Impact of growth hormone treatment on scoliosis development and progression: analysis of 1128 patients with idiopathic short stature
-
Se-Jun Park
,
Chong-Suh Lee
Abstract
Objectives
The purpose of this study was to evaluate the impact of recombinant human growth hormone (rhGH) on the development and progression of scoliosis in patients with idiopathic short stature (ISS).
Methods
Patients with ISS who underwent rhGH treatment from 1997 to 2017 and were followed up for scoliosis screening with serial radiographic examination were included. For assessing scoliosis development, patients who did not have scoliosis at the time of rhGH treatment were included and followed up to determine whether de novo scoliosis developed during the treatment. For evaluating scoliosis progression, patients who already had scoliosis were analyzed. Univariate and multivariate Cox regression analyses of demographic and radiographic variables were performed to determine the related factors in the development and progression of scoliosis.
Results
For assessing scoliosis development, 1093 patients were included. The average duration of rhGH treatment was about 2 years. De novo scoliosis developed in 32 patients (3.7%). The analysis revealed that sex (p=0.016) and chronological age (p=0.048) were statistically significant factors associated with scoliosis development. However, no relationship was observed between scoliosis development and rhGH treatment types or duration. Among 67 patients who already had scoliosis at the time of rhGH treatment, 11 (16.4%) showed scoliosis progression. However, the rhGH types and duration also did not affect scoliosis progression.
Conclusions
De novo scoliosis developed in 3.7% and scoliosis progressed in 16.4% of the patients during rhGH treatment. However, scoliosis development or progression was not affected by the types or duration of rhGH treatment in patients with ISS.
Research funding: None declared.
Author contributions: Conception and design: SJ Park. Acquisition of data: SJ Park, CS Lee, MS Kim, J Kim, SY Cho, DK Jin. Analysis and interpretation of data: KH Lee. Drafting the article: SJ Park, KH Lee. Critically revising the article: SJ Park, JH Jang, DH Shin. Reviewed submitted version of manuscript: SJ Park. Statistical analysis: SJ Park. Administrative/technical/material support: CS Lee, KT Kim. Study supervision: CS Lee, KT Kim. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Competing interests: None declared.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.
References
1. Cheng, JC, Castelein, RM, Chu, WC, Danielsson, AJ, Dobbs, MB, Grivas, TB, et al.. Adolescent idiopathic scoliosis. Nat Rev Dis Primers 2015;1:15030. https://doi.org/10.1038/nrdp.2015.68.Search in Google Scholar
2. Kikanloo, SR, Tarpada, SP, Cho, W. Etiology of adolescent idiopathic scoliosis: a literature review. Asian Spine J 2019;13:519–26. https://doi.org/10.31616/asj.2018.0096.Search in Google Scholar
3. Ng, S-Y, Bettany-Saltikov, J, Cheung, IYK, Chan, KKY. The role of vitamin D in the pathogenesis of adolescent idiopathic scoliosis. Asian Spine J 2018;12:1127. https://doi.org/10.31616/asj.2018.12.6.1127.Search in Google Scholar
4. Dimeglio, A, Canavese, F. Progression or not progression? How to deal with adolescent idiopathic scoliosis during puberty. J Child Orthop 2013;7:43–9. https://doi.org/10.1007/s11832-012-0463-6.Search in Google Scholar
5. Negrini, S, Donzelli, S, Aulisa, AG, Czaprowski, D, Schreiber, S, de Mauroy, JC, et al.. SOSORT guidelines: orthopaedic and rehabilitation treatment of idiopathic scoliosis during growth. Scolios Spinal Disord 2016;13:3, 2018.10.1186/s13013-017-0145-8Search in Google Scholar PubMed PubMed Central
6. Bell, J, Parker, KL, Swinford, RD, Hoffman, AR, Maneatis, T, Lippe, B. Long-term safety of recombinant human growth hormone in children. J Clin Endocrinol Metab 2010;95:167–77. https://doi.org/10.1210/jc.2009-0178.Search in Google Scholar
