Antiresorptive therapy in asthmatic patients receiving high-dose inhaled steroids: A prospective study for 18 months,☆☆,,★★

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Abstract

Background: Inhaled steroid therapy is an effective and well tolerated mode of therapy for asthma. Although systemic side-effects of inhaled steroids are much less common than those found with systemic steroids, the drugs may be absorbed through mucosal surfaces. Inhaled steroids have been reported to disturb normal bone metabolism, and they are associated with a decrease in bone mineral density. Objective: We conducted this study to investigate bone density in asthmatic subjects receiving long-term high-dose inhaled steroids and the effects of supplementation with oral calcium with or without etidronate. Methods: We evaluated thirty-eight Chinese subjects (24 men and 14 premenopausal women; 28 patients and 10 healthy control subjects) in this prospective study. Patients were randomized into three arms: those receiving no supplement, those receiving 1000 mg/day calcium supplement, and those receiving 400 mg/day cyclical sodium etidronate with 1000 mg/day calcium, respectively. The patients and control subjects were matched for age, sex, and dose of inhaled steroids. Bone density at lumbar spine and hip region was measured by dual energy x-ray absorptiometry with a densitometer at baseline and at 6, 12, and 18 months for the asthmatic groups and at baseline and at 12 and 18 months for the control group. Serum calcium, phosphate, alkaline phosphatase, osteocalcin, parathyroid hormone, 25-hydroxyvitamin D, and urinary hydroxyproline/creatine were measured simultaneous to bone density assessments. Results: There were 10 control subjects, 10 asthmatic subjects receiving no supplement, eight asthmatic subjects receiving calcium supplement, and 10 asthmatic subjects receiving calcium and etidronate therapy, respectively. The mean (± SEM) dosages of beclomethasone or budesonide for the three groups of asthmatic subjects were 2.2 ± 0.3, 2.0 ± 0.2, and 2.0 ± 0.2 mg/day, respectively. Mean dietary calcium intake of the study subjects was 766 ± 39 mg/day. At baseline, bone mineral density of the spine in the group receiving no supplement was significantly lower than that found in the control group ( p < 0.05). At 18 months, patients receiving no supplement had significantly greater bone loss at the lumbar spine than patients receiving etidronate plus calcium lactate-gluconate (CaLG) or CaLG alone (p < 0.05). The increase in bone mineral density versus baseline observed in patients receiving CaLG with or without etidronate (p < 0.05) probably did not result from increased bone formation because serum osteocalcin levels showed a significant reduction in all three groups of patients (p < 0.05). An increase in mean serum calcium (p < 0.05) was seen in patients receiving CaLG with or without etidronate. Conclusion: Our results suggest that long-term administration of high-dose inhaled steroid (>1.5 mg/day) induces bone loss that is preventable with calcium supplementation with or without cyclical etidronate. Long-term studies involving more patients should follow to confirm these preliminary findings.

Section snippets

Subjects

Patients were recruited and followed up at the Asthma Clinic at the University of Hong Kong between May 1994 and May 1997. Inclusion criteria included Chinese ancestry, age 30 to 50 years, premenopausal status, and a history of inhaled beclomethasone dipropionate or budesonide (>1.5 mg/day) therapy for at least 12 months. Exclusion criteria included chronic systemic steroid use (defined as continuous administration of oral steroids for more than 1 month in the previous 12 months); more than

RESULTS

Forty subjects were recruited (10 each of normal control subjects, patients without supplementation, patients with CaLG, and patients with CaLG plus etidronate). The results of two patients in the CaLG group were excluded from the analysis because the patients' body weight increased significantly within the study period.13 The clinical characteristics of the four groups of subjects are summarized in Tables I and II.The mean (± SEM) dosage of beclomethasone and budesonide in the three groups of

DISCUSSION

Despite the small sample size and relatively short duration of follow-up, this 18-month prospective study has provided supporting evidence for the adverse effects of inhaled steroids on bone density, previously demonstrated in cross-sectional studies. 7, 14 It has also provided evidence that such effects may be amenable to preventive measures.

In agreement with published data on steroid-induced osteoporosis,15 the reduction in BMD in the patients receiving no supplement was most obvious in the

Acknowledgements

We thank Mr. Stanley Yeung, Scientific Officer, University Department of Medicine for assistance in statistical analysis.

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    From the University Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong.

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    Supported by a grant from the Committee on Research and Conference Grants, and W. Q. Wang is the recipient of an Ivy Wu Fellowship of the Medical Faculty, The University of Hong Kong.

    Reprint requests: Karen S. L. Lam, MD, FRCP, University Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.

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