Background and aim <p>Fibrosis and cirrhosis are the results of the progressive degradation and regeneration of the liver parenchyma in chronic liver disease (CLD). Chronic disorders frequently result in low bone mass and have an impact on the skeletal development and bone health of children and adolescents. Metabolic bone disease is also prevalent in children having end-stage liver illness or chronic cholestasis. Dipeptidyl peptidase-4 (DPP-4) substrates have been demonstrated to influence bone metabolism. The objective of the investigation was to assess the serum level of sDPP-4 in pediatric patients with chronic liver diseases with osteoporosis and if sDPP-4 could be used as a biomarker for assessing the severity of osteoporosis associated with CLD.</p> Methods <p>In a comparative case–control study, 60 children having CLD and 60 healthy children of the same age and gender were compared. The health of every participant was assessed by reviewing their medical records, performing imaging and laboratory tests, and measuring bone marrow density by DEXA scan. Additionally, their serum DPP-4 levels were analyzed. An assessment of dipeptidyl peptidase-4 serum level was used with the Human dipeptidyl peptidase-4 ELISA kit (Sunred Biotechnology Company) (Catalogue No. 201–12-2186) (DAS Plat Reader SRL SN 1912 Italy).</p> Results <p>A significant increase of serum DPP-4 statistically Was present in the CLD group (1874.6 ± 507.7&#xa0;pg/dl) more than the control group (859.2 ± 252.7&#xa0;pg/dl), p &lt; 0.001. DPP-4 increases with the increased degree of fibrosis and histological activity index. Statistically, there was a significant negative link between serum DPP-4 and bone mineral density in the CLD group, as well as a positive correlation between serum DPP-4 and the severity of liver problems.</p> Conclusion <p>Serum DPP-4 could serve as a dual biomarker reflecting both hepatic injury progression and bone metabolism impairment in children with CLD.</p>