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Background: Recovery from osteoporosis in anorexia nervosa (AN) is uncertain., Objective: The purpose of this study was to understand the changes in bone mineral density (BMD) in women with AN and the mechanisms of recovery from osteopenia., Design: We studied BMD and markers of bone formation and resorption, osteocalcin and N-telopeptide (NTX), in patients with AN (n=28) who were following a behavioral weight-gain protocol., Results: Anorexic patients experienced significant percentage increases in BMD (4.38 +/- 7.48% for spine; 3.77 +/- 8.8% for hip; P<0.05 for both) from admission until recovery of 90% ideal body weight, achieved over 2.2 mo. NTX concentrations were higher in patients with AN at admission than in healthy control subjects (n=11; 69.0 +/- 31.09 and 48.3 +/- 14.38 nmol/mmol creatinine, respectively; P<0.05) and in reference control subjects (n=30; 69.0 +/- 31.09 and 37.0+/-6.00 nmol/mmol creatinine, respectively; P<0.001). In weight-recovered subjects with AN, osteocalcin increased (from 8.0 +/- 3.05 to 11.2 +/- 6.54 ng/mL; P<0.05), whereas NTX remained elevated (from 69.0 +/- 31.09 to 66.7 +/- 45.5 nmol/mmol creatinine; NS). A decrease in NTX (from 70.7 +/- 40.84 to 45.9 +/- 22.72 nmol/mmol creatinine; NS) occurred only in the subgroup of subjects who regained menses with weight recovery., Conclusions: Nutritional rehabilitation induces a powerful anabolic effect on bone. However, a fall of NTX and a shift from the dominant resorptive state, which we postulate involves full recovery, may involve a hormonal mechanism and require a return of menses. Nutritional rehabilitation appears to be critical to bone recovery and may explain the ineffectiveness of estrogen treatment alone on BMD in the cachectic state.

Objective: To evaluate the effects of estrogen deficiency and exercise on body composition and leptin in young women., Design: Cross-sectional clinical study., Setting: Volunteers in an academic research environment., Patient(s): Three age- and body mass index-matched groups: normal-weight women with exercise-associated amenorrhea, regularly menstruating exercising control women, and regularly menstruating normally active control women., Intervention(s): Collection of blood samples and measurement of body fat and regional fat distribution by dual-energy x-ray absorptiometry., Main Outcome Measure(s): Central fat accumulation (i.e., ratio of trunk to extremity fat) and serum concentrations of E(2) and leptin., Result(s): In both regularly menstruating control groups, but not in the amenorrheic women, there was a negative correlation between the serum E(2) concentrations and the trunk-to-extremity fat ratio (r = -0.4), independent of age, exercise, body fat, and serum T concentrations. In all women, E(2) concentrations were positively and exercise inversely correlated to leptin concentrations, independent of body fat., Conclusion(s): Estradiol level is inversely associated with central fat accumulation only in women with regular menstrual cycles. In all young premenopausal subjects, estrogen secretion influences leptin concentrations independently of body fat.