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Bone turnover response is linked to both acute and established metabolic changes in ultra-marathon runners

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Abstract

Bone and energy metabolisms regulation depends on a two-way street aimed at regulating energy utilization. Mountain ultra-marathons are highly demanding aerobic performances that deeply affect the whole body homeostasis. In this study we aimed to investigate and characterize the metabolic profile (in terms of hormones involved in energy metabolism), the inflammatory adipokines, and the bone turnover; in particular the osteocalcin-mediated response has been compared in experienced mountain ultra-marathons runners versus control subjects. Serum concentrations of specific markers of bone turnover (pro-collagen type I N-terminal propeptide, carboxylated/undercarboxylated osteocalcin), measured by enzyme-linked immunosorbent assay, and metabolic hormones (C-peptide, insulin, glucagon, glucagon-like peptide, gastric-inhibitory peptide, ghrelin, leptin, resistin, and visfatin), measured by fluorescent-based multiplex assay, were compared before and after a 65 km mountain ultra-marathons in 17 trained runners and 12 age-matched controls characterized by a low physical activity profile. After the mountain ultra-marathons, runners experienced a reduction in pro-collagen type I N-terminal propeptide, though it remained higher than in controls; while carboxylated osteocalcin remained unchanged. Among the metabolic hormones, only glucagon and leptin were different between runners and controls at rest. C-peptide and leptin decreased after the mountain ultra-marathons in runners; while glucagon, glucagon-like peptide 1, resistin, and visfatin were all increased. Uncarboxylated osteocalcin (and uncarboxylated/carboxylated osteocalcin ratio) was decreased and this highly correlated with insulin and C-peptide levels. In conditions of high energy expenditure, homeostasis is maintained at expenses of bone metabolism. Changes in the uncarboxylated osteocalcin clearly mark the global energy needs of the body.

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References

  1. D.M. Bramble, D.E. Lieberman, Endurance running and the evolution of Homo. Nature 432(7015), 345–352 (2004)

    Article  CAS  PubMed  Google Scholar 

  2. World Health Organization. Global Database on Blood Safety: Report 2004–2005. World Health Organization, Geneva (2008)

    Google Scholar 

  3. Z.C. Thent, S. Das, L.J. Henry, Role of exercise in the management of diabetes mellitus: the global scenario. PLoS One 8(11), e80436 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  4. G. Lombardi, F. Sanchis-Gomar, S. Perego, V. Sansoni, G. Banfi, Implications of exercise-induced adipo-myokines in bone metabolism. Endocrine (2015). [Epub ahead of print]. doi:10.1007/s12020-015-0834-0

  5. H. Wallberg-Henriksson, J.R. Zierath, Metabolism. Exercise remodels subcutaneous fat tissue and improves metabolism. Nat. Rev. Endocrinol. 11(4), 198–200 (2015)

    Article  CAS  PubMed  Google Scholar 

  6. M. Gleeson, N.C. Bishop, D.J. Stensel, M.R. Lindley, S.S. Mastana, M.A. Nimmo, The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat. Rev. Immunol. 11(9), 607–615 (2011)

    Article  CAS  PubMed  Google Scholar 

  7. A. Sahin-Efe, F. Katsikeris, C.S. Mantzoros, Advances in adipokines. Metabolism 61(12), 1659–1665 (2012)

    Article  CAS  PubMed  Google Scholar 

  8. M.A. Nimmo, M. Leggate, J.L. Viana, J.A. King, The effect of physical activity on mediators of inflammation. Diabetes Obes. Metab. 15(Suppl 3), 51–60 (2013)

    Article  CAS  PubMed  Google Scholar 

  9. G. Banfi, G. Lombardi, A. Colombini, G. Lippi, Bone metabolism markers in sports medicine. Sports Med. 40, 697–714 (2010)

    Article  PubMed  Google Scholar 

  10. J. Xu, G. Lombardi, W. Jiao, G. Banfi, Effects of exercise on bone status in female subjects, from young girls to postmenopausal women: an overview of systematic reviews and meta-analyses. Sports Med. (2016). [Epub ahead of print]. doi:10.1007/s40279-016-0494-0

  11. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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)

    Article  CAS  PubMed  Google Scholar 

  13. 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)

    CAS  PubMed  Google Scholar 

  14. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. T. Otani, A. Mizokami, Y. Hayashi, J. Gao, Y. Mori, S. Nakamura, H. Takeuchi, M. Hirata, Signaling pathway for adiponectin expression in adipocytes by osteocalcin. Cell. Signal. 27(3), 532–544 (2015)

    Article  CAS  PubMed  Google Scholar 

  16. G. Lombardi, S. Perego, L. Luzi, G. Banfi, A four-season molecule: osteocalcin. Updates in its physiological roles. Endocrine 48, 394–404 (2015)

    Article  CAS  PubMed  Google Scholar 

  17. G. Vernillo, A. Savoldelli, A. Zignoli, P. Trabucchi, B. Pellegrini, G.P. Millet, F. Schena, Influence of the world’s most challenging mountain ultra-marathon on energy cost and running mechanics. Eur. J. Appl. Physiol. 114(5), 929–939 (2014)

