Effects of 24-week jumping exercise on bone mineral density and linear growth in children with short stature: a prospective controlled trial

Abstract

Objective

To investigate the effects of structured jumping exercise on femoral neck bone mineral density (BMD) and linear growth in children with short stature. Methods: A prospective controlled trial enrolled 47 prepubertal children (aged 8–11 years; intervention group, n = 20; control group, n = 27). The intervention group completed a 24-week progressive jumping protocol (3 sessions/week, 50 min/session), while controls maintained usual routines. Dual-energy X-ray absorptiometry (DXA) assessed lumbar spine and femoral neck BMD. Height gain and BMD changes were evaluated, with mediation analysis exploring indirect effects. Results: The intervention group showed significant improvement in femoral neck BMD Z-scores (Δ = 1.075, p < 0.001, Cohen’s d = 0.869) and greater height gain (Δ = 4.200 cm vs. 2.478 cm in controls; p = 0.001). Mediation analysis suggested an indirect effect of jumping on height via femoral neck BMD change (β = − 0.442, 95% CI: − 1.474 to − 0.009), with no direct effects observed (p > 0.05). Lumbar spine BMD did not differ between groups (p > 0.05). Conclusions: Jumping exercise appears to preferentially benefit femoral neck BMD; however, further investigation is needed to determine whether this effect is region-specific. These results support structured high-impact activity as a potential adjunctive approach in pediatric growth promotion.

Trial registration

The study protocol, which was predicated on a true experimental design, was registered with ClinicalTrials.gov (postregistration number ChiCTR2500095544).Registration date 20,250,108.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13102-025-01376-z.

Introduction

Short stature (SS), clinically defined as height >2 standard deviations below the mean or below the 3rd percentile for age-, sex-, and ethnicity-matched references, demonstrates a worldwide prevalence of 2.3%−5.2% [1].Within China’s pediatric population, SS affects approximately 3% of children aged 5–14 years [2].Beyond anthropometric impairments, SS presents with concomitant reductions in bone mineral density (BMD), metabolic abnormalities, and elevated cardiovascular risks [3].Of particular clinical significance, the psychological sequelae of SS—notably diminished self-esteem and social withdrawal tendencies—may persist throughout adulthood [4].While current therapeutic paradigms prioritize etiological management, idiopathic short stature (ISS)—comprising 80% of clinical presentations—remains diagnostically challenging due to its undefined pathological mechanisms, necessitating rigorous investigation of novel therapeutic approaches.

Although recombinant human growth hormone (rhGH) received FDA approval for idiopathic short stature (ISS) management, its clinical application remains controversial. Meta-analyses indicate that rhGH administration achieves modest height gains (0.3–0.5 SDS improvement) after 24-month therapy [5], while imposing substantial financial burdens (exceeding $20,000 annually) [6].Furthermore, the subcutaneous injection regimen demonstrates suboptimal adherence rates (< 40%), with prolonged administration potentially exacerbating metabolic complications including insulin resistance (IR) and slipped capital femoral epiphysis (SCFE) [7].Pharmacovigilance data from a multicenter cohort (n = 15,432) revealed marginal associations between rhGH exposure and all-cause mortality (HR 1.15, 95% CI 1.01–1.32), substantially complicating risk-benefit assessments in therapeutic decision-making [8].

Physical exercise serves as a non-pharmacological intervention modality, exerting mechanotransductive effects on bone remodeling and growth plate activation via cyclic mechanical loading [9].Longitudinal investigations have demonstrated that structured exercise regimens augment annual bone mineral density (BMD) accretion rates by 150% in typically developing children [10], while therapeutic benefits in SS populations remain inconclusive. Current scientific discourse centers on exercise modality and dose-response relationships: while aerobic training enhances cardiopulmonary capacity with minimal osteogenic impact [11], high-impact activities (e.g., jumping protocols) generating vertical ground reaction forces exceeding 400% body weight [12],preferentially activate Wnt/β-catenin signaling to stimulate osteogenic differentiation [13, 14].Preclinical models have established that controlled vertical impact loading induces 18% increases in growth plate thickness [15], whereas human trials remain predominantly focused on healthy cohorts, demonstrating a paucity of longitudinal randomized controlled trial (RCT) data specific to SS pathophysiology.

