Aim: The bone mineral density (BMD) effects of calcitonin (CT) and alendronate (ALEN) therapy either alone or in combination were evaluated in patients with rheumatoid arthritis (RA). Method: Eighty out of 100 patients with RA using methotrexate 5-12.5 mg/week and prednisone 5-10 mg/day were included in the study. These were randomly divided into four groups: the first group was given ALEN 70 mg/week; the second was given 200 IU/day CT nasal spray; and the third group was given combined therapy of 70 mg/week ALEN and 200 IU/day CT nasal spray. The fourth group (control) as well as the other three groups were given 600 mg calcium and 400 IU vitamin D. Dual-energy X-ray absorptiometry BMD of lumbar, hip and forearm regions and laboratory investigations were performed before and at the 12th month of the therapy. Results: Only the combined therapy group displayed significant decreases of alkaline phosphatase levels, pointing out that the high bone turnover seen in RA patients can only be normalized by combination therapy. Also the combined therapy group showed significant increases at the lumbar and hip regions, whereas at the forearm regions BMD values stabilized. Conclusion: We recommend the use of CT and ALEN combined therapy, especially in severe active cases of RA, but further prospective studies consisting of larger patient populations are needed to confirm the additive effects of this combined therapy on fracture risk in these patients. © 2007 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.