    Article  PubMed  Google Scholar 

  18. G. Vernillo, N. Rinaldo, A. Giorgi, F. Esposito, P. Trabucchi, G.P. Millet, F. Schena, Changes in lung function during an extreme mountain ultramarathon. Scand. J. Med. Sci. Sports 25(4), e374–e380 (2015)

    Article  CAS  PubMed  Google Scholar 

  19. G. Vernillo, A. Savoldelli, A. Zignoli, S. Skafidas, A. Fornasiero, A. La Torre, L. Bortolan, B. Pellegrini, F. Schena, Energy cost and kinematics of level, uphill and downhill running: fatigue-induced changes after a mountain ultramarathon. J. Sports Sci. 33(19), 1998–2005 (2015)

    Article  PubMed  Google Scholar 

  20. G.P. Millet, G.Y. Millet, Ultramarathon is an outstanding model for the study of adaptive responses to extreme load and stress. BMC Med. 10, 77 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  21. I. Mujika, S. Padilla, Scientific bases for precompetition tapering strategies. Med. Sci. Sports Exerc. 35(7), 1182–1187 (2003)

    Article  PubMed  Google Scholar 

  22. ACSM: American College of Sports Medicine. ACSM’s Guidelines for Exercise Testing and Prescription, 8th edn., Philadephia, PA (2010)

  23. G. Lombardi, P. Lanteri, A. Colombini, G. Banfi, Blood biochemical markers of bone turnover: pre-analytical and technical aspects of sample collection and handling. Clin. Chem. Lab. Med. 50(5), 771–789 (2012)

    Article  CAS  PubMed  Google Scholar 

  24. F. Curtin, P. Schulz, Multiple correlations and Bonferroni’s correction. Biol. Psychiatry 44(8), 775–777 (1998)

    Article  CAS  PubMed  Google Scholar 

  25. C. Fiuza-Luces, J.R. Ruiz, G. Rodriguez-Romo, C. Santiago, F. Gomez-Gallego, T. Yvert, A. Cano-Nieto, N. Garatachea, M. Moran, A. Lucia, Are ‘endurance’ alleles ‘survival’ alleles? Insights from the ACTN3 R577X polymorphism. PLoS One 6(3), e17558 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. S.L. Booth, A. Centi, S.R. Smith, C. Gundberg, The role of osteocalcin in human glucose metabolism: marker or mediator? Nat. Rev. Endocrinol. 9(1), 43–55 (2013)

    Article  CAS  PubMed  Google Scholar 

  27. 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)

    Article  PubMed  PubMed Central  Google Scholar 

  28. K. Kerschan-Schindl, M. Thalmann, G.H. Sodeck, K. Skenderi, A.L. Matalas, S. Grampp, C. Ebner, P. Pietschmann, A 246-km continuous running race causes significant changes in bone metabolism. Bone 45(6), 1079–1083 (2009)

    Article  CAS  PubMed  Google Scholar 

  29. 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)

    Article  CAS  PubMed  Google Scholar 

  30. T. Hew-Butler, K.J. Stuempfle, M.D. Hoffman, Bone: an acute buffer of plasma sodium during exhaustive exercise? Horm. Metab. Res. 45(10), 697–700 (2013)

    Article  CAS  PubMed  Google Scholar 

  31. T. Bobbert, K. Mai, L. Brechtel, H.M. Schulte, B. Weger, A.F. Pfeiffer, J. Spranger, S. Diederich, Leptin and endocrine parameters in marathon runners. Int. J. Sports Med. 33(3), 244–248 (2012)

    Article  CAS  PubMed  Google Scholar 

  32. L.M. Burke, Nutrition strategies for the marathon: fuel for training and racing. Sports Med. 37(4-5), 344–347 (2007)

    Article  PubMed  Google Scholar 

  33. T. Montalcini, P. Gallotti, A. Coppola, V. Zambianchi, M. Fodaro, E. Galliera, M.G. Marazzi, S. Romeo, S. Giannini, M.M. Corsi Romanelli, A. Pujia, C. Gazzaruso, Association between low C-peptide and low lumbar bone mineral density in postmenopausal women without diabetes. Osteoporos. Int. 26(5), 1639–1646 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. D. Hansen, R. Meeusen, A. Mullens, P. Dendale, Effect of acute endurance and resistance exercise on endocrine hormones directly related to lipolysis and skeletal muscle protein synthesis in adult individuals with obesity. Sports Med. 42(5), 415–431 (2012)

    Article  PubMed  Google Scholar 

  35. G. Banfi, A. Colombini, G. Lombardi, A. Lubkowska, Metabolic markers in sports medicine. Adv. Clin. Chem. 56, 1–54 (2012)

