Serum biomarkers associated with radiographic skeletal maturity indicators: A systematic review and meta-analysis

Objective: To evaluate the relevant scientific literature to determine the association between different serum biomarker levels and radiographic skeletal maturity indicators. Data Search, Screening and Eligibility: A literature search was carried out on PubMed, Cochrane Library, Google Scholar, Semantic Scholar, Science Direct and Opengrey.eu up to November 2021 and 7466 records were retrieved via the electronic search. Study selection, data extraction and subsequent risk of bias assessment (RoB) was carried out independently by two authors. In case of any discrepancy, a third author was consulted. Results: After the exclusion of duplicates and the application of inclusion exclusion criteria, 19 studies (published in 25 articles) were included in the systematic review out of which 17 had a cross-sectional and two had a cohort study design. For the meta-analysis, based on the homogeneity, five cross-sectional studies measuring serum IGF-1 levels were incorporated. The meta-analysis revealed that the serum IGF-1 levels peak at the CS4 stage (401.77 ng/mL [333.50 - 470.05]) in the pooled group. However, in the subgroup analysis, it was found that the serum IGF-1 levels peak at CS3 in women (422.82 ng,/mL [377.46-468.18]) and CS4 in men (487.04 ng,/mL [391.83-582]). Conclusion: Among the various biomarkers evaluated, serum IGF-1 was the most associated with different stages of radiographic skeletal maturity indicators with its levels peaking at CS3 in women and CS4 in men.