Cyclosporines: correlation of immunosuppressive activity and inhibition of bone resorption

Cyclosporine A (CsA) is a potent immunosuppressive agent that inhibits stimulated bone resorption in vitro. To study the mechanism of this effect, we have compared CsA with several cyclosporine analogs that vary in immunosuppressive potency. CsA as well as another potent immunosuppressive analog, CsG, inhibited parathyroid hormone (PTH) and interleukin-1 (IL-1)-stimulated resorption of fetal rat limb bones. The nonimmuno-suppressive analogs CsH and CsF did not inhibit PTH or IL-1-stimulated bone resorption. Likewise, the weakly immunosuppressive analog CsD did not significantly inhibit PTH-stimulated bone resorption. Although other mechanisms cannot be excluded, our data are consistent with the concept that bone resorption may involve an immune cell-derived mediator.