Editing Development of the human body (section)

== Linear growth ==
During childhood, the bones undergo a complex process of elongation that occurs in a specific area called the [[epiphyseal growth plates]] (EGP). This process is regulated by various [[hormone]]s and factors, including the growth hormone, vitamin D, and others. These hormones promote the production of insulin-like growth factor-1 (IGF-1), which plays a key role in the formation of new bone cells. Adequate [[nutrient intake]] is essential for the production of these hormones, which are critical for proper bone growth. However, a lack of proper nutrition can hinder this process and result in [[stunted growth]].

Linear growth takes place in the epiphyseal growth plates (EGP) of long bones.<ref name="Gat-Yablonski G p M">Gat-Yablonski G, Phillip M. Nutritionally-induced catch-up growth. Nutrients 2015; 7(1): 517–51.</ref> In the growth plate, [[chondrocyte]]s proliferate, hypertrophy and secrete cartilage extracellular matrix. New cartilage is subsequently remodeled into bone tissue, causing bones to grow longer.<ref>Kronenberg HM. Developmental regulation of the growth plate. Nature 2003; 423(6937): 332–6.</ref> Linear growth is a complex process regulated by the growth hormone (GH) – insulin-like growth factor-1 ([[Insulin-like growth factor 1|IGF-1]]) axis, the thyroxine/triiodothyronine axis, androgens, estrogens, vitamin D, glucocorticoids and possibly leptin.<ref name="ReferenceA">Millward DJ. Nutrition, infection and stunting: the roles of deficiencies of individual nutrients and foods, and of inflammation, as determinants of reduced linear growth of children. Nutr Res Rev 2017; 30(1): 50–72.</ref> GH is secreted by the anterior pituitary gland in response to hypothalamic, pituitary and circulating factors. It affects growth by binding to receptors in the EGP,<ref name="Gat-Yablonski G p M"/> and inducing production and release of IGF-1 by the liver.<ref>Le Roith D. The insulin-like growth factor system. Exp Diabesity Res 2003; 4(4): 205–12.</ref> IGF-1 has six binding proteins (IGFBPs), exhibiting different effects on body tissues, where [[IGFBP3|IGFBP-3]] is most abundant in human circulation.<ref>Rajaram S, Baylink DJ, Mohan S. Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev 1997; 18(6): 801–31.</ref> IGF-1 initiates growth through differentiation and maturation of osteoblasts, and regulates release of GH from the pituitary through feedback mechanisms.<ref>Daughaday WH. Growth hormone axis overview—somatomedin hypothesis. Pediatr Nephrol 2000; 14(7): 537–40.</ref> The GH/IGF-1 axis is responsive to dietary intake and infections. The endocrine system seems to allow for rapid growth only when the organism is able to consume sufficient amounts of nutrients and signaling from key nutrients such as amino acids and zinc to induce production of IGF-1 is present.<ref name="ReferenceA"/> At the same time inflammation and increased production of pro-inflammatory cytokines may cause GH resistance and a decrease in circulating IGF-1 and IGFBP-3 which in turn reduces endochondrial ossification and growth.<ref name="ReferenceA"/><ref>DeBoer MD, Scharf RJ, Leite AM, et al. Systemic inflammation, growth factors, and linear growth in the setting of infection and malnutrition. Nutrition 2017; 33: 248–53.</ref> However, the EGP appears to conserve much growth capacity to allow for catch-up growth.<ref>Lui JC, Nilsson O, Baron J. Growth plate senescence and catch-up growth. Endocr Dev 2011; 21: 23–9.</ref> Concerns have been raised about associations between catch-up growth and increased risk of non-communicable diseases in adulthood.<ref>Victora CG, Adair L, Fall C, et al. Maternal and child undernutrition: consequences for adult health and human capital. Lancet 2008; 371(9609): 340–57.</ref> In a large study based on 5 birth cohorts in Brazil, Guatemala, India, the Philippines and South Africa, faster linear growth at 0–2 years was associated with improvements in adult stature and school performance, but also an increased likelihood of overweight (mainly related to lean mass) and a slightly elevated blood pressure in young adulthood.<ref>Adair LS, Fall CH, Osmond C, et al. Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies. Lancet 2013; 382(9891): 525–34.</ref>