Abstract
The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.
Acknowledgments
FW is supported by an ELI Lilly grant.
References
1. Kado DM, Huang MH, Karlamangla AS, Barrett-Connor E, Greendale GA. Hyperkyphotic posture predicts mortality in older community-dwelling men and women: a prospective study. J Am Geriatr Soc 2004;52:1662–7.10.1111/j.1532-5415.2004.52458.xSearch in Google Scholar
2. Rossner S. Obesity: the disease of the twenty-first century. Int J Obes Relat Metab Disord 2002;26(Suppl 4):S2–4.10.1038/sj.ijo.0802209Search in Google Scholar
3. Hu FB. Overweight and obesity in women: health risks and consequences. J Women Health (Larchmt) 2003;12: 163–72.10.1089/154099903321576565Search in Google Scholar
4. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000;894:1–253.Search in Google Scholar
5. Reid IR. Relationships among body mass, its components, and bone. Bone 2002;31:547–55.10.1016/S8756-3282(02)00864-5Search in Google Scholar
6. NIH Consensus development panel on osteoporosis. J Am Med Assoc 2001;285:785–95.10.1001/jama.285.6.785Search in Google Scholar
7. Migliaccio S, Greco EA, Fornari R, Donini LM, Lenzi A. Is obesity in women protective against osteoporosis? Diabetes Metab Syndr Obes 2011;4:273–82.10.2147/DMSO.S11920Search in Google Scholar
8. Cagnacci A, Zanin R, Cannoletta M, Generali M, Caretto S, Volpe A. Menopause, estrogens, progestins, or their combination on body weight and anthropometric measures. Fertil Steril 2007;88:1603–8.10.1016/j.fertnstert.2007.01.039Search in Google Scholar
9. Lebovitz HE. The relationship of obesity to the metabolic syndrome. Int J Clin Pract Suppl 2003;134:18–27.Search in Google Scholar
10. Sowers JR. Obesity as a cardiovascular risk factor. Am J Med 2003;8:37S–41S.10.1016/j.amjmed.2003.08.012Search in Google Scholar
11. Albala C, Yanez M, Devoto E, Sostin C, Zeballos L, Santos JL. Obesity as a protective factor for postmenopausal osteoporosis. Int J Obes Relat Metab Disord 1996;20:1027–32.Search in Google Scholar
12. Brown S, Rosen CJ. Osteoporosis. Med Clin North Am 2003;87:1039–63.10.1016/S0025-7125(03)00065-8Search in Google Scholar
13. Migliaccio S, Fornari R, Greco EA, Di Luigi L, Lenzi A. New therapeutical horizons in the management of postmenopausal osteoporosis. Aging Clin Exper Res 2013;25:117–9.10.1007/s40520-013-0106-xSearch in Google Scholar PubMed
14. Migliaccio S, Falcone S, Spera G. Bone modeling and remodeling: from biology to clinical application. Aging Clin Exp Res 2004;16(Suppl):20–2.Search in Google Scholar
15. Goulding A, Jones IE, Taylor RW, Williams SM, Manning PJ. Bone mineral density and body composition in boys with distal forearm fractures: a dual-energy X-ray absorptiometry study. J Pediatr 2001;139:509–15.10.1067/mpd.2001.116297Search in Google Scholar
16. Kveiborg M, Flyvbjerg A, Rattan SI, Kassem M. Changes in the insulin-like growth factor-system may contribute to in vitro agerelate impaired osteoblast functions. Exp Geronto 2000;35:1061–74.10.1016/S0531-5565(00)00125-XSearch in Google Scholar
17. Johansson C, Black D, Johnell O, Oden A, Mellstrom D. Bone mineral density is a predictor of survival. Calcif Tissue Int 1998;63:190–6.10.1007/s002239900513Search in Google Scholar
18. Von der Recke P, Hansen MA, Hassager C. The association between low bone mass at the menopause and cardiovascular mortality. Am J Med 1999;106:273–8.10.1016/S0002-9343(99)00028-5Search in Google Scholar
19. Rosenberg IH. Sarcopenia: origins and clinical relevance. Clin Geriatr Med 2011;27:337–9.10.1016/j.cger.2011.03.003Search in Google Scholar PubMed
20. Rolland Y, Czerwinski S, Abellan Van Kan G, Morley JE, Cesari M, Onder G, Woo J, Baumgartner R, Pillard F, Boirie Y, Chumlea WM, Vellas B. Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging 2008;12:433–50.10.1007/BF02982704Search in Google Scholar PubMed PubMed Central
21. Janssen I. The epidemiology of sarcopenia. Clin Geriatr Med 2011;27:355–63.10.1016/j.cger.2011.03.004Search in Google Scholar PubMed