To address this research gap, we conducted a 24-week prospective randomized controlled trial (RCT) investigating the effects of structured vertical impact training on bone mineral density (BMD) and linear growth in children with idiopathic short stature (ISS). Utilizing a double-blind, double-dummy design, the control group received standard care while the intervention group underwent a progressive jump training protocol (3 supervised sessions/week, moderate-intensity exercise, 24-week intervention period). Lumbar spine BMD changes were quantified using dual-energy X-ray absorptiometry (DXA) with daily phantom calibration (Hologic Discovery WI, precision error < 0.5%). By integrating mechanobiology principles with ISS rehabilitation science, these findings establish an evidence-based framework for optimizing non-pharmacological interventions through controlled mechanical loading.

Subjects and methods

Sample size Estimation

Sample size calculation was performed using G*Power 3.1 (Faul, Erdfelder, Buchner, & Lang, 2007). An a priori power analysis was conducted based on a two-tailed independent-samples t-test, with significance level α = 0.05, statistical power (1–β) = 0.80, and an anticipated effect size of Cohen’s d = 0.90. The selected effect size was derived from pilot data and prior literature reporting large effects of high-impact exercise interventions on femoral neck bone mineral density (BMD) in prepubertal children (Cohen’s d ≥ 0.8) [16]. Based on a 1:1 allocation ratio, the estimated minimum sample size was 40 participants (20 per group). Initially, the study aimed to enroll 20 participants in both the experimental and control groups, assuming complete data collection without attrition. During recruitment, the actual allocation ratio was adjusted to 1:1.3 to enhance generalizability, resulting in final group sizes of 20 participants in the experimental group and 26 in the control group.

Study design and registration

This was a 24-week prospective controlled trial investigating the effects of a structured jumping exercise intervention on bone mineral density (BMD) and linear growth in prepubertal children with idiopathic short stature (ISS). The study protocol was registered with the Chinese Clinical Trial Registry (ChiCTR2500095544) on January 8, 2025. Ethical approval was obtained from the Institutional Review Board of Shanghai University of Sport (No.102772023RT137), and informed consent was obtained from the legal guardians of all participants. The trial adhered to the Declaration of Helsinki (2013 revision) and followed CONSORT 2025 guidelines.

The experimental phase spanned from January 1 to December 30, 2021, with participant recruitment conducted in two phases: 15 children with idiopathic short stature (ISS) were initially enrolled from a primary school in Wuzhi County, followed by supplemental recruitment of 5 participants from a neighboring school. The exercise intervention period extended from July 3 to December 30, 2021. The control group (n = 26) comprised age-matched children with ISS under health surveillance, recruited through pediatric endocrinologists at the Second People’s Hospital of Jiaozuo City. This cohort underwent 24-week observational monitoring from January 1, 2021 to January 1, 2022. Strict adherence to predefined inclusion/exclusion criteria was maintained throughout recruitment.

Participants and randomization

The experimental group comprised 20 children with idiopathic short stature (8 males, 12 females; mean age: 9.55 ± 1.28 years), all of whom were boarding students with standardized dietary intake, daily routines, and classroom physical activity levels. The control group included 27 children (11 males, 16 females; mean age: 9.48 ± 1.27 years). Baseline characteristics are presented in Table 1. Chi-square analysis indicated no significant difference in gender distribution (p > 0.05), and independent samples t-tests showed no significant between-group differences in age, height, weight, BMI, lumbar spine BMD, or femoral neck BMD (all p > 0.05). Notably, both groups exhibited significantly lower BMD in the femoral neck compared to the lumbar spines (t = 6.549, p < 0.001). Randomization was conducted at the school level rather than at the individual participant level. Specifically, using a computer-generated random sequence (SPSS 29.0). All students within each school who met the inclusion criteria were then recruited for participation. While participant blinding was not feasible due to the visible nature of the intervention, outcome assessors and data analysts remained blinded to group allocation.

Table 1.

