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. 2025 Jul 1;25:476. doi: 10.1186/s12887-025-05821-3

24-Week jumping exercise influence on growth speed and GH-IGF-1-IGFBP-3 axis among short-stature children

Huiming Wang 1, Xing Wang 1,✉, Xiang Wang 2, Xin Xin 1, Hui Zhang 3, Shuqi Jia 1, Wenyuan Wang 4
PMCID: PMC12219976  PMID: 40597964

Abstract

Objective

To explore the effect of jumping exercises on improving short-stature symptoms and changes of serum GH, IGF-1, IGFBP-3, and IGF-1/IGFBP-3 in short-stature patients, so as to provide potential theoretical reference for short-stature treatment.

Methods

A non-randomized controlled intervention study was registered on January 8, 2025, with the China Clinical Trial Registry (ChiCTR2500095544). This study was conducted with the recruitment of 15 short-stature children in the same environment (Exercise Experimental Group 1); 20 children with normal development level (Blank Control Group 2); and 27 healthy short-stature children in this area (Short Blank Control Group 3). Children in Group 1 were given exercise intervention for 24 weeks, and those in the other two groups were provided with natural observation for 24 weeks. After the experiment, this study further analyzed the growth values of height, growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein 3 (IGF-BP-3) and IGF-1/IGF-BP-3 of the three groups.

Results

After 24 weeks of exercise intervention, Group 1 had higher height, serum IGF-1, and the growth value of molar ratio of IGF-1/IGFBP-3 than those of Group 2 and Group 3, with statistically significant difference between Group 1 and Group 3 (all p < 0.05). However, there was no significant difference in serum GH level and its growth value among groups before and after the experiment (p > 0.05),. In addition, the serum IGFBP-3 in Group 1 was lower than that in Group 2 and Group 3 (both p < 0.01).

Conclusion

The 24-week jumping exercise intervention can effectively improve the height of short-stature children. It can enhance the function of GH-IGF-1-IGFBP-3 axis through improving serum IGF-3 level and molar ratio of IGF-1/IGFBP-3, while decreasing the level of serum IGFBP-3. Nevertheless, exercise intervention has no effect on morning GH secretion in short-stature children.

Keywords: Short-stature, Exercise to improve height, GH, IGF-1, IGFBP-3, Molar ratio of IGF-1/IGFBP-3

Short-stature is defined as a height of at least 2 standard deviations lower than the average height of a specific population of the same age, the same gender and the same living environment. The incidence of short-stature is 2% worldwide and about 3% in China [1]. In general, the longitudinal bone growth of children may be mediated by the axis of growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGF-BP-3) [2, 3, 4]. Children may show delayed growth and development in case of a dysfunction in the GH-IGF-1-IGFBP-3 axis [5, 6], which will lead to short-stature. In addition to lower body height than ordinary people, short-stature patients may also experience obesity, insulin resistance, abnormal glucose tolerance and sensorineural deafness in adulthood [7, 8]. Simultaneously, there is a decrease in bone mass and an increase in the risk of fracture [9]. Short-stature may also trigger potential adverse effects on children’s mental health, such as anxiety and depression [10]. In addition, short-stature children have impairment in behavioral adaptability, cognitive and self-awareness to vary degrees [11, 12].

According to existing data, running and jumping exercises with intensity close to the anaerobic threshold can accelerate the growth of short-stature children [13]. Flexible training can also boost the growth of children [14]. Meanwhile, exercise has been revealed to elevate GH level, and resistance training can also improve the levels of IGF-1 and IGFBP-3 in obese girls [15]. According to Wolff’s law, the growth, absorption and reconstruction of bone are all related to the stress state of bone. Significantly, jumping exercise can increase the stress of lower limb bone and obviously accelerate the growth of bone cells in specific children. Various evidence show that exercise can accelerate the growth of short-stature children and affect the level of GH-IGF-1-IGFBP-3 in children.

