, Volume 54, Issue 2, pp 284–305 | Cite as

Implications of exercise-induced adipo-myokines in bone metabolism

  • Giovanni LombardiEmail author
  • Fabian Sanchis-Gomar
  • Silvia Perego
  • Veronica Sansoni
  • Giuseppe Banfi


Physical inactivity has been recognized, by the World Health Organization as the fourth cause of death (5.5 % worldwide). On the contrary, physical activity (PA) has been associated with improved quality of life and decreased risk of several diseases (i.e., stroke, hypertension, myocardial infarction, obesity, malignancies). Bone turnover is profoundly affected from PA both directly (load degree is the key determinant for BMD) and indirectly through the activation of several endocrine axes. Several molecules, secreted by muscle (myokines) and adipose tissues (adipokines) in response to exercise, are involved in the fine regulation of bone metabolism in response to the energy availability. Furthermore, bone regulates energy metabolism by communicating its energetic needs thanks to osteocalcin which acts on pancreatic β-cells and adipocytes. The beneficial effects of exercise on bone metabolism depends on the intermittent exposure to myokines (i.e., irisin, IL-6, LIF, IGF-I) which, instead, act as inflammatory/pro-resorptive mediators when chronically elevated; on the other hand, the reduction in the circulating levels of adipokines (i.e., leptin, visfatin, adiponectin, resistin) sustains these effects as well as improves the whole-body metabolic status. The aim of this review is to highlight the newest findings about the exercise-dependent regulation of these molecules and their role in the fine regulation of bone metabolism.


Physical activity Adipokines Myokines Bone turnover Energy metabolism Inflammation 



This work has been funded by the Italian Ministry of Health.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflicts of interest concerning this article.


  1. 1.
    H.B. Simon, Exercise and health: dose and response, considering both ends of the curve. Am. J. Med. 128(11), 1171–1177 (2015)PubMedCrossRefGoogle Scholar
  2. 2.
    D. Bishop-Bailey, Mechanisms governing the health and performance benefits of exercise. Br. J. Pharmacol. 170(6), 1153–1166 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    M.P. Mattson, Evolutionary aspects of human exercise–born to run purposefully. Ageing Res. Rev. 11(3), 347–352 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    D.M. Bramble, D.E. Lieberman, Endurance running and the evolution of Homo. Nature 432(7015), 345–352 (2004)PubMedCrossRefGoogle Scholar
  5. 5.
    World Health Organization, Global database on blood safety: report 2004–2005 (World Health Organization, Geneva, 2008)Google Scholar
  6. 6.
    G. Banfi, G. Lombardi, A. Colombini, G. Lippi, Bone metabolism markers in sports medicine. Sports Med. 40, 697–714 (2010)PubMedCrossRefGoogle Scholar
  7. 7.
    A.D. DiVasta, C.M. Gordon, Exercise and bone: where do we stand? Metabolism 62(12), 1714–1717 (2013)PubMedCrossRefGoogle Scholar
  8. 8.
    G. Lombardi, S. Perego, L. Luzi, G. Banfi, A four-season molecule: osteocalcin. Updates in its physiological roles. Endocrine 48, 394–404 (2015)PubMedCrossRefGoogle Scholar
  9. 9.
    C.B. Confavreux, R.L. Levine, G. Karsenty, A paradigm of integrative physiology, the crosstalk between bone and energy metabolisms. Mol. Cell. Endocrinol. 310(1–2), 21–29 (2009)PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    K.L. Scofield, S. Hecht, Bone health in endurance athletes: runners, cyclists, and swimmers. Curr Sports Med Rep 11(6), 328–334 (2012)PubMedCrossRefGoogle Scholar
  11. 11.
    H. Olmedillas, A. Gonzalez-Aguero, L.A. Moreno, J.A. Casajus, G. Vicente-Rodriguez, Bone related health status in adolescent cyclists. PLoS ONE 6(9), e24841 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    M.R. Carmont, Bike racing, recreational riding, impact sport and bone health. BMC Med. 10, 169 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    H.C. Emslander, M. Sinaki, J.M. Muhs, E.Y. Chao, H.W. Wahner, S.C. Bryant, B.L. Riggs, R. Eastell, Bone mass and muscle strength in female college athletes (runners and swimmers). Mayo Clin. Proc. 73(12), 1151–1160 (1998)PubMedCrossRefGoogle Scholar
  14. 14.
    C.S. Duncan, C.J. Blimkie, C.T. Cowell, S.T. Burke, J.N. Briody, R. Howman-Giles, Bone mineral density in adolescent female athletes: relationship to exercise type and muscle strength. Med. Sci. Sports Exerc. 34(2), 286–294 (2002)PubMedCrossRefGoogle Scholar
  15. 15.
    R.S. Rector, R. Rogers, M. Ruebel, P.S. Hinton, Participation in road cycling vs running is associated with lower bone mineral density in men. Metabolism 57, 226–232 (2008)PubMedCrossRefGoogle Scholar
  16. 16.
    G. Lombardi, P. Lanteri, G. Graziani, A. Colombini, G. Banfi, R. Corsetti, Bone and energy metabolism parameters in professional cyclists during the Giro d’Italia 3-weeks stage race. PLoS ONE 7(7), e42077 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    D. Grasso, R. Corsetti, P. Lanteri, C. Di Bernardo, A. Colombini, R. Graziani, G. Banfi, G. Lombardi, Bone-muscle unit activity, salivary steroid hormones profile, and physical effort over a 3-week stage race. Scand. J. Med. Sci. Sports 25(1), 70–80 (2015)PubMedCrossRefGoogle Scholar
  18. 18.
    G. Lombardi, R. Corsetti, P. Lanteri, D. Grasso, E. Vianello, M.G. Marazzi, R. Graziani, A. Colombini, E. Galliera, M.M. Corsi Romanelli, G. Banfi, Reciprocal regulation of calcium-/phosphate-regulating hormones in cyclists during the Giro d’Italia 3-week stage race. Scand. J. Med. Sci. Sports 24(5), 779–787 (2014)PubMedCrossRefGoogle Scholar
  19. 19.
    A. Colombini, R. Corsetti, R. Graziani, G. Lombardi, P. Lanteri, G. Banfi, Evaluation of creatinine, cystatin C and eGFR by different equations in professional cyclists during the Giro d’Italia 3-weeks stage race. Scand. J. Clin. Lab. Invest. 72(2), 114–120 (2012)PubMedCrossRefGoogle Scholar
  20. 20.
    W. Qin, L. Sun, J. Cao, Y. Peng, L. Collier, Y. Wu, G. Creasey, J. Li, Y. Qin, J. Jarvis, W.A. Bauman, M. Zaidi, C. Cardozo, The central nervous system (CNS)-independent anti-bone-resorptive activity of muscle contraction and the underlying molecular and cellular signatures. J. Biol. Chem. 288(19), 13511–13521 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    G. Lombardi, A. Colombini, M. Freschi, R. Tavana, G. Banfi, Seasonal variation of bone turnover markers in top-level female skiers. Eur. J. Appl. Physiol. 111(3), 433–440 (2011)PubMedCrossRefGoogle Scholar
  22. 22.
    N.S. Datta, Muscle-bone and fat-bone interactions in regulating bone mass: do PTH and PTHrP play any role? Endocrine 47(2), 389–400 (2014)PubMedCrossRefGoogle Scholar
  23. 23.
    C. Cassell, M. Benedict, B. Specker, Bone mineral density in elite 7- to 9-yr-old female gymnasts and swimmers. Med. Sci. Sports Exerc. 28(10), 1243–1246 (1996)PubMedCrossRefGoogle Scholar
  24. 24.
    S.S. Moon, Relationship of lean body mass with bone mass and bone mineral density in the general Korean population. Endocrine 47(1), 234–243 (2014)PubMedCrossRefGoogle Scholar
  25. 25.
    A. Heinonen, P. Oja, P. Kannus, H. Sievanen, A. Manttari, I. Vuori, Bone mineral density of female athletes in different sports. Bone Miner. 23(1), 1–14 (1993)PubMedCrossRefGoogle Scholar
  26. 26.
    M. Martyn-St James, S. Carroll, Effects of different impact exercise modalities on bone mineral density in premenopausal women: a meta-analysis. J. Bone Miner. Metab. 28(3), 251–267 (2010)PubMedCrossRefGoogle Scholar
  27. 27.
    E.A. Marques, J. Mota, L. Machado, F. Sousa, M. Coelho, P. Moreira, J. Carvalho, Multicomponent training program with weight-bearing exercises elicits favorable bone density, muscle strength, and balance adaptations in older women. Calcif. Tissue Int. 88(2), 117–129 (2011)PubMedCrossRefGoogle Scholar
  28. 28.
    L.M. Giangregorio, A. Papaioannou, N.J. Macintyre, M.C. Ashe, A. Heinonen, K. Shipp, J. Wark, S. McGill, H. Keller, R. Jain, J. Laprade, A.M. Cheung, Too fit to fracture: exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture. Osteoporos. Int. 25(3), 821–835 (2014)PubMedCrossRefGoogle Scholar
  29. 29.
    E.A. Marques, J. Mota, J.L. Viana, D. Tuna, P. Figueiredo, J.T. Guimaraes, J. Carvalho, Response of bone mineral density, inflammatory cytokines, and biochemical bone markers to a 32-week combined loading exercise programme in older men and women. Arch. Gerontol. Geriatr. 57(2), 226–233 (2013)PubMedCrossRefGoogle Scholar
  30. 30.
    A. Heinonen, P. Oja, P. Kannus, H. Sievanen, H. Haapasalo, A. Manttari, I. Vuori, Bone mineral density in female athletes representing sports with different loading characteristics of the skeleton. Bone 17(3), 197–203 (1995)PubMedCrossRefGoogle Scholar
  31. 31.
    M.P. Mosti, T. Carlsen, E. Aas, J. Hoff, A.K. Stunes, U. Syversen, Maximal strength training improves bone mineral density and neuromuscular performance in young adult women. J. Strength Cond. Res. 28(10), 2935–2945 (2014)PubMedCrossRefGoogle Scholar
  32. 32.
    C.T. Rubin, Skeletal strain and the functional significance of bone architecture. Calcif. Tissue Int. 36(Suppl 1), S11–S18 (1984)PubMedCrossRefGoogle Scholar
  33. 33.
    C.H. Turner, M.R. Forwood, M.W. Otter, Mechanotransduction in bone: do bone cells act as sensors of fluid flow? FASEB J. 8(11), 875–878 (1994)PubMedGoogle Scholar
  34. 34.
    A.G. Robling, F.M. Hinant, D.B. Burr, C.H. Turner, Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts. J. Bone Miner. Res. 17(8), 1545–1554 (2002)PubMedCrossRefGoogle Scholar
  35. 35.
    Y. Wang, L.M. McNamara, M.B. Schaffler, S. Weinbaum, Strain amplification and integrin based signaling in osteocytes. J. Musculoskelet. Neuronal Interact. 8(4), 332–334 (2008)PubMedPubMedCentralGoogle Scholar
  36. 36.
    T. Adachi, Y. Aonuma, M. Tanaka, M. Hojo, T. Takano-Yamamoto, H. Kamioka, Calcium response in single osteocytes to locally applied mechanical stimulus: differences in cell process and cell body. J. Biomech. 42(12), 1989–1995 (2009)PubMedCrossRefGoogle Scholar
  37. 37.
    S. Tatsumi, K. Ishii, N. Amizuka, M. Li, T. Kobayashi, K. Kohno, M. Ito, S. Takeshita, K. Ikeda, Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 5(6), 464–475 (2007)PubMedCrossRefGoogle Scholar
  38. 38.
    G.Y. Rochefort, S. Pallu, C.L. Benhamou, Osteocyte: the unrecognized side of bone tissue. Osteoporos. Int. 21(9), 1457–1469 (2010)PubMedCrossRefGoogle Scholar
  39. 39.
