Calcified Tissue International

, Volume 100, Issue 5, pp 500–513 | Cite as

The Impact of Fat and Obesity on Bone Microarchitecture and Strength in Children

  • Joshua N. Farr
  • Paul Dimitri
Original Research


A complex interplay of genetic, environmental, hormonal, and behavioral factors affect skeletal development, several of which are associated with childhood fractures. Given the rise in obesity worldwide, it is of particular concern that excess fat accumulation during childhood appears to be a risk factor for fractures. Plausible explanations for this higher fracture risk include a greater propensity for falls, greater force generation upon fall impact, unhealthy lifestyle habits, and excessive adipose tissue that may have direct or indirect detrimental effects on skeletal development. To date, there remains little resolution or agreement about the impact of obesity and adiposity on skeletal development as well as the mechanisms underpinning these changes. Limitations of imaging modalities, short duration of follow-up in longitudinal studies, and differences among cohorts examined may all contribute to conflicting results. Nonetheless, a linear relationship between increasing adiposity and skeletal development seems unlikely. Fat mass may confer advantages to the developing cortical and trabecular bone compartments, provided that gains in fat mass are not excessive. However, when fat mass accumulation reaches excessive levels, unfavorable metabolic changes may impede skeletal development. Mechanisms underpinning these changes may relate to changes in the hormonal milieu, with adipokines potentially playing a central role, but again findings have been confounding. Changes in the relationship between fat and bone also appear to be age and sex dependent. Clearly, more work is needed to better understand the controversial impact of fat and obesity on skeletal development and fracture risk during childhood.


Obesity Children Fat Bone microarchitecture HRpQCT Adipokine 


Compliance with Ethical Standards

Conflict of interest

Joshua N. Farr and Paul Dimitri have no conflict of interest.

Human and Animal Rights and Informed Consent

The research described was conducted in accordance with Human and Animal Rights and informed written consent was obtained from human participants.


  1. 1.
    Heaney RP, Abrams S, Dawson-Hughes B, Looker A, Marcus R, Matkovic V, Weaver C (2000) Peak bone mass. Osteoporos Int 11:985–1009PubMedCrossRefGoogle Scholar
  2. 2.
    Robling AG, Castillo AB, Turner CH (2006) Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 8:455–498PubMedCrossRefGoogle Scholar
  3. 3.
    Wang Q, Cheng S, Alen M, Seeman E (2009) Bone’s structural diversity in adult females is established before puberty. J Clin Endocrinol Metab 94:1555–1561PubMedCrossRefGoogle Scholar
  4. 4.
    Chavassieux P, Seeman E, Delmas PD (2007) Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease. Endocr Rev 28:151–164PubMedCrossRefGoogle Scholar
  5. 5.
    Wang Y, Lobstein T (2006) Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 1:11–25PubMedCrossRefGoogle Scholar
  6. 6.
    Lobstein T, Jackson-Leach R, Moodie ML, Hall KD, Gortmaker SL, Swinburn BA, James WP, Wang Y, McPherson K (2015) Child and adolescent obesity: part of a bigger picture. Lancet 385:2510–2520PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Ogden CL, Carroll MD, Lawman HG, Fryar CD, Kruszon-Moran D, Kit BK, Flegal KM (2016) Trends in obesity prevalence among children and adolescents in the United States, 1988–1994 through 2013–2014. JAMA 315:2292–2299PubMedCrossRefGoogle Scholar
  8. 8.
    Goulding A, Cannan R, Williams SM, Gold EJ, Taylor RW, Lewis-Barned NJ (1998) Bone mineral density in girls with forearm fractures. J Bone Miner Res 13:143–148PubMedCrossRefGoogle Scholar
  9. 9.
    Goulding A, Jones L, Taylor RW, Manning PJ, Williams SM (2000) More broken bones: a 4-year double cohort study of young girls with and without distal forearm fractures. J Bone Miner Res 15:2011–2018PubMedCrossRefGoogle Scholar
  10. 10.
    Skaggs DL, Loro ML, Pitukcheewanont P, Tolo V, Gilsanz V (2001) Increased body weight and decreased radial cross-sectional dimensions in girls with forearm fractures. J Bone Miner Res 16:1337–1342PubMedCrossRefGoogle Scholar
  11. 11.
    Goulding A, Jones IE, Taylor RW, Williams SM, Manning PJ (2001) Bone mineral density and body composition in boys with distal forearm fractures: a dual-energy X-ray absorptiometry study. J Pediatr 139:509–515PubMedCrossRefGoogle Scholar
  12. 12.
    Davidson PL, Goulding A, Chalmers DJ (2003) Biomechanical analysis of arm fracture in obese boys. J Paediatr Child Health 39:657–664PubMedCrossRefGoogle Scholar
  13. 13.
    Goulding A, Grant AM, Williams SM (2005) Bone and body composition of children and adolescents with repeated forearm fractures. J Bone Miner Res 20:2090–2096PubMedCrossRefGoogle Scholar
  14. 14.
    Taylor ED, Theim KR, Mirch MC, Ghorbani S, Tanofsky-Kraff M, Adler-Wailes DC, Brady S, Reynolds JC, Calis KA, Yanovski JA (2006) Orthopedic complications of overweight in children and adolescents. Pediatrics 117:2167–2174PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Dimitri P, Wales JK, Bishop N (2010) Fat and bone in children: differential effects of obesity on bone size and mass according to fracture history. J Bone Miner Res 25:527–536PubMedCrossRefGoogle Scholar
  16. 16.
