Treatment of vitamin D deficiency in transfusion‐dependent thalassemia

Fung, Ellen B.; Aguilar, Catherine; Micaily, Ida; Haines, Drucilla; Lal, Ashutosh

doi:10.1002/ajh.22117

Cited by 40 publications

(42 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1F). An investigation in thalassemic patients further suggested that the abnormal circulating vitamin D levels were sex independent (14). Moreover, our previous study using quantitative real-time PCR did not show differences in the expression of key vitamin D-dependent calcium transporter genes, i.e., TRPV5, TRPV6, calbindin-D 9k , and Values are means Ϯ SE; n ϭ 5 males and 7 females in each group.…”

Section: Discussionmentioning

confidence: 83%

Hepcidin and 1,25(OH)₂D₃effectively restore Ca²⁺transport in β-thalassemic mice: reciprocal phenomenon of Fe²⁺and Ca²⁺absorption

Kraidith

Svasti

Teerapornpuntakit

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

-Previously, ␤-thalassemia, an inherited anemic disorder with iron overload caused by loss-of-function mutation of ␤-globin gene, has been reported to induce osteopenia and impaired whole body calcium metabolism, but the pathogenesis of aberrant calcium homeostasis remains elusive. Herein, we investigated how ␤-thalassemia impaired intestinal calcium absorption and whether it could be restored by administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or hepcidin, the latter of which was the liver-derived antagonist of intestinal iron absorption. The results showed that, in hemizygous ␤-globin knockout (BKO) mice, the duodenal calcium transport was lower than that in wild-type littermates, and severity was especially pronounced in female mice. Both active and passive duodenal calcium fluxes in BKO mice were found to be less than those in normal mice. This impaired calcium transport could be restored by 7-day 1,25(OH)2D3 treatment. The 1,25(OH)2D3-induced calcium transport was diminished by inhibitors of calcium transporters, e.g., L-type calcium channel, NCX1, and PMCA1b, as well as vesicular transport inhibitors. Interestingly, the duodenal calcium transport exhibited an inverse correlation with transepithelial iron transport, which was markedly enhanced in thalassemic mice. Thus, 3-day subcutaneous hepcidin injection and acute direct hepcidin exposure in the Ussing chamber were capable of restoring the thalassemia-associated impairment of calcium transport; however, the positive effect of hepcidin on calcium transport was completely blocked by proteasome inhibitors MG132 and bortezomib. In conclusion, both 1,25(OH)2D3 and hepcidin could be used to alleviate the ␤-thalassemia-associated impairment of calcium absorption. Therefore, our study has shed light on the development of a treatment strategy to rescue calcium dysregulation in ␤-thalassemia.

show abstract

Section: Discussionmentioning

confidence: 83%

Hepcidin and 1,25(OH)₂D₃effectively restore Ca²⁺transport in β-thalassemic mice: reciprocal phenomenon of Fe²⁺and Ca²⁺absorption

Kraidith

Svasti

Teerapornpuntakit

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Nonetheless, bone demineralization of varying severity and low 25OH-vitamin D levels were present in most cases. The persistence of inadequate vitamin D status despite supplementation and the possibility of reduced skin production or impaired liver metabolism of the vitamin have been previously described in β -TM patients [31, 32]. If β -TI patients had similarly increased vitamin D requirements in order to produce adequate 25-OH D serum levels, they would need high dose supplementation, as indicated by Soliman et al, recommending repletion therapy with 50000 IU of vitamin D weekly for 8 weeks, followed by maintenance with doses up to 50000 IU per month [32].…”

