Metabolismo óseo en ciclistas adolescentes

Laburpena

La práctica del ciclismo aporta grandes beneficios para la salud ya que produce una mejora de la condición física general, principalmente a través de un aumento en el consumo máximo de oxígeno, un aumento de la masa muscular, además de prevenir la acumulación de grasa corporal, lo que lleva a disminuir los riesgos de padecer enfermedades cardiovasculares y diferentes tipos de cáncer, entre otras enfermedades. Sin embargo, en términos de masa ósea, las evidencias parecen indicar que presenta un efecto neutro o incluso negativo, ya que un alto porcentaje de los ciclistas profesionales presentan osteopenia en la edad adulta. En lo que respecta a la práctica de actividad física y deportiva en niños y adolescentes, se ha determinado que es beneficiosa para la salud del hueso, aunque no todos los deportes tienen el mismo efecto, siendo los deportes de impacto los que presentan un mayor efecto osteogénico. El ciclismo es considerado un deporte de bajo impacto y varios estudios señalan que los ciclistas adolescentes podrían presentar niveles de masa ósea inferiores a los obtenidos por sujetos de su misma edad. En este sentido, el estudio de los marcadores metabólicos del hueso y de la vitamina D en ciclistas adolescentes podría aportar información relevante sobre los procesos de formación y resorción ósea en este grupo poblacional. Por lo tanto, el objetivo principal de la presente Tesis Doctoral ha sido mejorar el conocimiento sobre el efecto que tiene la práctica del ciclismo sobre el metabolismo óseo en una muestra española de adolescentes ciclistas entrenados. El estudio abarca una parte teórica de análisis y revisión de la literatura, plasmado en una revisión sistemática, y otra parte experimental en la que participaron 22 ciclistas varones adolecentes, junto a 20 adolescentes varones sanos normo-activos, que constituyeron el grupo control. Se evaluó su composición corporal mediante antropometría; los marcadores metabólicos objeto de estudio, es decir, la osteocalcina (OC), el propéptido aminoterminal del procolágeno de tipo I (PINP), y el isómero beta de telopéptido carboxilo terminal del colágeno tipo 1 (beta-CTx), se midieron en suero y se determinaron por inmunoensayo de electroquimioluminiscencia (ECLIA), cuantificándose además en plasma la forma activa de la vitamina D [25(OH)D], mediante ensayo por inmunoabsorción ligado a enzimas (ELISA). Los resultados de este documento muestran que los valores de los marcadores óseos varían en función de la edad tanto en ciclistas como en controles, siendo los sujetos más jóvenes los que presentan un mayor remodelado óseo en relación a los más mayores. En el caso de los ciclistas, los tres marcadores analizados, es decir, los marcadores de formación OC y PINP, y el marcador de resorción beta-CTx, son mayores en los sujetos más jóvenes (menores de 17 años). En el grupo control, únicamente el marcador de formación PINP difiere en función de la edad, siendo mayor en los sujetos más jóvenes (menores de 17 años). Los ciclistas menores de 17 años presentan valores más altos en los marcadores de formación (OC, PINP) y en la forma activa de la vitamina D, respecto a los controles de su misma edad. Se encontró una interacción significativa de edad x grupo en los tres marcadores analizados. En el periodo de 1 año de duración disminuyen los marcadores de formación (OC y PINP) tanto en ciclistas como en controles. En relación a la vitamina D, sólo disminuye en los ciclistas, pasado un año. En conclusión, los resultados sugieren que el remodelado óseo disminuye a lo largo de la adolescencia, tanto en los ciclistas como en los controles normo-activos. Por otro lado, la disminución de la vitamina D en los ciclistas adolescentes, tras un año de seguimiento, podría ser un indicador evaluable para predecir posibles deficiencias en la salud ósea, aunque serían necesarios más estudios que lo corroborasen. Referencias: 1. Adachi JD, Adami S, Gehlbach S, Anderson FA, Jr., Boonen S, Chapurlat RD, Compston JE, Cooper C, Delmas P, Diez-Perez A, Greenspan SL, Hooven FH, LaCroix AZ, Lindsay R, Netelenbos JC, Wu O, Pfeilschifter J, Roux C, Saag KG, Sambrook PN, Silverman S, Siris ES, Nika G, Watts NB. Impact of prevalent fractures on quality of life: baseline results from the global longitudinal study of osteoporosis in women. Mayo Clin Proc 2010; 85(9): 806-13. 