Different effects of cyclosporin A on bone remodeling in young and adult rats.
Reported effects of cyclosporin A (Sandimmun, CsA) on bone have been both contradictory and controversial. Thus, stimulation of new bone formation as well as increased mineral and matrix resorption have been observed. To investigate the response of basal mineral and matrix turnover to CsA treatment at different stages of skeletal development, comparative experiments were conducted in young growing female rats and in adults. Fifty-six young animals (study A) and 40 adults (study B) received orally either the carrier substance or 5, 15, and 30 mg/kg CsA for 30 days. The following parameters were measured: (a) total skeletal mineral content by dual energy X-ray absorptiometry (DEXA) on days 1 and 30; (b) tibial trabecular volume at day 30; (c) serum osteocalcin at 5-day intervals; (d) urinary deoxypyridinoline (Dpd) excretion (days 1, 15, and 30); and (e) plasma levels of CsA. Results can be summarized as follows: in young rats (study A), total skeletal mineral was not modified by the 5- and 15-mg/kg doses of CsA, whereas 30 mg/kg induced a significant decrease (-15%, p < 0.01). This parameter was not significantly modified in adult animals (study B) subjected to the same doses. The administration of 5 mg/kg CsA did not alter tibial trabecular volume in young rats, but 15 and 30 mg/kg significantly lowered this parameter (-16.3%, p < 0.02, and -42%, p < 0.001, respectively). In adult rats, tibial trabecular volume remained unchanged with the exception of the group receiving 30 mg/kg which exhibited significantly lower values (-28%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
del Pozo
E
E
Sandoz Research Institute, Berne, Switzerland.
Lippuner
K
K
Ruch
W
W
Casez
J P
JP
Payne
T
T
MacKenzie
A
A
Jaeger
P
P
D015502:Absorptiometry, Photon; D000284:Administration, Oral; D000375:Aging / Q000502:physiology; D000596:Amino Acids / Q000652:urine; D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D015675:Osteocalcin; D016572:Cyclosporine; C036020:deoxypyridinoline; D003404:Creatinine