Vanderschueren D, Boonen S, Ederveen A G, de Coster R, Van Herck E, Moermans K, Vandenput L, Verstuyf A, Bouillon R
Laboratory for Experimental Medicine and Endocrinology, Onderwijs en Navorsing, Gasthuisberg, Belgium.
Bone. 2000 Nov;27(5):611-7. doi: 10.1016/s8756-3282(00)00363-x.
Aromatization of androgens into estrogens may be important for maintenance of the male skeleton. To address this hypothesis, we evaluated the skeletal effects of selective estrogen deficiency as induced by the aromatase inhibitor vorozole (Vor), with or without 17beta-estradiol (E(2)) administration (1.35 microg/day), in aged (12-month-old) male rats. A baseline group was killed at the start of the experiment (Base). The control group (Control), the group treated with vorozole alone (Vor), the group treated with E(2) alone (E(2)), or the group with a combination of both (Vor + E(2)) were killed 15 weeks later. Vorozole significantly increased serum testosterone (T) and reduced serum E(2) compared with Control. Body weight gain and serum insulin-like growth factor-I (IGF-I) were also lower in Vor, whereas significant weight loss and decrease of serum IGF-I occurred as a result of E(2) administration. Bone formation as assessed by serum osteocalcin was unaffected but osteoid surface in the proximal metaphysis of the tibia was increased in Vor-treated rats. Bone resorption as evaluated by urinary deoxypyridinoline excretion was increased in Vor. Biochemical parameters of bone turnover were reduced significantly in all E(2) treated rats. Premature closure of the growth plates and decreased osteoid and mineralizing surfaces were also observed in E(2) and Vor + E(2). Apparent bone density of lumbar vertebrae and femur, as measured by dual-energy X-ray absorptiometry (DXA), was significantly reduced in Vor. Vorozole decreased femoral bone density mainly in the distal femur (trabecular and cortical region). This decrease of bone density was not present in E(2) and Vor + E(2). Similar findings were observed when bone density was assessed by peripheral quantitative computed tomography (pQCT); that is, trabecular density of the distal femur, the proximal tibia, and the distal lumbar vertebra were all lower in Vor. This decrease in density was not observed in all E(2)-treated animals. In conclusion, administration of the aromatase inhibitor, vorozole, to aged male rats induces net trabecular bone loss in both the appendicular and axial skeleton, despite a concomitant increase in serum testosterone. E(2) administration is able to prevent this trabecular bone loss in vorozole-treated animals.
雄激素向雌激素的芳香化作用对于维持雄性骨骼可能很重要。为了验证这一假设，我们评估了芳香化酶抑制剂伏罗唑（Vor）单独或联合给予17β-雌二醇（E₂，1.35微克/天）对老年（12月龄）雄性大鼠骨骼的影响。实验开始时处死一组作为基线组（Base）。15周后处死对照组（Control）、单独给予伏罗唑的组（Vor）、单独给予E₂的组（E₂）或两者联合的组（Vor + E₂）。与对照组相比，伏罗唑显著提高了血清睾酮（T）水平并降低了血清E₂水平。伏罗唑组的体重增加和血清胰岛素样生长因子-I（IGF-I）水平也较低，而给予E₂导致体重显著减轻和血清IGF-I水平下降。血清骨钙素评估的骨形成未受影响，但伏罗唑处理的大鼠胫骨近端干骺端的类骨质表面增加。伏罗唑组尿脱氧吡啶啉排泄评估的骨吸收增加。所有E₂处理的大鼠骨转换的生化参数均显著降低。在E₂组和Vor + E₂组中还观察到生长板过早闭合以及类骨质和矿化表面减少。双能X线吸收法（DXA）测量的腰椎和股骨的表观骨密度在伏罗唑组显著降低。伏罗唑主要降低股骨远端（小梁和皮质区域）的骨密度。E₂组和Vor + E₂组未出现这种骨密度降低的情况。当通过外周定量计算机断层扫描（pQCT）评估骨密度时观察到类似结果；即，伏罗唑组股骨远端、胫骨近端和腰椎远端的小梁密度均较低。并非所有E₂处理的动物都出现这种密度降低的情况。总之，给老年雄性大鼠施用芳香化酶抑制剂伏罗唑会导致附肢骨骼和中轴骨骼的小梁骨净丢失，尽管血清睾酮同时升高。给予E₂能够预防伏罗唑处理动物的这种小梁骨丢失。
