The Morbidity of Bone Disease in Thalassemia

Abstract

As thalassemia patients age, bone disease becomes a serious cause of morbidity. The frequency and type of bone disease is affected by the underlying type of thalassemia and its treatment. Problems include rickets, scoliosis, spinal deformities, nerve compression, fractures and severe osteoporosis. In early stages, patients may be asymptomatic but can present with back pain, a limp, dyspnea, neurological emergencies, or sudden fractures. The etiologies are often multifactorial, culminating with increased bone resorption and remodeling. They include hormonal deficiency, bone marrow expansion, nutritional deficiency, or desferal toxicity. Particular risk factors include older patients, low baseline hemoglobin, delayed puberty, hormonal failure, and high iron stores. Nutritional deficiencies may further compound the patient's risk for bone disease. Increasing evidence suggests that these complications and their associated long-term morbidity can be prevented if an annual screening is done, followed by long-term intervention. Patients treated with amino biphosphonates inhibit bone resorption and may demonstrate rapid healing. Intra-nasal calcitonin has also been successful in treating osteopenia. Early use of estrogen and testosterone appears to markedly lower the risk for selective patients. Both transfused and non-transfused patients should be educated about risk factors and early symptoms. All patients should be screened annually for bone disease. Once adolescence occurs, annual testing in selected cases should include bone density studies with X-ray absorptiometry.

Sickle cell bone disease: Response to vitamin D and calcium

“…In patients with b-thalassemia, another red cell disorder characterized by anemia, chronic hemolysis, and low BMD, the pathophysiology of the low BMD is related in part to increased bone resorption [24] and antiresorptive therapy could be useful in its management [25]. A low BMD is rare in children and most cases occurs as a complication of diseases like diabetes mellitus, juvenile rheumatoid arthritis, hyperthyroidism, and rickets, or with the use of corticosteroids and antiseizure medications or prolonged immobilization.…”

A Review of Endocrine Disorders in Thalassaemia

“…Prevention, early diagnosis and effective chelation therapy is most effective in arresting the progression of the disease. Diet rich in calcium and Vitamin D and exercise can improve the outcome [57]. Patients with hypogonadism should be treated with hormone replacement therapy.…”

“…Moreover selective oxidative damage to pancreatic beta cells may also occur as a result of autoimmunity [56]. Beta cell function remains normal until the later stages of disease [9] but insulin sensitivity correlates inversely with iron overload and age [57]. Fasting pro-insulin and pro-insulin to insulin ratio is significantly increased and correlate positively with hepatic iron [58] but C-peptide levels are variable indicating variable beta cell function [59,60].…”

Response of biochemical markers of bone turnover to oral glucose load in diseases that affect bone metabolism

“…b-thalassemia major is a hereditary hemoglobinopathy characterized by profound anemia due to a defect in the ability of erythroblasts to synthesize the b-chain of adult hemoglobin (14). Low bone mass and increased bone fragility in patients with b-thalassemia major lead to increased risk of fractures and represent an important cause of morbidity in this population (15,16). The pathogenesis of thalassemia-induced bone disease is multifactorial and includes bone marrow expansion, endocrine dysfunction, and iron overload, as well as genetic susceptibility to attainment of low peak bone mass (17,18).…”