Improvement in Growth in Adolescents with Average Height Using A Massage Chair: A Prospective Single Arm Pre-Post and National Standard Data Comparison Study

Article information

Perspect Integr Med. 2023;2(3):164-172

Publication date (electronic) : 2023 October 23

doi : https://doi.org/10.56986/pim.2023.10.004

Sul Gi Park ¹

, Gyu Tae Chang ²

, Jin Yong Lee ³

, Sun Haeng Lee ⁴^,

¹Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea

²Department of Pediatrics, College of Korean Medicine, Kyung Hee University, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea

³Korea Institute of Oriental Medicine, Daejeon, Republic of Korea

⁴Department of Pediatrics, College of Korean Medicine, Kyung Hee University, Kyung Hee University Medical Center, Seoul, Republic of Korea

^*Corresponding author: Sun Haeng Lee, Department of Pediatrics, College of Korean Medicine, Kyung Hee University, Kyung Hee University Medical Center, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea, Email: civil011@khu.ac.kr

Received 2023 August 21; Revised 2023 September 16; Accepted 2023 September 17.

Abstract

Background

This study aimed to examine the changes in height, weight, and bone age between pre- and post-intervention when using a BEG-100 massage chair daily.

Methods

Thirty-five children aged 11 years who were close to the average height (145–155 cm) were included in the study. There were 34 participants who used the BEG-100 massage chair for 24 weeks. Daily intervention consisted of 20 minutes of lower body massage and 10 minutes of whole-body massage. Height, weight, and adverse events were checked every five visits, while a hand X-ray was used before and after massages. The height percentile and height standard deviation score (SDS) were calculated using the 2017 Korean growth chart. The bone age and predicted adult height using radiographs were computed using the Tanner-Whitehouse method. The paired t-test or Wilcoxon signed-rank test was used according to normality of data to determine statistical significance.

Results

A total of 31 children were included in the final analysis. The height percentile and height SDS significantly increased after BEG-100 massage chair use (2.39; p = 0.032, and 0.07; p = 0.036, respectively). However, these changes were not significant in children whose baseline height was shorter than the average. There were no significant differences in bone age, height for bone age, predicted adult height, or sitting height/height ratio. None of the participants complained of adverse events.

Conclusion

The height percentile and SDS of teenagers increased after use of massage chair therefore, it is necessary to perform larger randomized controlled clinical studies. Trial registration: KCT0004673.

Keywords: adolescent; body height; growth; massage;

Visual abstract

Introduction

The majority of children with short stature do not have growth hormone (GH) deficiency or other pathological diseases interfering with normal growth [1]. Treatment with GH is approved for children with idiopathic short stature by the United States Food and Drug Administration. However, routine application of GH treatment is not recommended for every child with short stature because of interindividual variability in responsiveness of GH [2]. Therefore, many other alternative therapies have been conducted to promote growth, such as herbal medicine, acupuncture, chiropractic, and pressing-kneading massage [3].

Massage promotes blood and lymphatic flow, reduces swelling of muscles and connective tissues, relaxes stiff muscles, and improves organ function [4]. In addition, massage stimulates the skin and muscles on the body’s surface to activate sensory, heat, vibration, and pain receptors, and transmits the stimulus to the autonomic and central nervous system, thereby improving pain, anxiety, and sleep quality [5].

With rapid technological developments, manual techniques can be implemented using mechanical devices without the need for manual handling; hence, mechanical massage can be performed using a skilled manual technique at any time in a private, convenient, and controlled setting [6,7]. Previous studies demonstrated the effects of mechanical massage using a massage chair on muscle relaxation [7], reducing back pain [4] and stress [8], ameliorating heart rate, blood pressure, and temperature [9], regulating muscle fatigue and sympathetic and parasympathetic balance [10], enhancing sleep quality [7], recovering mental fatigue, and improving cognition [11].

Research on pediatric massage therapy has been reported to be prolific [12], but the growth-promoting effect of massage has been mostly observed in preterm infants [13,14]. In a situation where studies exploring the growth effect of massage post infancy are rare, confirming the growth effect of massage may provide evidence for complimentary therapy for pediatric growth. A massage chair developed in 2019, the BEG-100, enhances stretching around the knee after fixation of the knee and ankle regions [15]. Periodic stretching of the soft substrate helps the formation and growth of fibrous tissue by changing the stiffness of the substrate [16]. Massage chair stretching is projected to have a favorable impact on growth. The purpose of this study was to investigate the effect and possible adverse events (AEs) of massage chairs on growth promotion in children with average height and compare the results with the Korean national standard statistical dataset.

