Skip to main content

Advertisement

SpringerLink
Log in

Body Composition and Skeletal Health: Too Heavy? Too Thin?

  • Evaluation and Management (M Kleerekoper, Section Editor)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

The relationship between body composition and skeletal metabolism has received growing recognition. Low body weight is an established risk factor for fracture. The effect of obesity on skeletal health is less well defined. Extensive studies in patients with anorexia nervosa and obesity have illuminated many of the underlying biologic mechanisms by which body composition modulates bone mass. This review examines the relationship between body composition and bone mass through data from recent research studies throughout the weight spectrum ranging from anorexia nervosa to obesity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006;17:1726–33.

    Article  PubMed  CAS  Google Scholar 

  2. National Osteoporosis Foundation: Fast Facts. Available at http://www.nof.org/node/40. Accessed March 2012.

  3. Scheidt PC, Harel Y, Trumble AC, et al. The epidemiology of nonfatal injuries among US children and youth. Am J Public Health. 1995;85:932–8.

    Article  PubMed  CAS  Google Scholar 

  4. Walsh SS, Jarvis SN, Towner EM, Aynsley-Green A. Annual incidence of unintentional injury among 54,000 children. Inj Prev. 1996;2:16–20.

    Article  PubMed  CAS  Google Scholar 

  5. Landin LA. Epidemiology of children’s fractures. J Pediatr Orthop B. 1997;6:79–83.

    Article  PubMed  CAS  Google Scholar 

  6. Jones IE, Williams SM, Dow N, Goulding A. How many children remain fracture-free during growth? A longitudinal study of children and adolescents participating in the Dunedin multidisciplinary health and development study. Osteoporos Int. 2002;13:990–5.

    Article  PubMed  CAS  Google Scholar 

  7. Hoek HW, van Hoeken D. Review of the prevalence and incidence of eating disorders. Int J Eat Disord. 2003;34:383–96.

    Article  PubMed  Google Scholar 

  8. Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA. 2012;307:491–7.

    Article  PubMed  Google Scholar 

  9. Lobstein T, Baur L, Uauy R. International Obesity Task Force. Obesity in children and young people: a crisis in public health. Obesity Rev. 2004;5:4–104.

    Article  Google Scholar 

  10. Miller KK, Grinspoon SK, Ciampa J, et al. Medical findings in outpatients with anorexia nervosa. Arch Intern Med. 2005;165:561–6.

    Article  PubMed  Google Scholar 

  11. Rigotti NA, Neer RM, Skates SJ, et al. The clinical course of osteoporosis in anorexia nervosa: a longitudinal study of cortical bone mass. JAMA. 1991;265:1133–8.

    Article  PubMed  CAS  Google Scholar 

  12. Lucas AR, Melton 3rd LJ, Crowson CS, O’Fallon WM. Long-term fracture risk among women with anorexia nervosa: a population based cohort study. Mayo Clin Proc. 1999;74:972–7.

    PubMed  CAS  Google Scholar 

  13. Bouxsein ML, Szulc P, Munoz F, et al. Contribution of trochanteric soft tissues to fall force estimates, the factor of risk, and prediction of hip fracture risk. J Bone Miner Res. 2007;22:825–31.

    Article  PubMed  Google Scholar 

  14. Roberts BJ, Thrall E, Muller JA, Bouxsein ML. Comparison of hip fracture risk prediction by femoral aBMD to experimentally measured factor of risk. Bone. 2010;46:742–6.

    Article  PubMed  Google Scholar 

  15. Finkelstein EA, Chen H, Prabhu M, et al. The relationship between obesity and injuries among U.S. adults. Am J Health Promot. 2007;21:460–8.

    Article  PubMed  Google Scholar 

  16. Mignardot JB, Olivier I, Promayon E, Nougier V. Obesity impact on the attentional cost for controlling posture. PLoS One. 2010;5:e14387.

    Article  PubMed  CAS  Google Scholar 

  17. van Geel TA, van den Bergh JP, Dinant GJ, Geusens PP. Individualizing fracture risk prediction. Maturitas. 2010;65:143–8.

    Article  PubMed  Google Scholar 

  18. Soyka L, Misra M, Frenchman A, et al. Abnormal bone mineral accrual in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab. 2002;87:4177–85.

    Article  PubMed  CAS  Google Scholar 

  19. Bachrach LK, Guido D, Katzman D, et al. Decreased bone density in adolescent girls with anorexia nervosa. Pediatrics. 1990;86:440–7.

