Influence of adult age on the skeletal response to phosphate and estrogen in rats.

Sixteen-month-old ("aged") female rats were less susceptible than 6-month-old ("mature") females to parathyroid hormone (PTH)-mediated bone resorption induced by excess dietary phosphate. Ovariectomy enhanced 45Ca loss from the bones of mature rats but not of aged rats. In mature ovariectomized (OX) females, estradiol initially suppressed phosphate-induced bone resorption but its effectiveness decreased with continued administration. Diethylstilbestrol (DES) administered continuously or on a 3-weeks-on, 1-week-off schedule in the diet suppressed the increase in 45Ca loss in OX mature females fed a high (1.2%) P diet. In contrast, DES had no consistent effect on 45Ca loss by the aged animals. Urinary cyclic adenosine monophosphate (cAMP) was increased to a similar extent in both groups by feeding excess phosphate, indicating that the reduced effect of phosphate on 45Ca loss in the aged females was due to decreased bone response to PTH. Ovariectomies produced an increase in cAMP excretion which was suppressed by DES administration. DES also suppressed the increase in urinary cAMP induced by dietary phosphate, signifying that the decrease in bone resorption produced by estrogen is associated with an inhibition either of PTH synthesis or function.