Objective: To evaluate the diagnostic efficacy and additive interaction of serum insulin-like growth factor-binding protein-3(IGFBP-3) and 25-hydroxyvitamin D3[25(OH)D3] in children with short stature. Methods: A total of 102 children with short stature treated at our hospital from November 2022 to May 2025 were enrolled as the observation group(n=102), and 78 healthy children who underwent physical examinations and had retained serum samples during the same period were selected as the control group(n=78). Serum levels of IGFBP-3 and 25(OH)D3 were measured in both groups. Physical parameters(body weight, height, body mass index) and bone mineral density Z-scores were compared between the two groups. Pearson correlation analysis was used to assess the correlations between serum biomarkers and physical parameters as well as bone mineral density. Three diagnostic models(parental height only, serum markers only, and combined) were constructed using Logistic regression. Internal validation was conducted using the Bootstrap method, and the additive interaction between the two biomarkers was analyzed. Results: Serum IGFBP-3, 25(OH)D3, body weight, height and parental height in the observation group were lower than those in the control group(all P<0.05). In the observation group, Serum IGFBP-3 was positively correlated with body weight and height(r:0.512, 0.485, all P<0.001), 25(OH)D3 was positively correlated with body weight and bone density Z-score(r:0.578, 0.405, all P<0.001). Parental height, IGFBP-3 and 25(OH)D3 were risk factors for short stature(all P<0.05). The area under the receiver operating characteristic curve(AUC) of the serum-only model was 0.973, and increased to 0.982 when parental height was added. DeLong test showed no significant difference between the two models(P=0.106). Interaction analysis revealed that coexistence of low IGFBP-3 and low 25(OH)D3 conferred a risk higher than the sum of their individual risks(RERI=3.81, Bootstrap 95%CI:0.52-7.10), with a synergy index of 1.45(Bootstrap 95%CI: 1.06-1.98). Conclusion: Serum IGFBP-3 and 25(OH)D3 levels are low in children with short stature. Combined detection of serum markers has high auxiliary diagnostic value, but its generalizability requires external validation. The coexistence of low levels of both markers exerts a synergistic effect on short stature, warranting comprehensive assessment and early intervention. |
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