    PubMed  CAS  Google Scholar 

  20. Grinspoon S, Thomas E, Pitts S, et al. Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann Intern Med. 2000;133:790–4.

    PubMed  CAS  Google Scholar 

  21. Vestergaard P, Emborg C, Støving RK, et al. Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders–a nationwide register study. Int J Eat Disord. 2002;32:301–8.

    Article  PubMed  Google Scholar 

  22. • Reid IR. Fat and bone. Arch Biochem Biophys. 2010;503:20–7. In this review the author illustrates an excellent example of the statistical consequences of inappropriately treating highly collinear variables as independent factors. Some papers’ methods to adjust fat mass for body size lack adequate statistical rigor and may yield erroneous conclusions..

    Article  PubMed  CAS  Google Scholar 

  23. Wells JC, Cole TJ. ALSPAC study steam: adjustment of fat-free mass and fat mass for height in children aged 8 y. Int J Obes Relat Metab Disord. 2002;26:947–52.

    Article  PubMed  CAS  Google Scholar 

  24. • Compston JE, Watts NB, Chapurlat R, et al. Obesity is not protective against fracture in postmenopausal women: GLOW. Am J Med. 2011;124:1043–50. This is a large longitudinal study that demonstrates site specificity in regard to fracture risk in an obese population.

    Article  PubMed  Google Scholar 

  25. Beck TJ, Petit MA, Wu G, et al. Does obesity really make the femur stronger? BMD, geometry, and fracture incidence in the women’s health initiative-observational study. J Bone Miner Res. 2009;24:1369–79.

    Article  PubMed  Google Scholar 

  26. Prieto-Alhambra D, Premaor MO, et al. The association between fracture and obesity is site-dependent: a population-based study in postmenopausal women. J Bone Miner Res 2011, Epub.

  27. Frost HM. Bone “mass” and the “mechanostat”: a proposal. Anat Rec. 1987;219:1–9.

    Article  PubMed  CAS  Google Scholar 

  28. Liskova M, Hert J. Reaction of bone to mechanical stimuli. Part 2. Periosteal and endosteal reaction to tibial diaphysis in rabbit to intermittent loading. Folia Morphol. 1971;19:301–17.

    CAS  Google Scholar 

  29. Lanyon LE, Rubin CT. Static vs dynamic loads as an influence on bone remodeling. J Biomech. 1984;17:897–905.

    Article  PubMed  CAS  Google Scholar 

  30. Rubin CT, McLeod KJ. Promotion of bony ingrowth by frequency-specific, low-amplitude mechanical strain. Clin Orthop Rel Res. 1994;298:165–74.

    Google Scholar 

  31. Pauwels F. Gesammelte Abhandlungen zur Funktionellen Anatomie des Bewegungsapparates. Berlin: Springer; 1965.

    Google Scholar 

  32. Lu TW, O’Conner JJ, Taylor SJG, Walker PS. Influence of muscle activity on the forces in the femur: comparison between in vivo measurement and calculation. Trans Orthop Res Soc. 1997;22:721.

    Google Scholar 

  33. Waugh EJ, Woodside DB, Beaton DE, et al. Effects of exercise on bone mass in young women with anorexia nervosa. Med Sci Sports Exerc. 2011;43:755–63.

    PubMed  Google Scholar 

  34. Beaumont P, Chambers T, Rouse L, Abraham S. The diet composition and nutritional knowledge of patients with anorexia nervosa. J Hum Nutr. 1981;35:265–73.

    PubMed  CAS  Google Scholar 

  35. Hadigan CM, Anderson EJ, Miller KK, et al. Assessment of macronutrient and micronutrient intake in women with anorexia nervosa. Int J Eat Disord. 2000;28:284–92.

    Article  PubMed  CAS  Google Scholar 

  36. Misra M, Tsai P, Anderson EJ, et al. Nutrient intake in community-dwelling adolescent girls with anorexia nervosa and in healthy adolescents. Am J Clin Nutr. 2006;84:698–706.

    PubMed  CAS  Google Scholar 

  37. Ernst B, Thurnheer M, Schmid SM, Schultes B. Evidence for the necessity to systematically assess micronutrient status prior to bariatric surgery. Obes Surg. 2009;19:66–73.

    Article  PubMed  Google Scholar 

  38. Strohmayer E, Via MA, Yanagisawa R. Metabolic management following bariatric surgery. Mt Sinai J Med. 2010;77:431–45.

