Denosumab increases spine bone density in women with anorexia nervosa: a randomized clinical trial.

Objective: Anorexia nervosa is complicated by high bone resorption, low bone mineral 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 end point was postero-anterior (PA) lumbar spine aBMD by dual-energy x-ray absorptiometry. Secondary end points 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 (FEA), and markers of bone turnover. Results: Baseline mean (±s.d.) age (29 ± 8 (denosumab) vs 29 ± 7 years (placebo)), BMI (19.0 ± 1.7 vs 18.0 ± 2.0 kg/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). 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. The change in 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.

Posttraumatic stress disorder and eating disorders: maintaining mechanisms and treatment targets.

Many individuals with lifetime histories of eating disorders (EDs) report exposure to interpersonal trauma and posttraumatic stress disorder (PTSD). However, this relationship is not well-understood, and there are no established, evidence-based therapies for the concurrent treatment of EDs and PTSD. This review focuses on studies of the mechanisms associating trauma exposure and/or PTSD with EDs. Possible mechanisms of the trauma-ED association identified from the literature include self-criticism, low self-worth, guilt, shame, depression, anxiety, emotion dysregulation, anger, and impulsivity/compulsivity. ED behaviors may be used as coping strategies to manage PTSD symptoms and negative affect. Avoidance of hyperarousal symptoms by engaging in binge eating, purging, and/or restriction may serve to maintain both the ED as well as the PTSD. Given the evidence of the bidirectional relationship between EDs and PTSD, we describe an integrated cognitive behavioral theory that may account for the persistence of comorbid PTSD and EDs. The integrated model is based on the theoretical models that underpin existing evidence-based treatments for PTSD and ED and incorporates many of the potential mechanisms highlighted to date. The primary aim of the model is to identify potential treatment targets as well as elucidate future directions for research.