    G. Colaianni, G. Brunetti, M.F. Faienza, S. Colucci, M. Grano, Osteoporosis and obesity: role of Wnt pathway in human and murine models. World J. Orthop. 5(3), 242–246 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    X. Li, M.S. Ominsky, Q.T. Niu, N. Sun, B. Daugherty, D. D’Agostin, C. Kurahara, Y. Gao, J. Cao, J. Gong, F. Asuncion, M. Barrero, K. Warmington, D. Dwyer, M. Stolina, S. Morony, I. Sarosi, P.J. Kostenuik, D.L. Lacey, W.S. Simonet, H.Z. Ke, C. Paszty, Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J. Bone Miner. Res. 23(6), 860–869 (2008)PubMedCrossRefGoogle Scholar
  41. 41.
    P. Schwab, K. Scalapino, Exercise for bone health: rationale and prescription. Curr. Opin. Rheumatol. 23(2), 137–141 (2011)PubMedCrossRefGoogle Scholar
  42. 42.
    A.M. Cheung, L. Giangregorio, Mechanical stimuli and bone health: what is the evidence? Curr. Opin. Rheumatol. 24(5), 561–566 (2012)PubMedCrossRefGoogle Scholar
  43. 43.
    E. Ozcivici, Y.K. Luu, B. Adler, Y.X. Qin, J. Rubin, S. Judex, C.T. Rubin, Mechanical signals as anabolic agents in bone. Nat. Rev. Rheumatol. 6(1), 50–59 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    C.T. Rubin, E. Capilla, Y.K. Luu, B. Busa, H. Crawford, D.J. Nolan, V. Mittal, C.J. Rosen, J.E. Pessin, S. Judex, Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals. Proc. Natl. Acad. Sci. USA 104(45), 17879–17884 (2007)PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Y.K. Luu, E. Capilla, C.J. Rosen, V. Gilsanz, J.E. Pessin, S. Judex, C.T. Rubin, Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J. Bone Miner. Res. 24(1), 50–61 (2009)PubMedCrossRefGoogle Scholar
  46. 46.
    A.G. Robling, P.J. Niziolek, L.A. Baldridge, K.W. Condon, M.R. Allen, I. Alam, S.M. Mantila, J. Gluhak-Heinrich, T.M. Bellido, S.E. Harris, C.H. Turner, Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J. Biol. Chem. 283(9), 5866–5875 (2008)PubMedCrossRefGoogle Scholar
  47. 47.
    N. Bonnet, K.N. Standley, E.N. Bianchi, V. Stadelmann, M. Foti, S.J. Conway, S.L. Ferrari, The matricellular protein periostin is required for sost inhibition and the anabolic response to mechanical loading and physical activity. J. Biol. Chem. 284(51), 35939–35950 (2009)PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    K. Amrein, S. Amrein, C. Drexler, H.P. Dimai, H. Dobnig, K. Pfeifer, A. Tomaschitz, T.R. Pieber, A. Fahrleitner-Pammer, Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults. J. Clin. Endocrinol. Metab. 97(1), 148–154 (2012)PubMedCrossRefGoogle Scholar
  49. 49.
    G. Lombardi, P. Lanteri, A. Colombini, M. Mariotti, G. Banfi, Sclerostin concentrations in athletes: role of load and gender. J. Biol. Regul. Homeost. Agents 26(1), 157–163 (2012)PubMedGoogle Scholar
  50. 50.
    J. Jurimae, V. Tillmann, A. Cicchella, C. Stefanelli, K. Vosoberg, A.L. Tamm, T. Jurimae, Increased sclerostin and preadipocyte factor-1 levels in prepubertal rhythmic gymnasts: associations with bone mineral density, body composition, and adipocytokine values. Osteoporos. Int. (2015). doi: 10.1007/s00198-015-3301-0 PubMedGoogle Scholar
  51. 51.
    L.B. Meakin, C. Udeh, G.L. Galea, L.E. Lanyon, J.S. Price, Exercise does not enhance aged bone’s impaired response to artificial loading in C57Bl/6 mice. Bone 81, 47–52 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    K. Kerschan-Schindl, M.M. Thalmann, E. Weiss, M. Tsironi, U. Foger-Samwald, J. Meinhart, K. Skenderi, P. Pietschmann, Changes in Serum Levels of Myokines and Wnt-Antagonists after an Ultramarathon Race. PLoS ONE 10(7), e0132478 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    D.L. Belavy, N. Baecker, G. Armbrecht, G. Beller, J. Buehlmeier, P. Frings-Meuthen, J. Rittweger, H.J. Roth, M. Heer, D. Felsenberg, Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest. J. Bone Miner. Metab. (2015). doi: 10.1007/s00774-015-0681-3 PubMedGoogle Scholar
  54. 54.
    I. Bergstrom, P. Parini, S.A. Gustafsson, G. Andersson, J. Brinck, Physical training increases osteoprotegerin in postmenopausal women. J. Bone Miner. Metab. 30(2), 202–207 (2012)PubMedCrossRefGoogle Scholar
  55. 55.
    J.L. Ferretti, R.F. Capozza, G.R. Cointry, S.L. Garcia, H. Plotkin, M.L. Alvarez Filgueira, J.R. Zanchetta, Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age. Bone 22(6), 683–690 (1998)PubMedCrossRefGoogle Scholar
  56. 56.
    L.H. Bogl, A. Latvala, J. Kaprio, O. Sovijarvi, A. Rissanen, K.H. Pietilainen, An investigation into the relationship between soft tissue body composition and bone mineral density in a young adult twin sample. J. Bone Miner. Res. 26(1), 79–87 (2011)PubMedCrossRefGoogle Scholar
  57. 57.
    J. Rittweger, G. Beller, J. Ehrig, C. Jung, U. Koch, J. Ramolla, F. Schmidt, D. Newitt, S. Majumdar, H. Schiessl, D. Felsenberg, Bone-muscle strength indices for the human lower leg. Bone 27(2), 319–326 (2000)PubMedCrossRefGoogle Scholar
  58. 58.
    E. Schoenau, From mechanostat theory to development of the “Functional Muscle-Bone-Unit”. J. Musculoskelet. Neuronal Interact. 5(3), 232–238 (2005)PubMedGoogle Scholar
  59. 59.
    F. Rauch, D.A. Bailey, A. Baxter-Jones, R. Mirwald, R. Faulkner, The ‘muscle-bone unit’ during the pubertal growth spurt. Bone 34(5), 771–775 (2004)PubMedCrossRefGoogle Scholar
  60. 60.
    T. Matsuoka, P.E. Ahlberg, N. Kessaris, P. Iannarelli, U. Dennehy, W.D. Richardson, A.P. McMahon, G. Koentges, Neural crest origins of the neck and shoulder. Nature 436(7049), 347–355 (2005)PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    H.M. Frost, E. Schonau, The “muscle-bone unit” in children and adolescents: a 2000 overview. J. Pediatr. Endocrinol. Metab. 13(6), 571–590 (2000)PubMedCrossRefGoogle Scholar
  62. 62.
    C. Tagliaferri, Y. Wittrant, M.J. Davicco, S. Walrand, V. Coxam, Muscle and bone, two interconnected tissues. Ageing Res. Rev. 21, 55–70 (2015)PubMedCrossRefGoogle Scholar
  63. 63.
    L. Cianferotti, M.L. Brandi, Muscle-bone interactions: basic and clinical aspects. Endocrine 45(2), 165–177 (2014)PubMedCrossRefGoogle Scholar
  64. 64.
    C. Gomez, V. David, N.M. Peet, L. Vico, C. Chenu, L. Malaval, T.M. Skerry, Absence of mechanical loading in utero influences bone mass and architecture but not innervation in Myod-Myf5-deficient mice. J. Anat. 210(3), 259–271 (2007)PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Y. Bren-Mattison, M. Hausburg, B.B. Olwin, Growth of limb muscle is dependent on skeletal-derived Indian hedgehog. Dev. Biol. 356(2), 486–495 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    A. Sharir, T. Stern, C. Rot, R. Shahar, E. Zelzer, Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis. Development 138(15), 3247–3259 (2011)PubMedCrossRefGoogle Scholar
  67. 67.
    N.C. Nowlan, J. Sharpe, K.A. Roddy, P.J. Prendergast, P. Murphy, Mechanobiology of embryonic skeletal development: insights from animal models. Birth Defects Res. C Embryo Today 90(3), 203–213 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    J. Kahn, Y. Shwartz, E. Blitz, S. Krief, A. Sharir, D.A. Breitel, R. Rattenbach, F. Relaix, P. Maire, R.B. Rountree, D.M. Kingsley, E. Zelzer, Muscle contraction is necessary to maintain joint progenitor cell fate. Dev. Cell 16(5), 734–743 (2009)PubMedCrossRefGoogle Scholar
  69. 69.
    S.I. Zacks, M.F. Sheff, Periosteal and metaplastic bone formation in mouse minced muscle regeneration. Lab. Invest. 46(4), 405–412 (1982)PubMedGoogle Scholar
  70. 70.
    S.E. Utvag, O. Grundnes, D.B. Rindal, O. Reikeras, Influence of extensive muscle injury on fracture healing in rat tibia. J. Orthop. Trauma 17(6), 430–435 (2003)PubMedCrossRefGoogle Scholar
  71. 71.
    H. Kaufman, A. Reznick, H. Stein, M. Barak, G. Maor, The biological basis of the bone-muscle inter-relationship in the algorithm of fracture healing. Orthopedics 31(8), 751 (2008)PubMedCrossRefGoogle Scholar
  72. 72.
    M.W. Hamrick, X. Shi, W. Zhang, C. Pennington, H. Thakore, M. Haque, B. Kang, C.M. Isales, S. Fulzele, K.H. Wenger, Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading. Bone 40(6), 1544–1553 (2007)PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    M.R. Morissette, J.C. Stricker, M.A. Rosenberg, C. Buranasombati, E.B. Levitan, M.A. Mittleman, A. Rosenzweig, Effects of myostatin deletion in aging mice. Aging Cell 8(5), 573–583 (2009)PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    M.E. Chan, B.J. Adler, D.E. Green, C.T. Rubin, Bone structure and B-cell populations, crippled by obesity, are partially rescued by brief daily exposure to low-magnitude mechanical signals. FASEB J. 26(12), 4855–4863 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    A. Seabra, E. Marques, J. Brito, P. Krustrup, S. Abreu, J. Oliveira, C. Rego, J. Mota, A. Rebelo, Muscle strength and soccer practice as major determinants of bone mineral density in adolescents. Joint Bone Spine 79(4), 403–408 (2012)PubMedCrossRefGoogle Scholar
  76. 76.
    P. Krustrup, P.R. Hansen, L.J. Andersen, M.D. Jakobsen, E. Sundstrup, M.B. Randers, L. Christiansen, E.W. Helge, M.T. Pedersen, P. Sogaard, A. Junge, J. Dvorak, P. Aagaard, J. Bangsbo, Long-term musculoskeletal and cardiac health effects of recreational football and running for premenopausal women. Scand. J. Med. Sci. Sports 20(Suppl 1), 58–71 (2010)PubMedCrossRefGoogle Scholar
  77. 77.
    E. Ozcivici, Y.K. Luu, C.T. Rubin, S. Judex, Low-level vibrations retain bone marrow’s osteogenic potential and augment recovery of trabecular bone during reambulation. PLoS ONE 5(6), e11178 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    J. Rittweger, H.M. Frost, H. Schiessl, H. Ohshima, B. Alkner, P. Tesch, D. Felsenberg, Muscle atrophy and bone loss after 90 days’ bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study. Bone 36(6), 1019–1029 (2005)PubMedCrossRefGoogle Scholar
  79. 79.