22. Davison KK, Ford ES, Cogswell ME, Dietz WH. Percentage of body fat and body mass index are associated with mobility limitations in people aged 70 and older from NHANES III. J Am Geriatr Soc 2002;50:1802–9.10.1046/j.1532-5415.2002.50508.xSearch in Google Scholar PubMed
23. Schrager MA, Kelly VE, Price R, Ferrucci L, Shumway-Cook A. The effects of age on medio-lateral stability during normal and narrow base walking. Gait Posture 2008;28:466–71.10.1016/j.gaitpost.2008.02.009Search in Google Scholar PubMed PubMed Central
24. Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Ferrucci L. Sarcopenic obesity: definition, cause and consequences. Curr Opin Clin Nutr Metab Care 2008;11: 693–700.10.1097/MCO.0b013e328312c37dSearch in Google Scholar PubMed PubMed Central
25. Reid IR, Plank LD, Evans MC. Fat mass is an important determinant of whole body bone density in premenopausal women but not in men. J Clin Endoc Metab 1992;75:779–82.Search in Google Scholar
26. Felson DT, Zhang Y, Hannan MT, Anderson JJ. Effects of weight and body mass index on bone mineral density in men and women: the Framingham study. J Bone Miner Res 1993;8:567–73.10.1002/jbmr.5650080507Search in Google Scholar
27. Marcus R, Greendale G, Blunt BA, Bush TL, Sherman S, Sherwin R, Wahner H, Wells B. Correlates of bone mineral density in the postmenopausal estrogen/progestin interventions trial. J Bone Miner Res 1994;9:1467–76.10.1002/jbmr.5650090920Search in Google Scholar
28. Reid IR, Ames R, Evans MC, Sharpe S, Gamble G, France JT, Lim TM, Cundy TF. Determinants of total body and regional bone mineral density in normal postmenopausal women-a key role for fat mass. J Clin Endocrinol Metab 1992;75:45–51.Search in Google Scholar
29. Khosla S, Atkinson EJ, Riggs BL, Melton LJ III. Relationship between body composition and bone mass in women. J Bone Miner Res 1996;11:857–63.10.1002/jbmr.5650110618Search in Google Scholar
30. Pluijm SM, Visser M, Smit JH, Popp-Snijders C, Roos JC, Lips P. Determinants of bone mineral density in older men and women: body composition as mediator. J Bone Miner Res 2001;16:2142–51.10.1359/jbmr.2001.16.11.2142Search in Google Scholar
31. Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsberg TC, Riggs BL. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 1988;241:84–6.10.1126/science.3388021Search in Google Scholar
32. Komm BS, Terpening CM, Benz DJ, Graeme KA, Gallegos A, Korc M, Greene GL, O’Malley BW, Haussler MR. Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. Science 1988;241:81–4.10.1126/science.3164526Search in Google Scholar
33. Migliaccio S, Davis VL, Gibson MK, Gray TK, Korach KS. Estrogens modulate the responsiveness of osteoblast-like cells (ROS 17/2.8) stably transfected with estrogen receptor. Endocrinology 1992;130:2617–24.10.1210/endo.130.5.1572285Search in Google Scholar
34. Kim HJ. New understanding of glucocorticoid action in bone cells. BMB Rep 2010;43:524–9.10.5483/BMBRep.2010.43.8.524Search in Google Scholar
35. Fukumoto S, Martrin TJ. Bone as an endocrine organ. Trends Endocrinol Metab 2009;20:230–6.10.1016/j.tem.2009.02.001Search in Google Scholar
36. Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TM. Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet 1993;341:72–5.10.1016/0140-6736(93)92555-8Search in Google Scholar
37. Melton LJ III, Atkinson EJ, O’Fallon WM, Wahner HW, Riggs BL. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res 1993;8:1227–33.10.1002/jbmr.5650081010Search in Google Scholar PubMed
38. Ravn P, Cizza G, Bjarnason NH, Thompson D, Daley M, Wasnich RD, McClung M, Hosking D, Yates AJ, Christiansen C. Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group. J Bone Miner Res 1999;14:1622–7.10.1359/jbmr.1999.14.9.1622Search in Google Scholar PubMed
39. Zhao LJ, Jiang H, Papasian CJ, Maulik D, Drees B, Hamilton J, Deng HW. Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res 2008;23:17–29.10.1359/jbmr.070813Search in Google Scholar PubMed PubMed Central
