Bone mineral density in prepubertal children with β-thalassemia: Correlation with growth and hormonal data

Soliman, Ashraf T.; Banna, Nagwa El; Fattah, Mohammed Abdel; ElZalabani, Mahmoud M.; Ansari, B. M.

doi:10.1016/s0026-0495(98)90237-2

Cited by 75 publications

(58 citation statements)

References 79 publications

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“…We recently showed that daily subcutaneous injection of 1 g/kg 1,25(OH) 2 D 3 for 3 days did not enhance the duodenal calcium absorption in BKO mice, probably due to a decrease in the duodenal 1,25(OH) 2 D 3 responsiveness (7), thereby reducing calcium supply for bone mineralization. Other investigators also reported the presence of hypoparathyroidism and decreased 1,25(OH) 2 D 3 production in thalassemia (30,43,50), which might, in turn, aggravate calcium malabsorption and might also diminish osteoblast function (5,54). A reduction in the circulating levels of certain endocrine factors, particularly IGF-I (13), could also contribute to the impaired bone formation since IGF-I was an important regulator of both osteoblastogenesis and intestinal calcium absorption (4,20,61).…”

Section: Discussionmentioning

confidence: 97%

“…Inadequate production or absence of ␤-globin is found in a hereditary disease known as ␤-thalassemia, which is a common autosomal recessive anemic disorder in several populations, such as Chinese, Southeast Asian, and Mediterranean populations (6,15,34,59). Thalassemic patients and rodents both manifest ineffective erythropoiesis, extramedullary erythropoiesis, splenomegaly, iron overload, growth retardation, short stature, and skeletal deformity (16,28,31,38,43,56,62). However, little is known regarding the detailed changes in bone mineral density (BMD) and microstructural defect as well as the cellular mechanism of bone loss, especially at the early stages of the disease in young growing and adolescent mice.…”

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confidence: 99%

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Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice

Thongchote

Svasti

Teerapornpuntakit

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Thongchote K, Svasti S, Teerapornpuntakit J, Krishnamra N, Charoenphandhu N. Running exercise alleviates trabecular bone loss and osteopenia in hemizygous ␤-globin knockout thalassemic mice. Am J Physiol Endocrinol Metab 306: E1406 -E1417, 2014. First published April 29, 2014; doi:10.1152/ajpendo.00111.2014.-A marked decrease in ␤-globin production led to ␤-thalassemia, a hereditary anemic disease associated with bone marrow expansion, bone erosion, and osteoporosis. Herein, we aimed to investigate changes in bone mineral density (BMD) and trabecular microstructure in hemizygous ␤-globin knockout thalassemic (BKO) mice and to determine whether endurance running (60 min/day, 5 days/wk for 12 wk in running wheels) could effectively alleviate bone loss in BKO mice. Both male and female BKO mice (1-2 mo old) showed growth retardation as indicated by smaller body weight and femoral length than their wild-type littermates. A decrease in BMD was more severe in female than in male BKO mice. Bone histomorphometry revealed that BKO mice had decreases in trabecular bone volume, trabecular number, and trabecular thickness, presumably due to suppression of osteoblast-mediated bone formation and activation of osteoclast-mediated bone resorption, the latter of which was consistent with elevated serum levels of osteoclastogenic cytokines IL-1␣ and -1␤. As determined by peripheral quantitative computed tomography, running increased cortical density and thickness in the femoral and tibial diaphyses of BKO mice compared with those of sedentary BKO mice. Several histomorphometric parameters suggested an enhancement of bone formation (e.g., increased mineral apposition rate) and suppression of bone resorption (e.g., decreased osteoclast surface), which led to increases in trabecular bone volume and trabecular thickness in running BKO mice. In conclusion, BKO mice exhibited pervasive osteopenia and impaired bone microstructure, whereas running exercise appeared to be an effective intervention in alleviating bone microstructural defect in ␤-thalassemia. bone histomorphometry; bone mineral density; endurance exercise; running wheel; osteoporosis HEMOGLOBIN-OXYGEN-CARRYING METALLOPROTEIN in the erythrocytes-is composed of two ␣-globin chains and two ␤-globin chains. Inadequate production or absence of ␤-globin is found in a hereditary disease known as ␤-thalassemia, which is a common autosomal recessive anemic disorder in several populations, such as Chinese, Southeast Asian, and Mediterranean populations (6,15,34,59). Thalassemic patients and rodents both manifest ineffective erythropoiesis, extramedullary erythropoiesis, splenomegaly, iron overload, growth retardation, short stature, and skeletal deformity (16,28,31,38,43,56,62). However, little is known regarding the detailed changes in bone mineral density (BMD) and microstructural defect as well as the cellular mechanism of bone loss, especially at the early stages of the disease in young growing and adolescent mice.Our recent study has provided evidence that defective bone matrix ...

