Current Osteoporosis Reports

, Volume 12, Issue 1, pp 82–89 | Cite as

Bone Metabolism in Anorexia Nervosa

  • Pouneh K. Fazeli
  • Anne Klibanski
Epidemiology and Pathophysiology (PR Ebeling and EF Eriksen, Section Editors)


Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed, chronic nutritional deprivation and distorted body image. AN is associated with a number of medical comorbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population.


Anorexia nervosa Bone mineral density 


Compliance with Ethics Guidelines

Conflict of Interest

PK Fazeli has received research support from the NIH (K23 DK094820). A Klibanski has received research supplies from Ipsen (drug and placebo only for study) and Eli Lilly (drug and placebo only for study); and research support from the NIH (R24 DK092759).

Human and Animal Rights and Informed Consent

All studies by PK Fazeli and A Klibanski involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-IV); 4th ed. Washington, DC; 1994.Google Scholar
  2. 2.
    Keski-Rahkonen A, Hoek HW, Susser ES, Linna MS, Sihvola E, Raevuori A, et al. Epidemiology and course of anorexia nervosa in the community. Am J Psychiatry. 2007;164(8):1259–65. doi: 10.1176/appi.ajp.2007.06081388.PubMedCrossRefGoogle Scholar
  3. 3.
    Lucas AR, Crowson CS, O'Fallon WM, Melton III LJ. The ups and downs of anorexia nervosa. Int J Eating Disorders. 1999;26(4):397–405.CrossRefGoogle Scholar
  4. 4.
    Trickey H. Eating disorders exact toll on adults, too. 2006. Accessed 15 Oct 2013.
  5. 5.
    Harris EC, Barraclough B. Excess mortality of mental disorder. Br J Psychiatry. 1998;173:11–53.PubMedCrossRefGoogle Scholar
  6. 6.
    Miller KK, Grinspoon SK, Ciampa J, Hier J, Herzog D, Klibanski A. Medical findings in outpatients with anorexia nervosa. Arch Int Med. 2005;165(5):561–6. doi: 10.1001/archinte.165.5.561.CrossRefGoogle Scholar
  7. 7.
    Grinspoon S, Thomas E, Pitts S, Gross E, Mickley D, Miller K, et al. Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann Int Med. 2000;133(10):790–4.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Lucas AR, Melton III LJ, Crowson CS, O'Fallon WM. Long-term fracture risk among women with anorexia nervosa: a population-based cohort study. Mayo Clin Proc. 1999;74(10):972–7. doi: 10.4065/74.10.972.PubMedGoogle Scholar
  9. 9.
    Rigotti NA, Neer RM, Skates SJ, Herzog DB, Nussbaum SR. The clinical course of osteoporosis in anorexia nervosa. A longitudinal study of cortical bone mass. JAMA. 1991;265(9):1133–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Misra M, Tsai P, Anderson EJ, Hubbard JL, Gallagher K, Soyka LA, et al. Nutrient intake in community-dwelling adolescent girls with anorexia nervosa and in healthy adolescents. Am J Clin Nutrit. 2006;84(4):698–706.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Haagensen AL, Feldman HA, Ringelheim J, Gordon CM. Low prevalence of vitamin D deficiency among adolescents with anorexia nervosa. Osteoporosis Int. 2008;19(3):289–94. doi: 10.1007/s00198-007-0476-z.CrossRefGoogle Scholar
  12. 12.
    Stefanis N, Mackintosh C, Abraha HD, Treasure J, Moniz C. Dissociation of bone turnover in anorexia nervosa. Ann Clin Biochem. 1998;35(Pt 6):709–16.PubMedCrossRefGoogle Scholar
  13. 13.
    Soyka LA, Grinspoon S, Levitsky LL, Herzog DB, Klibanski A. The effects of anorexia nervosa on bone metabolism in female adolescents. J Clin Endocrinol Metabol. 1999;84(12):4489–96.Google Scholar
  14. 14.
