Osteoporosis is known to complicate outcomes after lung transplantation (Tx). To determine the efficacy of bisphosphonate therapy combined with the osteogenic stimulus of mechanical loading, 30 lung transplant recipients (LTRs) were randomly assigned either to alendronate (10 mg/day; n = 10), alendronate (10 mg/day) + resistance exercise (n = 10) or to a control group (n = 10). Alendronate was initiated at 7 days after Tx. Bone mineral density (BMD) of the lumbar spine was measured by dual-energy X-ray absorptiometry before and 2 and 8 months after Tx. Resistance training was initiated at 2 months after Tx and consisted of lumbar extension exercise performed 1 day/week for 6 months. Lumbar BMD decreased significantly to below pre-transplant baseline at 2 months after Tx in controls (-12.5 +/- 2.1%), but not in the alendronate (1.5 +/- 1.2%) or alendronate + training (1.5 +/- 0.9%) groups. At 8 months after Tx, lumbar BMD in controls was 14.1 +/- 3.9% below baseline (p < or = 0.05), but was 1.4 +/- 1.1% above baseline in alendronate recipients (p > or = 0.05). The alendronate + training group showed a significantly increased lumbar BMD with values 10.8 +/- 2.3% greater than before Tx. These results suggest that resistance exercise plus alendronate is more effective than alendronate alone in restoring BMD. Anti-osteoporosis therapy in LTRs should include both an anti-resorptive agent and an osteogenic stimulus, such as mechanical loading.