2. Algarra JL. Ciclismo, 1ª edn Comité Olímpico Español: Madrid, 1990. 3. Anonymous. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. The American journal of medicine 1993; 94(6): 646-50. 4. Ashizawa N, Ouchi G, Fujimura R, Yoshida Y, Tokuyama K, Suzuki M. Effects of a single bout of resistance exercise on calcium and bone metabolism in untrained young males. Calcified tissue international 1998; 62(2): 104-8. 5. Bachrach LK. Acquisition of optimal bone mass in childhood and adolescence. Trends in endocrinology and metabolism: TEM 2001; 12(1): 22-8. 6. Bailey DA, Faulkner RA, McKay HA. Growth, physical activity, and bone mineral acquisition. Exerc Sport Sci Rev 1996; 24: 233-66. 7. Bailey DA, McKay HA, Mirwald RL, Crocker PR, Faulkner RA. A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of Saskatchewan bone mineral accrual study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1999; 14(10): 1672-9. 8. Banfi G, Dolci A. Preanalytical phase of sport biochemistry and haematology. The Journal of sports medicine and physical fitness 2003; 43(2): 223-30. 9. Banfi G, Lombardi G, Colombini A, Lippi G. Bone metabolism markers in sports medicine. Sports Med 2010; 40(8): 697-714. 10. Barrack MT, Van Loan MD, Rauh MJ, Nichols JF. Physiologic and behavioral indicators of energy deficiency in female adolescent runners with elevated bone turnover. Am J Clin Nutr 2010; 92(3): 652-9. 11. Beck TJ, Oreskovic TL, Stone KL, Ruff CB, Ensrud K, Nevitt MC, Genant HK, Cummings SR. Structural adaptation to changing skeletal load in the progression toward hip fragility: the study of osteoporotic fractures. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2001; 16(6): 1108-19. 12. Bell NH. Assays for osteocalcin: all are not equal. The Journal of laboratory and clinical medicine 1997; 129(4): 396-7. 13. Bjarnason NH, Christiansen C. Early response in biochemical markers predicts long-term response in bone mass during hormone replacement therapy in early postmenopausal women. Bone 2000; 26(6): 561-9. 14. Bouee S, Lafuma A, Fagnani F, Meunier PJ, Reginster JY. Estimation of direct unit costs associated with non-vertebral osteoporotic fractures in five European countries. Rheumatol Int 2006; 26(12): 1063-72. 15. Cameron N, Tanner JM, Whitehouse RH. A longitudinal analysis of the growth of limb segments in adolescence. Annals of human biology 1982; 9(3): 211-20. 16. Campion F, Nevill AM, Karlsson MK, Lounana J, Shabani M, Fardellone P, Medelli J. Bone status in professional cyclists. Int J Sports Med 2010; 31(7): 511-5. 17. Carmeliet G, Verstuyf A, Daci E, Bouillon R. The vitamin D hormone and its nuclear receptor: genomic mechanisms involved in bone biology. In: Seibel M, Robins S, Bilezikian J (eds). Dynamics of bone and cartilage metabolism: San Diego, California: Academic Press, 1999. 18. Castel H BD, Sherf M, Liel Y. Awareness of osteoporosis and compliance with management guidelines in patients with newly diagnosed low-impact fractures. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2001; 12: 559-64. 19. Collins E, Norman A. Vitamin D. In: Rucker R, Suttie J, McCormick D, Machlin L (eds). Handbook of vitamins, 3th ed. edn: New York: Marcel Dekker, Inc, 2001, pp 51-113. 