# Serum osteocalcin as a novel biomarker for differentiating growth hormone deficiency from idiopathic short stature

**Authors:** Yuling Wang, Huanzhen Zhou, Hongye Wang, Jianying Ma, Xingyu Chen, Hongmei Yang, Hongcun Zheng, Aiping Wang

PMC · DOI: 10.3389/fendo.2026.1745971 · Frontiers in Endocrinology · 2026-03-11

## TL;DR

This study shows that measuring serum osteocalcin can help doctors tell the difference between growth hormone deficiency and idiopathic short stature in children.

## Contribution

Serum osteocalcin is identified as a novel, non-invasive biomarker for differentiating GHD from ISS with high diagnostic accuracy.

## Key findings

- Osteocalcin levels were significantly lower in children with GHD compared to those with ISS.
- Osteocalcin demonstrated high sensitivity and specificity (86.49% and 100%) in distinguishing GHD from ISS.
- Osteocalcin levels correlated positively with peak growth hormone levels.

## Abstract

The differentiation between Growth Hormone Deficiency (GHD) and Idiopathic Short Stature (ISS) primarily relies on the growth hormone stimulation test (GHST),which is invasive and can cause adverse effects.

To evaluate the diagnostic value of bone turnover markers in distinguishing GHD from ISS.

A cross-sectional study was conducted, enrolling 76 children aged 3–11 years with short stature (37 in the GHD group and 39 in the ISS group). Clinical data including height, weight, bone age, Insulin-like Growth Factor 1(IGF-1), and Peak Growth Hormone (GHP) levels were collected. Eight bone turnover markers were measured: Osteocalcin (OC), β-C-terminal telopeptide of type I collagen (β-CTX), 25-Hydroxyvitamin D (25(OH)D), Vitamin D (VitD), Alkaline Phosphatase (ALP), Parathyroid Hormone (PTH), serum Calcium (Ca), and serum Phosphorus (P). Nonparametric tests were used for intergroup comparisons. Logistic regression and Receiver Operating Characteristic (ROC) curve analyses were performed to assess diagnostic efficacy, and Spearman correlation analysis was employed for correlation evaluation.

The OC level in the GHD group was significantly lower than that in the ISS group (P < 0.001), while serum P was higher in the GHD group (P < 0.05). Multivariate analysis identified OC as an independent discriminative factor (OR = 182.585, P < 0.001). ROC curve analysis revealed that OC had an area under the curve (AUC) of 0.949, At a cutoff of 1.026 ng/mL, sensitivity was 86.49% and specificity was 100%. Correlation analysis indicated a positive association between OC levels and GHP (r = 0.6, P < 0.05).

Serum OC shows high diagnostic value for distinguishing GHD from ISS, demonstrating significant clinical utility.

## Linked entities

- **Proteins:** bglap2 (bone gamma-carboxyglutamate (gla) protein (osteocalcin) 2)
- **Chemicals:** 25-Hydroxyvitamin D (PubChem CID 5353325), Alkaline Phosphatase (PubChem CID 18985873)
- **Diseases:** Idiopathic Short Stature (MONDO:1010112)

## Full-text entities

- **Genes:** IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, GH1 (growth hormone 1) [NCBI Gene 2688] {aka GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B}
- **Diseases:** short stature (MESH:D006130), GHD (MESH:D004393), Idiopathic Short Stature (MESH:C565805)
- **Chemicals:** P (MESH:D010758), VitD (MESH:D014807), 25-Hydroxyvitamin D (MESH:C104450), 25(OH)D (-), Ca (MESH:D002118)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13013015/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC13013015/full.md

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Source: https://tomesphere.com/paper/PMC13013015