Introduction: The purpose of this study was to evaluate the effects of alendronate (ALN) on bone mineral density (BMD) and bone turnover markers in patients with orthotopic liver transplantation (OLT). Methods: In the prospective, controlled, open study with 24 months of follow-up, 98 patients with OLT were randomised to receive ALN 70 mg weekly or no ALN; calcium (Ca) 1,000 mg daily and 0.5 mcg calcitriol daily were provided to all patients. Lumbar spine (LS) and hip BMDs were measured at 6-month intervals by dual-energy X-ray absorptiometry (DEXA). Spinal radiographs were obtained to assess vertebral fractures. Additionally, bone turnover markers, serum parathyroid hormone (PTH) and biochemical parameters were determined every 3 months. Results: Compared with the control group, the ALN group showed significant increases in BMD of the LS (5.1 +/- 3.9% vs 0.4 +/- 4.2%, p < 0.05 at 12 months, 8.9 +/- 5.7% vs 1.4 +/- 4.9%, p < 0.05 at 24 months), femoral neck (4.3 +/- 3.8% vs -1.1 +/- 3.1%, p < 0.05 at 12 months, 8.7 +/- 4.8% vs 0.6 +/- 4.5%, p < 0.05 at 24 months) and total femur (3.6 +/- 3.8% vs -0.6 +/- 4.0%, p < 0.05 at 12 months, 6.2 +/- 3.8% vs 0.3 +/- 4.6%, p < 0.05 at 24 months). In the ALN group, osteocalcin and urinary deoxypyridinoline (DPD) decreased significantly at the sixth month, with no further change, by -35.6% and -63.0%, on average, respectively (p < 0.05). In the control group, a significant increase in biochemical markers of bone turnover was observed in comparison to baseline values (p < 0.05). PTH increased within reference levels without a difference between groups. Two nonvertebral fractures (4.2%) and nine vertebral fractures (18.8%) in the control group and three vertebral fractures (6.8%) in the ALN group occurred during the follow-up. The weekly ALN was well tolerated, and no severe side effects occurred. Conclusion: This is the first randomised study including a control group to demonstrate that weekly ALN was able to significantly increase BMD in patients with OLT when compared with Ca and calcitriol alone. However, ALN did not appear to offer protection against fractures.