20. Cooper C, Cawley M, Bhalla A, Egger P, Ring F, Morton L, Barker D. Childhood growth, physical activity, and peak bone mass in women. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1995; 10(6): 940-7. 21. Cooper C, Fall C, Egger P, Hobbs R, Eastell R, Barker D. Growth in infancy and bone mass in later life. Annals of the rheumatic diseases 1997; 56(1): 17-21. 22. Creighton DL, Morgan AL, Boardley D, Brolinson PG. Weight-bearing exercise and markers of bone turnover in female athletes. J Appl Physiol (1985) 2001; 90(2): 565-70. 23. CSD. Federaciones Deportivas Españolas: http://www.csd.gob.es/csd/asociaciones/1fedagclub/03Lic/, 2015 24. Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TM. Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet 1993; 341(8837): 72-5. 25. Cheng S, Volgyi E, Tylavsky FA, Lyytikainen A, Tormakangas T, Xu L, Cheng SM, Kroger H, Alen M, Kujala UM. Trait-specific tracking and determinants of body composition: a 7-year follow-up study of pubertal growth in girls. BMC medicine 2009; 7: 5. 26. Christo K, Prabhakaran R, Lamparello B, Cord J, Miller KK, Goldstein MA, Gupta N, Herzog DB, Klibanski A, Misra M. Bone metabolism in adolescent athletes with amenorrhea, athletes with eumenorrhea, and control subjects. Pediatrics 2008; 121(6): 1127-36. 27. Darelid A, Nilsson M, Kindblom JM, Mellstrom D, Ohlsson C, Lorentzon M. Bone turnover markers predict bone mass development in young adult men: a five-year longitudinal study. The Journal of clinical endocrinology and metabolism 2015; 100(4): 1460-8. 28. Delmas PD. Biochemical markers of bone turnover for the clinical investigation of osteoporosis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 1993; 3 Suppl 1: 81-6. 29. Demay MB, Kiernan MS, DeLuca HF, Kronenberg HM. Sequences in the human parathyroid hormone gene that bind the 1,25-dihydroxyvitamin D3 receptor and mediate transcriptional repression in response to 1,25-dihydroxyvitamin D3. Proceedings of the National Academy of Sciences of the United States of America 1992; 89(17): 8097-101. 30. Derman O, Cinemre A, Kanbur N, Dogan M, Kilic M, Karaduman E. Effect of swimming on bone metabolism in adolescents. The Turkish journal of pediatrics 2008; 50(2): 149-54. 31. Díaz M, García JJ, Carrasco JL, Honorato J, Pérez R, Rapado A. Prevalencia de osteoporosis determinada por densitometría en la población femenina española. Med Clin (Barc) 2001; 116: 86-8. 32. Duncan CS, Blimkie CJ, Cowell CT, Burke ST, Briody JN, Howman-Giles R. Bone mineral density in adolescent female athletes: relationship to exercise type and muscle strength. Medicine and science in sports and exercise 2002; 34(2): 286-94. 33. Duppe H, Cooper C, Gardsell P, Johnell O. The relationship between childhood growth, bone mass, and muscle strength in male and female adolescents. Calcified tissue international 1997; 60(5): 405-9. 34. Eapen E, Grey V, Don-Wauchope A, Atkinson SA. Bone Health in Childhood: Usefulness of Biochemical Biomarkers. Ejifcc 2008; 19(2): 123-36. 35. Fiore CE, Dieli M, Vintaloro G, Gibilaro M, Giacone G, Cottini E. Body composition and bone mineral density in competitive athletes in different sports. International journal of tissue reactions 1996; 18(4-6): 121-4. 36. Garnero P, Gineyts E, Arbault P, Christiansen C, Delmas P. Different effects of bisphosphonate and estrogen therapy on free and peptide-bound bone cross-links excretion. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1995; 10: 641-9. 37. Gass M, Dawson-Hughes B. Preventing osteoporosis-related fractures: an overview. The American journal of medicine 2006; 119(4 Suppl 1): S3-S11. 38. Gomez-Bruton A, Gonzalez-Aguero A, Olmedillas H, Gomez-Cabello A, Matute-Llorente A, Julian-Almarcegui C, Casajus JA, Vicente-Rodriguez G. Do calcium and vitamin D intake influence the effect of cycling on bone mass through adolescence? Nutr Hosp 2013; 28(4): 1136-9. 