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice

Thongchote

Svasti

Teerapornpuntakit

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…Numerous and partially unknown pathogenetic factors could be involved in this bone imbalance: excessive iron accumulation in the cells of the bone marrow that may be altered and cause inhibition or defective bone growth and osteoblastic activity [25]; desferioxamine, which inhibits DNA synthesis [26]; low levels of insulin-like growth factor 1 (IGF-1), a very important anabolic factor for bone, that were found in these patients [27,28]. Moreover, varying degrees of anemia due to ineffective red cell production may decrease oxygen levels in the bone cells and lead to poor bone cell growth.…”

Section: Discussionmentioning

confidence: 99%

Bisphosphonates in the Treatment of Thalassemia-Induced Osteoporosis

et al. 2002

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The aim of our randomized, placebo-controlled study was to investigate the effects of 2 years' daily oral administration of alendronate or intramuscular administration of clodronate every 10 days, on bone remodeling parameters and bone mineral density (BMD), safety and tolerability in a group of osteoporotic thalassemic patients. Twenty-five young patients (mean age 26.6 +/- 7.1 years) with beta-thalassemia major were randomly divided to receive placebo or 100 mg of clodronate intramuscularly every 10 days or 10 mg of alendronate per os daily. All patients took 500 mg of elemental calcium and 400 IU cholecalciferol in the evening at meal time. After 2 years, pyridinium crosslinks, which are bone resorption markers, did not differ significantly from baseline values in the placebo group, whereas they had decreased significantly in the clodronate and alendronate groups. Osteocalcin, a bone formation marker, did not change significantly in the placebo group, whereas it decreased slightly, but not significantly, in the clodronate and alendronate groups after 12 and 24 months. At the end of the study, the lumbar spine BMD had decreased significantly in the placebo group; it did not change significantly in the clodronate group; in the alendronate group it had increased but not significantly, whereas the increase was significant with respect to the placebo group. Femoral neck BMD decreased significantly in the placebo group; it did not change significantly in the clodronate group, but increased significantly in the alendronate group. No relevant side effects were recorded during our study. In conclusion, in patients with thalassemia-induced osteoporosis, the daily administration of alendronate significantly increases BMD, the most important predictor of the risk of fracture at several sites. Clodronate treatment at our dosage is ineffective in this pathology in spite of the good compliance of patients.

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“…It is well documented that the GH-IGF axis is defective in TM. Thalassemia patients have significantly lower circulating levels of IGF-I and the corresponding binding protein (IGFBP-III) than normal individuals; thus, leading to increased bone resorption, decreased bone formation, and finally to bone loss (31)(32).…”

Section: Acquired Factorsmentioning

confidence: 99%

Bone Disease in Haemoglobin Disorders

Voskaridou

Terpos

2013

Thalassemia Reports

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Bone disease represents a prominent cause of morbidity in patients with thalassaemia and other haemoglobin disorders. The delay in sexual maturation, the presence of diabetes and hypothyroidism, the parathyroid gland dysfunction, the haemolytic anaemia, the progressive marrow expansion, the iron toxicity on osteoblasts, the iron chelators, and the deficiency of growth hormone or insulin growth factors have been identified as major causes of osteoporosis in thalassaemia. Adequate hormonal replacement, effective iron chelation, improvement of hemoglobin levels, calcium and vitamin D administration, physical activity, and smoking cessation are the main to-date measures for the management of the disease. During the last decade, novel pathogenetic data suggest that the reduced osteoblastic activity, which is believed to be the basic mechanism of bone loss in thalassemia, is accompanied by a comparable or even greater increase in bone resorption. Therefore, potent inhibitors of osteoclast activation, such as the aminobisphosphonates, arise as key drugs for the management of osteoporosis in thalassaemia patients and other haemoglobin disorders.

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Bone mineral density in prepubertal children with β-thalassemia: Correlation with growth and hormonal data

Cited by 75 publications

References 79 publications

Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice

Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice

Bisphosphonates in the Treatment of Thalassemia-Induced Osteoporosis

Bone Disease in Haemoglobin Disorders

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