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Serum Osteoprotegerin in Adolescent Girls with Anorexia Nervosa

Neuroendocrine Unit (M.M., K.K.M., S.G., A.K.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Pediatrics (L.A.S.), University of Massachusetts Medical School, Worcester, Massachusetts 01655; Eating Disorders Unit (D.B.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Amgen (D.D.C.), Thousand Oaks, California 91320; and General Clinical Research Center (G.N.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Anne Klibanski, M.D., Neuroendocrine Unit, Bulfinch 457, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: aklibanski{at}partners.org.

Low bone mineral density (BMD) in adolescents with anorexia nervosa (AN) is associated with a low bone turnover state. Osteoprotegerin (OPG), a cytokine that acts as a decoy receptor for receptor activator of nuclear factor-B ligand, decreases bone resorption by inhibiting differentiation of osteoclast precursors and activation of mature osteoclasts, and by stimulating osteoclast apoptosis. We compared OPG levels in 43 adolescent girls with AN with 38 controls and examined bone density, bone turnover, and hormonal parameters. Girls with AN had lower fat mass, lean body mass, lumbar BMD z-scores, and lumbar bone mineral apparent density than controls. OPG levels were higher in girls with AN than in controls (44.5 ± 22.5 pg/ml vs. 34.5 ± 12.7 pg/ml, P = 0.02). Osteocalcin, deoxypyridinoline, estradiol, free testosterone, IGF-I, and leptin were lower in AN than in healthy adolescents. OPG values correlated negatively with body mass index (r = -0.27, P = 0.02), percent fat mass (r = -0.35, P = 0.0002), leptin (r = -0.28, P = 0.02), lumbar BMD z-scores (r = -0.25, P = 0.03), and lumbar bone mineral apparent density (r = -0.26, P = 0.03). In conclusion, adolescent girls with AN have higher serum OPG values than controls. OPG values correlate negatively with markers of nutritional status and lumbar bone density z-scores and may be a compensatory response to the bone loss seen in this population.

This work was supported in part by NIH Grants M01-RR-01066 and DK-52625-05.

Abbreviations: AN, Anorexia nervosa; BA, bone age; BCE, bone collagen equivalent; BMD, bone mineral density; BMI, body mass index; BSAP, bone-specific alkaline phosphatase; CA, chronological age; CV, coefficient of variation; DHEAS, dehydroepiandrosterone sulfate; DPD, deoxypyridinoline; IGFBP, IGF binding protein; LBMAD, lumbar bone mineral apparent density; LBMD, lumbar BMD; NTX, N-telopeptide; OC, osteocalcin; OPG, osteoprotegerin; RANK, receptor activator of nuclear factor-B; RANKL, RANK ligand.

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