Association of Hemoglobin and Iron Overload with Bone Turnover Markers in β-Thalassemia Major Patients: A Novel Biomarker Approach

Abstract: BACKGROUND: β-thalassemia major is a severe genetic disorder characterized by chronic anemia and iron overload due to frequent transfusions. These pathological changes can significantly disrupt bone metabolism, increasing the risk of osteoporosis and fractures. OBJECTIVES: The objective is to investigate the association between hemoglobin (Hb) levels, iron overload (serum ferritin), bone turnover markers, osteoprotegerin (OPG), receptor activator of nuclear factor-kappa β ligand (RANKL), bone-specific alkaline phosphatase (BAP), and C-terminal telopeptides of type I collagen (CTX), in patients with β-thalassemia major. MATERIALS AND METHODS: In Thi-Qar Province, a case–control research was carried out at the Genetic and Hematology Center. Fifty β-thalassemia major patients (25 males, 25 females; 18–45 years) receiving regular blood transfusions were compared to 49 healthy controls (24 males, 25 females; 18–49 years). Serum ferritin, Hb, OPG, RANKL, BAP, and CTX levels were measured using automated analyzers and enzyme-linked immunosorbent assay kits. Statistical analyses included t -tests, correlation coefficients, and frequency distributions. RESULTS: Compared to controls, β-thalassemia major patients had significantly lower Hb levels (mean 7.45 ± 1.22 g/dL, P < 0.001) and markedly elevated ferritin (mean 1434 ± 1079 ng/mL, P < 0.001). OPG, RANKL, BAP, and CTX levels were all elevated in the patient group ( P < 0.05 for all), indicating a significant change in bone turnover markers. Thus, RANKL and CTX ( r = 0.91), CTX and BAP ( r = 0.94), and RANKL and OPG ( r = 0.90) all showed strong positive correlations, suggesting coordinated dysregulation of bone metabolism. CONCLUSIONS: Iron overload and chronic anemia are the primary drivers of the severe disruptions in bone turnover linked to β-thalassemia major. A high bone turnover state is suggested by elevated bone resorption and formation biomarkers, which could be a factor in skeletal consequences. The possible use of these indicators to manage bone disease and diagnose β-thalassemia major early is supported by these results.