Materials and Methods

The study protocol was registered with the Clinical Research Information Service (KCT0004673) and published in 2020 [15].

1. Study design

This was a single-arm pilot study with a pre-post evaluation using a Korean national standard data comparison, designed to assess the improvement in height growth in children aged 11 years with an average height following 24 weeks use of a massage chair.

2. Participants

Thirty-eight children were enrolled between January 2020 and April 2021 at the Kyung Hee University Medical Center. The sample size was determined based on comparative human studies that confirmed the effect of massage on growth, as there are few prior studies that have verified the growth effect of massage chairs. In previous studies, 30 children per group were selected to assess the growth effect of massage [7,17]. Based on a 20% dropout rate, the optimum total number of participants was determined to be 38 or more. Considering the size of the massage chair, male and female children with heights of 145–155 cm were targeted. To control for age as a confounding factor, the age of the participants was limited to 11 years (average height ranged from 144.7 cm to 151.3 cm for both males and females). The participants were given a complete explanation of the study, and a written informed consent was obtained from the children and their representatives.

Children with growth retardation due to endocrinopathy, history of intrauterine growth retardation, chronic or terminal diseases, musculoskeletal conditions or diseases that make the implementation of the massage chair difficult, clinically significant diseases, and psychopathy were excluded from the study. Children who received growth-related treatment or participated in a clinical study within four weeks of screening, were planning to receive a growth-related treatment within the study period, were judged unsuitable for participation by the researcher, or were outside the normal range for related tests were also excluded.

Other medications, Korean medicines, health functional foods, and treatments that could affect growth should not be taken by the participants. Participants receiving: (1) growth hormones; (2) growth-promoting Korean medicines such as herbal medicine tonifying Qi, tonifying blood, or improving digestion; (3) growth-promoting health functional foods such as nutritional supplements; or (4) growth-promoting treatments such as leg correction, orthotherapy, physical therapy, rehabilitation, acupuncture, electroacupuncture, pharmacopuncture, bee venom, moxibustion, cupping, cognitive behavior therapy, and mind-body therapy were excluded from the study.

3. Intervention

All eligible patients were assigned to the intervention and were required to use the massage chair growth mode for 30 minutes once a day for 24 weeks. The BEG-100 massage chair (Bodyfriend, Inc., Seoul, Republic of Korea) was used to potentially promote height growth. After enrolling, the manufacturer delivered the BEG-100 massage chair to the participants’ homes and was also responsible for the massage chair’s care and return. The growth mode on the BEG-100 massage chair consisted of 20 minutes of lower-body and 10 minutes of whole-body massage. The lower-body growth mode is described as massage to stimulate the growth plate of the knee by focusing on stretching the knee and lower extremities. It provides traction and axial pressure on the distal end of the femur, which is the upper part of the knee, and the foot is fixed by an airbag. In the whole-body growth mode, the massage stretches both the upper and lower body. The upper-body growth mode stretches the spine and upper body. To achieve a massage experience like warm hands, the BEG-100 massage chair employs a thermal massage ball and a thermal airbag for heat delivery. The leg portions of the BEG-100 massage chair automatically adapted to the user’s leg length, which ranged from 9 cm to 20 cm. Two rollers massaged the soles of their feet, while heels were massaged through three airbags.

If AEs linked to BEG-100 massage chair occurred, such as abrasion, bruising, contusion, muscle and tendon injury, allergic reactions, burns, and spinal sprain or fracture, the participants were guided to discontinue using the massage chair and receive appropriate treatment.

Face-to-face adherence reminder sessions were conducted at each visit every 8 weeks following participant allocation. Compliance when using the BEG-100 massage chair was measured by participants’ reports. The participants might report more or less frequency about the intervention, but this was unlikely because of the absence of a related reward or penalty. The reminder sessions included the importance of using the device for 30 minutes once a day and maintaining a compliance of 70% or higher, how to use the device, and calling the clinic in case of problems such as abnormal symptoms or device failure. At follow-up visits, participants were asked if they had experienced any problems using the massage chair.

