We conducted a one-year comparative study of 25 patients with corticosteroid-induced osteoporosis associated with diffuse connective tissue disease. The patients were randomly divided into 2 groups: group A (9 patients), monotherapy with active vitamin D3 (V.D3); and group B (16 patients), combination therapy with V.D3 and etidronate. Four markers were employed: as an bonegenic marker, serum alkaline phosphatase (ALP); as a bone resorption marker, urinary deoxypyridinoline (DPD); as a bone salt minerals assay level, young adult mean (YAM); and bonefracture ratio. Results showed that: ALP decreased in both groups with no significant difference between groups; DPD increased significantly from baseline (p<0.05) in group A, but it decreased significantly from baseline (p<0.05) in group B, but again without a significant difference between groups; YAM resulted in no significant improvement in group A, but a significant improvement from baseline (p<0.01) was shown in group B, with a significant difference between groups (p<0.05); and a new spinal compression fracture ratio was extremely lower in group A than in group B. The findings indicated cyclical/intermittent etidronate therapy is effective in preventing corticosteroid-induced osteoporosis.