40. Hsu YH, Venners SA, Terwedow HA, Feng Y, Niu T, Li Z, Laird N, Brain JD, Cummings SR, Bouxsein ML, Rosen CJ, Xu X. Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women. Am J Clin Nutr 2006;83:146–54.10.1093/ajcn/83.1.146Search in Google Scholar PubMed
41. Greco EA, Fornari R, Rossi F, Santiemma V, Prossomariti G, Annoscia C, Aversa A, Brama M, Marini M, Donini LM, Spera G, Lenzi A, Lubrano C, Migliaccio S. Is obesity protective for osteoporosis? Evaluation of bone mineral density in individuals with high body mass index. Int J Clin Pract 2010;64:817–20.10.1111/j.1742-1241.2009.02301.xSearch in Google Scholar PubMed
42. Greco EA, Francomano D, Fornari R, Marocco C, Lubrano C, Papa V, Wannenes F, Di Luigi L, Donini LM, Lenzi A, Aversa A, Migliaccio S. Negative association between trunk fat, insulin resistance and skeleton in obese women. World J Diabetes 2013;4:31–9.10.4239/wjd.v4.i2.31Search in Google Scholar PubMed PubMed Central
43. Migliaccio S, Francomano D, Bruzziches R, Greco EA, Fornari R, Donini LM, Lenzi A, Aversa A. Trunk fat negatively influences skeletal and testicular functions in obese men: clinical implications for the aging male. Int J Endocrinol 2013;2013:182753.10.1155/2013/182753Search in Google Scholar PubMed PubMed Central
44. Blum M, Harris SS, Must A, Naumova EN, Phillips SM, Rand WM, Dawson-Hughes B. Leptin, body composition and bone mineral density in premenopausal women. Calcif Tissue Int 2003;73:27–32.10.1007/s00223-002-1019-4Search in Google Scholar PubMed
45. Kim KC, Shin DH, Lee SY, Im JA, Lee DC. Relation between obesity and bone mineral density and vertebral fractures in Korean Postmenopausal Women. Yonsei Med J 2010;51:857–63.10.3349/ymj.2010.51.6.857Search in Google Scholar PubMed PubMed Central
46. Castro JP, Joseph LA, Shin JJ, Arora SK, Nicasio J, Shatzkes J, Raklyar I, Erlikh I, Pantone V, Bahtiyar G, Chandler L, Pabon L, Choudhry S, Ghadiri N, Gosukonda P, Muniyappa R, von-Gicyzki H, McFarlane SI. Differential effect of obesity on bone mineral density in White, Hispanic and African American women: a cross sectional study. Nutr Metab (Lond) 2005;2:9.10.1186/1743-7075-2-9Search in Google Scholar PubMed PubMed Central
47. Afghani A, Goran MI. Racial differences in the association of subcutaneous and visceral fat on bone mineral content in prepubertal children. Calcif Tissue Int 2006;79:383–8.10.1007/s00223-006-0116-1Search in Google Scholar
48. Reid IR, Legge M, Stapleton JP, Evans MC, Grey AB. Regular exercise dissociates fat mass and bone density in premenopausal women. J Clin Endocrinol Metab 1995;80:1764–8.Search in Google Scholar
49. Reid IR. Therapy of osteoporosis: calcium, vitamin D, and exercise. Am J Med Sci 1996;312:278–86.10.1016/S0002-9629(15)41843-9Search in Google Scholar
50. Manson JE, Martin KA. Postmenopausal hormonereplacement therapy. N Engl J Med 2001;345:34–40.10.1056/NEJM200107053450106Search in Google Scholar
51. Sorensen MB, Rosenfalck AM, Hojgaard L, Ottesen B. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Obes Res 2001;9:622–6.10.1038/oby.2001.81Search in Google Scholar
52. De Gregorio LH, Lacativa PG, Melazzi AC, Russo LA. Glucocorticoid-induced osteoporosis. Arq Bras Endocrinol Metabol 2006;50:793–801.10.1590/S0004-27302006000400024Search in Google Scholar
53. Steinbuch M, Youket TE, Cohen S. Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int 2004;15:323–8.10.1007/s00198-003-1548-3Search in Google Scholar
54. Gaillard D, Wabitsch M, Pipy B, Negrel R. Control of terminal differentiation of adipose precursor cells by glucocorticoids. J Lipid Res 1991;32:569–79.10.1016/S0022-2275(20)42044-9Search in Google Scholar
55. Livingstone DE, Jones GC, Smith K, Jamieson PM, Andrew R, Kenyon CJ, Walker BR. Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats. Endocrinology 2000;141:560–3.10.1210/endo.141.2.7297Search in Google Scholar PubMed
56. Mieczkowska A, Baslé MF, Chappard D, Mabilleau G. Thiazolidinediones induce osteocyte apoptosis by a G protein-coupled receptor 40-dependent mechanism. J Biol Chem 2012;287:23517–26.10.1074/jbc.M111.324814Search in Google Scholar PubMed PubMed Central
