Influence of Ovariectomy and Estradiol Treatment on Calcium Homeostasis During Aging in Rats

Study was carried out on Wistar female rats to evaluate the consequences of ovariectomy and 17β-estradiol substitutive treatment during aging on bone, Ca metabolism and calciotropic hormones. Three groups of fifteen rats, mature, old and senescent (4-, 10-, and 28 month-old) female were fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi. Within each group, 10 rats were surgically ovariectomized (OVX). From day 1 until day 60 after OVX, they were subcutaneously injected with either 17β-estradiol (E: 10 µg/kg BW/48 h; n = 5) or with solvent alone (OVX; n = 5). Five other rats were sham operated (SH) and received solvent alone. Animals were put in balance 1 day per week to determine Ca and Pi intestinal apparent absorption and urinary pyridinium cross-links excretion was measured by HPLC. All rats were killed by exsanguination 60 days after OVX. Plasma was collected for measurement of intact parathyroid hormone (PTH), calcitonin (CT), insulin-like growth factor-1 (IGF-1), Ca and Pi. The success of OVX was confirmed at necropsy by observation of marked atrophy of the uterine horns. The right femur was collected, cleaned from adjacent tissue and used for mineral analysis. Despite correct matching for feeding, BW was significantly larger in 6 and 12 month-old OVX rats. OVX and 17β-estradiol had no significant effect upon plasma Ca, Pi and CT concentrations. Aging is associated with increased circulating PTH levels (pg/ml) (SH - 6 months: 50.8 ± 12.6; 12 months: 219.1 ± 34.9; 30 months: 158.7 ± 23.5; P < 0.05). Ur inary and fecal Ca and Pi excretion in senescent animals were higher than in adult or old rats, thus resulting in a drastic fall in both intestinal apparent absorption and retention of Ca and Pi in 30 month-old animals. In each group, urinary pyridinium cross-links excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. In the same way, OVX increased and estrogen decreased the plasma IGF-1 levels. We conclude that 17β-estradiol prevents high turnoverinduced osteopenia even in 30 month-old rats.