Flutamide-mediated androgen blockade evokes osteopenia in the female rat.
Androgens are believed to play a role in building and maintaining bone in the female, as well as in the male. The antiandrogen drug flutamide inhibits responses to androgens from both the gonads and the adrenals. Antiandrogens prevent androgens stimulating bone cell proliferation and differentiation in vitro, but effects of androgen blockade on bone metabolism in vivo have not been tested. The present study was undertaken to determine whether androgen blockade with flutamide (15 mg/kg body weight orally daily) would influence bone turnover or bone composition (1) in female rats with intact ovaries and (2) in rats made estrogen-deficient with the luteinizing hormone releasing hormone (LHRH) agonist, buserelin (25 micrograms/kg body weight per day SC). Four groups of rats with 45Ca-labeled skeletons were studied for 4 weeks: group A, placebo; group B, buserelin; group C, flutamide; group D, flutamide+buserelin. Total-body calcium values (mean +/- SD) were (mg) 2007 +/- 109, 1779 +/- 138 (P < 0.01 versus group A), 1818 +/- 140 (P < 0.01 versus group A), and 1690 +/- 75 (P < 0.01 versus group A) in groups A-D, respectively. Thus both buserelin and flutamide induced osteopenia. Skeletal 45Ca changes suggested buserelin-mediated estrogen deficiency bone loss was due to increased bone resorption, but flutamide-mediated androgen deficiency bone thinning was caused principally by reduced bone formation. These findings support the view that androgens play an important role in preserving bone mass in the female rat. Importantly, adequate estrogen status did not compensate for flutamide-mediated osteopenia.(ABSTRACT TRUNCATED AT 250 WORDS)
Goulding
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Department of Medicine, University of Otago, Dunedin, New Zealand.
Gold
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E
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000503:physiopathology; D002064:Buserelin / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000494:pharmacology*; D006909:Hydroxyproline / Q000652:urine; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects
D000728:Androgens; D005485:Flutamide; D002064:Buserelin; D006909:Hydroxyproline