Pediatric Endocrinology Diabetes and Metabolism

Wpływ otyłości dziecięcej na rozwój układu kostnego

Ewa Baran 1
,
Małgorzata Wójcik 2

  1. Students’ Scientific Group, Department of Paediatric and Adolescent Endocrinology, Chair of Paediatrics, Paediatric Institute, Jagiellonian University Medical College, Krakow, Poland

  2. Department of Paediatric and Adolescent Endocrinology, Chair of Paediatrics, Paediatric Institute,
    Jagiellonian University Medical College, Krakow, Poland

Pediatr Endocrinol Diabetes Metab 2026; 32 (4):

DOI: https://doi.org/10.5114/pedm.2026.166032
Data publikacji online: 2026/11/09
Plik artykułu
0438_The impact.pdf
  1. Fintini D, Cianfarani S, Cofini M, et al. The bones of children with obesity. Front Endocrinol (Lausanne) 2020; 11: 200. doi: 10.3389/fendo.2020.00200.
  2. Rosen CJ, Klibanski A. Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. Am J Med 2009; 122: 409–414. doi: 10.1016/j.amjmed.2008.11.027.
  3. Ward LM. A practical guide to the diagnosis and management of osteoporosis in childhood and adolescence. Front Endocrinol (Lausanne) 2024; 14: 1266986. doi: 10.3389/fendo.2023.1266986.
  4. Fewtrell MS. Bone densitometry in children assessed by dual x ray absorptiometry: uses and pitfalls. Arch Dis Child 2003; 88: 795–798. doi: 10.1136/adc.88.9.795.
  5. Ferrer FS, Castell EC, Marco FC, et al. Influence of weight status on bone mineral content measured by DXA in children. BMC Pediatr 2021; 21: 185. doi: 10.1186/s12887-021-02665-5.
  6. Lane JC, Butler KL, Poveda-Marina JL, et al. Preschool obesity is associated with an increased risk of childhood fracture: a longitudinal cohort study of 466,997 children and up to 11 years of follow-up in Catalonia, Spain. J Bone Miner Res 2020; 35: 1022–1030. doi: 10.1002/jbmr.3984.
  7. Rocher E, Chappard C, Jaffre C, et al. Bone mineral density in prepubertal obese and control children: relation to body weight, lean mass, and fat mass. J Bone Miner Metab 2008; 26: 73–78. doi: 10.1007/s00774-007-0786-4.
  8. Seo YG, Kim Y, Lim H, et al. Relationship between bone mineral density and body composition according to obesity status in children. Endocr Pract 2021; 27: 983–991. doi: 10.1016/j.eprac.2021.06.006.
  9. Dimitri P. Fat and bone in children – where are we now? Ann Pediatr Endocrinol Metab 2018; 23: 62–69. doi: 10.6065/apem.2018.23.2.62.
  10. Leonard MB, Zemel BS, Wrotniak BH, et al. Tibia and radius bone geometry and volumetric density in obese compared to non-obese adolescents. Bone 2015; 73: 69–76. doi: 10.1016/j.bone.2014.12.002.
  11. Pezzuti IL, Kakehasi AM, Filgueiras MT, et al. Imaging methods for bone mass evaluation during childhood and adolescence: an update. J Pediatr Endocrinol Metab 2017; 30: 485–497. doi: 10.1515/jpem-2016-0252.
  12. Hasan S, Naseer S, Zamzam M, et al. Nutrient and hormonal effects on long bone growth in healthy and obese children: a literature review. Children (Basel) 2024; 11: 817. doi: 10.3390/children11070817.
  13. Goltzman D. Functions of vitamin D in bone. Histochem Cell Biol 2018; 149: 305–312. doi: 10.1007/s00418-018-1648-y.
  14. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet 1998; 351: 805–806. doi: 10.1016/s0140-6736(05)78933-9.
  15. Al-Othman A, Al-Musharaf S, Al-Daghri NM, et al. Effect of physical activity and sun exposure on vitamin D status of Saudi children and adolescents. BMC Pediatr 2012; 12: 92. doi: 10.1186/1471-2431-12-92.
  16. Wortsman J, Matsuoka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000; 72: 690–693. doi: 10.1093/ajcn/72.3.690.