    J. Nam, P. Perera, R. Gordon, Y.H. Jeong, A.D. Blazek, D.G. Kim, B.C. Tee, Z. Sun, T.D. Eubank, Y. Zhao, B. Lablebecioglu, S. Liu, A. Litsky, N.L. Weisleder, B.S. Lee, T. Butterfield, A.L. Schneyer, S. Agarwal, Follistatin-like 3 is a mediator of exercise-driven bone formation and strengthening. Bone 78, 62–70 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    E. Assier, M.C. Boissier, J.M. Dayer, Interleukin-6: from identification of the cytokine to development of targeted treatments. Joint Bone Spine 77(6), 532–536 (2010)PubMedCrossRefGoogle Scholar
  81. 81.
    B.K. Pedersen, Muscles and their myokines. J. Exp. Biol. 214(Pt 2), 337–346 (2011)PubMedCrossRefGoogle Scholar
  82. 82.
    B.K. Pedersen, M.A. Febbraio, Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol. Rev. 88(4), 1379–1406 (2008)PubMedCrossRefGoogle Scholar
  83. 83.
    M.A. Febbraio, P. Ott, H.B. Nielsen, A. Steensberg, C. Keller, P. Krustrup, N.H. Secher, B.K. Pedersen, Hepatosplanchnic clearance of interleukin-6 in humans during exercise. Am. J. Physiol. Endocrinol. Metab. 285(2), E397–E402 (2003)PubMedCrossRefGoogle Scholar
  84. 84.
    A.L. Serrano, B. Baeza-Raja, E. Perdiguero, M. Jardi, P. Munoz-Canoves, Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 7(1), 33–44 (2008)PubMedCrossRefGoogle Scholar
  85. 85.
    T.A. Washington, J.P. White, J.M. Davis, L.B. Wilson, L.L. Lowe, S. Sato, J.A. Carson, Skeletal muscle mass recovery from atrophy in IL-6 knockout mice. Acta Physiol. (Oxf.) 202(4), 657–669 (2011)PubMedCentralCrossRefGoogle Scholar
  86. 86.
    J.M. Peake, P. Della Gatta, K. Suzuki, D.C. Nieman, Cytokine expression and secretion by skeletal muscle cells: regulatory mechanisms and exercise effects. Exerc. Immunol. Rev. 21, 8–25 (2015)PubMedGoogle Scholar
  87. 87.
    C.P. Fischer, Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc. Immunol. Rev. 12, 6–33 (2006)PubMedGoogle Scholar
  88. 88.
    G. Banfi, A. Colombini, G. Lombardi, A. Lubkowska, Metabolic markers in sports medicine. Adv. Clin. Chem. 56, 1–54 (2012)PubMedCrossRefGoogle Scholar
  89. 89.
    S.L. Nehlsen-Cannarella, O.R. Fagoaga, D.C. Nieman, D.A. Henson, D.E. Butterworth, R.L. Schmitt, E.M. Bailey, B.J. Warren, A. Utter, J.M. Davis, Carbohydrate and the cytokine response to 2.5 h of running. J. Appl. Physiol. 82(5), 1662–1667 (1997)PubMedGoogle Scholar
  90. 90.
    H. Ullum, P.M. Haahr, M. Diamant, J. Palmo, J. Halkjaer-Kristensen, B.K. Pedersen, Bicycle exercise enhances plasma IL-6 but does not change IL-1 alpha, IL-1 beta, IL-6, or TNF-alpha pre-mRNA in BMNC. J. Appl. Physiol. 77(1), 93–97 (1994)PubMedGoogle Scholar
  91. 91.
    R.L. Starkie, D.J. Angus, J. Rolland, M. Hargreaves, M.A. Febbraio, Effect of prolonged, submaximal exercise and carbohydrate ingestion on monocyte intracellular cytokine production in humans. J. Physiol. 528(Pt 3), 647–655 (2000)PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    R.L. Starkie, J. Rolland, D.J. Angus, M.J. Anderson, M.A. Febbraio, Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-alpha levels after prolonged running. Am. J. Physiol. Cell Physiol. 280(4), C769–C774 (2001)PubMedGoogle Scholar
  93. 93.
    C. Keller, Y. Hellsten, A. Steensberg, B.K. Pedersen, Differential regulation of IL-6 and TNF-alpha via calcineurin in human skeletal muscle cells. Cytokine 36(3–4), 141–147 (2006)PubMedCrossRefGoogle Scholar
  94. 94.
    B.K. Pedersen, Muscular interleukin-6 and its role as an energy sensor. Med. Sci. Sports Exerc. 44(3), 392–396 (2012)PubMedCrossRefGoogle Scholar
  95. 95.
    B.K. Pedersen, A. Steensberg, C. Fischer, C. Keller, P. Keller, P. Plomgaard, E. Wolsk-Petersen, M. Febbraio, The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proc. Nutr. Soc. 63(2), 263–267 (2004)PubMedCrossRefGoogle Scholar
  96. 96.
    N.B. Ruderman, C. Keller, A.M. Richard, A.K. Saha, Z. Luo, X. Xiang, M. Giralt, V.B. Ritov, E.V. Menshikova, D.E. Kelley, J. Hidalgo, B.K. Pedersen, M. Kelly, Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes 55(Suppl 2), S48–S54 (2006)PubMedCrossRefGoogle Scholar
  97. 97.
    M.A. Febbraio, A. Steensberg, C. Keller, R.L. Starkie, H.B. Nielsen, P. Krustrup, P. Ott, N.H. Secher, B.K. Pedersen, Glucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans. J. Physiol. 549(Pt 2), 607–612 (2003)PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    C.P. Fischer, P. Plomgaard, A.K. Hansen, H. Pilegaard, B. Saltin, B.K. Pedersen, Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 287(6), E1189–E1194 (2004)PubMedCrossRefGoogle Scholar
  99. 99.
    M. De Lisio, G. Parise, Characterization of the effects of exercise training on hematopoietic stem cell quantity and function. J. Appl. Physiol. 113(10), 1576–1584 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    C. Keller, A. Steensberg, A.K. Hansen, C.P. Fischer, P. Plomgaard, B.K. Pedersen, Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J. Appl. Physiol. 99(6), 2075–2079 (2005)PubMedCrossRefGoogle Scholar
  101. 101.
    B.K. Pedersen, M.A. Febbraio, Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat. Rev. Endocrinol. 8(8), 457–465 (2012)PubMedCrossRefGoogle Scholar
  102. 102.
    A.L. Carey, G.R. Steinberg, S.L. Macaulay, W.G. Thomas, A.G. Holmes, G. Ramm, O. Prelovsek, C. Hohnen-Behrens, M.J. Watt, D.E. James, B.E. Kemp, B.K. Pedersen, M.A. Febbraio, Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55(10), 2688–2697 (2006)PubMedCrossRefGoogle Scholar
  103. 103.
    G. van Hall, A. Steensberg, M. Sacchetti, C. Fischer, C. Keller, P. Schjerling, N. Hiscock, K. Moller, B. Saltin, M.A. Febbraio, B.K. Pedersen, Interleukin-6 stimulates lipolysis and fat oxidation in humans. J. Clin. Endocrinol. Metab. 88(7), 3005–3010 (2003)PubMedCrossRefGoogle Scholar
  104. 104.
    C.R. Bruce, D.J. Dyck, Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-alpha. Am. J. Physiol. Endocrinol. Metab. 287(4), E616–621 (2004)PubMedCrossRefGoogle Scholar
  105. 105.
    B.B. Kahn, T. Alquier, D. Carling, D.G. Hardie, AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1(1), 15–25 (2005)PubMedCrossRefGoogle Scholar
  106. 106.
    S.M. Phillips, H.J. Green, M.A. Tarnopolsky, G.F. Heigenhauser, R.E. Hill, S.M. Grant, Effects of training duration on substrate turnover and oxidation during exercise. J. Appl. Physiol. 81(5), 2182–2191 (1996)PubMedGoogle Scholar
  107. 107.
    M.A. Febbraio, N. Hiscock, M. Sacchetti, C.P. Fischer, B.K. Pedersen, Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. Diabetes 53(7), 1643–1648 (2004)PubMedCrossRefGoogle Scholar
  108. 108.
    G.R. Steinberg, M.J. Watt, M.A. Febbraio, Cytokine Regulation of AMPK signalling. Front. Biosci. (Landmark Ed.) 14, 1902–1916 (2009)CrossRefGoogle Scholar
  109. 109.
    M.J. Watt, N. Dzamko, W.G. Thomas, S. Rose-John, M. Ernst, D. Carling, B.E. Kemp, M.A. Febbraio, G.R. Steinberg, CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat. Med. 12(5), 541–548 (2006)PubMedCrossRefGoogle Scholar
  110. 110.
    V. Wallenius, K. Wallenius, B. Ahren, M. Rudling, H. Carlsten, S.L. Dickson, C. Ohlsson, J.O. Jansson, Interleukin-6-deficient mice develop mature-onset obesity. Nat. Med. 8(1), 75–79 (2002)PubMedCrossRefGoogle Scholar
  111. 111.
    S. Nielsen, B.K. Pedersen, Skeletal muscle as an immunogenic organ. Curr. Opin. Pharmacol. 8(3), 346–351 (2008)PubMedCrossRefGoogle Scholar
  112. 112.
    A.M. Petersen, B.K. Pedersen, The anti-inflammatory effect of exercise. J. Appl. Physiol. 98(4), 1154–1162 (2005)PubMedCrossRefGoogle Scholar
  113. 113.
    R.L. Jilka, G. Hangoc, G. Girasole, G. Passeri, D.C. Williams, J.S. Abrams, B. Boyce, H. Broxmeyer, S.C. Manolagas, Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 257(5066), 88–91 (1992)PubMedCrossRefGoogle Scholar
  114. 114.
    B. Le Goff, F. Blanchard, J.M. Berthelot, D. Heymann, Y. Maugars, Role for interleukin-6 in structural joint damage and systemic bone loss in rheumatoid arthritis. Joint Bone Spine 77(3), 201–205 (2010)PubMedCrossRefGoogle Scholar
  115. 115.
    R. Axmann, C. Bohm, G. Kronke, J. Zwerina, J. Smolen, G. Schett, Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum. 60(9), 2747–2756 (2009)PubMedCrossRefGoogle Scholar
  116. 116.
    P. Palmqvist, E. Persson, H.H. Conaway, U.H. Lerner, IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae. J. Immunol. 169(6), 3353–3362 (2002)PubMedCrossRefGoogle Scholar
  117. 117.
    N. Saidenberg-Kermanac’h, M. Cohen-Solal, N. Bessis, M.C. De Vernejoul, M.C. Boissier, Role for osteoprotegerin in rheumatoid inflammation. Joint Bone Spine 71(1), 9–13 (2004)PubMedCrossRefGoogle Scholar
  118. 118.
    F. De Benedetti, P. Pignatti, M. Vivarelli, C. Meazza, G. Ciliberto, R. Savino, A. Martini, In vivo neutralization of human IL-6 (hIL-6) achieved by immunization of hIL-6-transgenic mice with a hIL-6 receptor antagonist. J. Immunol. 166(7), 4334–4340 (2001)PubMedCrossRefGoogle Scholar
  119. 119.
    P.K. Wong, J.M. Quinn, N.A. Sims, A. van Nieuwenhuijze, I.K. Campbell, I.P. Wicks, Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum. 54(1), 158–168 (2006)PubMedCrossRefGoogle Scholar
  120. 120.
    Y.A. Mezil, D. Allison, K. Kish, D. Ditor, W.E. Ward, E. Tsiani, P. Klentrou, Response of bone turnover markers and cytokines to high-intensity low-impact exercise. Med. Sci. Sports Exerc. 47(7), 1495–1502 (2015)PubMedCrossRefGoogle Scholar
  121. 121.
