Bone and mineral metabolism in aged male rats: short and long term effects of androgen deficiency.

Abstract

Both short and long term effects of androgen deficiency and steroid replacement therapy on skeletal homeostasis were investigated in aged (13-month-old) male rats. The animals were either sham operated (n = 28) or orchidectomized (orch; n = 89). The orch animals were divided into 5 groups; 26 rats received an empty sc Silastic implant (orch), all others received an implant containing testosterone (T), 5 alpha-dihydrotestosterone (DHT), 17 beta-estradiol (E2), or nandrolone (Nandro; 15-16 rats in each group). Half of the rats were killed 1 month (short term experiment) after implantation; the others were killed 4 months after implantation (long term experiment). Short term androgen deficiency caused a significant increase in both serum osteocalcin and histomorphometric parameters of bone turnover measured at the proximal tibial metaphysis, but not in a significant decrease in bone mass at this site. This increase in bone turnover was prevented not only by T and DHT, but also by E2 and Nandro. Long term androgen deficiency resulted in a decrease in the calcium content of both tibia and lumbar vertebrae. Cancellous bone volume in the proximal tibial metaphysis was +/- 50% lower in the orch group (P less than 0.001) 4 months after orchidectomy. At the same time, cortical bone was lost in orch rats; femoral cortical thickness was reduced by 12% (P less than 0.01), and cortical density tended to be lower. T, DHT, E2, or Nandro treatment completely prevented this decrease in cortical thickness and density. T and Nandro were also able to prevent the cancellous bone loss. DHT could only partly prevent cancellous bone loss. E2 treatment resulted not only in a sustained decrease in both serum osteocalcin concentrations and histomorphometric indices of bone turnover, but also in a net gain of cancellous bone volume (P less than 0.05 vs. sham). No significant differences in serum concentrations of vitamin D metabolites or nephrogenous cAMP were observed between groups in both short and long term experiments. We conclude that bone mass in aged male rats was significantly decreased 4 months after orchidectomy, preceded by an early increase in bone turnover. Both the early increase in bone turnover and the later decrease in bone mass were prevented by aromatizable and nonaromatizable androgens by estrogen and by nandralone.