In the ovariectomized rat, tamoxifen conserves bone similarly in parathyroid-intact and parathyroidectomized animals.
To examine the ability of tamoxifen (TAM) to conserve bone in the estrogen-deficient ovariectomized (OVX) rat in the presence and absence of parathyroid hormone (PTH) six groups of rats with 45Ca-labeled bones were studied for 12 weeks. Rats were OVX, parathyroidectomized (PTX), or given sham operations and treated with TAM (10 mg/kg body wt./wk subcutaneously) or TAM-vehicle. Treatments were: group 1 = Sham-OVX; group 2 = Sham-OVX + TAM; group 3 = OVX; group 4 = OVX + TAM; group 5 = OVX + PTX; and group 6 = OVX + PTX + TAM. To monitor bone resorption serial measurements of urinary hydroxyproline and 45Ca excretion were made during the study. Ovariectomy raised these markers of bone breakdown and caused significant osteopenia, whereas TAM prevented ovariectomy increasing urinary hydroxyproline or 45Ca and conserved bone. Final total body calcium values (TBCa) in groups 1-6, respectively, were (mg +/- SD): 3240 +/- 300; 3260 +/- 289; 2750 +/- 231; 3212 +/- 312; 2742 +/- 199; and 3387 +/- 252. Thus ovariectomy reduced TBCa similarly in the presence and absence of the parathyroids (p < 0.001). In contrast TAM fully protected both PT-intact and PTX rats from the osteopenic effect of ovariectomy, despite the fact that PTX rats had a lower rate of bone turnover than PT-intact rats. However, TAM-treated OVX rats had shorter femora than OVX rats given TAM-vehicle, suggesting that TAM suppresses growth of the long bones to some degree in estrogen-deficient animals.(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
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy*; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004967:Estrogens / Q000172:deficiency; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D007279:Injections, Subcutaneous; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010052:Ovariectomy / Q000009:adverse effects; D010281:Parathyroid Hormone / Q000502:physiology*; D016105:Parathyroidectomy; D051381:Rats; D017208:Rats, Wistar; D013054:Spectrophotometry, Atomic; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D004967:Estrogens; D010281:Parathyroid Hormone; D013629:Tamoxifen; D006909:Hydroxyproline; D002118:Calcium