Objectives: Previous studies showed that low bone mineral density (BMD) is highly prevalent in Hb E/βthalassemia, who received occasional transfusion. Concerning the clinical heterogeneity of this syndrome, we determine whether adequate transfusion and chelation therapy in severe cases with Hb E/β0 thalassemia could ameliorate this complication.
Methods: 50 pre-pubertal patients, age from 8–13, were recruited after informed consent. 26 were classified as severe group using Thalassemia International Federation (TIF) criteria, while 24 were mild. In severe patients, each received transfusion every 3 weeks (12–15 ml/kg) to keep their pre-transfusion Hb at 10 g/dL and they received iron chelation either by deferioxamine (20–40 mg/kg/d) or deferaxirox (25–30 mg/kg/d). Demographic data and history of chelation therapy were recorded. Serum free T4, TSH, PTH, cortisol, 25-OH Vit D, osteocalcin, alkaline phosphatase, serum ferritin (SF), Ca and P were determined. We measured the BMD of lumbar spines (L2-L4) and total body using DEXA (Lunar, Prodigy) and adjusted for height-age (HA) and bone age (BA). WHO criteria for BMD was Z-score −1 to −2.5 = osteopenia and < −2.5 = osteoporosis.
Results: They were compound heterozygotes of Hb E with either codon 41/41 (50.6%), codon 17 (19%), IVS2#654 (14%), IVS1#1 (4%), IVS1#5 (3%) and codon 71/72 (2%) mutations. In severe group, 15 cases had poor compliance for chelation therapy (group A) (average SF; 6027 ± 2564 ng/ml) while 11 cases had good compliance (group B) (average SF; 2374.3 ± 189 ng/ml) and the ferritin level in mild group (group C) were 197 ± 89.4 ng/ml. There were no statistical significances among these three groups regarding baseline Hb, age and sex-distribution, weight, height and their corrected Z-scores for the standard of Thai children. Only the onset of anemia was significant lower in group C (5.4 ±1.8 yrs) compared to 2.12 ± 1.35 and 2.24 ± 2 yrs in group A and B respectively. All had normal free T4, TSH, PTH, Ca and P. As expected, 7 cases (78%) of group A with marked iron overload had osteopenia while one (7%) had osteoporosis. A strong invert correlation between BMD and serum ferritin in this group was observed. To our surprise, 6 out of 11 (54%) in group B and 14 out of 24 (58%) in group C also had osteopenia. However, there was no correlation between BMD and baseline Hb, ferritin and other clinical parameters in the group B and C.
Conclusion: Low BMD in thalassemia might be resulted from ineffective erythropoiesis, bone marrow expansion and iron deposition in the bone marrow. In severe Hb E/βthalassemia, despite adequate transfusion, osteopenia and osteoporosis remain highly prevalent especially when iron overload is a co-factor. However, detecting this complication in a “so-call’ milder group was surprising since this group of patients was less anemia and rarely required blood transfusion. These suggest that several factors beside anemia and bone marrow expansion might play roles on developing this complication. Moreover, the current standard transfusion and chelation protocol might not be preventable our patients from bone complications and they were at a greater risk of fracture in adulthood. It will be of interest to investigate whether calcium and Vit D supplement with or without osteoclast inhibitors could prevent osteopenia in this highly common hereditary anemia.