    Article  PubMed  Google Scholar 

  39. Konradsen S, Ag H, Lindberg F, et al. Serum 1,25-dihydroxy vitamin D is inversely associated with body mass index. Eur J Nutr. 2008;47:87–91.

    Article  PubMed  CAS  Google Scholar 

  40. Parikh SJ, Edelman M, Uwaifo GI, et al. The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab. 2004;89:1196–9.

    Article  PubMed  CAS  Google Scholar 

  41. Wortsman J, Matsuoka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72:690–3.

    PubMed  CAS  Google Scholar 

  42. Kamycheva E, Sundsfjord J, Jorde R. Serum parathyroid hormone level is associated with body mass index. The 5th Tromso study. Eur J Endocrinol. 2004;151:167–72.

    Article  PubMed  CAS  Google Scholar 

  43. Hultin H, Edfeldt K, Sundbom M, Hellman P. Left-shifted relation between calcium and parathyroid hormone in obesity. J Clin Endocrinol Metab. 2010;95:3973–81.

    Article  PubMed  CAS  Google Scholar 

  44. Boyar RM, Katz J, Finkelstein JW, et al. Anorexia nervosa. Immaturity of the 24-hour luteinizing hormone secretory pattern. N Engl J Med. 1974;291:861–5.

    Article  PubMed  CAS  Google Scholar 

  45. Giusti M, Torre R, Traverso L, et al. Endogenous opioid blockade and gonadotropin secretion: role of pulsatile luteinizing hormone-releasing hormone administration in anorexia nervosa and weight loss amenorrhea. Fertil Steril. 1988;49:797–801.

    PubMed  CAS  Google Scholar 

  46. Biller BM, Saxe V, Herzog DB, et al. Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa. J Clin Endocrinol Metab. 1989;68:548–54.

    Article  PubMed  CAS  Google Scholar 

  47. Miller KK, Grinspoon S, Gleysteen S, et al. Preservation of neuroendocrine control of reproductive function despite severe undernutrition. J Clin Endocrinol Metab. 2004;89:4434–8.

    Article  PubMed  CAS  Google Scholar 

  48. Grinspoon S, Baum H, Lee K, et al. Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metab. 1996;81:3864–70.

    Article  PubMed  CAS  Google Scholar 

  49. Klibanski A, Biller BM, Schoenfeld DA, et al. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J Clin Endocrinol Metab. 1995;80:898–904.

    Article  PubMed  CAS  Google Scholar 

  50. Grinspoon S, Thomas L, Miller K, et al. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab. 2002;87:2883–91.

    Article  PubMed  CAS  Google Scholar 

  51. •• Misra M, Katzman D, Miller KK, et al. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. J Bone Miner Res. 2011;26:2430–8. Treatment with physiologic estradiol restored normal bone accrual in adolescent girls with AN.

    Article  PubMed  CAS  Google Scholar 

  52. Weissberger AJ, Ho KK, Lazarus L. Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women. J Clin Endocrinol Metab. 1991;72:374–81.

    Article  PubMed  CAS  Google Scholar 

  53. Canalis E, Giustina A, Bilezikian JP. Mechanisms of anabolic therapies for osteoporosis. N Engl J Med. 2007;357:905–16.

    Article  PubMed  CAS  Google Scholar 

  54. Scacchi M, Pincelli AI, Caumo A, et al. Spontaneous nocturnal growth hormone secretion in anorexia nervosa. J Clin Endocrinol Metab. 1997;82:3225–9.

    Article  PubMed  CAS  Google Scholar 

  55. Misra M, Miller K, Bjornson J, et al. Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metab. 2003;88:5615–23.

    Article  PubMed  CAS  Google Scholar 

  56. • Fazeli PK, Lawson EA, Prabhakaran R, et al. Effects of recombinant human growth hormone in anorexia: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2010;95:4889–97. This study demonstrates the presence of GH resistance in AN as the basis for relative IGF-1 deficiency.

    Article  PubMed  CAS  Google Scholar 

  57. Lawson EA, Miller KK, Bredella MA, et al. Hormone predictors of abnormal bone microarchitecture in women with anorexia nervosa. Bone. 2010;46:458–63.

    Article  PubMed  CAS  Google Scholar 

  58. Misra M, McGrane J, Miller KK, et al. Effects of rhIGF-1 administration on surrogate markers of bone turnover in adolescents with anorexia nervosa. Bone. 2009;45:493–8.

