Persistent Skeletal Deficits Following Weight Restoration in a Rodent Model of Anorexia Nervosa

Purpose: Anorexia nervosa (AN) is associated with significant changes in bone density and microstructure. However, the extent and nature of skeletal recovery following weight restoration is unclear. The aim of this study was to investigate these changes in bone during simulated AN in rats across short- and long-term recovery. Methods: Female Sprague Dawley rats were exposed to 50-60% food restriction for 30 days to simulate AN, followed by recovery periods of 5, 15, and 30 days. Bone parameters were assessed longitudinally using peripheral quantitative computed tomography (pQCT) and micro-computed tomography (µCT). Bodyweight and muscle strength were correlated with bone parameters. Results: AN resulted in significant reductions in total and trabecular bone density, as well as impairments in cortical and trabecular microarchitecture. Even with weight restoration, these deficits persisted and the compensatory responses were not sufficient for bone recovery. Bodyweight showed an association with total and trabecular bone density. Measures of muscle strength also correlated with total and trabecular density and were additive in multiple regression analysis prediction of total and trabecular bone density when combined with bodyweight. Conclusion: Recovery from AN-induced bone disorders is incomplete even after weight restoration and likely requires targeted interventions beyond nutritional rehabilitation. Furthermore, muscle function is an important predictor of bone health when combined with bodyweight.