    Kessler J, Koebnick C, Smith N, Adams A (2013) Childhood obesity is associated with increased risk of most lower extremity fractures. Clin Orthop Relat Res 471:1199–1207PubMedCrossRefGoogle Scholar
  17. 17.
    Fornari ED, Suszter M, Roocroft J, Bastrom T, Edmonds EW, Schlechter J (2013) Childhood obesity as a risk factor for lateral condyle fractures over supracondylar humerus fractures. Clin Orthop Relat Res 471:1193–1198PubMedCrossRefGoogle Scholar
  18. 18.
    Sabhaney V, Boutis K, Yang G, Barra L, Tripathi R, Tran TT, Doan Q (2014) Bone fractures in children: is there an association with obesity? J Pediatr 165(313–318):e311Google Scholar
  19. 19.
    Rosen CJ, Klibanski A (2009) Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. Am J Med 122:409–414PubMedCrossRefGoogle Scholar
  20. 20.
    Kawai M, de Paula FJ, Rosen CJ (2012) New insights into osteoporosis: the bone-fat connection. J Intern Med 272:317–329PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Dimitri P, Bishop N, Walsh JS, Eastell R (2012) Obesity is a risk factor for fracture in children but is protective against fracture in adults: a paradox. Bone 50:457–466PubMedCrossRefGoogle Scholar
  22. 22.
    Kontulainen SA, Johnston JD, Liu D, Leung C, Oxland TR, McKay HA (2008) Strength indices from pQCT imaging predict up to 85% of variance in bone failure properties at tibial epiphysis and diaphysis. J Musculoskelet Neuronal Interact 8:401–409PubMedGoogle Scholar
  23. 23.
    Kirmani S, Christen D, van Lenthe GH, Fischer PR, Bouxsein ML, McCready LK, Melton LJ 3rd, Riggs BL, Amin S, Muller R, Khosla S (2009) Bone structure at the distal radius during adolescent growth. J Bone Miner Res 24:1033–1042PubMedCrossRefGoogle Scholar
  24. 24.
    Nishiyama KK, Macdonald HM, Moore SA, Fung T, Boyde SK, McKay HA (2012) Cortical porosity is higher in boys compared with girls at the distal radius and distal tibia during pubertal growth: an HR-pQCT study. J Bone Miner Res 27:273–282PubMedCrossRefGoogle Scholar
  25. 25.
    Farr JN, Amin S, Melton LJ 3rd, Kirmani S, McCready LK, Atkinson EJ, Muller R, Khosla S (2014) Bone strength and structural deficits in children and adolescents with a distal forearm fracture resulting from mild trauma. J Bone Miner Res 29:590–599PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Goulding A (2007) Risk factors for fractures in normally active children and adolescents. In: Daily RM, Petit MA (eds) Optimizing bone mass and strength: the role of physical activity and nutrition during growth. Karger, Basel, pp 102–120CrossRefGoogle Scholar
  27. 27.
    Landin LA (1983) Fracture patterns in children. Analysis of 8682 fractures with special reference to incidence, etiology and secular changes in a Swedish urban population 1950–1979. Acta Orthop Scand Suppl 202:1–109PubMedCrossRefGoogle Scholar
  28. 28.
    Bailey DA, Wedge JH, McCulloch RG, Martin AD, Bernhardson SC (1989) Epidemiology of fractures of the distal end of the radius in children as associated with growth. J Bone Joint Surg 71-A:1225–1231CrossRefGoogle Scholar
  29. 29.
    Khosla S, Melton LJ III, Dekutoski MB, Achenbach SJ, Oberg AL, Riggs BL (2003) Incidence of childhood distal forearm fractures over 30 years: a population-based study. JAMA 290:1479–1485PubMedCrossRefGoogle Scholar
  30. 30.
    Mora S, Gilsanz V (2003) Establishment of peak bone mass. Endocrinol Metab Clin North Am 32:39–63PubMedCrossRefGoogle Scholar
  31. 31.
    Willing MC, Torner JC, Burns TL, Janz KF, Marshall T, Gilmore J, Deschenes SP, Warren JJ, Levy SM (2003) Gene polymorphisms, bone mineral density and bone mineral content in young children: the Iowa Bone Development Study. Osteoporos Int 14:650–658PubMedCrossRefGoogle Scholar
  32. 32.
    Laitinen J, Kiukaanniemi K, Heikkinen J, Koiranen M, Nieminen P, Sovio U, Keinanen-Kiukaanniemi S, Jarvelin MR (2005) Body size from birth to adulthood and bone mineral content and density at 31 years of age: results form the northern Finland 1966 birth cohort study. Osteoporos Int 16:1417–1424PubMedCrossRefGoogle Scholar
  33. 33.
    Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC, Sheffield-Moore M, Mauras N, Bowers CY (2005) Endocrine control of body composition in infancy, childhood, and puberty. Endocr Rev 26:114–146PubMedCrossRefGoogle Scholar
  34. 34.
    Petridou E, Karpathios T, Dessypris N, Simou E, Trichopoulos D (1997) The role of dairy products and non alcoholic beverages in bone fractures among schoolage children. Scand J Soc Med 25:119–125PubMedGoogle Scholar
  35. 35.
