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 metabolism is not clearly established. To test the hypothesis that endogenous CT has a role in bone conservation, we compared the bone-resorbing effect of exogenous PTH between CT-deficient [thyroparathyroidectomized (TPTX)] and CT-sufficient [parathyroidectomized (PTX)] rats. Studies were carried out with two doses (30 and 40 pmol/h) of bovine PTH-(1-34) to examine dose responsiveness and with or without T4 replacement in TPTX rats to exclude the influence of thyroid function on the results. Sham-operated control rats received vehicle. At comparable hypercalcemia (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 significantly (P < 0.05) higher in PTX rats (66.0 +/- 8.0 pg/ml) than in TPTX rats (17.7 +/- 4.3). CT-deficient TPTX rats showed a significant cancellous 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 no bone loss in CT-sufficient PTX rats (BV/TV, 10.9 +/- 0.5%). A similar 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 rats infused with 40 pmol/h PTH. The magnitude of bone loss in TPTX rats was not different between T4-supplemented and nonsupplemented groups. Unlike cancellous bone, the PTH-induced decrease in the cortical thickness of the tibia was comparable in TPTX and PTX rats. The extent of increase in serum osteocalcin after PTH infusion was not different between TPTX and PTX groups. These results indicate that in the rat, endogenous CT has a protective effect against PTH-stimulated cancellous bone loss, but not cortical bone loss.
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
M
M
Yamamoto
J G
JG
Seedor
G A
GA
Rodan
R
R
Balena
D000818:Animals; D001835:Body Weight; D016723:Bone Remodeling / Q000187:drug effects; D002116:Calcitonin / Q000172:deficiency / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000652:urine; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism*; D016105:Parathyroidectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000494:pharmacology*; D013977:Tibia / Q000378:metabolism* / Q000473:pathology
D010281:Parathyroid Hormone; D002116:Calcitonin; D013974:Thyroxine; D002118:Calcium