THE CONTRIBUTION OF HYPOGONADISM TO THE DEVELOPMENT OF OSTEOPOROSIS IN THALASSEMIA MAJOR - NEW THERAPEUTIC APPROACHES

OBJECTIVE The osteoporosis seen in thalassaemia major is of multifacto rial origin. The aim of the study was to evaluate the contribution of hypogonadism to the development of this osteoporosis and to assess the efficacy of new sex hormone replacement therapy regimens. DESIGN AND PATIENTS Sixty-seven patients were studied: 12 were hypogonadal, 32 ha d been on previous hormone replacement therapy (conjugated oestrogens plus medroxyprogesterone for females, depot testosterone esters for ma les); 10 had received continuous courses of treatment and 22 3-monthly on/off courses, and 22 were eugonadal without previous replacement th erapy. Twenty-seven of the above patients were evaluated prospectively at 16 and 32 months during different therapeutic approaches (12 witho ut treatment, 7 on continuous replacement and 8 on/off schemes followe d by continuous therapy during the second observation period). The con tinuous schemes comprised either transdermal oestradiol (100 mu g) plu s medroxyprogesterone for females or hCG to produce serum testosterone concentrations within normal range, for males. MEASUREMENTS Bone mine ral density (BMD) end bone mineral content (BMC) of lumbar spine and d istal end of radius were measured by dual-energy X-ray absorptiometry. RESULTS Spinal BMD was found to be more than 30% lower than that of c ontrols matched for sex and age with no difference between sexes. Radi al BMD was less impaired and showed significantly (P < 0.01) higher le vels in males (decrease of 5.8% +/- 2.3, mean +/- SD) than in females (- 14.5 +/- 3.4%, mean +/- SD). In the retrospective evaluation it was found that the hypogonadal group had the lowest (P < 0.0001) BMD leve ls (0.62 +/- 0.01, mean +/- SE) and the highest were observed on the c ontinuous replacement group (0.83 +/- 0.04), whereas the values of the other groups were similar. In a multiple regression analysis model it was found that only sex steroid levels were related to the BMD measur ements (for oestradiol t = 2.6, P = 0.01 and for testosterone t = 6.5, P = 0.0001), whereas parameters related to haemolytic anaemia and des ferrioxamine treatment were not. In the prospective study the continuo us replacement group increased BMD and BMC values more than the on/off treatment courses (P = 0.01). CONCLUSIONS Hypogonadism seems to play an important role in the development of osteopenia-osteoporosis in tha lassaemia major; continuous hormone replacement therapy with transderm al oestrogen for females or hCG for responding males best improves the bone density parameters.