    Article  PubMed  CAS  Google Scholar 

  59. Brabant G, von zur Mühlen A, Wüster C, et al. Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res. 2003;60:53–60.

    Article  PubMed  CAS  Google Scholar 

  60. Utz AL, Yamamoto A, Hemphill L, Miller KK. Growth hormone deficiency by growth hormone releasing hormone-arginine testing criteria predicts increased cardiovascular risk markers in normal young overweight and obese women. J Clin Endocrinol Metab. 2008;93:2507–14.

    Article  PubMed  CAS  Google Scholar 

  61. Rasmussen MH, Hvidberg A, Juul A, et al. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-1 levels in obese subjects. J Clin Endocrinol Metab. 1995;80:1407–15.

    Article  PubMed  CAS  Google Scholar 

  62. Brick DJ, Gerweck AV, Meenaghan E, Miller KK, et al. Determinants of IGF1 and GH across the weight spectrum: from anorexia nervosa to obesity. Eur J Endocrinol. 2010;163:185–91.

    Article  PubMed  CAS  Google Scholar 

  63. Pijl H, Langendonk JG, Burggraaf J, et al. Altered neuroregulation of GH secretion in viscerally obese premenopausal women. J Clin Endocrinol Metab. 2001;86:5509–15.

    Article  PubMed  CAS  Google Scholar 

  64. Bredella MA, Torriani M, Ghomi RH, et al. Determinants of bone mineral density in obese premenopausal women. Bone. 2011;48:748–54.

    Article  PubMed  Google Scholar 

  65. Misra M, Miller KK, Almazan C, et al. Alterations in cortisol secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metab. 2004;89:4972–80.

    Article  PubMed  CAS  Google Scholar 

  66. Lawson EA, Donoho D, Miller KK, et al. Hypercortisolemia is associated with severity of bone loss and depression in hypothalamic amenorrhea and anorexia nervosa. J Clin Endocrinol Metab. 2009;94:4710–6.

    Article  PubMed  CAS  Google Scholar 

  67. Misra M, Aggarwal A, Miller KK, et al. Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone density parameters in community-dwelling adolescent girls. Pediatrics. 2004;114:1574–83.

    Article  PubMed  Google Scholar 

  68. Padmanabhan V, Keech C, Convey EM. Cortisol inhibits and adrenocorticotropin has no effect on luteinizing hormone-releasing hormone-induced release of luteinizing hormone ffrom bovine pituitary cells in vitro. Endocrinology. 1983;112:1782–7.

    Article  PubMed  CAS  Google Scholar 

  69. Kimberg DV, Baerg RD, Gershon E, Graudusius RT. Effect of cortisone treatment on the active transport of calcium by the small intestine. J Clin Invest. 1971;50:1309–21.

    Article  PubMed  CAS  Google Scholar 

  70. Feher JJ, Wasserman RH. Intestinal calcium-binding protein and calcium absorption in cortisol-treated chicks: effects of vitamin D3 and 1,25-dihydroxyvitamin D3. Endocrinology. 1979;104:547–51.

    Article  PubMed  CAS  Google Scholar 

  71. Hardy R, Cooper MS. Adrenal gland and bone. Arch Biochem Biophys. 2010;503:137–45.

    Article  PubMed  CAS  Google Scholar 

  72. Blüher M. Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes. 2009;117:241–50.

    Article  PubMed  CAS  Google Scholar 

  73. Abdallah BM, Boissy P, Qihua T, et al. dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors. J Biol Chem. 2007;282:7339–51.

    Article  PubMed  CAS  Google Scholar 

  74. O’Connell J, Lynch L, Hogan A, et al. Preadipocyte factor-1 is associated with metabolic profile in severe obesity. J Clin Endocrinol. 2011;96:E680–684.

    Article  CAS  Google Scholar 

  75. Bredella MA, Torriani M, Ghomi RH, et al. Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women. Obesity. 2011;19:49–53.

    Article  PubMed  CAS  Google Scholar 

  76. Shen W, Chen J, Punyanitya M, et al. MRI-measured bone marrow adipose tissue is inversely related to DXA-measured bone mineral in Caucasian women. Osteoporos Int. 2007;18:641–7.

    Article  PubMed  CAS  Google Scholar 

  77. Afghani A, Goran MI. The interrelationships between abdominal adiposity, leptin and bone mineral content in overweight Latino children. Horm Res. 2009;72:82–7.

