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Determinants of Skeletal Loss and Recovery in Anorexia Nervosa

Neuroendocrine Unit (K.K.M., E.E.L., E.A.L., M.M., J.M., S.K.G., A.K.) and Eating Disorders Unit (D.H.), Massachusetts General Hospital and Department of Internal Medicine, Beth Israel Deaconess Medical Center (S.G.), Harvard Medical School, Boston, Massachusetts 02114; and Wilkins Center for Eating Disorders (D.M.), Greenwich, Connecticut 06831

Address all correspondence and requests for reprints to: Karen K. Miller, Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: kkmiller{at}partners.org.

Context: Anorexia nervosa (AN) is complicated by severe bone loss. The effects of persistent undernutrition and consequent neuroendocrine dysfunction on bone mass and the factors influencing skeletal recovery have not been well characterized.

Objective: The objective of the study was to determine the rate of bone loss at the spine and hip in women with AN and whether resumption of menstrual function and/or improvement in weight are determinants of skeletal recovery in AN.

Design: The study had a longitudinal design.

Setting: The study was conducted at a clinical research center.

Study Participants: Participants included 75 ambulatory women with AN.

Main Outcome Measures: Bone mineral density (BMD) and body composition were measured with dual x-ray absorptiometry.

Results: In women not receiving oral contraceptives, those who did not improve weight or resume menses had a mean annual rate of decline of 2.6% at the spine and 2.4% at the hip. Those who resumed menses and improved weight had a mean annual increase of 3.1% at the posteroanterior spine and 1.8% at the hip. Women who recovered menses demonstrated a mean increase of posteroanterior spine but not hip BMD, independent of weight gain. Women who improved weight, regardless of whether they recovered menstrual function, demonstrated a mean increase of hip, but not spine, BMD. Increase in fat-free mass was a more significant determinant of increased BMD than weight or fat mass gain. In women receiving oral contraceptives, there was no increase in BMD at any site despite a mean 11.7% weight increase.

Conclusions: These data suggest that rapid bone loss, at an average annual rate of about 2.5%, occurs in young women with active AN. Resumption of menstrual function is important for spine BMD recovery, whereas weight gain is critical for hip BMD recovery. We did not observe an increase in BMD with weight gain in women receiving oral contraceptives. Therefore, improvements in reproduction function and weight, with increases in lean body mass a critical component, are both necessary for skeletal recovery in women with AN.

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