Musculoskeletal and estrous cycle aberrations in a rodent model of anorexia nervosa: a pilot study

Anorexia Nervosa (AN) is a highly pervasive psychiatric disorder that is notoriously difficult to treat. Treatment challenges contribute to high mortality rates and prolonged recovery trajectories in individuals with AN. AN results in muscle loss, which may not be reversible with weight gain. Muscle health is a significant predictor of quality of life and morbidity across many pathological conditions, yet has not been thoroughly investigated in AN. Purpose: Evaluate musculoskeletal and other physiological consequences of severe caloric restriction in a rodent model of AN. Methods: Female Sprague Dawley rats were fed 50% of their normal food consumption starting at 8 weeks of age simulating AN (n=8). Animals were given 2 hours/day to consume food. Control (CON) rats were allowed ab libitum access to food (n=6). After 30 days of interventions, muscle function and other physiological parameters were evaluated. Results: AN rats had ~30% lower bodyweight compared to CON. AN rodents had ~29% lower plantar flexion force production compared to CON in addition to ~20% slower muscle contraction and ~18% slower relaxation speed. AN animals also had ~23% lower muscle endurance. AN animals also had ~32% smaller muscle mass compared to CON. Corresponding to the human clinical condition, AN rats also had 19% lower bone mineral density and hormonal alterations. AN rats spent more time in low estrogens phases of the estrous cycle (~83% time in low estrogens phases in AN v. ~50% time in CON). Conclusion: Our rodent model of AN appropriately recapitulates body weight, musculoskeletal, and other physiological changes noted in the clinical AN population and can be utilized to further understand biological consequences of AN.