    Cromer B, Harel Z (2000) Adolescents: at increased risk for osteoporosis? Clin Pediatr (Phila) 39:565–574CrossRefGoogle Scholar
  36. 36.
    Ma D, Jones G (2003) Television, computer, and video viewing; physical activity; and upper limb fracture risk in children: a population-based case control study. J Bone Miner Res 18:1970–1977PubMedCrossRefGoogle Scholar
  37. 37.
    Ma D, Jones G (2004) Soft drink and milk consumption, physical activity, bone mass, and upper limb fractures in children: a population-based case-control study. Calcif Tissue Int 75:286–291PubMedCrossRefGoogle Scholar
  38. 38.
    Jones IE, Williams SM, Goulding A (2004) Associations of birth weight and length, childhood size, and smoking with bone fractures during growth: evidence from a birth cohort study. Am J Epidemiol 159:343–350PubMedCrossRefGoogle Scholar
  39. 39.
    Manias K, McCabe D, Bishop N (2006) Fractures and recurrent fractures in children; varying effects of environmental factors as well as bone size and mass. Bone 39:652–657PubMedCrossRefGoogle Scholar
  40. 40.
    Yeh FJ, Grant AM, Williams SM, Goulding A (2006) Children who experience their first fracture at a young age have high rates of fracture. Osteoporos Int 17:267–272PubMedCrossRefGoogle Scholar
  41. 41.
    Clark EM, Tobias JH, Ness AR (2006) Association between bone density and fractures in children: a systematic review and meta-analysis. Pediatrics 117:291–297CrossRefGoogle Scholar
  42. 42.
    Bishop N, Arundel P, Clark E, Dimitri P, Farr J, Jones G, Makitie O, Munns CF, Shaw N (2014) Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2013 Pediatric Official Positions. J Clin Densitom 17:275–280PubMedCrossRefGoogle Scholar
  43. 43.
    Wang Q, Wang XF, Iuliano-Burns S, Ghasem-Zadeh A, Zebaze R, Seeman E (2010) Rapid growth produces transient cortical weakness: a risk factor for metaphyseal fractures during puberty. J Bone Miner Res 25:1521–1526PubMedCrossRefGoogle Scholar
  44. 44.
    Parfitt AM (1994) The two faces of growth: benefits and risks to bone integrity. Osteoporos Int 4:382–398PubMedCrossRefGoogle Scholar
  45. 45.
    Rauch F, Neu C, Manz F, Schoenau E (2001) The development of metaphyseal cortex–implications for distal radius fractures during growth. J Bone Miner Res 16:1547–1555PubMedCrossRefGoogle Scholar
  46. 46.
    Hernandez CJ, Beaupre’ GS, Carter DR (2003) A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis. Osteoporos Int 14:843–847PubMedCrossRefGoogle Scholar
  47. 47.
    Havill LM, Mahaney MC, Binkley TL, Specker BL (2007) Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD. J Bone Miner Res 22:737–746PubMedCrossRefGoogle Scholar
  48. 48.
    Johnson W, Stovitz SD, Choh AC, Czerwinski SA, Towne B, Demerath EW (2012) Patterns of linear growth and skeletal maturation from birth to 18 years of age in overweight young adults. Int J Obes (Lond) 36:535–541CrossRefGoogle Scholar
  49. 49.
    Goulding A, Jones IE, Taylor RW, Piggot JM, Taylor D (2003) Dynamic and static tests of balance and postural sway in boys: effects of previous wrist bone fractures and high adiposity. Gait Posture 17:136–141PubMedCrossRefGoogle Scholar
  50. 50.
    Frost HM (1997) Obesity, and bone strength and “mass”: a tutorial based on insights from a new paradigm. Bone 21:211–214PubMedCrossRefGoogle Scholar
  51. 51.
    Pollock NK (2015) Childhood obesity, bone development, and cardiometabolic risk factors. Mol Cell Endocrinol 410:52–63PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Loder RT, Aronson DD, Greenfield ML (1993) The epidemiology of bilateral slipped capital femoral epiphysis. A study of children in Michigan. J Bone Joint Surg Am 75:1141–1147PubMedCrossRefGoogle Scholar
  53. 53.
    Davids JR, Huskamp M, Bagley AM (1996) A dynamic biomechanical analysis of the etiology of adolescent tibia vara. J Pediatr Orthop 16:461–468PubMedCrossRefGoogle Scholar
  54. 54.
    Leonard MB, Shults J, Wilson BA, Tershakovec AM, Zemel BS (2004) Obesity during childhood and adolescence augments bone mass and bone dimensions. Am J Clin Nutr 80:514–523PubMedGoogle Scholar
  55. 55.
    Clark EM, Ness AR, Tobias JH (2006) Adipose tissue stimulates bone growth in prepubertal children. J Clin Endocrinol Metab 91:2534–2541PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Goulding A, Taylor RW, Jones IE, McAuley KA, Manning PJ, Williams SM (2000) Overweight and obese children have low bone mass and area for their weight. Int J Obes Relat Metab Disord 24:627–632PubMedCrossRefGoogle Scholar
  57. 57.