39. Gonzalez-Aguero A, Olmedillas H, Gomez-Cabello A, Casajus JA, Vicente-Rodriguez G. Bone Structure and Geometric Properties at the Radius and Tibia in Adolescent Endurance-Trained Cyclists. Clin J Sport Med 2016. 40. Gonzalez-Aguero A, Vicente-Rodriguez G, Casajus JA. Ciclismo y salud ósea del adolescente. Apunts Med Esport 2012; 47(176): 169. 41. Gonzalez-Aguero A, Vicente-Rodriguez G, Gomez-Cabello A, Ara I, Moreno LA, Casajus JA. A 21-week bone deposition promoting exercise programme increases bone mass in young people with Down syndrome. Dev Med Child Neurol 2012; 54(6): 552-6. 42. Gracia-Marco L, Ortega FB, Jimenez-Pavon D, Rodriguez G, Valtuena J, Diaz-Martinez AE, Gonzalez-Gross M, Castillo MJ, Vicente-Rodriguez G, Moreno LA. Contribution of bone turnover markers to bone mass in pubertal boys and girls. Journal of pediatric endocrinology & metabolism : JPEM 2011; 24(11-12): 971-4. 43. Gracia-Marco L, Vicente-Rodriguez G, Valtuena J, Rey-Lopez JP, Diaz Martinez AE, Mesana MI, Widhalm K, Ruiz JR, Gonzalez-Gross M, Castillo MJ, Moreno LA. Bone mass and bone metabolism markers during adolescence: The HELENA Study. Horm Res Paediatr 2010; 74(5): 339-50. 44. Guillaume G, Chappard D, Audran M. Evaluation of the bone status in high-level cyclists. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry 2012; 15(1): 103-7. 45. Haentjens P, Magaziner J, Colon-Emeric CS, Vanderschueren D, Milisen K, Velkeniers B, Boonen S. Meta-analysis: excess mortality after hip fracture among older women and men. Annals of internal medicine 2010; 152(6): 380-90. 46. Hauschka PV, Lian JB, Cole DE, Gundberg CM. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiological reviews 1989; 69(3): 990-1047. 47. Heinonen A, Oja P, Kannus P, Sievanen H, Manttari A, Vuori I. Bone mineral density of female athletes in different sports. Bone and mineral 1993; 23(1): 1-14. 48. Herrmann M, Muller M, Scharhag J, Sand-Hill M, Kindermann W, Herrmann W. The effect of endurance exercise-induced lactacidosis on biochemical markers of bone turnover. Clin Chem Lab Med 2007; 45(10): 1381-9. 49. Hinton PS, Rolleston A, Rehrer NJ, Hellemans IJ, Miller BF. Bone formation is increased to a greater extent than bone resorption during a cycling stage race. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 2010; 35(3): 344-9. 50. Holroyd C, Cooper C, Dennison E. Epidemiology of osteoporosis. Best Practice & Research Clinical Endocrinology & Metabolism 2008; 22(5): 671-685. 51. Ilich JZ, Skugor M, Hangartner T, Baoshe A, Matkovic V. Relation of nutrition, body composition and physical activity to skeletal development: a cross-sectional study in preadolescent females. Journal of the American College of Nutrition 1998; 17(2): 136-47. 52. Kanis JA, Melton LJ, 3rd, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1994; 9(8): 1137-41. 53. Kannus P, Haapasalo H, Sankelo M, Sievanen H, Pasanen M, Heinonen A, Oja P, Vuori I. Effect of starting age of physical activity on bone mass in the dominant arm of tennis and squash players. Annals of internal medicine 1995; 123(1): 27-31. 54. Kelly PJ, Eisman JA, Sambrook PN. Interaction of genetic and environmental influences on peak bone density. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 1990; 1(1): 56-60. 55. Kohrt WM, Bloomfield SA, Little KD, Nelson ME, Yingling VR. American College of Sports Medicine Position Stand: physical activity and bone health. Medicine and science in sports and exercise 2004; 36(11): 1985-96. 56. Lee NK, Karsenty G. Reciprocal regulation of bone and energy metabolism. Trends in endocrinology and metabolism: TEM 2008; 19(5): 161-6. 57. Lehtonen-Veromaa M, Mottonen T, Irjala K, Nuotio I, Leino A, Viikari J. A 1-year prospective study on the relationship between physical activity, markers of bone metabolism, and bone acquisition in peripubertal girls. The Journal of clinical endocrinology and metabolism 2000; 85(10): 3726-32. 