ENDOGENOUS CALCITONIN ATTENUATES PARATHYROID HORMONE-INDUCED CANCELLOUS BONE LOSS IN THE RAT

Although calcitonin (CT) treatment has been shown to prevent bone loss in estrogen-deficient states, the function of endogenous CT in bone m etabolism is not clearly established. To test the hypothesis that endo genous CT has a role in bone conservation, we compared the bone-resorb ing effect of exogenous PTH between CT-deficient [thyroparathyroidecto mized (TPTX)] and CT-sufficient [parathyroidectomized (PTX)] rats. Stu dies were carried out with two doses (30 and 40 pmol/h) of bovine PTH- (1-34) to examine dose responsiveness and with or without T-4 replacem ent in TPTX rats to exclude the influence of thyroid function on the r esults. Sham-operated control rats received vehicle. At comparable hyp ercalcemia (mean +/- SEM, 13.6 +/- 0.8 vs. 12.7 +/- 1.0 mg/dl) after 3 days of sc infusion of 30 pmol/h PTH, serum CT levels were significan tly (P < 0.05) higher in PTX rats (66.0 +/- 8.0 pg/ml) than in TPTX ra ts (17.7 +/- 4.3). CT-deficient TPTX rats showed a significant cancell ous bone loss in the proximal tibia [bone volume (BV/TV), 4.2 +/- 1.0% ] compared with control rats (10.4 +/- 1.2%). In contrast, there was n o bone loss in CT-sufficient PTX rats (BV/TV, 10.9 +/- 0.5%). A simila r difference in the serum CT level and more marked difference in BV/TV (0.9 +/- 0.3% vs. 8.1 +/- 1.3%) were observed between TPTX and PTX ra ts infused with 40 pmol/h PTH. The magnitude of bone loss in TPTX rats was not different between T-4-supplemented and nonsupplemented groups . Unlike cancellous bone, the PTH-induced decrease in the cortical thi ckness of the tibia was comparable in TPTX and PTX rats. The extent of increase in serum osteocalcin after PTH infusion was not different be tween TPTX and PTX groups. These results indicate that in the rat, end ogenous CT has a protective effect against PTH-stimulated cancellous b one loss, but not cortical bone loss.