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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thalassemia/hemoglobinopathy is a hereditary disease that causes chronic anemia and increased erythropoiesis. Consequently, an expansion of bone marrow spaces may contribute to osteopenia/osteoporosis. However, the pathogenesis of bone changes is not yet known. We, therefore, carried out the study on bone histomorphometry and biochemical and hormonal profiles in children and adolescents with suboptimally treated beta-thalassemia disease with the hope of gaining some new insight into the cellular and structural alterations of thalassemic bone. Seventeen patients underwent iliac crest bone biopsy for histomorphometric analyses. Bone mineral density (BMD) measurements were performed by dual energy x-ray absorptiometry. Most patients had growth retardation and delayed bone age. BMD was low especially at the lumbar spine. Serum IGF-I levels were almost always low. Bone histomorphometry revealed increased osteoid thickness, osteoid maturation time, and mineralization lag time, which indicate impaired bone matrix maturation and defective mineralization. In addition, iron deposits appeared along mineralization fronts and osteoid surfaces. Moreover, focal thickened osteoid seams were found together with focal iron deposits. Dynamic bone formation study revealed reduced bone formation rate. These findings indicate that delayed bone maturation and focal osteomalacia are the pathogenesis of bone disease in suboptimally blood-transfused thalassemics with iron overload. Iron deposits in bone and low circulating IGF-I levels may partly contribute to the above findings.
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PMID:Bone histomorphometry in children and adolescents with beta-thalassemia disease: iron-associated focal osteomalacia. 1291 94

Osteopathy, as a major feature of homozygous beta-thalassaemia, is a multifactorial disorder, not fully understood. We studied the lumbar vertebrae of 48 patients using Dual-Energy X-ray Absorptiometry (DXA) and Quantitative Computed Tomography (QCT), and we focused on structural properties, assessed by High Resolution Computed Tomography (HRCT). Bone Mineral Density (BMD) values were expressed as Z-scores and the results were correlated. The effect of age, sex, and type of thalassaemia and hormonal factors on BMD was assessed. We estimated, with HRCT, the cortex integrity and the number and thickness of trabeculae; the latter were classified to a three-grade scale. Our results showed the overall prevalence of osteoporosis to be 44% with DXA and 6% with QCT. Both techniques revealed an inverse correlation between age and BMD, whereas hormonal factors demonstrated associations with QCT and DXA measurements. The correlation coefficient between DXA's BMD and QCT's trabecular BMD was 0.545 (P < 0.001) whereas the corresponding value for Z-scores was r = 0.491 (P < 0.001). The classification of the patients into normal, osteopenic and osteoporotic categories, using QCT's Z, was in better agreement with the assignment based on trabecular number (K = 0.209, P = 0.053) than the classification using DXA's Z (K = 0.145, P = 0.120). Cortex evaluation by HRCT showed discontinuity in 15 patients. Both methods indicate a progression of osteoporosis with age. Hormonal deficiency is associated with thalassaemic osteoporosis whereas the visual estimation of cortex indicates that Thalassaemia Intermedia (TI) patients could be more affected than Thalassaemia Major (TM). Using the trabecular number as an indicator of osteoporosis, it seems that QCT may evaluate osteopathy better than DXA. Since the former has the ability to measure trabecular and cortical BMD separately, it could give early indication of which changes more rapidly and to what degree.
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PMID:Comparison of DXA, QCT and trabecular structure in beta-thalassaemia. 1581 18

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.
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PMID:Bone disease in thalassemia: a frequent and still unresolved problem. 1850 76

Modifier genes are defined as inherited genetic variation that leads to a qualitative or quantitative difference in disease phenotype. This has made the prediction of the phenotype based upon the genotype more difficult. Beta-thalassemia phenotype is modified by co-existent other genetic alterations. Changes alpha/beta-globin ratio can either ameliorate the disease phenotype or increase the severity of the disease in beta-thalassemia. Primary modifiers primarily affecting the clinical presentation include alpha gene changes, XmnI polymorphism and hereditary persistence of fetal hemoglobin (HPFH) variants. 'Thalassemia intermedia' is a heterogenous group with interplay of several genetic factors. The nature of the beta-genotype as well as the knowledge of the presence or absence of alleviating factors help the physician to decide on commencement of a regular transfusion regime or other lines of management including hydroxyurea therapy. The secondary modifiers affect the severity of jaundice, bone disease, cardiac and thrombotic complications. The present review gives a concise discussion of various modifying genes and the influence on the phenotype of beta-thalassemia.
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PMID:Genetic determinants of phenotype in beta-thalassemia. 1879 52

Thalassemia is an inherited blood disorder due to an imbalanced globin chain synthesis leading to anaemia that requires regular blood transfusions and iron-chelating therapy. Of all organ failures secondary to iron deposit, and all the complications, heart failure still represents the first cause of death. Osteopenia and osteoporosis can be considered important causes of morbidity in a population whose lifespan is getting longer, with a strong impact on their quality of life. Authors have reported mainly bone, oral and maxillofacial abnormalities and relative complications, especially in terms of traumatic risk, in patients affected by thalassemia. As examples, this study reports bone modifications in three clinical cases; one of these was also complicated with a femoral fracture, surgically treated with the same criteria of metastatic femoral bone disease. More research on this topic is necessary for the prevention of several complications caused by this disease, and to carefully plan dental or traumatologic operations.
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PMID:Bone and maxillofacial abnormalities in thalassemia: a review of the literature. 1903 22

