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Comparative Study
. 1996 Jun;149(3):503-8.
doi: 10.1677/joe.0.1490503.

Selective toxic effects of tamoxifen on osteoclasts: comparison with the effects of oestrogen

T R Arnett  1 , R Lindsay, J M Kilb, B S Moonga, M Spowage, D W Dempster
Affiliations
Comparative Study

Selective toxic effects of tamoxifen on osteoclasts: comparison with the effects of oestrogen

T R Arnett et al. J Endocrinol. 1996 Jun.

Abstract

We investigated the actions of the trans- and cis-isomers of tamoxifen on the function of neonatal rat osteoclasts in vitro. Both compounds inhibited resorption pit formation by osteoclast-containing mixed bone cell cultures incubated for 24 h on cortical bone slices. Cell counts revealed that the inhibition was closely related to a cytotoxic effect, to which osteoclasts appeared particularly sensitive. Partial inhibition of resorption was seen in the presence of 2 microM trans-tamoxifen, whereas complete abolition of resorption and osteoclast viability occurred with 10 microM trans-tamoxifen; survival of mononuclear cells was unimpaired at either concentration. Cis-tamoxifen appeared to be slightly more toxic, with significant inhibitions of osteoclast viability and thus resorption pit formation at a concentration of 2 microM, and also of mononuclear cell numbers at 10 microM. Time-lapse video observations indicated that osteoclast death occurred rapidly (within 2-3 h) following exposure to 10 microM of either trans-tamoxifen or cis-tamoxifen. The morphological appearance of the dying cells was consistent with apoptosis. These results may help to explain the anti-resorptive action of tamoxifen seen in vivo in rats and humans. In contrast, oestradiol-17 beta consistently exerted no significant effects on resorption pit formation by rat osteoclasts over 24 h, even at grossly supraphysiological concentrations (up to 10 microM).

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