Ionized calcium and bone turnover in the estrogen-deficient rat

The long-term effects of high bone resorption on blood ionized calcium and calciotropic hormone levels following oophorectomy in 6-month-old Sprague-Dawley female rats were investigated. Fasting urine and blood samples were collected from 16 sham and 16 oophorectomized (oophx) rats preoperatively and up to 130 days postoperatively. From 50 days postoperation, daily injections of 17-beta estradiol (E2) (20 microg/kg body weight) were administered subcutaneously to eight of the oophx rats. Urine hydroxyproline excretion (OHPrE) and serum osteocalcin were significantly elevated (P < 0.001) as a result of oophorectomy and normalized within 6 days of E2 replacement. Urine deoxypyridinoline and total serum alkaline phosphatase were significantly elevated (P < 0.001) following oophorectomy and suppressed to control levels after 37 days of E2 replacement. Blood ionized calcium was significantly reduced in oophx rats (P < 0.001) compared with sham rats and was normalized by E2 replacement at 55 days posttreatment. Serum 1,25 dihydroxyvitamin D (1,25(OHD)2D3) was significantly elevated (P < 0.001) in oophx rats and again was normalized by E2 at 55 days posttreatment. Serum parathyroid hormone (PTH) was unaffected by oophorectomy. These data indicate that despite increased bone resorption following oophorectomy, blood ionized calcium levels are decreased. The increased bone turnover in oophx rats was rapidly suppressed by E2 replacement before ionized calcium levels were normalized, suggesting a direct effect of estrogen on the modulation of bone cell activity. The depression of blood ionized calcium levels following oophorectomy, 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.