7. Fong, DY, Lee, CF, Cheung, KM, Cheng, JC, Ng, BK, Lam, TP, et al.. A meta-analysis of the clinical effectiveness of school scoliosis screening. Spine Phila Pa 1976;35:1061–71, 2010.10.1097/BRS.0b013e3181bcc835Search in Google Scholar PubMed
8. Grimberg, A, DiVall, SA, Polychronakos, C, Allen, DB, Cohen, LE, Quintos, JB, et al.. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr 2016;86:361–97. https://doi.org/10.1159/000452150.Search in Google Scholar
9. Sitoula, P, Verma, K, Holmes, LJr., Gabos, PG, Sanders, JO, Yorgova, P, et al.. Prediction of curve progression in idiopathic scoliosis: validation of the sanders skeletal maturity staging system. Spine Phila Pa 1976;40:1006–13, 2015.10.1097/BRS.0000000000000952Search in Google Scholar PubMed
10. Allen, DB. Safety of growth hormone treatment of children with idiopathic short stature: the US experience. Horm Res Paediatr 2011;76(3 Suppl):45–7. https://doi.org/10.1159/000330159.Search in Google Scholar
11. Wang, ED, Drummond, DS, Dormans, JP, Moshang, T, Davidson, RS, Gruccio, D. Scoliosis in patients treated with growth hormone. J Pediatr Orthop 1997;17:708–11. https://doi.org/10.1097/01241398-199711000-00003.Search in Google Scholar
12. Yun, YH, Kwon, SS, Koh, Y, Kim, DJ, Ahn, J, Lee, SY. Influence of growth hormone treatment on radiographic indices of the spine: propensity-matched analysis. J Orthop Surg Res 2017;12:130. https://doi.org/10.1186/s13018-017-0630-z.Search in Google Scholar
13. Wit, JM, Clayton, PE, Rogol, AD, Savage, MO, Saenger, PH, Cohen, P. Idiopathic short stature: definition, epidemiology, and diagnostic evaluation. Growth Horm IGF Res 2008;18:89–110. https://doi.org/10.1016/j.ghir.2007.11.004.Search in Google Scholar
14. Suh, SW, Modi, HN, Yang, JH, Hong, JY. Idiopathic scoliosis in Korean schoolchildren: a prospective screening study of over 1 million children. Eur Spine J 2011;20:1087–94. https://doi.org/10.1007/s00586-011-1695-8.Search in Google Scholar
15. Quigley, CA, Gill, AM, Crowe, BJ, Robling, K, Chipman, JJ, Rose, SR, et al.. Safety of growth hormone treatment in pediatric patients with idiopathic short stature. J Clin Endocrinol Metab 2005;90:5188–96. https://doi.org/10.1210/jc.2004-2543.Search in Google Scholar
16. Day, GA, McPhee, IB, Batch, J, Tomlinson, FH. Growth rates and the prevalence and progression of scoliosis in short-statured children on Australian growth hormone treatment programmes. Scoliosis 2007;2:3. https://doi.org/10.1186/1748-7161-2-3.Search in Google Scholar
17. Sung, IK. Monitoring growth in childhood: practical clinical guide. J Korean Med Assoc 2009;52:211–24. https://doi.org/10.5124/jkma.2009.52.3.211.Search in Google Scholar
18. Goldberg, CJ, Moore, DP, Fogarty, EE, Dowling, FE. Scoliosis: a review. Pediatr Surg Int 2008;24:129–44. https://doi.org/10.1007/s00383-007-2016-5.Search in Google Scholar
19. Reamy, BV, Slakey, J. Adolescent idiopathic scoliosis: review and current concepts. Am Fam Physician 2001;64:111.Search in Google Scholar
20. Ohtsuka, Y, Yamagata, M, Arai, S, Kitahara, H, Minami, S. School screening for scoliosis by the Chiba University Medical School screening program. Results of 1.24 million students over an eight-year period. Spine 1988;13:1251–7. https://doi.org/10.1097/00007632-198811000-00008.Search in Google Scholar
21. Wong, H-K, Hui, JH, Rajan, U, Chia, H-P. Idiopathic scoliosis in Singapore schoolchildren: a prevalence study 15 years into the screening program. Spine 2005;30:1188–96. https://doi.org/10.1097/01.brs.0000162280.95076.bb.Search in Google Scholar
22. Lonstein, JE, Carlson, JM. The prediction of curve progression in untreated idiopathic scoliosis during growth. J Bone Joint Surg Am 1984;66:1061–71. https://doi.org/10.2106/00004623-198466070-00013.Search in Google Scholar
23. Trobisch, P, Suess, O, Schwab, F. Idiopathic scoliosis. Dtsch Arztebl Int 2010;107:875–83. https://doi.org/10.3238/arztebl.2010.0875 quiz 84.Search in Google Scholar
