Longitudinal changes of endocrine and bone disease in adults with β-thalassemia major receiving different iron chelators over 5 years

Abstract

In this study, we compared the long-term effects of different iron chelation regimens (deferoxamine, deferiprone, deferoxamine + deferiprone, and deferasirox) in preventing or reversing endocrinopathy (diabetes mellitus, hypothyroidism, or hypogonadism) and bone disease (measured through DEXA) in 165 adults with β-thalassemia major (TM) (mean age 39.9 ± 8.3 years, 43 % males). After five consecutive years of therapy, patients on deferasirox had the highest decrease in the prevalence of any endocrinopathy compared to other chelators which either had no change (deferiprone and deferoxamine) or had an increase (deferoxamine + deferiprone), p = 0.015. This was attributed to a lower proportion of patients on deferasirox developing new-onset endocrinopathy and higher proportion showing reversal of disease, compared to other chelators. A serum ferritin level of >1300 ng/mL predicted the development of new endocrinopathy (p = 0.025) while a level of <200 ng/mL predicted reversal of existing endocrinopathy (p = 0.147). A significant increase in mean BMD T-score (p < 0.001) and a considerable decrease in osteoporosis prevalence were observed in patients receiving deferasirox but not other chelators. Iron chelation therapy with deferasirox has a role in the prevention of endocrinopathy and reversal of existing disease.

Hepcidin is an endogenous protective factor for osteoporosis by reducing iron levels

“…It has been reported that postmenopausal women often suffer from iron accumulation, and traditional treatment has often been ineffective for such patients. The use of an iron chelator will be an ideal therapy for significantly increasing bone mineral density (BMD) in patients with hematonosis, whose serum ferritin levels reach iron overload (>1000 ng/mL) (Poggi et al 2016). Moreover, osteoblast are inhibited by high iron levels, and this inhibition is reversed upon treatment with iron chelators or hepcidin , Baschant et al 2016.…”

A Phase II, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with β-Thalassemia Major

“…In transfusion-dependent patients with TM, deferasirox significantly reduces systemic, hepatic, and cardiac iron overload and helps patients transition from high-risk to low-risk thresholds in the respective iron indices, as evidenced from a large clinical trial program involving patients as young as 2 years [12,[18][19][20]. It also helps preserve cardiac function, stabilizes or improves hepatic fibrosis, and can reverse endocrinopathies and osteoporosis [18,19,[21][22][23][24]. High deferasirox doses of >30 mg/kg/day are often needed in patients with severe iron overload [25].…”

Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss

“…Importantly, the observed changes were independent of bisphosphonate therapy, hormonal replacement therapy, and calcium or vitamin D supplementation, suggesting a direct positive effect of iron chelation on bone status in those patients (Casale et al, 2014 ). In a recent study, Poggi et al ( 2016 ) compared the long-term effects of different iron chelation regimens, in preventing bone disease in patients with β-thalassemia major. In agreement with the previously mentioned study (Casale et al, 2014 ), they observed a significant increase in mean BMD T-score and a decrease in the prevalence of osteoporosis in the patients receiving deferasirox (Poggi et al, 2016 ).…”

“…In a recent study, Poggi et al ( 2016 ) compared the long-term effects of different iron chelation regimens, in preventing bone disease in patients with β-thalassemia major. In agreement with the previously mentioned study (Casale et al, 2014 ), they observed a significant increase in mean BMD T-score and a decrease in the prevalence of osteoporosis in the patients receiving deferasirox (Poggi et al, 2016 ). Surprisingly, the other iron chelation regimens (DFO and deferiprone alone, or in combination) used in this study, did not provide any beneficial effects on BMD (Poggi et al, 2016 ).…”