INFLUENCE OF OVARIECTOMY ON BONE METABOLISM IN VERY OLD RATS

Twenty-five 30-month-old Lou rats fed a diet (6 g/100 g BW/day) contai ning 0.9% Ca and 0.8% Pi were divided into five groups. Four groups we re surgically ovariectomized. From day 2 until day 29 after ovariectom y, they were S.C, injected either with 17 beta estradiol (E(2); 10 mu g/kg BW/48 hours) or progesterone (P; 140 mu g/kg BW/48 hours), or 17 beta estradiol + progesterone (E(2)P) at the same doses, or solvent al one (OVX). The fifth group was sham operated (SH) and injected with so lvent. Urine was collected in metabolic cages from day 24 to 29 after OVX, and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excret ion (markers of bone resorption) was measured by HPLC. All animals wer e killed 30 days after ovariectomy. Serum was then collected for measu rement of osteocalcin (OC), alkaline phosphatase (ALP), parathyroid ho rmone (PTH), and calcitonin (CT). At necropsy, the success of ovariect omy was checked by marked atrophy of the uterine horns. Left and right femur were harvested for densitometric and mineral analysis, respecti vely. Ovariectomy had no significant effect upon plasma calcium and PT H concentrations. E(2) or E(2)P treatment significantly increased plas ma PTH and calcitonin concentrations. Plasma OC concentration and ALP were not different in any of the groups. In contrast, urinary excretio n of PYD and DPD was higher in OVX than in SH rats. Bone mineral densi ty (BMD) of the distal femur was decreased by OVX, but was not differe nt in the E(2)P and SH groups. A similar pattern was observed for the mineral or Ca content of whole femur. Thus, OVX decreased BMD and bone mineral content (BMC) in very old female rats. Plasma OC concentratio n and ALP activity failed to demonstrate any significant effect of OVX , whereas PYD and DPD were elevated. These results suggest that bone r esorption is increased in OVX rats, even when supplemented with E(2) o r P alone. However, no significant difference was observed between SH and OVX rats treated with supplementation of both E(2) and P. Thus, in very old rats, a combination of E(2) and P is much more effective tha n E(2) or P alone to prevent bone loss following ovariectomy.