Casodex (a nonsteroidal antiandrogen) reduces cancellous, endosteal, and periosteal bone formation in estrogen-replete female rats.
Testosterone has been implicated in the preservation of the skeleton in women and female rats. In this study we investigated the role of androgens in estrogen-replete female rats by giving Casodex (pure nonsteroidal anti-androgen) daily and analyzing the effects on the skeleton using static and dynamic histomorphometric parameters after 3 weeks. There was a significant reduction in the bone formation rate in both the cancellous bone of the tibial metaphysis and in the periosteal and corticoendosteal diaphyseal bone (90%, 30%, and 100% reduction, respectively), compared with control animals, which was unaccompanied by a change in the indices of bone resorption. Casodex had no effect on cancellous bone volume and cortical bone area but this can be accounted for by the short duration of the experiment. The serum levels of dehydroepiandrosterone-sulfate and androstenedione were significantly reduced in the Casodex-treated rats compared with the control animals and there was no difference in the plasma levels of estrone, estradiol, or testosterone between the two groups. This study demonstrates that androgens play a physiological role in regulating osteoblast activity in female rats.
Lea
C
C
Department of Histopathology, St. Mary's Hospital Medical School, London, UK.
Kendall
N
N
Flanagan
A M
AM
D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000502:physiology*; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004967:Estrogens / Q000502:physiology*; D005260:Female; D009570:Nitriles; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000502:physiology; D014105:Tosyl Compounds; D014599:Uterus / Q000502:physiology; D015430:Weight Gain
D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D004967:Estrogens; D009570:Nitriles; D014105:Tosyl Compounds; D019314:Dehydroepiandrosterone Sulfate; C053541:bicalutamide