SHORT-TERM PROPHYLAXIS AGAINST ESTROGEN DEPLETION-INDUCED BONE LOSS WITH CALCITRIOL DOES NOT PROVIDE LONG-TERM BENEFICIAL-EFFECTS ON CANCELLOUS BONE MASS OR STRUCTURE IN OVARIECTOMIZED RATS

It was the aim of the present study to investigate whether a 2-month p rophylaxis of postovariectomy bone loss with low-dose calcitriol would have long-lasting beneficial effects on cancellous bone mass or struc ture after its withdrawal in rats, Six-month-old female Fischer 344 ra ts were either ovariectomized (OVX) or sham-operated (SHAM). Groups of SHAM and OVX rats were orally treated with either 0.05 mu g calcitrio l/kg per day or vehicle for 2 months postovariectomy starting immediat ely after ovariectomy. Thereafter, the rats were maintained without tr eatment for another 4 months. Half the animals in each group were kill ed 2 months postovariectomy; the rest of the rats were killed 6 months postovariectomy. Cancellous bone histomorphometry was performed on th e first lumbar vertebral body and on the proximal tibial metaphysis. A dminstration of low-dose calcitriol to SHAM and OVX rats resulted in h yper calciuria, but not hypercalcemia. By 2 months postovariectomy, ca lcitriol treatment of OVX rats had completely prevented tibial trabecu lar bone loss, and had increased vertebral cancellous bone mass in SHA M and OVX rats by about 30% over the level observed in SHAM vehicle co ntrols. However, at the end of the experiment, i.e. 4 months after wit hdrawal of calcitriol, cancellous bone mass and structure in both the vertebrae and the tibiae of calcitriol-treated OVX rats were almost id entical to those of vehicle-treated OVX rats. We conclude that prevent ion of bone loss with low-dose calcitriol during the phase of acute es trogen deficiency, when bone turnover is maximally increased, does not provide long-term beneficial effects on cancellous bone mass or struc ture in OVX rats. If extrapolated to postmenopausal women, this study would suggest that prophylaxis against postmenopausal bone loss with s hort-acting antiresorptive substances during only the first few years after menopause will probably not reduce the risk of postmenopausal os teoporosis later in life.