    Weiler HA, Janzen L, Green K, Grabowski J, Seshia MM, Yuen KC (2000) Percent body fat and bone mass in healthy Canadian females 10 to 19 years of age. Bone 27:203–207PubMedCrossRefGoogle Scholar
  58. 58.
    Manzoni P, Brambilla P, Pietrobelli A, Beccaria L, Bianchessi A, Mora S, Chiumello G (1996) Influence of body composition on bone mineral content in children and adolescents. Am J Clin Nutr 64:603–607PubMedGoogle Scholar
  59. 59.
    Petit MA, Beck TJ, Shults J, Zemel BS, Foster BJ, Leonard MB (2005) Proximal femur bone geometry is appropriately adapted to lean mass in overweight children and adolescents. Bone 36:568–576PubMedCrossRefGoogle Scholar
  60. 60.
    Bachrach LK (2004) Bare-bones fact: children are not small adults. N Engl J Med 351:924–926PubMedCrossRefGoogle Scholar
  61. 61.
    Bachrach LK (2006) Measuring bone mass in children: can we really do it? Horm Res 65:11–16PubMedCrossRefGoogle Scholar
  62. 62.
    Janicka A, Wren TA, Sanchez MM, Dorey F, Kim PS, Mittelman SD, Gilsanz V (2007) Fat mass is not beneficial to bone in adolescents and young adults. J Clin Endocrinol Metab 92:143–147PubMedCrossRefGoogle Scholar
  63. 63.
    Pollock NK, Laing EM, Baile CA, Hamrick MW, Hall DB, Lewis RD (2007) Is adiposity advantageous for bone strength? A peripheral quantitative computed tomography study in late adolescent females. Am J Clin Nutr 86:1530–1538PubMedGoogle Scholar
  64. 64.
    Wetzsteon RJ, Petit MA, Macdonald HM, Hughes JM, Beck TJ, McKay HA (2008) Bone structure and volumetric BMD in overweight children: a longitudinal study. J Bone Miner Res 23:1946–1953PubMedCrossRefGoogle Scholar
  65. 65.
    Farr JN, Chen Z, Lisse JR, Lohman TG, Going SB (2010) Relationship of total body fat mass to weight-bearing bone volumetric density, geometry, and strength in young girls. Bone 46:977–984PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Brotto M, Bonewald L (2015) Bone and muscle: interactions beyond mechanical. Bone 80:109–114PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Farr JN, Amin S, LeBrasseur NK, Atkinson EJ, Achenbach SJ, McCready LK, Joseph Melton L, Khosla S 3rd (2014) Body composition during childhood and adolescence: relations to bone strength and microstructure. J Clin Endocrinol Metab 99:4641–4648PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Wey HE, Binkley TL, Beare TM, Wey CL, Specker BL (2011) Cross-sectional versus longitudinal associations of lean and fat mass with pQCT bone outcomes in children. J Clin Endocrinol Metab 96:106–114PubMedCrossRefGoogle Scholar
  69. 69.
    Wren TA, Kalkwarf HJ, Zemel BS, Lappe JM, Oberfield S, Shepherd JA, Winer KK, Gilsanz V (2014) Longitudinal tracking of dual-energy X-ray absorptiometry bone measures over 6 years in children and adolescents: persistence of low bone mass to maturity. J Pediatr 164(1280–1285):e1282Google Scholar
  70. 70.
    Foley S, Quinn S, Jones G (2009) Tracking of bone mass from childhood to adolescence and factors that predict deviation from tracking. Bone 44:752–757PubMedCrossRefGoogle Scholar
  71. 71.
    Laddu DR, Farr JN, Laudermilk MJ, Lee VR, Blew RM, Stump C, Houtkooper L, Lohman TG, Going SB (2013) Longitudinal relationships between whole body and central adiposity on weight-bearing bone geometry, density, and bone strength: a pQCT study in young girls. Arch Osteoporos 8:156PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Moon RJ, Cole ZA, Crozier SR, Curtis EM, Davies JH, Gregson CL, Robinson SM, Dennison EM, Godfrey KM, Inskip HM, Cooper C, Harvey NC (2015) Longitudinal changes in lean mass predict pQCT measures of tibial geometry and mineralisation at 6–7 years. Bone 75:105–110PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Dalskov S, Ritz C, Larnkjaer A, Damsgaard CT, Petersen RA, Sorensen LB, Ong KK, Astrup A, Michaelsen KF, Molgaard C (2016) Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children. Osteoporos Int 27:1619–1629PubMedCrossRefGoogle Scholar
  74. 74.
    Heidemann M, Holst R, Schou AJ, Klakk H, Husby S, Wedderkopp N, Molgaard C (2015) The influence of anthropometry and body composition on children’s bone health: the childhood health, activity and motor performance school (the CHAMPS) study, Denmark. Calcif Tissue Int 96:97–104PubMedCrossRefGoogle Scholar
  75. 75.
    Sudhagoni RG, Wey HE, Djira GD, Specker BL (2012) Longitudinal effects of fat and lean mass on bone accrual in infants. Bone 50:638–642PubMedCrossRefGoogle Scholar
  76. 76.
    Sayers A, Marcus M, Rubin C, McGeehin MA, Tobias JH (2010) Investigation of sex differences in hip structure in peripubertal children. J Clin Endocrinol Metab 95:3876–3883PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Burrows M, Baxter-Jones A, Mirwald R, Macdonald H, McKay H (2009) Bone mineral accrual across growth in a mixed-ethnic group of children: are Asian children disadvantaged from an early age? Calcif Tissue Int 84:366–378PubMedCrossRefGoogle Scholar
  78. 78.
