title: The effect of acute and chronic stress on growth.
abstract: Impaired bone growth is observed in many children exposed to stress, but whether the underlying cause is psychological or secondary to a variety of chronic disorders is unclear. The growth plate is specifically targeted by stress through many different mechanisms, including increased serum concentrations of proinflammatory cytokines and cortisol, as well as impaired actions of the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis. Both glucocorticoids, such as cortisol, and proinflammatory cytokines adversely affect several aspects of chondrogenesis in the growth plate, and these effects can be ameliorated by raising local IGF-1 concentrations. However, this intervention does not completely normalize growth. In children with stress related to chronic inflammation, the cornerstone of improving stress-impaired growth remains the judicious use of glucocorticoids while ensuring effective control of the disease process. Specific immunomodulatory therapy that targets the actions of tumor necrosis factor-α (TNFα) is at least partially effective at rescuing linear growth in many children with juvenile idiopathic arthritis (JIA). Patients who do not respond to anti-TNF treatment may be candidates for therapeutic agents that target other proinflammatory cytokines and for GH intervention. Although GH treatment rescues linear growth in some patients with JIA, it is unknown whether GH can rescue growth in those patients who do not respond to anticytokine therapy. Further experimental and clinical studies are needed to explore these and other new potential treatment strategies that could improve bone growth in patients who do not respond to conventional therapy.
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm SE-17176, Sweden. lars.savendahl@ki.se
authors.forename: Lars
authors.initials: L
authors.lastname: Sävendahl
mesh_terms: D000818:Animals; D001171:Arthritis, Juvenile / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D001846:Bone Development; D002648:Child; D002675:Child, Preschool; D020219:Chondrogenesis; D005938:Glucocorticoids / Q000378:metabolism; D006132:Growth Plate / Q000378:metabolism* / Q000473:pathology; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D013312:Stress, Physiological; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I