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-mu-g/kg body wt/day s.c.). Four groups of rats with Ca-45-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 Ca-45 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 < 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.