58. Lombardi G, Lanteri P, Graziani R, Colombini A, Banfi G, Corsetti R. Bone and energy metabolism parameters in professional cyclists during the Giro d'Italia 3-weeks stage race. PloS one 2012; 7(7): e42077. 59. Looker AC, Orwoll ES, Johnston CC, Jr., Lindsay RL, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP. Prevalence of low femoral bone density in older U.S. adults from NHANES III. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1997; 12(11): 1761-8. 60. Lu J, Shin Y, Yen MS, Sun SS. Peak Bone Mass and Patterns of Change in Total Bone Mineral Density and Bone Mineral Contents From Childhood Into Young Adulthood. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry 2016; 19(2): 180-91. 61. Maimoun L, Coste O, Mariano-Goulart D, Galtier F, Mura T, Philibert P, Briot K, Paris F, Sultan C. In peripubertal girls, artistic gymnastics improves areal bone mineral density and femoral bone geometry without affecting serum OPG/RANKL levels. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2011; 22(12): 3055-66. 62. Maimoun L, Coste O, Mura T, Philibert P, Galtier F, Mariano-Goulart D, Paris F, Sultan C. Specific bone mass acquisition in elite female athletes. The Journal of clinical endocrinology and metabolism 2013; 98(7): 2844-53. 63. Maimoun L, Coste O, Philibert P, Briot K, Mura T, Galtier F, Castes-de-Paulet B, Mariano-Goulart D, Sultan C, Paris F. Testosterone secretion in elite adolescent swimmers does not modify bone mass acquisition: a 1-year follow-up study. Fertil Steril 2013; 99(1): 270-8. 64. Maïmoun L, Coste O, Philibert P, Briot K, Mura T, Galtier F, Mariano-Goulart D, Paris F, Sultan C. Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry. Metabolism 2013; 62(8): 1088-1098. 65. Maimoun L, Mariano-Goulart D, Couret I, Manetta J, Peruchon E, Micallef JP, Verdier R, Rossi M, Leroux JL. Effects of physical activities that induce moderate external loading on bone metabolism in male athletes. J Sports Sci 2004; 22(9): 875-83. 66. Maïmoun L, Mariano-Goulart D, Couret I, Manetta J, Peruchon E, Micallef JP, Verdier R, Rossi M, Leroux JL. Effects of physical activities that induce moderate external loading on bone metabolism in male athletes. Journal of Sports Sciences 2004; 22(9): 875-883. 67. Malina RM, Bouchard C, Bar-Or O. Growth, maturation, and physical activity. Champaign, IL: Human Kinetics 2004. 68. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312(7041): 1254-9. 69. Medelli J, Lounana J, Menuet JJ, Shabani M, Cordero-MacIntyre Z. Is osteopenia a health risk in professional cyclists? Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry 2009; 12(1): 28-34. 70. Meier C, Seibel MJ, Kraenzlin ME. Use of bone turnover markers in the real world: are we there yet? Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2009; 24(3): 386-8. 71. Melton LJ, 3rd. How many women have osteoporosis now? Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1995; 10(2): 175-7. 72. Mora S, Pitukcheewanont P, Kaufman FR, Nelson JC, Gilsanz V. Biochemical markers of bone turnover and the volume and the density of bone in children at different stages of sexual development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1999; 14(10): 1664-71. 73. Nevill A, Holder R, Stewart A. Do sporting activities convey benefits to bone mass throughout the skeleton? J Sports Sci 2004; 22(7): 645-50. 74. Nickols-Richardson SM, O'Connor PJ, Shapses SA, Lewis RD. Longitudinal bone mineral density changes in female child artistic gymnasts. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1999; 14(6): 994-1002. 75. Nichols JF, Palmer JE, Levy SS. Low bone mineral density in highly trained male master cyclists. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2003; 14(8): 644-9. 