    Garfinkel PE, Brown GM, Stancer HC, Moldofsky H. Hypothalamic-pituitary function in anorexia nervosa. Arch Gen Psychiatry. 1975;32(6):739–44.PubMedCrossRefGoogle Scholar
  15. 15.
    Scacchi M, Pincelli AI, Caumo A, Tomasi P, Delitala G, Baldi G, et al. Spontaneous nocturnal growth hormone secretion in anorexia nervosa. J Clin Endocrinol Metabol. 1997;82(10):3225–9.CrossRefGoogle Scholar
  16. 16.
    Stoving RK, Veldhuis JD, Flyvbjerg A, Vinten J, Hangaard J, Koldkjaer OG, et al. Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis. J Clin Endocrinol Metabol. 1999;84(6):2056–63.Google Scholar
  17. 17.
    Misra M, Miller KK, Bjornson J, Hackman A, Aggarwal A, Chung J, et al. Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metabol. 2003;88(12):5615–23.CrossRefGoogle Scholar
  18. 18.
    Grinspoon SK, Baum HB, Peterson S, Klibanski A. Effects of rhIGF-I administration on bone turnover during short-term fasting. J Clin Invest. 1995;96(2):900–6. doi: 10.1172/JCI118137.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Counts DR, Gwirtsman H, Carlsson LM, Lesem M, Cutler Jr GB. The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins. J Clin Endocrinol Metabol. 1992;75(3):762–7.Google Scholar
  20. 20.
    Hotta M, Fukuda I, Sato K, Hizuka N, Shibasaki T, Takano K. The relationship between bone turnover and body weight, serum insulin-like growth factor (IGF) I, and serum IGF-binding protein levels in patients with anorexia nervosa. J Clin Endocrinol Metabol. 2000;85(1):200–6.Google Scholar
  21. 21.
    Gianotti L, Pincelli AI, Scacchi M, Rolla M, Bellitti D, Arvat E, et al. Effects of recombinant human insulin-like growth factor I administration on spontaneous and growth hormone (GH)-releasing hormone-stimulated GH secretion in anorexia nervosa. J Clin Endocrinol Metabol. 2000;85(8):2805–9.Google Scholar
  22. 22.
    Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, et al. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol. 2001;145(5):669–73.PubMedGoogle Scholar
  23. 23.
    Misra M, Miller KK, Herzog DB, Ramaswamy K, Aggarwal A, Almazan C, et al. Growth hormone and ghrelin responses to an oral glucose load in adolescent girls with anorexia nervosa and controls. J Clin Endocrinol Metabol. 2004;89(4):1605–12.CrossRefGoogle Scholar
  24. 24.
    Misra M, Miller KK, Kuo K, Griffin K, Stewart V, Hunter E, et al. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiol Endocrinol Metabol. 2005;289(2):E347–56. doi: 10.1152/ajpendo.00615.2004.CrossRefGoogle Scholar
  25. 25.
    Zhao TJ, Liang G, Li RL, Xie X, Sleeman MW, Murphy AJ, et al. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Proc Natl Acad Sci U S A. 2010;107(16):7467–72. doi: 10.1073/pnas.1002271107.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Gahete MD, Cordoba-Chacon J, Luque RM, Kineman RD. The rise in growth hormone during starvation does not serve to maintain glucose levels or lean mass but is required for appropriate adipose tissue response in female mice. Endocrinology. 2013;154(1):263–9. doi: 10.1210/en.2012-1849.PubMedCrossRefGoogle Scholar
  27. 27.
    Nakasaki M, Yoshioka K, Miyamoto Y, Sasaki T, Yoshikawa H, Itoh K. IGF-I secreted by osteoblasts acts as a potent chemotactic factor for osteoblasts. Bone. 2008;43(5):869–79. doi: 10.1016/j.bone.2008.07.241.PubMedCrossRefGoogle Scholar
  28. 28.