Section: Discussionmentioning

confidence: 99%

Beta-Thalassaemia Intermedia: Evaluation of Endocrine and Bone Complications

Baldini

Marcon

Cassin

et al. 2014

BioMed Research International

View full text Add to dashboard Cite

Objective. Data about endocrine and bone disease in nontransfusion-dependent thalassaemia (NTDT) is scanty. The aim of our study was to evaluate these complications in β-TI adult patients. Methods. We studied retrospectively 70 β-TI patients with mean followup of 20 years. Data recorded included age, gender, haemoglobin and ferritin levels, biochemical and endocrine tests, liver iron concentration (LIC) from T2*, transfusion regimen, iron chelation, hydroxyurea, splenectomy, and bone mineralization by dual X-ray absorptiometry. Results. Thirty-seven (53%) males and 33 (47%) females were studied, with mean age 41 ± 12 years, mean haemoglobin 9.2 ± 1.5 g/dL, median ferritin 537 (range 14–4893), and mean LIC 7.6 ± 6.4 mg Fe/g dw. Thirty-three patients (47%) had been transfused, occasionally (24/33; 73%) or regularly (9/33; 27%); 37/70 (53%) had never been transfused; 34/70 patients had been splenectomized (49%); 39 (56%) were on chelation therapy; and 11 (16%) were on hydroxyurea. Endocrinopathies were found in 15 patients (21%): 10 hypothyroidism, 3 hypogonadism, 2 impaired glucose tolerance (IGT), and one diabetes. Bone disease was observed in 53/70 (76%) patients, osteoporosis in 26/53 (49%), and osteopenia in 27/53 (51%). Discussion and Conclusions. Bone disease was found in most patients in our study, while endocrinopathies were highly uncommon, especially hypogonadism. We speculate that low iron burden may protect against endocrinopathy development.

show abstract

“…Adolescents had lower 25OH D levels than children and adults 20. In Tehran, 37.2% of 220 thalassemic patients had VDD ( < 27 nmol/L) 21…”

Section: Epidemiology Of Vdd In Thalassemiamentioning

confidence: 96%

“…PTH enhances the tubular reabsorption of calcium and stimulates the kidneys to produce 1,25-dihydroxyvitamin D 20–25. It also activates osteoblasts, which stimulate the transformation of preosteoclasts into mature osteoclasts.…”

Section: Vitamin D and Bonesmentioning

confidence: 99%

Vitamin D Status in Thalassemia Major: An Update

Soliman¹

2013

Mediterr J Hematol Infect Dis

View full text Add to dashboard Cite

The survival of patients with thalassemia major has progressively improved with advances in therapy; however, osteoporosis and cardiac dysfunction remain frequent complications. Adequate circulating levels of vitamin D are essential for optimal skeletal health and reducing fracture risk. Vitamin D deficiency and insufficiency is reported to be high in thalassemic patients in many countries despite the presence of good sunshine and routine prescription of 400–1,000 IU vitamin D per day. The risk of vitamin D deficiency in thalassemia and its relation to bone disease; including osteoporosis, rickets, scoliosis, spinal deformities and fractures as well as to cardiac dysfunction is discussed in this mini-review. Monitoring and maintaining normal serum level of 25-OH vitamin D through oral intake of vitamin D and early correction of VDD by oral or parental use of vitamin D may significantly improve bone mineral accretion and ameliorate cardiac function.

show abstract

Treatment of vitamin D deficiency in transfusion‐dependent thalassemia

Cited by 40 publications

References 17 publications

Hepcidin and 1,25(OH)₂D₃effectively restore Ca²⁺transport in β-thalassemic mice: reciprocal phenomenon of Fe²⁺and Ca²⁺absorption

Hepcidin and 1,25(OH)₂D₃effectively restore Ca²⁺transport in β-thalassemic mice: reciprocal phenomenon of Fe²⁺and Ca²⁺absorption

Beta-Thalassaemia Intermedia: Evaluation of Endocrine and Bone Complications

Vitamin D Status in Thalassemia Major: An Update

Contact Info

Product

Resources

About

Treatment of vitamin D deficiency in transfusion‐dependent thalassemia

Cited by 40 publications

References 17 publications

Hepcidin and 1,25(OH)2D3effectively restore Ca2+transport in β-thalassemic mice: reciprocal phenomenon of Fe2+and Ca2+absorption

Hepcidin and 1,25(OH)2D3effectively restore Ca2+transport in β-thalassemic mice: reciprocal phenomenon of Fe2+and Ca2+absorption

Beta-Thalassaemia Intermedia: Evaluation of Endocrine and Bone Complications

Vitamin D Status in Thalassemia Major: An Update

Contact Info

Product

Resources

About

Hepcidin and 1,25(OH)₂D₃effectively restore Ca²⁺transport in β-thalassemic mice: reciprocal phenomenon of Fe²⁺and Ca²⁺absorption

Hepcidin and 1,25(OH)₂D₃effectively restore Ca²⁺transport in β-thalassemic mice: reciprocal phenomenon of Fe²⁺and Ca²⁺absorption