Salmon calcitonin prevents cyclosporin-A-induced high turnover bone loss.
Cyclosporin-A (CsA) has greatly influenced the outcome of organ transplantation and has also been effective in the treatment of many autoimmune diseases. Unfortunately, it has deleterious effects on bone remodelling, causing a high turnover bone loss, with bone resorption exceeding bone formation. Salmon calcitonin (SCtn) has been shown to inhibit bone resorption in high turnover states such as Paget's disease and postmenopausal osteoporosis. In an attempt to attenuate the high turnover bone remodelling caused by CsA alone, we studied the bone mineral effects of CsA in combination with SCtn in male Sprague-Dawley rats. Group A (n = 20) received vehicle as control, group B (n = 20) received CsA (15 mg/kg BW) by daily gavage and SCtn vehicle sc, group C (n = 20) received SCtn (1.3 IU/kg BW) daily sc and CsA vehicle, and group D (n = 20) received a combination of CsA and Ctn daily, as described above. Rats were bled weekly for determination of circulating biochemical bone parameters. Eight rats from each group were killed on day 14 (short term), and the remaining rats were killed on day 28 (long term). Tibiae were removed for bone histomorphometry after death, which revealed a reduction of trabecular bone volume and an increase in osteoclast number induced by CsA alone. These changes were significantly attenuated by the combination of CsA and SCtn to resemble the histomorphometry of the control group. The inhibition of osteoclast number by SCtn is the most plausible mechanism by which the combination therapy attenuates the high turnover bone loss induced by CsA alone.
Stein
B
B
Albert Einstein Medical Center, University of Pennsylvania, Philadelphia 19141.
Takizawa
M
M
Katz
I
I
Joffe
I
I
Berlin
J
J
Fallon
M
M
Epstein
S
S
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000473:pathology; D002116:Calcitonin / Q000627:therapeutic use*; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D002452:Cell Count; D003524:Cyclosporins / Q000633:toxicity*; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D010281:Parathyroid Hormone; D015675:Osteocalcin; C028815:salmon calcitonin; D002116:Calcitonin; D002117:Calcitriol; D002118:Calcium