4. Outcome measurements and assessments

4.1. Height

Height was measured while the participant was barefoot, and the value was rounded off to two decimal places. Height was measured by a trained nurse at the same time of the day (±1 hour) to reduce height deviation during the day. Height was be measured using a portable stadiometer (Seca 213, Seca GmbH, Hamburg, Germany) that can gauge heights ranging from 20 cm to 205 cm. Height was assessed from screening to closing.

The height percentile and standard deviation score [SDS (Z score)] were computed from the 2017 growth chart for Korean children and adolescents [18]. The growth rate was calculated by dividing the height difference following intervention by the number of days required. The seated height-to-standing height ratio was computed by detecting the height in the seated position (Seca 213, Seca GmbH, Hamburg, Germany).

4.2. Bone age

Single posteroanterior X-rays of the participants’ left hand were taken at the 2^nd and 5^th visits, and bone age was calculated using the Tanner-Whitehouse (TW) method. The maturity of the hand ossification centers were rated as a radius-ulnar-short bone (RUS) score from 0 to 1,000 as compared with the bone age Korean growth chart for each sex and age [19]. The TW3 RUS score was generated by researchers who had been trained for > 3 months before performing this assessment.

Predicted adult height was computed from the measured height and RUS score using the TW3 equations, which were developed for males, females before menarche, and females after menarche. The height SDS for bone age was estimated using the 2017 Korean growth chart for children and adolescents.

4.3. Weight

Weight was measured whilst the children wore light clothing, and the value was rounded to two decimal places. Measurements were taken by a trained nurse using a load cell scale (Jenix DS-103 M, Dong Sahn Jenix Co., Ltd, Seoul, Republic of Korea) that can weigh loads ranging from 10 kg to 200 kg. Weight was also assessed from screening until close-out of the clinical trial. Body mass index (BMI) was calculated by dividing the weight by the square of the height.

4.4. Adverse events

To verify clinical safety, the researchers collected all self-reported AEs during each visit and recorded the event, date, severity, course, seriousness, causality, and treatment performed for the AEs in the case report form. When the child did not report any AEs, the severity was considered minor or nonexistent. When the reported AEs were insufficient for the participant to withdraw from the study, the severity was considered moderate. When a child had to be excluded from the study to undergo treatment for AE, the severity was considered severe.

5. Statistical design and analysis

A full analysis set (FAS) and per-protocol set (PPS) were used to analyze the outcomes of the clincal trial. The FAS was designed for all participants whose heights were assessed more than once after beginning the intervention on the BEG-100 massage chair and who did not significantly violate any of the inclusion criteria. The PPS was aimed at all individuals who had been in a massage chair for ≥ 118 days (70% of the total 168 days). The safety analysis targeted all participants with relevant safety data which had been gathered by phone or during a face-to-face visit.

Continuous data were presented as the mean and standard deviation. The primary outcome of height percentile, and secondary outcomes of height SDS, height SDS for bone age, predicted adult height estimated by bone age, sitting height-to-standing height ratio, and BMI were analyzed using a paired t-test or Wilcoxon signed-rank test according to normality of the data. For height and weight, a paired t-test or Wilcoxon signed-rank test was used to compare the final height and weight, and estimated from the standard growth after 24 weeks of the initial percentile as an existing parameter. The final bone age and age at 0.5 years of initial bone age were compared using the paired t-test or Wilcoxon signed-rank test. The growth rate following the intervention was assessed using the paired t-test or Wilcoxon signed-rank test. Additional analyses were conducted by grouping according to baseline height SDS. The number of each AEs was counted in all visits.

All statistical tests were performed with a significance threshold of 0.05 in two-tailed testing. The last-observation-carried-forward approach was used to impute the missing data.

6. Data monitoring

Three Korean medicine doctors who were not involved in the study organized the data monitoring committee. They monitored confidential documents, protocol violations, and monthly AEs. The Korean Medicine Clinical Trial Center of Kyung Hee University Korean Medicine Hospital a standard operating procedure for interim reports and discontinuance criteria be pursued. The principal investigator addressed any issues that were discovered.

