Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem

Department of Pediatrics, Weill Medical College of Cornell, New York, New York, USA.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research (Impact Factor: 6.59). 03/2009; 24(3):543-57. DOI: 10.1359/jbmr.080505
Source: PubMed

ABSTRACT Adults with beta thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, > or =6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X-ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty-one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1-75 yr), were studied. Spine and femur BMD Z-scores < -2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty-six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although for many decades bisphosphonates were used for adult bone loss, bisphosphonate administration in pediatric patients is new and was initiated in the past 15-year. The indications for pediatric bisphosphonates was extended to childhood malignancies with bone involvement, after additional effects were unveiled for bisphosphonates with recent research. In this article we review childhood bone loss and conditions with bone involvement in which bisphosphonate therapy have been used. We also review mechanisms of action of bisphosphonates, and present indications of bisphosphonate therapy in pediatric patients based on results of clinical trials.
    12/2014; 13(1):109. DOI:10.1186/s40200-014-0109-y
  • [Show abstract] [Hide abstract]
    ABSTRACT: The pathogenesis of bone resorption in β-Thalassemia Major is multifactorial and our understanding of the underlying molecular and cellular mechanisms remains incomplete. Considering the emerging importance of the endocannabinoid/endovanilloid system in bone metabolism, examining a potential role for this system in the development of osteoporosis in β-Thalassemia Major and its relationship with iron overload and iron chelation therapy is warranted. This study demonstrates that, in thalassemic-derived osteoclasts, Tartrate-resistant Acid Phosphatase expression inversely correlates with femoral and lumbar bone mineral density, and directly correlates with ferritin levels and liver iron concentration. The vanilloid agonist resiniferatoxin dramatically reduces cathepsin K levels and osteoclast numbers in vitro, without affecting Tartrate-resistant Acid Phosphatase expression. The iron chelators deferoxamine, deferiprone and deferasirox decrease both Tartrate-resistant Acid Phosphatase and cathepsin K expression, as well as osteoclast activity. Taken together, these data show that Transient Receptor Potential Vanilloid type 1 activation/desensitization influence Tartrate-resistant Acid Phosphatase expression and activity, and this is dependent on iron, suggesting a pivotal role for iron overload in the dysregulation of bone metabolism in Thalassemia Major patients. Our applied pharmacology provides evidence for the potential of iron chelators to abrogate these effects by reducing osteoclast activity. Whether iron chelation therapy is capable of restoring bone health in humans requires further study, but the potential to provide dual benefits for patients with β-Thalassemia Major, in respect to preventing iron-overload and alleviating associated osteoporotic changes is exciting indeed.
    Haematologica 09/2014; 99(12). DOI:10.3324/haematol.2014.104463 · 5.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with non-transfusion-dependent thalassaemia (NTDT) have a genetic defect or combination of defects that affect haemoglobin synthesis, but which is not severe enough to require regular blood transfusions. The carrier frequency of NTDT is high (up to 80% in some parts of the world) but the prevalence of symptomatic patients varies with geography and is estimated to be from 1 in 100,000 to 1 in 100. NTDT has a variable presentation that may include mild to severe anaemia, enlarged spleen and/or liver, skeletal deformities, growth retardation, elevated serum ferritin and iron overload. The contributing factors to disease progression are ineffective erythropoiesis and increased haemolysis, which lead to chronic anaemia. The body¿s attempts to correct the anaemia result in constantly activated erythropoiesis, leading to marrow expansion and extramedullary haematopoiesis. Diagnosis of NTDT is largely clinical but can be confirmed by genetic sequencing. NTDT must be differentiated from other anaemias including sideroblastic anaemia, paroxysmal nocturnal haemoglobinuria, congenital dyserythropoietic anaemia, myelodysplastic syndromes and iron-deficiency anaemia. Management of NTDT is based on managing symptoms, and includes blood transfusions, hydroxyurea treatment, iron chelation and sometimes splenectomy. Prognosis for well managed patients is good, with most patients living a normal life. Since NTDT is mainly prevalent in sub-tropical regions, patients who present in other parts of the world, in particular the Northern hemisphere, might not been correctly recognised and it can be considered a `rare¿ condition. It is particularly important to identify and diagnose patients early, thereby preventing complications.
    Orphanet Journal of Rare Diseases 09/2014; 9(1):131. DOI:10.1186/s13023-014-0131-7 · 3.96 Impact Factor

Full-text (2 Sources)

Available from
May 28, 2014