24. Hresko, MT. Clinical practice. Idiopathic scoliosis in adolescents. N Engl J Med 2013;368:834–41. https://doi.org/10.1056/nejmcp1209063.Search in Google Scholar
25. Cheung, JPY, Cheung, PWH, Samartzis, D, Luk, KD-K. APSS-ASJ best clinical research award: predictability of curve progression in adolescent idiopathic scoliosis using the distal radius and ulna classification. Asian spine journal 2018;12:202. https://doi.org/10.4184/asj.2018.12.2.202.Search in Google Scholar
26. Zhang, J, Cheuk, KY, Xu, L, Wang, Y, Feng, Z, Sit, T, et al.. A validated composite model to predict risk of curve progression in adolescent idiopathic scoliosis. E Clin Med 2020;18:100236. https://doi.org/10.1016/j.eclinm.2019.12.006.Search in Google Scholar
27. Fukami, M, Seki, A, Ogata, T. SHOX haploinsufficiency as a cause of syndromic and nonsyndromic short stature. Mol Syndromol 2016;7:3–11. https://doi.org/10.1159/000444596.Search in Google Scholar
28. Petteys, RJ, Spitz, SM, Goodwin, CR, Abu-Bonsrah, N, Bydon, A, Witham, TF, et al.. Factors associated with improved survival following surgery for renal cell carcinoma spinal metastases. Neurosurg Focus 2016;41:E13. https://doi.org/10.3171/2016.5.focus16145.Search in Google Scholar
29. Dias, C, Giordano, M, Frechette, R, Bellone, S, Polychronakos, C, Legault, L, et al.. Genetic variations at the human growth hormone receptor (GHR) gene locus are associated with idiopathic short stature. J Cell Mol Med 2017;21:2985–99. https://doi.org/10.1111/jcmm.13210.Search in Google Scholar
30. Rogers, DG, Aswini, RS. Response to growth hormone treatment in a patient with 18p-syndrome. J Pediatr Endocrinol Metab 2012;25:1023–5. https://doi.org/10.1515/jpem-2012-0100.Search in Google Scholar
31. Rogers, DG, Nasomyont, N. Growth hormone treatment in a patient with Hurler-Scheie syndrome. J Pediatr Endocrinol Metab 2014;27:957–60. https://doi.org/10.1515/jpem-2013-0340.Search in Google Scholar
32. Inzaghi, E, Reiter, E, Cianfarani, S. The challenge of defining and investigating the causes of idiopathic short stature and finding an effective therapy. Horm Res Paediatr 2019;92:71–83. https://doi.org/10.1159/000502901.Search in Google Scholar
33. Cohen, P, Bright, GM, Rogol, AD, Kappelgaard, AM, Rosenfeld, RG. American norditropin clinical trials group. Effects of dose and gender on the growth and growth factor response to GH in GH-deficient children: implications for efficacy and safety. J Clin Endocrinol Metab 2002;87:90–8. https://doi.org/10.1210/jcem.87.1.8150.Search in Google Scholar
34. Cohen, P, Rogol, AD, Deal, CL, Saenger, P, Reiter, EO, Ross, JL, et al.. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the growth hormone research society, the lawson wilkins pediatric endocrine society, and the European society for paediatric endocrinology workshop. J Clin Endocrinol Metab 2008;93:4210–7. https://doi.org/10.1210/jc.2008-0509.Search in Google Scholar
35. Poidvin, A, Carel, JC, Ecosse, E, Levy, D, Michon, J, Coste, J. Increased risk of bone tumors after growth hormone treatment in childhood: a population-based cohort study in France. Cancer Med 2018;7:3465–73. https://doi.org/10.1002/cam4.1602.Search in Google Scholar
36. Okuda, A, Shigematsu, H, Fujii, H, Iwata, E, Tanaka, M, Morimoto, Y, et al.. Reliability comparison between “distal radius and ulna” and “simplified tanner–whitehouse III” assessments for patients with adolescent idiopathic scoliosis. Asian Spine J 2020;14:280–6. https://doi.org/10.31616/asj.2019.0162.Search in Google Scholar
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review Article
- The current review of adolescent obesity: the role of genetic factors
- Original Articles
- Trends in abdominal obesity among Chinese children and adolescents, 1993–2015
- Association of childhood obesity with retinal microvasculature and corneal endothelial cell morphology
- Communication frequency between visits is associated with improved glycemic control in pediatric diabetes