    Wosje KS, Khoury PR, Claytor RP, Copeland KA, Kalkwarf HJ, Daniels SR (2009) Adiposity and TV viewing are related to less bone accrual in young children. J Pediatr 154(79–85):e72Google Scholar
  79. 79.
    Jones IE, Taylor RW, Williams SM, Manning PJ, Goulding A (2002) Four-year gain in bone mineral in girls with and without past forearm fractures: a DXA study. J Bone Miner Res 17:1065–1072PubMedCrossRefGoogle Scholar
  80. 80.
    Koster A, Stenholm S, Alley DE, Kim LJ, Simonsick EM, Kanaya AM, Visser M, Houston DK, Nicklas BJ, Tylavsky FA, Satterfield S, Goodpaster BH, Ferrucci L, Harris TB (2010) Body fat distribution and inflammation among obese older adults with and without metabolic syndrome. Obesity (Silver Spring) 18:2354–2361CrossRefGoogle Scholar
  81. 81.
    Shah RV, Murthy VL, Abbasi SA, Blankstein R, Kwong RY, Goldfine AB, Jerosch-Herold M, Lima JA, Ding J, Allison MA (2014) Visceral adiposity and the risk of metabolic syndrome across body mass index: the MESA Study. JACC Cardiovasc Imaging 7:1221–1235PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Gilsanz V, Chalfant J, Mo AO, Lee DC, Dorey FJ, Mittelman SD (2009) Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab 94:3387–3393PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Russell M, Mendes N, Miller KK, Rosen CJ, Lee H, Klibanski A, Misra M (2010) Visceral fat is a negative predictor of bone density measures in obese adolescent girls. J Clin Endocrinol Metab 95:1247–1255PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Pollock NK, Bernard PJ, Wenger K, Misra S, Gower BA, Allison JD, Zhu H, Davis CL (2010) Lower bone mass in prepubertal overweight children with prediabetes. J Bone Miner Res 25:2760–2769PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Sugerman HJ, Sugerman EL, DeMaria EJ, Kellum JM, Kennedy C, Mowery Y, Wolfe LG (2003) Bariatric surgery for severely obese adolescents. J Gastrointest Surg 7:102–107; discussion 107–108Google Scholar
  86. 86.
    Collins J, Mattar S, Qureshi F, Warman J, Ramanathan R, Schauer P, Eid G (2007) Initial outcomes of laparoscopic Roux-en-Y gastric bypass in morbidly obese adolescents. Surg Obes Relat Dis 3:147–152PubMedCrossRefGoogle Scholar
  87. 87.
    Inge T, Wilson KA, Gamm K, Kirk S, Garcia VF, Daniels SR (2007) Preferential loss of central (trunk) adiposity in adolescents and young adults after laparoscopic gastric bypass. Surg Obes Relat Dis 3:153–158PubMedCrossRefGoogle Scholar
  88. 88.
    Mahdy T, Atia S, Farid M, Adulatif A (2008) Effect of Roux-en Y gastric bypass on bone metabolism in patients with morbid obesity: mansoura experiences. Obes Surg 18:1526–1531PubMedCrossRefGoogle Scholar
  89. 89.
    von Mach MA, Stoeckli R, Bilz S, Kraenzlin M, Langer I, Keller U (2004) Changes in bone mineral content after surgical treatment of morbid obesity. Metabolism 53:918–921CrossRefGoogle Scholar
  90. 90.
    Duran de Campos C, Dalcanale L, Pajecki D, Garrido AB Jr, Halpern A (2008) Calcium intake and metabolic bone disease after eight years of Roux-en-Y gastric bypass. Obes Surg 18:386–390PubMedCrossRefGoogle Scholar
  91. 91.
    Fleischer J, Stein EM, Bessler M, Della Badia M, Restuccia N, Olivero-Rivera L, McMahon DJ, Silverberg SJ (2008) The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss. J Clin Endocrinol Metab 93:3735–3740PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Brzozowska MM, Sainsbury A, Eisman JA, Baldock PA, Center JR (2013) Bariatric surgery, bone loss, obesity and possible mechanisms. Obes Rev 14:52–67PubMedCrossRefGoogle Scholar
  93. 93.
    Yu EW, Bouxsein ML, Putman MS, Monis EL, Roy AE, Pratt JS, Butsch WS, Finkelstein JS (2015) Two-year changes in bone density after Roux-en-Y gastric bypass surgery. J Clin Endocrinol Metab 100:1452–1459PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Frederiksen KD, Hanson S, Hansen S, Brixen K, Gram J, Jorgensen NR, Stoving RK (2016) Bone structural changes and estimated strength after gastric bypass surgery evaluated by HR-pQCT. Calcif Tissue Int 98:253–262PubMedCrossRefGoogle Scholar
  95. 95.
    Stein EM, Silverberg SJ (2014) Bone loss after bariatric surgery: causes, consequences, and management. Lancet Diabetes Endocrinol 2:165–174PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Lu CW, Chang YK, Chang HH, Kuo CS, Huang CT, Hsu CC, Huang KC (2015) Fracture risk after bariatric surgery: a 12-year nationwide cohort study. Medicine (Baltimore) 94:e2087CrossRefGoogle Scholar
  97. 97.
