Osteoporosis and osteopenia are frequent complications of thalassemia major (TM) and intermedia (TI). Osteoporosis was found in 23/25 patients with TI and in 115/239 patients with TM. In TM, no association was found with specific polymorphisms in candidate genes (vitamin D receptor, estrogen receptor, calcitonin receptor, and collagen type 1 alpha 1). Osteoporosis in female patients with TM was strongly associated with primary amenorrhea (P < .0001), while in male patients with TM, hypogonadism was not significantly related to bone mineral density (BMD) (P = .0001). Low BMD was also associated with cardiomiopathy (P = .01), diabetes mellitus (P = .0001), chronic hepatitis (P = .0029), and increased ALT (P = .01).