title: State of the art systematic review of bone disease in anorexia nervosa.
abstract: OBJECTIVE
  Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management.
  
  
  METHODS
  Search terms included "anorexia nervosa" AND "bone density" for the period 1995-2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995.
  
  
  RESULTS
  AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN.
  
  
  CONCLUSIONS
  To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN.
authors: Division of Pediatric Endocrinology and the Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts.
authors: Madhusmita
authors: M
authors: Misra
authors: Division of Adolescent Medicine, Stanford University School of Medicine, Palo Alto, California.
authors: Neville H
authors: NH
authors: Golden
authors: Division of Adolescent Medicine, Hospital for Sick Children and University of Toronto, Toronto, Canada.
authors: Debra K
authors: DK
authors: Katzman
mesh_terms: D000856:Anorexia Nervosa / Q000150:complications*; D001847:Bone Diseases / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies
keywords: adolescents; anorexia nervosa; bisphosphonates; bone density; bone microarchitecture; eating disorders; estrogen; fracture; insulin like growth factor-1; menstruation