Deferasirox at therapeutic doses is associated with dose-dependent hypercalciuria

Wong, Phillip; Polkinghorne, Kevan R.; Kerr, Peter G.; Doery, James C.G.; Gillespie, Matthew T.; Larmour, Ian; Fuller, Peter J.; Bowden, Donald Keith; Milat, Frances

doi:10.1016/j.bone.2016.01.011

Cited by 28 publications

(38 citation statements)

References 21 publications

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“…Of significance, stone formers in this study cohort were found to have higher serum creatinine and lower ferritin levels suggesting a possible causative role for deferasirox (111). The recent finding that deferasirox leads to dose-dependent hypercalciuria not only provides a biological mechanism for both increased kidney stones and accelerated bone loss in thalassemia major (33); this is an area deserving of further research.…”

Section: Renal-bone Dysfunction In Thalassemiamentioning

confidence: 78%

“…This is particularly pertinent in the context of iron overload and increasing number of reports of urine phosphate wasting in thalassemia (149). More recently, therapeutic doses of deferasirox has been shown to cause dose-dependent hypercalciuria in thalassemia major (33). Increased urine phosphate and calcium loss in association with deferasirox may therefore be an important risk factor for the development of osteomalacia in thalassemia.…”

Section: Renal-bone Dysfunction In Thalassemiamentioning

confidence: 97%

“…Increasing and worrying reports of renal tubular dysfunction including hypercalciuria have emerged with deferasirox (31, 32) but this has not been examined systematically. Recently, studies have confirmed that deferasirox when used in therapeutic doses leads to dose-dependent hypercalciuria (33).…”

Section: A Iron Chelatorsmentioning

confidence: 97%

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Bone Disease in Thalassemia: A Molecular and Clinical Overview

et al. 2016

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Thalassemia bone disease is a common and severe complication of thalassemia-an inherited blood disorder due to mutations in the α or β hemoglobin gene. In its more severe form, severe anemia is present, and treatment with frequent red blood cell transfusion is necessary. Because the body has limited capacity to excrete iron, concomitant iron chelation is required to prevent the complications of iron overload. The effects of chronic anemia and iron overload can lead to multiple end-organ complications such as cardiomyopathy, increased risks of blood-borne diseases, and liver, pituitary, and bone disease. However, our understanding of thalassemia bone disease is incomplete and is composed of a complex piecemeal of risk factors that include genetic factors, hormonal deficiency, marrow expansion, skeletal dysmorphism, iron toxicity, chelators, and increased bone turnover. The high prevalence of bone disease in transfusion-dependent thalassemia is seen in both younger and older patients as life expectancy continues to improve. Indeed, hypogonadism and GH deficiency contribute to a failure to achieve peak bone mass in this group. The contribution of kidney dysfunction to bone disease in thalassemia is a new and significant complication. This coincides with studies confirming an increase in kidney stones and associated accelerated bone loss in the thalassemia cohort. However, multiple factors are also associated with reduced bone mineral density and include marrow expansion, iron toxicity, iron chelators, increased bone turnover, GH deficiency, and hypogonadism. Thalassemia bone disease is a composite of not only multiple hormonal deficiencies but also multiorgan diseases. This review will address the molecular mechanisms and clinical risk factors associated with thalassemia bone disease and the clinical implications for monitoring and treating this disorder.

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Section: Renal-bone Dysfunction In Thalassemiamentioning

confidence: 78%

Section: Renal-bone Dysfunction In Thalassemiamentioning

confidence: 97%

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Bone Disease in Thalassemia: A Molecular and Clinical Overview

et al. 2016

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“…The above authors pointed out that data on DFX remain limited, indicating no sufficient evidence for recommending the first-line use of DFX in sickle cell disease or myelodysplastic syndrome. However, recent reports have confirmed that long-term use of DFX at optimal dosage significantly reduces LIC and SF in iron-overloaded beta-thalassemia patients [40, 41]; meanwhile, others reported serious side effects after use [42-46]. …”

Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Deferasirox in Thalassemia with Iron Overload: A Meta-Analysis

et al. 2018

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Deferasirox (DFX) has recently been used to treat thalassemia with iron overload; however, its long-term effectiveness and safety await multi-year studies. In this study, a systematic meta-analysis was performed to assess the effectiveness and safety of DFX in the treatment of thalassemia with iron overload. We performed a systematic electronic literature search for randomized controlled studies of DFX in the Embase, Medline, Cochrane, and Chinese Biomedical Literature (CBM) databases from January 1990 to May 2018. Particular attention was paid to mortality, serum ferritin (SF), liver iron concentration (LIC), myocardial iron concentration, and adverse events (AEs). Six studies comparing DFX with deferoxamine (DFO) and placebo were enrolled. DFX was not better than DFO in lowering SF and LIC, with an exception that high DFX dose (> 30 mg/kg/day) was superior to DFO in LIC. Otherwise, AEs such as gastrointestinal problems appeared to be more common with DFX. DFX does not seem to be superior to DFO at low dose. Similar efficacy seems to be achievable depending on dose. However, the convenient oral administration of DFX has a higher compliance rate.

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“…A recent study demonstrated hypercalciuria was present in 92% of individuals with thalassemia treated with deferasirox in a positive dose-dependent relationship [2]. Thiazide diuretic use reduces urine calcium loss and is associated with improved bone density and reduced risk of hip fracture in observational studies [3].…”

mentioning

confidence: 99%

A role for thiazide diuretic therapy in preventing bone loss, fracture, and nephrolithiasis in individuals with thalassemia and hypercalciuria?

Morton

2017

Osteoporos Int

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Deferasirox at therapeutic doses is associated with dose-dependent hypercalciuria

Cited by 28 publications

References 21 publications

Bone Disease in Thalassemia: A Molecular and Clinical Overview

Bone Disease in Thalassemia: A Molecular and Clinical Overview

Effectiveness and Safety of Deferasirox in Thalassemia with Iron Overload: A Meta-Analysis

A role for thiazide diuretic therapy in preventing bone loss, fracture, and nephrolithiasis in individuals with thalassemia and hypercalciuria?

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