ANTIRESORPTIVE THERAPY IN ASTHMATIC-PATIENTS RECEIVING HIGH-DOSE INHALED STEROIDS - A PROSPECTIVE-STUDY FOR 18 MONTHS

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 as sociated with a decrease in bone mineral density. Objective: We conduc ted this study to investigate bone density in asthmatic subjects recei ving long-term high-dose inhaled steroids and the effects of supplemen tation with oral calcium with or without etidronate. Methods: We evalu ated thirty-eight Chinese subjects (24 men and 14 premenopausal women; 28 patients and 10 healthy control subjects) in this prospective stud y. Patients were randomized into three arms: those receiving no supple ment, those receiving 1000 mg/day calcium supplement, and those receiv ing 400 mg/day cyclical sodium etidronate with 1000 mg/day calcium, re spectively, The patients and control subjects were matched for age, se x, and dose of inhaled steroids. Bone density at lumbar spine and hip region was measured by dual energy x-ray absorptiometry with a densito meter 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 hor mone, 25-hydroxyvitamin D, and urinary hydroxyproline/creatine were me asured simultaneous to bone density assessments. Results: There were 1 0 control subjects, 10 asthmatic subjects receiving no supplement, eig ht asthmatic subjects receiving calcium supplement, and 10 asthmatic s ubjects receiving calcium and etidronate therapy, respectively. The me an (+/- SEM) dosages of beclomethasone or budesonide for the three gro ups 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 subj ects was 766 +/- 39 mg/day, At baseline, bone mineral density of the s pine in the group receiving no supplement was significantly lower than that found in the control group (p < 0.05), At 18 months, patients re ceiving no supplement had significantly greater bone loss at the lumba r spine than patients receiving etidronate plus calcium lactate-glucon ate (CaLG) or CaLG alone (p < 0.05), The increase in bone mineral dens ity versus baseline observed in patients receiving CaLG with or withou t etidronate (p < 0.05) probably did not result from increased bone fo rmation because serum osteocalcin levels showed a significant reductio n in all three groups of patients (p < 0.05), An increase in mean seru m calcium (p < 0.05) was seen in patients receiving CaLG with or witho ut etidronate. Conclusion: Our results suggest that long-term administ ration of high-dose inhaled steroid (21.5 mg/day) induces bone loss th at is preventable with calcium supplementation with or without cyclica l etidronate. Long-term studies involving more patients should follow to confirm these preliminary findings.