57. Drøyvold WB, Nilsen TI, Krüger O, Holmen TL, Krokstad S, Midthjell K, Holmen J. Change in height, weight and body mass index: longitudinal data from the HUNT Study in Norway. Int J Obes 2006;30:935–9.10.1038/sj.ijo.0803178Search in Google Scholar PubMed
58. Koster A, Ding J, Stenholm S, Caserotti P, Houston DK, Nicklas BJ, You T, Lee JS, Visser M, Newman AB, Schwartz AV, Cauley JA, Tylavsky FA, Goodpaster BH, Kritchevsky SB, Harris TB. Health ABC study. Does the amount of fat mass predict age-related loss of lean mass, muscle strength, and musclequality in older adults? J Gerontol A Biol Sci Med Sci 2011;66:888–95.Search in Google Scholar
59. Lauretani F, Russo CR, Bandinelli S, Bartali B, Cavazzini C, Di Iorio A, Corsi M, Rantanen T, Guralnik JM, Ferrucci L. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol 2003;95:1851–60.10.1152/japplphysiol.00246.2003Search in Google Scholar
60. Bassey EJ. Longitudinal changes in selected physical capabilities: muscle strength, flexibility and body size. Age Ageing 1998;27(Suppl 3):12–16.10.1093/ageing/27.suppl_3.12Search in Google Scholar
61. Frontera WR, Zayas AR, Rodriguez N. Aging of human muscle: understanding sarcopenia at the single muscle cell level. Phys Med Rehabil Clin N Am 2012;23:201–7.10.1016/j.pmr.2011.11.012Search in Google Scholar
62. Morio B, Hocquette JF, Montaurier C, Boirie Y, Bouteloup-Demange C, McCormack C, Fellmann N, Beaufrère B, Ritz P. Muscle fatty acid oxidative capacity is a determinant of whole body fat oxidation in elderly people. Am J Physiol Endocrinol Metab 2001;280:E143–9.10.1152/ajpendo.2001.280.1.E143Search in Google Scholar
63. Coin A, Perissinotto E, Enzi G, Zamboni M, Inelmen EM, Frigo AC, Manzato E, Busetto L, Buja A, Sergi G. Predictors of low bone mineral density in the elderly: the role of dietary intake, nutritional status and sarcopenia. Eur J Clin Nutr 2008;62:802–9.10.1038/sj.ejcn.1602779Search in Google Scholar
64. Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, Abellan van Kan G, Andrieu S, Bauer J, Breuille D, Cederholm T, Chandler J, De Meynard C, Donini L, Harris T, Kannt A, Keime Guibert F, Onder G, Papanicolaou D, Rolland Y, Rooks D, Sieber C, Souhami E, Verlaan S, Zamboni M. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 2011;12:249–56.10.1016/j.jamda.2011.01.003Search in Google Scholar
65. Horber FF, Gruber B, Thomi F, Jensen EX, Jaeger P. Effects of sex and age on bone mass, body composition and fuel metabolism in humans. Nutrition 1997;13:524–34.10.1016/S0899-9007(97)00031-2Search in Google Scholar
66. Visser M, Kritchevsky SB, Goodpaster BH, Newman AB, Nevitt M, Stamm E, Harris TB. Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70 to 79: the health, aging and body composition study. J Am Geriatr Soc 2002;50:897–904.10.1046/j.1532-5415.2002.50217.xSearch in Google Scholar PubMed
67. Elia M, Stratton R, Stubbs J. Techniques for the study of energy balance in man. Proc Nutr Soc 2003;62:529–37.10.1079/PNS2003255Search in Google Scholar PubMed
68. Marcell TJ. Sarcopenia: causes, consequences, and preventions. J Gerontol A Biol Sci Med Sci 2003;58:M911–6.10.1093/gerona/58.10.M911Search in Google Scholar
69. Morley JE, Malmstrom TK. Frailty, sarcopenia, and hormones. Endocrinol Metab Clin North Am 2013;42:391–405.10.1016/j.ecl.2013.02.006Search in Google Scholar PubMed
70. Doherty TJ. Invited review: aging and sarcopenia. J Appl Physiol (1985) 2003;95:1717–27.10.1152/japplphysiol.00347.2003Search in Google Scholar PubMed
71. Schroeder ET, Castaneda-Sceppa C, Wang Y, Binder EF, Kawakubo M, Stewart Y, Storer T, Roubenoff R, Bhasin S, Yarasheski KE, Sattler FR, Azen SP. Hormonal regulators of muscle and metabolism in aging (HORMA): design and conduct of a complex, double masked multicenter trial. Clin Trials 2007;4:560–71.10.1177/1740774507083569Search in Google Scholar PubMed PubMed Central
72. Blair SN, LaMonte MJ, Nichaman MZ. The evolution of physical activity recommendations: how much is enough? Am J Clin Nutr 2004;79:913S–20S.10.1093/ajcn/79.5.913SSearch in Google Scholar PubMed