    Nakamura KM, Haglind EG, Clowes JA, Achenbach SJ, Atkinson EJ, Melton LJ 3rd, Kennel KA (2014) Fracture risk following bariatric surgery: a population-based study. Osteoporos Int 25:151–158PubMedCrossRefGoogle Scholar
  98. 98.
    Lalmohamed A, de Vries F, Bazelier MT, Cooper A, van Staa TP, Cooper C, Harvey NC (2012) Risk of fracture after bariatric surgery in the United Kingdom: population based, retrospective cohort study. BMJ 345:e5085PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Johnson JM, Maher JW, Samuel I, Heitshusen D, Doherty C, Downs RW (2005) Effects of gastric bypass procedures on bone mineral density, calcium, parathyroid hormone, and vitamin D. J Gastrointest Surg 9:1106–1110; discussion 1110–1101Google Scholar
  100. 100.
    Chakhtoura MT, Nakhoul NN, Shawwa K, Mantzoros C, El Hajj Fuleihan GA (2016) Hypovitaminosis D in bariatric surgery: a systematic review of observational studies. Metabolism 65:574–585PubMedCrossRefGoogle Scholar
  101. 101.
    Chakhtoura MT, Nakhoul N, Akl EA, Mantzoros CS, El Hajj Fuleihan GA (2016) Guidelines on vitamin D replacement in bariatric surgery: identification and systematic appraisal. Metabolism 65:586–597PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Beamish AJ, Gronowitz E, Olbers T, Flodmark CE, Marcus C, Dahlgren J (2016) Body composition and bone health in adolescents after Roux-en-Y gastric bypass for severe obesity. Pediatr Obes. doi: 10.1111/ijpo.12134 PubMedGoogle Scholar
  103. 103.
    Kaulfers AM, Bean JA, Inge TH, Dolan LM, Kalkwarf HJ (2011) Bone loss in adolescents after bariatric surgery. Pediatrics 127:e956–e961PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Duckham RL, Rantalainen T, Ducher G, Hill B, Telford RD, Telford RM, Daly RM (2016) Effects of habitual physical activity and fitness on tibial cortical bone mass, structure and mass distribution in pre-pubertal boys and girls: the look study. Calcif Tissue Int 99(1):56–65. doi: 10.1007/s00223-016-0128-4 PubMedCrossRefGoogle Scholar
  105. 105.
    Fritz J, Rosengren BE, Dencker M, Karlsson C, Karlsson MK (2016) A seven-year physical activity intervention for children increased gains in bone mass and muscle strength. Acta Paediatr 105(10):1216–1224. doi: 10.1111/apa.13440 PubMedCrossRefGoogle Scholar
  106. 106.
    Burrows M (2007) Exercise and bone mineral accrual in children and adolescents. J Sports Sci Med 6:305–312PubMedPubMedCentralGoogle Scholar
  107. 107.
    Klentrou P (2016) Influence of exercise and training on critical stages of bone growth and development. Pediatr Exerc Sci 28:178–186PubMedCrossRefGoogle Scholar
  108. 108.
    Miller KK, Biller BM, Lipman JG, Bradwin G, Rifai N, Klibanski A (2005) Truncal adiposity, relative growth hormone deficiency, and cardiovascular risk. J Clin Endocrinol Metab 90:768–774PubMedCrossRefGoogle Scholar
  109. 109.
    Misra M, Bredella MA, Tsai P, Mendes N, Miller KK, Klibanski A (2008) Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls. Am J Physiol Endocrinol Metab 295:E385–E392PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Brick DJ, Gerweck AV, Meenaghan E, Lawson EA, Misra M, Fazeli P, Johnson W, Klibanski A, Miller KK (2010) Determinants of IGF1 and GH across the weight spectrum: from anorexia nervosa to obesity. Eur J Endocrinol 163:185–191PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Palmer G, Bonjour JP, Caverzasio J (1996) Stimulation of inorganic phosphate transport by insulin-like growth factor I and vanadate in opossum kidney cells is mediated by distinct protein tyrosine phosphorylation processes. Endocrinology 137:4699–4705PubMedGoogle Scholar
  112. 112.
    Ammann P, Bourrin S, Bonjour J, Meyer J, Rizzoli R (2000) Protein undernutrition-induced bone loss is associated with decreased IGF-I levels and estrogen deficiency. J Bone Miner Res 15:683–690PubMedCrossRefGoogle Scholar
  113. 113.
    Bonjour JP (2016) The dietary protein, IGF-I, skeletal health axis. Horm Mol Biol Clin Investig 28(1):39–53. doi: 10.1515/hmbci-2016-0003 PubMedGoogle Scholar
  114. 114.
    Abu EO, Horner A, Kusec V, Triffitt JT, Compston JE (1997) The localization of androgen receptors in human bone. J Clin Endocrinol Metab 82:3493–3497PubMedCrossRefGoogle Scholar
  115. 115.
    Kasperk CH, Wakley GK, Hierl T, Ziegler (1997) Gonadal and adrenal androgens are potent regulators of human bone cell metabolism in vitro. J Bone Miner Res 12:464–471PubMedCrossRefGoogle Scholar
  116. 116.
