Cyclosporin A does not affect the absolute rate of cortical bone resorption at the organ level in the growing rat.
The weanling rat, an animal model of rapid bone turnover, was used to evaluate the effects of various doses of cyclosporin A (CsA) on various bones during different time periods. Sprague-Dawley male rats were extensively prelabeled with 3H-tetracycline during 1-3 weeks of age. At 4 weeks of age, four groups of rats were given daily subcutaneous injections: vehicle or CsA--low dose (10 mg/kg), intermediary dose (20 mg/kg), or high dose (30 mg/kg) for 7, 14, or 28 days. Three different whole bones--the femur (low turnover), scapula (moderate turnover), and lumbar-6 vertebra (high turnover) were harvested intact at 4, 5, 6, and 8 weeks of age. The whole bones were assayed weekly for total dry defatted weight, calcium mass (formation), and loss of 3H-tetracycline (bone resorption) following treatment with CsA. Serum CsA levels, calcium creatinine, and alkaline phosphatase were measured weekly. Significant decreases in serum calcium and alkaline phosphatase were observed at 1 and 2 weeks, and were normalized by 4 weeks of treatment. No significant changes in serum creatinine were noted. For all three doses of CsA, no effect was observed on the absolute rate of cortical bone resorption of three different, whole bones over three time periods. Body weight and bone formation in treated animals was significantly smaller in a dose- and time-related fashion compared with control animals at sacrifice. However, compared with the initial control animals, body weights and bone masses of the final treated animals were much larger, suggesting that the smaller bone masses were due to insufficient growth and slow gain in bone mass.(ABSTRACT TRUNCATED AT 250 WORDS)
Klein
L
L
Department of Orthopaedics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Lemel
M S
MS
Wolfe
M S
MS
Shaffer
J
J
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000139:chemically induced; D001862:Bone Resorption / Q000139:chemically induced*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D016572:Cyclosporine; D000469:Alkaline Phosphatase; D002118:Calcium