At present, short-stature children are mainly treated through the injection of recombinant GH, with significant therapeutic effect on GH deficiency patients and other types of dwarfism [16]. Given a single clinical treatment, the present study was conducted to explore the effect of exercise as a therapeutic intervention on the growth rate of short-stature children. Simultaneously, we known little about the effect of exercise on the GH-IGF-1-IGFBP-3 axis of short-stature children considering that relevant research on this topic is still at infancy. For the first time, this study investigated the GH, IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio in short-stature children. It is anticipated that the proposed treatment for short-stature children may facilitate a reduction in the financial burden of parents, and the psychological burden of children, as well as promoting the all-round development of children.

In light of this, this study observed the changes of GH-IGF-1-IGFBP-3 axis in short-stature children through 24 weeks of exercise intervention. It may reveal the endocrine mechanism of the impact of exercise on height, which may shed light on exercise-based treatment of short-stature.

Methods

Subjects

This experiment was completed from October 20, 2023 to April 30, 2024 This study included short-stature children who have not yet entered the peak growth period and those with normal height at the same developmental level. from a primary school in Wuzhi County, Jiaozuo City, Henan Province (Northern China). Subjects o Meanwhile, under the assistance of pediatricians of Jiaozuo Second People’s Hospital, short-stature subjects were recruited for health observation in this region. The observation lasted 24 weeks or 6 months. All participants had the same physical education and health course under the same intensity, twice a week for 45 min each time. Moreover, all participants had the same dietary habits, sleep schedule, and did not contract any other chronic diseases during the experimental period.

The Exercise Experimental Group (Group 1) and Short Blank Control Group (Group 3) included children: (1) proportional build body at birth, with normal height and weight; (2) with height 2 standard deviations lower or after the 3th percentile of the height of normal children of the same age, sex and region; (3) normal or delayed bone age; (4) without systemic diseases related to the endocrine, chromosome and nutrition; (5) with annual growth rate of less than 5 cm; and (6) aged between 8 and 11 years old. Exclusion criteria: (1) those with ankle or knee injuries; (2) those who couldn’t participate in moderate-intensity physical exercise; (3) those with GH therapy; (4) non-boarding students; and (5) those with other chronic diseases.

The inclusion criteria in the Blank Control Group (Group 2) were: (1) those with proportional build body at birth, with normal height and weight; (2) without systemic diseases related to the endocrine, chromosome and nutrition; (3) height range of between − 1 and + 1 for normal children of the same age, gender and region; (4) annual growth rate of > 5 cm; and (5) aged between 7 and 10 years old.

These eligibility criteria were strictly followed in the process of recruiting subjects, with voluntarily signed informed consent forms. This study was conducted based on the latest ethical requirements of Declaration of Helsinki and was approved by the Ethics Committee of Shanghai University of Sport (Approval No. 102772023RT137), Registration date is October 16th, 2023。This study has been registered as a clinical trial in China with registration number (ChiCTR2500095544, Passed on January 8th, 2025。For subjects under the age of 16, this study obtained the consent of their parents or legal guardians before conducting the test.

As a result, there were 15 short-stature children in Group 1, including 8 boys and 7 girls, with an average age of 9.9 ± 1.98. In Group 2, there were 20 children with normal height, including 13 boys and 7 girls, with an age of 8.5 ± 1.07. All participants were boarding students, had the same diet, daily-routine and physical in-class activities. There were 27 children in Group 3, including 11 boys and 16 girls, with an average age of 9.48 ± 1.27. As shown in Table 1, there was no significant difference in gender (chi-square test, p > 0.408), age (univariate analysis of variance, p < 0.05) or height (p > 0.05) among groups, and age between Group 1 and Group 3 (p > 0.05).

Table 1.

Basic information of subjects

Gender, Boys/girls Age Height
Group 1 8/7 9.87 ± 1.18 125.61 ± 5.70
Group 2 12/8 8.48 ± 1.08 128.43 ± 7.70
Group 3 11/16 9.48 ± 1.27 124.20 ± 6.79
X²/F 1.793 6.663 2.203
p 0.408 0.002 0.120
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Note: Data are expressed as mean ± standard deviation

Recruitment flow chart of subjects

The subject recruitment process is shown in Fig. 1.

Fig. 1.

