Management of thalassemia major has shown substantial clinical and prognostic improvement, suggesting the need for major attention to quality of life. We studied bone health in 25 patients (13 males, 12 females; 15-23 years old) affected by beta-thalassemia major. In all patients, bone mineral density (BMD), biochemical markers of bone and calcium metabolism (calcium, phosphate, magnesium, alkaline phosphatase, urinary calcium, 25-hydroxyvitamin D [25OH-D], 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone [PTH]), hematological parameters and gonadal steroids status were assessed and related to each other and to auxological parameters (chronological, statural and bone ages, height, weight, stage of puberty). BMD of the lumbar spine (L1-L4) (g/cm2) and expressed as Z-scores, was assessed by dual energy X-ray absorptiometry. PTH levels were low in seven patients (28%), and in the normal range in 18 (72%). 25OH-D serum levels were normal in 16 patients (64%) and low in nine (36%). 1,25(OH)2D values were reduced in 19 patients (76%) and normal in six (24%). Alkaline phosphatase correlated with bone age delay (r = 0.414; p = 0.039); no other statistically significant correlation was found. Mean BMD values in patients with thalassemia were significantly reduced in comparison with that of age- and sex-matched controls (Z-score: -2.8 +/- 2.0, p <0.001; -3.3 +/- 2.1 in males, and -2.2 +/- 1.9 in females). Twenty-one patients (84%) showed reduced BMD. Overall, BMD reduction was in the osteopenia range in five patients (20%) and in the osteoporosis range in 16 patients (64%). Our data indicate that low BMD is often present in patients with thalassemia, although recognized late, as in the present series. Early diagnosis should be done during childhood, in order to improve the quality of life in adulthood.