T lymphocytes play a critical role in the development of cyclosporin A-induced osteopenia.
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.
Buchinsky
F J
FJ
Department of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, USA.
Ma
Y
Y
Mann
G N
GN
Rucinski
B
B
Bryer
H P
HP
Romero
D F
DF
Jee
W S
WS
Epstein
S
S
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000276:immunology*; D014508:Urea / Q000097:blood
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D010281:Parathyroid Hormone; D015675:Osteocalcin; D016572:Cyclosporine; D014508:Urea; D003404:Creatinine; D002117:Calcitriol; D002118:Calcium