Abstract
Background:
The process of growth and maturation of long (radius and ulna) and short (metacarpals and phalanges) bones of the hand (enchondroplasia) differs from that of the carpal cuboid bones (chondral osteogenesis). This study aimed to assess the impact of growth hormone (GH) on these two processes of bone maturation.
Methods:
Subjects of the study were 95 prepubertal children: 30 children with GH deficiency and 65 children with idiopathic short stature, aged 7.4 ± 1.9 y (mean ± SD) (trial registration number 98-0198-033). Bone maturation was assessed by the Greulich and Pyle method from X-rays obtained at the start and at 1 and 2 y of GH treatment, separately for carpals, long bones, and short bones, and was expressed as years of delay relative to chronological age.
Results:
At GH start, the delay in bone maturation in the GH-deficient group was significantly greater for carpals (3.6 ± 1.3 y) than for long (3.0 ± 1.3 y) and short (1.7 ± 1.1 y) bones. The delay was nonsignificantly greater for carpal bones in GH-deficient subjects than in subjects with idiopathic short stature (3.6 ± 1.3 vs. 3.1 ± 1.1 y, respectively) and was normalized after 2 y of GH treatment.
Conclusion:
The dominant effect of GH was on chondral osteogenesis, with milder effect on enchondroplasia. A distinct delay in carpal and long-bone maturation, which normalizes during 2 y of GH treatment, was typical in GH-deficient children. Therefore, separate carpal bone assessment in bone age reading is needed.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Hochberg Z . Endocrine Control of Bone Maturation. Basel, Switzerland: Karger, 2002.
Hunziker EB, Wagner J, Zapf J . Differential effects of insulin-like growth factor I and growth hormone on developmental stages of rat growth plate chondrocytes in vivo. J Clin Invest 1994;93:1078–86.
Greulich WWW, Pyle SI . Radiographic Atlas of the Hand and Wrist. Stanford, CA: Stanford University Press, 1959.
Tanner JM, Whitehouse RH, Cameron N, Marshall WA, Healy MJR, Goldstein H . Assessment of Skeletal Maturity and Prediction of Adult Height (TW-2 Method). 2nd edn. London: Academic Press; 1983.
Greulich WW, Pyle SI . Radiographic Atlas of Skeletal Development of the Hand and Wrist. 2nd edn. Stanford, CA: Stanford University Press, 1991.
Saggese G, Baroncelli GI, Bertelloni S, Cinquanta L, Di Nero G . Effects of long-term treatment with growth hormone on bone and mineral metabolism in children with growth hormone deficiency. J Pediatr 1993;122:37–45.
Shore RM, Chesney RW, Mazess RB, Rose PG, Bargman GJ . Bone mineral status in growth hormone deficiency. J Pediatr 1993;122:37–45.
Zamboni G, Antoniazzi F, Radetti G, Musumeci C, Tatò L . Effects of two different regimens of recombinant human growth hormone therapy on the bone mineral density of patients with growth hormone deficiency. J Pediatr 1991;119:483–5.
Henneman PH, Forbes AP, Moldawer M, Dempsey EF, Carroll EL . Effects of human growth hormone in man. J Clin Invest 1960;39:1223–38.
Albertsson-Wikland K, Aronson AS, Gustafsson J, et al. Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency. J Clin Endocrinol Metab 2008;93:4342–50.
Benso L, Vannelli S, Pastorin L, Benso A, Milani S . Variation of bone age progression in healthy children. Acta Paediatr Suppl 1997;423:109–12.
Todd TW . Atlas av Skeletal Maturation (Hand). St Louis, MO: Mosby, 1937.
Martin DD, Wit JM, Hochberg Z, et al. The use of bone age in clinical practice - part 1. Horm Res Paediatr 2011;76:1–9.
