Skeletal effects of calcitonin treatment and withdrawal in ovariectomized rats

The study was designed to determine, by histomorphometric techniques, bone changes as a function of time during long-term treatment with salmon calcitonin (CT) and after withdrawal of the hormone in ovariectomized (OVX) rats. Groups of OVX rats were treated with vehicle alone or CT on alternate days for 30, 60, or 90 days. Additional groups of sham-operated control rats were treated with vehicle alone. Rats from each of the three groups were sacrificed at each time point. All treatments in the remaining rats were then terminated at 90 days, followed by sacrifice of rats from each group at 30 and 60 days after withdrawal of vehicle or CT treatment. The proximal tibia from each animal was processed undecalcified for quantitative bone histomorphometry. Compared with control rats, the proximal tibiae of vehicle-treated OVX rats were characterized by cancellous osteopenia and significant increases in osteoclast surface, osteoblast surface, mineralizing surface, mineral apposition rate, and bone formation rate. CT treatment of OVX rats partially prevented cancellous bone loss by approximately 50% and significantly decreased most of the above indices of bone turnover relative to vehicle-treated OVX rats. However, soon after withdrawal of CT, OVX rats previously treated with the hormone exhibited rapid loss of cancellous bone associated with increased bone turnover. These results in an animal model of estrogen depletion suggest that early postmenopausal women who are withdrawn from prophylactic CT treatment may be at high risk for subsequent bone loss.