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Tamoxifen prevents bone loss in castrated male mice
1Third Medical Clinic, First Medical Faculty, Charles University, Prague, Czech Republic.
Abstract:
The selective estrogen receptor modulator tamoxifen was administered to intact and castrated male mice, and its effects on tibial bones and circulatory calcium, phosphate and testosterone were compared with controls and castrated animals. Tamoxifen in a dose used in humans for treatment of breast cancer decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone, but did not have any negative effect on bone density or mineral content in intact mice. When castrated mice with extraordinarily low concentrations of testosterone and weights of seminal vesicles were treated with tamoxifen, the changes in bone density and bone mineral resulting from castration were not only entirely prevented, but increased above the values of intact mice. At the same time, cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of femur was completely prevented by tamoxifen treatment. Pharmacological therapy with estrogen agonist on bone, tamoxifen in androgen deficient adult male mice prevents bone loss.
Insights
Tamoxifen, used for breast cancer, surprisingly prevented bone loss in male mice with low testosterone. This selective estrogen receptor modulator enhanced bone density and mineral content, even in castrated animals.
Area of Science:
- Endocrinology
- Bone Biology
- Pharmacology
Background:
- Androgen deficiency in adult males leads to bone loss.
- Selective estrogen receptor modulators (SERMs) like tamoxifen have complex effects on male physiology.
- The impact of tamoxifen on bone metabolism in the context of androgen deficiency requires further elucidation.
Purpose of the Study:
- To investigate the effects of tamoxifen on bone density, mineral content, and cortical thickness in intact and castrated male mice.
- To compare the effects of tamoxifen with controls and castrated animals regarding bone health and circulatory factors.
- To determine if tamoxifen can prevent or reverse bone loss associated with androgen deficiency.
Main Methods:
- Administration of tamoxifen to intact and castrated male mice.
- Measurement of tibial bone density and mineral content.
- Assessment of seminal vesicle weight and serum testosterone concentrations.
- Evaluation of cortical bone thickness in the femur.
Main Results:
- Tamoxifen decreased seminal vesicle weight and testosterone levels in intact mice but did not negatively affect bone density or mineral content.
- In castrated mice, tamoxifen completely prevented bone density and mineral content reduction caused by castration, increasing them above intact levels.
- Tamoxifen treatment fully prevented the decrease in cortical thickness of the femur observed in orchidectomized mice.
Conclusions:
- Tamoxifen acts as an estrogen agonist on bone in adult male mice.
- Pharmacological therapy with tamoxifen effectively prevents bone loss in androgen-deficient male mice.
- Tamoxifen demonstrates potential as a therapeutic agent for managing bone loss in conditions of male hypogonadism or androgen deficiency.