Elsevier

Clinical Biochemistry

Volume 96, October 2021, Pages 63-70
Clinical Biochemistry

Comparison of the difference in serum insulin growth factor-1 levels between chronological age and bone age among children

https://doi.org/10.1016/j.clinbiochem.2021.07.008Get rights and content

Highlights

  • There can be a significant difference between bone age and chronological age in evaluating IGF-1 levels in children.

  • This can significantly reduce the proportion of IGF-1 values above the upper limit of the kit reference range in children.

  • This suggests that it is more appropriate to use BA to determine the results of IGF-1 in puberty.

Abstract

Objective

By measuring serum insulin-like growth factor-1 (IGF-1) levels in children aged 2–16, we aimed to analyze the changes in IGF-1 levels in different sex and age groups, and compare the consistency of IGF-1 results evaluated by chronological age (CA) and bone age (BA) in children.

Methods

A cross-sectional study was conducted between January 2017 and December 2020 among 2979 relatively healthy children who attended the Department of Growth and Development outpatient clinic and health care center of the Affiliated Children’s Hospital of the Capital Institute of Pediatrics and underwent health examination and development assessment. Height, weight, and Tanner pubertal stage were measured by pediatricians. The CHN method was used to estimate BA. Venous blood samples were collected from the children, and IGF-1 levels were determined via chemiluminescence.

Results

IGF-1 levels in childhood increased slowly with age, dramatically during puberty, and continuously with growth until to 15 years for boys and reached a peak value at 13 years for girls based on CA. IGF-1 levels reached peak values at 14 and 13 years for boys and girls, respectively, based on BA. There were differences in IGF-1 values between the CA and BA groups at the age of 10–11 years for boys and 7–11 years for girls. A total of 103 boys (7.7%) and 17 girls (1.0%) had IGF-1 levels below the lower limit of the reference range based on CA; evaluating based on BA, there were 82 boys (6.1%) and 15 girls (0.9%) still had IGF-1 values less than the lower limit of the reference range. Eighteen boys (1.3%) and 173 girls (10.5%) had IGF-1 levels above the upper limit of the reference range based on CA; evaluating based on BA, these numbers reduced to 5 (0.4%) among boys and 41 (2.5%) among girls.

Conclusions

There is a significant difference between BA and CA in evaluating IGF-1 levels in children, which can significantly reduce the proportion of IGF-1 values above the upper limit of the kit reference range in children. This suggests that children with BA advanced in pubertal period, the evaluating results of IGF-1 should be corrected by using BA.

Introduction

The growth hormone (GH)–insulin-like growth factor-1 (IGF-1) axis is a master endocrine regulator for growth and development in children. GH and IGF-1 play significant roles in regular biological processes in childhood and puberty, including cell proliferation and differentiation, organ growth and development, skeletal growth, and metabolism [1]. IGF-1 is stable in blood samples and can objectively reflect GH levels. Therefore, IGF-1 is more favorable for clinical application [2].

Similar to physical growth, IGF-1 levels are affected by factors, such as genetics, age, sex, hormonal and environmental factors, nutritional status, and puberty [3], [4]. IGF-1 levels tend to increase slowly with age in childhood, increase rapidly during puberty, and decrease gradually in late adolescence [5], [6], [7], [8], [9], [10]. Therefore, the clinical interpretation of IGF-1 results needs to be comprehensively evaluated using a variety of factors. Determining the results of IGF-1 according to the range of IGF-1 reference values of chronological age (CA) alone may not be accurate enough.

Bone age (BA) is a better indicator of biological development, which is largely represented by the degree of physiological maturity. It has been reported that BA is strongly associated with the pubertal growth spurt, secondary sexual development and menarche [11], [12]. Advanced BA is often accompanied by an elevated level of IGF-1. GH deficiency and low IGF-1 levels in childhood are associated with delayed bone maturation [13]. Some scholars have pointed out that compared with CA, a combination of IGF-1 and BA can be a more objective and reliable measure to assess the maturity status of children [14], [15]. Due to the time of puberty onset and the pace of pubertal progression, which varies among children, there are great individual differences in the level of physical growth during puberty, which lead to CA usually not correspond to BA. Therefore, the accurate assessment of IGF-1 levels in clinical practice is very important. A review paper, titled “Short stature in Childhood–Challenges and Choices,” published in the New England Journal of Medicine in 2013, pointed out that since IGF-1 levels increase rapidly with the onset of puberty, its results must be interpreted relative to BA, rather than CA [16]; however, to the best of our knowledge, no study has verified this point of view. The main purpose of this study was to compare the differences in IGF-1 levels based on CA and BA groups, and to verify the rationality of using BA to assess IGF-1 levels.

