The aged male rat as a model for human osteoporosis: Evaluation by nondestructive measurements and biomechanical testing

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Abstract
Effects of androgen deficiency and androgen replacement on bone density, as measured with dual-energy X-ray absorptiometry (DXA) and single photon absorptiometry (SPA), cortical ratio (cortical thickness/outside bone diameter x 100), and biomechanical properties were evaluated in 14-month-old (1 month after orchiectomy (orch) or sham-operation) and in 17-month-old (4 months after orch or sham) male rats. Whole femoral bone mineral content (BMC) and density (BMD) measured with DXA were not significantly decreased 1 month after orch. Whole femoral BMC and BMD were 10% and 8% lower in 4 months after orch (P < 0.01 andP < 0.001, respectively). This decrease was prevented by testosterone replacement. There was an excellent correlation (R = 0.99) between whole femoral BMC and femoral ash weight. Selective scanning of cortical and cancellous sites of the femur showed that both cancellous and cortical BMC and BMD were significantly decreased 4 months after orch. SPA of the right tibia confirmed a 7% decrease in cancellous BMC and BMD 4 months after orch (preventable by testosterone) but not in cortical BMD and BMC. Femoral cortical ratio decreased with age (47 ± 2 in 14-month-old and 40 ± 2 in 17-month-old sham rats versus 63 ± 1 in 6-month-old male rats) due to a continuously enlarging femoral shaft. Androgen deficiency resulted in an even greater decrease of the cortical ratio 4 months after orch (36 ± 2 in 17-month-old orch rats) that was again prevented by testosterone (47 ± 3). These changes in femoral cortical, cancellous density, and cortical ratio did not affect biomechanical properties of the femur as evaluated by torsion testing. The lack of an effect on bone biomechanics was most likely due to the protection afforded by an increased femoral shaft diameter. We conclude that 4 months after orch, aged male orch rats had a lower femoral cortical and cancellous density and a lower cortical ratio without decrease of biomechanical properties of the femoral shaft. Testosterone replacement was effective not only in preventing the decrease of cancellous and cortical density but also in preventing the age-related thinning of the femoral cortex.