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Flutamide‐mediated androgen blockade evokes osteopenia in the female rat
Author(s) -
Goulding Ailsa,
Gold E.
Publication year - 1993
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650080615
Subject(s) - flutamide , endocrinology , antiandrogen , medicine , osteopenia , androgen , buserelin , testosterone (patch) , estrogen , bone remodeling , bone resorption , osteoporosis , agonist , hormone , prostate cancer , androgen receptor , bone mineral , cancer , receptor
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 μg/kg body weight per day SC). Four groups of rats with 45 Ca‐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 45 Ca 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. Although this work was done in an animal model, it seems possible that antiandrogen drugs cause osteopenia in people as well as in the rat. Further study of the likely bone‐protective effects of androgen are also warranted in women.