    Article  CAS  PubMed  Google Scholar 

  36. J. Pettus, I. Hirsch, S. Edelman, GLP-1 agonists in type 1 diabetes. Clin. Immunol. 149(3), 317–323 (2013)

    Article  CAS  PubMed  Google Scholar 

  37. T. Yada, B. Damdindorj, R.S. Rita, T. Kurashina, A. Ando, M. Taguchi, M. Koizumi, H. Sone, M. Nakata, M. Kakei, K. Dezaki, Ghrelin signalling in beta-cells regulates insulin secretion and blood glucose. Diabetes Obes. Metab. 16(Suppl 1), 111–117 (2014)

    Article  CAS  PubMed  Google Scholar 

  38. G. Fernandez-Formoso, S. Perez-Sieira, D. Gonzalez-Touceda, C. Dieguez, S. Tovar, Leptin, 20 years of searching for glucose homeostasis. Life Sci. 140, 4–9 (2015)

    Article  CAS  PubMed  Google Scholar 

  39. M. Zaccaria, A. Ermolao, E. Brugin, M. Bergamin, Plasma leptin and energy expenditure during prolonged, moderate intensity, treadmill exercise. J. Endocrinol. Invest. 36(6), 396–401 (2013)

    CAS  PubMed  Google Scholar 

  40. N.D. Roupas, I. Mamali, S. Maragkos, L. Leonidou, A.K. Armeni, G.K. Markantes, A. Tsekouras, G.C. Sakellaropoulos, K.B. Markou, N.A. Georgopoulos, The effect of prolonged aerobic exercise on serum adipokine levels during an ultra-marathon endurance race. Hormones (Athens) 12(2), 275–282 (2013)

    Article  Google Scholar 

  41. 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)

    Article  PubMed  Google Scholar 

  42. 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)

    Article  CAS  PubMed  Google Scholar 

  43. B. Lecka-Czernik, C.J. Rosen, Energy excess, glucose utilization and skeletal remodeling: new insights. J. Bone Miner. Res. 30(8), 1356–1361 (2015)

    Article  CAS  PubMed  Google Scholar 

  44. J. Upadhyay, O.M. Farr, C.S. Mantzoros, The role of leptin in regulating bone metabolism. Metabolism 64(1), 105–113 (2015)

    Article  CAS  PubMed  Google Scholar 

  45. P.J. Delhanty, B.C. van der Eerden, J.P. van Leeuwen, Ghrelin and bone. Biofactors 40(1), 41–48 (2014)

    Article  CAS  PubMed  Google Scholar 

  46. R. Corsetti, G. Lombardi, P. Lanteri, A. Colombini, R. Graziani, G. Banfi, Haematological and iron metabolism parameters in professional cyclists during the Giro d’Italia 3-weeks stage race. Clin. Chem. Lab. Med. 50(5), 949–956 (2012)

    Article  CAS  PubMed  Google Scholar 

  47. G. Banfi, G.S. Roi, A. Dolci, Erythrocytes, haemoglobin and packed cell volume in athletes performing races in altitude environment. Haematologica 85(E-letters), E12 (2000)

    CAS  PubMed  Google Scholar 

  48. G. Banfi, G.S. Roi, A. Dolci, D. Susta, Behaviour of haematological parameters in athletes performing marathons and ultramarathons in altitude (‘skyrunners’). Clin. Lab. Haematol. 26(6), 373–377 (2004)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work has been funded by the Italian Ministry of Health and the Italian Ministry of Education, University, and Research. The authors are indebted to Jincheng Xu, PhD, and Spyros Skafidas, MD, for their invaluable aid in performing and managing blood samplings. The authors would like to express their gratitude to Alberto Fondriest, Herbert Lorenzoni, Roberta Casagranda, and the Vigolana Trail® Organizing Committee. Finally, special thanks to the participants.

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Authors and Affiliations

  1. Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, Milano, Italy

    Veronica Sansoni, Silvia Perego, Giuseppe Banfi & Giovanni Lombardi

  2. Department of Biomedical Sciences for Health, University of Milano, Milano, Italy

    Gianluca Vernillo, Giampiero Merati & Antonio La Torre

  3. CeRiSM, Research Centre “Sport, Mountain and Health”, University of Verona, Rovereto, Italy

    Gianluca Vernillo & Federico Schena

  4. Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada

    Gianluca Vernillo

  5. Department of Biosciences, Università degli Studi di Milano, Milano, Italy

    Andrea Barbuti

  6. Interuniversity Centre for Molecular Medicine and Applied Biophysics (CIMMBA), Università degli Studi di Milano, Milano, Italy

    Andrea Barbuti

  7. IRCCS Fondazione Don Carlo Gnocchi, Milano, Italy

    Giampiero Merati

  8. Department of Neurological and Movement Sciences, Università degli Studi di Verona, Verona, Italy

    Federico Schena

  9. Vita-Salute San Raffaele University, Milano, Italy

    Giuseppe Banfi

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  1. Veronica Sansoni
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  2. Gianluca Vernillo
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Correspondence to Giovanni Lombardi.

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Sansoni, V., Vernillo, G., Perego, S. et al. Bone turnover response is linked to both acute and established metabolic changes in ultra-marathon runners. Endocrine 56, 196–204 (2017). https://doi.org/10.1007/s12020-016-1012-8

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