Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem

Abstract

Adults with β thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, ≥6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X-ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty-one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1–75 yr), were studied. Spine and femur BMD Z-scores < −2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty-six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.

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

“…Osteoclasts were homogenized in chloroform/methanol/TRISHCl 50 mM pH 7.4 (2: 5 -2-AG as internal deuterated standards. The extract was purified and the eluted fraction containing AEA and 2-AG was analyzed as previously described.…”

“…[1][2][3][4] The pathogenesis of OP is multifactorial and includes environmental (diet and lifestyle), iatrogenic (drugs), acquired (bone marrow expansion, hemochromatosis, hepatitis, deficiency of growth hormone or insulin growth factor I, and hypogonadism) and genetic factors. [1][2][3][4][5][6][7] The relative contribution of these factors to TM-OP is uncertain, and the role of iron overload and iron chelation therapy is the subject of increasing interest. Interestingly, reports have shown different responses to bisphosphonate treatment between patients with TM and those with thalassemia intermedia: in a prospective study, individuals with TM were shown to have high turnover bone disease and responded more favorably to treatment with pamidronate and hormone replacement therapy, as compared with patients with thalassemia intermedia.…”

Untitled

“…11,20,31,33 Vogiatzi and associates found that adolescence is a critical period for the augmentation of loss of bone mass in thalassemia and suggested that bone turnover plays an important role in this process. 33 These findings may better explain why our patients, who were all < 16 years of age, showed no significant changes in BMD. In our previous study of transplant patients we found that patients with a mean age of 7.4 years did not have z scores < -2 initially and 12 months after HSCT.…”

Pathogenesis of Thalassemia Major–Associated Osteoporosis: Review of the Literature and Our Experience

“…In some studies (23,24), in order to reduce the u n c o r r e c t e d p r o o f influence of bone size on BMD measurements in the growing skeleton, the apparent volumetric density of the lumbar spine has been calculated using a specific formula (25). In TM patients, it is very common to find low BMD values (osteopenia or osteoporosis) and in some studies up to 90%, even in optimally transfused and chelated patients, as is shown in Table 1 (7,(26)(27)(28)(29)(30)(31). Prevalence of fractures in TM patients is depicted in Table 2 and ranges from 16% to 49%, depending on study population and method of data collection (3,5, [32][33][34][35].…”

“…Prevalence of fractures in TM patients is depicted in Table 2 and ranges from 16% to 49%, depending on study population and method of data collection (3,5, [32][33][34][35]. Extremity fractures are the most common (27), in particular at the upper extremity (5). Vertebral fractures are usually underestimated, and their prevalence varies from 2.6% to 13% (27,36).…”