Effect of Iron Overload on Bone Mineral Density in Patients with Transfusion-dependent Thalassemia

Bone disease is an increasingly recognized complication in patients with transfusion-dependent thalassemia (TDT). Multiple factors contribute to impaired bone metabolism, including bone marrow expansion, iron overload, chelation toxicity, calcium and vitamin D deficiencies, and endocrine disturbances, particularly hypogonadism.

To evaluate the correlation between serum ferritin levels and bone mineral density (BMD) in patients with TDT.

This retrospective observational study was conducted at the Thalassemia Day Care Center of a tertiary care hospital in Punjab, India, from January to December 2022. All TDT patients aged >5 years who had undergone BMD assessment were included. BMD was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry (DXA). Z-scores were used for patients below 20 years, while T-scores were applied for those above 20 years. BMD results were categorized as normal, osteopenia, or osteoporosis. Anthropometric data (age, weight, and height), serum ferritin, calcium, phosphorus, alkaline phosphatase, and vitamin D levels were recorded and correlated with BMD.

A total of 124 patients were included, with a mean age of 15.65 ± 9.09 years (range: 5-50 years). At the femoral neck, BMD was normal in 37%, osteopenic in 60%, and osteoporotic in 3.2% of patients. At the lumbar spine, normal BMD was observed in 20.9%, osteopenia in 61.2%, and osteoporosis in 17.7%. The 10-20 years age-group had the highest prevalence of bone loss (p = 0.099). Serum ferritin levels were significantly higher in patients with osteoporosis compared to those with osteopenia and normal BMD at both femoral neck (4 794.75 ± 2 637.82 vs 2 915.86 ± 1 360.20 vs 1 797.85 ± 1 304.89 ng/mL; p < 0.001) and lumbar spine (4 627.50 ± 1 282.97 vs 2 454.03 ± 1 116.80 vs 1 128.58 ± 702.83 ng/mL; p < 0.001). Receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.873 (95% CI: 0.795-0.950), with a ferritin cutoff of 1918 ng/mL (sensitivity: 80.4%, specificity: 87.5%).

The study revealed a substantial prevalence of low BMD among TDT patients, particularly at the lumbar spine. Elevated serum ferritin levels were strongly associated with osteopenia and osteoporosis, indicating the impact of iron overload on bone health. Early and routine BMD assessments are recommended for timely identification and management of bone complications in this population.