Association Between Serum Calcium And Phosphorus Levels And Insulin-like Growth Factor-1 In Chinese Children And Adolescents With Short Stature

Objective: This study was designed to investigate the effect of serum calcium and phosphorus levels on the insulin-like growth factor 1(IGF-1)in Chinese children and adolescents with short stature.Methods: 747 subjects from the Growth and Development Diseases in Shandong Province: a cohort follow-up study(GDDSD study)and were diagnosed as short stature(height below-2 SD)in the Endocrinology Department of the Affiliated Hospital of Jining Medical University from March 2013 to February 2019.The research collected basic information including patient’s essential information;physical examination data including height(Ht),weight(Wt),Tanner stage,etc.;laboratory indicators including blood routine,electrolytes,fasting plasma glucose,IGF-1,lipid profiles,liver function,kidney function,growth hormone;Imaging examinations mainly include bone age radiographs of the hands and wrists,magnetic resonance imaging of the pituitary gland,and gynecological B-ultrasound(for female patients).The cross-sectional analysis method was used to analyze the relationship between serum calcium and phosphorus levels and IGF-1 in the included population.Furthermore,the population was divided into growth hormone deficiency(GHD)and idiopathic short stature(ISS),compared the differences in related clinical indicators,and the correlation between serum calcium and phosphorus levels and IGF-1 was analyzed respectively.Results: In all children with short stature,the univariate analysis results showed that serum calcium or phosphorus was significantly associated with IGF-1 SDS.In addition,after adjusting for possible confounding factors,a linear relationship between serum calcium and IGF-1 SDS and a non-linear relationship between serum phosphorus and IGF-1 SDS were observed by smooth curve fitting.The results of the fully adjusted linear regression demonstrated that serum calcium was positively associated with IGF-1 SDS(β 1.07,95% CI 0.21,1.92;P =0.015).In the multivariate piecewise linear regression,when the serum phosphorus level was greater than 1.26 mmol/L,the IGF-1 SDS increased with the increase in serum phosphorus(β 1.92,95% CI 1.36,2.48;P <0.001).However,we did not distinguish a significant relationship when the serum phosphorus level was < 1.26 mmol/L(P = 0.223).In the GHD population,the results of univariate analysis showed that there was no correlation between serum calcium and IGF-1 SDS.However,serum phosphorus was significantly related to IGF-1 SDS.After adjusting for possible confounding factors,the linear relationship between serum calcium and IGF-1 SDS and the nonlinear relationship between serum phosphorus and IGF-1 SDS were observed by smooth curve fitting.A fully adjusted linear regression model showed that serum calcium was positively correlated with IGF-1 SDS(β 1.07,95% CI 0.05,2.08;P = 0.041).In multiple piecewise linear regression,when the serum phosphorus level > 1.26 mmol/L,IGF-1 SDS increased with the increase of serum phosphorus(β 1.83,95% CI 1.17,2.49;P < 0.001).However,when the serum phosphorus level < 1.26 mmol/L,we also did not observe a significant relationship(P = 0.314).In the ISS population,the results of univariate analysis showed that serum calcium was not correlated with IGF-1 SDS(P = 0.064),and serum phosphorus was significantly correlated with IGF-1 SDS(P =0.007).After adjusting for possible confounding factors,a linear relationship between serum calcium and phosphorus and IGF-1 SDS was observed by smooth curve fitting.The results of multivariate regression analysis show that serum phosphorus was positively correlated with IGF-1 SDS(β 1.78,95% CI 0.87,2.70;P < 0.001),and serum calcium was not correlated with IGF-1 SDS(P = 0.144).Conclusions: This study demonstrated that in Chinese children and adolescents with short stature,IGF-1 SDS has a linear relationship with serum calcium and a non-linear relationship with serum phosphorus.After subgroup analysis,this relationship is still significant in the population with GHD.In the ISS population,the concentration of serum phosphorus is significantly positively correlated with IGF-1 SDS and there is no significant correlation between serum calcium and IGF-1 SDS.This indicates that in Chinese children and adolescents with short stature,circulating serum calcium and phosphorus concentrations may have a regulatory effect on IGF-1 levels,but this relationship deserves further study.