Inhaled Corticosteroid Use and Bone-Mineral Density in Patients With Asthma
ABSTRACT & COMMENTARY
Synopsis: This study demonstrated an inverse relationship between inhaled corticosteroid dose and bone-mineral density in adults ages 20-40 years.
Source: Wong CA, et al. Lancet 2000;355:1399-1403.
Inhaled steroids are a key therapy for patients with asthma and related conditions such as allergic rhinitis and chronic allergic sinusitis. One in three British asthmatic patients takes an inhaled corticosteroid regularly and frequently for a prolonged duration. While it is commonly believed that inhaled steroids are devoid of the systemic effects and risks seen with oral use, this notion has been called into question. Inhaled steroids have been associated with bruising, cataracts, and glaucoma. Doses in the range of 1000-1500 mg daily can suppress adrenal function. This study was undertaken to determine if inhaled glucocorticoids also retard bone accretion. To avoid confounding variables such as menopause and other effects of age, Wong and associates studied 196 adults (119 women) between the ages of 20-40 years who regularly used inhaled steroids for the management of asthma, but who had minimal exposure to other routes of delivery. Bone mineral density (BMD) of the lumbar spine and left hip (femoral neck, Ward’s triangle, and trochanter) was determined by dual energy X-ray absorptiometry using Lunar equipment. The median duration of inhaled steroid use was six years with a median cumulative dose of 876 mg. There was a clear negative correlation between dose and BMD at all sites. The effect was comparable for cortical and trabecular bone. In univariate analysis, BMD was also related to weight, body mass index, never smoking, calcium intake, cumulative estrogen exposure, and physical activity. None of the subjects had severe asthma that limited activity and the mean forced expiratory volume was 93% of expected. Thus, inactivity and disease severity are unlikely to account for the findings. The inverse association was comparable in men and women. The effect size was not dramatic. One would have to use a dose of 2000 mg daily for seven years to reduce bone mass by one standard deviation and thereby theoretically double the risk of fracture. However, chronic use is common because asthma rarely remits with time. Further, some studies have suggested that fracture occurs at a higher BMD in individuals exposed to exogenous glucocorticoids. Thus, Wong et al suggest that the results of this study have important public health implications.
COMMENT BY SARAH L. BERGA, MD
Several smaller studies have suggested that inhaled glucocorticoids impair bone accretion, but this is the first to demonstrate the impact so clearly. Thus, the point can no longer be reasonably argued. There has always been this fantasy that drugs delivered by nonoral routes stay where they are put. In fact, drugs delivered to the lung are very well absorbed, as are drugs delivered vaginally and transdermally. Oral delivery may be one of the least effective routes of administration because the liver metabolizes a certain fraction of that drug prior to delivery into the circulation. The same obviously doesn’t hold for nonoral routes of delivery.
The take-home message is clear. Add chronic use of inhaled glucocorticoids to the list of reasons to screen for osteoporosis. Patients who must use inhaled glucocorticoids should use the least dose possible. If BMD is low, it may be worthwhile to take a bisphosphonate. Although glucocorticoids primary impair bone formation and bisphosphonates primarily lessen bone resorption, bisphosphonates nonetheless do help to maintain BMD in this context.
Which of the following modifiable factors was not associated with better bone accretion in this study?
a. Cumulative estrogen exposure.
b. Smoking.
c. Body-mass index.
d. Calcium intake.
e. Physical activity.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content. TESTING
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content