    Article  PubMed  CAS  Google Scholar 

  78. Russell M, Mendes N, Miller KK, et al. Visceral fat is a negative predictor of bone density measures in obese adolescent girls. J Clin Endocrinol Meta. 2010;95:1247–55.

    Article  CAS  Google Scholar 

  79. Gilsanz V, Chalfant J, Mo AO, et al. Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab. 2009;94:3387–93.

    Article  PubMed  CAS  Google Scholar 

  80. Farr JN, Funk JL, Chen Z, et al. Skeletal muscle fat content is inversely associated with bone strength in young girls. J Bone Miner Res. 2011;26:2217–25.

    Article  PubMed  Google Scholar 

  81. Yerges-Armstrong LM, Miljkovic I, Cauley JA, et al. Adipose tissue and volumetric bone mineral density of older Afro-Caribbean men. J Bone Miner Res. 2010;25:2221–8.

    Article  PubMed  Google Scholar 

  82. Grinspoon S, Gulick T, Askari H, et al. Serum leptin levels in women with anorexia nervosa. J Clin Endocrinol Metab. 1996;81:3861–3.

    Article  PubMed  CAS  Google Scholar 

  83. Misra M, Miller KK, Kuo K, et al. Secretory dynamics of leptin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiol Endocrinol Metab. 2005;289:E373–381.

    Article  PubMed  CAS  Google Scholar 

  84. Sinha MK, Ohannesian JP, Heiman ML, et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest. 1996;97:1344–7.

    Article  PubMed  CAS  Google Scholar 

  85. Cornish J, Callon K, Bava U, et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol. 2002;175:405–15.

    Article  PubMed  CAS  Google Scholar 

  86. Hamrick M, Pennington C, Newton D, et al. Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. Bone. 2004;34:376–83.

    Article  PubMed  CAS  Google Scholar 

  87. Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100:197–207.

    Article  PubMed  CAS  Google Scholar 

  88. Gordeladze JO, Drevon CA, Syversen U, Reseland JE. Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: Impact on differentiation markers, apoptosis, and osteoclastic signaling. J Cell Biochem. 2002;85:825–36.

    Article  PubMed  CAS  Google Scholar 

  89. Hamrick MW, Della-Fera MA, Choi YH, et al. Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res. 2005;20:994–1001.

    Article  PubMed  CAS  Google Scholar 

  90. Holloway WR, Collier FM, Aitken CJ, et al. Leptin inhibits osteoclast generation. J Bone Miner Res. 2002;17:200–9.

    Article  PubMed  CAS  Google Scholar 

  91. Paz-Filho G, Mastronardi C, Delibasi T, et al. Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy. Arq Bras Endocrinol Metabol. 2010;54:690–7.

    Article  PubMed  Google Scholar 

  92. Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002;110:1093–103.

    PubMed  CAS  Google Scholar 

  93. Biver E, Salliot C, Combescure C, et al. Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96:2703–13.

    Article  PubMed  CAS  Google Scholar 

  94. Welt CK, Chan JL, Bullen J, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med. 2004;351:987–97.

    Article  PubMed  CAS  Google Scholar 

  95. Chou SH, Chamberland JP, Liu X, et al. Leptin is an effective treatment for hypothalamic amenorrhea. Proc Natl Acad Sci USA. 2011;108:6585–90.

    Article  PubMed  CAS  Google Scholar 

  96. Mantzoros CS, Magkos F, Brinkoetter M, et al. Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab. 2011;301:E567–584.

    Article  PubMed  CAS  Google Scholar 

  97. Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257:79–83.

    Article  PubMed  CAS  Google Scholar 

  98. Lenchik L, Register TC, Hsu FC, et al. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone. 2003;33:646–51.

    Article  PubMed  CAS  Google Scholar 

  99. Pannacciulli N, Vettor R, Milan G, et al. Anorexia nervosa is characterized by increased adiponectin plasma levels and reduced nonoxidative glucose metabolism. J Clin Endocrinol Metab. 2003;88:1748–52.

    Article  PubMed  CAS  Google Scholar 

  100. Tagami T, Satoh N, Usui T, et al. Adiponectin in anorexia nervosa and bulimia nervosa. J Clin Endocrinol Metab. 2004;89:1833–7.

    Article  PubMed  CAS  Google Scholar 

  101. Misra M, Miller KK, Cord J, et al. Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa. J Clin Endocrinol Metab. 2007;92:2046–52.

