Treatment with Denosumab Reduces the Incidence of New Vertebral and Hip Fractures in Postmenopausal Women at High Risk

Context: The FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial showed denosumab significantly reduced the risk of fractures in postmenopausal women with osteoporosis. Objective: We evaluated the effect of denosumab on the incidence of new vertebral and hip fractures in subgroups of women at higher risk for these fractures. Design: FREEDOM was a 3-yr, randomized, double-blind, placebo-controlled, phase 3 trial. Participants and Setting: Postmenopausal women (N = 7808) with osteoporosis were enrolled at 213 study sites worldwide. Interventions: Subjects received sc denosumab (60 mg) or placebo every 6 months and daily supplements of calcium (>= 1000 mg) and vitamin D (>= 400 IU). Main Outcome Measures: This post hoc analysis evaluated fracture incidence in women with known risk factors for fractures including multiple and/or moderate or severe prevalent vertebral fractures, aged 75 yr or older, and/or femoral neck bone mineral density T-score of -2.5 or less. Results: Compared with placebo, denosumab significantly reduced the risk of new vertebral fractures in women with multiple and/or severe prevalent vertebral fractures (16.6% placebo vs. 7.5% denosumab; P < 0.001). Similarly, denosumab significantly reduced the risk of hip fractures in subjects aged 75 yr or older (2.3% placebo vs. 0.9% denosumab; P < 0.01) or with a baseline femoral neck bone mineral density T-score of -2.5 or less (2.8% placebo vs. 1.4% denosumab; P = 0.02). These risk reductions in higher-risk individuals were consistent with those seen in patients at lower risk of fracture. Conclusions: Denosumab reduced the incidence of new vertebral and hip fractures in postmenopausal women with osteoporosis at higher risk for fracture. These results highlight the consistent antifracture efficacy of denosumab in patients with varying degrees of fracture risk. (J Clin Endocrinol Metab 96: 1727-1736, 2011)