Zoledronic Acid for Treatment of Low Bone Mineral Density in Patients with Beta Thalassemia Major.

Abstract

To determine the efficacy of zoledronic acid (ZA) in thalassemia major associated low bone mineral density. Prospective, open label, single arm trial. Bone mineral density (BMD) at lumbar, hip and forearm region were performed at baseline and after 1year of therapy. Initial, 9 patients received a first dose of 4mg. Due to severe adverse effects, further doses for these patients and all new recruited patients were 1mg once every 3months for 4 doses. All patients were receiving 500mg of calcium carbonate twice daily and 0.25μg alfacalcidol once daily before and during the entire study period. Dual energy X-ray absoptiometry was performed at baseline and after 1year. Twenty-seven patients with transfusion dependent thalassemia with a median age 19.5year (15-38years) were eligible for ZA treatment. Seven patients had bony pains. Four patients developed grade 4 hypocalcemia (3 developed tetany) and 2 developed infusion related toxicity with initial dose of 4mg. One mg dose was well tolerated. At the end of 1year, bone pains had completely resolved. There was significant increase in BMD at lumbar (p = 0.002) and forearm regions (p = 0.04) and intertrochantric area (p = 0.041). The % change in BMD at 1year was +3.7 ± 3.2%. ZA is an efficacious agent in treatment of low BMD in these patients. ZA produces significant adverse reactions at 4mg dose but 1mg dose is well tolerated and is efficacious.