SAGE-Hindawi Access to Research Journal of Osteoporosis Volume 2011, Article ID 720328, 7 pages doi:10.4061/2011/720328 Clinical Study Bone Mineral Density Accrual Determines Energy Expenditure with Refeeding in Anorexia Nervosa and Supersedes Return of Menses Melissa Sum, Laurel Mayer, and Michelle P. Warren Columbia University College of Physicians and Surgeons, 622 West 168th Street, PH 16-128, New York, NY 10032, USA Correspondence should be addressed to Melissa Sum, ms2452@columbia.edu Received 14 August 2010; Revised 1 July 2011; Accepted 1 July 2011 Academic Editor: Tomasz Miazgowski Copyright © 2011 Melissa Sum et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Osteopenia and osteoporosis are major complications of anorexia nervosa (AN). Since bone is a tissue requiring large amounts of energy, we examined the disproportionate increase in resting energy expenditure (REE) that occurs with refeeding of AN patients to determine if it was related to bone accretion. Thirty-seven AN patients aged 23.4 ± 4.8 years underwent a behavioral weight-gain protocol lasting a median of 66 days; 27 remained amenorrheic, and 10 regained menses. Sixteen controls aged 25.1 ± 4.7 years were age- and % IBW matched with patients. REE was measured using a respiratory chamber-indirect calorimeter. Signiﬁcant correlations were found between REE and changes in spine (r = 0.48, P < 0.02) and leg (r = 0.43, P < 0.05) BMDs in AN patients. Further subgroup analysis of the amenorrheics revealed signiﬁcant correlation between REE and change in spine BMD (r = 0.59, P < 0.02) and higher IGF-1 after weight gain compared to controls. Amenorrheics also had lower BMDs. These ﬁndings were absent in the regained menses group. The increase in REE seen in women with AN during nutritional rehabilitation may be related to active bone formation, which is not as prominent when menses have returned. 1. Introduction Anorexia nervosa (AN) is an eating disorder characterized by severe voluntary restriction of food with resultant major weight loss aﬀecting up to 1% of women in Western societies [1]. Patients with AN typically have primary or secondary amenorrhea likely due to suppression of the reproductive axis by means of inadequate energy stores [2]. Another consequence of the decreased caloric intake in AN patients is a consistently reported decrease in resting energy expenditure (REE). REE, also known as resting meta- bolic rate, represents the amount of calories required in a 24-hour period by the body during a nonactive period. Metabolic rate is mainly a function of the activity of lean body mass also known as fat-free mass (FFM). Although a reduced REE theoretically facilitates weight gain during refeeding, REE has also been consistently found to increase with nutritional rehabilitation, thereby potentially rendering weight gain more diﬃcult for patients. Several small studies have proposed explanations for this phenomenon, including that the increase in REE is a reﬂection of lean body mass growth [3], a reversal of the initial adaptation to malnutri- tion [4], or a defense of low body weight [5]. Most puzzling is that others have found the increase in REE to be dispro- portionately greater than weight gain and deemed this clear evidence of a strong cellular “waste” phenomenon [6] or an energy drain of unknown source accounting for the use of extra calories. One possible hypothesis is that reversal of the metabolic consequences of caloric restriction necessitates ac- tivation of systems requiring energy. Recently, bone has been recognized as a highly metabol- ically active tissue requiring energy [7] such that new bone formation is appropriately suppressed with inadequate nutri- tion. Indeed, reduction in bone mass to the degree of oste- openia and osteoporosis has been observed in over 90% of adolescents with AN who have been amenorrheic for more than 6 months [8]. Despite consideration of various ther- apies, weight restoration, which occurs prior to return of menses, along with menstrual recovery is regarded as the foundation of bone recovery [9]. Signiﬁcant increases of