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      Factors affecting bone age maturation during 3 years of growth hormone treatment in patients with idiopathic growth hormone deficiency and idiopathic short stature : Analysis of data from the LG growth study

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          Abstract

          To investigate the progression rate of bone age (BA) and associated factors during the first 3 years of growth hormone (GH) treatment in children with idiopathic GH deficiency (iGHD) and idiopathic short stature (ISS).

          Data for prepubertal children with iGHD and ISS who were treated with recombinant human GH were obtained from the LG Growth Study Database and analyzed. Height, weight, BA, insulin-like growth factor-1 (IGF-1) level, and GH dose were recorded every 6 months. Differences between BA and chronological age (CA), BA-CA, were calculated at each measurement. This study included 92 (78 iGHD and 14 ISS) subjects.

          After 3 years of GH treatment, the height z-score was −1.09 ± 0.71 ( P < .001 compared to baseline), BA-CA was −1.21 ± 1.18 years ( P < .001), and IGF-1 standard deviation score (SDS) was 0.43 ± 1.21 ( P < .001) in the iGHD subjects; the change in BA over the 3 years was 3.68 ± 1.27 years. In the ISS subjects, the height z-score was −1.06 ± 0.59 ( P < .001), BA-CA was −0.98 ± 1.23 years ( P = .009), and IGF-1 SDS was 0.16 ± 0.76 ( P = .648); the change in BA over the 3 years was 3.88 ± 1.36 years. The only significant factor associated with the BA progression was the BA-CA at 1 year of GH treatment (OR = 2.732, P = .001). The baseline BA-CA, IGF-1 SDS, and GH dose did not influence BA progression.

          Prepubertal subjects with iGHD and ISS showed height improvement and mild BA acceleration over the first 3 years of GH treatment. However, because the BA progression rate was considered to be clinically acceptable, GH treatment may increase the predicted adult height during this period.

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          Most cited references27

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          Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards.

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            Short and tall stature: a new paradigm emerges.

            In the past, the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis was often considered to be the main system that regulated childhood growth and, therefore, determined short stature and tall stature. However, findings have now revealed that the GH-IGF-1 axis is just one of many regulatory systems that control chondrogenesis in the growth plate, which is the biological process that drives height gain. Consequently, normal growth in children depends not only on GH and IGF-1 but also on multiple hormones, paracrine factors, extracellular matrix molecules and intracellular proteins that regulate the activity of growth plate chondrocytes. Mutations in the genes that encode many of these local proteins cause short stature or tall stature. Similarly, genome-wide association studies have revealed that the normal variation in height seems to be largely due to genes outside the GH-IGF-1 axis that affect growth at the growth plate through a wide variety of mechanisms. These findings point to a new conceptual framework for understanding short and tall stature that is centred not on two particular hormones but rather on the growth plate, which is the structure responsible for height gain.
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              Endocrine Regulation of the Growth Plate

              Longitudinal bone growth occurs at the growth plate by endochondral ossification. Within the growth plate, chondrocyte proliferation, hypertrophy, and cartilage matrix secretion result in chondrogenesis. The newly formed cartilage is invaded by blood vessels and bone cells that remodel the newly formed cartilage into bone tissue. This process of longitudinal bone growth is governed by a complex network of endocrine signals, including growth hormone, insulin-like growth factor I, glucocorticoid, thyroid hormone, estrogen, androgen, vitamin D, and leptin. Many of these signals regulate growth plate function, both by acting locally on growth plate chondrocytes and also indirectly by modulating other endocrine signals in the network. Some of the local effects of hormones are mediated by changes in paracrine factors that control chondrocyte proliferation and differentiation. Many human skeletal growth disorders are caused by abnormalities in the endocrine regulation of the growth plate. This review provides an overview of the endocrine signals that regulate longitudinal bone growth, their interactions, and the mechanisms by which they affect growth plate chondrogenesis.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                June 2019
                05 April 2019
                : 98
                : 14
                : e14962
                Affiliations
                [a ]Department of Pediatrics, Hallym University College of Medicine, Chuncheon-si, Gangwon-do
                [b ]Life Science R&D, LG Chem, Ltd., Gangseo-gu, Seoul, Republic of Korea.
                Author notes
                []Correspondence: Il Tae Hwang, Department of Pediatrics, Kangdong Sacred Heart Hospital, 150, Seongan-ro, Gangdong-gu, Seoul 05355, Republic of Korea (e-mail: ithwang83@ 123456hallym.or.kr ).
                Article
                MD-D-18-04403 14962
                10.1097/MD.0000000000014962
                6456092
                30946320
                ac8f6d4f-0de8-4a9f-addb-2e79ee8687a7
                Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 25 June 2018
                : 28 February 2019
                : 2 March 2019
                Categories
                6200
                Research Article
                Observational Study
                Custom metadata
                TRUE

                bone age,growth hormone,growth hormone deficiency,idiopathic short stature

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