Fig. 1

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Recruitment flow chart of subjects

Experimental process chart

The experimental process of subjects is shown in Fig. 2.

Fig. 2.

Fig. 2

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Experimental process chart

Indicator measurement

  1. Height.

    The height of all subjects was measured at the same time on the same day 。 The height and weight meter (RGZ-120, Jiangsu Deliberate Technology Co. Ltd., China) was used to measure the height at least three times until the difference of the data was small and stable.

  2. Serum GH.

    Blood samples of the included subjects were collected at 9 AM on the same day to measure serum GH using Roche 601 electrochemical luminescence analyzer (Sweden).

  3. Serum IGF-1 and IGF-BP-3.

    After the collection of blood samples of the included subjects at 9 AM on the same day, this study further measured the serum levels of IGF-1 and IGF-BP-3 using immulite2000 Chemical luminescence immunity analyzer (Siemens, Germany).

Experimental plan

In accordance with Wolff’s law and by referring to previous literature [13, 14], this experimental plan was developed with strict control of the exercise intensity and form during intervention to ensure the exercise cycle and duration.

From November 1, 2023 to April 1, 2024 (24 weeks in total), participants received training subjects for three times a week, namely 4:40 − 5:30 pm on every Monday, Wednesday and Friday. The specific contents are as follows:

  1. Intervention Content.
    • ① Preparation: Jog for 5 min to warm up, and then stretch the joints.
    • ② Basic part: 35 min in total.
      10 groups of 45-second rope-jumping with an interval of 75 s per group,
      6 groups of one-leg jumping (jumping on pedals with one leg only, and not change the leg throughout the exercise), with a distance of 1 m between each pedal (5 pedals totally), with the interval of 30 s per group,
      6 groups of jumping on pedals (jumping on pedals with two legs), with a distance of 1 m between each pedal (5 pedals totally), with the interval of 30 s per group.
      2 groups of 10-meter crawling, with the interval of 30 s per group.
    • ③ Ending part: 5 min of relaxation exercise.

Control and monitoring of exercise amount

The intensity of exercise intervention was calculated by Gelish method following the equation of HRmax = 207 − 0.7*age. A moderate exercise intensity was adopted, with the intensity range of 64-77% (HRmax = 207 − 0.7*9.9 = 200.03, HRmax(64) = 200.03*0.64 = 128.19, HRmax (77) = 200.03*0.77 = 154.231). Furthermore, The target heart rate was ranged 128–155 based on a comprehensive consideration.

The heart rate was monitored by wearing PolarH10 heart rate belt, and the target heart rate was between 128–155.If the average heart rate was lower than 120 times during four training sessions within a week, the duration of the original 45-second rope-jumping would be extended by 3–5 s, with the rest time reduced by 3–5 s correspondingly. Similarly, the rope-jumping duration would reduce by 3–5 s in case of the heart rate of > 160 times to ensure that the duration of two minutes/group was unchanged.

Data analyses

According to the preliminary experiment, Group 1, Group 2, and Group 3 had a height increase of 4.60 ± 0.10, 3.43 ± 0.12, and 3.32 ± 1.55, respectively. The difference test effect size was η 2 = 0.226, 1:1:2 for the control group, with α = 0.05, power = 0.90. The sample sizes calculated using PASS 2021 software for Group 1, Group 2, and Group 3 were at least 13, 13, and 26 cases, respectively. The final sample sizes for each group were 15, 20, and 27 cases, respectively, which met the requirements.

Statistical analyses of all experimental data were conducted in SPSS25.0 statistical software. Measurement data were expressed by “mean ± standard deviation”, and counting data were expressed by percentage (%), with the use of X2 test. After the test of normality, the inter-group and intra-group comparisons used one-way analysis of variance (ANOVA)/H test, and paired sample T/non-parametric test, respectively. P < 0.05 suggested a significant difference, and P < 0.01 meant highly significant difference.

