THE EFFECT OF ESTROGEN DEFICIENCY ON BONE-MINERAL DENSITY, RENAL CALCIUM AND PHOSPHORUS HANDLING AND CALCITROPIC HORMONES IN THE RAT

The oophorectomized (OOX) rat has been proposed as a good model of pos tmenopausal osteroporosis in women. The aim of this study was to compa re the effect of OOX in 6-month-old rats to the effects of menopause i n women with respect to bone mass, the renal handling of calcium and p hosphorus, and calcitropic hormones. To more closely replicate the hum an situation the rats were pair fed a 0.1% calcium diet. Thirty four, 6-month-old rats were randomized to sham operation or OOX. Whole body and regional bone density was performed at baseline and 6 weeks postop eration. Blood and 24-hour urine samples were obtained at baseline, 1, 3, and 6 weeks and assayed for various biochemical variables, parathy roid hormone (PTH), and calcitriol. The OOX rats lost significantly mo re bone than the sham-operated rats (change in global bone mineral den sity, sham -1.7 +/- 2.0%, OOX -3.9 +/- 2.6%, P < 0.001). In the OOX an imals, an increase in the 24-hour urine calcium was observed at 1 and 3 weeks, which had returned to sham-operated levels by 6 weeks. In the whole group, the increase in urine calcium at 1 week was negatively c orrelated with the change in bone mass at 6 weeks (r = 0.39, P = 0.029 ). OOX resulted in an increased filtered load of calcium and phosphoru s. There was an increase in the maximal renal tubular reabsorption of phosphorus (TmP-GFR) but no clear change in renal calcium handling. Ne ither calcitriol nor parathyroid hormone showed a significant change a s a result of OOX. As in postmenopausal women, following oophorectomy in the rat, there was significant generalized bone loss and a negative calcium balance. This was associated with an initial rise in urine ca lcium due to a rise in the filtered calcium load; plasma phosphorus an d TmP-GFR also rose. The rat model may differ from postmenopausal bone loss in that the initial rise in urine calcium was not present at lat er time points as occurs in natural menopause in women. Calcitropic ho rmone levels did not change. This study has shown that the 6-month-old OOX rat fed a 0.1% calcium diet has many similarities of calcium and phosphorus homeostasis to that seen at menopause in women.