Thalassaemic bone disease is a composite entity in which structural damage to bone is brought about by several influences, each of which may affect the bone in a different way and to a variable degree, but which may co-exist in individual patients. Understanding these damaging factors in each patient should lead to an orthologistic approach to management. However there is currently no agreed investigational protocol for the elucidation of these factors and no evidence based protocol for management. In this article the role of each of the causative influences is reviewed according to current literature and a critical examination of investigation and management is made. The conclusion is that there is a lack of agreed guidelines for the investigation and monitoring of thalassaemia patients and a lack of evidence based protocol for management of patients whose bone disease starts at an early age and continues for the rest of their lives. The natural history of this complex osteopathy and the long term effects of therapy are not well documented.
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PMID:Thalassaemic bone disease. An overview. 1933 59

Bone disease (BDT) represents a prominent cause of morbidity in patients of both sexes with thalassaemia major (TM). The exact pathogenesis of BDT in TM is multifactorial, still unclear and complicated. Peak bone mass is achieved shortly after completion of puberty and normally remains stable until the third decade of life. After the age of 30 years, age related bone loss begins. Growth hormone (GH) and sex steroids have a crucial role in bone remodelling and therefore are important in helping to establish and maintain peak bone mass for both sexes. The anabolic effects of GH and IGF-1 in bone are important not only for the acquisition of bone mass during adolescence but also for the maintenance of skeletal architecture during adult life. GH deficiency is not a rare finding in adult patients with TM, thus contributing to the development of BDT. Furthermore, patients with TM are often hypogonadal, and therefore the lack of sex steroids in critical periods, such as puberty, contributes to the failure to achieve optimal peak bone mass and to maintain bone mass later in life. Sex steroids probably act by increasing the expression of RANKL by osteoblastic cells, and alterations in the RANK/RANKL/OPG system in favour of osteoclasts are characteristic in TM, where the ratio of sRANKL/OPG is increased. It is still not clear whether DEXA scan is the gold standard for determination of bone density in thalassaemics and if so, whether the WHO criteria for defining osteopenia and osteoporosis are relevant to patients with TM. The question therefore arises whether other methods should be adopted, since DEXA may often overestimate BDT in these patients. BDT in thalassaemia represents a unique clinical entity with a multifactorial aetiology and of complex mechanisms which need to be clarified. It is essential for us to understand the underlying mechanisms of bone destruction and the bony defect at the ultrastructural level in order to be able to design not only preventive strategies but also therapeutic measures.
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PMID:Hormonal dysregulation and bones in thalassaemia--an overview. 1933 63

Bone disease in thalassemia in the form of low bone mass remains a frequent, debilitating and poorly understood problem, even among well transfused and chelated pre-pubertal and adult patients. In this work we attempted to delineate calcium status and bone mineral density in a group of transfusion dependent thalassemic adolescents of both sexes. Bone mineral density (BMD) at both the lumbar spine and femoral neck was measured in 40 adolescents with beta thalassemia major (TM) by DXA scanning and correlated to biochemical parameters including calcium, phosphorus, alkaline phosphatase, bone alkaline phosphatase, intact parathyroid hormone and 25-OH vitamin D as well as vitamin D receptor (VDR) gene polymorphisms at exon 2 (Fok1). Z-score of BMD at the lumbar spine (-3.3, +/-1.4) was significantly lower than at the femoral neck (-0.68, -/+1.3), (p=0.001). Serum ferritin and VDR genotype were related to BMD only at the femoral neck indicating that the factors determining the BMD at these 2 sites might be different. Seventy-five percent of patients had a low calcium level and hypoparathyroidism was present in 72.5% of patients. The low calcium level was probably caused by a combination of hypoparathyroidism and osteomalacia evidenced by elevated bone alkaline phosphatase presumably resulting from deficient calcium intake. To optimize BMD in TM, it is important to ensure adequate iron chelation and adequate intake of calcium and vitamin D.
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PMID:Bone mineral density and calcium metabolism in adolescents with beta-thalassemia major. 1933 66

Over the last few decades, the use of regular blood transfusions and adequate iron chelation beginning in the first years of life has modified the clinical picture and the natural course of thalassemia major. With the rise in the average age of these patients new problems have emerged, in particular bone disease: osteopenia, osteoporosis and the increased risk of fractures have become important causes of morbidity in a population whose longevity is continuously increasing. The Authors describe the case of a 41 year old patient affected by clinical thalassemia intermedia who presented with vertebral collapse after mild trauma. The physiopathology of osteoporosis and vertebral fractures in thalassemic patients and related management is presented.
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PMID:Vertebral collapse in thalassemia intermedia: case report. 1933 67

With increased life expectancy, thalassaemic bone disease including osteopenia osteoporosis syndrome (OOS) is a major cause of bone pain and fragility fractures especially of the lumbar spine, which may be found in 70-80% adult patients with beta-thalassaemia worldwide, accounting for significant bone morbidity. The causes of OOS in thalassaemia syndromes are multifactorial, and the exact treatment is far from ideal. We undertook a prospective study of 34 thalassaemic patients to evaluate the effect of pamidronate and hormone replacement therapy (if hypogonadal) on bone quantity by DXA scan quality by histomorphometry of bone biopsy and bone dynamics by biochemical markers of bone turnover.Our results show that all patients had osteopenia with abnormal bones on histomorphometry before commencement of treatment. Thalassaemia major patients had high turnover bone disease and all responded favourably to treatment whereas intermedia patients had low turnover bone disease and responded poorly to treatment. Our data also showed that ICTP and PICP is a discriminatory test but histomorphometry is the only test for characterisation of bone morphology.
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PMID:Osteopenia-osteoporosis syndrome in patients with thalassemia: understanding of type of bone disease and response to treatment. 2000 17


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