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Source: Israel E, et al. N Engl J Med. 2001;345:941-947.
One hundred nine premenopausal women with the diagnosis of asthma, between 18 and 45 years of age, were cohorted into 3 groups: those not taking inhaled glucocorticoids (n = 28); those taking 4-8 puffs per day of inhaled glucocorticoids (n = 39); and those taking more than 8 puffs per day (n = 42). No clinically relevant differences were seen among the 3 groups in weight, height, calcium intake, FEV1, physical activity, smoking history, oral contraceptive use, bone-density, or biochemical values except for age, history of oral glucocorticoid therapy, and past or current use of topical inhaled glucocorticoids. Among the exclusion criteria were women who had received more than 2 short courses (lasting 2 weeks or less) of oral or parenteral glucocorticoids in the preceding year or any oral or parenteral glucocorticoids in the preceding 3 months.
At baseline, spirometry and bone density of the total hip, trochanter, femoral neck, and lumbar spine were performed with measurement of biochemical markers. Physical activity was assessed by a validated questionnaire. At subsequent visits at 6 months, 1, 2, and 3 years, information on medication use, diet and activities, measured bone density, and biochemical markers were reviewed and updated.
Israel and colleagues demonstrated a negative linear association between the average number of puffs per day of inhaled glucocorticoids and the yearly change in bone density at both the total hip and the trochanter (P = 0.01 and P = 0.005, respectively). Each additional daily puff of the inhaled glucocorticoid was associated with a decline in bone density of 0.00044 g per square centimeter per year at both sites, but there was no significant association with the degree of decline at the femoral neck and spine (-0.00005 and -0.00008 g per square centimeter per year per puff, respectively [P = 0.85 and P = 0.68, respectively]). This negative association was present even after adjustment for parental glucocorticoids, topical nasal glucocorticoids, and oral contraceptives. No correlation was found with urinary N-telopeptides, calcium, and cortisol values and serum osteocalcin, calcium, cortisol, and parathyroid hormones.
Inhaled glucocorticoids have become a key element in the maintenance treatment of bronchial asthma.1 It is well known that long-term systemic steroids cause osteoporosis,2 whereas inhaled glucocorticoids have been believed to avoid such side effects. The results of previous prospective and cross-sectional studies of the effects of inhaled glucocorticoids on bone loss have been inconsistent.3-6 These studies have been limited by small sample size, short duration, and presence of confounding factors such as intermittent use of systemic glucocorticoids, lack of appropriate controls, superimposed menopausal bone loss, and differences among participants in the severity of asthma that might have affected physical activity.
In the present study, Israel et al were able to demonstrate a dose-related negative effect of inhaled glucocorticoids on bone density even among patients who did not receive systemic steroids and who had adequate intake of calcium and vitamin D. Furthermore, urinary and serum biochemical markers did not predict the extent of bone loss.
1. National Asthma Education and Prevention Program. Expert panel report 2: Guidelines for the diagnosis and management of asthma. Bethesda, Md.: National Heart Lung and Blood Institute, 1997. NIH publication 97-4051.
2. Baylink DJ. N Engl J Med. 1983;309:306-308.
3. Ip M, et al. Chest. 1994;105:1722-1727.
4. Wisniewski AF, et al. Thorax. 1997;52:853-860.
5. Hughes JA, et al. Thorax. 1999;54:223-229.
6. Boulet LP, et al. Am J Resp Crit Care Med. 1999; 159:838-844.
Dr. Ost is Assistant Professor of Medicine, NYU School of Medicine, Director of Interventional Pulmonology, Division of Pulmonary and Critical Care Medicine, Northshore University Hospital, Manhasset, NY.