Tamoxifen in the rat prevents estrogen-deficiency bone loss elicited with the LHRH agonist buserelin.
In young women chronic use of luteinizing hormone releasing hormone (LHRH) agonists such as buserelin to treat endometriosis leads to estrogen-deficiency bone loss. Tamoxifen citrate is an estrogen agonist/antagonist which protects the skeleton from osteopenia when ovarian hormones are depleted. The present study was undertaken to determine whether tamoxifen citrate (20 mg/kg body wt/week s.c.) could prevent the osteopenic effect of buserelin (25 micrograms/kg body wt/day s.c.). Four groups of rats with 45Ca-labelled bones were studied for 4 weeks: group A--placebo controls; group B--buserelin; Group C--tamoxifen; group D--buserelin+tamoxifen. Bone resorption was monitored by measuring the urinary excretion of 45Ca and hydroxyproline. Interestingly buserelin lowered both blood 17 beta-estradiol values and uterine weights in the presence and absence of tamoxifen. However, tamoxifen slowed bone breakdown and inhibited the bone-thinning effects of buserelin. Total body calcium values (mg; means +/- S.D.) were: 2227 +/- 137; 1926 +/- 124; 2233 +/- 94 and 2268 +/- 163, in groups A to D respectively. Osteopenia was thus present only in group B (P less than 0.001). Because tamoxifen inhibits estrogen-deficiency bone loss in buserelin-treated rats without depressing the hypoestrogenic actions of this LHRH-agonist, we suggest that use of tamoxifen to protect the skeleton during LHRH-agonist therapy in young women should be explored. Tamoxifen citrate might also help to prevent postmenopausal osteoporosis.
Goulding
A
A
Department of Medicine, University of Otago Medical School, Dunedin, New Zealand.
Gold
E
E
Feng
W
W
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000517:prevention & control; D001862:Bone Resorption / Q000139:chemically induced* / Q000517:prevention & control; D002064:Buserelin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000652:urine; D004195:Disease Models, Animal; D004347:Drug Interactions; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006909:Hydroxyproline / Q000652:urine; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
D004967:Estrogens; D013629:Tamoxifen; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D002064:Buserelin; D006909:Hydroxyproline; D002118:Calcium