    E. Galliera, G. Lombardi, M.G. Marazzi, D. Grasso, E. Vianello, R. Pozzoni, G. Banfi, M.M. Corsi Romanelli, Acute exercise in elite rugby players increases the circulating level of the cardiovascular biomarker GDF-15. Scand. J. Clin. Lab. Invest. 74(6), 492–499 (2014)PubMedCrossRefGoogle Scholar
  122. 122.
    R.K. Evans, A.J. Antczak, M. Lester, R. Yanovich, E. Israeli, D.S. Moran, Effects of a 4-month recruit training program on markers of bone metabolism. Med. Sci. Sports Exerc. 40(11 Suppl), S660–S670 (2008)PubMedCrossRefGoogle Scholar
  123. 123.
    L. Li, X. Chen, S. Lv, M. Dong, L. Zhang, J. Tu, J. Yang, L. Zhang, Y. Song, L. Xu, J. Zou, Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis. PLoS ONE 9(11), e112845 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    L. Aguirre, N. Napoli, D. Waters, C. Qualls, D.T. Villareal, R. Armamento-Villareal, Increasing adiposity is associated with higher adipokine levels and lower bone mineral density in obese older adults. J. Clin. Endocrinol. Metab. 99(9), 3290–3297 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    J.H. Park, K.H. Park, S. Cho, Y.S. Choi, S.K. Seo, B.S. Lee, H.S. Park, Concomitant increase in muscle strength and bone mineral density with decreasing IL-6 levels after combination therapy with alendronate and calcitriol in postmenopausal women. Menopause 20(7), 747–753 (2013)PubMedCrossRefGoogle Scholar
  126. 126.
    F. Haugen, F. Norheim, H. Lian, A.J. Wensaas, S. Dueland, O. Berg, A. Funderud, B.S. Skalhegg, T. Raastad, C.A. Drevon, IL7 is expressed and secreted by human skeletal muscle cells. Am. J. Physiol. Cell Physiol. 298(4), 807–816 (2010)CrossRefGoogle Scholar
  127. 127.
    R. Zhao, Immune regulation of osteoclast function in postmenopausal osteoporosis: a critical interdisciplinary perspective. Int. J. Med. Sci. 9(9), 825–832 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    S.K. Lee, C.D. Surh, Role of interleukin-7 in bone and T-cell homeostasis. Immunol. Rev. 208, 169–180 (2005)PubMedCrossRefGoogle Scholar
  129. 129.
    M.N. Weitzmann, S. Cenci, L. Rifas, C. Brown, R. Pacifici, Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood 96(5), 1873–1878 (2000)PubMedGoogle Scholar
  130. 130.
    G. Toraldo, C. Roggia, W.P. Qian, R. Pacifici, M.N. Weitzmann, IL-7 induces bone loss in vivo by induction of receptor activator of nuclear factor kappa B ligand and tumor necrosis factor alpha from T cells. Proc. Natl. Acad. Sci. USA 100(1), 125–130 (2003)PubMedCrossRefGoogle Scholar
  131. 131.
    D.G. Remick, Interleukin-8. Crit. Care Med. 33(12 Suppl), S466–S467 (2005)PubMedCrossRefGoogle Scholar
  132. 132.
    T.J. Standiford, S.L. Kunkel, M.A. Basha, S.W. Chensue, J.P. Lynch 3rd, G.B. Toews, J. Westwick, R.M. Strieter, Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. J. Clin. Invest. 86(6), 1945–1953 (1990)PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    S. Apostolakis, K. Vogiatzi, V. Amanatidou, D.A. Spandidos, Interleukin 8 and cardiovascular disease. Cardiovasc. Res. 84(3), 353–360 (2009)PubMedCrossRefGoogle Scholar
  134. 134.
    D.C. Nieman, J.M. Davis, D.A. Henson, S.J. Gross, C.L. Dumke, A.C. Utter, D.M. Vinci, J.A. Carson, A. Brown, S.R. McAnulty, L.S. McAnulty, N.T. Triplett, Muscle cytokine mRNA changes after 2.5 h of cycling: influence of carbohydrate. Med. Sci. Sports Exerc. 37(8), 1283–1290 (2005)PubMedCrossRefGoogle Scholar
  135. 135.
    E. Goussetis, A. Spiropoulos, M. Tsironi, K. Skenderi, A. Margeli, S. Graphakos, P. Baltopoulos, I. Papassotiriou, Spartathlon, a 246 kilometer foot race: effects of acute inflammation induced by prolonged exercise on circulating progenitor reparative cells. Blood Cells Mol. Dis. 42(3), 294–299 (2009)PubMedCrossRefGoogle Scholar
  136. 136.
    K. Suzuki, S. Nakaji, M. Yamada, Q. Liu, S. Kurakake, N. Okamura, T. Kumae, T. Umeda, K. Sugawara, Impact of a competitive marathon race on systemic cytokine and neutrophil responses. Med. Sci. Sports Exerc. 35(2), 348–355 (2003)PubMedCrossRefGoogle Scholar
  137. 137.
    L. Malaval, J.E. Aubin, Biphasic effects of leukemia inhibitory factor on osteoblastic differentiation. J. Cell Biochem. Suppl. 36, 63–70 (2001)PubMedCrossRefGoogle Scholar
  138. 138.
    C. Broholm, O.H. Mortensen, S. Nielsen, T. Akerstrom, A. Zankari, B. Dahl, B.K. Pedersen, Exercise induces expression of leukaemia inhibitory factor in human skeletal muscle. J. Physiol. 586(8), 2195–2201 (2008)PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    N.A. Sims, R.W. Johnson, Leukemia inhibitory factor: a paracrine mediator of bone metabolism. Growth Factors 30(2), 76–87 (2012)PubMedCrossRefGoogle Scholar
  140. 140.
    L. Laviola, A. Natalicchio, F. Giorgino, The IGF-I signaling pathway. Curr. Pharm. Des. 13(7), 663–669 (2007)PubMedCrossRefGoogle Scholar
  141. 141.
    A. Giustina, G. Mazziotti, E. Canalis, Growth hormone, insulin-like growth factors, and the skeleton. Endocr. Rev. 29(5), 535–559 (2008)PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    D. Le Roith, C. Bondy, S. Yakar, J.L. Liu, A. Butler, The somatomedin hypothesis: 2001. Endocr. Rev. 22(1), 53–74 (2001)PubMedCrossRefGoogle Scholar
  143. 143.
    C. Ohlsson, A. Nilsson, O. Isaksson, A. Lindahl, Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate. Proc. Natl. Acad. Sci. USA 89(20), 9826–9830 (1992)PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    T.L. McCarthy, M. Centrella, E. Canalis, Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast-enriched cultures. J. Biol. Chem. 265(26), 15353–15356 (1990)PubMedGoogle Scholar
  145. 145.
    M. Ernst, G.A. Rodan, Estradiol regulation of insulin-like growth factor-I expression in osteoblastic cells: evidence for transcriptional control. Mol. Endocrinol. 5(8), 1081–1089 (1991)PubMedCrossRefGoogle Scholar
  146. 146.
    M. Kassem, R. Okazaki, S.A. Harris, T.C. Spelsberg, C.A. Conover, B.L. Riggs, Estrogen effects on insulin-like growth factor gene expression in a human osteoblastic cell line with high levels of estrogen receptor. Calcif. Tissue Int. 62(1), 60–66 (1998)PubMedCrossRefGoogle Scholar
  147. 147.
    A.M. Delany, D. Durant, E. Canalis, Glucocorticoid suppression of IGF I transcription in osteoblasts. Mol. Endocrinol. 15(10), 1781–1789 (2001)PubMedCrossRefGoogle Scholar
  148. 148.
    P. Lakatos, M.D. Caplice, V. Khanna, P.H. Stern, Thyroid hormones increase insulin-like growth factor I content in the medium of rat bone tissue. J. Bone Miner. Res. 8(12), 1475–1481 (1993)PubMedCrossRefGoogle Scholar
  149. 149.
    B.K. Huang, L.A. Golden, G. Tarjan, L.D. Madison, P.H. Stern, Insulin-like growth factor I production is essential for anabolic effects of thyroid hormone in osteoblasts. J. Bone Miner. Res. 15(2), 188–197 (2000)PubMedCrossRefGoogle Scholar
  150. 150.
    E. Canalis, J. Pash, B. Gabbitas, S. Rydziel, S. Varghese, Growth factors regulate the synthesis of insulin-like growth factor-I in bone cell cultures. Endocrinology 133(1), 33–38 (1993)PubMedGoogle Scholar
  151. 151.
    E. Canalis, A.N. Economides, E. Gazzerro, Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr. Rev. 24(2), 218–235 (2003)PubMedCrossRefGoogle Scholar
  152. 152.
    E. Canalis, Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria. J. Clin. Invest. 66(4), 709–719 (1980)PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    T.L. McCarthy, M. Centrella, E. Canalis, Regulatory effects of insulin-like growth factors I and II on bone collagen synthesis in rat calvarial cultures. Endocrinology 124(1), 301–309 (1989)PubMedCrossRefGoogle Scholar
  154. 154.
    T. Thomas, F. Gori, T.C. Spelsberg, S. Khosla, B.L. Riggs, C.A. Conover, Response of bipotential human marrow stromal cells to insulin-like growth factors: effect on binding protein production, proliferation, and commitment to osteoblasts and adipocytes. Endocrinology 140(11), 5036–5044 (1999)PubMedGoogle Scholar
  155. 155.
    M.P. Playford, D. Bicknell, W.F. Bodmer, V.M. Macaulay, Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Proc. Natl. Acad. Sci. USA 97(22), 12103–12108 (2000)PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    V. Krishnan, H.U. Bryant, O.A. Macdougald, Regulation of bone mass by Wnt signaling. J. Clin. Invest. 116(5), 1202–1209 (2006)PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    H. Mochizuki, Y. Hakeda, N. Wakatsuki, N. Usui, S. Akashi, T. Sato, K. Tanaka, M. Kumegawa, Insulin-like growth factor-I supports formation and activation of osteoclasts. Endocrinology 131(3), 1075–1080 (1992)PubMedGoogle Scholar
  158. 158.
    P. Hou, T. Sato, W. Hofstetter, N.T. Foged, Identification and characterization of the insulin-like growth factor I receptor in mature rabbit osteoclasts. J. Bone Miner. Res. 12(4), 534–540 (1997)PubMedCrossRefGoogle Scholar
  159. 159.
    T. Niu, C.J. Rosen, The insulin-like growth factor-I gene and osteoporosis: a critical appraisal. Gene 361, 38–56 (2005)PubMedCrossRefGoogle Scholar
  160. 160.
    T. Moriwake, H. Tanaka, S. Kanzaki, J. Higuchi, Y. Seino, 1,25-Dihydroxyvitamin D3 stimulates the secretion of insulin-like growth factor binding protein 3 (IGFBP-3) by cultured human osteosarcoma cells. Endocrinology 130(2), 1071–1073 (1992)PubMedGoogle Scholar
  161. 161.
    K. Rajkumar, D. Barron, M.S. Lewitt, L.J. Murphy, Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 136(9), 4029–4034 (1995)PubMedGoogle Scholar
  162. 162.
    V.E. DeMambro, D.R. Clemmons, L.G. Horton, M.L. Bouxsein, T.L. Wood, W.G. Beamer, E. Canalis, C.J. Rosen, Gender-specific changes in bone turnover and skeletal architecture in igfbp-2-null mice. Endocrinology 149(5), 2051–2061 (2008)PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    J.V. Silha, S. Mishra, C.J. Rosen, W.G. Beamer, R.T. Turner, D.R. Powell, L.J. Murphy, Perturbations in bone formation and resorption in insulin-like growth factor binding protein-3 transgenic mice. J. Bone Miner. Res. 18(10), 1834–1841 (2003)PubMedCrossRefGoogle Scholar
  164. 164.
