Abstract

Objectives: This study was conducted to assess bone mineral density (BMD) and bone mineral content (BMC) in patients with ß-thalassemia major and intermedia, and to correlate them with biochemical and hematological profile. Design: 106 thalassemic patients (49 major and 57 intermedia) were scanned by dual energy x-ray absorptiometry technique for BMD and BMC at lumbar spine and femoral neck. The effects of sex, transfusion/chelation program as well as hemoglobin, calcium, phosphorus, alkaline phosphatase and serum ferritin level were also evaluated on BMD and BMC. Results: Patients with thalassemia major and intermedia, younger than 20 yr, showed lower BMD and BMC in the lumbar region (p < 0.05). Both parameters correlated significantly with hemoglobin level; other biochemical and hematological parameters did not influence BMD and BMC values. Conclusion: Bone marrow density is a good index of bone status in patients with Thalassemia and should be done in these patients annually.

Keywords: Bone mineral density, Osteoporosis, Thalassemia.

Thalassemic patients show a variety of bone disorders including bone pain, bone deformity, bone age delay, growth failure, rickets, scoliosis, spinal deformities, nerve compression, pathologic fracture, osteopenia and osteoporosis(1,2). Osteoporosis is characterized by low bone mass and disruption of bone architecture, resulting in reduced bone strength and increased risk of fractures(3). Thalassemia used to be a potentially lethal condition in childhood, but treatment with optimized transfusion programs and chelating therapy has substantially improved patients’ life expectancy and quality of life(2,4). Thus, as thalassemic patients age, osteoporosis is emerging as an important cause of morbidity(5).

Bone mineral density (BMD) is a good index of bone status and the most important predictor of fracture risk(5,6). Dual energy X-ray absorptiometry (DEXA) is an excellent non-invasive choice for repeated measurements of any temporal changes of BMD because of 1% precision rate and low radiation exposure(6).

There are more than 20,000 thalassemic patients in Iran, but there are no data reflecting their bone health status(7). In this study, we determined the Bone Mineral Density (BMD) and Bone Mineral Content (BMC) of patients with thalassemia major and intermedia and correlated these with biochemical and hematological profiles to identify potential risk factors.

A total of 106 Iranian patients affected by thalassemia (49 thalassemia major, 57 thalassemia intermedia) were enrolled in this study, from February 2002 to October 2004. These subjects were categorized into two groups: children (< 20 y) and adults (³ 20 y). As the normal data of bone mass for children group was not available, we also selected 85 sex and age matched controls. Adults were stratified based on BMD expressed as T-score, i.e., normal, osteopenic (between –1 to –2.5 SD) and osteoporotic patients (below –2.5 SD)(7,8). An informed consent was obtained from participants, their parents or legal guardians.

Enrolled subjects were scanned for bone mineral density (BMD) and bone mineral content (BMC) at anteroposterior lumbar spine (L1-L4) and femoral neck, using dual energy X-ray absorptiometry (LUNAR DPXMD#7164), which was daily calibrated according to manufacturer’s instructions. The BMD and BMC results were respectively expressed as mean values (g/cm2) ± SD and (g) ± SD, and as T-score (difference in SD from healthy age matched subjects).

Venous blood samples were obtained for serum calcium, phosphorus, alkaline phosphatase, and hematological parameters; hemoglobin and ferritin. Biochemical and hematological parameters, packed cell transfusion/deferoxamine injection programs and incidence of bone fractures were followed and recorded during the whole of study period when patients had continuous periodical referrals to Cooley’s center.

Data were analyzed using SPSS software (version 11.5; SPSS Inc., Chicago, Ill, USA). Students’ t-test was applied to compare the means. Association between variables was compared using Pearson’s Chi-Square test. p <0.05 was considered significant.

The study included 49 patients with thalassemia major (26 males and 23 females; mean age: 13.2 ± 5.8 yr) and 57 cases with thalassemia intermedia (29 males and 28 females; mean age: 14.2 ± 6.9 yr).

Mean lumbar BMD and BMC values of patients (age <20 yr) with thalassemia major were not significantly different from ones with thalassemia intermedia. However, thalassemic patients showed significant lower lumbar BMD and BMC values comparing normal controls (Table I). The incidence of pathologic fractures was similar in thalassemia major (5/49, 10.27) and thalassemia intermedia (5/57, 8.7%) (p = 0.5).

* BMD = Bone Mineral Density (g/cm2), BMC = Bone Mineral Content (g).

The mean BMD and BMC values were significantly higher in patients with thalassemia major whose Hb level was greater than 10 g/dL (0.72 g/cm² vs. 0.63 g/cm², p = 0.013 and 21.1 g vs. 17.23 g, p = 0.004, respectively). Other biochemical and hematological parameters as well as sex, blood transfusion and chelation programs did not influence BMD and BMC values.

Nine major thalassemic patients and 12 intermedia thalassemic patients were older than 20 years. The number of patients with BMD values more than –1 SD below the mean was more frequent at both regions [15 (71.4%) at lumbar and 21 (100%) at femoral], but the number of cases was not enough to permit statistical analysis.

Data regarding bone density in thalassemia intermedia are limited(9). In our study, the bone mineral values and incidence of pathological fracture did not differ between patients with thalassemia intermedia and thalassemia major even if their treatment programs were different. This may suggest the similarity in bone status between these patients. Previous studies have shown a remarkable decrease in BMD values either at both femoral and lumbar(7,8,10) or only at lumbar(6,11) regions. Our findings are in agreement with latter suggesting that the lumbar spine may be more affected in thalassemia.

We similarly observed a significant correlation between low bone mass and low Hb level in major thalassemic patients and not intermedia(1). It might be due to an acceptable level of hemoglobin in patients with thalassemia intermedia.

No correlation was observed between treatment details and bone mass values. One may again argue that the low bone mass in thalassemia is more the reflection of endocrine abnormalities rather than the hematological problems(12).

There was no significant difference between genders regarding bone mineral values contrary to other groups indicating more bone changes in males than in females(13). Shamshirsaz, et al. and others have similarly showed no significant difference in prevalence of osteoporosis between boys and girls(7,9).

Since Iranian thalassemic patients have shown a considerable decrease in bone mass according to our study and the others(7); annual evaluation of bone mineral status is recommended.