Elsevier

The Lancet

Volume 355, Issue 9213, 22 April 2000, Pages 1399-1403
The Lancet

Articles
Inhaled corticosteroid use and bone-mineral density in patients with asthma

https://doi.org/10.1016/S0140-6736(00)02138-3Get rights and content

Summary

Background

Inhaled corticosteroids are absorbed into the systemic circulation, but the extent to which they have adverse effects on bone is uncertain. The question is important since 3% of the European population take an inhaled corticosteroid regularly and may do so for many years.

Methods

We studied the dose-response relation between cumulative inhaled corticosteroid dose and bone-mineral density at the lumbar spine and proximal femur in 196 adults (119 women) with asthma aged 20–40 years. Patients had taken an inhaled corticosteroid regularly for at least 6 months, and had had limited exposure to systemic steroids. Cumulative dose of inhaled corticosteroid was calculated from questionnaires and computerised and written general-practice records, and its effect on bone-mineral density was estimated by multiple regression analysis.

Findings

Median duration of inhaled corticosteroid treatment was 6 years (range 0·5–24), and median cumulative dose was 876 mg (87–4380). There was a negative association between cumulative dose of inhaled corticosteroid and bone-mineral density at the lumbar spine (L2–L4), femoral neck, Ward's triangle, and trochanter, both before and after adjustment for the effects of age and sex. A doubling in dose of inhaled corticosteroid was associated with a decrease in bone-mineral density at the lumbar spine of 0·16 SD (95% CI 0·04–0·28). Similar decreases were found at the femoral neck, Ward's triangle, and trochanter. Adjustment for potential confounding factors including physical activity and past oral, nasal, dermal, and parenteral corticosteroids did not weaken the associations.

Interpretation

This study provides evidence of a negative relation between total cumulative dose of inhaled corticosteroid and bone-mineral density in patients with asthma.

Introduction

Inhaled corticosteroids are highly effective in the treatment of asthma, and are often required for long-term control. One in three asthmatic patients in the UK takes an inhaled corticosteroid regularly, and a third are prescribed 800 μg or more per day.1 Administration of a corticosteroid by inhalation enables it to be targeted to the airways with substantially fewer adverse effects than by the oral route.2 Nevertheless, inhaled corticosteroids are absorbed into the systemic circulation from the lung, and more variably from the gastrointestinal tract,2 and their use has been associated with bruising,3 cataracts,4 and glaucoma.5 Whether and to what extent they have clinically important effects on bone is uncertain. Because inhaled corticosteroids are widely prescribed, and because osteoporotic fracture is common, a small increase in the relative risk of osteoporosis would have important public-health implications.

Studies investigating the association between inhaled corticosteroid use and bone-mineral density in adults have given inconsistent results.6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 These studies have been small, the duration of treatment has been short, and most have been confounded by patients' previous use of oral corticosteroids. We therefore tested the hypothesis that there is a relation between cumulative inhaled corticosteroid use and bone-mineral density at the lumbar spine in a much larger group of patients with little prior use of oral corticosteroids; we also aimed to quantify the relation after allowing for potential confounding factors. We restricted our study to patients aged 20–40 years to keep confounding by age and menopause to a minimum.

Section snippets

Patients

Patients were recruited between April, 1996, and December, 1997, from 51 general practices in and around Nottingham, UK, that had at least a year's worth of computerised details of patients and prescriptions. The practices were identified by the Nottinghamshire and Derbyshire Family Health Service Associations, and those within 35 miles of Nottingham were invited to participate. Additional patients were recruited from our register of asthma-research volunteers provided that their general

Results

We studied 196 patients (119 women) of whom 176 were recruited from general practice and 20 from our volunteer database. Their median age was 32 years and mean FEV1 was 93% predicted (table 1). Median duration of treatment with an inhaled corticosteroid was 6 years (range 0·5–24), and the median cumulative dose was 876 mg (range 88–4380). At the time of recruitment, beclometasone dipropionate, budesonide, and fluticasone propionate were being taken by 157 (80%), 27 (14%), and 12 (6%) of the

Discussion

This large, cross-sectional survey looked at the relation between inhaled corticosteroid use and bone-mineral density in patients with asthma. We found a clear inverse relation between cumulative inhaled corticosteroid dose and bone-mineral density at the lumbar spine and proximal femur.

Our study was specifically designed to address some of the drawbacks associated with previous studies. By enrolling patients from a primary-care population, we obtained a much larger sample size, and by

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