Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The skeletal changes of untreated thalassaemia result from ineffective erythropoiesis and expansion of the bone marrow and affect every part of the skeleton. These changes include osteoporosis, growth retardation, platyspondyly and kyphosis. Erythropoiesis occurs at extra-medullary sites, most commonly resulting in a paraspinal mass but occasionally affecting organs containing pluripotential stem cells. Repeated transfusion unaccompanied by iron chelation causes haemosiderosis; iron is deposited at various sites causing functional impairment. Iron-chelation therapy with desferrioxamine (DFX) prevents haemosiderosis but causes a skeletal dysplasia predominantly affecting the rapidly growing long bones, in particular the distal ulna, and causing irregularity and sclerosis of the physeal-metaphyseal junction and splaying of the metaphysis. DFX also exacerbates the observed growth retardation. DFX-induced skeletal dysplasia may herald toxicity, which is associated with visual and auditory impairment. Therefore, careful balancing of the transfusion regimen and iron-chelation therapy is required. Magnetic resonance imaging (MRI) is the most sensitive technique for the detection of DFX-induced dysplasia.
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PMID:The radiological appearances of thalassaemia. 1635 15

Osteoporosis is a common, multifactorial cause of morbidity in patients with beta-thalassemia. The present study was performed to compare bone mineral density (BMD) results in the lumbar spine of thalassemic patients measured by both dual-energy x-ray absorptiometry (DEXA) and quantitative computed tomography (QCT), and to determine their correlations with the markers of bone turnover. BMD was measured in the lumbar spine of 13 regularly transfused patients with beta-thalassemia major by both DEXA and QCT. Blood and urine samples were obtained for the determination of biochemical and hormonal profiles. Both T-scores and Z-scores were higher when measured by QCT (T-score = -0.41 +/- 1.31, Z-score = -0.56 +/- 1.08, mean +/- SD) compared with the values given by DEXA (T-score = -2.57 +/- 0.88, Z-score = -2.32 +/- 1.11, P = 0.0005). In comparison to DEXA, QCT T-scores were more closely correlated with age (r = -0.19 vs. r = -0.70, P = 0.0068). Strong negative correlation was found between QCT values and age (r = -0.67, P = 0.01). In comparison to DEXA T-scores, QCT T-scores were more closely correlated with osteocalcin, urine N-telopeptide cross-links of type I collagen, and deoxypyridinoline, but without statistical significance. DEXA T-scores were better correlated only with urine C-terminal telopeptides of type I collagen, but again without statistical significance. These results imply that the two methods cannot be used interchangeably in assessing BMD in thalassemic patients. However, which one of these two techniques more precisely determines the overall strength of vertebrae in patients with beta-thalassemia remains to be investigated.
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PMID:Evaluation of bone mineral density of the lumbar spine in patients with beta-thalassemia major with dual-energy x-ray absorptiometry and quantitative computed tomography: a comparison study. 1646 77

Increased marrow erythropoiesis in patients with thalassemia syndromes results in the expansion of bone marrow cavities and consequently decreases bone tissues, leading to osteoporosis. Whether the soluble transferrin receptor (sTfR), a marker of erythropoietic activity, correlates with the bone mineral density (BMD) in thalassemic patients has not previously been addressed. Forty-six children and adolescents with thalassemia syndromes, who were either not transfused or suboptimally transfused, were studied. BMD was determined by dual-energy X-ray absorptiometry. Blood samples were obtained in order to determine sTfR and hemoglobin. The patients were categorized into four groups: 1, beta-thalassemia/hemoglobin E (beta-thal/E) with transfusion-dependency (TD) (n = 18); 2, beta-thal/E with transfusion-independency (TI) (n = 15); 3, beta-thalassemia major (beta-major) (n = 6); 4, hemoglobin H (HbH) (n = 7). All patients had normal serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH), and intact parathyroid hormone (PTH), serum calcium (Ca), phosphate (P), and 25-OH-vitamin D levels. The BMD of patients in the beta-major and beta-thal/E with TD groups were not significantly different. In comparison with the beta-major and beta-thal/E with TD groups, the beta-thal/E with TI and HbH groups had significantly higher BMD of the total body (TB), femoral neck (FN), and lumbar spine (LS), as well as higher levels of hemoglobin. In contrast, the sTfR levels of the beta-major, beta-thal/E with TI, and HbH groups were significantly lower than those of the beta-thal/E with TD group. The BMD of TB, FN, and LS was negatively correlated with the sTfR level, but positively correlated with the hemoglobin level. In conclusion, increased marrow erythropoiesis is one of the major determinants of reduced bone mass in thalassemic patients with either no transfusion or suboptimal transfusion.
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PMID:Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes. 1650 22