73. Duvigneaud N, Matton L, Wijndaele K, Deriemaeker P, Lefevre J, Philippaerts R, Thomis M, Delecluse C, Duquet W. Relationship of obesity with physical activity, aerobic fitness and muscle strength in Flemish adults. J Sports Med Phys Fitness 2008;48:201–10.Search in Google Scholar
74. Zhou Q, Du J, Hu Z, Walsh K, Wang XH. Evidence for adipose-muscle cross talk: opposing regulation of muscle proteolysis by adiponectin and Fatty acids. Endocrinology 2007;148: 5696–705.10.1210/en.2007-0183Search in Google Scholar PubMed
75. Frimel TN, Sinacore DR, Villareal DT. Exercise attenuates the weight-loss-induced reduction in muscle mass in frail obese older adults. Med Sci Sports Exerc 2008;40:1213–9.10.1249/MSS.0b013e31816a85ceSearch in Google Scholar PubMed PubMed Central
76. Baumgartner RN, Wayne SJ, Waters DL, Janssen I, Gallagher D, Morley JE. Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes Res 2004;12: 1995–2004.10.1038/oby.2004.250Search in Google Scholar PubMed
77. Koster A, Ding J, Stenholm S, Caserotti P, Houston DK, Nicklas BJ, You T, Lee JS, Visser M, Newman AB, Schwartz AV, Cauley JA, Tylavsky FA, Goodpaster BH, Kritchevsky SB, Harris TB; Health ABC study. Does the amount of fat mass predict age-related loss of lean mass, muscle strength, and musclequality in older adults? J Gerontol A Biol Sci Med Sci 2011;66:888–95.10.1093/gerona/glr070Search in Google Scholar PubMed PubMed Central
78. Gomez-Ambrosi J, Rodrıguez A, Catalan V, Fruhbeck G. The bone-adipose axis in obesity and weight loss. Obes Surg 2008;18:1134–43.10.1007/s11695-008-9548-1Search in Google Scholar PubMed
79. Takeda S. Effect of obesity on bone metabolism. Clin Calcium 2008;18:632–7.Search in Google Scholar
80. Gimble JM, Zvonic S, Floyd ZE, Kassem M, Nuttall ME. Playing with bone and fat. J Cell Biochem 2006;98:251–66.10.1002/jcb.20777Search in Google Scholar PubMed
81. Vettor R, Milan G, Franzin C, Sanna M, De Coppi P, Rizzuto R, Federspil G. The origin of intermuscular adipose tissue and its pathophysiological implications. Am J Physiol Endocrinol Metab 2009;297:E987–98.10.1152/ajpendo.00229.2009Search in Google Scholar
82. Buehring B, Binkley N. Myostatin–the holy grail for muscle, bone, and fat? Current Osteoporos Rep 2013;11:407–14.10.1007/s11914-013-0160-5Search in Google Scholar
83. Smorlesi A, Frontini A, Giordano A, Cinti S. The adipose organ: white-brown adipocyte plasticity and metabolic inflammation. Obes Rev 2012;13(Suppl 2):83–96.10.1111/j.1467-789X.2012.01039.xSearch in Google Scholar
84. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med 2013;19:1252–63.10.1038/nm.3361Search in Google Scholar
85. Steppan CM, Crawford DT, Chidsey-Frink KL, Ke H, Swick AG. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept 2000;92:73–78.10.1016/S0167-0115(00)00152-XSearch in Google Scholar
86. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005;26:439–51.10.1210/er.2005-0005Search in Google Scholar PubMed
87. Vendrell J, Broch M, Vilarrasa N, Molina A, Gómez JM, Gutiérrez C, Simón I, Soler J, Richart C. Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obes Res 2004;12:962–71.10.1038/oby.2004.118Search in Google Scholar PubMed
88. Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med 2008;14:222–31.10.2119/2007-00119.TilgSearch in Google Scholar PubMed PubMed Central
89. Magni P, Dozio E, Galliera E, Ruscica M, Corsi MM. Molecular Aspects of Adipokine-Bone Interactions. Curr Mol Med 2010;10:522–32.Search in Google Scholar
90. Berthier MT, Paradis AM, Tchernof A. The interleukin 6–174G/C polymorphism is associated with indices of obesity in men. J Hum Genet 2003;48:14–9.10.1007/s100380300002Search in Google Scholar PubMed
91. Fernandez-Real JM, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 2003;24:278–301.10.1210/er.2002-0010Search in Google Scholar PubMed
92. Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS. Estrogen resistance caused by a mutation in the estrogen receptor gene in a man. N Engl J Med 1994;331:1056–61.10.1056/NEJM199410203311604Search in Google Scholar
93. Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 1995;80:3689–98.Search in Google Scholar
94. Cooke PS, Heine PA, Taylor JA, Lubahn DB. The role of estrogen and estrogen receptor-alpha in male adipose tissue. Mol Cell Endocrinol 2001;178:147–54.10.1016/S0303-7207(01)00414-2Search in Google Scholar
95. Maffei L, Murata Y, Rochira V, Tubert G, Aranda C, Vazquez M, Clyne CD, Davis S, Simpson ER, Carani C. Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate, and estradiol treatment. J Clin Endocrinol Metab 2004;89:61–70.10.1210/jc.2003-030313Search in Google Scholar
96. Tchernof A, Calles-Escandon J, Sites CK, Poehlman ET. Menopause, central body fatness, and insulin resistance: Effects of hormone-replacement therapy. Coron Artery Dis 1998;9:503–11.10.1097/00019501-199809080-00006Search in Google Scholar
97. Gambacciani M, Ciaponi M, Cappagli B, De Simone L, Orlandi R, Genazzani AR. Prospective evaluation of body weight and body fat distribution in early postmenopausal women with and without hormonal replacement therapy. Maturitas 2001;39:125–32.10.1016/S0378-5122(01)00194-3Search in Google Scholar
98. Jensen LB, Vestergaard P, Hermann AP, Gram J, Eiken P, Abrahamsen B, Brot C, Kolthoff N, Sørensen OH, Beck-Nielsen H, Nielsen SP, Charles P, Mosekilde L. Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study. J Bone Miner Res 2003;18:333–42.10.1359/jbmr.2003.18.2.333Search in Google Scholar
99. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. J Am Med Assoc 2002;288:321–33.10.1001/jama.288.3.321Search in Google Scholar
100. Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2001;2:165–71.10.1023/A:1011513223894Search in Google Scholar
101. Mantzoros CS. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med 1999;130:671–80.10.7326/0003-4819-130-8-199904200-00014Search in Google Scholar
102. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000;100:197–207.10.1016/S0092-8674(00)81558-5Search in Google Scholar
103. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G. Leptin regulates bone formation via the sympathetic nervous system. Cell 2002;111:305–17.10.1016/S0092-8674(02)01049-8Search in Google Scholar
104. Wisse BE, Schwartz MW. Role of melanocortins in control of obesity. Lancet 2001;358:857–9.10.1016/S0140-6736(01)06037-8Search in Google Scholar
105. Kontogianni MD, Dafni UG, Routsias JG, Skopouli FN. Blood leptin and adiponectin as possible mediators of the relation between fat mass and BMD in perimenopausal women. J Bone Miner Res 2004;19:546–51.10.1359/JBMR.040107Search in Google Scholar
106. Goulding A, Taylor RW. Plasma leptin values in relation to bone mass and density and to dynamic biochemical markers of bone resorption and formation in postmenopausal women. Calcif Tissue Int 1998;63:456–58.10.1007/s002239900557Search in Google Scholar
107. Yamauchi M, Sugimoto T, Yamaguchi T. Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol (Oxf) 2001;55:341–7.10.1046/j.1365-2265.2001.01361.xSearch in Google Scholar
108. Pasco JA, Henry MJ, Kotowicz MA, Collier GR, Ball MJ, Ugoni AM, Nicholson GC. Serum leptin levels are associated with bone mass in nonobese women. J Clin Endocrinol Metab 2001;86:1884–7.10.1210/jc.86.5.1884Search in Google Scholar
109. Thomas T, Burguera B. Is leptin the link between fat and bone mass? J Bone Miner Res 2002;17:1563–9.10.1359/jbmr.2002.17.9.1563Search in Google Scholar
110. Thomas T. Leptin: a potential mediator for protective effects of fat mass on bone tissue. Joint Bone Spine 2003; 70:18–21.10.1016/S1297-319X(02)00005-2Search in Google Scholar
111. Thomas T. The complex effects of leptin on bone metabolism through multiple pathways. Curr Opin Pharmacol 2004;4: 295–300.10.1016/j.coph.2004.01.009Search in Google Scholar PubMed
112. Martin A, de Vittoris R, David V, Moraes R, Bégeot M, Lafage-Proust MH, Alexandre C, Vico L, Thomas T. Leptin modulate both resorption and formation while preventing disuse-induced bone loss in tail-suspended female rats. Endocrinology 2005;146:3652–9.10.1210/en.2004-1509Search in Google Scholar PubMed
