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 mu g) plus medroxyprogesterone for females or hCG to
produce serum testosterone concentrations within normal range, for
males.
MEASUREMENTS Bone mineral density (BMD) end 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
