Bone Disease in Thalassemia: A Molecular and Clinical Overview

Abstract

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.

Urolithiasis is prevalent and associated with reduced bone mineral density in β‐thalassaemia major

“…Whether the relationship between bone loss and deferasirox is causal remains to be defined; but reports of dose‐dependent hypercalciuria and renal phosphate wasting from Fanconi syndrome are possible mechanisms for bone loss. Moreover, the findings of an increased serum creatinine and reduced ferritin concentrations in calcium stone formers in this study may implicate deferasirox in the renal‐bone axis in thalassaemia …”

“…Moreover, the findings of an increased serum creatinine and reduced ferritin concentrations in calcium stone formers in this study may implicate deferasirox in the renal-bone axis in thalassaemia. 1 The particularly high prevalence of struvite and cysteine stones in this cohort is in contrast to the general population. Struvite stones (calcium, phosphate and magnesium) are often associated with urinary tract infections and high urine pH.…”

“…In its more severe form, it requires treatment with chronic transfusion and concomitant iron chelation therapy to prevent iron overload. The long‐term complications include cardiac, liver, hormonal and metabolic bone disease but the nature of renal dysfunction in thalassaemia is poorly characterised …”

“…The long-term complications include cardiac, liver, hormonal and metabolic bone disease but the nature of renal dysfunction in thalassaemia is poorly characterised. 1 In a retrospective analysis, we reported symptomatic urolithiasis to be present in 18.1% of patients with transfusion-dependent thalassaemia, 2 compared with 5.2% in the general population. 3 Urolithiasis is associated with osteoporosis in the general population, 4 and we have previously identified an association between symptomatic urolithiasis and reduced bone mineral density (BMD) in patients with β-thalassaemia major.…”

Effects of Home-Care Training on the Self-Efficacy of Patients with Beta Thalassemia Major

“…Similar to other chronic diseases, thalassemia, as a chronic disease, imposes serious physical, socio-mental, congenital and economic effects to the patients and their families (8). Physical problems such as chronic anemia, bone deformation, growth change, short height and delayed physical maturing on the one hand and unpleasant as well as long and repetitive therapies on the other hand affect different life aspects of the patients (9, 10). Disease duration and treatment period, increased hospitalization and therapy costs, mental status and social harms are among complexities affecting thalassemia patients and their families (11).…”