Baseline characteristics of participants

Baseline Characteristics		Intervention Group(n = 20)	Control Group(n = 27)	t/χ2	P
Sex	Male	8(40.00)	11(40.74)	0.003	0.959
	Female	12(60.00)	16(59.26)
Age (years)		9.55 ± 1.28	9.22 ± 1.37	0.835	0.408
Weight (kg)		22.83 ± 2.45	21.96 ± 3.30	0.99	0.328
Height (cm)		125.27 ± 5.92	124.20 ± 6.79	0.565	0.575
BMI		14.52 ± 0.84	14.15 ± 0.76	1.599	0.117
Lumbar spine BMD		−0.50 ± 0.82	−0.63 ± 0.84	0.547	0.587
Femoral neck BMD		−1.63 ± 0.85	−1.52 ± 0.85	−0.44	0.662

Inclusion Criteria:

1. Normal anthropometric measurements (length and weight) at birth.

2. Height <−2SD or below the 3rd percentile for age- and sex-matched regional reference values.

3. Bone age within ± 1 year of chronological age or delayed.

4. Absence of systemic pathologies (endocrine, chromosomal, or nutritional disorders).

5. Annual growth velocity < 5 cm/year.

6. Age 8–11 years (prepubertal status confirmed by Tanner stage I).

Exclusion Criteria:

• 7.History of ankle/knee injuries requiring medical intervention within 6 months.
• 8.Contraindications to moderate-intensity physical activity (ACSM guidelines).
• 9.Current use of growth-related medications (e.g., GH therapy, steroids).
• 10.Non-boarding school students (to control environmental variables).
• 11.Chronic medical conditions affecting growth.

Content of the test

Physical fitness

Height and weight were measured using a calibrated RGZ-120 stadiometer (Jiangsu ST Medical Technology Co., Ltd., China). Each participant’s height was measured at least three times, with measurements repeated until consistency was achieved (variation < 0.2 cm). To minimize the influence of diurnal spinal compression, all anthropometric assessments were conducted under fasting conditions within a standardized morning time window (08:00–10:00).

Bone mineral density

Bone mineral density (BMD) measurements were performed using a dual-energy X-ray absorptiometry (DXA) system (Hologic Discovery W QDR4500, Hologic Inc., USA). Measurements were taken at the lumbar spine (L1–L4) and femoral neck (right hip). Lumbar spine BMD was used to represent axial (trunk) bone density, and femoral neck BMD as the representative of appendicular (lower extremity) density. Z-scores were calculated based on age-, sex-, and ethnicity-matched Chinese pediatric reference data (ages 3–18 years). Bone health was classified as follows: Z > − 1.0 (normal), − 1.5 < Z ≤ − 1.0 (mild osteopenia), − 2.0 < Z ≤ − 1.5 (moderate osteopenia), and Z ≤ − 2.0 (severe osteopenia).

Experimental protocol

Intervention program

The 24-week primary intervention protocol was implemented from January 1 to June 17, 2021, with triweekly training sessions conducted Mondays, Wednesdays, and Fridays (16:40 − 17:30). A supplemental experimental cohort underwent identical programming from July 3 to December 30, 2021. The structured exercise regimen comprised:

Intervention Design:

1. Dynamic Warm-up Protocol (10 min):5-minute progressive-intensity jogging.Full-body joint mobilization exercises.

2. Neuromuscular Training Circuit (35 min):10 × 45 s rope jumping intervals (75s active recovery)0.6×single-leg hop drills across 5 staggered platforms (1 m spacing, 30 s inter-set recovery)0.6×drop jumps from 5-tiered platforms (20–40 cm, 1 m progression, 30 s inter-set recovery)0.2 × 10-meter prone crawling sequences (30s inter-set recovery).

3. Structured Cool-down Protocol (5 min): Myofascial release techniques.Proprioceptive neuromuscular facilitation stretching.

Control and monitoring of exercise volume

Exercise Intensity Regulation: The Gelish calculation methodology (HR_max = 207 − 0.7 × age) established moderate-intensity parameters at 64%–77% HR_max. For the study cohort (mean age 9.9 years), calculated HR_max = 200.03, yielding target zones: Lower threshold: 128.19 bpm (200.03 × 0.64);Upper threshold: 154.23 bpm (200.03 × 0.77) Operational heart rate parameters were standardized at 128–155 bpm.

Adaptive Training Protocol: Continuous cardiac monitoring via Polar H10 chest straps enforced compliance with the 120–160 bpm target range. Weekly performance evaluations guided progressive programming adjustments:

1. Subthreshold Adaptation (mean HR < 120 bpm): Rope-jump intervals increased by 3–5 s increments (from baseline 45-second intervals).Recovery phases reduced commensurately (3–5 s decrements).

