Journal of Osteoporosis Characteristic Agea (years) Weighta,b (kg) BMIa,b,c (kg/m2) REEa (kcal/d) Fat free mass indexa (kg/m2) Patients with AN at admission (n) 23.4 ± 4.8 (36) 41.5 ± 5.4 (37) 15.8 ± 1.6 (37) 1087 ± 128 (23) 14.4 ± 1.3 (36) Table 1: Age and anthropometric measures (mean ± SD). Patients with AN at Amenorrheics at 90% 90% IBW IBW (n) (n) Regained menses at 90% IBW (n) 23.6 ± 4.7 (36) 53.8 ± 4.7 (37) 20.4 ± 1.0 (37) 1378 ± 191 (23) 15.5 ± 1.1 (36) 23.1 ± 4.2 (26) 53.6 ± 5.0 (27) 20.3 ± 1.1 (27) 1395 ± 211 (17) 15.6 ± 1.2 (27) 24.8 ± 5.8 (10) 54.5 ± 3.9 (10) 20.8 ± 0.6 (10) 1327 ± 113 (6) 15.4 ± 0.8 (9) Signiﬁcance set at P < 0.05 for all comparisons and is noted in the table. aSigniﬁcant diﬀerence between patients with AN at admission and patients with AN at 90% IBW. bSigniﬁcant diﬀerence between patients with AN at 90% IBW and controls. cSigniﬁcant diﬀerence between amenorrheics at 90% IBW and controls. Controls (n) 24.8 ± 4.7 (16) 56.7 ± 4.4 (16) 21.2 ± 0.9 (16) 1451 ± 135 (12) 15.6 ± 1.0 (16) 3 continued until patients reached 90% IBW with weight gain rates as previously described [10]. Formal exercise was not allowed during hospitalization although no eﬀort was made to control for previous exercise load. Next, a 4–6 wk period of weight maintenance ensued during which patients gained independence and transitioned to outpatient care. Mean caloric intake on discharge was 2600 kcal. No calcium or vitamin D supplements were given. 2.6. Statistical Analysis. Data was analyzed using multiple t- tests, and the probability level was adjusted using the Bon- ferroni correction to compare patients at baseline and after weight gain, those with amenorrhea, those who regained menses, and controls. All data are expressed as mean ± SD. We used independent and dependent t-tests to measure diﬀerences between groups. Multiple comparisons were made with use of the Bonferroni method, available in SPSS software (version 12; SPSS Inc, Chicago, IL). Signiﬁcance was set at P < 0.05 for all comparisons. Initially, patients were analyzed as one group with the use of independent t-tests; later, menstrual status was taken into account. For comparisons with controls, 2-factor repeated-measures anal- ysis of variance with Bonferroni correction was conducted. Repeated-measures analyses were performed for LH, FSH, estradiol, testosterone, DHEAS, serum osteocalcin, urine NTX, and leptin after a log transformation that resulted in a SD < 20% value for each parameter. Correlations between REE and change in BMD and between REE and FFMI were tested using the Pearson linear correlation. 3. Results Thirty-seven patients and 16 healthy control subjects entered and completed the study. Of the 37 study patients, 10 regained normal menstruation at 90% IBW. Age and anthro- pometric measures are shown in Table 1. Bone marker, BMD, and hormone data are shown in Table 2. When the AN patients were refed to 90% IBW, signiﬁcant increases were observed in BMI, REE, FFMI, osteocalcin, spine and pelvis BMDs, LH, FSH, estradiol, leptin, total T3, and IGF-1 while cortisol and ghrelin decreased. As the metabolic rate is a function of metabolically active tissues, all of them contained in the FFM, we controlled for diﬀerences in FFM between patients with anorexia and controls by using REE/FFM and REE/FFMI [16]. At 90% IBW, signiﬁcant correlations were observed between REE and changes in spine (r = 0.48, P < 0.02) and leg (r = 0.43, P < 0.05) BMDs as shown in Figures 1 and 2, respectively. At 90% IBW, both BMI and weight correlated with change in leg BMD, and total T3 correlated with change in spine BMD (P < 0.05). The REE correlations with spine and leg BMDs were even more signiﬁcant after controlling for weight gain, an important predictor of BMD (r = 0.65, P < 0.005) and (r = 0.56, P < 0.02), respectively. The correlations remained signiﬁcant after controlling for T3. No signiﬁcant correlations were found between REE and FFMI at baseline or at 90% IBW or between REE and the hormonal parameters including leptin, ghrelin, and IGF-1. Comparison of the patients with AN at 90% IBW to controls showed signiﬁcantly lower BMI, spine, pelvis, leg, and total BMDs, LH, FSH, estradiol, and free T4 and higher urine NTX and IGF-1. Osteocalcin was higher in patients with AN but not signiﬁcantly so. In contrast to the patients with AN, controls exhibited high correlation between REE and FFMI (r = 0.71, P < 0.01). As a further analysis, patients were divided into two groups according to menstrual status at the time of treatment after 90% IBW testing: those who remained amenorrheic and those who regained menses. Of note, there was no diﬀerence in baseline weight (41.1 kg versus 42.3 kg, amenorrheic versus regained menses). After weight rehabilitation, no diﬀerences were observed between the groups in weight, BMI, or REE, but the amenorrheic group had higher urine NTX (P < 0.02) and lower estradiol (P < 0.006) than those