  17. Drincic AT, Armas LA, Van Diest EE, Heaney RP. Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring) 2012; 20: 1444–1448. doi: 10.1038/oby.2011.404.
  18. Saggese G, Vierucci F, Boot AM, et al. Vitamin D in childhood and adolescence: an expert position statement. Eur J Pediatr 2015; 174: 565–576. doi: 10.1007/s00431-015-2524-6.
  19. Giustina A, Bilezikian JP, Adler RA, et al. Consensus statement on vitamin D status assessment and supplementation: whys, whens, and hows. Endocr Rev 2024; 45: 625–654. doi: 10.1210/endrev/bnae009.
  20. Dimitri P, Jacques RM, Paggiosi M, et al. Leptin may play a role in bone microstructural alterations in obese children. J Clin Endocrinol Metab 2015; 100: 594–602. doi: 10.1210/jc.2014-3199.
  21. Geserick M, Vogel M, Eckelt F, et al. Children and adolescents with obesity have reduced serum bone turnover markers and 25-hydroxyvitamin D but increased parathyroid hormone concentrations – results derived from new pediatric reference ranges. Bone 2020; 132: 115124. doi: 10.1016/j.bone.2019.115124.
  22. Radetti G, Franceschi R, Adami S, et al. Higher circulating parathormone is associated with smaller and weaker bones in obese children. Calcif Tissue Int 2014; 95: 1–7. doi: 10.1007/s00223-014-9853-8.
  23. Schrager S. Dietary calcium intake and obesity. J Am Board Fam Pract 2005; 18: 205–210. doi: 10.3122/jabfm.18.3.205.
  24. Piuri G, Zocchi M, Della Porta M, et al. Magnesium in obesity, metabolic syndrome, and type 2 diabetes. Nutrients 2021; 13: 320. doi: 10.3390/nu13020320.
  25. Abrams SA, Chen Z, Hawthorne KM. Magnesium metabolism in 4-year-old to 8-year-old children. J Bone Miner Res 2014; 29: 118–122. doi: 10.1002/jbmr.2021.
  26. Rude RK, Gruber HE, Wei LY, et al. Magnesium deficiency: effect on bone and mineral metabolism in the mouse. Calcif Tissue Int 2003; 72: 32–41. doi: 10.1007/s00223-001-1091-1.
  27. Idelevich A, Baron R. Brain to bone: what is the contribution of the brain to skeletal homeostasis? Bone 2018; 115: 31–42. doi: 10.1016/j.bone.2018.05.018.
  28. Lamghari M, Tavares L, Camboa N, Barbosa MA. Leptin effect on RANKL and OPG expression in MC3T3-E1 osteoblasts. J Cell Biochem 2006; 98: 1123–1129. doi: 10.1002/jcb.20853.
  29. Scheller EL, Song J, Dishowitz MI, et al. Leptin functions peripherally to regulate differentiation of mesenchymal progenitor cells. Stem Cells 2010; 28: 1071–1080. doi: 10.1002/stem.432.
  30. Gomes MM, da Silva MMR, de Araújo IM, de Paula FJA. Bone, fat, and muscle interactions in health and disease. Arch Endocrinol Metab 2022; 66: 611–620. doi: 10.20945/2359-3997000000550.
  31. Roy B, Curtis ME, Fears LS, et al. Molecular mechanisms of obesity-induced osteoporosis and muscle atrophy. Front Physiol 2016; 7: 439. doi: 10.3389/fphys.2016.00439.
  32. Souza PP, Lerner UH. The role of cytokines in inflammatory bone loss. Immunol Invest 2013; 42: 555–622. doi: 10.3109/08820139.2013.822766.
  33. Schett G. Effects of inflammatory and anti-inflammatory cytokines on the bone. Eur J Clin Invest 2011; 41: 1361–1366. doi: 10.1111/j.1365-2362.2011.02545.x.
  34. Ambroszkiewicz J, Chełchowska M, Mazur J, et al. Relationships between body weight status and serum levels of adipokine, myokine and bone metabolism parameters in healthy normal weight and thin children. J Clin Med 2022; 11: 4013. doi: 10.3390/jcm11144013.
  35. Wang Y, Zhang X, Shao J, et al. Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/-catenin pathway. Sci Rep 2017; 7: 3652. doi: 10.1038/s41598-017-03899-z.