Results

According to the inclusion and exclusion criteria of this study, three out of 38 initial volunteers were excluded from the clinical trial and 35 were assigned to the intervention. Excluding one participant who withdrew from the study because of difficulty in placing the massage chair in the house, there were 34 participants who completed the study, Among the 34 study participants, although they passed the screening, three children with a height of less than 145 cm and greater than 155 cm at the 2^nd visit before the intervention were excluded from the final analysis. The compliance rate of the 31 participants was 71.7–100%; therefore, 31 participants were analyzed without distinguishing between the FAS and PPS analysis. However, safety analysis was performed for 34 children who used the BEG-100 massage chair more than once (Fig. 1; Table 1). There were no significant abnormalities in the initial vital signs, electrocardiogram, hematologic, endocrine, serum biochemical, or urine tests.

Fig. 1

Flow diagram of the phases throughout this clinical trial.

Table 1

Demographic Data of Participants (n = 31).

To observe the change in height growth before and after use of the massage chair, the difference in height percentile between the 2^nd and 5^th visits was analyzed. After mechanical massage with a massage chair, paired-sample t-tests indicated that the height percentile increased significantly (mean difference, 2.39; 95% CI, 0.22–4.55, p = 0.032; Table 2). For the height SDS, there was a significant change before and after the massage chair (mean difference, 0.07; 95% CI, 0.01–0.14, p = 0.036; Table 2). However, these changes in height percentile and SDS were not significant in children whose baseline height was shorter than the average (Table 3).

Table 2

Comparison of the Changes in the Parameters Following 24 weeks of Intervention.

Table 3

Subgroup Analysis of Height Standard Deviation Score.

Among the outcome measurements, the height and BMI increased significantly (p = 0.032 and < 0.001, respectively), and the difference between the presumed weight based on the 2^nd visit and the final weight was significant (p = 0.006). However, there were no significant differences in the height SDS for bone age, predicted adult height estimated by bone age, and sitting height/height ratio when comparing before and after the intervention. The height and weight at the 5^th visit were significantly higher than the presumed data only in the children whose baseline height was taller than the average (p = 0.042 and 0.016, respectively). The bone age and growth rate following the intervention was not significantly different compared with the presumed data based on Visit 2.

None of the participants reported AEs, and the changes in blood and urine biomarkers, vital signs, or electrocardiogram readings were not statistically different when comparing before and after the intervention.

Discussion

Massage has individual effects depending on the competence level or technique of the practitioner. To reduce this bias, a preliminary study was conducted using a massage chair that provides massage of a uniform strength and frequency. A massage chair can deliver an expert massage including pressing, tapping, patting, and stretching [20]. The BEG-100 massage chair, consists of airbags, rollers, and thermal massage balls to deliver 12 program of automated massage. Whole-body growth mode and lower-body growth program modes were used in this study.

The height of the participants naturally increased over the course of 24 weeks as to be expected of an 11-year-old child. Therefore, the height percentile was used as the primary indicator to determine whether values increased due to the intervention or improved due to general growth as compared with the national growth chart for Korean children and adolescents. The percentile was calculated according to the least mean square estimation using the nonlinear least square method. The improvement in height percentile of the participant indicated that he or she has grown more than the average Korean child of the same age and sex, and the growth was more than the usual estimation.

Height percentile and height SDS increased during the use of massage chairs in growing children of average height. The improvement in the height SDS of 0.07 over 24 weeks could be converted to an improvement of 0.14 in one year, which is 28%–46% of the first year’s response to GH treatment in children who are short in stature (standard treatment) [21]. However, the height percentile was significantly increased only in children taller than average whom accounted for the 64.5% of the participants. This result might be influenced by the intrinsic growth potential of taller participants, however, this would also be reflected in the growth chart for Korean children and adolescents. In addition, the height and weight were significantly higher than the presumed data only in taller children.

The height SDS for bone age was not significantly changed; hence, the predicted adult height estimated by bone age was not signifcantly improved. The growth rate following the intervention was not significantly different compared with the national data. A change in the treatment period or intensity may be necessary to achieve clearer results for height growth.

The sitting height/height ratio was the same before and after intervention. Despite the longer intervention time of the lower body massage (20 min out of 30 min), the massage chair evenly affected the growth of the upper and lower body.

