Bone loss in anorexia nervosa: leptin, serotonin, and the sympathetic nervous system.
Anorexia nervosa (AN), a disorder characterized by the refusal to sustain a healthy weight, has the highest mortality of any psychiatric disorder. This review presents a model of AN that ties together advances in our understanding of how leptin, serotonin, and hypogonadism are brought about in AN and how they influence bone mass. Serotonin (5-hydroxytryptamine) is a key regulator of satiety and mood. The primary disturbance in AN results from alterations in serotonin signaling. AN patients suffer from serotonergic hyperactivity of Htr1a-dependent pathways that causes dysphoric mood and promotes restrictive behavior. By limiting carbohydrate ingestion, anorexics decrease their serotonin levels. Reduced serotonergic signaling in turn suppresses appetite through Htr1a/2b, decreases dysphoric mood through Htr1a/2a, and activates the sympathetic nervous system (SNS) through Htr2c receptors in the ventromedial hypothalamus. Activation of the SNS decreases bone mass through β2-adrenergic signaling in osteoblasts. Additional topics reviewed here include osteoblastic feedback of metabolism in anorexia, mechanisms whereby dietary changes exacerbate bone loss, the role of caloric restriction and Sirt1 in bone metabolism, hypothalamic hypogonadism's effects on bone mass, and potential treatments.
Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Kevin K
KK
Kumar
Stephanie
S
Tung
Jameel
J
Iqbal
D000818:Animals; D000856:Anorexia Nervosa / Q000378:metabolism* / Q000503:physiopathology; D015519:Bone Density / Q000502:physiology; D001851:Bone Diseases, Metabolic / Q000378:metabolism / Q000503:physiopathology; D001862:Bone Resorption / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013564:Sympathetic Nervous System / Q000378:metabolism* / Q000503:physiopathology
D020738:Leptin; D012701:Serotonin