    Canalis E. Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria. J Clin Invest. 1980;66(4):709–19. doi: 10.1172/JCI109908.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metabol. 2002;87(6):2883–91.CrossRefGoogle Scholar
  30. 30.
    Grinspoon S, Baum H, Lee K, Anderson E, Herzog D, Klibanski A. Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metabol. 1996;81(11):3864–70.Google Scholar
  31. 31.
    Misra M, McGrane J, Miller KK, Goldstein MA, Ebrahimi S, Weigel T, et al. Effects of rhIGF-1 administration on surrogate markers of bone turnover in adolescents with anorexia nervosa. Bone. 2009;45(3):493–8. doi: 10.1016/j.bone.2009.06.002.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Nishimura T, Nakatake Y, Konishi M, Itoh N. Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta. 2000;1492(1):203–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Zhang X, Yeung DC, Karpisek M, Stejskal D, Zhou ZG, Liu F, et al. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes. 2008;57(5):1246–53. doi: 10.2337/db07-1476.PubMedCrossRefGoogle Scholar
  34. 34.
    Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, et al. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005;115(6):1627–35. doi: 10.1172/JCI23606.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, et al. Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metabol. 2007;5(6):415–25. doi: 10.1016/j.cmet.2007.05.003.CrossRefGoogle Scholar
  36. 36.
    Inagaki T, Lin VY, Goetz R, Mohammadi M, Mangelsdorf DJ, Kliewer SA. Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. Cell Metabol. 2008;8(1):77–83. doi: 10.1016/j.cmet.2008.05.006.CrossRefGoogle Scholar
  37. 37.
    Fazeli PK, Misra M, Goldstein M, Miller KK, Klibanski A. Fibroblast growth factor-21 may mediate growth hormone resistance in anorexia nervosa. J Clin Endocrinol Metabol. 2010;95(1):369–74. doi: 10.1210/jc.2009-1730.CrossRefGoogle Scholar
  38. 38.
    Gillum MP, Erion DM, Shulman GI. Sirtuin-1 regulation of mammalian metabolism. Trends Molec Med. 2010;17(1):8–13. doi: 10.1016/j.molmed.2010.09.005.Google Scholar
  39. 39.
    Yamamoto M, Iguchi G, Fukuoka H, Suda K, Bando H, Takahashi M, et al. SIRT1 regulates adaptive response of the growth hormone—insulin-like growth factor-I axis under fasting conditions in liver. Proc Natl Acad Sci U S A. 2013;110(37):14948–53. doi: 10.1073/pnas.1220606110.PubMedCrossRefGoogle Scholar
  40. 40.
    Baxter RC, Turtle JR. Regulation of hepatic growth hormone receptors by insulin. Biochem Biophys Res Commun. 1978;84(2):350–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Leung KC, Doyle N, Ballesteros M, Waters MJ, Ho KK. Insulin regulation of human hepatic growth hormone receptors: divergent effects on biosynthesis and surface translocation. J Clin Endocrinol Metabol. 2000;85(12):4712–20.Google Scholar
  42. 42.
    Boyar RM, Katz J, Finkelstein JW, Kapen S, Weiner H, Weitzman ED, et al. Anorexia nervosa. Immaturity of the 24-hour luteinizing hormone secretory pattern. N Engl J Med. 1974;291(17):861–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Wiegelmann W, Solbach HG. Effects of LH-RH on plasma levels of LH and FSH in anorexia nervosa. Horm Metab Res. 1972;4(5):404. doi: 10.1055/s-0028-1097104.PubMedCrossRefGoogle Scholar
  44. 44.
    Mecklenburg RS, Loriaux DL, Thompson RH, Andersen AE, Lipsett MB. Hypothalamic dysfunction in patients with anorexia nervosa. Medicine. 1974;53(2):147–59.PubMedCrossRefGoogle Scholar
  45. 45.