    C. Richman, D.J. Baylink, K. Lang, C. Dony, S. Mohan, Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo. Endocrinology 140(10), 4699–4705 (1999)PubMedGoogle Scholar
  165. 165.
    M.W. Hamrick, P.L. McNeil, S.L. Patterson, Role of muscle-derived growth factors in bone formation. J. Musculoskelet. Neuronal Interact. 10(1), 64–70 (2010)PubMedPubMedCentralGoogle Scholar
  166. 166.
    M.B. Alzghoul, D. Gerrard, B.A. Watkins, K. Hannon, Ectopic expression of IGF-I and Shh by skeletal muscle inhibits disuse-mediated skeletal muscle atrophy and bone osteopenia in vivo. FASEB J. 18(1), 221–223 (2004)PubMedGoogle Scholar
  167. 167.
    J. Banu, L. Wang, D.N. Kalu, Effects of increased muscle mass on bone in male mice overexpressing IGF-I in skeletal muscles. Calcif. Tissue Int. 73(2), 196–201 (2003)PubMedCrossRefGoogle Scholar
  168. 168.
    S. Elis, Y. Wu, H.W. Courtland, H. Sun, C.J. Rosen, M.L. Adamo, S. Yakar, Increased serum IGF-1 levels protect the musculoskeletal system but are associated with elevated oxidative stress markers and increased mortality independent of tissue igf1 gene expression. Aging Cell 10(3), 547–550 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    C. Ehrnborg, K.H. Lange, R. Dall, J.S. Christiansen, P.A. Lundberg, R.C. Baxter, M.A. Boroujerdi, B.A. Bengtsson, M.L. Healey, C. Pentecost, S. Longobardi, R. Napoli, T. Rosen, G.H.S. Group, The growth hormone/insulin-like growth factor-I axis hormones and bone markers in elite athletes in response to a maximum exercise test. J. Clin. Endocrinol. Metab. 88, 394–401 (2003)PubMedCrossRefGoogle Scholar
  170. 170.
    L.A. Milliken, S.B. Going, L.B. Houtkooper, H.G. Flint-Wagner, A. Figueroa, L.L. Metcalfe, R.M. Blew, S.C. Sharp, T.G. Lohman, Effects of exercise training on bone remodeling, insulin-like growth factors, and bone mineral density in postmenopausal women with and without hormone replacement therapy. Calcif. Tissue Int. 72(4), 478–484 (2003)PubMedCrossRefGoogle Scholar
  171. 171.
    T. Soot, T. Jurimae, J. Jurimae, Relationships between bone mineral density, insulin-like growth factor-1 and sex hormones in young females with different physical activity. J. Sports Med. Phys. Fitness 46(2), 293–297 (2006)PubMedGoogle Scholar
  172. 172.
    T. Pomerants, V. Tillmann, K. Karelson, J. Jurimae, T. Jurimae, Impact of acute exercise on bone turnover and growth hormone/insulin-like growth factor axis in boys. J. Sports Med. Phys. Fitness 48(2), 266–271 (2008)PubMedGoogle Scholar
  173. 173.
    R. Gruodyte, J. Jurimae, M. Saar, T. Jurimae, The relationships among bone health, insulin-like growth factor-1 and sex hormones in adolescent female athletes. J. Bone Miner. Metab. 28(3), 306–313 (2010)PubMedCrossRefGoogle Scholar
  174. 174.
    S. Perrini, L. Laviola, M.C. Carreira, A. Cignarelli, A. Natalicchio, F. Giorgino, The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J. Endocrinol. 205(3), 201–210 (2010)PubMedCrossRefGoogle Scholar
  175. 175.
    Y. Tsuchiya, K. Sakuraba, E. Ochi, High force eccentric exercise enhances serum tartrate-resistant acid phosphatase-5b and osteocalcin. J. Musculoskelet. Neuronal Interact. 14(1), 50–57 (2014)PubMedGoogle Scholar
  176. 176.
    D.A. Rubin, D.M. Castner, H. Pham, J. Ng, E. Adams, D.A. Judelson, Hormonal and metabolic responses to a resistance exercise protocol in lean children, obese children and lean adults. Pediatr. Exerc. Sci. 26(4), 444–454 (2014)PubMedCrossRefGoogle Scholar
  177. 177.
    D.A. Rubin, H.N. Pham, E.S. Adams, A.R. Tutor, A.C. Hackney, J.W. Coburn, D.A. Judelson, Endocrine response to acute resistance exercise in obese versus lean physically active men. Eur. J. Appl. Physiol. 115(6), 1359–1366 (2015)PubMedCrossRefGoogle Scholar
  178. 178.
    M.R. MohajeriTehrani, M. Tajvidi, S. Kahrizi, M. Hedayati, Does endurance training affect igf-1/igfbp-3 and insulin sensitivity in patients with type 2 diabetes? J. Sports Med. Phys. Fitness 55(9), 1004–1012 (2015)Google Scholar
  179. 179.
    B.C. Nindl, J.R. Pierce, Insulin-like growth factor I as a biomarker of health, fitness, and training status. Med. Sci. Sports Exerc. 42(1), 39–49 (2010)PubMedCrossRefGoogle Scholar
  180. 180.
    B.C. Nindl, Insulin-like growth factor-I, physical activity, and control of cellular anabolism. Med. Sci. Sports Exerc. 42(1), 35–38 (2010)PubMedCrossRefGoogle Scholar
  181. 181.
    E. Albrecht, F. Norheim, B. Thiede, T. Holen, T. Ohashi, L. Schering, S. Lee, J. Brenmoehl, S. Thomas, C.A. Drevon, H.P. Erickson, S. Maak, Irisin—a myth rather than an exercise-inducible myokine. Sci. Rep. 5, 8889 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    F. Sanchis-Gomar, R. Alis, G. Lippi, Circulating irisin detection: does it really work? Trends Endocrinol. Metab. 26(7), 335–336 (2015)PubMedCrossRefGoogle Scholar
  183. 183.
    M.P. Jedrychowski, C.D. Wrann, J.A. Paulo, K.K. Gerber, J. Szpyt, M.M. Robinson, K.S. Nair, S.P. Gygi, B.M. Spiegelman, Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell Metab. 22(4), 734–740 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    P. Bostrom, J. Wu, M.P. Jedrychowski, A. Korde, L. Ye, J.C. Lo, K.A. Rasbach, E.A. Bostrom, J.H. Choi, J.Z. Long, S. Kajimura, M.C. Zingaretti, B.F. Vind, H. Tu, S. Cinti, K. Hojlund, S.P. Gygi, B.M. Spiegelman, A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481(7382), 463–468 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    J. Wu, P. Bostrom, L.M. Sparks, L. Ye, J.H. Choi, A.H. Giang, M. Khandekar, K.A. Virtanen, P. Nuutila, G. Schaart, K. Huang, H. Tu, W.D. van Marken Lichtenbelt, J. Hoeks, S. Enerback, P. Schrauwen, B.M. Spiegelman, Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150(2), 366–376 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    F. Sanchis-Gomar, C. Perez-Quilis, The p38-PGC-1alpha-irisin-betatrophin axis: exploring new pathways in insulin resistance. Adipocyte 3(1), 67–68 (2014)PubMedCrossRefGoogle Scholar
  187. 187.
    S.S. Daskalopoulou, A.B. Cooke, Y.H. Gomez, A.F. Mutter, A. Filippaios, E.T. Mesfum, C.S. Mantzoros, Plasma irisin levels progressively increase in response to increasing exercise workloads in young, healthy, active subjects. Eur. J. Endocrinol. 171(3), 343–352 (2014)PubMedCrossRefGoogle Scholar
  188. 188.
    R.R. Kraemer, P. Shockett, N.D. Webb, U. Shah, V.D. Castracane, A transient elevated irisin blood concentration in response to prolonged, moderate aerobic exercise in young men and women. Horm. Metab. Res. 46(2), 150–154 (2014)PubMedGoogle Scholar
  189. 189.
    F. Norheim, T.M. Langleite, M. Hjorth, T. Holen, A. Kielland, H.K. Stadheim, H.L. Gulseth, K.I. Birkeland, J. Jensen, C.A. Drevon, The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 281(3), 739–749 (2014)PubMedCrossRefGoogle Scholar
  190. 190.
    F. Sanchis-Gomar, R. Alis, H. Pareja-Galeano, E. Sola, V.M. Victor, M. Rocha, A. Hernandez-Mijares, M. Romagnoli, Circulating irisin levels are not correlated with BMI, age, and other biological parameters in obese and diabetic patients. Endocrine 46(3), 674–677 (2014)PubMedCrossRefGoogle Scholar
  191. 191.
    A. Palermo, R. Strollo, E. Maddaloni, D. Tuccinardi, L. D’Onofrio, S.I. Briganti, G. Defeudis, M. De Pascalis, M.C. Lazzaro, G. Colleluori, S. Manfrini, P. Pozzilli, N. Napoli, Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin. Endocrinol. (Oxf.) 82(4), 615–619 (2015)CrossRefGoogle Scholar
  192. 192.
    A.D. Anastasilakis, S.A. Polyzos, P. Makras, A. Gkiomisi, I. Bisbinas, A. Katsarou, A. Filippaios, C.S. Mantzoros, Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months. Osteoporos. Int. 25(5), 1633–1642 (2014)PubMedCrossRefGoogle Scholar
  193. 193.
    G. Colaianni, C. Cuscito, T. Mongelli, A. Oranger, G. Mori, G. Brunetti, S. Colucci, S. Cinti, M. Grano, Irisin enhances osteoblast differentiation in vitro. Int. J. Endocrinol. 2014, 902186 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    M. Mountjoy, J. Sundgot-Borgen, L. Burke, S. Carter, N. Constantini, C. Lebrun, N. Meyer, R. Sherman, K. Steffen, R. Budgett, A. Ljungqvist, The IOC consensus statement: beyond the Female Athlete Triad-Relative Energy Deficiency in Sport (RED-S). Br. J. Sports Med. 48(7), 491–497 (2014)PubMedCrossRefGoogle Scholar
  195. 195.
    V. Singhal, E.A. Lawson, K.E. Ackerman, P.K. Fazeli, H. Clarke, H. Lee, K. Eddy, D.A. Marengi, N.P. Derrico, M.L. Bouxsein, M. Misra, Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates. PLoS ONE 9(6), e100218 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  196. 196.
    T. Klangjareonchai, H. Nimitphong, S. Saetung, N. Bhirommuang, R. Samittarucksa, S. Chanprasertyothin, R. Sudatip, B. Ongphiphadhanakul, Circulating sclerostin and irisin are related and interact with gender to influence adiposity in adults with prediabetes. Int. J. Endocrinol. 2014, 261545 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    B. Garcia-Fontana, R. Reyes-Garcia, S. Morales-Santana, V. Avila-Rubio, A. Munoz-Garach, P. Rozas-Moreno, M. Munoz-Torres, Relationship between myostatin and irisin in type 2 diabetes mellitus: a compensatory mechanism to an unfavourable metabolic state? Endocrine (2015). doi: 10.1007/s12020-015-0758-8 PubMedGoogle Scholar
  198. 198.
    G. Thomas, P. Moffatt, P. Salois, M.H. Gaumond, R. Gingras, E. Godin, D. Miao, D. Goltzman, C. Lanctot, Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype. J. Biol. Chem. 278(50), 50563–50571 (2003)PubMedCrossRefGoogle Scholar
  199. 199.
    H. Nishizawa, M. Matsuda, Y. Yamada, K. Kawai, E. Suzuki, M. Makishima, T. Kitamura, I. Shimomura, Musclin, a novel skeletal muscle-derived secretory factor. J. Biol. Chem. 279(19), 19391–19395 (2004)PubMedCrossRefGoogle Scholar
  200. 200.