76. Nikander R, Sievanen H, Heinonen A, Kannus P. Femoral neck structure in adult female athletes subjected to different loading modalities. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2005; 20(3): 520-8. 77. Nordstrom A, Olsson T, Nordstrom P. Sustained benefits from previous physical activity on bone mineral density in males. The Journal of clinical endocrinology and metabolism 2006; 91(7): 2600-4. 78. O'Kane JW, Hutchinson E, Atley LM, Eyre DR. Sport-related differences in biomarkers of bone resorption and cartilage degradation in endurance athletes. Osteoarthritis Cartilage 2006; 14(1): 71-6. 79. Oja P, Titze S, Bauman A, de Geus B, Krenn P, Reger-Nash B, Kohlberger T. Health benefits of cycling: a systematic review. Scand J Med Sci Sports 2011; 21(4): 496-509. 80. Olmedillas H, Gonzalez-Aguero A, Moreno LA, Casajus JA, Vicente-Rodriguez G. Bone related health status in adolescent cyclists. PloS one 2011; 6(9): e24841. 81. Olmedillas H, Gonzalez-Aguero A, Moreno LA, Casajus JA, Vicente-Rodriguez G. Cycling and bone health: a systematic review. BMC medicine 2012; 10: 168. 82. Organization WH. Assesment of fracture risk and its application to screening for postmenopausal osteoporosis. WHO. Technical report series. Ginebra. Suiza 1994. 83. Paulino J, Paulino M. Osteoporosis: importancia, epidemiología y manifestaciones clínicas. . Medicine (Madrid) 2000; 8 15-21. 84. Penteado VS, Castro CH, Pinheiro Mde M, Santana M, Bertolino S, de Mello MT, Szejnfeld VL. Diet, body composition, and bone mass in well-trained cyclists. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry 2010; 13(1): 43-50. 85. Rector RS, Rogers R, Ruebel M, Hinton PS. Participation in road cycling vs running is associated with lower bone mineral density in men. Metabolism 2008; 57(2): 226-32. 86. Rico H, Revilla M, Villa LF, Hernandez ER, Alvarez de Buergo M, Villa M. Body composition in children and Tanner's stages: a study with dual-energy x-ray absorptiometry. Metabolism 1993; 42(8): 967-70. 87. Riggs BL, Khosla S, Melton LJ, 3rd. Sex steroids and the construction and conservation of the adult skeleton. Endocrine reviews 2002; 23(3): 279-302. 88. Rizzoli R, Bianchi ML, Garabedian M, McKay HA, Moreno LA. Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly. Bone 2010; 46(2): 294-305. 89. Rosen CJ. Clinical practice. Postmenopausal osteoporosis. The New England journal of medicine 2005; 353(6): 595-603. 90. Rudberg A, Magnusson P, Larsson L, Joborn H. Serum isoforms of bone alkaline phosphatase increase during physical exercise in women. Calcified tissue international 2000; 66(5): 342-7. 91. Russell M, Stark J, Nayak S, Miller KK, Herzog DB, Klibanski A, Misra M. Peptide YY in adolescent athletes with amenorrhea, eumenorrheic athletes and non-athletic controls. Bone 2009; 45(1): 104-9. 92. Ryan AS, Elahi D. Loss of bone mineral density in women athletes during aging. Calcified tissue international 1998; 63(4): 287-92. 93. Sabo D, Bernd L, Pfeil J, Reiter A. Bone quality in the lumbar spine in high-performance athletes. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 1996; 5(4): 258-63. 94. Sambrook P, Cooper C. Osteoporosis. Lancet 2006; 367(9527): 2010-8. 95. Seeman E. An exercise in geometry. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2002; 17(3): 373-80. 96. Seeman E. Periosteal bone formation--a neglected determinant of bone strength. The New England journal of medicine 2003; 349(4): 320-3. 97. Seibel MJ. Biochemical markers of bone remodeling. Endocrinology and metabolism clinics of North America 2003; 32(1): 83-113, vi-vii. 98. Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev 2005; 26(4): 97-122. 99. Silva CC, Goldberg TB, Nga HS, Kurokawa CS, Capela RC, Teixeira AS, Dalmas JC. Impact of skeletal maturation on bone metabolism biomarkers and bone mineral density in healthy Brazilian male adolescents. Jornal de pediatria 2011; 87(5): 450-6. 