    Travaglini P, Beck-Peccoz P, Ferrari C, Ambrosi B, Paracchi A, Severgnini A, et al. Some aspects of hypothalamic-pituitary function in patients with anorexia nervosa. Acta Endocrinol (Copenh). 1976;81(2):252–62.Google Scholar
  46. 46.
    Nillius SJ, Fries H, Wide L. Successful induction of follicular maturation and ovulation by prolonged treatment with LH-releasing hormone in women with anorexia nervosa. Am J Obstet Gynecol. 1975;122(8):921–8.PubMedGoogle Scholar
  47. 47.
    Riis BJ, Rodbro P, Christiansen C. The role of serum concentrations of sex steroids and bone turnover in the development and occurrence of postmenopausal osteoporosis. Calcif Tissue Int. 1986;38(6):318–22.PubMedCrossRefGoogle Scholar
  48. 48.
    Klibanski A, Biller BM, Schoenfeld DA, Herzog DB, Saxe VC. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J Clin Endocrinol Metabol. 1995;80(3):898–904.Google Scholar
  49. 49.
    •• Misra M, Katzman D, Miller KK, Mendes N, Snelgrove D, Russell M, et al. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. J Bone Min Res. 2011;26(10):2430–8. doi: 10.1002/jbmr.447. Demonstrates an increase in bone mineral density in response to physiologic estrogen replacement in adolescent girls with anorexia nervosa.CrossRefGoogle Scholar
  50. 50.
    van Binsbergen CJ, Coelingh Bennink HJ, Odink J, Haspels AA, Koppeschaar HP. A comparative and longitudinal study on endocrine changes related to ovarian function in patients with anorexia nervosa. J Clin Endocrinol Metabol. 1990;71(3):705–11.CrossRefGoogle Scholar
  51. 51.
    Miller KK, Lawson EA, Mathur V, Wexler TL, Meenaghan E, Misra M, et al. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. J Clin Endocrinol Metabol. 2007;92(4):1334–9. doi: 10.1210/jc.2006-2501.CrossRefGoogle Scholar
  52. 52.
    •• Miller KK, Meenaghan E, Lawson EA, Misra M, Gleysteen S, Schoenfeld D, et al. Effects of risedronate and low-dose transdermal testosterone on bone mineral density in women with anorexia nervosa: a randomized, placebo-controlled study. J Clin Endocrinol Metabol. 2011;96(7):2081–8. doi: 0.1210/jc.2011-0380. Demonstrates an increase in bone mineral density in response to one year of bisphosphonate therapy in anorexia nervosa. The 2%–4% increase in bone mineral density is the greatest increase reported to date in response to a treatment in women with anorexia nervosa.CrossRefGoogle Scholar
  53. 53.
    Zumoff B, Walsh BT, Katz JL, Levin J, Rosenfeld RS, Kream J, et al. Subnormal plasma dehydroisoandrosterone to cortisol ratio in anorexia nervosa: a second hormonal parameter of ontogenic regression. J Clin Endocrinol Metabol. 1983;56(4):668–72.CrossRefGoogle Scholar
  54. 54.
    Gordon CM, Goodman E, Emans SJ, Grace E, Becker KA, Rosen CJ, et al. Physiologic regulators of bone turnover in young women with anorexia nervosa. J Pediatrics. 2002;141(1):64–70. doi: 10.1067/mpd.2002.125003.CrossRefGoogle Scholar
  55. 55.
    Gordon CM, Grace E, Emans SJ, Feldman HA, Goodman E, Becker KA, et al. Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial. J Clin Endocrinol Metabol. 2002;87(11):4935–41.CrossRefGoogle Scholar
  56. 56.