    Google Scholar 

  102. Sayers A, Timpson NJ, Sattar N, et al. Adiponectin and its association with bone mass accrual in childhood. J Bone Miner Res. 2010;25:2212–20.

    Article  PubMed  CAS  Google Scholar 

  103. Richards JB, Valdes AM, Burling K, et al. Serum adiponectin and bone mineral density in women. J Clin Endocrinol Metab. 2007;92:1517–23.

    Article  PubMed  CAS  Google Scholar 

  104. Shinoda Y, Yamaguchi M, Ogata N, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem. 2006;99:196–208.

    Article  PubMed  CAS  Google Scholar 

  105. Berner HS, Lyngstadaas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone-forming cells. Bone. 2004;35:842–9.

    Article  PubMed  CAS  Google Scholar 

  106. Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signaling pathway. J Bone Miner Res. 2006;21:1648–56.

    Article  PubMed  CAS  Google Scholar 

  107. Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res. 2005;309:99–109.

    Article  PubMed  CAS  Google Scholar 

  108. Oshima K, Nampei A, Matsuda M, et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun. 2005;331:520–6.

    Article  PubMed  CAS  Google Scholar 

  109. Cambuli VM, Musiu MC, Incani M, et al. Assessment of adiponectin and leptin as biomarkers of positive metabolic outcomes after lifestyle intervention in overweight and obese children. J Clin Endocrinol Metab. 2008;93:3051–7.

    Article  PubMed  CAS  Google Scholar 

  110. Xie H, Tang SY, Luo XH, et al. Insulin-like effects of visfatin on human osteoblasts. Calcif Tissue Int. 2007;80:201–10.

    Article  PubMed  CAS  Google Scholar 

  111. Thommesen L, Stunes AK, Monjo M, et al. Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism. J Cell Biochem. 2006;99:824–34.

    Article  PubMed  CAS  Google Scholar 

  112. Dimitri P, Wales JK, Bishop N. Adipokines, bone-derived factors and bone turnover in obese children; evidence for altered fat-bone signaling resulting in reduced bone mass. Bone. 2011;48:189–96.

    Article  PubMed  CAS  Google Scholar 

  113. Michel MC, Beck-Sickinger A, Cox H, et al. XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev. 1998;50:143–50.

    PubMed  CAS  Google Scholar 

  114. Grandt D, Schimiczek M, Beglinger C, et al. Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1–36 and PYY 3–36. Regul Pept. 1994;51:151–9.

    Article  PubMed  CAS  Google Scholar 

  115. Misra M, Miller KK, Tsai P, et al. Elevated peptide YY levels in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab. 2006;91:1027–33.

    Article  PubMed  CAS  Google Scholar 

  116. Pfluger PT, Kampe J, Castaneda TR, et al. Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36. J Clin Endocrinol Metab. 2007;92:583–8.

    Article  PubMed  CAS  Google Scholar 

  117. Utz AL, Lawson EA, Misra M, et al. Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa. Bone. 2008;43:135–9.

    Article  PubMed  CAS  Google Scholar 

  118. Allison SJ, Baldock P, Sainsbury A, et al. Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice. J Biol Chem. 2006;281:23436–44.

    Article  PubMed  CAS  Google Scholar 

  119. Lee NJ, Doyle KL, Sainsbury A, et al. Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity. J Bone Miner Res. 2010;25:1736–47.

    Article  PubMed  CAS  Google Scholar 

  120. Fernandez-Fernandez R, Aguilar E, Tena-Sempere M, Pinilla L. Effects of polypeptide YY(3–36) upon luteinizing hormone-releasing hormone and gonadotropin secretion in prepubertal rats: in vivo and in vitro studies. Endocrinology. 2005;146:1403–10.

    Article  PubMed  CAS  Google Scholar 

  121. Pinilla L, Fernández-Fernández R, Roa J, et al. Selective role of neuropeptide Y receptor subtype Y2 in the control of gonadotropin secretion in the rat. Am J Physiol Endocrinol Metab. 2007;293:E1385–1392.

    Article  PubMed  CAS  Google Scholar 

  122. Gasco V, Beccuti G, Marotta F, et al. Endocrine and metabolic actions of ghrelin. Endocr Dev. 2010;17:86–95.

    Article  PubMed  CAS  Google Scholar 

  123. Misra M, Miller KK, Kuo K, et al. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiol Endocrinol Metab. 2005;289:E347–356.

