Bone structure after two sequential regimens of tamoxifen and Arimidex in an ovariectomized rat model: a light and scanning electron microscopic study. Issue 1 (March 2016) - El-Nefiawy, Nagwa E.
Abstract : Background: Tamoxifen and Arimidex are two standard drugs for endocrinal therapy in breast cancer patients. However, it is not well established as to which of the two drugs should be prescribed first in the sequential regimens. Aim: The present study was designed to investigate bone structure characteristics after two alternative sequential regimens of tamoxifen and Arimidex to determine the superior regimen conserving bone in postmenopausal rats. Materials and methods: Adult female rats were divided into six groups: group I included control rats; group II included ovariectomized (ovx) nontreated rats; group III included ovx rats treated with tamoxifen; group IV included ovx rats treated with Arimidex; group V included ovx rats treated sequentially with tamoxifen plus Arimidex; and group VI included ovx rats treated sequentially with Arimidex plus tamoxifen (tamoxifen→Arimidex vs. Arimidex→tamoxifen). Daily oral drug treatments were given for 1 month for each drug. Tamoxifen was administered at a dose of 60 μg/day/ rat. Arimidex was administered at a dose of 40 μg/rat/day. At the end of the experiment, all rats were sacrificed, and the tibias were extracted and processed for paraffin block embedding or scanning electron microscopic examination. Cortical and trabecular bone thickness were measured by means of image analysis. Results: Histological and scanning electron microscopic observations revealed widening of the haversian canals, with marked loss of cancellous bone trabeculae following ovariectomy. This was confirmed by a significant decrease in bone thickness on histomorphometry. Single drug treatment with Arimidex revealed extensive cavitation and widening of the haversian canals with severe erosion cavities. The tamoxifen-treated group showed apparently preserved bone structure compared with the Arimidex group. Group of the first sequential therapy (group V) demonstrated histologically few cancellous bone trabeculae. However, the second sequential regimen (group VI) showed severe rarefaction, thinning, and bone fractures. Scanning microscopy and bone measurements confirmed the histological findings. Conclusion: Sequential hormonal treatment starting with tamoxifen followed by Arimidex is likely to preserve bone structure compared with the other sequential regimen. Single drug treatment with tamoxifen gave best bone preservation. To our knowledge, this is the first experimental report in this regard.