A. Goulding et E. Gold, IN THE OVARIECTOMIZED RAT, TAMOXIFEN CONSERVES BONE SIMILARLY IN PARATHYROID-INTACT AND PARATHYROIDECTOMIZED ANIMALS, Bone, 15(5), 1994, pp. 497-503
To examine the ability of tamoxifen (TAM) to conserve bone in the estr
ogen-deficient ovariectomized (OVX) rat in the presence and absence of
parathyroid hormone (PTH) six groups of rats with Ca-45-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 s
ubcutaneously) or TAM-vehicle. Treatments were: group 1 = Sham-OVX; gr
oup 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 s
erial measurements of urinary hydroxyproline and Ca-45 excretion were
made during the study. Ovariectomy raised these markers of bone breakd
own and caused significant osteopenia, whereas TAM prevented ovariecto
my increasing urinary hydroxyproline or Ca-45 and conserved bone. Fina
l total body calcium values (TBCa) in groups 1-6, respectively, were (
mg +/- SD): 3240 +/- 300; 3260 +/- 289; 2750 +/- 231; 3212 +/- 312; 27
42 +/- 199; and 3387 +/- 252. Thus ovariectomy reduced TBCa similarly
in the presence and absence of the parathyroids (p < 0.001). In contra
st TAM fully protected both PT-intact and PTX rats from the osteopenic
effect of ovariectomy, despite the fact that PTX rats had a lower rat
e of bone turnover than PT-intact rats. However, TAM-treated OVX rats
had shorter femora than OVX rats given TAM-vehicle, suggesting that TA
M sup presses growth of the long bones to some degree in estrogen-defi
cient animals. We conclude that, in the rat, TAM conserves the skeleto
n from estrogen-deficiency bone loss independently of changes in PT fu
nction. Estrogen-deficiency bone loss is no greater in rats with a hig
h rate of PTH-mediated bone breakdown than in rats with a low rate of
PTH-mediated bone turnover.