Anapliotou M L, Kastanias I T, Psara P, Evangelou E A, Liparaki M, Dimitriou P
Department of Pathophysiology, Medical School, University of Athens, Greece.
Clin Endocrinol (Oxf). 1995 Mar;42(3):279-87. doi: 10.1111/j.1365-2265.1995.tb01876.x.
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.
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.
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.
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).
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.
重型地中海贫血患者的骨质疏松是多因素导致的。本研究旨在评估性腺功能减退对该骨质疏松症发生发展的影响，并评估新型性激素替代治疗方案的疗效。
对67例患者进行了研究：12例性腺功能减退，32例曾接受过激素替代治疗（女性使用结合雌激素加甲羟孕酮，男性使用长效睾酮酯）；10例接受连续疗程治疗，22例接受每3个月一次的间断治疗，22例性腺功能正常且未接受过替代治疗。上述患者中有27例在不同治疗方法实施的16个月和32个月时进行了前瞻性评估（12例未治疗，7例接受连续替代治疗，8例采用间断治疗方案，随后在第二个观察期接受连续治疗）。连续治疗方案包括女性使用经皮雌二醇（100微克）加甲羟孕酮，或男性使用人绒毛膜促性腺激素以使血清睾酮浓度维持在正常范围内。
采用双能X线吸收法测量腰椎和桡骨远端的骨密度（BMD）和骨矿物质含量（BMC）。
发现脊柱BMD比年龄和性别匹配的对照组低30%以上，且男女之间无差异。桡骨BMD受损较轻，男性（下降5.8%±2.3%，均值±标准差）的水平显著高于女性（-14.5%±3.4%，均值±标准差）（P<0.01）。回顾性评估发现，性腺功能减退组的BMD水平最低（P<0.0001）（0.62±0.01，均值±标准误），连续替代治疗组最高（0.83±0.04），而其他组的值相似。在多元回归分析模型中发现，只有性类固醇水平与BMD测量值相关（雌二醇t=2.6，P=0.01；睾酮t=6.5，P=0.0001），而与溶血性贫血和去铁胺治疗相关的参数则无关。在前瞻性研究中，连续替代治疗组的BMD和BMC值增加幅度大于间断治疗组（P=0.01）。
性腺功能减退似乎在重型地中海贫血患者骨质减少-骨质疏松的发生发展中起重要作用；女性使用经皮雌激素或男性使用人绒毛膜促性腺激素进行连续激素替代治疗能最好地改善骨密度参数。
