UMMS Affiliation

Division of Endocrinology, Department of Pediatrics; Department of Radiology; Department of Population and Quantitative Health Sciences

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Endocrinology, Diabetes, and Metabolism | Hormones, Hormone Substitutes, and Hormone Antagonists | Pediatrics


Context: There is no consensus on the effect of recombinant human GH (rhGH) therapy on skeletal maturation in children despite the current practice of annual monitoring of skeletal maturation with bone age in children on rhGH therapy.

Aims: To investigate the effects of long-term rhGH therapy on skeletal age in children and explore the accuracy of bone age-predicted adult height (BAPAH) at different ages based on 13 years of longitudinal data.

Methods: A retrospective longitudinal study of 71 subjects aged 2 to 16 years, mean 9.9 +/- 3.8 years, treated with rhGH for nonsyndromic short stature for a duration of 2 to 14 years, mean, 5.5 +/- 2.6 years. Subjects with syndromic short stature and systemic illnesses such as renal failure were excluded.

Results: Bone age minus chronological age (BA-CA) did not differ significantly between baseline and the end of rhGH therapy (-1.05 +/- 1.42 vs -0.69 +/- 1.63, P = 0.09). Piecewise regression, however, showed a quantifiable catch-up phenomenon in BA of 1.5 months per year of rhGH therapy in the first 6.5 years (P = 0.017) that plateaued thereafter (P = 0.88). BAPAH overestimated near-adult height in younger subjects but became more accurate in older subjects (P < 0.0001). IGF-I levels correlated significantly with increases in child's height and BA-CA.

Conclusion: Long-term rhGH therapy demonstrated an initial catch-up phenomenon in skeletal maturation in the first 6.5 years that plateaued thereafter with no overall significant advancement in bone age. These findings are reassuring and support strategic, but not the insurance company mandated reflexive annual monitoring of skeletal maturation with bone age in children receiving rhGH therapy.


bone age, growth hormone deficiency, height velocity, short stature

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Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (, which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact

DOI of Published Version



Nwosu BU, Jasmin G, Parajuli S, Rogol AD, Wallace EC, Lee AF. Long-term GH Therapy Does Not Advance Skeletal Maturation in Children and Adolescents. J Endocr Soc. 2021 Mar 5;5(5):bvab036. doi: 10.1210/jendso/bvab036. PMID: 33860132; PMCID: PMC8035984. Link to article on publisher's site

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Journal of the Endocrine Society

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Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.