  36. Luque RM, Kineman RD. Impact of obesity on the growth hormone axis: evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function. Endocrinology 2006; 147: 2754–2763. doi: 10.1210/en.2005-1549.
  37. Zhang W, Shen X, Wan C, et al. Effects of insulin and insulin-like growth factor 1 on osteoblast proliferation and differentiation: differential signalling via Akt and ERK. Cell Biochem Funct 2012; 30: 297–302. doi: 10.1002/cbf.2801.
  38. Levy JR, Murray E, Manolagas S, Olefsky JM. Demonstration of insulin receptors and modulation of alkaline phosphatase activity by insulin in rat osteoblastic cells. Endocrinology 1986; 119: 1786–1792. doi: 10.1210/endo-119-4-1786.
  39. Dimitri P. The impact of childhood obesity on skeletal health and development. J Obes Metab Syndr 2019; 28: 4–17. doi: 10.7570/jomes.2019.28.1.4.
  40. Cuenca Alcocel J, Villalba-Heredia L, Martínez Redondo I, et al. Bone metabolism in children with normal weight and overweight/obesity in a northeastern region of Spain. Adv Lab Med 2024; 5: 66–74. doi: 10.1515/almed-2024-0026.
  41. Gajewska J, Klemarczyk W, Ambroszkiewicz J, et al. Associations between IGF-I, IGF-binding proteins and bone turnover markers in prepubertal obese children. J Pediatr Endocrinol Metab 2015; 28: 563–569. doi: 10.1515/jpem-2014-0326.
  42. Karampatsou SI, Paltoglou G, Genitsaridi SM, et al. The effect of a comprehensive life-style intervention program of diet and exercise on four bone-derived proteins, FGF-23, osteopontin, NGAL and sclerostin, in overweight or obese children and adolescents. Nutrients 2022; 14: 3772. doi: 10.3390/nu14183772.
  43. Martin A, David V, Quarles LD. Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev 2012; 92: 131–155. doi: 10.1152/physrev.00002.2011.
  44. Ali FN, Falkner B, Gidding SS, et al. Fibroblast growth factor-23 in obese, normotensive adolescents is associated with adverse cardiac structure. J Pediatr 2014; 165: 738–743. doi: 10.1016/j.jpeds.2014.06.027.
  45. Bostan Gayret Ö, Taşdemir M, Erol M, et al. Are there any new reliable markers to detect renal injury in obese children? Ren Fail 2018; 40: 416–422. doi: 10.1080/0886022X.2018.1489284.
  46. Yan QW, Yang Q, Mody N, et al. The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes 2007; 56: 2533–2540. doi: 10.2337/db07-0007.
  47. Capulli M, Ponzetti M, Maurizi A, et al. A complex role for lipocalin 2 in bone metabolism: global ablation in mice induces osteopenia caused by an altered energy metabolism. J Bone Miner Res 2018; 33: 1141–1153. doi: 10.1002/jbmr.3406.
  48. Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316: 889–894. doi: 10.1126/science.1141634.
  49. Li Q, Huang Y, Liu X, et al. Rhein inhibits AlkB repair enzymes and sensitizes cells to methylated DNA damage. J Biol Chem 2016; 291: 11083–11093. doi: 10.1074/jbc.M115.711895.
  50. Huang M, Xu S, Liu L, et al. m6A methylation regulates osteoblastic differentiation and bone remodeling. Front Cell Dev Biol 2021; 9: 783322. doi: 10.3389/fcell.2021.783322.
  51. Chen LS, Zhang M, Chen P, et al. The m6A demethylase FTO promotes the osteogenesis of mesenchymal stem cells by downregulating PPARG. Acta Pharmacol Sin 2022; 43: 1311–1323. doi: 10.1038/s41401-021-00756-8.
  52. Shen GS, Zhou HB, Zhang H, et al. The GDF11-FTO-PPAR axis controls the shift of osteoporotic MSC fate to adipocyte and inhibits bone formation during osteoporosis. Biochim Biophys Acta Mol Basis Dis 2018; 1864: 3644–3654. doi: 10.1016/j.bbadis.2018.09.015.
