Role of Vitamin D Supplementation in Reducing Bone Mineral Density Loss in Patients With Thalassemia: A Randomized Controlled Trial

Abstract

Background: Thalassemia is associated with progressive skeletal morbidity, including low bone mineral density, osteopenia, osteoporosis, and fracture risk, yet local randomized evidence on supportive bone-protective interventions remains limited. Objective: To evaluate the effect of oral vitamin D supplementation on bone mineral density and related biochemical parameters in patients with transfusion-dependent thalassemia. Methods: This randomized controlled trial was conducted at a tertiary care hospital in Lahore, Pakistan, from January 2022 to June 2024. Seventy-two eligible patients aged 10-25 years were randomized to vitamin D supplementation plus standard care or standard care alone: 68 completed follow-up. Baseline and follow-up assessments included serum 25-hydroxyvitamin D, calcium, phosphate, alkaline phosphatase, ferritin, and DEXA-based bone mineral density at the lumbar spine and femoral neck. Results: Compared with controls, the supplementation group showed a markedly greater rise in serum 25-hydroxyvitamin D (net difference +12.8 ng/mL; p<0.001), improved serum calcium (p=0.002), and a larger decline in alkaline phosphatase (p=0.04). Lumbar spine BMD Z-score improved by +0.22 in the intervention group but declined by -0.21 in controls, while femoral neck BMD changed by +0.11 and -0.12, respectively. Bone pain reduction was more frequent with supplementation (61.8% vs 26.5%; p=0.004). Conclusion: Vitamin D supplementation was associated with improved biochemical status and a more favorable bone mineral density trajectory in transfusion-dependent thalassemia, supporting its use as a practical adjunct within comprehensive long-term care.