Results

Baseline analyses among groups

As shown in Table 2, according to chi-square test, there was no significant difference in gender among groups (p > 0.05). One-way ANOVA revealed statistical difference in the comparison of the age of Group 2 with that of Group 1 and Group 3 (p < 0.05), but no difference between Group 1 and Group 3 (p > 0.05). Furthermore, based on the analysis of one-way ANOVA/H test, there was no significant difference during the pre-test in height, IGF-1, IGF-BP-3 and IGF-1/IGF-BP-3 molar ratio among groups (p > 0.05). There was a significant difference in IGF-BP-3 between Group 2 and Group 1&3 (p < 0.05), but no difference in IGF-BP-3 between Group 1 and Group 3 (p > 0.05). Due to the pulse-like release of GH in body, GH was only used as reference data, indicating that Group 1 and Group 3 were at the same baseline level; while the age and IGF-BP-3 were inconsistent between Group 2 and Group 1&3 as Group 2 was healthy controls with normal height.

Table 2.

Baseline analyses among groups

Group 1 Group 2 Group 3 F/H P

Age

Gender

Pre-test Height (cm)

9.87 ± 1.18

8/7

125.61 ± 5.70

8.48 ± 1.08

12/8

128.43 ± 7.70

9.48 ± 1.27

11/16

124.20 ± 6.79

F = 6.663

χ = 1.793

F = 2.203

0.002

0.408

0.120
At Rest GH (ng/ml) 4.74 ± 3.01 1.98 ± 2.76 1.41 ± 1.79 F = 9.316 < 0.001
Pre-test IGF (ug/L) 195.20 ± 54.45 196.86 ± 83.31 187.11 ± 59.32 H = 0.291 0.869
Pre-test IGFBP3 (mg/L) 4.89 ± 0.55 4.22 ± 0.57 4.83 ± 0.83 H = 9.108 0.011
Pre-test IGF1/IGFBP-3 Molar Ratio 0.04 ± 0.01 0.05 ± 0.02 0.04 ± 0.01 H = 92.340 0.310
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Pre-test difference analyses among groups

As depicted in Fig. 3 regarding pre-test differences, there was no significant difference in pre-test height, IGF-1, IGFBP-3 and IGF-1/IGF BP-3 molar ratio among groups (one-way ANOVA/H test, p > 0.05). Significant differences were observed in GH and IGFBP3 in different groups at rest (p < 0.05). Specifically, there were statistically significant differences of GH in the comparison of Group 1 and Group 2 (p < 0.05), as well as that of Group 1 and Group 3 (p < 0.01). Meanwhile, there also existed statistically significant differences in IGFBP-3 between Group 1 and Group 2 (p < 0.05), as well as that between Group 2 and Group 3 (p < 0.01).

Fig. 3.

Fig. 3

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Pre-test difference analyses among groups

Post-test difference analyses among groups

Post-test comparison is shown in Fig. 4. Through one-way ANOVA/H test, there were significant differences in height, IGFBP-3 and IGF-1/IGFBP-3 molar ratio among groups (p < 0.05), except for GH, IGF-1 (p > 0.05). It was found that there were statistical significant differences in height between Group 2 and Group 3, as well as in IGFBP-3 between Group 1 and Group 2 was statistically significant (p < 0.05). and the IGFBP-3 of Group 1and Group 3 was statistically significant (p < 0.05). In addition, there was statistically significant difference in the molar ratio of IGF-1/IGFBP-3 between Group 1 and Group 3 (p < 0.05).

Fig. 4.

Fig. 4

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Post-test difference analyses of groups

Difference analyses of growth value among groups

In Fig. 5, there were significant differences in the growth values of height, IGF-1, IGFBP-3 and IGF1/IGFBP3 among groups (one-way ANOVA/H test, p < 0.05), but no such result was found in the growth value of GH among groups at rest (p > 0.05). To be specific, there were statistically significant differences in the height of Group 2 and Group 3 (p < 0.05), as well as that of Group 1 and Group 3 (p < 0.01); in IGF-1 of Group 1 and Group 3 (p < 0.01), as well as that of Group 2 and Group 3 (p < 0.05); and in IGFBP-3 of Group 1 and Group 2, as well as that of Group 1 and Group (both p < 0.01). Meanwhile, differences were statistically significant in molar ratios of IGF-1/IGFBP-3 between Group 1 and Group 2 as well as between Group 1 and Group 3 (both p < 0.01). Collectively, exercise had a significant effect on the height growth of Group 1, and it could improve the function if the GH-IGF-1-IGFBP-3 axis.

