Osteoporosis with Parathyroid Hormone Study Group*

(PTH) increases bone mass and strength and improves bone quality by stimulating new bone formation. Objective: To determine the safety of PTH and its effect on the incidence of vertebral fractures in postmenopausal women with osteoporosis. Design: 18-month, randomized, double-blind, placebo-controlled, parallel-group study. Setting: 168 centers in 9 countries. Patients: 2532 postmenopausal women with low bone mineral density at the hip or lumbar spine. Interventions: Women received 100 g of recombinant human PTH or placebo daily by subcutaneous injection. All received cal-cium, 700 mg/d, and vitamin D3, 400 U/d. Measurements: New or worsened vertebral fractures (primary out-come) and changes in bone mineral density and safety (secondary outcomes). Results: 67.2 % of patients who received at least 1 dose of the study drug completed the study. Parathyroid hormone reduced the risk for new or worsened vertebral fractures, but in sensitivity anal-yses, the magnitude of the reduction was changed with assump-tions about fracture incidence in patients who did not complete the study (relative risk assuming no fractures, 0.42 [95 % CI, 0.24 to 0.72] [P 0.001]; relative risk assuming fracture incidence ob-served in all patients who completed the trial, 0.60 [CI, 0.36 to 1.00] [P 0.05]; relative risk assuming fracture incidence observed in the placebo group, 0.62 [CI, 0.37 to 1.04] [P 0.07]). Com-pared with placebo, mean bone mineral density increased at the spine by 6.9 % (CI, 6.4 % to 7.4%) and at the hip by 2.1 % (CI, 1.7 % to 2.5%) but decreased at the forearm in the PTH-treated group. Parathyroid hormone treatment increased the percentage of participants with hypercalciuria, hypercalcemia, and nausea by 24