Improvement of Bone Metabolism in Prepubertal Girls with Turner Syndrome Following Long-term Pegylated Growth Hormone Treatment

Abstract

The study aims to assess the improvement in bone metabolism in prepubertal girls with Turner Syndrome (TS) after long-term polyethylene glycol recombinant human Growth Hormone (PEG-rhGH) treatment. A 12-month longitudinal prospective study was conducted with 28 prepubertal girls diagnosed with TS. Participants were divided into two groups: 18 received PEG-rhGH therapy (0.1–0.25 mg/kg/week) and 10 did not. Anthropometric measurements, bone turnover markers (BTMs), and serum levels of IGF-1, calcium, and phosphate were collected at baseline and after 12 months. BTMs included bone alkaline phosphatase (BAP), Type I collagen propeptide (CICP), Type I collagen telopeptide (CTX), and fibroblast growth factor 23 (FGF23). After 12 months of PEG-rhGH therapy, the treatment group showed significant increases in growth velocity (GV) and height standard deviation scores (HtSDS). Serum IGF-1 levels increased rapidly within one month and remained elevated. BTMs indicated enhanced bone formation, significantly increasing BAP and CICP, while CTX levels remained low. FGF23 levels initially rose slightly but declined below baseline by 12 months. Elevated blood phosphate levels were observed. PEG-rhGH therapy in children with TS significantly improves linear growth and enhances bone formation markers, benefiting bone metabolism.

Keywords

bone turnover markers - long-acting growth hormone - treatment

Publikationsverlauf

Eingereicht: 18. Juni 2024

Angenommen nach Revision: 23. August 2024

Artikel online veröffentlicht:
11. Oktober 2024

• References

• 1 Han TS, Cadge B, Conway GS. Hearing impairment and low bone mineral density increase the risk of bone fractures in women with Turner's syndrome. Clin Endocrinol 2010; 65: 643-647
• 2 Landin-Wilhelmsen K, Bryman I, Windh M. et al. Osteoporosis and fractures in Turner syndrome-importance of growth promoting and oestrogen therapy. Clin Endocrinol 2010; 51: 497-502
• 3 Gravholt CH, Andersen NH, Christin-Maitre S. et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2023 Aarhus International Turner Syndrome Meeting. Eur J Endocrinol 2024; 190: G53-G151
• 4 Gravholt CH, Andersen NH, Conway GS. et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol 2017; 177: G1-G70
• 5 Ikegawa K, Hasegawa Y. Fracture risk, underlying pathophysiology, and bone quality assessment in patients with Turner syndrome. Front Endocrinol (Lausanne) 2022; 13: 967857
• 6 Nanao K, Tsuchiya Y, Kotoh S. et al. Low vertebral cancellous bone density in peripubertal girls with Turnerʼs syndrome and boys with hypogonadism. J Pediatr Endocrinol Metab 2002; 15: 1537-1542
• 7 Faienza MF, Brunetti G, Ventura A. et al. Mechanisms of enhanced osteoclastogenesis in girls and young women with Turnerʼs Syndrome. Bone 2015; 81: 228-236
• 8 Jeddi M, Hatami M, Omrani N. et al. Fibroblast growth factor 23 and its role in phosphate homeostasis in growing children compared to adults. J Pediatr Endocrinol Metab 2020; 33: 1065
• 9 Lappe JM, Watson P, Gilsanz V. et al. The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development. J Bone Miner Res 2015; 30: 156-164
• 10 Rodríguez-Arnao J, James I, Jabbar A. et al. Serum collagen crosslinks as markers of bone turn-over during GH replacement therapy in growth hormone deficient adults. Clin Endocrinol (Oxf) 1998; 48: 455-462
• 11 Locatelli V, Bianchi VE. Effect of GH/IGF-1 on bone metabolism and osteoporsosis. Int J Endocrinol 2014; 235060: 1-25
• 12 Zadik Z, Landau H, Chen M. et al. Assessment of growth hormone (GH) axis in Turnerʼs syndrome using 24-hour integrated concentrations of GH, insulin-like growth factor-I, plasma GH-binding activity, GH binding to IM9 cells, and GH response to pharmacological stimulation. J Clin Endocrinol Metab 1992; 75: 412-416
• 13 Gravholt CH, Frystyk J, Flyvbjerg A. et al. Reduced free IGF-I and increased IGFBP-3 proteolysis in Turner syndrome: modulation by female sex steroids. Am J Physiol Endocrinol Metab 2001; 280: E308-E314
• 14 van Pareren YK, de Muinck Keizer-Schrama SM, Stijnen T. et al Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens. J Clin Endocrinol Metab 2003; 88: 1119-1125
• 15 Wang L, Huang P, Du H. et al. Assessment of bone densitometry using radiography with a step-wedge phantom: a pilot study of the forearm. Quant Imaging Med Surg 2022; 12: 3340-3350
• 16 Gao X, Chen J, Cao B. et al. First clinical study on long-acting growth hormone therapy in children with Turner sydrome. Horm Metab Res 2022; 54: 389-395
• 17 Zhang Yaqin LH, Ji Chengye Study on the body proportion growth pattern of normal children and adolescents aged 0 to 18 years in China. Chin J Evidence-Based Pediatr. 2010 5. 349-354
• 18 Group of China Obesity Task Force Body mass index reference norm for screening overweight and obesity in Chinese children and adolescents. Zhonghua Liu Xing Bing Xue Za Zhi. 2004 25. 97-102
• 19 Idell Pyle S, Hoerr NL. Radiographic atlas of skeletal development of the knee. A standard of reference. J Bone Joint Surg British. 1956 38-B 961-962
• 20 Luo X, Hou L, Liang L. et al. Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies. Eur J Endocrinol 2017; 177: 195-205
• 21 Luo X, Zhao S, Yang Y. et al. Long-acting PEGylated growth hormone in children with idiopathic short stature. Eur J Endocrinol 2022; 187: 709-718
• 22 Zhang Y, Huang X, Li C. et al. Broad application prospects of bone turnover markers in pediatrics. J Clin Lab Anal 2022; 36: e24656
• 23 Huang Y, Eapen E, Steele S. et al. Establishment of reference intervals for bone markers in children and adolescents. Clin Biochem 2011; 44: 771-778
• 24 Chubb SAP, Vasikaran SD, Gillett MJ. Reference intervals for plasma β-CTX and P1NP in children: a systematic review and pooled estimates. Clin Biochem 2023; 118: 110582
• 25 Choi JS, Park I, Lee SJ. et al. Serum procollagen type I N-terminal propeptide and osteocalcin levels in Korean children and adolescents. Yonsei Med J 2019; 60: 1174-1180
• 26 Bayer M. Reference values of osteocalcin and procollagen type I N-propeptide plasma levels in a healthy Central European population aged 0-18 years. Osteoporos Int 2014; 25: 729-736
• 27 Gardner J, Ashraf A, You Z. et al. Changes in plasma FGF23 in growth hormone deficient children during rhGH therapy. J Pediatr Endocrinol Metab 2011; 24: 645-650
• 28 Efthymiadou A, Kritikou D, Mantagos S. et al. The effect of GH treatment on serum FGF23 and Klotho in GH-deficient children. Eur J Endocrinol 2016; 174: 473-479