Bone mineral density (BMD) was evaluated in 52 patients with HbS/beta-thalassemia. Seventeen (32%) patients had osteopenia/osteoporosis and 30 (57%) had osteosclerosis. Bone resorption was diminished in patients with osteosclerosis and increased in those with osteopenia/osteoporosis. The sRANKL/osteoprotegerin ratio was elevated in the osteosclerotic group. Osteoporosis patients had mild renal impairment and their BMD correlated with osteoprotegerin, and bone resorption markers. Osteosclerosis patients had multiple infarctions in the studied bones that led to reduced osteoclast activity and increased BMD. In conclusion, HbS/beta-thalassemia patients may develop osteopenia/osteoporosis mainly due to marrow expansion or osteosclerosis because of ischemia after a vaso-occlusive crisis. The RANKL/ osteoprotegerin axis participates in these phenomena.
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PMID:Osteoporosis and osteosclerosis in sickle cell/beta-thalassemia: the role of the RANKL/osteoprotegerin axis. 1670 59

Osteoporosis is an important cause of morbidity in beta-thalassemia patients. Bisphosphonates have been recently used for the treatment of osteoporosis in beta-thalassemia. This study is a prospective quasi-experimental study to assess the efficacy and safety of zoledronic acid in thalassemics with osteoporosis. Eighteen thalassemia patients with osteoporosis were given zoledronic acid 4 mg intravenously every 3 months over a period of 12 months. The efficacy of treatment was assessed by measuring (BMD) at the lumbar spine, femoral neck, and hip at baseline, 6, and 12 months. Z-score was used to measure the BMD. Other medical assessments included markers of bone formation and resorption (bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline), and the assessment of pain score, analgesic score, and performance score. Ten thalassemic osteoporotic patients were followed up only with serial BMDs as controls. Both groups had no significant difference with respect to age, gender, and baseline BMD. Patients taking zoledronic acid had a significant increase in their lumbar spine, femoral neck, trochanter, and total hip BMD measurements over the 12-month period. Patients in the control group did not have any significant change in BMD measurements. There was a significant change in the levels of OC and BAP over the 12-month follow-up period. There was also a significant decrease in the number of painful sites experienced by the patients. Treatment of thalassemic osteoporotic patients with zoledronic acid is very effective in increasing BMD at the lumbar spine and hip and in reducing pain; it is also well-tolerated.
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PMID:Intravenous zoledronic acid treatment in thalassemia-induced osteoporosis: results of a phase II clinical trial. 1683 Jan 43

Osteoporosis has emerged as an important cause of morbidity in patients with thalassemia major. Studies regarding the efficacy of bisphosphonates in thalassemia-induced osteoporosis have yielded conflicting results. We performed this prospective study to evaluate the efficacy of zoledronic acid in osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg zoledronic acid intravenously every 3 months for a total of four doses. Twenty age- and sex-matched healthy blood donors served as controls. Before each infusion and 3 months after the last infusion, we determined serum levels of osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral density (BMD) of the lumbar spine was measured at baseline and after the treatment's completion. At baseline, OPG did not differ significantly between patients and controls (p=0.2), NTX were higher in patients although not significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1 levels significantly lower in patients than in controls (p<0.001 and p<0.006, respectively). Zoledronic acid administration resulted in a significant decrease in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a significant increase in OPG and BMD (p<0.05 for both comparisons). The change in NTX, osteocalcin and IGF-1 became significant as early as 3 months after the first administration of zoledronic acid, while the change in OPG reached significance only after three infusions. Our study supports the effectiveness of bisphosphonates in the treatment of thalassemia-induced osteoporosis.
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PMID:Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia. 1701 45

