Bone quality in beta-thalassemia intermedia: relationships with bone quantity and endocrine and hematologic variables.

We report the first evaluation of bone quality in 70 thalassemia intermedia (TI) patients (37 males, 33 females, age 41 ± 12 years). Thirty-three patients (47%) had been transfused, 34 (49%) had been splenectomized, 39 (56%) were on iron chelation therapy, and 11 (16%) were on hydroxyurea. Mean hemoglobin was 9.2 ± 1.5 g/dl, median ferritin 537 ng/dl (range 14-4893), and mean liver iron concentration 7.6 ± 6.4 mg Fe/g dw. Fifteen patients (21%) had endocrinopathies, and 29 (41%) had vitamin D deficiency. Bone quantity (bone mineral density, BMD) and bone quality (trabecular bone score, TBS) were evaluated by densitometry. In 53/70 patients (76%), osteopathy was found (osteoporosis in 26/53, osteopenia in 27/53). BMD values were higher in the never-transfused patients and in the not-chelated group. A highly significant correlation was found between splenectomy and BMD at all the sites, with lower values in the splenectomized patients. TBS values were significantly lower in TI patients than in 65 non-thalassemic controls (1.22 vs 1.36, p < 0.01), mainly in those splenectomized and in the transfused and chelated groups (p < 0.01). TBS did not correlate with liver iron concentration values. Our data disclose the major role of non-invasive bone quality evaluation in TI patients, especially those with the worst health state, to obtain a comprehensive assessment of fracture risk. Splenectomy seems to play a major part in bone complications.

Beta-thalassaemia intermedia: evaluation of endocrine and bone complications.

OBJECTIVE: Data about endocrine and bone disease in nontransfusion-dependent thalassaemia (NTDT) is scanty. The aim of our study was to evaluate these complications in ß-TI adult patients. METHODS: We studied retrospectively 70 ß-TI patients with mean followup of 20 years. Data recorded included age, gender, haemoglobin and ferritin levels, biochemical and endocrine tests, liver iron concentration (LIC) from T2*, transfusion regimen, iron chelation, hydroxyurea, splenectomy, and bone mineralization by dual X-ray absorptiometry. RESULTS: Thirty-seven (53%) males and 33 (47%) females were studied, with mean age 41 ± 12 years, mean haemoglobin 9.2 ± 1.5 g/dL, median ferritin 537 (range 14-4893), and mean LIC 7.6 ± 6.4 mg Fe/g dw. Thirty-three patients (47%) had been transfused, occasionally (24/33; 73%) or regularly (9/33; 27%); 37/70 (53%) had never been transfused; 34/70 patients had been splenectomized (49%); 39 (56%) were on chelation therapy; and 11 (16%) were on hydroxyurea. Endocrinopathies were found in 15 patients (21%): 10 hypothyroidism, 3 hypogonadism, 2 impaired glucose tolerance (IGT), and one diabetes. Bone disease was observed in 53/70 (76%) patients, osteoporosis in 26/53 (49%), and osteopenia in 27/53 (51%). DISCUSSION AND CONCLUSIONS: Bone disease was found in most patients in our study, while endocrinopathies were highly uncommon, especially hypogonadism. We speculate that low iron burden may protect against endocrinopathy development.

The effect of dietary magnesium supplementation on the cellular abnormalities of erythrocytes in patients with beta thalassemia intermedia.

BACKGROUND AND OBJECTIVE: Reduced serum or erythrocyte Mg have been reported in human beta thalassemia. These deficiencies may play a role in the cellular abnormalities characteristic of this disorder. We have therefore studied the effect of dietary Mg supplementation in patients with beta thalassemia intermedia in order to establish whether it improves the abnormalities of thalassemic erythrocytes. DESIGN AND METHODS: Plasma and erythrocyte Mg were determined in 11 patients with b thalassemia intermedia, not requiring chronic transfusion therapy, and in 17 normal controls. Inclusion criteria included normal renal and liver function and performance status of 70% or greater. Seven patients were enrolled for the Mg supplementation study, after the appropriate informed consent was obtained. They were given a starting dose of 0.6 mEq/kg/day of magnesium pidolate, divided into two oral daily doses, for four weeks. In a 70-kg subject, a daily Mg dose of 42 mEq corresponds to 504 mg of Mg, with the daily Mg intake of normal subjects being 418 +/- 120 mg for males and 343 +/- 94 mg for females. After 28 days of treatment, five of the patients continued the protocol with a daily dosage increased to 1.2 mEq magnesium pidolate/kg/day, divided into two oral administrations, for an additional four weeks. RESULTS: In patients with untransfused beta thalassemia intermedia we found reduced erythrocyte Mg (in mmol/kg Hb, 6.12 +/- 1.5, n = 11 vs. 8.69 +/- 0.89, n = 17, respectively, p < 0.0001) and normal serum Mg. In the seven patients given oral Mg supplements, at Mg dosages of 0.6 mEq/kg/day we observed significant increases in erythrocyte Mg, and significant improvement in some of the characteristic abnormalities of beta that erythrocytes (increased Na-K pump, KCl cotransport, cell dehydration, increased osmotic resistance). These changes were maintained in the 5 patients who were treated with 1.2 mEq of Mg/kg/day. Follow-up studies showed a return to baseline conditions. There were no signs of Mg toxicity, with the only side effect being diarrhea, which was generally mild, but led to discontinuation for one patient after the first four weeks. INTERPRETATION AND CONCLUSIONS: These data indicate that dietary Mg supplementation improves some of the characteristic cellular function abnormalities of b thalassemia intermedia. The possible therapeutic value of this strategy should be further tested in these patients.