  53. Zhang Q, Riddle RC, Yang Q, et al. The RNA demethylase FTO is required for maintenance of bone mass and functions to protect osteoblasts from genotoxic damage. Proc Natl Acad Sci U S A 2019; 116: 17980–17989. doi: 10.1073/pnas.1905489116.
  54. Rinonapoli G, Pace V, Ruggiero C, et al. Obesity and bone: a complex relationship. Int J Mol Sci 2021; 22: 13662. doi: 10.3390/ijms222413662.
  55. Forte YS, Renovato-Martins M, Barja-Fidalgo C. Cellular and molecular mechanisms associating obesity to bone loss. Cells 2023; 12: 521. doi: 10.3390/cells12040521.
  56. Huang T, Yan G, Guan M. Zinc homeostasis in bone: zinc transporters and bone diseases. Int J Mol Sci 2020; 21: 1236. doi: 10.3390/ijms21041236.
  57. Liu MJ, Bao S, Bolin ER, et al. Zinc deficiency augments leptin production and exacerbates macrophage infiltration into adipose tissue in mice fed a high-fat diet. J Nutr 2013; 143: 1036–1045. doi: 10.3945/jn.113.175158.
  58. International Zinc Nutrition Consultative Group (IZiNCG); Brown KH, Rivera JA, Bhutta Z, et al. International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 2004; 25(Suppl 2): S99–S203.
  59. World Health Organization. Vitamin A deficiency. Available at: https:// www.who.int/data/nutrition/nlis/info/vitamin-a-deficiency (accessed 8 Mar 2026).
  60. García OP. Effect of vitamin A deficiency on the immune response in obesity. Proc Nutr Soc 2012; 71: 290–297. doi: 10.1017/S0029665112000079.
  61. Skinner AM, Vlachopoulos D, Barker AR, et al. Physical activity volume and intensity distribution in relation to bone, lean and fat mass in children. Scand J Med Sci Sports 2023; 33: 267–282. doi: 10.1111/sms.14255.
  62. Suhett LG, Filgueiras MS, de Novaes JF, et al. Role of diet quality in bone health in children and adolescents: a systematic review. Nutr Rev 2024; 82: 47–59. doi: 10.1093/nutrit/nuad036.
  63. Liu H, Wang P, Cao M, et al. Protective role of oligomycin against intestinal epithelial barrier dysfunction caused by IFN- and TNF-. Cell Physiol Biochem 2012; 29: 799–808. doi: 10.1159/000188076.
  64. Saad MJ, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology (Bethesda) 2016; 31: 283–293. doi: 10.1152/physiol.00041.2015.
  65. Eaimworawuthikul S, Tunapong W, Chunchai T, et al. Altered gut microbiota ameliorates bone pathology in the mandible of obese-insulin-resistant rats. Eur J Nutr 2020; 59: 1453–1462. doi: 10.1007/s00394-019-02002-8.
  66. Zhang Z, Lin T, Meng Y, et al. FOS/GOS attenuates high-fat diet induced bone loss via reversing microbiota dysbiosis, high intestinal permeability and systemic inflammation in mice. Metabolism 2021; 119: 154767. doi: 10.1016/j.metabol.2021.154767.
  67. Hawkes CP, Mostoufi-Moab S. Fat-bone interaction within the bone marrow milieu: impact on hematopoiesis and systemic energy metabolism. Bone 2019; 119: 57–64. doi: 10.1016/j.bone.2018.03.012.
  68. Singhal V, Kaur S, Haidar LA, et al. Differences in bone accrual over one year in young girls with obesity compared to normal weight controls. Bone 2023; 172: 116757. doi: 10.1016/j.bone.2023.116757.
  69. Singhal V, Huynh C, Nimmala S, et al. Load-to-strength ratio at the radius is higher in adolescent and young adult females with obesity compared to normal-weight controls. Bone 2022; 164: 116515. doi: 10.1016/j.bone.2022.116515.
  70. Laddu DR, Farr JN, Laudermilk MJ, et al. 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 2013; 8: 156. doi: 10.1007/s11657-013-0156-x.

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