    Clarke BL, Khosla S (2009) Androgens and bone. Steroids 74:296–305PubMedCrossRefGoogle Scholar
  117. 117.
    Kasperk C, Helmboldt A, Borcsok I, Heuthe S, Cloos O, Niethard F, Ziegler R (1997) Skeletal site-dependent expression of the androgen receptor in human osteoblastic cell populations. Calcif Tissue Int 61:464–473PubMedCrossRefGoogle Scholar
  118. 118.
    Bellido T, Jilka RL, Boyce BF, Girasole G, Broxmeyer H, Dalrymple SA, Murray R, Manolagas SC (1995) Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens: the role of the androgen receptor. J Clin Invest 95:2886–2895PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Reinehr T, de Sousa G, Roth CL, Andler W (2005) Androgens before and after weight loss in obese children. J Clin Endocrinol Metab 90:5588–5595PubMedCrossRefGoogle Scholar
  120. 120.
    Thrailkill KM, Liu L, Wahl EC, Bunn RC, Perrien DS, Cockrell GE, Skinner RA, Hogue WR, Carver AA, Fowlkes JL, Aronson J, Lumpkin CK Jr (2005) Bone formation is impaired in a model of type 1 diabetes. Diabetes 54:2875–2881PubMedCrossRefGoogle Scholar
  121. 121.
    Verhaeghe J, Suiker AM, Visser WJ, Van Herck E, Van Bree R, Bouillon R (1992) The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats. J Endocrinol 134:485–492PubMedCrossRefGoogle Scholar
  122. 122.
    Farr JN, Drake MT, Amin S, Melton LJ 3rd, McCready LK, Khosla S (2014) In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res 29:787–795PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Furst JR, Bandeira LC, Fan WW, Agarwal S, Nishiyama KK, McMahon DJ, Dworakowski E, Jiang H, Silverberg SJ, Rubin MR (2016) Advanced glycation endproducts and bone material strength in type 2 diabetes. J Clin Endocrinol Metab jc20161437Google Scholar
  124. 124.
    Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL (1999) Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 140:1630–1638PubMedGoogle Scholar
  125. 125.
    Holloway WR, Collier FM, Aitken CJ, Myers DE, Hodge JM, Malakellis M, Gough TJ, Collier GR, Nicholson GC (2002) Leptin inhibits osteoclast generation. J Bone Miner Res 17:200–209PubMedCrossRefGoogle Scholar
  126. 126.
    Martin A, David V, Malaval L, Lafage-Proust MH, Vico L, Thomas T (2007) Opposite effects of leptin on bone metabolism: a dose-dependent balance related to energy intake and insulin-like growth factor-I pathway. Endocrinology 148:3419–3425PubMedCrossRefGoogle Scholar
  127. 127.
    Afghani A, Goran MI (2009) The interrelationships between abdominal adiposity, leptin and bone mineral content in overweight Latino children. Horm Res 72:82–87PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Dimitri P, Wales JK, Bishop N (2011) Adipokines, bone-derived factors and bone turnover in obese children; evidence for altered fat-bone signalling resulting in reduced bone mass. Bone 48:189–196PubMedCrossRefGoogle Scholar
  129. 129.
    Dimitri P, Jacques RM, Paggiosi M, King D, Walsh J, Taylor ZA, Frangi AF, Bishop N, Eastell R (2015) Leptin may play a role in bone microstructural alterations in obese children. J Clin Endocrinol Metab 100:594–602PubMedCrossRefGoogle Scholar
  130. 130.
    Roemmich JN, Clark PA, Mantzoros CS, Gurgol CM, Weltman A, Rogol AD (2003) Relationship of leptin to bone mineralization in children and adolescents. J Clin Endocrinol Metab 88:599–604PubMedCrossRefGoogle Scholar
  131. 131.
    Garnett SP, Hogler W, Blades B, Baur LA, Peat J, Lee J, Cowell CT (2004) Relation between hormones and body composition, including bone, in prepubertal children. Am J Clin Nutr 80:966–972PubMedGoogle Scholar
  132. 132.
    Huang KC, Cheng WC, Yen RF, Tsai KS, Tai TY, Yang WS (2004) Lack of independent relationship between plasma adiponectin, leptin levels and bone density in nondiabetic female adolescents. Clin Endocrinol (Oxf) 61:204–208CrossRefGoogle Scholar
  133. 133.
    Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903–908PubMedCrossRefGoogle Scholar
  134. 134.
    Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O’Rahilly S (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341:879–884PubMedCrossRefGoogle Scholar
  135. 135.
    Hannema SE, Wit JM, Houdijk ME, van Haeringen A, Bik EC, Verkerk AJ, Uitterlinden AG, Kant SG, Oostdijk W, Bakker E, Delemarre-van de Waal HA, Losekoot M (2016) Novel leptin receptor mutations identified in two girls with severe obesity are associated with increased bone mineral density. Horm Res Paediatr 85(6):412–420. doi: 10.1159/000444055 PubMedCrossRefGoogle Scholar
  136. 136.
    Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317PubMedCrossRefGoogle Scholar
  137. 137.
    Elefteriou F, Takeda S, Ebihara K, Magre J, Patano N, Kim CA, Ogawa Y, Liu X, Ware SM, Craigen WJ, Robert JJ, Vinson C, Nakao K, Capeau J, Karsenty G (2004) Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci USA 101:3258–3263PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G (2005) Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434:514–520PubMedCrossRefGoogle Scholar
  139. 139.