It has been reported that massage improved growth parameters such as weight, lean mass, and bone mineral density in preterm infant studies [13,14]. The weight of older children in this current study also increased compared with the growth chart for Korean children and adolescents’ national data, and the BMI also increased after using the BEG-100 massage chair. These results might be due to parasympathetic activity caused by the stimulation of pressure receptors in the skin and muscles [22]. Vagal activity increases intestinal peristalsis and accelerates gastric emptying so the child quickly feels hungry and food intake may increase [23]. Biological evidence associated with growth other than vagus stimulation by massage needs to be studied.

There was no significant difference between bone age and the presumed data indicating that the BEG-100 massage chair did not affect bone maturation. The 34 participants who received treatment using the BEG-100 massage chair reported no AEs. Generally, massage increases gastric motility [24] and insulin-like growth factor-1 [25], and also stimulates vagal activity which is associated with improved sleep-arousal behavior [26]. Thus, the massage chair may have the potential to stimulate growth with low risk to the user.

This study was a single-arm pre-post and national standard data comparison study; therefore, the growth effect due to the BEG-100 massage chair could not be proven because of the absence of a comparison group. However, with the possibility that the massage chair affects the growth of children, it is necessary to perform larger randomized controlled clinical studies.

Manual massage consists of not only stimulation through touch but also through the sense of smell in the essential oils used, and in a soothing comfortable environment with relaxing music and a trusted practioner. As the massage chair simply implements body pressure and heat, the growth-promoting effect of the massage chair may be less effective than manual massage. A massage chair with aromatherapy or music therapy may have a closer effect to manual massage.

Conclusion

The height percentile and height SDS of the growing teenagers increased after the massage intervention using the massage chair. However, the causality of intervention cannot be determined because this was a single arm study involving many unaccounted variables. Given that no AEs occurred, the BEG-100 massage chair may have the potential to increase growth with a low risk to the user. The growth effect of massage chairs should be determined in larger randomized controlled clinical studies.

Acknowledgements

We would like to thank Bodyfriend, Inc. for supporting the study.

Notes

Author Contributions

Conceptualization: JYL. Data curation: SGP. Formal analysis: SGP. Funding acquisition: SHL. Investigation: SGP. Methodology: GTC. Project administration: SHL. Resources: GTC. Software: SGP. Supervision: SHL. Validation: SGP. Visualization: SHL. Writing original draft: SGP. Writing - review and editing: GTC, JYL, and SHL.

Conflicts of Interest

The authors declare that they have no competing interests.

Funding

Conduction of the study was supported by the Bodyfriend, Inc. (Seoul, Republic of Korea).

Ethical Statement

The study was performed in accordance with the principles of the Declaration of Helsinki, and the Ethical Guidelines for Clinical Research, and the Institutional Review Board of Kyung Hee University Korean Medicine Hospital (no.: KOMCIRB 2019-03-002). The participants were given a complete explanation of the study, and written informed consent was obtained from the children and their parent, carer, or guardian.

Data Availability

The data that supports the findings of this study are available from Bodyfriend, Inc. but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission from Bodyfriend, Inc.

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Article information Continued

This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

Funded by : Bodyfriend, Inc. (Seoul, Republic of Korea)

Funding : Conduction of the study was supported by the Bodyfriend, Inc. (Seoul, Republic of Korea).

Table 1

Demographic Data of Participants (n = 31).

Characteristics	Total	Male	Female
General characteristics

Sex (M/F)	31	17	14
Maternal height (cm)	159.63 ± 5.14	160.91 ± 4.25	158.07 ± 5.84
Paternal height (cm)	173.55 ± 4.83	174.59 ± 5.04	172.29 ± 4.41
Mid parental height (cm)	167.23 ± 8.71	174.25 ± 4.01	158.68 ± 3.45