2. Supra-threshold Adaptation (mean HR > 160 bpm): Rope-jump intervals decreased by 3–5 s decrements.Recovery phases extended proportionally.All modifications preserved the 2-minute per-set temporal framework (exercise + recovery).

Control group

The control group followed their routine school activities and did not participate in any additional structured physical training. No active intervention was delivered during the study period.

Outcome measures

Anthropometry: Height and weight were measured using calibrated devices within a 2-hour morning window (08:00–10:00) under fasting conditions. Height was recorded in triplicate with variation < 0.2 cm. Bone Mineral Density: Lumbar spine (L1–L4) and femoral neck BMD were assessed using DXA.

Statistical analysis

All statistical analyses were conducted using SPSS 29.0 (IBM Corp.) and JASP 0.17.10. Group randomization was implemented using SPSS, and data distribution was assessed via frequency histograms. Normally distributed continuous variables were expressed as mean ± standard deviation (SD) and analyzed using independent-samples and paired-samples t-tests. Skewed variables were reported as median (P25, P75) and analyzed using Mann–Whitney U tests. Categorical variables were summarized as frequencies and percentages [n (%)] and compared using chi-square tests. Primary intervention effects were examined using two-way repeated-measures analysis of variance (RM ANOVA) with time (T1 vs. T2) as the within-subject factor and group (intervention vs. control) as the between-subject factor. Significant interactions were followed by post hoc pairwise comparisons with Bonferroni correction. Effect sizes and 95% confidence intervals (CIs) were calculated using JASP, and data visualizations (including raincloud plots) were generated to illustrate distributional changes. Pearson correlation coefficients were used to examine associations between changes in bone mineral density and height (ΔT2–T1). Mediation analyses were performed using the PROCESS macro (version 4.1, Model 4) with standardized variables and 5,000 bootstrap samples to generate bias-corrected 95% CIs. All statistical tests were two-tailed with a significance threshold set at α = 0.05. Significance levels were denoted as *p < 0.05, **p < 0.01, and ***p < 0.001. Effect sizes were interpreted according to Cohen’s conventions (d = 0.2/0.5/0.8 for small/medium/large; r = 0.1/0.3/0.5).

Results

Participant flow and baseline characteristics

A total of 47 children were enrolled, with 20 allocated to the intervention group and 27 to the control group. No dropouts occurred during the study. Baseline characteristics, including age, height, weight, body mass index (BMI), lumbar spine BMD Z-scores, and femoral neck BMD Z-scores, were comparable between groups (all p > 0.05). See Table 1.

Effects on BMD and height (Group × time Interaction)

Repeated-measures ANOVA revealed a significant Group × Time interaction for femoral neck BMD Z-scores (F = 22.296, p < 0.001) and height (F = 1.262, p < 0.001). Post hoc tests indicated that the intervention group had significantly greater increases in femoral neck BMD (ΔZ = 1.075 vs. 0.067, p < 0.001, d = 0.869) and height (Δ = 4.200 cm vs. 2.070 cm, p < 0.001, d = 1.705). No significant between-group difference was observed in lumbar spine BMD change (p = 0.083). See Table 2; Fig. 1.

Table 2.

Changes in height and BMD after 24 weeks

Outcome	Group	T1 (Mean ± SD)	T2 (Mean ± SD)	Δ (Change)	p-value	Cohen’s d
Height (cm)	Intervention	125.27 ± 5.92	128.47 ± 5.91	4.200 ± 0.381	< 0.001	1.705
	Control	124.20 ± 6.79	126.28 ± 6.70	2.070 ± 0.166
Femoral Neck BMD Z	Intervention	–1.63 ± 0.85	–0.82 ± 0.81	1.075 ± 0.162	< 0.001	0.869
	Control	–1.52 ± 0.85	–1.43 ± 0.83	0.067 ± 0.139
Lumbar Spine BMD Z	Intervention	–0.50 ± 0.82	–0.29 ± 0.80	0.300 ± 0.092	0.083	0.411
	Control	–0.63 ± 0.84	–0.56 ± 0.83	0.082 ± 0.079

Fig. 1.

Pre- and Post-Intervention Changes in Height and BMD Z-scores (Note: bar graphs with standard error; T1 = baseline, T2 = post-intervention)

Correlation between BMD and height gain

Pearson correlation revealed a significant positive relationship between change in femoral neck BMD Z-score and height gain (r = 0.510, p < 0.001). No significant correlation was found between lumbar spine BMD change and height gain (p = 0.247). See Table 3.