    Article  PubMed  CAS  Google Scholar 

  124. Tschöp M, Weyer C, Tataranni PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50:707–9.

    Article  PubMed  Google Scholar 

  125. Kluge M, Schüssler P, Uhr M, et al. Ghrelin suppresses secretion of luteinizing hormone in humans. J Clin Endocrinol Metab. 2007;92:3202–5.

    Article  PubMed  CAS  Google Scholar 

  126. Fernández-Fernández R, Tena-Sempere M, Navarro VM, et al. Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats: in vivo and in vitro studies. Neuroendocrinology. 2005;82:245–55.

    Article  PubMed  CAS  Google Scholar 

  127. Fukushima N, Hanada R, Teranishi H, et al. Ghrelin directly regulates bone formation. J Bone Miner Res. 2005;20:790–8.

    Article  PubMed  CAS  Google Scholar 

  128. Misra M, Miller KK, Stewart V, et al. Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents. J Clin Endocrinol Metab. 2005;90:5082–7.

    Article  PubMed  CAS  Google Scholar 

  129. Gonnelli S, Caffarelli C, Del Santo K, et al. The relationship of ghrelin and adiponectin with bone mineral density and bone turnover markers in elderly men. Calcif Tissue Int. 2008;83:55–60.

    Article  PubMed  CAS  Google Scholar 

  130. van der Lely AJ. Ghrelin and new metabolic frontiers. Horm Res. 2009;71 Suppl 1:129–33.

    Article  PubMed  CAS  Google Scholar 

  131. Thrailkill KM, Liu L, Wahl EC, et al. Bone formation is impaired in a model of type 1 diabetes. Diabetes. 2005;54:2875–81.

    Article  PubMed  CAS  Google Scholar 

  132. Verhaeghe J, Suiker AM, Visser WJ, et al. The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats. J Endocrinol. 1992;134:485–92.

    Article  PubMed  CAS  Google Scholar 

  133. Fulzele K, Riddle RC, DiGirolamo DJ, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142:309–19.

    Article  PubMed  CAS  Google Scholar 

  134. Yang J, Zhang X, Wang W, Liu J. Insulin stimulates osteoblast proliferation and differentiation through ERK and PI3K in MG-63 cells. Cell Biochem Funct. 2010;28:334–41.

    Article  PubMed  CAS  Google Scholar 

  135. Stolk RP, Van Daele PL, Pols HA, et al. Hyperinsulinemia and bone mineral density in an elderly population: The Rotterdam Study. Bone. 1996;18:545–9.

    Article  PubMed  CAS  Google Scholar 

  136. Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007;166:495–505.

    Article  PubMed  Google Scholar 

  137. Bernet F, Dedieu JF, Laborie C, et al. Circulating neuropeptide Y (NPY) and catecholamines in rat under resting and stress conditions. Arguments for extra-adrenal origin of NPY, adrenal and extra-adrenal sources of catecholamines. Neurosci Lett. 1998;250:45–8.

    Article  PubMed  CAS  Google Scholar 

  138. de Quidt ME, Emson PC. Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system–II. Immunohistochemical analysis. Neuroscience. 1986;18:545–618.

    Article  PubMed  Google Scholar 

  139. Kuo LE, Kitlinska JB, Tilan JU, et al. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med. 2007;13:803–11.

    Article  PubMed  CAS  Google Scholar 

  140. Yang K, Guan H, Arany E, et al. Neuropeptide Y is produced in visceral adipose tissue and promotes proliferation of adipocyte precursor cells via the Y1 receptor. FASEB. 2008;22:2452–64.

    Article  CAS  Google Scholar 

  141. Kos K, Harte AL, James S, et al. Secretion of neuropeptide Y in human adipose tissue and its role in maintenance of adipose tissue mass. Am J Physiol Endocrinol Metab. 2007;293:E1335–40.

    Article  PubMed  CAS  Google Scholar 

  142. Igwe JC, Jiang X, Paic F, et al. Neuropeptide Y is expressed by osteocytes and can inhibit osteoblastic activity. J Cell Biochem. 2009;108:621–30.

    Article  PubMed  CAS  Google Scholar 

  143. Shi YC, Baldock PA. Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue. Bone. 2012;50:430–6.

    Article  PubMed  CAS  Google Scholar 

  144. Sedláčková D, Kopečková J, Papežová H, et al. Changes of plasma obestatin, ghrelin and NPY in anorexia and bulimia nervosa patients before and after a high-carbohydrate breakfast. Physiol Res. 2011;60:165–73.

