Prakasam G, Yeh J K, Chen M M, Castro-Magana M, Liang C T, Aloia J F
Department of Pediatrics, Winthrop-University Hospital, Mineola, NY 11501, USA.
Bone. 1999 May;24(5):491-7. doi: 10.1016/s8756-3282(99)00018-6.
Osteoporosis in men is a disease that is increasing in incidence, and with an increasing elderly population it poses a serious health problem. Since both testosterone (T) and growth hormone (GH) have an anabolic effect on bone and both decrease with aging, we were prompted to test whether the administration of these hormones in combination would increase bone mass in orchiectomized (orx) senile rats more than administration of either agent alone. Twenty-month-old male Wistar rats were divided into five groups with seven animals each: (a) age-matched intact control, (b) orx, (c) orx+GH (2.5 mg/kg/day), (d) orx+T [10 mg/kg, subcutaneous (s.c.), injection given twice a week], and (e) orx+GH+T. Testosterone and GH were given subcutaneously for 4 weeks. Bone histomorphometry of the tibial shaft showed that the orx group had lower cortical bone area than the intact control group. The decrease in cortical bone area was due to increased intracortical porosis as well as decreased periosteal bone formation rate (BFR). Administration of T to the orx animals prevented the development of the porosis and the decrease in periosteal BFR. The bone mineral content (BMC) and bone mineral density (BMD) of the femur as tested by dual-energy X-ray absorptiometry were significantly higher in the orx+T than in the orx group and were not significantly different from that of the intact control group. Administration of GH to the orx rats increased periosteal BFR significantly; however, the BMC and BMD measured were not increased significantly in comparison to the orx group. When GH and T were combined in treatment, the cortical bone area, periosteal BFR, and femoral BMD were all significantly higher than that of the orx and even higher than the intact control rats. Two-way analysis of variance shows that the individual effect of GH and T treatment on the periosteal BFR and cortical bone area was significant. The effect of T, but not GH, on femoral BMC and BMD was also significant; however, there is no synergistic interaction between the two treatments. Four weeks of orx with or without GH or T administration had no significant effect on tibial metaphyseal cancellous bone volume. In conclusion, this short-term study suggests that the combined intervention of GH and T in androgen-deficient aged male rats may have an independent effect in preventing osteopenia. The significant effect of GH+T may be attributed to the prevention of intracortical porosis, and an increase in periosteal bone formation and cortical bone mass.
男性骨质疏松症的发病率正在上升，随着老年人口的增加，它构成了一个严重的健康问题。由于睾酮（T）和生长激素（GH）对骨骼都有合成代谢作用，且二者都会随着年龄增长而减少，因此我们进行了试验，以测试联合给予这两种激素是否比单独给予其中任何一种药物能更有效地增加去势（orx）老年大鼠的骨量。将20月龄的雄性Wistar大鼠分为五组，每组7只：（a）年龄匹配的完整对照组，（b）去势组，（c）去势+GH（2.5mg/kg/天）组，（d）去势+T组[10mg/kg，皮下（s.c.）注射，每周两次]，以及（e）去势+GH+T组。皮下给予睾酮和生长激素，持续4周。胫骨骨干的骨组织形态计量学显示，去势组的皮质骨面积低于完整对照组。皮质骨面积的减少是由于皮质内孔隙率增加以及骨膜骨形成率（BFR）降低所致。给去势动物注射睾酮可防止孔隙率的发展和骨膜BFR的降低。通过双能X线吸收法检测，去势+T组股骨的骨矿物质含量（BMC）和骨矿物质密度（BMD）显著高于去势组，且与完整对照组无显著差异。给去势大鼠注射生长激素可显著增加骨膜BFR；然而，与去势组相比，所测的BMC和BMD并未显著增加。当生长激素和睾酮联合治疗时，皮质骨面积、骨膜BFR和股骨BMD均显著高于去势组，甚至高于完整对照大鼠。双向方差分析表明，生长激素和睾酮治疗对骨膜BFR和皮质骨面积的个体效应显著。睾酮对股骨BMC和BMD有显著影响，而生长激素则无；然而，两种治疗之间没有协同相互作用。无论是否给予生长激素或睾酮，去势4周对胫骨近端干骺端松质骨体积均无显著影响。总之，这项短期研究表明，在雄激素缺乏的老年雄性大鼠中，生长激素和睾酮的联合干预可能对预防骨质减少具有独立作用。生长激素+睾酮的显著作用可能归因于预防皮质内孔隙率、增加骨膜骨形成和皮质骨量。
