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

Abstract.

It was the aim of the present study to investigate whether a 2-month prophylaxis of postovariectomy bone loss with low-dose calcitriol would have long-lasting beneficial effects on cancellous bone mass or structure after its withdrawal in rats. Six-month-old female Fischer 344 rats were either ovariectomized (OVX) or sham-operated (SHAM). Groups of SHAM and OVX rats were orally treated with either 0.05 μg calcitriol/kg per day or vehicle for 2 months postovariectomy, starting immediately after ovariectomy. Thereafter, the rats were maintained without treatment for another 4 months. Half the animals in each group were killed 2 months postovariectomy; the rest of the rats were killed 6 months postovariectomy. Cancellous bone histomorphometry was performed on the first lumbar vertebral body and on the proximal tibial metaphysis. Administration of low-dose calcitriol to SHAM and OVX rats resulted in hypercalciuria, but not hypercalcemia. By 2 months postovariectomy, calcitriol treatment of OVX rats had completely prevented tibial trabecular bone loss, and had increased vertebral cancellous bone mass in SHAM and OVX rats by about 30% over the level observed in SHAM vehicle controls. However, at the end of the experiment, i.e. 4 months after withdrawal of calcitriol, cancellous bone mass and structure in both the vertebrae and the tibiae of calcitriol-treated OVX rats were almost identical to those of vehicle-treated OVX rats. We conclude that prevention of bone loss with low-dose calcitriol during the phase of acute estrogen deficiency, when bone turnover is maximally increased, does not provide long-term beneficial effects on cancellous bone mass or structure in OVX rats. If extrapolated to postmenopausal women, this study would suggest that prophylaxis against postmenopausal bone loss with short-acting antiresorptive substances during only the first few years after menopause will probably not reduce the risk of postmenopausal osteoporosis later in life.