Bone metabolism in anorexia nervosa: molecular pathways and current treatment modalities

Abstract

Eating disorders are associated with a multitude of metabolic abnormalities which are known to adversely affect bone metabolism and structure. We aimed to comprehensively review the literature on the effects of eating disorders, particularly anorexia nervosa (AN), on bone metabolism, bone mineral density (BMD), and fracture incidence. Furthermore, we aimed to highlight the risk factors and potential management strategies for patients with eating disorders and low BMD. We searched the MEDLINE/OVID (1950-July 2011) and EMBASE (1980-July 2011) databases, focussing on in vitro and in vivo studies of the effects of eating disorders on bone metabolism, bone mineral density, and fracture incidence. Low levels of estrogen, testosterone, dehydroepiandrosterone, insulin-like growth factor-1 (IGF-1), and leptin, and high levels of cortisol, ghrelin, and peptide YY (PYY) are thought to contribute to the 'uncoupling' of bone turnover in patients with active AN, leading to increased bone resorption in comparison to bone formation. Over time, this results in a high prevalence and profound degree of site-specific BMD loss in women with AN, thereby increasing fracture risk. Weight recovery and increasing BMI positively correlate with levels of IGF-1 and leptin, normalisation in the levels of cortisol, as well as markers of bone formation and resorption in both adolescent and adult patients with AN. The only treatments which have shown promise in reversing the BMD loss associated with AN include: physiologic dose transdermal and oral estrogen, recombinant human IGF-1 alone or in combination with the oral contraceptive pill, and bisphosphonate therapy.