Introduction: Oral glucocorticoid therapy reduces bone mineral density (BMD) and increases fracture risk. It is uncertain whether inhaled glucocorticoids, the most commonly used long-term therapy for asthma, have a similar effect. If bone loss does occur, it is unclear whether this is preventable by calcitriol. Patients with asthma receiving inhalational plus intermittent oral glucocorticoids lose bone, and treatment with 0.5 μg/day of calcitriol will prevent bone loss. Methods: A 2-year randomized double-blind placebo-controlled trial. One hundred eight patients with asthma were stratified by gender, age, and inhaled glucocorticoid dose and treated with calcitriol (n=55) or placebo (n=53). There were 41 men (mean age 53.2±1.7 years) and 67 women (mean age 49.1±1 years) with moderate to severe asthma (requiring ≥800 μg/day of beclomethasone dipropionate or equivalent maintenance therapy). BMD values at the lumbar spine (LS) and femoral neck (FN) were measured at baseline and at 6, 12, and 24 months using dual x-ray absorptiometry. Results: Changes in LS and FN BMD. Bone loss occurred in both groups at the FN (both p<0.03) and at the LS in the calcitriol (p<0.001), but not the control, group. Bone loss was not less in the calcitriol group at either site. Conclusions: Patients with asthma receiving inhalational plus intermittent short courses of oral glucocorticoids lose bone. Calcitriol is unlikely to be appropriate therapy against this bone loss.