The long-term effects of high bone resorption on blood ionized calcium and
calciotropic hormone levels following oophorectomy in 6-month-old Sprague-D
awley female rats were investigated. Fasting urine and blood samples were c
ollected from 16 sham and 16 oophorectomized (oophx) rats preoperatively an
d up to 130 days postoperatively. From 50 days postoperation, daily injecti
ons of 17-beta estradiol (E-2) (20 mu g/kg body weight) were administered s
ubcutaneously to eight of the oophx rats. Urine hydroxyproline excretion (O
HPrE) and serum osteocalcin were significantly elevated (P < 0.001) as a re
sult of oophorectomy and normalized within 6 days of E-2 replacement. Urine
deoxypyridinoline and total serum alkaline phosphatase were significantly
elevated (P < 0.001) following oophorectomy and suppressed to control level
s after 37 days of E-2 replacement. Blood ionized calcium was significantly
reduced in oophx rats (P < 0.001) compared with sham rats and was normaliz
ed by E-2 replacement at 55 days posttreatment. Serum 1,25 dihydroxyvitamin
D (1,25(OHD)(2)D-3) was significantly elevated (P < 0.001) in oophx rats a
nd again was normalized by E-2 at 55 days posttreatment. Serum parathyroid
hormone (PTH) was unaffected by oophorectomy. These data indicate that desp
ite increased bone resorption following oophorectomy, blood ionized calcium
levels are decreased. The increased bone turnover in oophx rats was rapidl
y suppressed by E-2 replacement before ionized calcium levels were normaliz
ed, suggesting a direct effect of estrogen on the modulation of bone cell a
ctivity. The depression of blood ionized calcium levels following oophorect
omy, which is not mediated by calciotropic hormones, suggests an effect of
estrogen on intestinal calcium absorption, renal handling of calcium, or a
combination of both.