Objectives: To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children.
Methods: A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes.
Results: There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05).
Conclusions: The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.
目的: 比较重组人生长激素（recombinant human growth hormone, rhGH）治疗前后特发性矮小症（idiopathic short stature, ISS）患儿血清Klotho、成纤维细胞生长因子23（fibroblast growth factor, FGF23）和胰岛素样生长因子（insulin-like growth factor, IGF）-1水平变化，探讨Klotho和FGF23与ISS患儿生长激素（growth hormone, GH）/IGF-1生长轴的关系。方法: 前瞻性选择2021年3月10日—2022年12月1日在河北省人民医院儿科确诊为ISS的33例儿童为ISS组，选择同期于儿童保健科就诊，年龄、性别与ISS组匹配的29例健康儿童为健康对照组。ISS组给予rhGH治疗，比较治疗前及治疗3、6、9个月血清Klotho、FGF23、IGF-1水平，并进行相关性分析。结果: ISS组与健康对照组的血清IGF-1、Klotho、FGF23水平比较差异无统计学意义（P>0.05）。rhGH治疗3、6、9个月的ISS组血清Klotho、FGF23、IGF-1水平均较治疗前显著升高（均P<0.05）。ISS组治疗前Klotho、FGF23与磷酸盐水平均呈正相关（P<0.05）；治疗前及治疗3、6、9个月的Klotho与IGF-1水平均呈正相关（P<0.05），FGF23与IGF-1水平均呈正相关（P<0.05），Klotho与FGF23水平均呈正相关（P<0.05），Klotho、FGF23水平与身高标准差积分无相关性（P>0.05）。结论: rhGH治疗可上调Klotho、FGF23及IGF-1水平，实现ISS患儿的追赶生长。Klotho、FGF23可能并非直接促进ISS患儿线性生长，而是可能通过IGF-1及磷酸盐代谢等途径产生间接影响。Klotho、FGF23与IGF-1的一致变化表明三者在调节ISS线性生长中存在协同关系。.
Keywords: Child; Fibroblast growth factor 23; Idiopathic short stature; Insulin-like growth factor-1; Klotho; Physical development.