Table 3.

Correlation between changes in BMD and height

Variable Pair	Pearson’s r	p	95% CI Lower	95% CI Upper	Effect size (Fisher’s z)
Height Gain – Femoral Neck BMD Δ	0.172	0.247	−0.121	0.438	0.174
Height Gain – Lumbar Spine BMD Δ	0.510	< 0.001	0.262	0.696	0.563
Femoral Neck BMD Δ– Lumbar Spine BMD Δ	0.042	0.781	−0.193	0.415	0.042

注. Confidence intervals based on 1000 bootstrap replicates.

* p < 0.05, ** p < 0.01, *** p < 0.001

Mediation analysis

Using PROCESS v4.1 (Model 4), we tested whether femoral neck BMD mediated the relationship between jumping exercise and height gain. The total effect of the intervention on height gain was significant (β = −2.130, p = 0.001). The indirect effect through femoral neck BMD was also significant (β = −0.140, 95% CI: −0.515 to −0.118), whereas the direct effect was (β = −2.003, p < 0.001). These results suggest partial mediation by femoral neck BMD. See Tables 4 and 5; Fig. 2 for details.

Table 4.

Regression analysis of bone mineral density as a mediator between jumping exercise and height

Outcome Variable	Predictor Variable	Model Fit			Regression Coefficients
		R²	F	P	β	t	P
Lumbar Spine BMD	Jumping Exercise	0.065	3.142	0.083	−0.215	−1.773	0.083
Femoral neck BMD	Jumping Exercise	0.331	22.296	< 0.001	−1.008	−4.722	< 0.001
Height	Jumping Exercise	0.608	69.878	< 0.001	−2.130	−3.422	< 0.001
Height	Jumping Exercise	0.614	3.000	< 0.001	−2.002	−6.073	< 0.001
	Lumbar Spine BMD				0.061	−0.190	0.850
	Femoral neck BMD				0.139	0.762	0.450

Table 5.

Bootstrap mediation analysis of bone mineral density effects

Independent Variable	Effect Type	Effect Size	Boot SE	Bootstrap 95%CI
				Lower	Upper
Jumping Exercise	Total Effect	−2.130	0.255	−2.642	−1.617
	Direct Effect	−2.003	0.330	−2.668	−1.338
	Total Mediation	−0.127	0.168	−0.507	0.155
	Lumbar Spine BMD	0.013	0.047	−0.081	0.120
	Femoral neck BMD	−0.140	0.158	−0.515	−0.118

Fig. 2.

Path relationships between Height, Femoral neck BMD, Lumbar Spine BMD, and Physical Training

Adverse event reporting

No adverse events or injuries were reported during the intervention period.

Discussion

This study provides evidence that a 24-week structured jumping exercise program can significantly improve femoral neck BMD and support linear growth in prepubertal children with idiopathic short stature (ISS). The intervention resulted in a clinically meaningful increase in femoral neck BMD Z-scores and height gain, while lumbar spine BMD remained largely unchanged. These findings highlight the site-specific osteogenic responsiveness of weight-bearing skeletal regions to mechanical loading during growth [17].

The increase in femoral neck BMD is consistent with previous research showing that high-impact activities, such as jumping, generate ground reaction forces that stimulate osteogenesis, particularly in lower-extremity bones [17]. The lack of significant change in lumbar spine BMD may reflect the anatomical specificity of load distribution during jumping exercises, which target the hips and legs more directly than the axial skeleton. Notably, the baseline femoral neck BMD Z-scores were markedly lower than lumbar spine values, suggesting a vulnerability in weight-bearing bone development among children with ISS [15, 18].

Importantly, mediation analysis revealed that femoral neck BMD fully mediated the relationship between jumping intervention and height gain. This finding suggests that improvements in bone mineralization may contribute to enhanced linear growth, potentially through mechanisms such as increased sensitivity of growth plate cartilage to mechanical loading [19],corresponding alterations in trochanteric BMD during impact exercise [20], or locally elevated IGF-1 secretion [21]. While causal pathways cannot be definitively confirmed in this study design, the observed statistical mediation provides a hypothesis-generating basis for future mechanistic research [22].

