Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure, and reduced bone strength, all of which contribute to increased fracture risk. Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising additional concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, and hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen–progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiological estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age, given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN.
Madhusmita Misra and Anne Klibanski
Pouneh K Fazeli and Anne Klibanski
States of undernutrition are characterized by GH resistance. Decreased total energy intake, as well as isolated protein–calorie malnutrition and isolated nutrient deficiencies, result in elevated GH levels and low levels of IGF1. We review various states of malnutrition and a disease state characterized by chronic undernutrition – anorexia nervosa – and discuss possible mechanisms contributing to the state of GH resistance, including fibroblast growth factor 21 and Sirtuin 1. We conclude by examining the hypothesis that GH resistance is an adaptive response to states of undernutrition, in order to maintain euglycemia and preserve energy.