Interaction of cyclosporine A and calcitonin on bone resorption in vitro

Cyclosporine A (CsA), which is a potent immunosuppressive agent, inhibits bone resorption in vitro. The inhibition of bone resorption by CsA is sustained, unlike the transient inhibition of bone resorption produced by calcitonin (CT). These different patterns of inhibition were studied by examining the interaction between CsA and CT on stimulated bone resorption in the neonatal mouse calvarial resorptive system. 'Escape' from the CT inhibition of PTH stimulated bone resorption occurred after 24 hr of organ culture. Coincubation with CsA (1 μg/ml) delayed the 'escape' response of CT + PTH treated bones, so that the full 'escape' response did not occur until after 48 hr of organ culture. Likewise, a pretreatment of 24 hr with CsA (1 μg/ml) was sufficient to delay 'escape' from CT inhibition of PTH stimulated bone resorption until after 48 hr of organ culture. A higher concentration of CsA (10 μg/ml) completely prevented the 'escape' response. Our data could indicate an interaction between the CsA and CT inhibitory effects on resorption.