113. Cornish J, Callon KE, Bava U, Lin C, Naot D, Hill BL, Grey AB, Broom N, Myers DE, Nicholson GC, Reid IR. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol 2002;175:405–15.10.1677/joe.0.1750405Search in Google Scholar PubMed
114. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548–56.10.1210/jc.2004-0395Search in Google Scholar PubMed
115. Franchimont N, Wertz S, Malaise M. Interleukin-6: an osteotropic factor influencing bone formation? Bone 2005;37:601–6.10.1016/j.bone.2005.06.002Search in Google Scholar PubMed
116. Lean ME. Brown adipose tissue in humans. Proc Nutr Soc 1989;48:243–56.10.1079/PNS19890036Search in Google Scholar
117. Enerbäck S. Human brown adipose tissue. Cell Metab 2010;11:248–52.10.1016/j.cmet.2010.03.008Search in Google Scholar PubMed
118. Van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med 2009;360:1500–8.10.1056/NEJMoa0808718Search in Google Scholar PubMed
119. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerbäck S, Nuutila P. Functional brown adipose tissue in healthy adults. N Engl J Med 2009;360:1518–25.10.1056/NEJMoa0808949Search in Google Scholar PubMed
120. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009;360:1509–17.10.1056/NEJMoa0810780Search in Google Scholar PubMed PubMed Central
121. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scimè A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM. PRDM16 controls a brown fat/skeletal muscle switch. Nature 2008;454:961–7.10.1038/nature07182Search in Google Scholar PubMed PubMed Central
122. Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev 2013;27:234–50.10.1101/gad.211649.112Search in Google Scholar PubMed PubMed Central
123. Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, Carpentier AC, Richard D. Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J Clin Endocrinol Metab 2011;96:192–9.10.1210/jc.2010-0989Search in Google Scholar
124. Lee P, Brychta RJ, Collins MT, Linderman J, Smith S, Herscovitch P, Millo C, Chen KY, Celi FS. Cold-activated brown adipose tissue is an independent predictor of higher bone mineral density in women. Osteoporos Int 2013;24:1513–8.10.1007/s00198-012-2110-ySearch in Google Scholar
125. Ponrartana S, Aggabao PC, Hu HH, Aldrovandi GM, Wren TA, Gilsanz V. Brown adipose tissue and its relationship to bone structure in pediatric patients. J Clin Endocrinol Metab 2012;97:2693–8.10.1210/jc.2012-1589Search in Google Scholar
126. Akune T, Ohba S, Kamekura S, Yamaguchi M, Chung UI, Kubota N, Terauchi Y, Harada Y, Azuma Y, Nakamura K, Kadowaki T, Kawaguchi H. PPARγ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 2004;113:846–55.10.1172/JCI200419900Search in Google Scholar
127. Gimble JM, Robinson CE, Wu X, Kelly KA, Rodriguez BR, Kliewer SA, Lehmann JM, Morris DC. Peroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells. Mol Pharmacol 1996;50:1087–94.Search in Google Scholar
128. Rodriguez JP, Montecinos L, Rios S, Reyes P, Martinez J. Mesenchymal stem cells from osteoporotic patients produce a type I collagen-deficient extracellular matrix favoring adipogenic differentiation. J Cell Biochem 2000;79:557–65.10.1002/1097-4644(20001215)79:4<557::AID-JCB40>3.0.CO;2-HSearch in Google Scholar
129. Sekiya I, Larson BL, Vuoristo JT, Cui JG, Prockop DJ. Adipogenic differentiation of human adult stem cells from bone marrow stroma (MSCs). J Bone Miner Res 2004;19:256–64.10.1359/JBMR.0301220Search in Google Scholar
130. Aubin JE. Bone stem cells. J Cell Biochem 1998;(Suppl 30–31):73–82.10.1002/(SICI)1097-4644(1998)72:30/31+<73::AID-JCB11>3.0.CO;2-LSearch in Google Scholar
131. Cohen PG. Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenicdisease and aging connection. Med Hypotheses 2001;56:702–8.10.1054/mehy.2000.1169Search in Google Scholar
132. Cheleuitte D, Mizuno S, Glowacki J. In vitro secretion of cytokines by human bone marrow: effects of age and estrogen status. J Clin Endocrinol Metab 1998;83:2043–51.10.1210/jc.83.6.2043Search in Google Scholar
133. Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell 2004;3:379–89.10.1111/j.1474-9728.2004.00127.xSearch in Google Scholar
134. Kajkenova O, Lecka-Czernik B, Gubrij I, Hauser SP, Takahashi K, Parfitt AM, Jilka RL, Manolagas SC, Lipschitz DA. Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6, a murine model of defective osteoblastogenesis and low turnover osteopenia. J Bone Miner Res. 1997;12:1772–9.10.1359/jbmr.1997.12.11.1772Search in Google Scholar PubMed
135. Duque G, Macoritto M, Kremer R. Vitamin D treatment of senescence accelerated mice (SAM-P/6) induces several regulators of stromal cell plasticity. Biogerontology 2004;5:421–9.10.1007/s10522-004-3192-5Search in Google Scholar PubMed
136. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004;20:781–810.10.1146/annurev.cellbio.20.010403.113126Search in Google Scholar PubMed
137. Bennett CN, Ross SE, Longo KA. Regulation of Wnt signaling during adipogenesis. J Biol Chem 2002;277:30998–1004.10.1074/jbc.M204527200Search in Google Scholar PubMed
138. Zhou S, Eid K, Glowacki J. Cooperation between TGFbeta and Wnt pathways during chondrocyte and adipocyte differentiation of human marrow stromal cells. J Bone Miner Res 2004;19:463–70.10.1359/JBMR.0301239Search in Google Scholar PubMed
139. Abdallah BM, Jensen CH, Gutierrez G, Leslie RG, Jensen TG, Kassem M. Regulation of human skeletal stem cells differentiation by Dlk1/Pref-1. J Bone Miner Res 2004; 19:841–52.10.1359/jbmr.040118Search in Google Scholar
140. Elkasrawy MN, Hamrick MW. Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact 2010;10:56–63.Search in Google Scholar
141. Yue H, He JW, Zhang H, Wang C, Hu WW, Gu JM, Ke YH, Fu WZ, Hu YQ, Li M, Liu YJ, Wu SH, Zhang ZL. Contribution of myostatin gene polymorphisms to normal variation in lean mass, fat mass and peak BMD in Chinese male offspring. Acta Pharmacol Sin 2012;33:660–7.10.1038/aps.2012.12Search in Google Scholar PubMed PubMed Central
142. Mitchell AD, Wall RJ. In vivo evaluation of changes in body composition of transgenic mice expressing the myostatin pro domain using dual energy X-ray absorptiometry. Growth Dev Aging 2007;70:25–37.Search in Google Scholar
143. Artaza JN, Bhasin S, Magee TR, Reisz-Porszasz S, Shen R, Groome NP, Meerasahib MF, Gonzalez-Cadavid NF. Myostatin inhibits myogenesis and promotes adipogenesis in C3H 10T(1/2) mesenchymal multipotent cells. Endocrinology 2005;146:3547–57.10.1210/en.2005-0362Search in Google Scholar PubMed
144. Cohen A, Dempster DW, Recker RR, Lappe JM, Zhou H, Zwahlen A, Müller R, Zhao B, Guo X, Lang T, Saeed I, Liu XS, Guo XE, Cremers S, Rosen CJ, Stein EM, Nickolas TL, McMahon DJ, Young P, Shane E. Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study. J Clin Endocrinol Metab 2013;98:2562–72.10.1210/jc.2013-1047Search in Google Scholar PubMed PubMed Central
145. Russell M, Mendes N, Miller KK, Rosen CJ, Lee H, Klibanski A, Misra M. Visceral fat is a negative predictor of bone density measures in obese adolescent girls. J Clin Endocrinol Metab 2010;95:1247–55.10.1210/jc.2009-1475Search in Google Scholar PubMed PubMed Central
146. Compston JE, Watts NB, Chapurlat R, Cooper C, Boonen S, Greenspan S, Pfeilschifter J, Silverman S, Díez-Pérez A, Lindsay R, Saag KG, Netelenbos JC, Gehlbach S, Hooven FH, Flahive J, Adachi JD, Rossini M, Lacroix AZ, Roux C, Sambrook PN, Siris ES, Glow Investigators. Obesity is not protective against fracture in postmenopausal women: GLOW. Am J Med 2011;124:1043–50.10.1016/j.amjmed.2011.06.013Search in Google Scholar PubMed PubMed Central
147. Donini LM, Poggiogalle E, Migliaccio S, Aversa A, Pinto A. Body composition in sarcopenic obesity: systematic review of the literature. Mediterranean J Nutr Metab 2013:6:191–8.10.1007/s12349-013-0135-1Search in Google Scholar
148. Migliaccio S, Greco EA, Fornari R, Donini LM, Lenzi A. Is obesity in women protective against osteoporosis? Diabetes Metab Syndr Obes 2011;4:273–82.10.2147/DMSO.S11920Search in Google Scholar PubMed PubMed Central
©2014 by Walter de Gruyter Berlin/Boston