Serum Concentrations of Insulin-like Growth Factor (IGF)-1 and IGF Binding Protein-3 (IGFBP-3), IGF-1/IGFBP-3 Ratio, and Markers of Bone Turnover: Reference Values for French Children and Adolescents and z-Score Comparability with Other References

Abstract

BACKGROUND A reference model for converting serum growth factor and bone metabolism markers into an SD score (SDS) is required for clinical practice. We aimed to establish reference values of serum insulin-like growth factor-1 (IGF-1) and IGF binding protein 3 (IGFBP-3) concentrations and bone metabolism markers in French children, to generate a model for converting values into SDS for age, sex, and pubertal stage. METHODS We carried out a cross-sectional study of 1119 healthy white children ages 6–20 years. We assessed concentrations of serum IGF-1, IGFBP-3, carboxyterminal telopeptide α1 chain of type I collagen (CrossLaps), and bone alkaline phosphatase concentrations and height, weight, and pubertal stage, and used semiparametric regression to develop a model. RESULTS A single regression model to calculate the SDSs with an online calculator was provided. A positive relationship was found between SDS for serum IGF-1 and IGFBP-3, IGF/IGFBP-3 mol/L ratio, and anthropometric parameters (P < 0.0001), with slightly greater effects observed for height than for body mass index (BMI). There was a negative relationship between serum CrossLaps concentration and BMI, and a positive relationship between serum CrossLaps concentration and height. A comparison of serum IGF-1 reference databases for children showed marked variation as a function of age and pubertal group; smooth changes with age and puberty were observed only in our model. CONCLUSIONS This new model for the assessment of SDS reference values specific for age, sex, and pubertal stage may help to increase the diagnostic power of these parameters for the assessment of growth and bone metabolism disorders. This study also provides information about the physiological role of height and BMI for the interpretation of these parameters.