The effects of salmon calcitonin-induced hypocalcemia on bone metabolism in ovariectomized rats.
The ovariectomized rat has proved to be a most useful model for preclinical testing of potential therapies for osteoporosis. We describe the immediate effects of a single treatment with salmon calcitonin (sCT) on calcium homeostasis and bone turnover markers in 6-month-old sham and ovariectomized (ovx) rats at 15 days postovariectomy. Rats were fasted for 24 h prior to and following administration of 0.3 microg/kg body weight sCT. Blood specimens were collected at 0 (pretreatment), 2, 4, and 8 h. Urine samples were collected during the intervening periods. sCT treatment produced a decrease in blood ionized calcium at 2 h posttreatment in sham and ovx rats (P < 0.001), which was exaggerated in the ovx rats (P < 0.001). Increased parathyroid hormone (PTH) levels (P < 0.001) accompanied the hypocalcemia in ovx rats. Furthermore, PTH levels were significantly higher in ovx rats compared with sham rats for the same ionized calcium range of 1.275-1.300 mmol/l (P < 0.05). sCT treatment in sham rats increased urine hydroxyproline (UHyp) at 6 h posttreatment (P < 0.01). In conclusion, the calcitonin-induced hypocalcemia and secondary hyperparathyroidism was more pronounced in the ovariectomized rats, consistent with the actions of calcitonin in states of increased bone turnover induced by estrogen deficiency. This study highlights the importance of considering the actions of PTH and estrogen status when interpreting changes in calcium homeostasis and bone turnover following treatment with calcitonin in rodent models and provides further evidence for a potential role of estrogen in parathyroid function.
Davey
Rachel A
RA
Hanson Institute, Frome Road, Adelaide, South Australia, Australia. r.davey@unimelb.edu.au
Morris
Howard A
HA
D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002116:Calcitonin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006706:Homeostasis; D006909:Hydroxyproline / Q000097:blood; D006996:Hypocalcemia / Q000378:metabolism*; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004967:Estrogens; D010281:Parathyroid Hormone; C028815:salmon calcitonin; D002116:Calcitonin; D006909:Hydroxyproline; D002118:Calcium