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Effects of Recombinant Human Insulin-Like Growth Factor (IGF)-I and Estrogen Administration on IGF-I, IGF Binding Protein (IGFBP)-2, and IGFBP-3 in Anorexia Nervosa: A Randomized-Controlled Study

Neuroendocrine Unit (S.G., K.M., A.K.) and The Eating Disorders Unit (D.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; and Endocrine Division (D.C.), University of North Carolina, Chapel Hill, North Carolina 25799

Address all correspondence and requests for reprints to: Steven Grinspoon, M.D., Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: sgrinspoon{at}partners.org.

Administration of recombinant human (rh) IGF-I has been shown to have positive effects on bone density in anorexia nervosa, but the effects of rhIGF-I and estrogen on IGF binding protein (IGFBP)-2 and IGFBP-3 in anorexia nervosa are not known. Sixty-five osteopenic women with anorexia nervosa were randomized to rhIGF-I (30 µg/kg sc twice daily) alone (n = 15), daily ethinyl estradiol (Ovcon 35) with rhIGF-I (n = 15), estradiol and placebo (n = 15), or placebo (n = 14) for 9 months. Subjects were 25.6 ± 0.8 yr of age, low weight (body mass index 16.6 ± 0.2 kg/m²) and osteopenic (T scores -2.06 ± 0.09 for spine and -1.76 ± 0.13 for hip). IGFBP-3 correlated with total hip bone density (r = 0.47, P = 0.0002) and was a significant predictor of hip bone density (P = 0.010) independent of IGF-I and body mass index in a multivariate regression model. During therapy, IGFBP-2 increased by 48 ± 19 ng/ml in response to rhIGF-I and decreased by -38 ± 22 ng/ml in response to placebo (P = 0.011). IGFBP-3 decreased (-895 ± 120 ng/ml) in response to rhIGF-I but showed a minimal change (-53 ± 99 ng/ml) in response to placebo (P < 0.0001). In contrast, no significant effect of estrogen was seen on IGF-I, IGFBP-2 or IGFBP-3. Among patients receiving rhIGF-I, the change in IGFBP-2 was inversely associated with the change in total hip bone density (R = -0.47, P = 0.013). In conclusion, our data suggest that chronic rhIGF-I administration increases IGF-I and IGFBP-2 and decreases IGFBP-3 in women with anorexia nervosa. IGFBP-2 and IGFBP-3 may be important determinants of bone density in this population.

This work was funded in part by NIH Grants DK-52625 (A.K.), AG-02331 (D.C.), M01-RR-01066, The Harvard Eating Disorders Center, and The Rubinstein Foundation. RhIGF-I was supplied by Genentech, Inc. under FDA IND 38,809. None of the authors received grant support or financial assistance from Genentech, Inc.

Abbreviations: ALS, Acid labile subunit; BID, twice daily; BMI, body mass index; DSM, Diagnostic and Statistical Manual of Mental Disorders; DXA, dual x-ray absorptiometry; IGFBP, IGF binding protein; NTX, N-telopeptide; PICP, procollagen carboxyl-terminal propeptide; PRL, prolactin; rh, recombinant human.

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