    PubMed  Google Scholar 

  145. Baltazi M, Katsiki N, Savopoulos C, et al. Plasma neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (a-MSH) levels in patients with or without hypertension and/or obesity: a pilot study. Am J Cardiovasc Dis. 2011;1:48–59.

    PubMed  CAS  Google Scholar 

  146. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  PubMed  CAS  Google Scholar 

  147. Qiu W, Andersen TE, Bollerslev J, et al. Patients with high bone mass phenotype exhibit enhanced osteoblast differentiation and inhibition of adipogenesis of human mesenchymal stem cells. J Bone Miner Res. 2007;22:1720–31.

    Article  PubMed  CAS  Google Scholar 

  148. Di Iorgi N, Rosol M, Mittelman SD, Gilsanz V. Reciprocal relation between marrow adiposity and the amount of bone in the axial and appendicular skeleton of young adult. J Clin Endocrinol Metab. 2008;93:2281–6.

    Article  PubMed  CAS  Google Scholar 

  149. Di Iorgi N, Mo AO, Grimm K, et al. Bone acquisition in healthy young females is reciprocally related to marrow adiposity. J Clin Endocrinol Metab. 2010;95:2977–82.

    Article  PubMed  CAS  Google Scholar 

  150. Wren TA, Chung SA, Dorey FJ, et al. Bone marrow fat is inversely related to cortical bone in young and old subjects. J Clin Endocrinol Metab. 2011;96:782–6.

    Article  PubMed  CAS  Google Scholar 

  151. Verma S, Rajaratnam JH, Denton J, et al. Adipocyte proportion of bone marrow is inversely related to bone formation in osteoporosis. J Clin Pathol. 2002;55:693–8.

    Article  PubMed  CAS  Google Scholar 

  152. Yeung DK, Griffith JF, Antonio GE, et al. Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. J Magn Reson Imaging. 2005;22:279–85.

    Article  PubMed  Google Scholar 

  153. Trudel G, Payne M, Madler B, et al. Bone marrow fat accumulation after 60 days of bed rest persisted 1 year after activities were resumed along with hemopoietic stimulation: the Women International Space Simulation for Exploration study. J Appl Physiol. 2009;107:540–8.

    Article  PubMed  Google Scholar 

  154. Bredella MA, Fazeli PK, Miller KK, et al. Increased bone marrow fat in anorexia nervosa. J Clin Endocrinol Metab. 2009;94:2129–36.

    Article  PubMed  CAS  Google Scholar 

  155. Zhao JW, Gao ZL, Mei H, et al. Differentiation of human mesenchymal stem cells: the potential mechanism for estrogen-induced preferential osteoblast versus adipocyte differentiation. Am J Med Sci. 2011;341:460–8.

    Article  PubMed  Google Scholar 

  156. Muruganandan S, Roman AA, Sinal CJ. Adipocyte differentiation of bone-marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program. Cell Mol Life Sci. 2009;66:236–53.

    Article  PubMed  CAS  Google Scholar 

  157. Mazziotti G, Angeli A, Bilezikian JP, et al. Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab. 2006;17:144–9.

    Article  PubMed  CAS  Google Scholar 

  158. Smas CM, Sul HS. Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation. Cell. 1993;73:725–34.

    Article  PubMed  CAS  Google Scholar 

  159. Laborda J. The role of the epidermal growth factor-like protein dlk in cell differentiation. Histol Histopathol. 2000;15:119–29.

    PubMed  CAS  Google Scholar 

  160. Wang Y, Sul HS. Pref-1 regulates mesenchymal cell commitment and differentiation through Sox9. Cell Metabolism. 2009;9:287–302.

    Article  PubMed  CAS  Google Scholar 

  161. Fazeli PK, Bredella MA, Misra M, et al. Preadipocyte factor-1 is associated with marrow adiposity and bone mineral density in women with anorexia nervosa. J Clin Endocrinol Metab. 2010;95:407–13.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. BUL 457, Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA

    Alexander Faje

  2. BUL 457, Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA

    Anne Klibanski

Authors
  1. Alexander Faje
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Klibanski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Klibanski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faje, A., Klibanski, A. Body Composition and Skeletal Health: Too Heavy? Too Thin?. Curr Osteoporos Rep 10, 208–216 (2012). https://doi.org/10.1007/s11914-012-0106-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-012-0106-3

Keywords

Search

Navigation