Elsevier

Bone

Volume 29, Issue 6, December 2001, Pages 506-510
Bone

Alendronate for the prevention of bone loss in patients on inhaled steroid therapy

https://doi.org/10.1016/S8756-3282(01)00611-1Get rights and content

Abstract

One hundred women on inhaled steroid therapy (dose range from 800 to <1600 μg per day) were randomized to receive 10 mg of oral alendronate or placebo (with 500 mg of calcium in the form of daily calcium carbonate). Bone mineral density (BMD) was measured at baseline, 6 months, and 12 months. The percentage changes in BMD were −0.80% in the placebo group and 2.99% in the alendronate group at the spine (p < 0.001 by analysis of covariance [ANCOVA]), and were −0.51% in the placebo group and 0.97% in the alendronate group at the femoral neck (p < 0.05 by ANCOVA). Five patients in the alendronate-treated group, and a similar number of patients in the placebo group, complained of mild gastric discomfort. We conclude that women on inhaled steroid therapy were at risk of accelerated bone loss, which could be prevented by a daily dose of 10 mg of alendronate.

Introduction

Osteoporosis is one of the most debilitating complications of long-term glucocorticoid therapy.5, 29, 40 The detrimental effects of glucocorticoids are not restricted to oral therapy. It has been demonstrated that high-dose inhaled steroid can also cause osteoporosis.19, 28, 33, 42 Although most studies have focused on the effects of high-doses of inhaled steroid, lower doses may not be entirely harmless. For instance, Merran et al.25 demonstrated that subjects on a daily dose of 1000 μg beclamethasone dipropionate experienced significant changes in osteocalcin level, and Reid et al.32 showed total body calcium to be reduced in a group of asthmatics receiving only inhaled steroid in doses up to 800 μg/day. Moreover, Packe et al.29 demonstrated that subjects on a median daily dose of 800 μg of inhaled steroid for >1 year had significantly lower bone mineral density (BMD) than controls. We have also recently demonstrated that Chinese subjects given moderate doses of inhaled steroid had reduced bone mass.21

Various modalities have been used for treating steroid-induced osteoporosis. Estrogen was found to be effective in preventing bone loss in prednisone-treated rheumatoid arthritis patients17 and asthmatic patients.24 Calcitonin was found to be effective in ameliorating bone loss in patients treated with prednisone.1, 18, 26 There is also some evidence to suggest that calcitriol may be effective.14, 33, 39

In several randomized controlled clinical trials, cyclical etidonate was found to be effective in preventing bone loss11, 27, 37, 41 and vertebral fracture.3 The efficacy of intermittent intravenous pamidronate in preventing steroid-induced bone loss was also demonstrated.6, 34, 35 More recently, residronate has also been found to be effective.31

The efficacy of alendronate in preventing glucocorticoid-induced bone loss has been reported in sarcoid patients,13 and a recent, large-scale study furnished evidence that alendronate increased bone density in patients receiving glucocorticoid therapy.38 However, the effect of alendronate in preventing bone loss in patients on inhaled steroid has not been studied, and herein we report a double-blind, placebo-controlled trial to evaluate this treatment regimen.

Section snippets

Study subjects

Study subjects included women with asthma or chronic obstructive airway diseases. These patients were on inhaled steroid in the form of beclomethasone, budesonide, or fluticasone (39% were on a daily dose of ≥1600 μg, 12% were on 1200 μg, and 49% were on 800 μg).

Subjects with the following medical or drug history were excluded from the study: those having received estrogen or calcitonin within the last 4 months; those having received fluoride treatment in the last year; those with a history of

Results

A total of 100 patients were recruited into the study, but only 78 had their final BMD measured. The results presented are for these subjects.

The baseline characteristics of the study subjects are shown in Table 1. There was no significant difference in age between the two treatment groups. More than 50% of study subjects reported previous use of oral steroid, with the mean duration of use being 19.7 weeks and 17.2 weeks in the alendronate and placebo treatment groups, respectively. Most

Discussion

In this study we have demonstrated that women on inhaled steroid (equivalent to ≥800 μg/day) had significant bone loss over time. Such loss was preventable by a daily dose of 10 μg of alendronate. The effects of alendronate on BMD observed in this study were compatible with observations made in recent large-scale clinical trials conducted by Gonnelli et al.13 and Saag et al.38 Gonnelli13 studied sarcoid patients on prednisolone, and found that alendronate treatment increased BMD by 1%. In the

Acknowledgements

This study was supported by Merck Sharp and Dohme Pharmaceuticals. The authors thank Aprille Sham for conducting the data analysis.

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