L-arginine prevents bone loss and bone collagen breakdown in cyclosporin A-treated rats.

Cyclosporin A is implicated in the pathogenesis of post-transplantation bon e disease. Because of recent evidence that cyclosporin A may cause renal an d cardiovascular toxicity by inhibiting nibric oxide (NO) activity, and tha t NO slows bone remodeling and bone loss in animal and human studies, we in vestigated a possible link between NO production and beneficial effects on bone health in cyclosporin A-treated rats. Thirty-six 10-week-old male rats were assigned to six groups of six animals each, and treated for 4 weeks w ith: vehicle; cyclosporin A; L-arginine, N-G-nitro-L-arginine methylester ( L-NAME, a general inhibitor of NO synthase activity); a combination of cycl osporin A + L-arginine; and a combination of cyclosporin A + L-NAME. Whole body and regional (spine and pelvis) bone mineral content of rats were meas ured under basal conditions and at: the end of the treatment period by dual -energy X-ray absorptiometry (DXA) scanning. Femur weights and serum concen trations of pyridinoline, a reliable marker of bone resorption, were measur ed at the end of the study period. Cyclosporin A-, L-NAME-, and cyclosporin A + L-NAME-treated rats had significantly lower bone mineral content and f emur weights, and significantly higher pyridinoline levels than did control animals. The administration of L-arginine appeared to prevent bone loss ca used by cyclosporin A, suggesting that this amino acid, which can be conver ted to produce NO, might prove useful in preventing disturbed bone modeling and inhibition of bone growth associated with cyclosporin A therapy. (C) 2 000 Elsevier Science B.V. All rights reserved.