Section snippets

Subjects

The study subjects were 2979 relatively healthy children (1338 boys and 1641 girls) who attended the Department of Growth and Development outpatient clinic and health care center of the Affiliated Children’s Hospital of the Capital Institute of Pediatrics for health examination and development assessment between January 2017 and December 2020. All children underwent physical examinations, measurement of IGF-1 levels, and BA assessment via radiography of the left hand. The exclusion criteria

Baseline characteristics

Among the 2979 children included in the present study, 1338 (44.9%) were boys and 1641 (55.1%) were girls. The average CA and BA of the boys were 8.91 ± 3.33 years and 8.88 ± 3.70 years, respectively, and the average CA and BA of the girls were 8.48 ± 2.32 years and 9.18 ± 2.71 years, respectively. Girls had higher mean IGF-1 values than boys. Table 1 summarizes the demographic, anthropometric, and IGF-1 values of this study.

IGF-1 levels according to CA

The distributions of IGF-1 levels according to CA and sex are shown in

Discussion

In this study, we summarized the changing pattern of IGF-1 based on CA and BA among boys and girls and compared the consistency in IGF-1 results evaluated by CA and BA among children. The results showed that the mean level of IGF-1 for girls was higher than that for boys, both in the CA and BA groups. IGF-1 levels were strongly associated with the level of growth and development. In childhood, IGF-1 value increase slowly with age, and then rapidly increase with accelerated physical linear

Conclusion

Compared with the CA group, the change in IGF-1 level in the BA group was more consistent with the characteristics of growth and development among children. For children with BA advanced in pubertal period, the evaluating results of IGF-1 should be corrected by using BA. This can help physicians to more comprehensively and accurately evaluate the development of children, screen growth disorders, monitor the effect of treatment, and achieve better efficacy under the premise of safety in children

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The authors thank Xin-Yu Yuan, superintendent radiographer of the Medical Imaging Center of Capital Institute of Pediatrics, and his team for their support with this study.

Funding information

This study was funded by the CAMS Innovation Fund for Medical Sciences (CIFMS) (grant number 2016-I2M-1-008), and the Public Service Development and Reform Pilot Project of Beijing Medical Research Institute (grant number BMR2019-11).

Author contributions statement

J.G., Y.L., and Y.Z. contributed to the collection of clinical data. J.G. designed the study and wrote the manuscript under the instruction of Professor H.L. All authors read and approved the final paper prior to submission.

Availability of data and materials

All data relevant to the study are included in the article.

References (30)

  • D.R. Clemmons

    Clinical utility of measurements of insulin-like growth factor 1

    Nat. Clin. Pract. Endocrinol. Metab.

    (2006)
  • M. Bidlingmaier et al.

    Reference intervals for insulin-like growth factor-1 (igf-i) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations

    J. Clin. Endocrinol. Metab.

    (2014)
  • C. Alberti et al.

    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

    Clin. Chem.

    (2011)
  • S. Xu et al.

    Reference ranges for serum IGF-1 and IGFBP-3 levels in Chinese children during childhood and adolescence

    Endocr. J.

    (2010)
  • C. Löfqvist et al.

    Reference values for insulin-like growth factor-binding protein-3 (IGFBP-3) and the ratio of insulin-like growth factor-I to IGFBP-3 throughout childhood and adolescence

    J. Clin. Endocrinol. Metab.

    (2005)
  • 1

    ORCID ID: 0000-0002-5270-8276.

    2

    ORCID ID: 0000-0003-2950-4942.

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