Vanderschueren D, van Herck E, Nijs J, Ederveen A G, De Coster R, Bouillon R
Laboratorium of Experimental Medicine and Endocrinology (LEGENDO), Onderwijs en Navorsing, Gasthuisberg, Leuven, Belgium.
Endocrinology. 1997 Jun;138(6):2301-7. doi: 10.1210/endo.138.6.5216.
Aromatization of androgens into estrogens may explain some of the skeletal action of androgens. We examined the effect of the aromatase inhibitor Vorozole (VOR) on skeletal growth and mineral accumulation in growing 6-week-old male Wistar rats. Rats were either Sham-operated (Sham) or Orchidectomized (Orch) and treated with or without the aromatase inhibitor VOR. One Sham-operated group was killed at Baseline (Base); the four other groups (Sham, Sham + VOR, Orch, Orch + VOR) were killed 18 weeks after surgery. As expected, all groups gained body weight, but body weight gain was significantly (-25%) lower in Orch, Orch + VOR, and Sham + VOR. Both bone formation, as assessed by serum osteocalcin, and bone resorption, as assessed by urinary (deoxy)pyridinoline, decreased significantly in all groups compared with Base. Orchidectomy resulted in a relative increase of biochemical markers of bone formation and resorption compared with Sham. Treatment with VOR, however, resulted only in a very moderate increase of (deoxy)pyridinoline compared with Sham. As expected, femoral length increased compared with Base, but orchidectomy reduced the relative growth of the femur whereas VOR did not influence femoral length. Ex vivo, densitometric and geometric properties of the femora were evaluated by peripheral computerized quantitative tomography (pQCT) and dual-energy x-ray absorptiometry (DXA). The lumbar vertebrae were measured by DXA. At the end of the experimental period, volumetric trabecular bone mineral density (vTBMD) measured at the distal end of the femur was significantly lower not only in both Orch groups but also in Sham + VOR. The decrease of cancellous bone density in Sham + VOR was lower than in the orchidectomized animals. A relative decrease of femoral inner and outer diameters compared with Sham and Base was observed in both Orch groups and in Sham + VOR, suggesting that both orchidectomy and VOR-treatment inhibited periosteal bone formation and endosteal bone resorption. Only orchidectomy, however, resulted in a decrease of cortical thickness. Bone area, mineral content, and density of both femora and lumbar vertebrae, measured by DXA, were decreased to a similar extent by VOR and Orch (bone mineral content of the femur was 467 +/- 18 mg in Orch and 461 +/- 10 mg in Sham +/- VOR vs. 521 +/- 11 mg in Sham; P < 0.001). In conclusion, treatment with the aromatase inhibitor VOR impairs body weight gain and skeletal modeling and decreases bone mineral density. Aromatase inhibition had similar final effects on bone mass and size as castration, but with less marked effects on bone turnover.
雄激素向雌激素的芳香化作用可能解释了雄激素的一些骨骼作用。我们研究了芳香化酶抑制剂伏罗唑（VOR）对6周龄雄性Wistar生长大鼠骨骼生长和矿物质积累的影响。大鼠分为假手术组（Sham）或去势组（Orch），并分别接受或不接受芳香化酶抑制剂VOR治疗。一个假手术组在基线期（Base）处死；其他四组（Sham、Sham + VOR、Orch、Orch + VOR）在手术后18周处死。正如预期的那样，所有组体重均增加，但Orch、Orch + VOR和Sham + VOR组的体重增加显著降低（-25%）。与Base组相比，所有组中通过血清骨钙素评估的骨形成以及通过尿（脱氧）吡啶啉评估的骨吸收均显著降低。与Sham组相比，去势导致骨形成和骨吸收的生化标志物相对增加。然而，与Sham组相比，VOR治疗仅导致（脱氧）吡啶啉非常适度的增加。正如预期的那样，与Base组相比股骨长度增加，但去势减少了股骨的相对生长，而VOR不影响股骨长度。体外通过外周计算机断层扫描（pQCT）和双能X线吸收法（DXA）评估股骨的密度和几何特性。通过DXA测量腰椎。在实验期结束时，不仅两个Orch组，而且Sham + VOR组在股骨远端测量的体积骨小梁骨密度（vTBMD）均显著降低。Sham + VOR组松质骨密度的降低低于去势动物。在两个Orch组和Sham + VOR组中均观察到与Sham组和Base组相比股骨内外径相对减小，表明去势和VOR治疗均抑制骨膜骨形成和骨内膜骨吸收。然而，只有去势导致皮质厚度降低。通过DXA测量的股骨和腰椎的骨面积、矿物质含量和密度，VOR和Orch组降低程度相似（Orch组股骨矿物质含量为467 +/- 18 mg，Sham +/- VOR组为461 +/- 10 mg，Sham组为521 +/- 11 mg；P < 0.001）。总之，芳香化酶抑制剂VOR治疗损害体重增加和骨骼塑形，并降低骨矿物质密度。芳香化酶抑制对骨量和大小的最终影响与去势相似，但对骨转换的影响较小。
