Abnormalities in Bone Mineral Density and Bone Histology in Thalassemia

Abstract

This study demonstrated that there was extensive iron staining on trabecular surface and marked reduction in trabecular bone volume without significant alteration in bone formation and bone resorption rates as well as significant reduction in bone mineral density in 18 thalassemic patients. Serum IGF-I was reduced and may modulate the reduction of bone mass.Introduction: Bone histomorphometric studies in thalassemia to show alterations in bone histology and their relationship to biochemical parameters are very limited. Therefore, this study was systematically conducted to determine the alterations in thalassemia patients. Methods: Serum biochemical parameters, trans-iliac crest bone biopsy, and determination of bone mineral density of femur and lumbar spine were done in 18 thalassemic patients (10 females and 8 males). Results: Serum osteocalcin, carboxy terminal teleopeptide fragment of type I collagen, and parathyroid hormone levels were within normal limits, but serum 25(OH) vitamin D (19.3 Ϯ 1.6 ng/ml) and 1,25(OH) 2 vitamin D (33.77 Ϯ 1.51 pg/ml) levels were decreased. Serum insulin-like growth factor I (IGF-I; 145.2 Ϯ 20 ng/ml) was suppressed, whereas serum ferritin (1366.6 Ϯ 253.9 ng/ml) was markedly elevated. Reduced bone mineral density was found in all studied areas. Trabecular bone volume was significantly decreased (16.65 Ϯ 1.12%), whereas bone formation rate, eroded surface, and other bone histomorphometric parameters were within normal limits. The trabecular bone volume varied significantly with bone mineral density of total femur (r ϭ 0.48, p ϭ 0.04). There was an extensive stainable iron surface on the mineral front (9 -60%). Significant correlation between serum IGF-I, serum ferritin, stainable iron surface, and bone mineral density, lumbar spine, and total femur were found. Serum IGF-I correlated with trabecular bone volume (r ϭ 0.6, p ϭ 0.03), inversely with both serum ferritin level (r ϭ Ϫ0.6, p Ͻ 0.01), and inversely with stainable iron surface (r ϭ Ϫ0.53, p ϭ 0.02). Multiple regression analysis demonstrated that IGF-I was the only independent variable that determined bone mineral density of lumbar spine and total femur. Conclusion: Low bone mineral density and reduced trabecular bone volume with extensive iron deposition are the predominant findings in thalassemic patients. There was no evidence of increased bone resorption or mineralization defect. A reduction in circulatory IGF-I may modulate the reduction of bone mass.

Bone Disease in Haemoglobin Disorders

“…Histomorphometry studies have revealed that increased osteoid thickness, increased osteoid maturation and min-eralization lag time, which indicate impaired bone matrix maturation, and defective mineralization is present in children and adolescents with TM (33). In addition, iron deposits appeared along mineralization fronts and osteoid surfaces, whereas focal thickened osteoid seams were found together with focal iron deposits (33,43). Finally, dynamic bone formation histomorphometry studies established reduced bone formation rate in TM patients (33).…”

Impaired bone formation and osteopenia in heterozygous βIVSII-654 knockin thalassemic mice

“…thalassemic mice with heterozygous b-globin gene deletion, bone loss as determined by microcomputed tomography was observed in both trabecular and cortical parts of long bone, presumably due to a decrease in the osteoblast-mediated bone formation (Vogiatzi et al 2010). In contrast, the osteoblast surface, bone formation rate, osteoclast number and osteoclast surface of the transiliac crest biopsy were not altered in b-thalassemia/hemoglobin E patients as compared to the control subjects with normal genotype (Domrongkitchaiporn et al 2003), suggesting that bone loss in this genotype might not have resulted from the suppressed bone formation and/or accelerated bone resorption. Moreover, the histological changes in trabecular microstructure in other genotypes, such as b IVSII-654 , have not been demonstrated; however, trabecular osteopenia is anticipated.…”

“…Domrongkitchaiporn et al 2003 by using trans-iliac crest bone histomorphometry showed that iron was extensively deposited on the trabecular surface, and that trabecular bone volume was markedly decreased in b-thalassemia/hemoglobin E patients. In th3/?…”

Study of Relationship Between Sp1 Polymorphism in the Collagen Type I Alpha -1 (Colia1) Gene and Osteoprosis in Patients With Beta-Thalassemia.

“…Several previous studies showed lower BMD in thalassemic patients [22], [23], [24], [25], [26]which due to their low physical improvement which affected by iron overload and iron chelation that can affect the liver and the endocrine system.…”