- Increased length of stay and hospital charges in adolescents with type 1 diabetes and psychiatric illness
- Distance from the endocrinology clinic and diabetes control in a rural pediatric population
- Care of children with type 1 diabetes mellitus in school – An interventional study
- Treatment and long-term follow-up of patients diagnosed with type 1 diabetes mellitus before age 5
- Diabetes distress in Indian children with type 1 diabetes mellitus and their mothers
- Impact of lockdown for COVID-19 pandemic in Indian children and youth with type 1 diabetes from different socio-economic classes
- First report on the nationwide prevalence of paediatric type 1 diabetes in Serbia and temporal trends of diabetes ketoacidosis at diagnosis—a multicentre study
- Factors affecting thyroid volume in adolescent students attending a rural middle school in East Hangzhou, China
- Impact of maternal thyroid disease on neonatal thyroid status
- Impact of growth hormone treatment on scoliosis development and progression: analysis of 1128 patients with idiopathic short stature
- Short Communication
- Are we ignoring coexisting rhabdomyolysis as an important aggravating factor for acute kidney injury among childhood diabetic ketoacidosis?
- Case Reports
- Microdeletion in the IGF-1 receptor gene of a patient with short stature and obesity: a case report
- SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature
- Familial neonatal nonautoimmune hyperthyroidism due to a gain-of-function (D619G) thyrotropin-receptor mutation
- Transient neonatal diabetes due to a disease causing novel variant in the ATP-binding cassette subfamily C member 8 (ABCC8) gene unmasks maturity-onset diabetes of the young (MODY) diabetes cases within a family
Articles in the same Issue
- Frontmatter
- Review Article
- The current review of adolescent obesity: the role of genetic factors
- Original Articles
- Trends in abdominal obesity among Chinese children and adolescents, 1993–2015
- Association of childhood obesity with retinal microvasculature and corneal endothelial cell morphology
- Communication frequency between visits is associated with improved glycemic control in pediatric diabetes
- Increased length of stay and hospital charges in adolescents with type 1 diabetes and psychiatric illness
- Distance from the endocrinology clinic and diabetes control in a rural pediatric population
- Care of children with type 1 diabetes mellitus in school – An interventional study
- Treatment and long-term follow-up of patients diagnosed with type 1 diabetes mellitus before age 5
- Diabetes distress in Indian children with type 1 diabetes mellitus and their mothers
- Impact of lockdown for COVID-19 pandemic in Indian children and youth with type 1 diabetes from different socio-economic classes
- First report on the nationwide prevalence of paediatric type 1 diabetes in Serbia and temporal trends of diabetes ketoacidosis at diagnosis—a multicentre study
- Factors affecting thyroid volume in adolescent students attending a rural middle school in East Hangzhou, China
- Impact of maternal thyroid disease on neonatal thyroid status
- Impact of growth hormone treatment on scoliosis development and progression: analysis of 1128 patients with idiopathic short stature
- Short Communication
- Are we ignoring coexisting rhabdomyolysis as an important aggravating factor for acute kidney injury among childhood diabetic ketoacidosis?
- Case Reports
- Microdeletion in the IGF-1 receptor gene of a patient with short stature and obesity: a case report
- SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature
- Familial neonatal nonautoimmune hyperthyroidism due to a gain-of-function (D619G) thyrotropin-receptor mutation
- Transient neonatal diabetes due to a disease causing novel variant in the ATP-binding cassette subfamily C member 8 (ABCC8) gene unmasks maturity-onset diabetes of the young (MODY) diabetes cases within a family