    L.R. Potter, S. Abbey-Hosch, D.M. Dickey, Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr. Rev. 27(1), 47–72 (2006)PubMedCrossRefGoogle Scholar
  201. 201.
    K.J. Motyl, L.R. McCabe, A.V. Schwartz, Bone and glucose metabolism: a two-way street. Arch. Biochem. Biophys. 503(1), 2–10 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    A. Yasui, H. Nishizawa, Y. Okuno, K. Morita, H. Kobayashi, K. Kawai, M. Matsuda, K. Kishida, S. Kihara, Y. Kamei, Y. Ogawa, T. Funahashi, I. Shimomura, Foxo1 represses expression of musclin, a skeletal muscle-derived secretory factor. Biochem. Biophys. Res. Commun. 364(2), 358–365 (2007)PubMedCrossRefGoogle Scholar
  203. 203.
    R. Meeusen, Exercise, nutrition and the brain. Sports Med. 44(Suppl 1), S47–S56 (2014)PubMedCrossRefGoogle Scholar
  204. 204.
    K. Iizuka, T. Machida, M. Hirafuji, Skeletal muscle is an endocrine organ. J. Pharmacol. Sci. 125(2), 125–131 (2014)PubMedCrossRefGoogle Scholar
  205. 205.
    C. Camerino, M. Zayzafoon, M. Rymaszewski, J. Heiny, M. Rios, P.V. Hauschka, Central depletion of brain-derived neurotrophic factor in mice results in high bone mass and metabolic phenotype. Endocrinology 153(11), 5394–5405 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  206. 206.
    K.L. Szuhany, M. Bugatti, M.W. Otto, A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J. Psychiatr. Res. 60, 56–64 (2015)PubMedCrossRefGoogle Scholar
  207. 207.
    C. Phillips, M.A. Baktir, M. Srivatsan, A. Salehi, Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Front Cell Neurosci. 8, 170 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  208. 208.
    M. Goekint, K. De Pauw, B. Roelands, R. Njemini, I. Bautmans, T. Mets, R. Meeusen, Strength training does not influence serum brain-derived neurotrophic factor. Eur. J. Appl. Physiol. 110(2), 285–293 (2010)PubMedCrossRefGoogle Scholar
  209. 209.
    I. Bos, P. De Boever, L.I. Panis, R. Meeusen, Physical activity, air pollution and the brain. Sports Med. 44(11), 1505–1518 (2014)PubMedCrossRefGoogle Scholar
  210. 210.
    O. Kilian, S. Hartmann, N. Dongowski, S. Karnati, E. Baumgart-Vogt, F.V. Hartel, T. Noll, R. Schnettler, K.S. Lips, BDNF and its TrkB receptor in human fracture healing. Ann. Anat. 196(5), 286–295 (2014)PubMedCrossRefGoogle Scholar
  211. 211.
    T. Yamashiro, T. Fukunaga, K. Yamashita, N. Kobashi, T. Takano-Yamamoto, Gene and protein expression of brain-derived neurotrophic factor and TrkB in bone and cartilage. Bone 28(4), 404–409 (2001)PubMedCrossRefGoogle Scholar
  212. 212.
    J.Z. Ilich, O.J. Kelly, J.E. Inglis, L.B. Panton, G. Duque, M.J. Ormsbee, Interrelationship among muscle, fat, and bone: connecting the dots on cellular, hormonal, and whole body levels. Ageing Res. Rev. 15, 51–60 (2014)PubMedCrossRefGoogle Scholar
  213. 213.
    F. Sanchis-Gomar, R. Alis, E. Rampinini, A. Bosio, D. Ferioli, A. La Torre, J. Xu, V. Sansoni, S. Perego, M. Romagnoli, G. Lombardi, Adropin and apelin fluctuations throughout a season in professional soccer players: are they related with performance? Peptides 70, 32–36 (2015)PubMedCrossRefGoogle Scholar
  214. 214.
    S. Migliaccio, E.A. Greco, R. Fornari, L.M. Donini, A. Lenzi, Is obesity in women protective against osteoporosis? Diabetes Metab. Syndr. Obes. 4, 273–282 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  215. 215.
    J.J. Cao, Effects of obesity on bone metabolism. J. Orthop. Surg. Res. 6, 30 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Y. Kim, O.J. Kelly, J.Z. Ilich, Synergism of alpha-linolenic acid, conjugated linoleic acid and calcium in decreasing adipocyte and increasing osteoblast cell growth. Lipids 48(8), 787–802 (2013)PubMedCrossRefGoogle Scholar
  217. 217.
    A. Pratesi, F. Tarantini, M. Di Bari, Skeletal muscle: an endocrine organ. Clin. Cases Miner. Bone Metab. 10(1), 11–14 (2013)PubMedPubMedCentralGoogle Scholar
  218. 218.
    I. Beyer, T. Mets, I. Bautmans, Chronic low-grade inflammation and age-related sarcopenia. Curr. Opin. Clin. Nutr. Metab. Care 15(1), 12–22 (2012)PubMedCrossRefGoogle Scholar
  219. 219.
    B. Cannon, J. Nedergaard, Brown adipose tissue: function and physiological significance. Physiol. Rev. 84(1), 277–359 (2004)PubMedCrossRefGoogle Scholar
  220. 220.
    S. Boeuf, M. Klingenspor, N.L. Van Hal, T. Schneider, J. Keijer, S. Klaus, Differential gene expression in white and brown preadipocytes. Physiol. Genomics 7(1), 15–25 (2001)PubMedCrossRefGoogle Scholar
  221. 221.
    J. Kopecky, M. Baudysova, F. Zanotti, D. Janikova, S. Pavelka, J. Houstek, Synthesis of mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture. J. Biol. Chem. 265(36), 22204–22209 (1990)PubMedGoogle Scholar
  222. 222.
    P. Puigserver, B.M. Spiegelman, Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr. Rev. 24(1), 78–90 (2003)PubMedCrossRefGoogle Scholar
  223. 223.
    S. Gesta, Y.H. Tseng, C.R. Kahn, Developmental origin of fat: tracking obesity to its source. Cell 131(2), 242–256 (2007)PubMedCrossRefGoogle Scholar
  224. 224.
    H. Wallberg-Henriksson, J.R. Zierath, Metabolism. Exercise remodels subcutaneous fat tissue and improves metabolism. Nat. Rev. Endocrinol. 11(4), 198–200 (2015)PubMedCrossRefGoogle Scholar
  225. 225.
    E.D. Rosen, B.M. Spiegelman, What we talk about when we talk about fat. Cell 156(1–2), 20–44 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  226. 226.
    T.T. Tran, Y. Yamamoto, S. Gesta, C.R. Kahn, Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab. 7(5), 410–420 (2008)PubMedPubMedCentralCrossRefGoogle Scholar
  227. 227.
    K.I. Stanford, R.J. Middelbeek, K.L. Townsend, M.Y. Lee, H. Takahashi, K. So, K.M. Hitchcox, K.R. Markan, K. Hellbach, M.F. Hirshman, Y.H. Tseng, L.J. Goodyear, A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis. Diabetes 64(6), 2002–2014 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  228. 228.
    M. Bosma, Lipid homeostasis in exercise. Drug Discov. Today 19(7), 1019–1023 (2014)PubMedCrossRefGoogle Scholar
  229. 229.
    H. Wang, J. Ye, Regulation of energy balance by inflammation: common theme in physiology and pathology. Rev. Endocr. Metab. Disord. 16(1), 47–54 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    J. Himms-Hagen, Exercise in a pill: feasibility of energy expenditure targets. Curr. Drug Targets CNS Neurol. Disord. 3(5), 389–409 (2004)PubMedCrossRefGoogle Scholar
  231. 231.
    E. Wolsk, H. Mygind, T.S. Grondahl, B.K. Pedersen, G. van Hall, IL-6 selectively stimulates fat metabolism in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 299(5), E832–E840 (2010)PubMedCrossRefGoogle Scholar
  232. 232.
    M. Petruzzelli, M. Schweiger, R. Schreiber, R. Campos-Olivas, M. Tsoli, J. Allen, M. Swarbrick, S. Rose-John, M. Rincon, G. Robertson, R. Zechner, E.F. Wagner, A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 20(3), 433–447 (2014)PubMedCrossRefGoogle Scholar
  233. 233.
    R. Armamento-Villareal, C. Sadler, N. Napoli, K. Shah, S. Chode, D.R. Sinacore, C. Qualls, D.T. Villareal, Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training. J. Bone Miner. Res. 27(5), 1215–1221 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  234. 234.
    J.R. Berggren, M.W. Hulver, J.A. Houmard, Fat as an endocrine organ: influence of exercise. J. Appl. Physiol. 99(2), 757–764 (2005)PubMedCrossRefGoogle Scholar
  235. 235.
    E. Biver, C. Salliot, C. Combescure, L. Gossec, P. Hardouin, I. Legroux-Gerot, B. Cortet, Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 96(9), 2703–2713 (2011)PubMedCrossRefGoogle Scholar
  236. 236.
    G. Duque, B.R. Troen, Understanding the mechanisms of senile osteoporosis: new facts for a major geriatric syndrome. J. Am. Geriatr. Soc. 56(5), 935–941 (2008)PubMedCrossRefGoogle Scholar
  237. 237.
    K. Gunaratnam, C. Vidal, J.M. Gimble, G. Duque, Mechanisms of palmitate-induced lipotoxicity in human osteoblasts. Endocrinology 155(1), 108–116 (2014)PubMedCrossRefGoogle Scholar
  238. 238.
    M. Zaidi, C. Buettner, L. Sun, J. Iqbal, Minireview: the link between fat and bone: does mass beget mass? Endocrinology 153(5), 2070–2075 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  239. 239.
    J. Upadhyay, O.M. Farr, C.S. Mantzoros, The role of leptin in regulating bone metabolism. Metabolism 64(1), 105–113 (2015)PubMedCrossRefGoogle Scholar
  240. 240.
    J.F. Caro, J.W. Kolaczynski, M.R. Nyce, J.P. Ohannesian, I. Opentanova, W.H. Goldman, R.B. Lynn, P.L. Zhang, M.K. Sinha, R.V. Considine, Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 348(9021), 159–161 (1996)PubMedCrossRefGoogle Scholar
  241. 241.
    C.T. Montague, I.S. Farooqi, J.P. Whitehead, M.A. Soos, H. Rau, N.J. Wareham, C.P. Sewter, J.E. Digby, S.N. Mohammed, J.A. Hurst, C.H. Cheetham, A.R. Earley, A.H. Barnett, J.B. Prins, S. O’Rahilly, Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387(6636), 903–908 (1997)PubMedCrossRefGoogle Scholar
  242. 242.
    R.V. Considine, E.L. Considine, C.J. Williams, M.R. Nyce, S.A. Magosin, T.L. Bauer, E.L. Rosato, J. Colberg, J.F. Caro, Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J. Clin. Invest. 95(6), 2986–2988 (1995)PubMedPubMedCentralCrossRefGoogle Scholar
  243. 243.
    S.G. Hassink, D.V. Sheslow, E. de Lancey, I. Opentanova, R.V. Considine, J.F. Caro, Serum leptin in children with obesity: relationship to gender and development. Pediatrics 98(2 Pt 1), 201–203 (1996)PubMedGoogle Scholar
  244. 244.
    S. Takeda, F. Elefteriou, R. Levasseur, X. Liu, L. Zhao, K.L. Parker, D. Armstrong, P. Ducy, G. Karsenty, Leptin regulates bone formation via the sympathetic nervous system. Cell 111(3), 305–317 (2002)PubMedCrossRefGoogle Scholar
  245. 245.
    E. Sienkiewicz, F. Magkos, K.N. Aronis, M. Brinkoetter, J.P. Chamberland, S. Chou, K.M. Arampatzi, C. Gao, A. Koniaris, C.S. Mantzoros, Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women. Metabolism 60(9), 1211–1221 (2011)PubMedCrossRefGoogle Scholar
  246. 246.
