Endocrinology, Vol 124, 2179-2184, Copyright © 1989 by Endocrine Society

ARTICLES

The effect of cyclosporin A administration and its withdrawal on bone mineral metabolism in the rat

M Schlosberg, C Movsowitz, S Epstein, F Ismail, MD Fallon and S Thomas
Division of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141.

The in vivo administration of cyclosporin A (CsA) has been associated with significant bone loss and increased bone remodeling. To observe whether these changes are reversible, we have investigated the consequences of the administration and withdrawal of CsA immunotherapy on bone mineral metabolism. Three groups of Sprague-Dawley rats were studied for 28 days. Group A received vehicle, and group B received CsA (15 mg/kg BW) for 28 days, while group C received CsA (15 mg/kg BW) for 14 days and then vehicle from days 15-28 by daily gavage. Serum ionized calcium (Ca2+), PTH, bone gla protein, blood urea nitrogen, creatinine, magnesium, phosphorus, and 1.25-dihydroxyvitamin D were measured weekly. Bone histomorphometry was analyzed on days 14 and 28 in groups A and B and on day 28 in group C. CsA administration resulted in reversible hypomagnesemia and mild transient elevation in circulating 1,25-dihydroxyvitamin D levels with no change in Ca2+, PTH, blood urea nitrogen, or phosphorus. Serum bone gla protein levels were significantly increased (P less than 0.002) during CsA therapy, but tended to return to control values after CsA withdrawal. Enhanced bone remodeling and significant trabecular bone loss accompanied CsA administration. Withdrawal of CsA resulted in all of the histomorphometric parameters, except for bone volume, returning to control values within 2 weeks. Incomplete restoration of bone volume occurred 5 weeks after CsA withdrawal. This limited restoration of bone volume despite CsA withdrawal may have important clinical implications.

This article has been cited by other articles:

				R. TAMLER and S. EPSTEIN Nonsteroid Immune Modulators and Bone Disease Ann. N.Y. Acad. Sci., April 1, 2006; 1068(1): 284 - 296. [Abstract] [Full Text] [PDF]

				N. M. Maalouf and E. Shane Osteoporosis after Solid Organ Transplantation J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2456 - 2465. [Abstract] [Full Text] [PDF]

				T. Beikler and T. F. Flemmig IMPLANTS IN THE MEDICALLY COMPROMISED PATIENT Crit. Rev. Oral. Biol. Med., July 1, 2003; 14(4): 305 - 316. [Abstract] [Full Text] [PDF]

				J.-P. Casez, K. Lippuner, F. F. Horber, A. Montandon, and P. Jaeger Changes in bone mineral density over 18 months following kidney transplantation: the respective roles of prednisone and parathyroid hormone Nephrol. Dial. Transplant., July 1, 2002; 17(7): 1318 - 1326. [Abstract] [Full Text] [PDF]

				E. Shane, M. Rivas, D. J. McMahon, R. B. Staron, S. J. Silverberg, M. J. Seibel, D. Mancini, R. E. Michler, K. Aaronson, V. Addesso, et al. Bone Loss and Turnover after Cardiac Transplantation J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1497 - 1506. [Abstract] [Full Text] [PDF]