Bone loss is recognized as worsening the quality of life in long-term survivors of Allo-SCT. This study evaluated the risk factors associated with bone loss and the role of zoledronic acid in preventing bone loss in allogeneic recipients. Fifty-three patients who underwent HLA-matched Allo-SCT were evaluated for their bone mineral density (BMD) in the lumbar spine and femoral neck at regular intervals. Zoledronic acid (4 mg) was given i.v. to 18 patients (ZA patients) at 2 months after SCT and then every 3 months until 2 years. Grade 2-4 acute GVHD was associated with bone loss (odds ratio (OR)=4.90, 95% confidence interval (CI)=1.41-16.99; P=0.012) at 1 year after SCT, whereas extensive chronic GVHD and steroid use were both unfavorable prognostic factors (OR=9.00 and 7.22, 95% CI=1.52-53.40 and 1.44-36.22; P=0.016, respectively) in terms of osteopenia/osteoporosis at 2 years after transplantation. The use of zoledronic acid significantly prevented bone loss in the femoral neck as well as the spine (OR=0.18, 95% CI=0.05-0.69, P=0.012). Therefore, BMD measurements and the use of zoledronic acid are recommended in cases of GVHD or long-term steroid use after Allo-SCT to prevent bone loss and threatening skeletal events.