Effects of growth hormone and testosterone on cortical bone formation and bone density in aged orchiectomized rats

Osteoporosis in men is a disease that is increasing in incidence, and with an increasing elderly population it poses a serious health problem. Since b oth testosterone (T) and growth hormone (GH) have an anabolic effect on bon e and both decrease with aging, we were prompted to test whether the admini stration of these hormones in combination would increase bone mass in orchi ectomized (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 grou p 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 p eriosteal BFR, The bone mineral content (BMC) and bone mineral density (BMD ) of the Femur as tested by dual-energy X-ray absorptiometry were significa ntly higher in the orx+T than in the orx group and were not significantly d ifferent from that of the intact control group. Administration of On to the orx rats increased periosteal BFR significantly; however, the BMC and BMD measured were not increased significantly in comparison to the orx group. W hen On and T were combined in treatment, the cortical bone area, periosteal BFR, and femoral BMD were all significantly higher than that of the orx an d even higher than the intact control rats. Two-way analysis of variance sh ows that the individual effect of On and T treatment on the periosteal BFR and cortical bone area was significant. The effect of T, but not GH, on fem oral BMC and BMD was also significant; however, there is no synergistic int eraction between the two treatments. Four weeks of orx with or without GH o r T administration had no significant effect on tibial metaphyseal cancello us bone volume, In conclusion, this short-term study suggests that the comb ined intervention of On 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 i ncrease in periosteal bone formation and cortical bone mass, (C) 1999 by El sevier Science Inc. All rights reserved.