The contribution of hypogonadism to the development of osteoporosis in thalassaemia major: new therapeutic approaches.

Objective: The osteoporosis seen in thalassaemia major is of multifactorial 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 had been on previous hormone replacement therapy (conjugated oestrogens plus medroxyprogesterone for females, depot testosterone esters for males); 10 had received continuous courses of treatment and 22 3-monthly on/off courses, and 22 were eugonadal without previous replacement therapy. Twenty-seven of the above patients were evaluated prospectively at 16 and 32 months during different therapeutic approaches (12 without treatment, 7 on continuous replacement and 8 on/off schemes followed by continuous therapy during the second observation period). The continuous schemes comprised either transdermal oestradiol (100 micrograms) plus medroxyprogesterone for females or hCG to produce serum testosterone concentrations within normal range, for males.

Measurements: Bone mineral density (BMD) and bone mineral content (BMC) of lumbar spine and distal 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 controls matched for sex and age with no difference between sexes. Radial BMD was less impaired and showed significantly (P < 0.01) higher levels 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 levels (0.62 +/- 0.01, mean +/- SE) and the highest were observed on the continuous 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 measurements (for oestradiol t = 2.6, P = 0.01 and for testosterone t = 6.5, P = 0.0001), whereas parameters related to haemolytic anaemia and desferrioxamine treatment were not. In the prospective study the continuous 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 thalassaemia major; continuous hormone replacement therapy with transdermal oestrogen for females or hCG for responding males best improves the bone density parameters.