Bull RK, Edwards PD, Kemp PM, Fry S, Hughes IA . Bone age assessment: a large scale comparison of the Greulich and Pyle, and Tanner and Whitehouse (TW2) methods. Arch Dis Child 1999;81:172–3.
Kriström B, Aronson AS, Dahlgren J, et al. Growth hormone (GH) dosing during catch-up growth guided by individual responsiveness decreases growth response variability in prepubertal children with GH deficiency or idiopathic short stature. J Clin Endocrinol Metab 2009;94:483–90.
Wikland KA, Kriström B, Rosberg S, Svensson B, Nierop AF . Validated multivariate models predicting the growth response to GH treatment in individual short children with a broad range in GH secretion capacities. Pediatr Res 2000;48:475–84.
Ankarberg-Lindgren C, Norjavaara E . Estradiol in pediatric endocrinology. Am J Clin Pathol 2009;132:978–80.
Martin DD, Neuhof J, Jenni OG, Ranke MB, Thodberg HH . Automatic determination of left- and right-hand bone age in the First Zurich Longitudinal Study. Horm Res Paediatr 2010;74:50–5.
Thodberg HH, Kreiborg S, Juul A, Pedersen KD . The BoneXpert method for automated determination of skeletal maturity. IEEE Trans Med Imaging 2009;28:52–66.
Hochberg Z . Growth hormone and IGF-I in growth plate growth. Curr Med Liter: Growth Growth Factors 1990;5:127–30.
Lewinson D, Shenzer P, Hochberg Z . Growth hormone involvement in the regulation of tartrate-resistant acid phosphatase-positive cells that are active in cartilage and bone resorption. Calcif Tissue Int 1993;52:216–21.
Even L, Bronstein V, Hochberg Z . Bone maturation in girls with Turner’s syndrome. Eur J Endocrinol 1998;138:59–62.
Wikland KA, Luo ZC, Niklasson A, Karlberg J . Swedish population-based longitudinal reference values from birth to 18 years of age for height, weight and head circumference. Acta Paediatr 2002;91:739–54.
Jansson C, Boguszewski C, Rosberg S, Carlsson L, Albertsson-Wikland K . Growth hormone (GH) assays: influence of standard preparations, GH isoforms, assay characteristics, and GH-binding protein. Clin Chem 1997;43:950–6.
Löfqvist C, Andersson E, Gelander L, Rosberg S, Blum WF, Albertsson Wikland K . Reference values for IGF-I throughout childhood and adolescence: a model that accounts simultaneously for the effect of gender, age, and puberty. J Clin Endocrinol Metab 2001;86:5870–6.
Karlberg J . On the construction of the infancy-childhood-puberty growth standard. Acta Paediatr Scand Suppl 1989;356:26–37.
Karlberg J, Luo ZC, Albertsson-Wikland K . Body mass index reference values (mean and SD) for Swedish children. Acta Paediatr 2001;90:1427–34.
Luo ZC, Albertsson-Wikland K, Karlberg J . Target height as predicted by parental heights in a population-based study. Pediatr Res 1998;44:563–71.
Acknowledgements
The authors thank all the patients, parents, and study teams involved in this research. We also thank the investigators of trial registration number 98-0198-003, Kerstin Albertsson-Wikland, Stefan Aronson, Jan Gustafsson, Sten A. Ivarsson, Berit Kriström, and Torsten Tuvemo. The language editing by Harriet Crofts is highly appreciated.
Author information
Authors and Affiliations
Corresponding author
PowerPoint slides
Rights and permissions
About this article
Cite this article
Even, L., Andersson, B., Kriström, B. et al. Role of growth hormone in enchondroplasia and chondral osteogenesis: evaluation by X-ray of the hand. Pediatr Res 76, 109–114 (2014). https://doi.org/10.1038/pr.2014.56
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2014.56
This article is cited by
-
Hand MRI and the Greulich-Pyle atlas in skeletal age estimation in adolescents
Skeletal Radiology (2018)
