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 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 microgram 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.
Institute of Physiology, Physiological Chemistry and Animal Nutrition, Veterinary Faculty, Ludwig Maximilians University, Munich, Germany. r.erben@lrz.uni-muenchen.de
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D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002117:Calcitriol / Q000627:therapeutic use*; D005260:Female; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D010024:Osteoporosis / Q000503:physiopathology / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D013977:Tibia / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors
D002117:Calcitriol