Background: Knee osteoarthritis is a common degenerative joint disorder and a major cause of pain and disability. Recent studies have suggested that bisphosphonates such as alendronate may have a role in the treatment of osteoarthritis. The purpose of the present study was to investigate the potential effect of alendronate on the symptoms of knee osteoarthritis. Methods: Thirty nine patients with mild to moderate knee osteoarthritis were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. The patients received either placebo or alendronate pills (70mg, weekly) in a blinded fashion for six months. Symptoms of osteoarthritis were scored by Western Ontario and McMaster Universities (WOMAC) osteoarthritis index at enrollment and at weeks 4, 12, and 24.Results: In both groups there was a significant improvement in total WOMAC score and WOMAC subscales scores of pain, stiffness, and function at 4, 12, and 24 weeks of treatment. Maximum improvement occurred at week 4. There was no statistically significant difference between the two groups regarding their total WOMAC score and its subscales at the end of weeks 4, 12, or 24 (P=0.94). Conclusion: Alendronate does not reduce symptoms of mild to moderate knee osteoarthritis.