Effect of alendronate administration on bone mineral density and bone strength in castrated rats

Castration of male rats leads to increased bone turnover and osteopenia. This study was conducted to examine the effects of the aminobisphosphonate alendronate on castration-induced bone changes. Bisphosphonates are drugs that inhibit bone turnover by decreasing the resorption. Since they suppress bone remodeling, they may also prevent the repair of microdamage and decrease bone strength. Although the mechanical properties of bones are directly related to the determination of fracture risk, bisphosphonate effects on the related variables have scarcely been investigated. Twenty-four male Wistar rats at two months of age were castrated or sham-operated to evaluate the effects of long-term administration (six months) of sodium alendronate at a dose of 1 mg/kg/day. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. High bone remodeling seen in castrated rats expressed by increased TrACP and B-ALP was suppressed by alendronate administration. Bone from castrated rats was characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone and femoral cortical thickness. When castrated rats were treated with high dose of alendronate, the changes in bone density resulting from castration were entirely prevented, and mechanical analysis revealed preserved mechanical strength of femur and cortical thickness. We conclude that castration induces cortical bone loss associated with high bone turnover in the male rat, and this bone loss can be prevented by alendronate through the inhibition of osteoclastic activity, while preserving the mechanical properties of bone. These results document the efficacy of alendronate, even at high doses, in preventing bone loss, loss of bone mechanical strength, and the rise in biochemical bone turnover indicators due to castration in rats, and raises the possibility that a alendronate could be equally effective in humans.