The effects of tamoxifen on the osteopenia induced by sciatic neurotomy in the rat: a histomorphometric study.

The effects of a 3-week treatment with the nonsteroidal "antiestrogen" tamoxifen were determined on cortical and trabecular bone mass of the tibiae of growing male rats that had undergone unilateral sciatic neurotomy (USN). USN resulted in decreases in cortical area (-11.3%), cross-sectional area (-8.4%), and periosteal bone formation rate (-32.6%) in cortical bone, indicating that the disuse osteopenia results in a decrease in bone formation in cortical bone. USN significantly reduced the amount of trabecular bone in our metaphyseal sampling site (-75%), markedly increasing the amount of bone surface lined by osteoclasts (+65%) without affecting the surface lined by osteoblasts. These results suggest that trabecular bone disuse osteopenia is due, at least in part, to increased bone resorption. Tamoxifen treatment significantly reduced the loss of trabecular bone, restoring resorbing surface length to the control (sham-operated) animal levels. Tamoxifen treatment of sham-operated animals increased trabecular bone area and surface by 35.7% (+/- 10.5) and 41.8% (+/- 7.8), respectively, and reduced resorbing surface by 21.5% (+/- 11.6) compared with sham-operated placebo-treated rats. Tamoxifen had no significant effect on cortical bone parameters in the sham-operated group. The results indicate that tamoxifen is able to reduce the trabecular bone loss that results from USN, but has no effect on cortical bone disuse osteopenia, or on trabecular bone formation. Moreover, tamoxifen treatment of control (intact) animals inhibited the normal levels of bone resorption occurring in these rapidly growing animals.