Bone mineral metabolism in adults with beta-thalassaemia major and intermedia

Abstract

Bone disease is an important cause of morbidity in older patients with beta-thalassaemia major and intermedia. We studied 27 women and 23 men with beta-thalassaemia major (37) and intermedia (13) whose mean age was 32.3 +/- 9.7 years. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius was determined by dual-energy X-ray absorbiometry (DXA). The longitudinal change in BMD over a mean of 5.6 years was determined in 19 patients. Serum 25-hydroxyvitamin D, insulin growth factor-1 (IGF-1), bone formation markers bone-alkaline phosphatase, osteocalcin and the resorption marker urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined. The BsmI vitamin D receptor (VDR) gene polymorphism was analysed. Reduced BMD (Z-score < -2) was present in 89%, 62% and 73% of patients in the spine, hip and radius respectively. Vitamin D deficiency was found in 62%, decreased IGF-1 in 72% and increased urinary NTx in 84% of patients. Serum IGF-1 correlated with spine and hip BMD (r = 0.4, r = 0.39, P < 0.01 respectively), and NTx correlated with the hip BMD Z-score (r = 0.35 P < 0.05). The mean annual percentage change in spine BMD was -1.36%. Patients with the VDR BB genotype had lower spine BMD than patients with the bb genotype. In conclusion, bone loss continues in adult thalassaemia patients and is associated with increased bone resorption and decreased IGF-1. The BsmI VDR gene polymorphism is associated with osteopenia in thalassaemia.

Bone Disease in Haemoglobin Disorders

“…The RANK/RANKL/OPG pathway is of great importance for the activation and prolifera-tion of osteoclast precursors. We and others have shown that the ratio of sRANKL/OPG in the serum was increased in thalassemia patients with osteopenia/osteoporosis, providing evidence for the role of RANKL/OPG system in the pathogenesis of osteoporosis in thalassemia (39)(40)(41). Serum levels of IL-1 , TNF-, IL-6, and TGF-, that are able to increase osteoclast function, were elevated in TM and correlated with bone resorption and lumbar BMD (42), suggesting their involvement in the pathogenesis of TM osteoporosis and supporting the role of the immune system in the bone loss of TM.…”

“…During the last decade, there was sufficient data supporting that increased osteoclast activation is present in TM patients. Patients with TM and osteoporosis have elevated markers of bone resorption, such as N-terminal cross-linking telopeptide of collagen type-I (NTX) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) (37,38) that correlated with BMD of the lumbar spine in these patients (38,39). This increased osteoclast activity seems to be at least partially due to an imbalance in the receptor-activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system and the overproduction of cytokines that are involved in the osteoclast differentiation and function (39).…”

Iron overload causes osteoporosis in thalassemia major patients through interaction with transient receptor potential vanilloid type 1 (TRPV1) channels

“…[14][15][16] The increased osteoclast activity seems to be at least partially a consequence of an imbalance in the receptor-activator of the nuclear factor-kappa B ligand (RANKL)/osteoprotegerin system, and the overproduction of cytokines involved in osteoclast differentiation and function. [17][18][19][20][21] However, no correlation has been found between RANKL or osteoprotegerin levels and bone The pathogenesis of bone resorption in b-thalassemia major is multifactorial and our understanding of the underlying molecular and cellular mechanisms remains incomplete. Considering the emerging importance of the endocannabinoid/endovanilloid system in bone metabolism, it may be instructive to examine a potential role for this system in the development of osteoporosis in patients with b-thalassemia major and its relationship with iron overload and iron chelation therapy.…”

Predictors of osteoclast activity in patients with sickle cell disease

“…1,2 Osteoporosis and osteopenia are common complications of these conditions, [3][4][5] with altered bone metabolism beginning in early childhood. 4,5 Multiple blood transfusions, bone marrow expansion, iron overload and inflammation are recognized risk factors for osteoporosis in patients with beta-thalassemia.…”