This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. Introduction: In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. Methods: Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (≤3 months) subpopulations] were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. Results: At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients ≤74 years (P < 0.05) in the treatment and 65-74 years (P = 0.0008) in the prevention subpopulation. At month 12, zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender (all P < 0.05), cumulative prednisone dose (all P < 0.01), and postmenopausal status (all P < 0.05). In premenopausal women, in both subpopulations, zoledronic acid significantly increased total hip BMD (all P < 0.05) versus risedronate at month 12 but not LS BMD. Osteoporotic patients in the prevention (P = 0.0189) and osteopenic patients in the treatment subpopulation (P = 0.0305) showed significant LS BMD increases with zoledronic acid versus risedronate at month 12. Conclusions: This post hoc analysis suggests that zoledronic acid is significantly more effective than risedronate in increasing LS BMD in prevention and treatment of glucocorticoid-induced osteoporosis across a wide range of patients © 2011 International Osteoporosis Foundation and National Osteoporosis Foundation.