    Divasta AD, Feldman HA, Giancaterino C, Rosen CJ, Leboff MS, Gordon CM. The effect of gonadal and adrenal steroid therapy on skeletal health in adolescents and young women with anorexia nervosa. Metabolism. 2012;61(7):1010–20. doi: 10.1016/j.metabol.2011.11.016.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Misra M, Miller KK, Almazan C, Ramaswamy K, Lapcharoensap W, Worley M, et al. Alterations in cortisol secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metabol. 2004;89(10):4972–80. doi: 10.1210/jc.2004-0723.CrossRefGoogle Scholar
  58. 58.
    Lawson EA, Donoho D, Miller KK, Misra M, Meenaghan E, Lydecker J, et al. Hypercortisolemia is associated with severity of bone loss and depression in hypothalamic amenorrhea and anorexia nervosa. J Clin Endocrinol Metabol. 2009;94(12):4710–6. doi: 10.1210/jc.2009-1046.CrossRefGoogle Scholar
  59. 59.
    Misra M, Klibanski A. The neuroendocrine basis of anorexia nervosa and its impact on bone metabolism. Neuroendocrinology. 2011;93(2):65–73. doi: 10.1159/000323771.PubMedCrossRefGoogle Scholar
  60. 60.
    Boyar RM, Hellman LD, Roffwarg H, Katz J, Zumoff B, O'Connor J, et al. Cortisol secretion and metabolism in anorexia nervosa. N Engl J Med. 1977;296(4):190–3. doi: 10.1056/NEJM197701272960403.PubMedCrossRefGoogle Scholar
  61. 61.
    Canalis E. Clinical review 83: mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. J Clin Endocrinol Metabol. 1996;81(10):3441–7.Google Scholar
  62. 62.
    Rauch A, Seitz S, Baschant U, Schilling AF, Illing A, Stride B, et al. Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor. Cell Metabol. 2010;11(6):517–31. doi: 10.1016/j.cmet.2010.05.005.CrossRefGoogle Scholar
  63. 63.
    McCarthy TL, Centrella M, Canalis E. Cortisol inhibits the synthesis of insulin-like growth factor-I in skeletal cells. Endocrinology. 1990;126(3):1569–75.PubMedCrossRefGoogle Scholar
  64. 64.
    Urena P, Iida-Klein A, Kong XF, Juppner H, Kronenberg HM, Abou-Samra AB, et al. Regulation of parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acid by glucocorticoids and PTH in ROS 17/2.8 and OK cells. Endocrinology. 1994;134(1):451–6.PubMedGoogle Scholar
  65. 65.
    Padmanabhan V, Keech C, Convey EM. Cortisol inhibits and adrenocorticotropin has no effect on luteinizing hormone-releasing hormone-induced release of luteinizing hormone from bovine pituitary cells in vitro. Endocrinology. 1983;112(5):1782–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Moshang Jr T, Parks JS, Baker L, Vaidya V, Utiger RD, Bongiovanni AM, et al. Low serum triiodothyronine in patients with anorexia nervosa. J Clin Endocrinol Metabol. 1975;40(3):470–3.CrossRefGoogle Scholar
  67. 67.
    Miyai K, Yamamoto T, Azukizawa M, Ishibashi K, Kumahara Y. Serum thyroid hormones and thyrotropin in anorexia nervosa. J Clin Endocrinol Metabol. 1975;40(2):334–8.CrossRefGoogle Scholar
  68. 68.
    Croxson MS, Ibbertson HK. Low serum triiodothyronine (T3) and hypothyroidism in anorexia nervosa. J Clin Endocrinol Metabol. 1977;44(1):167–74.CrossRefGoogle Scholar
  69. 69.
    Leslie RD, Isaacs AJ, Gomez J, Raggatt PR, Bayliss R. Hypothalamo-pituitary-thyroid function in anorexia nervosa: influence of weight gain. Br Med J. 1978;2(6136):526–8.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Casper RC, Frohman LA. Delayed TSH release in anorexia nervosa following injection of thyrotropin-releasing hormone (TRH). Psychoneuroendocrinology. 1982;7(1):59–68.PubMedCrossRefGoogle Scholar
  71. 71.