Mediation analysis confirmed that changes in femoral neck BMD partially mediated the effect of jumping exercise on height gain; however, the potential contributions of vertebral adaptation remain to be clarified. Although lumbar spine BMD did not significantly increase, this may reflect a confounding effect of vertebral growth. As vertebral body size increases (in both height and width), the bone area increases, potentially offsetting increases in mineral content and yielding stable BMD values. This phenomenon suggests that lumbar vertebrae may have undergone structural adaptation without being fully captured by areal BMD. Future studies should extract DXA-derived vertebral height and width metrics or apply 3D imaging modalities to clarify whether jump-induced stimuli also promote lumbar vertebral growth. While our findings suggest that jumping exercise appears to preferentially benefit femoral neck BMD, more evidence is needed to determine whether this effect is region-specific or reflects broader skeletal adaptation.

Compared to pharmacological treatments such as recombinant human growth hormone (rhGH), the jumping exercise protocol in this study yielded moderate height gains (3.2 cm vs. 2.1 cm in controls over 6 months), without adverse effects or economic burden. Although the effect size is modest relative to rhGH therapy [23, 24], structured exercise presents a viable adjunct or alternative, particularly for children with limited access to medication or those experiencing suboptimal response.

Several limitations should be acknowledged. First, the sample was recruited from a limited geographic region and included only boarding students, which may limit generalizability. Second, the intervention duration may have been insufficient to capture long-term growth trends or pubertal influences [25, 26].

Third, height-adjusted BMD Z-scores were not available due to technical limitations of the DXA system, complicating interpretations of BMD-height relationships. Finally, relevant biochemical markers such as serum IGF-1 or osteocalcin were not assessed.

Future studies should incorporate multicenter recruitment with larger, more diverse samples and longer follow-up durations extending into puberty. Incorporating biomarkers and imaging of growth plate morphology could clarify the biological underpinnings of exercise-induced growth. Additionally, comparative trials combining structured exercise with rhGH or nutritional interventions may inform integrated therapeutic strategies [27–29].

In summary, this study provides preliminary evidence that high-impact jumping exercise may preferentially enhance femoral neck bone mineral density and potentially contribute to linear growth in children with idiopathic short stature. While the results are promising, further longitudinal and mechanistic investigations are warranted to confirm these effects and to elucidate the underlying biological mechanisms.

Conclusion

A 24-week structured jumping exercise program was associated with significant improvements in femoral neck bone mineral density and may have contributed to modest height gains in prepubertal children with idiopathic short stature. The osteogenic adaptations appeared site-specific and potentially mediated linear growth via enhanced mineral deposition. These findings suggest that jumping exercise could be considered a promising and non-pharmacological adjunct to conventional growth management strategies; however, further longitudinal and mechanistic studies are warranted to confirm its efficacy and clarify underlying mechanisms.

Authors’ contributions

HW, and WJ: conception, design, and revision of the article. XW and SJ: conducted the study and edited the article. XW, and KY: data acquisition and analysis. HW, and WJ: wrote the manuscript. All authors contributed to the article and approved the submitted version.

Funding

Not Applicable.

Data availability

The findings of this study will be supported by data provided upon request by the study sponsor, Shanghai Sport University. In accordance with specific standards, conditions, and exceptions, relevant de-identified personal data of participants may also be provided by Shanghai Sport University. Additional information may be obtained by contacting Shanghai Sport University. Enquiries may also be directed to the corresponding author.

Declarations

Ethics approval and consent to participate

This study was reviewed by the Ethics Committee of Shanghai Sport University (Ethics registration number: 102772023RT137), and all participants provided informed consent. The design and reporting of this study adhere strictly to the CONSORT 2025 Statement. A completed CONSORT checklist is provided as an additional file alongside this manuscript to ensure transparency and reproducibility of the trial methodology, results, and discussion.Every human participant should provide their consent.All participants provided informed consent. Informed consent was obtained from legal guardians of participants under 16 years old, with ethical approval granted by the Shanghai University of Sport Institutional Review Board. The study was conducted in accordance with the Declaration of Helsinki. The study was conducted in accordance with the Declaration of Helsinki (2013 revision) and prospectively registered at the Chinese Clinical Trial Registry (ChiCTR2500095544) on January 8, 2025.

Consent for publication

Not Applicable.

Competing interests

The authors declare no competing interests.