100. Slemenda CW, Peacock M, Hui S, Zhou L, Johnston CC. Reduced rates of skeletal remodeling are associated with increased bone mineral density during the development of peak skeletal mass. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1997; 12(4): 676-82. 101. Slemenda CW, Reister TK, Hui SL, Miller JZ, Christian JC, Johnston CC, Jr. Influences on skeletal mineralization in children and adolescents: evidence for varying effects of sexual maturation and physical activity. The Journal of pediatrics 1994; 125(2): 201-7. 102. Smathers AM, Bemben MG, Bemben DA. Bone density comparisons in male competitive road cyclists and untrained controls. Medicine and science in sports and exercise 2009; 41(2): 290-6. 103. Stagi S, Cavalli L, Iurato C, Seminara S, Brandi ML, de Martino M. Bone metabolism in children and adolescents: main characteristics of the determinants of peak bone mass. Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases 2013; 10(3): 172-9. 104. Stewart AD, Hannan J. Total and regional bone density in male runners, cyclists, and controls. Medicine and science in sports and exercise 2000; 32(8): 1373-7. 105. Takeda S, Karsenty G. Molecular bases of the sympathetic regulation of bone mass. Bone 2008; 42(5): 837-40. 106. Tournis S, Michopoulou E, Fatouros IG, Paspati I, Michalopoulou M, Raptou P, Leontsini D, Avloniti A, Krekoukia M, Zouvelou V, Galanos A, Aggelousis N, Kambas A, Douroudos I, Lyritis GP, Taxildaris K, Pappaioannou N. Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls. The Journal of clinical endocrinology and metabolism 2010; 95(6): 2755-62. 107. Vaitkeviciute D, Latt E, Maestu J, Jurimae T, Saar M, Purge P, Maasalu K, Jurimae J. Adipocytokines and bone metabolism markers in relation to bone mineral values in early pubertal boys with different physical activity. Journal of pediatric endocrinology & metabolism : JPEM 2016; 29(6): 723-9. 108. van Coeverden SC, Netelenbos JC, de Ridder CM, Roos JC, Popp-Snijders C, Delemarre-van de Waal HA. Bone metabolism markers and bone mass in healthy pubertal boys and girls. Clinical endocrinology 2002; 57(1): 107-16. 109. Vicente-Rodriguez G. How does exercise affect bone development during growth? Sports Med 2006; 36(7): 561-9. 110. Vicente-Rodriguez G, Jimenez-Ramirez J, Ara I, Serrano-Sanchez JA, Dorado C, Calbet JA. Enhanced bone mass and physical fitness in prepubescent footballers. Bone 2003; 33(5): 853-9. 111. Villena J. El ciclista como usuario de las vías, vol. 4. 2000. 112. Warner SE, Shaw JM, Dalsky GP. Bone mineral density of competitive male mountain and road cyclists. Bone 2002; 30(1): 281-6. 113. Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O'Karma M, Wallace TC, Zemel BS. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2016; 27(4): 1281-386. 114. Welsh L, Rutherford OM, James I, Crowley C, Comer M, Wolman R. The acute effects of exercise on bone turnover. Int J Sports Med 1997; 18(4): 247-51. 115. Woitge HW, Friedmann B, Suttner S, Farahmand I, Muller M, Schmidt-Gayk H, Baertsch P, Ziegler R, Seibel MJ. Changes in bone turnover induced by aerobic and anaerobic exercise in young males. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 1998; 13(12): 1797-804. 116. Wolff I, van Croonenborg JJ, Kemper HC, Kostense PJ, Twisk JW. The effect of exercise training programs on bone mass: a meta-analysis of published controlled trials in pre- and postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 1999; 9(1): 1-12. 117. Yilmaz D, Ersoy B, Bilgin E, Gumuser G, Onur E, Pinar ED. Bone mineral density in girls and boys at different pubertal stages: relation with gonadal steroids, bone formation markers, and growth parameters. Journal of bone and mineral metabolism 2005; 23(6): 476-82.