cholecalciferol and Thalassemia

Patients with transfusion-dependent thalassemia (TDT) show disorders in calcium metabolism. The α-Klotho protein is predominantly expressed in tissues that are involved in calcium homeostasis, and lowered levels are associated with bone disease. The aim of the study is to examine the associations between low α-Klotho status and calcium metabolism in relation to iron status in children with TDT.. Calcium, α-Klotho, parathyroid hormone (PTH), calcyphosin, vitamin D3, phosphorous, fibroblast growth factor receptor 2 (FGFR2), as well as iron and erythron biomarkers were measured in 60 children with TDT and 30 healthy control children.. A meaningful part of TDT patients showed lowered α-Klotho levels, and those children also showed low serum total and ionized calcium concentrations. TDT patients showed increased PTH, FGFR2, and calcyphosin and lowered vitamin D3 as compared with healthy children. The α-Klotho levels were significantly correlated with total and ionized calcium (positively) and with iron overload and transfusions biomarkers (inversely). Partial Least Squares path analysis showed that 40.1% of the variance in serum total calcium could be explained by the regression on α-Klotho, vitamin D3 (both positively), and calcyphosin (inversely) and that the effects of the latter are mediated by iron overload and the number of blood transfusions.. In conclusion, the iron overload in TDT and its consequences may induce lowered levels of α-Klotho which in turn may lead to lower calcium thereby explaining at least in part the effects of TDT on bone metabolism including spontaneous pathological fractures, osteoporosis, osteopenia, and skeletal deformities.

Topics: Biomarkers; Calcium; Child; Cholecalciferol; Humans; Iron; Iron Overload; Parathyroid Hormone; Thalassemia

Parathyroidectomy is the only effective therapy for osteitis fibrosa cystica in hyperparathyroidism.. The objective of this study was to describe the changes of skeletal and nonskeletal manifestations in a patient with hyperparathyroidism and renal failure after oral vitamin D therapy.. This was a descriptive case report.. The patient was followed up in a referral center.. A 55-yr-old male patient with moderate renal failure was referred for expansile lytic lesions affecting several ribs and the spinous process of T12. His creatinine was 1.8 mg/dl; calcium, 8.9 mg/dl; PTH, 666 pg/ml; and 1,25 dihydroxy-vitamin D, 27 pg/ml. Bone mineral density (BMD) Z-scores by dual-energy x-ray absorptiometry were -4.1 at the spine, -1.7 at the hip, and -4.3 at the forearm.. The main outcome measures were the skeletal manifestations of hyperparathyroidism.. At 10 months of therapy, calcium level was 10 mg/d, PTH level declined to 71 pg/ml, and BMD increased by 12% at the spine and 18% at the hip. Computerized tomography (CT) cuts revealed marked regression in the lytic lesions. At 2 yr, BMD increased by an additional 6% at the spine, and there were no further changes in the lytic lesions by CT. The vitamin D receptor genotype using the restriction enzymes Bsm1, Taq1, and Apa1 was Bb, tt, and AA.. We showed regression of severe skeletal abnormalities of hyperparathyroidism documented by serial CT images in response to oral vitamin D therapy. It is possible that the vitamin D receptor genotype of the patient modulated this response.

Topics: Bone Density; Bone Diseases; Calcium; Cholecalciferol; Genotype; Humans; Hydroxycholecalciferols; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Osteitis Fibrosa Cystica; Osteoporosis; Receptors, Calcitriol; Thalassemia; Tomography, X-Ray Computed; Vitamin D

Topics: Bone Density; Bone Remodeling; Carrier Proteins; Case-Control Studies; Cholecalciferol; Female; Glycoproteins; Humans; Male; Membrane Glycoproteins; Osteoporosis; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Solubility; Thalassemia