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. CONCLUSIONS 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.