    Y.S. Kim, J.S. Nam, D.W. Yeo, K.R. Kim, S.H. Suh, C.W. Ahn, The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males. Clin. Endocrinol. (Oxf.) 82(5), 686–694 (2015)CrossRefGoogle Scholar
  247. 247.
    C. Yang, J. Chen, F. Wu, J. Li, P. Liang, H. Zhang, H. Wang, Y. Li, Y. Wan, L. Qin, K.S. Liang, Z. Dai, Y. Li, Effects of 60-day head-down bed rest on osteocalcin, glycolipid metabolism and their association with or without resistance training. Clin. Endocrinol. (Oxf.) 81(5), 671–678 (2014)CrossRefGoogle Scholar
  248. 248.
    R.M. Campos, M.T. de Mello, L. Tock, P.L. Silva, D.C. Masquio, A. de Piano, P.L. Sanches, J. Carnier, F.C. Corgosinho, D. Foschini, S. Tufik, A.R. Damaso, Aerobic plus resistance training improves bone metabolism and inflammation in adolescents who are obese. J. Strength Cond. Res. 28(3), 758–766 (2014)PubMedCrossRefGoogle Scholar
  249. 249.
    J.S. Lim, G.C. Jang, K.R. Moon, E.Y. Kim, Combined aerobic and resistance exercise is effective for achieving weight loss and reducing cardiovascular risk factors without deteriorating bone health in obese young adults. Ann. Pediatr. Endocrinol. Metab. 18(1), 26–31 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  250. 250.
    K. Shah, R. Armamento-Villareal, N. Parimi, S. Chode, D.R. Sinacore, T.N. Hilton, N. Napoli, C. Qualls, D.T. Villareal, Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones. J. Bone Miner. Res. 26(12), 2851–2859 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  251. 251.
    V.D. Sherk, D.W. Barry, K.L. Villalon, K.C. Hansen, P. Wolfe, W.M. Kohrt, Bone loss over 1 year of training and competition in female cyclists. Clin. J. Sport Med. 24, 331–336 (2013)CrossRefGoogle Scholar
  252. 252.
    M.J. Santos, J.E. Fonseca, Metabolic syndrome, inflammation and atherosclerosis—the role of adipokines in health and in systemic inflammatory rheumatic diseases. Acta Reumatol. Port 34(4), 590–598 (2009)PubMedGoogle Scholar
  253. 253.
    M. Ruscica, L. Steffani, P. Magni, Adiponectin interactions in bone and cartilage biology and disease. Vitam. Horm. 90, 321–339 (2012)PubMedCrossRefGoogle Scholar
  254. 254.
    N. Sucunza, M.J. Barahona, E. Resmini, J.M. Fernandez-Real, W. Ricart, J. Farrerons, J. Rodriguez Espinosa, A.M. Marin, T. Puig, S.M. Webb, A link between bone mineral density and serum adiponectin and visfatin levels in acromegaly. J. Clin. Endocrinol. Metab. 94(10), 3889–3896 (2009)PubMedCrossRefGoogle Scholar
  255. 255.
    A. Lubkowska, A. Dobek, J. Mieszkowski, W. Garczynski, D. Chlubek, Adiponectin as a biomarker of osteoporosis in postmenopausal women: controversies. Dis. Markers 2014, 975178 (2014)PubMedPubMedCentralCrossRefGoogle Scholar
  256. 256.
    H.S. Berner, S.P. Lyngstadaas, A. Spahr, M. Monjo, L. Thommesen, C.A. Drevon, U. Syversen, J.E. Reseland, Adiponectin and its receptors are expressed in bone-forming cells. Bone 35(4), 842–849 (2004)PubMedCrossRefGoogle Scholar
  257. 257.
    Y. Shinoda, M. Yamaguchi, N. Ogata, T. Akune, N. Kubota, T. Yamauchi, Y. Terauchi, T. Kadowaki, Y. Takeuchi, S. Fukumoto, T. Ikeda, K. Hoshi, U.I. Chung, K. Nakamura, H. Kawaguchi, Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J. Cell. Biochem. 99(1), 196–208 (2006)PubMedCrossRefGoogle Scholar
  258. 258.
    H. Sadie-Van Gijsen, N.J. Crowther, F.S. Hough, W.F. Ferris, The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity. Cell. Mol. Life Sci. 70(13), 2331–2349 (2013)PubMedCrossRefGoogle Scholar
  259. 259.
    Y. Zhang, P. Zhou, J.W. Kimondo, Adiponectin and osteocalcin: relation to insulin sensitivity. Biochem. Cell Biol. 90(5), 613–620 (2012)PubMedCrossRefGoogle Scholar
  260. 260.
    S. Balducci, S. Zanuso, A. Nicolucci, F. Fernando, S. Cavallo, P. Cardelli, S. Fallucca, E. Alessi, C. Letizia, A. Jimenez, F. Fallucca, G. Pugliese, Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutr. Metab. Cardiovasc. Dis. 20(8), 608–617 (2010)PubMedCrossRefGoogle Scholar
  261. 261.
    S. Lim, S.H. Choi, I.K. Jeong, J.H. Kim, M.K. Moon, K.S. Park, H.K. Lee, Y.B. Kim, H.C. Jang, Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women. J. Clin. Endocrinol. Metab. 93(6), 2263–2268 (2008)PubMedCrossRefGoogle Scholar
  262. 262.
    Y.H. Ku, K.A. Han, H. Ahn, H. Kwon, B.K. Koo, H.C. Kim, K.W. Min, Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus. J. Int. Med. Res. 38(3), 782–791 (2010)PubMedCrossRefGoogle Scholar
  263. 263.
    K.A. Simpson, M.A. Singh, Effects of exercise on adiponectin: a systematic review. Obesity (Silver Spring) 16(2), 241–256 (2008)CrossRefGoogle Scholar
  264. 264.
    A.L. Parm, J. Jurimae, M. Saar, K. Parna, V. Tillmann, K. Maasalu, I. Neissaar, T. Jurimae, Plasma adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts. J. Bone Miner. Metab. 29(6), 717–724 (2011)PubMedCrossRefGoogle Scholar
  265. 265.
    J. Jurimae, T. Kums, T. Jurimae, Adipocytokine and ghrelin levels in relation to bone mineral density in physically active older women: longitudinal associations. Eur. J. Endocrinol. 160(3), 381–385 (2009)PubMedCrossRefGoogle Scholar
  266. 266.
    J. Jurimae, R. Ramson, J. Maestu, T. Jurimae, P.J. Arciero, W.A. Braun, L.M. LeMura, S.P. Von Duvillard, Interactions between adipose, bone, and muscle tissue markers during acute negative energy balance in male rowers. J. Sports Med. Phys. Fitness 51(2), 347–354 (2011)PubMedGoogle Scholar
  267. 267.
    A. Fukuhara, M. Matsuda, M. Nishizawa, K. Segawa, M. Tanaka, K. Kishimoto, Y. Matsuki, M. Murakami, T. Ichisaka, H. Murakami, E. Watanabe, T. Takagi, M. Akiyoshi, T. Ohtsubo, S. Kihara, S. Yamashita, M. Makishima, T. Funahashi, S. Yamanaka, R. Hiramatsu, Y. Matsuzawa, I. Shimomura, Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307(5708), 426–430 (2005)PubMedCrossRefGoogle Scholar
  268. 268.
    G. Lombardi, G. Banfi, Effects of sample matrix and storage conditions on full-length visfatin measurement in blood. Clin. Chim. Acta 440, 140–142 (2015)PubMedCrossRefGoogle Scholar
  269. 269.
    G. Sommer, A. Garten, S. Petzold, A.G. Beck-Sickinger, M. Bluher, M. Stumvoll, M. Fasshauer, Visfatin/PBEF/Nampt: structure, regulation and potential function of a novel adipokine. Clin. Sci. (Lond.) 115(1), 13–23 (2008)CrossRefGoogle Scholar
  270. 270.
    L. Thommesen, A.K. Stunes, M. Monjo, K. Grosvik, M.V. Tamburstuen, E. Kjobli, S.P. Lyngstadaas, J.E. Reseland, U. Syversen, Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism. J. Cell. Biochem. 99(3), 824–834 (2006)PubMedCrossRefGoogle Scholar
  271. 271.
    H. Xie, S.Y. Tang, X.H. Luo, J. Huang, R.R. Cui, L.Q. Yuan, H.D. Zhou, X.P. Wu, E.Y. Liao, Insulin-like effects of visfatin on human osteoblasts. Calcif. Tissue Int. 80(3), 201–210 (2007)PubMedCrossRefGoogle Scholar
  272. 272.
    A.R. Moschen, S. Geiger, R. Gerner, H. Tilg, Pre-B cell colony enhancing factor/NAMPT/visfatin and its role in inflammation-related bone disease. Mutat. Res. 690(1–2), 95–101 (2010)PubMedCrossRefGoogle Scholar
  273. 273.
    Y. Li, X. He, Y. Li, J. He, B. Anderstam, G. Andersson, U. Lindgren, Nicotinamide phosphoribosyltransferase (Nampt) affects the lineage fate determination of mesenchymal stem cells: a possible cause for reduced osteogenesis and increased adipogenesis in older individuals. J. Bone Miner. Res. 26(11), 2656–2664 (2011)PubMedCrossRefGoogle Scholar
  274. 274.
    S.R. Costford, S. Bajpeyi, M. Pasarica, D.C. Albarado, S.C. Thomas, H. Xie, T.S. Church, S.A. Jubrias, K.E. Conley, S.R. Smith, Skeletal muscle NAMPT is induced by exercise in humans. Am. J. Physiol. Endocrinol. Metab. 298(1), E117–E126 (2010)PubMedCrossRefGoogle Scholar
  275. 275.
    A. Ghanbari-Niaki, M. Saghebjoo, R. Soltani, J.P. Kirwan, Plasma visfatin is increased after high-intensity exercise. Ann. Nutr. Metab. 57(1), 3–8 (2010)PubMedCrossRefGoogle Scholar
  276. 276.
    D. Friebe, M. Neef, J. Kratzsch, S. Erbs, K. Dittrich, A. Garten, S. Petzold-Quinque, S. Bluher, T. Reinehr, M. Stumvoll, M. Bluher, W. Kiess, A. Korner, Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans. Diabetologia 54(5), 1200–1211 (2011)PubMedPubMedCentralCrossRefGoogle Scholar
  277. 277.
    I. Brema, M. Hatunic, F. Finucane, N. Burns, J.J. Nolan, D. Haider, M. Wolzt, B. Ludvik, Plasma visfatin is reduced after aerobic exercise in early onset type 2 diabetes mellitus. Diabetes Obes. Metab. 10(7), 600–602 (2008)PubMedCrossRefGoogle Scholar
  278. 278.
    M.L. Jorge, V.N. de Oliveira, N.M. Resende, L.F. Paraiso, A. Calixto, A.L. Diniz, E.S. Resende, E.R. Ropelle, J.B. Carvalheira, F.S. Espindola, P.T. Jorge, B. Geloneze, The effects of aerobic, resistance, and combined exercise on metabolic control, inflammatory markers, adipocytokines, and muscle insulin signaling in patients with type 2 diabetes mellitus. Metabolism 60(9), 1244–1252 (2011)PubMedCrossRefGoogle Scholar
  279. 279.
    G. Banfi, G. Lombardi, A. Colombini, G. Melegati, Whole-body cryotherapy in athletes. Sports Med. 40(6), 509–517 (2010)PubMedCrossRefGoogle Scholar
  280. 280.