Baseline

Chronological age (y)	11.44 ± 0.33	11.40 ± 0.31	11.48 ± 0.35
Bone age (y)	11.91 ± 0.98	11.75 ± 1.13	12.11 ± 0.74
Sexual maturity rating (I/II/III/IV/V)	11/11/5/4/0	11/5/1/0/0	0/6/4/4/0
Nutrition intake (good/bad) ^§	31/0	17/0	14/0
Time spent exercising (0–0.5/0.5–1/1–2/ > 2 h/d)	10/11/10/0	3/7/7/0	7/4/3/0
Height percentile	59.06 ± 20.51	63.89 ± 20.47	53.20 ± 19.70
Height (cm)	149.67 ± 2.56	149.97 ± 2.90	149.31 ± 2.13
Height SDS (cm) ^†	0.27 ± 0.58	0.40 ± 0.58	0.10 ± 0.55
Height SDS for bone age (cm) ^†	−0.15 ± 0.98	0.07 ± 1.15	−0.42 ± 0.67
Expected height estimatied by bone age (cm) ^‡	174.16 ± 8.01	178.53 ± 4.17	163.56 ± 3.81
Sitting height (cm)	80.15 ± 1.83	80.22 ± 1.92	80.05 ± 1.78
Sitting height/height ratio	0.54 ± 0.01	0.53 ± 0.01	0.54 ± 0.01
Weight (kg)	45.57 ± 7.02	47.43 ± 6.61	43.32 ± 7.08
BMI (kg/m²)	20.34 ± 3.10	21.11 ± 3.03	19.42 ± 3.03
GH level (ng/ML)	1.70 ± 3.14	1.65 ± 3.77	1.79 ± 2.31
IGF-1 level (ng/ML)	327.81 ± 125.89	252.06 ± 100.13	419.79 ± 87.28
IGFBP-3 level (ng/ML)	6,105.81 ± 1125.26	5,667.06 ± 1,080.84	6,638.57 ± 962.7

End point

Chronological age (y)	12.41 ± 0.98	11.90 ± 0.31	11.98 ± 0.35
Bone age (y)	12.47 ± 0.77	12.38 ± 0.88	12.57 ± 0.63
Sexual maturity rating (I/II/III/IV/V)	7/10/10/4/0	7/8/2/0/0	0/2/8/4/0
Nutrition intake (good/bad)^§	29/2	15/2	14/0
Time spent exercising (0–0.5/0.5–1/1–2/ > 2 h/d)	15/10/5/1	7/6/3/1	8/4/2/0
Height percentile	61.45 ± 21.56	65.12 ± 21.59	56.99 ± 21.45
Height (cm)	153.31 ± 3.10	153.84 ± 3.50	152.66 ± 2.51
Height SDS^† (cm)	0.34 ± 0.62	0.45 ± 0.64	0.20 ± 0.60
Height SDS^† for bone age (cm)	−0.11 ± 0.84	−0.01 ± 0.91	−0.24 ± 0.76
Expected height estimated by bone age (cm) ^‡	174.87 ± 7.66	178.96 ± 4.12	163.94 ± 4.59
Sitting height (cm)	82.26 ± 2.00	82.41 ± 2.31	82.08 ± 1.62
Sitting height/height ratio	0.54 ± 0.01	0.54 ± 0.01	0.54 ± 0.01
Weight (kg)	49.86 ± 7.58	51.95 ± 7.26	47.34 ± 7.43
BMI (kg/m²)	21.04 ± 3.18	21.98 ± 3.27	19.90 ± 2.77

Continuous valuables are expressed as mean ± SD.

^†

SDS = (measured value - mean value of the reference population)/standard deviation of the reference population.

^‡

Seven patients (S-KH-01, 11, 21, 23, 25, 33, 37) had menarche before the age of 12 and were excluded from the estimation of predicted height.

^§

Nutrition intake was determined as good when bread, cereals and potatoes; fruit and vegetables; milk, cheese and dairy; meat, fish, and alternatives; fats, oils, and confectionery were all consumed according to nutrition survey.

BMI = body mass index; GH = growth hormone; IGF-1 = insulin-like growth factor-1; IGFBP-3 = insulin-like growth factor binding protein-3; SDS = standard deviation score.

Pre-post comparision (n = 31)	Pre-intervention	Post-intervention	Mean difference (95% CI)	Analysis	p
Height percentile	59.06 ± 20.51	61.45 ± 21.56	2.39 ± 5.91 (0.22–4.55)	Paired t-test	0.032^*
Height (cm)	149.67 ± 2.56	153.31 ± 3.10	3.64 ± 1.28 (3.17–4.11)	Paired t-test	< 0.001^***
Height SDS (cm)	0.27 ± 0.58	0.34 ± 0.62	0.07 ± 0.18 (0.01–0.14)	Paired t-test	0.036^*
Height SDS for bone age (cm)	−0.15 ± 0.98	−0.11 ± 0.84	0.04 ± 0.43 (−0.12–0.20)	Paired t-test	0.603
Predicted adult height estimatied by bone age (cm)^*	174.16 ± 8.01	174.87 ± 7.66	0.71 ± 1.78 (−0.04–1.46)	Paired t-test	0.063
Sitting height/height ratio	0.54 ± 0.01	0.54 ± 0.01	0.00 ± 0.01 (0.00–0.00)	Paired t-test	0.479
BMI (kg/m²)	20.34 ± 3.10	21.04 ± 3.18	0.70 ± 0.79 (0.41–0.99)	Paired t-test	< 0.001^***