Fig. 5.

Fig. 5

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Difference analyses of growth value among groups

Discussion

In this study, 24-week jumping exercise can evidently improve the growth rate of short-stature children to reach that of children with normal height. Meanwhile, it can increase the serum IGF-1 level and IGF-1/IGFBP-3 molar ratio, while reducing the serum IGFBP-3 level of short-stature children. The research results are consistent with those reported by Wang Peiyun [13], proving that jumping exercise is effective to improve the height of short-stature children. Exercise works to accelerate the growth of short-stature children by increasing IGF-1 level and IGF-1 molecular activity, reducing IGF-BP-3 level, and finally strengthening the function of GH-IGF-1-IGF-BP-3 axis.

Given the importance of GH and GH-IGF-1-IGFBP-3 axis in controlling body height [2, 3, 4], this study for the first time used the GH-IGF-1-IGFBP-3 axis of short-stature children for exercise intervention to clarify the effect of exercise on this growth axis. In terms of the role of exercise in improving children’ height, Wang Peiyun [13]foundincreased height of 3.43 cm in short boys and 3.60 cm in girls with the training program that the exercise intensity was close to the anaerobic threshold and that the exercise form was running and jumping. In this study, the height growth of the intervention group was 4.32, which was 3.39 higher than that of the normal controls and 2.48 higher than that of short blank controls, and was close to the 5 cm annual growth of normal children. It indicates that exercise intervention can evidently promote the height growth of short-stature children. GH is a protein hormone with a single peptide chain, which is secreted by eosinophils in the anterior pituitary. As the most important growth regulator, GH mainly stimulates the growth and differentiation of bone and cartilage cells, and it can also interact with various growth factors, especially IGF-1. GH acts mainly through the following two mechanisms. First, it can stimulate hepatocytes to release IGFs, and then it acts on target cells to promote cell proliferation and growth [17]. Second, GH can directly bind to GH receptors on the surface of target cells to stimulate cell growth [18]. Eventually, GH regulates the longitudinal growth of bone, bone metabolism and bone transformation synthetically. According to existing studies, after-school physical exercise can increase the GH level of girls [19], and one-time or acute exercise can increase the GH level [20]. Moreover, exercise can be used as a means to detect GH [21]. Some researchers proposed no obvious difference in GH between trained female basketball players and normal female college students [22]. Another study revealed no difference in GH level between U15 male soccer players in China and their peers, and long-term sports training produced no effect on GH level of U15 male soccer players [23]. In this experiment, after 24 weeks’ observation, there was no significant difference in pre-test and post-test GH levels, which was consistent with previous research results [22]. Therefore, it is ascertained that, during long-term exercise intervention, there is no effect on morning GH secretion among short-stature children. It can be determined that the promotion of height growth through exercise is not achieved by increasing GH levels, suggesting that GH supplementation in combination with exercise intervention will result in faster growth rate. IGF-1 is a basic peptide consisting of 70 amino acids encoded by a gene on chromosome 12, which is positively regulated by GH [24]. IGF-1 is an important hormone that causes the differentiation and regeneration of epiphyseal chondrocytes, and promotes bone formation; and it is an endocrine growth factor that effectively promotes bone anabolism and growth [25]. It has been reported that 5-week exhaustive exercise elevated the level of IGF-1 in adult rats after experiment when compared to that before experiment [26]. Meanwhile, another study revealed that adopting 60-minute physical activities (four times a week for 12 weeks, in various forms) produced a positive effect on obese girls in primary school after exercise [27]. In this study, the growth value of IGF-1 in children after exercise intervention was significantly higher than that in the other two groups. Great improvement in IGF-1 level can accelerate the differentiation and regeneration of bone cells are accelerated, as well as the growth of children’ longitudinal bones. It may therefore hint a rapid increase in the height after IGF-1 level improvement through exercise intervention. IGFBP-3 is a macromolecular protein that is positively regulated by GH. When IGFBP-3 binds to IGF-1, it can reduce the concentration of free IGF, which is beneficial to play and magnify the role of IGF-1 and enhance the activity of IGF-1 receptor [28]. Under the influence of GH, IGF-1 and IGFBP-3 can stimulate the proliferation of epiphyseal plate, promote the synthesis of collagen and sulfated mucopolysaccharide, participate in the regulation of protein metabolism, and hence promote growth and improve height [29]. At the same time, IGFBP-3, the binding protein of IGF-1, can regulate the IGF-1 activity in tissues to some extent, and the molar ratio of IGF-1/IGF-BP-3 can unveil the number of IGF-1 with biological activity [30, 31, 32]. For instance, a study developed an aerobic exercise scheme (4 h/day, six times/week, for 4 weeks) for 39 obese female teenagers, showing decreased IGFBP-3 level after experiment [15]. In this experiment, the level of IGF-BP-3 decreased significantly and that of IGF-1 increased after the intervention, resulting in greatly increased molar ratio of IGF-1/IGF-BP-3, significantly higher than that of the other two groups. Accordingly, long-term exercise intervention can reduce the level of IGF-BP-3 and improve the biological activity of IGF-1. Altogether, long-term jumping exercise can improve the height of short-stature children, while too high IGFBP-3 value may affect the growth pace of children.

