some point during the follow up.

The women were stratified according to their exposure to inhaled corticosteroids within the first 12-month period prior to their baseline BMD test and over the entire follow-up period to determine if level of exposure impacted on risk of fracture. Women who had no exposure to inhaled corticosteroids were the reference group.

No level of inhaled corticosteroid use was found to be associated with increased risk of fracture, when assessed by both duration and quantity. In the first year, exposure to inhaled corticosteroids was assessed according to the total of dispensed days (p = 0.90), and the total quantity dispensed in mcg of beclomethasone equivalent (p = 0.67). Over the entire follow up period, intensity of exposure was assessed by the medication possession ratio (MPR), which is the proportion of days a patient was on inhaled corticosteroids (p = 0.62), and the dispensed quantities in mcg/year (p = 0.58).

Potential confounders were controlled for, including disease severity, age, BMI, parental hip fractures, smoking, rheumatoid arthritis, high alcohol use, prior fractures, and use of oral corticosteroid and anti-osteoporosis medications.

“Rheumatologists may be concerned about the risk for corticosteroid-induced osteoporosis in older women who use inhaled corticosteroids to control asthma and/or COPD. Our study results suggest that the use of inhaled corticosteroids to control these chronic respiratory diseases does not increase risk of fracture in this at-risk population,” said Dr. Bill Leslie, professor of medicine and radiology at the University of Manitoba.

“Rheumatologists can reassure patients who are being appropriately managed for their osteoporosis and who require inhaled corticosteroids for management of their chronic respiratory disease that they should not discontinue inhaled corticosteroids due to concerns about fracture risk.”

He added that rheumatologists should find the results “particularly reassuring” because the older women in the study could be considered an especially high risk group as they had been referred for a bone mineral density test. “Individuals who received a BMD test may have been referred by their physicians because they were perceived to be at a higher risk for osteoporosis. Therefore, our results are particularly reassuring since we have shown no increased risk from ICS use even in this at-risk group.”

While inhaled corticosteroids did not increase fracture risk, it was a different story for oral corticosteroids. The study showed their long term use are associated with a marked increase in fracture risk.

“We saw a 57% increased risk of major osteoporotic fracture among the greatest users (>100 days in the first year),” Dr. Leslie said. “Fracture risk was not significantly increased in those with short-term oral corticosteroid exposure (<100 days in the first year).Therefore, whenever possible, oral corticosteroids should be used as bridge therapy at the lowest effective dose for the shortest possible interval.”

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REFERENCE: Ng BC, Leslie WD, Johnson KM, FitzGerald JM, Sadatsafavi M, Chen W. "Effects of long-term inhaled corticosteroid treatment on fragility fractures in older women: the Manitoba BMD registry study." Osteoporos Int. 2020;31(6):1155-1162. doi:10.1007/s00198-020-05361-9