Comparison with presumed data	Presumed Visit 5	Visit 5	Mean difference (95% CI)	Analysis^†	p

Height (cm)	152.87 ± 2.72	153.31 ± 3.10	0.44 ± 1.22 (−0.01–0.89)	Paired t-test	0.053
Weight (kg)	48.23 ± 7.45	49.86 ± 7.58	1.63 ± 3.07 (0.51–2.76)	Paired t-test	0.006^**
Bone age (y)	12.41 ± 0.98	12.47 ± 0.77	0.05 ± 0.45 (−0.11–0.22)	Paired t-test	0.526

	Visit 2 - Presumed Visit 5	Visit 2 - Visit 5	Mean difference (95% CI)	Analysis^†	p

Growth rate (mm/d)	0.18 ± 0.02	0.20 ± 0.07	0.02 ± 0.07 (0.00–0.05)	Paired t-test	0.054

Pre-post comparision	Baseline height SDS < 0 (n = 11)				Baseline height SDS ≥ 0 (n = 20)

	Pre-intervention	Post-intervention	Analysis	p	Pre-intervention	Post-intervention	Analysis	p
Height percentile	34.81 ± 6.84	36.42 ± 11.51	Wilcoxon signed-rank test^‡	0.898	72.40 ± 10.58	75.22 ± 10.10	Paired t-test	0.014^*
Height (cm)	147.48 ± 1.79	150.61 ± 2.03	Paired t-test	< 0.001^***	150.88 ± 2.09	154.80 ± 2.55	Paired t-test	< 0.001^***
Height SDS (cm)	−0.40 ± 0.18	−0.36 ± 0.31	Wilcoxon signed-rank test^‡	0.898	0.63 ± 0.34	0.72 ± 0.36	Paired t-test	0.025^*
Height SDS for bone age (cm)	−0.51 ± 0.71	−0.50 ± 0.59	Paired t-test	0.921	0.04 ± 1.07	0.10 ± 0.89	Paired t-test	0.546
Predicted adult height estimatied by bone age (cm) ^†	167.67 ± 7.32	168.27 ± 6.64	Paired t-test	0.391	178.06 ± 5.61	178.83 ± 5.14	Paired t-test	0.102
Sitting height/height ratio	0.54 ± 0.01	0.53 ± 0.01	Paired t-test	0.856	0.54 ± 0.01	0.54 ± 0.01	Paired t-test	0.294
BMI (kg/m²)	19.17 ± 2.12	19.72 ± 2.09	Paired t-test	0.039^*	20.99 ± 3.40	21.77 ± 3.49	Paired t-test	< 0.001^***

Comparison with presumed data	Presumed Visit 5	Visit 5	Analysis	p	Presumed Visit 5	Visit 5	Analysis	p

Height (cm)	150.42 ± 1.54	150.61 ± 2.03	Paired t-test	0.635	154.22 ± 2.25	154.80 ± 2.55	Paired t-test	0.042^*
Weight (kg)	44.02 ± 5.15	44.76 ± 5.07	Paired t-test	0.145	50.55 ± 7.59	52.67 ± 7.34	Paired t-test	0.016^*
Bone age (y)	12.43 ± 0.88	12.48 ± 0.59	Paired t-test	0.765	12.40 ± 1.05	12.46 ± 0.87	Wilcoxon signed-rank test^‡	0.694

	Visit 2 - Presumed Visit 5	Visit 2 - Visit 5	Analysis	p	Visit 2 - Presumed Visit 5	Visit 2 - Visit 5	Analysis	p

Growth rate (mm/d)	0.16 ± 0.03	0.17 ± 0.07	Wilcoxon signed-rank test^‡	0.922	0.18 ± 0.02	0.22 ± 0.07	Wilcoxon signed-rank test^‡	0.070