At present, research on short-stature patients mainly focuses on the detection of genetic genes [33] and related gene mutation [34]. Mutation in specific genes can block gene expression, thus compromising the growth rate of children. Genetic detection can benefit the determination of the cause of short-stature, and formulation of treatment plans in advance. At present, short-stature is generally treated by GH or IGF-1, and drugs that delay epiphyseal fusion [35]. Exercise can affect enzyme activity and the expression of certain DNA fragments when genes mutate or DNA expression is blocked. We should explore in the future whether exercise can affect the activity of certain enzymes or the expression of certain proteins. In addition, the combination of exercise and GH therapy should be a key focus of exploration in the future.

Limitations

  1. This study investigated the growth axis only, and the evidence of the results would be more sufficient if the metabolic characteristics of bone cells in short-stature children were considered in this study.

  2. This study was conducted based on relatively limited short-stature patients. Meanwhile, there were not enough samples to set up short-stature control groups in the same environment, which restricted the control of other interference factors.

  3. Due to the need to compare the growth rates of three groups during the experimental period, the difference in height SDS was not used to indicate the differences in growth rates when selecting outcome indicators.

  4. In this experimental plan, when determining exercise intervention for short-stature similar to ours, the intensity and frequency of exercise should be strictly controlled, and attention should be paid to upper limb training and post-exercise stretching training. In addition, a professional exercise expert is needed to develop the exercise plan.

Conclusion

The 24-week exercise intervention can accelerate the growth of short-stature children, which can be used as a treatment or prevention measure. This intervention can increase serum IFG-1 level, decrease the level of IGF-BP-3, and elevate the molar ratio of IGF-1/IGF-BP-3 among short-stature children, but has no effect on morning serum GH secretion. The results of this study support that the combination of growth hormone therapy and exercise will have a better growth effect.

Acknowledgements

We thank all of the staff who contributed their time to our research.

Author contributions

Huiming Wang and Xing Wang conceived and designed the study, Xiang Wang, Xin Xin, Shuqi Jia analyzed the data, Hui Zhang, Wenyuan Wang assisted in the experiment. All authors contributed sufficiently to this work. All authors read and approved the final manuscript.

Funding

This work was supported by Shanghai Key Lab of Human Performance (Shanghai University of sport) (NO. 11DZ2261100).

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This study is in line with and follows the Declaration of Helsinki.The studies involving humans were approved by Ethics Committee of the Shanghai University of Sport (No. 102772023RT137). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.Clinical registration number is ChiCTR2500095544. The registration date is January 8, 2025. For subjects under the age of 16, we have obtained the consent of their parents or legal guardians before conducting the test. Their parents or legal guardians, as well as participants in the study, have given their consent for the test information to be published. All experimental procedures complied with relevant ethical standards and guidelines.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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