Skeletal effects of estrogen deficiency as induced by an aromatase inhibitor in an aged male rat model

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 inhib itor vorozole (Vor), with or without 17 beta -estradiol (E-2) administratio n (1.35 mug/day), in aged (12-month-old) male rats. A baseline group was ki lled at the start of the experiment (Base), The control group (Control), th e 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 w eeks later. Vorozole significantly increased serum testosterone (T) and red uced serum E-2 compared with Control, Body weight gain and serum insulin-li ke growth factor-I (IGF-I) were also lower in Ver, whereas significant weig ht loss and decrease of serum IGF-I occurred as a result of E-2 administrat ion. Bone formation as assessed by serum osteocalcin was unaffected but ost eoid surface in the proximal metaphysis of the tibia was increased in Ver-t reated rats. Bone resorption as evaluated by urinary deoxypyridinoline excr etion was increased in Ver, Biochemical parameters of bone turnover were re duced significantly in all E-2 treated rats, Premature closure of the growt h 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 r educed in Ver. 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 t he distal lumbar vertebra were all lower in Ver. This decrease in density w as not observed in all E-2-treated animals. In conclusion, administration o f the aromatase inhibitor, vorozole, to aged male rats induces net trabecul ar bone loss in both the appendicular and axial skeleton, despite a concomi tant increase in serum testosterone, E-2 administration is able to prevent this trabecular bone loss in vorozole-treated animals, (C) 2000 by Elsevier Science Inc. All rights reserved.