Bone mass and metabolism in thalassemic children and adolescents treated with different iron-chelating drugs

Abstract

We evaluated bone mineral density (BMD) and bone turnover in 22 homozygous prepubertal beta-thalassemic patients treated with desferrioxamine. Ten patients underwent treatment with desferrioxamine for the whole study period, while 12 patients stopped desferrioxamine and were then treated with deferiprone (L1). Lumbar and femoral BMD and bone metabolism markers were examined at baseline and after 1 and 3 years of follow up. All patients were prepubertal at baseline and they all became pubertal over the 3 years of follow up. At baseline, the mean lumbar Z score value was -2.048 SD +/- 0.75; the Z score was less than -2 SD in 13 children, within -1 and -2 SD in 6, and within 0 and -1 SD in only 3 subjects. A significant BMD increase (P < 0.0001) was observed at both the lumbar (+8.466%/year) and the femoral level (average of +3.46%/year at neck and +5.83%/year at the intertrochanteric region) after 3 years, without any significant difference being shown between patients treated with desferrioxamine and those treated with L1. The mean Z score SD values increased to -1.957 +/- 0.975 at 1 year (not significantly different from baseline) and to -1.864 +/- 1.221 at 3 year follow up (P < 0.05 vs baseline); an increase in bone turnover was also observed. These findings show that low BMD, a hallmark of beta-thalassemia, improves significantly when puberty begins; this increase involves different skeletal sites, regardless of pharmacological treatment with different iron-chelating drugs.

Assessment of Vitamin D Status and Growth Parameters in Thalassemia Major Patients

“…Regarding serum calcium there was no significant (p>0.05) difference between cases and controls (Table2). Similar result was seen by Mahachoklertwattana P et al 11 , Di Stefano M et al 12 , Eren E et al 13 . However some workers found hypocalcemia in their thalassemic patients.…”

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“…Generally the mean age of participants in other studies was higher and the majority of patients had low BMD. 11,20,31,33 Vogiatzi and associates found that adolescence is a critical period for the augmentation of loss of bone mass in thalassemia and suggested that bone turnover plays an important role in this process. 33 These findings may better explain why our patients, who were all < 16 years of age, showed no significant changes in BMD.…”

Pathogenesis of Thalassemia Major–Associated Osteoporosis: Review of the Literature and Our Experience

“…Its chelating action is not totally specific for iron. In fact, deferoxamine inhibits DNA synthesis, collagen formation and osteoblast precursor differentiation, while it enhances osteoblast apoptosis (17,18). Data on bone safety of new oral chelating agents are still limited.…”

“…The pathogenesis of bone changes in TM is not fully clarified. Several studies have shown that multiple factors may act in concert to produce bone disease in TM: bone marrow expansion (8), hypogonadism (9,10), defective GH-IGF-1 axis (11-15), altered pattern of cytokines (16), iron deposit in bone (6-8, 15), deferoxamine bone toxicity (17,18) and vitamin D deficiency (19).Some of these pathogenic factors, directly and/or indirectly, affect osteoblastic population, leading to depressed bone formation, while others often increase osteoclastic bone resorption. In this review, in the light of our experience, we analysed the alterations of bone metabolism and the acquired and genetic factors that could be responsible for the development of osteopenia/osteoporosis in TM patients.…”