    Kiyohara K, Tamai H, Takaichi Y, Nakagawa T, Kumagai LF. Decreased thyroidal triiodothyronine secretion in patients with anorexia nervosa: influence of weight recovery. Am J Clin Nutrit. 1989;50(4):767–72.PubMedGoogle Scholar
  72. 72.
    Onur S, Haas V, Bosy-Westphal A, Hauer M, Paul T, Nutzinger D, et al. L-tri-iodothyronine is a major determinant of resting energy expenditure in underweight patients with anorexia nervosa and during weight gain. Eur J Endocrinol. 2005;152(2):179–84. doi: 10.1530/eje.1.01850.PubMedCrossRefGoogle Scholar
  73. 73.
    Moore R, Mills IH. Serum T3 and T4 levels in patients with anorexia nervosa showing transient hyperthyroidism during weight gain. Clin Endocrinol. 1979;10(5):443–9.CrossRefGoogle Scholar
  74. 74.
    Fraser SA, Anderson JB, Smith DA, Wilson GM. Osteoporosis and fractures following thyrotoxicosis. Lancet. 1971;1(7707):981–3.PubMedCrossRefGoogle Scholar
  75. 75.
    Kindblom JM, Gevers EF, Skrtic SM, Lindberg MK, Gothe S, Tornell J, et al. Increased adipogenesis in bone marrow but decreased bone mineral density in mice devoid of thyroid hormone receptors. Bone. 2005;36(4):607–16. doi: 10.1016/j.bone.2005.01.017.PubMedCrossRefGoogle Scholar
  76. 76.
    Bredella MA, Fazeli PK, Miller KK, Misra M, Torriani M, Thomas BJ, et al. Increased bone marrow fat in anorexia nervosa. J Clin Endocrinol Metabol. 2009;94(6):2129–36. doi: 10.1210/jc.2008-2532.CrossRefGoogle Scholar
  77. 77.
    Abu EO, Bord S, Horner A, Chatterjee VK, Compston JE. The expression of thyroid hormone receptors in human bone. Bone. 1997;21(2):137–42.PubMedCrossRefGoogle Scholar
  78. 78.
    Miell JP, Taylor AM, Zini M, Maheshwari HG, Ross RJ, Valcavi R. Effects of hypothyroidism and hyperthyroidism on insulin-like growth factors (IGFs) and growth hormone- and IGF-binding proteins. J Clin Endocrinol Metabol. 1993;76(4):950–5.Google Scholar
  79. 79.
    Grinspoon S, Gulick T, Askari H, Landt M, Lee K, Anderson E, et al. Serum leptin levels in women with anorexia nervosa. J Clin Endocrinol Metabol. 1996;81(11):3861–3.Google Scholar
  80. 80.
    Misra M, Miller KK, Kuo K, Griffin K, Stewart V, Hunter E, et al. Secretory dynamics of leptin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiol Endocrinol Metabol. 2005;289(3):E373–81. doi: 10.1152/ajpendo.00041.2005.CrossRefGoogle Scholar
  81. 81.
    Miller KK, Grinspoon S, Gleysteen S, Grieco KA, Ciampa J, Breu J, et al. Preservation of neuroendocrine control of reproductive function despite severe undernutrition. J Clin Endocrinol Metabol. 2004;89(9):4434–8. doi: 10.1210/jc.2004-0720.CrossRefGoogle Scholar
  82. 82.
    Legroux-Gerot I, Vignau J, Biver E, Pigny P, Collier F, Marchandise X, et al. Anorexia nervosa, osteoporosis and circulating leptin: the missing link. Osteoporosis Int. 2010;21(10):1715–22. doi: 10.1007/s00198-009-1120-x.CrossRefGoogle Scholar
  83. 83.
