1. T lymphocytes play a critical role in the development of cyclosporin A-induced osteopenia.
- Author
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Buchinsky FJ, Ma Y, Mann GN, Rucinski B, Bryer HP, Romero DF, Jee WS, and Epstein S
- Subjects
- Animals, Blood Glucose metabolism, Bone Diseases, Metabolic blood, Bone Diseases, Metabolic chemically induced, Bone Diseases, Metabolic pathology, Bone and Bones pathology, Calcitriol blood, Calcium blood, Creatinine blood, Male, Osteocalcin blood, Parathyroid Hormone blood, Rats, Rats, Nude, Rats, Sprague-Dawley, Urea blood, Bone Diseases, Metabolic immunology, Cyclosporine toxicity, Immunosuppressive Agents adverse effects, T-Lymphocytes immunology
- Abstract
The T lymphocyte suppressor, cyclosporin A, has been shown to cause high turnover osteoporosis. We postulated that cyclosporin A may exert its effects via the T cell rather than direct activity on bone. In this study we administered cyclosporin A (15 mg/kg.day by gavage) to 11 10-week-old Rowett athymic nude rats and to 12 age-matched immunocompetent Sprague-Dawley rats. Placebo was administered to control groups (n = 12 for both). After 28 days of treatment, the Sprague-Dawley rats displayed high turnover bone loss, but the nude rats were largely unaffected by the drug. Sprague-Dawley treated rats had less than half the percent trabecular area of their controls as measured at the secondary spongiosa of the proximal tibial metaphysis (P < 0.001; strain by treatment, P = 0.007). The same pattern was evident for trabecular number, separation, and thickness (strain by treatment, P = 0.034, P = 0.001, and P = 0.021, respectively). Only the Sprague-Dawley rats had an elevated percent eroded perimeter and an elevated bone area referent bone formation rate (strain by treatment, P = 0.002 and P = 0.0003, respectively). Mass, glucose, ionized calcium, PTH, osteocalcin, 1,25-dihydroxyvitamin D, and creatinine all responded similarly to cyclosporin A regardless of strain. T Lymphocytes thus appear to be a prerequisite for the development of cyclosporin A-induced osteopenia.
- Published
- 1996
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