Melatonin Supplementation Alleviates Bone Mineral Density Decline and Circulating Oxidative Stress in Iron‐Overloaded Thalassemia Patients

ABSTRACT Thalassemia patients often exhibit low bone mineral density (BMD). The iron overload associated with thalassemia elevates oxidative stress levels, leading to reduced BMD. Melatonin improves BMD in postmenopausal osteopenia, however, its effect on BMD in thalassemia patients with iron overload has not been investigated. A randomized controlled study was conducted at Hematology Clinic, Faculty of Medicine, Chiang Mai University. Thalassemia patients with osteopenia and iron overloaded condition, as indicated by BMD Z‐score <−2 at l ‐spine, femoral neck, or total hip, and serum ferritin level > 500 μg/L were recruited in this study. Patients were randomized to receive either melatonin 20 mg/day or placebo at bedtime for 12 months. BMD was re‐evaluated 12 months after interventions. Bone turnover markers (BTM), malondialdehyde (MDA as an oxidative stress marker), and pain scores were assessed at baseline, 6, and 12 months. The outcomes, including BMD, BTM, MDA, and pain scores, were evaluated in all patients. Forty‐one thalassemia patients (18 males) were enrolled in the study and randomly assigned to either the melatonin group ( n = 21) or the placebo group ( n = 20). Characteristics of patients were not differences between groups. Mean age was 30.8 ± 6.2 years old. Thirty‐three patients (80.4%) were transfusion‐dependent patients. At 12 months, mean BMD at l ‐spine in melatonin group was not significantly different from placebo group ( p = 0.069). However, l ‐spine BMD at 12 months in the melatonin group was significantly greater than baseline ( p = 0.029). Serum levels of P1NP and MDA were significantly reduced at 6 months compared to baseline following melatonin treatment. The melatonin group experienced a notable decrease in back pain scores after 12 months compared to the initial measurements. 20 mg daily melatonin supplementation for 12 months alleviated l ‐spine BMD loss in iron‐overloaded thalassemia with low BMD. Melatonin also significantly reduced circulating oxidative stress and mitigated back pain in these patients.