Objective Anorexia nervosa is complicated by high bone resorption, low bone density(BMD), and increased fracture risk. We investigated whether off-label antiresorptive therapy with denosumab increases BMD in women with anorexia nervosa. Design Twelve-month randomized, double-blind, placebo-controlled study Methods Thirty ambulatory women with anorexia nervosa and areal BMD(aBMD) T-score ∠-1.0 at ≥1 sites were randomized to 12 months of denosumab (60 mg subcutaneously q6 months)(n=20) or placebo (n=10). Primary endpoint was postero-anterior (PA) lumbar spine aBMD by DXA. Secondary endpoints included femoral neck aBMD; tibia and radius volumetric BMD and bone microarchitecture by high-resolution peripheral quantitative CT; tibia and radius failure load by finite element analysis; markers of bone turnover. Results Baseline mean(±SD) age [29±8 (denosumab) vs. 29±7y (placebo)], BMI (19.0±1.7 vs. 18.0±2.0kg/m2), and aBMD (PA spine Z-score -1.6±1.1 vs. -1.7±1.4) were similar between groups. PA lumbar spine aBMD increased in the denosumab vs. placebo group over 12 months (p=0.009). Descriptively, the mean(95% CI) increase in PA lumbar spine aBMD was 5.5 (3.8-7.2)% in the denosumab group and 2.2 (-0.3-4.7)% in the placebo group. Femoral neck aBMD was similar between groups. Radial trabecular number increased, radial trabecular separation decreased, and tibial cortical porosity decreased in the denosumab vs. placebo group (p≤0.006). Serum C-terminal telopeptide of type I collagen and procollagen type I N-terminal propeptide decreased in the denosumab vs. placebo group(p<0.0001). Denosumab was well tolerated. Conclusions Twelve months of antiresorptive therapy with denosumab reduced bone turnover and increased spine aBMD, the skeletal site most severely affected in women with anorexia nervosa.