Calcitonin prevents bone loss but decreases osteoblastic activity in ovariohysterectomized beagle dogs.
The antiresorptive effects of calcitonin are well documented. Recent in vitro and in vivo evidence points to an anabolic effect of calcitonin on osteoblasts. To assess the value of calcitonin in preventing the rapid and early bone loss after cessation of ovarian function and to investigate its effects on osteoblasts in vivo, 32 dogs were ovariohysterectomized (OHX) and 32 dogs were sham-operated (Sham). After the surgeries, half of the OHX and Sham dogs received every-other-day subcutaneous injections of human calcitonin (0.25 mg/dog/d), and the remaining dogs were given vehicle. Half of the animals had a bone biopsy at week 2 and were euthanized thereafter; the other half of the animals underwent a bone biopsy at month 1 and were euthanized at month 4. Blood drawings were done at baseline and at the time of each bone biopsy. Calcitonin prevented the increase in erosion depth seen in OHX animals and prevented the cancellous bone loss observed at 2 weeks and at 1 and 4 months. Calcitonin did not affect bone volume in Sham dogs. However, treatment with calcitonin induced a decrease in mineralizing surfaces and bone formation rates at the bone surface and cell level and an increase in mineralization lag time in both Sham and OHX animals without significantly affecting osteoblast number. This finding indicates that the negative effect of calcitonin on bone mineralization is not solely the result of a decrease in bone turnover. The data show that calcitonin, because of its antiresorptive effects, can prevent bone loss after cessation of ovarian function. However, short-term treatment with calcitonin does not stimulate osteoblast activity; on the contrary, it exerts a negative effect on osteoblastic bone formation and mineralization. Long-term studies are needed to investigate whether this unwanted effect of calcitonin on osteoblasts in vivo represents a transitory or persistent phenomenon.
Monier-Faugere
M C
MC
Department of Internal Medicine, University of Kentucky, Lexington, USA.
Geng
Z
Z
Qi
Q
Q
Arnala
I
I
Malluche
H H
HH
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002117:Calcitriol / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007085:Ilium / Q000187:drug effects; D015592:Immunoradiometric Assay; D007279:Injections, Subcutaneous; D008137:Longitudinal Studies; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000517:prevention & control*; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000097:blood; D011897:Random Allocation
D015415:Biomarkers; D010281:Parathyroid Hormone; D015675:Osteocalcin; D002116:Calcitonin; D002117:Calcitriol