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Am Fam Physician. 2007;75(6):903-906

Background: The use of inhaled corticosteroids is common. Although inhaled, they have been shown to impact the hypothalamic-pituitary-adrenal axis. Over time, one major potential adverse outcome is an increase in the risk of fractures. Results of bone mineral density studies of patients using inhaled corticosteroids have been inconsistent. Results of some studies that assessed the risk of fractures related to inhaled corticosteroid have been called into question because other compounding variables were found in the studies. Also, the studies were of short duration and lacked information about important variables such as physical activity, activities of daily living, and socioeconomic status. Hubbard and associates assessed the dose-response relationship of inhaled corticosteroids and the risk of fractures over an extended period.

The Study: The participants in the study were patients 75 years or older from 31 general practice offices in the United Kingdom. The study initiation period was from January 1995 through February 1999. Patients identified as having asthma, chronic obstructive pulmonary disease (COPD), or both were included in the study. Data were extracted from computerized records that included information about inhaled, oral, and injected corticosteroids; all fracture events; and comorbid conditions. Data were extracted by October 1, 2002.

Of the 1,671 study participants, 59 percent (n = 982) received treatment with inhaled corticosteroids. All inhaled corticosteroid doses were converted into four categories: 200 mcg or less; 201 to 400 mcg; 401 to 600 mcg; and 601 mcg or more. The average age of the participants was 80.6 years. The mean follow-up period was 9.4 years. The participants also completed a questionnaire that included demographic information and other compounding variables (e.g., alcohol consumption, smoking habits).

Results: Of those who received corticosteroids, 118 had a fracture during the study, whereas only 69 of those who had no exposure to corticosteroids had a fracture. For patients with the highest dose of inhaled corticosteroids (more than 600 mcg), after controlling for age and sex, there was a significant increase in the risk of fractures (rate ratio 2.53; 95% confidence interval [CI], 1.65 to 3.89). This significant risk factor was also present when controlling for activity level. Adjusting for oral corticosteroid use, airflow obstruction diagnosis, previous fracture, and bronchodilator use had a similar increase in the risk for fractures (rate ratio, 4.21; 95% CI, 2.19 to 8.13). Patients using inhaled corticosteroids who received no oral form of corticosteroids during the study were still at a significant risk of fractures.

Conclusion: The authors conclude that inhaled corticosteroids in older patients with COPD and asthma increase the risk of fractures. This increase is not explained solely by the use of oral corticosteroids or level of physical activity. They add that inhaled corticosteroids are highly effective in asthma treatment but that the lowest dose possible to control airflow obstruction should be used.

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