    Ealey KN, Archer MC (2009) Elevated circulating adiponectin and elevated insulin sensitivity in adiponectin transgenic mice are not associated with reduced susceptibility to colon carcinogenesis. Int J Cancer 124:2226–2230PubMedCrossRefGoogle Scholar
  140. 140.
    Lenchik L, Register TC, Hsu FC, Lohman K, Nicklas BJ, Freedman BI, Langefeld CD, Carr JJ, Bowden DW (2003) Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone 33:646–651PubMedCrossRefGoogle Scholar
  141. 141.
    Richards JB, Valdes AM, Burling K, Perks UC, Spector TD (2007) Serum adiponectin and bone mineral density in women. J Clin Endocrinol Metab 92:1517–1523PubMedCrossRefGoogle Scholar
  142. 142.
    Johansson H, Oden A, Karlsson MK, McCloskey E, Kanis JA, Ohlsson C, Mellstrom D (2014) Waning predictive value of serum adiponectin for fracture risk in elderly men: MrOS Sweden. Osteoporos Int 25:1831–1836PubMedCrossRefGoogle Scholar
  143. 143.
    Thommesen L, Stunes AK, Monjo M, Grosvik K, Tamburstuen MV, Kjobli E, Lyngstadaas SP, Reseland JE, Syversen U (2006) Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism. J Cell Biochem 99:824–834PubMedCrossRefGoogle Scholar
  144. 144.
    Liu Y, Song CY, Wu SS, Liang QH, Yuan LQ, Liao EY (2013) Novel adipokines and bone metabolism. Int J Endocrinol 2013:895045PubMedPubMedCentralGoogle Scholar
  145. 145.
    Alvarez Bartolome M, Borque M, Martinez-Sarmiento J, Aparicio E, Hernandez C, Cabrerizo L, Fernandez-Represa JA (2002) Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty. Obes Surg 12:324–327PubMedCrossRefGoogle Scholar
  146. 146.
    Mittelman SD, Klier K, Braun S, Azen C, Geffner ME, Buchanan TA (2010) Obese adolescents show impaired meal responses of the appetite-regulating hormones ghrelin and PYY. Obesity (Silver Spring) 18:918–925PubMedCentralCrossRefGoogle Scholar
  147. 147.
    Utz AL, Lawson EA, Misra M, Mickley D, Gleysteen S, Herzog DB, Klibanski A, Miller KK (2008) Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa. Bone 43:135–139PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Misra M, Miller KK, Stewart V, Hunter E, Kuo K, Herzog DB, Klibanski A (2005) Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents. J Clin Endocrinol Metab 90:5082–5087PubMedCrossRefGoogle Scholar
  149. 149.
    Campos RM, de Mello MT, Tock L, da Silva PL, Corgosinho FC, Carnier J, de Piano A, Sanches PL, Masquio DC, Tufik S, Damaso AR (2013) Interaction of bone mineral density, adipokines and hormones in obese adolescents girls submitted in an interdisciplinary therapy. J Pediatr Endocrinol Metab 26:663–668PubMedCrossRefGoogle Scholar
  150. 150.
    Pacifico L, Anania C, Poggiogalle E, Osborn JF, Prossomariti G, Martino F, Chiesa C (2009) Relationships of acylated and des-acyl ghrelin levels to bone mineralization in obese children and adolescents. Bone 45:274–279PubMedCrossRefGoogle Scholar
  151. 151.
    Robson MD, Gatehouse PD, Bydder M, Bydder GM (2003) Magnetic resonance: an introduction to ultrashort TE (UTE) imaging. J Comput Assist Tomogr 27:825–846PubMedCrossRefGoogle Scholar
  152. 152.
    Bae WC, Chen PC, Chung CB, Masuda K, D’Lima D, Du J (2012) Quantitative ultrashort echo time (UTE) MRI of human cortical bone: correlation with porosity and biomechanical properties. J Bone Miner Res 27:848–857PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Li C, Seifert AC, Rad HS, Bhagat YA, Rajapakse CS, Sun W, Lam SC, Wehrli FW (2014) Cortical bone water concentration: dependence of MR imaging measures on age and pore volume fraction. Radiology 272:796–806PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Rajapakse CS, Bashoor-Zadeh M, Li C, Sun W, Wright AC, Wehrli FW (2015) Volumetric cortical bone porosity assessment with MR imaging: validation and clinical feasibility. Radiology 276:526–535PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Lekadir K, Hoogendoorn C, Armitage P, Whitby E, King D, Dimitri P, Frangi AF (2016) Estimation of trabecular bone parameters in children from multisequence MRI using texture-based regression. Med Phys 43:3071PubMedCrossRefGoogle Scholar
  156. 156.
    Cianferotti L, Brandi ML (2014) Muscle-bone interactions: basic and clinical aspects. Endocrine 45:165–177PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Robert and Arlene Kogod Center on Aging and Endocrine Research UnitMayo Clinic College of MedicineRochesterUSA
  2. 2.The Academic Unit of Child Health, Department of Paediatric Endocrinology, Sheffield Children’s NHS Foundation TrustUniversity of SheffieldSheffieldUK

Personalised recommendations