    A. Lubkowska, W. Dudzinska, I. Bryczkowska, B. Dolegowska, Body composition, lipid profile, adipokine concentration, and antioxidant capacity changes during interventions to treat overweight with exercise programme and whole-body cryostimulation. Oxid. Med. Cell Longev. 2015, 803197 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  281. 281.
    S. Bo, G. Ciccone, I. Baldi, R. Gambino, C. Mandrile, M. Durazzo, L. Gentile, M. Cassader, P. Cavallo-Perin, G. Pagano, Plasma visfatin concentrations after a lifestyle intervention were directly associated with inflammatory markers. Nutr. Metab. Cardiovasc. Dis. 19(6), 423–430 (2009)PubMedCrossRefGoogle Scholar
  282. 282.
    S. Aggeloussi, A.A. Theodorou, V. Paschalis, M.G. Nikolaidis, I.G. Fatouros, E.O. Owolabi, D. Kouretas, Y. Koutedakis, A.Z. Jamurtas, Adipocytokine levels in children: effects of fatness and training. Pediatr. Exerc. Sci. 24(3), 461–471 (2012)PubMedCrossRefGoogle Scholar
  283. 283.
    J.P. Walhin, J.D. Richardson, J.A. Betts, D. Thompson, Exercise counteracts the effects of short-term overfeeding and reduced physical activity independent of energy imbalance in healthy young men. J. Physiol. 591(Pt 24), 6231–6243 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  284. 284.
    A. Petelin, M. Bizjak, M. Cernelic-Bizjak, M. Jurdana, T. Jakus, Z. Jenko-Praznikar, Low-grade inflammation in overweight and obese adults is affected by weight loss program. J. Endocrinol. Invest. 37(8), 745–755 (2014)PubMedCrossRefGoogle Scholar
  285. 285.
    J. Jurimae, R. Ramson, J. Maestu, P. Purge, T. Jurimae, P.J. Arciero, S.P. von Duvillard, Plasma visfatin and ghrelin response to prolonged sculling in competitive male rowers. Med. Sci. Sports Exerc. 41(1), 137–143 (2009)PubMedCrossRefGoogle Scholar
  286. 286.
    J.M. Haus, T.P. Solomon, C.M. Marchetti, V.B. O’Leary, L.M. Brooks, F. Gonzalez, J.P. Kirwan, Decreased visfatin after exercise training correlates with improved glucose tolerance. Med. Sci. Sports Exerc. 41(6), 1255–1260 (2009)PubMedCrossRefGoogle Scholar
  287. 287.
    E. Sliwicka, A. Nowak, W. Zep, P. Leszczynski, L. Pilaczynska-Szczesniak, Bone mass and bone metabolic indices in male master rowers. J. Bone Miner. Metab. 33(5), 540–546 (2015)PubMedCrossRefGoogle Scholar
  288. 288.
    H. Zhang, H. Xie, Q. Zhao, G.Q. Xie, X.P. Wu, E.Y. Liao, X.H. Luo, Relationships between serum adiponectin, apelin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in post-menopausal Chinese women. J. Endocrinol. Invest. 33(10), 707–711 (2010)PubMedCrossRefGoogle Scholar
  289. 289.
    X.D. Peng, H. Xie, Q. Zhao, X.P. Wu, Z.Q. Sun, E.Y. Liao, Relationships between serum adiponectin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in Chinese men. Clin. Chim. Acta 387(1–2), 31–35 (2008)PubMedCrossRefGoogle Scholar
  290. 290.
    M. Tohidi, S. Akbarzadeh, B. Larijani, M. Kalantarhormozi, A. Ostovar, M. Assadi, K. Vahdat, M. Farrokhnia, Z. Sanjdideh, R. Amirinejad, I. Nabipour, Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women. Bone 51(5), 876–881 (2012)PubMedCrossRefGoogle Scholar
  291. 291.
    R. Gruodyte, J. Jurimae, A. Cicchella, C. Stefanelli, C. Passariello, T. Jurimae, Adipocytokines and bone mineral density in adolescent female athletes. Acta Paediatr. 99(12), 1879–1884 (2010)PubMedCrossRefGoogle Scholar
  292. 292.
    G. Iacobellis, M. Iorio, N. Napoli, D. Cotesta, L. Zinnamosca, C. Marinelli, L. Petramala, S. Minisola, E. D’Erasmo, C. Letizia, Relation of adiponectin, visfatin and bone mineral density in patients with metabolic syndrome. J. Endocrinol. Invest. 34(1), e12–e15 (2011)PubMedCrossRefGoogle Scholar
  293. 293.
    P. Codoner-Franch, E. Alonso-Iglesias, Resistin: insulin resistance to malignancy. Clin. Chim. Acta 438, 46–54 (2015)PubMedCrossRefGoogle Scholar
  294. 294.
    K.W. Oh, W.Y. Lee, E.J. Rhee, K.H. Baek, K.H. Yoon, M.I. Kang, E.J. Yun, C.Y. Park, S.H. Ihm, M.G. Choi, H.J. Yoo, S.W. Park, The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clin. Endocrinol. (Oxf.) 63(2), 131–138 (2005)CrossRefGoogle Scholar
  295. 295.
    W. Pluskiewicz, P. Adamczyk, B. Marek, A. Czekajlo, B. Drozdzowska, D. Kajdaniuk, B. Kos-Kudla, W. Grzeszczak, Adiponectin and resistin in relationship with skeletal status in women from the RAC-OST-POL study. Endokrynol. Pol. 63(6), 427–431 (2012)PubMedGoogle Scholar
  296. 296.
    J. Mohiti-Ardekani, H. Soleymani-Salehabadi, M.B. Owlia, A. Mohiti, Relationships between serum adipocyte hormones (adiponectin, leptin, resistin), bone mineral density and bone metabolic markers in osteoporosis patients. J. Bone Miner. Metab. 32(4), 400–404 (2014)PubMedCrossRefGoogle Scholar
  297. 297.
    M.R. Sowers, R.P. Wildman, P. Mancuso, A.D. Eyvazzadeh, C.A. Karvonen-Gutierrez, E. Rillamas-Sun, M.L. Jannausch, Change in adipocytokines and ghrelin with menopause. Maturitas 59(2), 149–157 (2008)PubMedPubMedCentralCrossRefGoogle Scholar
  298. 298.
    A. Fisher, E. Southcott, R. Li, W. Srikusalanukul, M. Davis, P. Smith, Serum resistin in older patients with hip fracture: relationship with comorbidity and biochemical determinants of bone metabolism. Cytokine 56(2), 157–166 (2011)PubMedCrossRefGoogle Scholar
  299. 299.
    M.S. Albadah, H. Dekhil, S.A. Shaik, M.A. Alsaif, M. Shogair, S. Nawaz, A.A. Alfadda, Effect of weight loss on serum osteocalcin and its association with serum adipokines. Int. J. Endocrinol. 2015, 508532 (2015)PubMedPubMedCentralCrossRefGoogle Scholar
  300. 300.
    E. Hopps, B. Canino, G. Caimi, Effects of exercise on inflammation markers in type 2 diabetic subjects. Acta Diabetol. 48(3), 183–189 (2011)PubMedCrossRefGoogle Scholar
  301. 301.
    A. Jamurtas, A. Stavropoulos-Kalinoglou, S. Koutsias, Y. Koutedakis, I. Fatouros, Adiponectin, resistin and visfatin in childhood obesity and exercise. Pediatr. Exerc. Sci. (2015). doi: 10.1123/pes.2014-0072 PubMedGoogle Scholar
  302. 302.
    E. Joy, M.J. De Souza, A. Nattiv, M. Misra, N.I. Williams, R.J. Mallinson, J.C. Gibbs, M. Olmsted, M. Goolsby, G. Matheson, M. Barrack, L. Burke, B. Drinkwater, C. Lebrun, A.B. Loucks, M. Mountjoy, J. Nichols, J.S. Borgen, 2014 female athlete triad coalition consensus statement on treatment and return to play of the female athlete triad. Curr. Sports Med. Rep. 13(4), 219–232 (2014)PubMedCrossRefGoogle Scholar
  303. 303.
    J. Sundgot-Borgen, N.L. Meyer, T.G. Lohman, T.R. Ackland, R.J. Maughan, A.D. Stewart, W. Muller, How to minimise the health risks to athletes who compete in weight-sensitive sports review and position statement on behalf of the Ad Hoc Research Working Group on Body Composition, Health and Performance, under the auspices of the IOC Medical Commission. Br. J. Sports Med. 47(16), 1012–1022 (2013)PubMedCrossRefGoogle Scholar
  304. 304.
    E. Stice, K. South, H. Shaw, Future directions in etiologic, prevention, and treatment research for eating disorders. J. Clin. Child Adolesc. Psychol. 41(6), 845–855 (2012)PubMedCrossRefGoogle Scholar
  305. 305.
    J. Sundgot-Borgen, M.K. Torstveit, Aspects of disordered eating continuum in elite high-intensity sports. Scand. J. Med. Sci. Sports 20(Suppl 2), 112–121 (2010)PubMedCrossRefGoogle Scholar
  306. 306.
    G.N. Wade, J.E. Jones, Neuroendocrinology of nutritional infertility. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287(6), R1277–R1296 (2004)PubMedCrossRefGoogle Scholar
  307. 307.
    A. Nattiv, A.B. Loucks, M.M. Manore, C.F. Sanborn, J. Sundgot-Borgen, M.P. Warren, M. American, College of Sports, American College of Sports Medicine position stand. The female athlete triad. Med. Sci. Sports Exerc. 39(10), 1867–1882 (2007)PubMedCrossRefGoogle Scholar
  308. 308.
    J.L. Areta, L.M. Burke, M.L. Ross, D.M. Camera, D.W. West, E.M. Broad, N.A. Jeacocke, D.R. Moore, T. Stellingwerff, S.M. Phillips, J.A. Hawley, V.G. Coffey, Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J. Physiol. 591(Pt 9), 2319–2331 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  309. 309.
    D. Li, C.L. Hitchcock, S.I. Barr, T. Yu, J.C. Prior, Negative spinal bone mineral density changes and subclinical ovulatory disturbances—prospective data in healthy premenopausal women with regular menstrual cycles. Epidemiol. Rev. 36, 137–147 (2014)PubMedCrossRefGoogle Scholar
  310. 310.
    K.E. Ackerman, M. Putman, G. Guereca, A.P. Taylor, L. Pierce, D.B. Herzog, A. Klibanski, M. Bouxsein, M. Misra, Cortical microstructure and estimated bone strength in young amenorrheic athletes, eumenorrheic athletes and non-athletes. Bone 51(4), 680–687 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  311. 311.
    I. Lambrinoudaki, D. Papadimitriou, Pathophysiology of bone loss in the female athlete. Ann. N. Y. Acad. Sci. 1205, 45–50 (2010)PubMedCrossRefGoogle Scholar
  312. 312.
    A.D. Keen, B.L. Drinkwater, Irreversible bone loss in former amenorrheic athletes. Osteoporos. Int. 7(4), 311–315 (1997)PubMedCrossRefGoogle Scholar
  313. 313.
    M.T. Barrack, M.D. Van Loan, M.J. Rauh, J.F. Nichols, Physiologic and behavioral indicators of energy deficiency in female adolescent runners with elevated bone turnover. Am. J. Clin. Nutr. 92(3), 652–659 (2010)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Giovanni Lombardi
    • 1
    Email author
  • Fabian Sanchis-Gomar
    • 2
  • Silvia Perego
    • 1
  • Veronica Sansoni
    • 1
  • Giuseppe Banfi
    • 1
    • 3
  1. 1.Laboratory of Experimental Biochemistry & Molecular BiologyI.R.C.C.S. Istituto Ortopedico GaleazziMilanItaly
  2. 2.Research Institute Hospital 12 de Octubre (‘i + 12’)MadridSpain
  3. 3.Vita-Salute San Raffaele UniversityMilanItaly

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