Osteoporosis represents an important cause of morbidity in patients with beta-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-kappaB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age +/- SEM, 24.26 +/- 1.29 years; range, 13-41 years) and females (n = 31; age, 24.59 +/- 0.95 years; range, 12-34 years) with beta-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 +/- 0.12 vs. 3.25 +/- 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 +/- 0.03 vs. 0.295 +/- 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = -0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = -0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in beta-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.
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PMID:Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system in patients with beta-thalassemia major. 1718 95

The life expectancy of patients with thalassemia has greatly improved over the last decade as a result of regular transfusions and increased compliance with iron chelation therapy, however, this improvement is often accompanied by a series of serious complications including osteopenia and osteoporosis. The pathogenesis of these skeletal disorders is multifactorial which may be due to hormonal deficiency, compromised nutritional status, bone marrow expansion due to erythroid hyperplasia, increased iron stores or desferrioxamine toxicity. The non invasive assessment of bone turnover has markedly improved with the development of specific and sensitive markers of bone formation. The aim of this work is to assess the value of bone formation markers in patients with beta-thalassemia. To achieve this goal, 36 patients with thalassemia were recruited in this study. There were 20 males (56.6%) and 16 females (44.4%) and their ages ranged from 3 to 18 years. A control group of 20 apparently healthy subjects of matched age and sex was used. The patients were selected from the outpatient clinic and inpatients of the Hematology/Oncology Unit of Mansoura University Children's Hospital (MUCH). The selected subjects were subjected to thorough history taking, clinical examination, radiological evaluation and laboratory investigations in the form of: complete blood count, serum iron, serum ferritin, total iron binding capacity, serum calcium, serum phosphorus and estimation of bone formation markers as alkaline phosphatase and osteocalcin. The results were as follows: serum calcium level was within normal range and showed no statistical significance (p = 0.176) when compared to the control group, while serum phosphorus level was significantly higher in thalassemic patients than the controls (p = 0.002); this may reflect hypoparathyroidism. Analysis of the level of bone formation markers showed serum alkaline phosphatase levels slightly higher in patients than controls but not significant (p = 0.055), and this elevation can be referred to associated liver disease in these patients. On the other hand, osteocalcin level was significantly lower in patients than controls (p = 0.011), and this may be due to osteoblast poisoning by iron overload. In conclusion, thalassemic patients have unbalanced bone turnover between the bone formation and resorption markers and this is evidenced by non significant changes or decreased levels of bone formation markers, while bone resorption is an active process.
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PMID:Unbalanced bone turnover in children with beta-thalassemia. 1732 62

The term thalassaemia intermedia includes a large spectrum of conditions of varying severity. Blood transfusion and chelation are necessary in some patients, especially during childhood, in order to promote growth and prevent bone deformities. Alloimunisation, however, is frequent and can be difficult to control. Splenectomy is usually needed at some time because of hypersplenism and mechanical encumbrance. Reactivation of HbF is possible only in a small proportion of patients: hydroxycarbamide (also known as hydroxyurea) appears to be the most effective drug for this purpose. Antioxidant agents, although theoretically useful, do not improve haemoglobin levels. Stem cell transplantation is an option limited to the severe forms. Gene therapy and other molecular approaches are subjects of intense study. Numerous complications, including pulmonary hypertension, thrombotic events, pseudoxanthoma elasticum and osteoporosis, have been described and all contribute to complicate the treatment of a disease that represents a significant burden for the patients and their families.
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PMID:Modern treatment of thalassaemia intermedia. 1756 68

Osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) have been recently implicated in the pathogenesis of various types of osteoporosis. The aim of this study was to investigate bone turnover in eugonadal female patients with this disease and characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. Markers of bone turnover and bone mineral density (BMD) were measured in 16 eugonadal young females with beta-thalassemia major and 18 age- and sex-matched healthy controls. Bone turnover was significantly increased in thalassemic patients compared to controls but OPG was significantly higher in healthy subjects. BMD values negatively correlated with urine markers of bone resorption but not with OPG/sRANKL system.
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PMID:Markers of bone metabolism in eugonadal female patients with beta-thalassemia major. 1778 84


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