Anorexia nervosa (AN) is a condition of severe
undernutrition associated with adaptive changes in many endocrine axes. These changes include
hypogonadotropic hypogonadism, acquired
growth hormone resistance with low
insulin-like growth factor 1 (IGF-1) levels, hypercortisolemia, altered secretion of
adipokines and appetite-regulating
hormones, and
low bone mineral density (BMD). Bone health is impaired subsequent to a low body mass index, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high
peptide YY levels, and
ghrelin dynamics may not completely normalize. In some patients,
hypogonadotropic hypogonadism persists despite weight restoration.
Weight gain and menstrual recovery are critical for improving bone health in AN; however, residual deficits may persist. Physiologic
estrogen replacement using transdermal, but not oral,
estrogen increases bone accrual in adolescents with AN, while
bisphosphonates improve BMD in adults. Recombinant human
IGF-1 and
teriparatide have been used in a few studies as bone anabolic
therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN.