The efficacy of alendronate for the treatment of thalassemia-associated osteoporosis: a randomized controlled trial.

Background: With adequate blood transfusion and iron chelation, thalassemia patients have a longer life expectancy and experience long-term metabolic complications, including osteoporosis, fractures, and bone pain. Alendronate, an oral bisphosphonate, is currently used to treat various types of osteoporosis. However, the efficacy for the treatment of thalassemia-associated osteoporosis remains unclear. Methods: We conducted a randomized controlled trial to evaluate the efficacy of alendronate for the treatment of osteoporosis in thalassemia patients. Patients were included if they were males (18-50 years) or premenopausal females with low bone mineral density (BMD) (Z-score < -2.0 SD) or positive vertebral deformities from vertebral fracture analysis (VFA). Stratified randomization was performed according to sex and transfusion status. Patients were 1:1 allocated to receive once weekly alendronate 70 mg orally or placebo for a total duration of 12 months. BMD and VFA were re-evaluated at 12 months. Markers of bone resorption (C-terminal crosslinking telopeptide of type I collagen; CTX) and bone formation (Procollagen type I N-terminal propeptide; P1NP), and pain scores were measured at baseline, 6 months, and 12 months. The primary outcome was the change of BMD. The secondary endpoints were changes in bone turnover markers (BTM) and pain scores. Results: A total of 51 patients received the study drug, 28 patients were assigned to receive alendronate and 23 patients to receive placebo. At 12 months, patients in the alendronate group had significant improvement of BMD at L1-L4 compared to their baseline (0.72 ± 0.11 vs 0.69 ± 0.11 g/cm2, p = 0.004), while there was no change in the placebo group (0.69 ± 0.09 vs 0.70 ± 0.06 g/cm2, p = 0.814). There was no significant change of BMD at femoral neck in both groups. Serum BTMs were significantly decreased among patients receiving alendronate at 6 and 12 months. The mean back pain score was significantly reduced compared to the baseline in both groups (p = 0.003). Side effects were rarely found and led to a discontinuation of the study drug in 1 patient (grade 3 fatigue). Conclusion: Alendronate 70 mg orally once weekly for 12 months effectively improves BMD at L-spine, reduces serum BTMs, and alleviates back pain in thalassemia patients with osteoporosis. The treatment was well tolerated and had a good safety profile.

Benefits and Risks in Polypathology and Polypharmacotherapy Challenges in the Era of the Transition of Thalassaemia from a Fatal to a Chronic or Curable Disease.

Beta thalassaemia major (TM), a potentially fatal haemoglobinopathy, has transformed from a fatal to a chronic disease in the last 30 years following the introduction of effective, personalised iron chelation protocols, in particular the use of oral deferiprone, which is most effective in the removal of excess iron from the heart. This transition in TM has been achieved by the accessibility to combination therapy with the other chelating drugs deferoxamine and deferasirox but also therapeutic advances in the treatment of related co-morbidities. The transition and design of effective personalised chelation protocols was facilitated by the development of new non-invasive diagnostic techniques for monitoring iron removal such as MRI T2*. Despite this progress, the transition in TM is mainly observed in developed countries, but not globally. Similarly, potential cures of TM with haemopoietic stem cell transplantation and gene therapy are available to selected TM patients but potentially carry high risk of toxicity. A global strategy is required for the transition efforts to become available for all TM patients worldwide. The same strategy could also benefit many other categories of transfusional iron loaded patients including other thalassaemias, sickle cell anaemia, myelodysplasia and leukaemia patients.

Sofosbuvir/Ledipasvir for Treatment of Chronic Hepatitis C Infection in Adult Patients with ß- Thalassemia Major: A Real-Life Study.

BACKGROUND & AIMS: Patients with thalassemia have a lifelong need for blood transfusion, which makes them more risky to hepatitis C virus (HCV). Iron overload and chronic HCV are considered risk factors for patients with thalassemia to develop liver insults. The aim of the present study is to investigate the safety and efficacy of sofosbuvir/ledipasvir in the treatment of chronic HCV infection in Egyptian adult patients with ß- thalassemia major. METHODS: A retrospective study included 53 patients with ß-thalassemia major with chronic HCV treated with sofosbuvir (400 mg) and ledipasvir (90 mg) as a single pill fixed-dose combination once daily for 12 weeks. The effectiveness of the treatment was assessed by the sustained virologic response (SVR) at 12 weeks after the end of the treatment. RESULTS: SVR was achieved in 96.23% of patients. 47.17% of patients had minor side effects. There was a significant reduction in ALT, AST, and serum ferritin 12 weeks post-therapy. There was an insignificant change in hemoglobin level or blood transfusion requirement 12 weeks posttherapy. There was no change in iron chelators doses throughout the study period. CONCLUSION: Sofosbuvir/ledipasvir regimen seems to be safe and highly effective in the treatment of chronic HCV in patients with ß-thalassemia major.

[Iron overload and cardiotoxicity: from thalassemia to reperfusion damage]. / Ferro e cardiotossicità: dalla talassemia al danno da riperfusione.

The role of iron toxicity is well known in gastroenterology and hematology: hemochromatosis, thalassemia major and myelodysplastic syndromes represent iron toxicity models with evidence of serious damages to target organs such as the heart, the liver and endocrine tissues. Iron chelation therapy has dramatically changed the survival rate of thalassemia major since the introduction of desferoxamine with quantitative assessment of tissue iron overload by magnetic resonance imaging. Reperfusion hemorrhage is an independent predictor of left ventricular remodeling after acute myocardial infarction. Hemorrhage may be a source of iron toxicity and a mediator of inflammation, directly contributing to left ventricular remodeling. Iron chelation may potentially alleviate these cardiotoxic effects. Cardiac magnetic resonance imaging can provide insights into miocrovascular obstruction, hemorrhage and iron chelation.

Glucose induced insulin release in beta-thalassemia heterozygotes

Os genes da beta-globina e insulina estäo localizados no braço curto do cromossomo 11, com evidências de ligaçäo gênica entre os mesmos. estudos recentes demonstraram que na anemia falciformee no trao siclêmico há uma anormalidade na secreçäo de insulina. Com o objetivo de investigar se a beta-talassemia associa-se a uma anormalidade na secreçäo de insulina, foi realizado teste de tolerància à glicose endovenoso (GTT-EV) em 9 pacientes hetrozigotos para beta-talassemia e 15 controles normais. Näo houve diferença significativa entre pacientes e controles quando os níveis de glicose plasmática, em cada tempo do GTT-EV, foram comparados; a velocidade de desaparecimento da glicose também foisemelhante nos dois grupos. Näo houve diferença entre os dois grupos quando comparados os níveis de insulina antes e após a infusäo de glicose. Todos os índices de avaliaçäo da fase rápida de secreçäo de insulina induzida por glicose foram semelhantes nos dois grupos. Os resultados deste trabalho, sugerem que näo há alteraçäo na secreçäo de insulina em pacientes beta-talassemicos, provavelmente porque este defeito seja uma anormalidade independente em ligaçäo gênica com o gene Bs, mas näo com genes da beta-talassemia

Lead poisoning and thalassemia trait or iron deficiency. The value of the red blood cell distribution width.

The cause of microcytosis and anemia in lead poisoning was investigated using red blood cell distribution width as a screening parameter in 21 consecutive patients with lead poisoning and seven nonrandomly selected patients with iron deficiency and lead poisoning. Of the 21 consecutive patients, 11 had microcytosis as defined by a mean corpuscular volume of less than 72 fL, nine had thalassemia trait (alpha or beta), one had both alpha thalassemia trait and iron deficiency, and one had iron deficiency. The red blood cell distribution width was less than 17.0 in those with thalassemia trait and greater than 17.0 in the iron-deficient subjects. Results of our study suggest that microcytosis in children with lead poisoning is due to coexistent iron deficiency or thalassemia trait. The red blood cell distribution width may be of value in the rapid assessment of the cause of microcytosis in children with lead poisoning.