Glucocorticoid-induced osteoporosis is the most common cause of secondary osteoporosis. To compare the effects of recombinant teriparatide (recombinant parathyroid hormone) with those of alendronate for the treatment of patients with osteoporosis who have had long-term exposure to glucocorticoids and are at high risk for fracture. In a 18-month randomized, double-blind, controlled trial compared teriparatide with alendronate in 428 women and men with osteoporosis (345 women and 83 men; ages 22 to 89 years) who had received glucocoticoids for at least 3 months (prednisone equivalent 5 mg/die or more). A total of 214 patients (172 women, age 56.1±13.4) received 20 µg of teriparatide once daily and 214 received 10 mg of alendronate once daily (173 women; age 57.3±14). The primary outcome was the change in bone mineral density at the lumbar spine. Secondary outcomes included changes in bone mineral density at the total hip and in markers of bone turnover, the amount of time to effect change in the BMD. Bone mineral density at the lumbar spine had increased more in the teriparatide group than in the alendronate group (7.2%±0.7% vs 3.4±0.7%). A significant difference between the groups was reached by 6 months. At 12 months, bone mineral density at the total hip had increased more in the teriparatide group. Fewer new vertebral fractures occured in the teriparatide group than in the alendronate group (0.6% vs 0.1%). The incidence of nonvertebral fractures was similar in the two groups (5.6% vs 3.7%). Significantly more patients in the teriparatide group had at least one elevated measure of serum calcium. Among patients with osteoporosis who were at high risk for fracture, bone mineral density increased more in patients receiving teriparatide than in those receiving alendronate.