    Lawson EA, Miller KK, Bredella MA, Phan C, Misra M, Meenaghan E, et al. Hormone predictors of abnormal bone microarchitecture in women with anorexia nervosa. Bone. 2010;46(2):458–63. doi: 10.1016/j.bone.2009.09.005.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med. 2004;351(10):987–97. doi: 10.1056/NEJMoa040388.PubMedCrossRefGoogle Scholar
  85. 85.
    Misra M, Miller KK, Tsai P, Gallagher K, Lin A, Lee N, et al. Elevated peptide YY levels in adolescent girls with anorexia nervosa. J Clin Endocrinol Metabol. 2006;91(3):1027–33. doi: 10.1210/jc.2005-1878.CrossRefGoogle Scholar
  86. 86.
    Utz AL, Lawson EA, Misra M, Mickley D, Gleysteen S, Herzog DB, et al. Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa. Bone. 2008;43(1):135–9. doi: 10.1016/j.bone.2008.03.007.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Baldock PA, Sainsbury A, Couzens M, Enriquez RF, Thomas GP, Gardiner EM, et al. Hypothalamic Y2 receptors regulate bone formation. J Clin Invest. 2002;109(7):915–21. doi: 10.1172/JCI14588.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Misra M, Prabhakaran R, Miller KK, Goldstein MA, Mickley D, Clauss L, et al. Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II. J Clin Endocrinol Metabol. 2008;93(4):1292–7. doi: 10.1210/jc.2007-2419.CrossRefGoogle Scholar
  89. 89.
    Fukushima N, Hanada R, Teranishi H, Fukue Y, Tachibana T, Ishikawa H, et al. Ghrelin directly regulates bone formation. J Bone Min Res. 2005;20(5):790–8. doi: 10.1359/JBMR.041237.CrossRefGoogle Scholar
  90. 90.
    Misra M, Miller KK, Stewart V, Hunter E, Kuo K, Herzog DB, et al. Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents. J Clin Endocrinol Metabol. 2005;90(9):5082–7. doi: 10.1210/jc.2005-0512.CrossRefGoogle Scholar
  91. 91.
    Misra M, Miller KK, Cord J, Prabhakaran R, Herzog DB, Goldstein M, et al. Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa. J Clin Endocrinol Metabol. 2007;92(6):2046–52. doi: 10.1210/jc.2006-2855.CrossRefGoogle Scholar
  92. 92.
    Tagami T, Satoh N, Usui T, Yamada K, Shimatsu A, Kuzuya H. Adiponectin in anorexia nervosa and bulimia nervosa. J Clin Endocrinol Metabol. 2004;89(4):1833–7.CrossRefGoogle Scholar
  93. 93.
    Housova J, Anderlova K, Krizova J, Haluzikova D, Kremen J, Kumstyrova T, et al. Serum adiponectin and resistin concentrations in patients with restrictive and binge/purge form of anorexia nervosa and bulimia nervosa. J Clin Endocrinol Metabol. 2005;90(3):1366–70. doi: 10.1210/jc.2004-1364.CrossRefGoogle Scholar
  94. 94.
    Luo XH, Guo LJ, Xie H, Yuan LQ, Wu XP, Zhou HD, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signaling pathway. J Bone Min Res. 2006;21(10):1648–56. doi: 10.1359/jbmr.060707.CrossRefGoogle Scholar
  95. 95.
    Lowe B, Zipfel S, Buchholz C, Dupont Y, Reas DL, Herzog W. Long-term outcome of anorexia nervosa in a prospective 21-year follow-up study. Psycholog Med. 2001;31(5):881–90.CrossRefGoogle Scholar
  96. 96.
    Miller KK, Lee EE, Lawson EA, Misra M, Minihan J, Grinspoon SK, et al. Determinants of skeletal loss and recovery in anorexia nervosa. J Clin Endocrinol Metabol. 2006;91(8):2931–7. doi: 10.1210/jc.2005-2818.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Neuroendocrine UnitMassachusetts General HospitalBostonUSA

Personalised recommendations